s-1-(combination) and Stomach-Neoplasms

S-1-based and capecitabine-based adjuvant treatments are proved efficacious for patients with gastric cancer, but conventional meta-analyses of the direct comparisons between two alternative adjuvant regimens to resection of GC have not been attempted.. The aim of this review was to compare the disease-free survival, overall survival and adverse events in patients receiving the S-1- and capecitabine-based adjuvant chemotherapies for treatment of gastric cancer (GC) patients undergoing resection.. A search of the academic literature was performed in PUBMED, SCOPUS, CENTRAL and EMBASE databases along with manual search in relevant journals for studies in English, to identify comparative studies comparing the effect of S-1-based chemotherapy and capecitabine-based adjuvant chemotherapy (AC), used in combination with surgical resection for treatment of gastric cancer. Both qualitative and quantitative analyses was carried out for all the included studies. The hazard ratios (HR) of disease-free survival (DFS) and overall survival (OS) were pooled using generic inverse variance method. The included studies were assessed for risk of bias using ROBINS-E (risk of bias in non-randomized studies of exposures) tool.. Seven retrospective cohort studies, two prospective cohort studies and one randomized clinical trial were included. Both S-1- and capecitabine-based adjuvant chemotherapy for treatment of stage 2 or 3 gastric cancer had similar effects on the 3-year and 5-year DFS rates, overall survival and adverse events in the included studies. There was no difference in the adjusted hazard ratios (HR) of OS and DFS (0.86 95% CI (0.68, 1.09); p = 0.21 and 0.96 95% CI (0.75, 1.24), respectively). Oral mucositis was increasingly associated with S-1-based AC, while incidences of adverse events such as neutropenia, anaemia and thrombocytopenia were similar to those of capecitabine-based regimen. The quality of the included studies was found to be low to moderate.. S-1- and capecitabine-based adjuvant chemotherapies can be used interchangeably as an adjuvant chemotherapeutic regimen postradical gastrectomy with D2 lymph node dissection.

Topics: Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Chemotherapy, Adjuvant; Disease-Free Survival; Drug Combinations; Gastrectomy; Humans; Neoplasm Staging; Oxonic Acid; Stomach Neoplasms; Tegafur

Gastric and gastroesophageal junction (GEJ) cancers represent the third leading cause of malignancy-associated death worldwide. Approximately 15-20% of these adenocarcinomas overexpress the human epidermal growth factor receptor 2 (HER2), a pro-proliferative receptor tyrosine kinase that has been therapeutically exploited in other disease contexts. The landmark ToGA trial demonstrated that trastuzumab, an anti-HER2 antibody, could improve overall survival for patients with HER2 overexpressing advanced gastric and GEJ adenocarcinomas. In the ensuing decade, great effort has been made to refine and expand this therapeutic strategy through a variety of avenues including optimization of chemotherapy backbones, identifying potential synergy with immune checkpoint inhibition, deployment of alternative HER2-targeted antibodies, use of small molecule inhibitors, and development of HER2-directed antibody drug conjugates. While the results of these efforts have had variable success, they have led to a greater understanding of the mechanisms of both primary and acquired resistance to HER2-directed therapies, laying the groundwork for future investigations. Recently, KEYNOTE-811 and DESTINY-Gastric01 have led to the FDA approvals of pembrolizumab in combination with trastuzumab and chemotherapy in the 1st-line advanced setting and trastuzumab deruxtecan (fam-trastuzumab deruxtecan-nxki) in the 2nd-line setting, respectively. Herein, we review these significant works as well as discuss the ongoing investigations they have inspired, which aim to find and utilize additional means for targeting HER2 in gastric and GEJ cancers.

Topics: Adenocarcinoma; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Cisplatin; Clinical Trials as Topic; Drug Combinations; Drug Resistance, Neoplasm; Esophagogastric Junction; Fluorouracil; Humans; Irinotecan; Lapatinib; Oxaliplatin; Oxonic Acid; Paclitaxel; Receptor, ErbB-2; Stomach Neoplasms; Tegafur; Trastuzumab

The standard treatment for locally advanced gastric cancer differs across the world. In western countries, perioperative chemotherapy or postoperative adjuvant chemoradiotherapy are the preferred treatment options, whereas in Asia, D2 gastrectomy followed by postoperative adjuvant chemotherapy is standard. In Japan, adjuvant chemotherapy with S-1 is the standard treatment for pStage II gastric cancer, whereas adjuvant chemotherapy with a doublet regimen is preferred for pStage III gastric cancer. The efficacy of preoperative neoadjuvant chemotherapy using S-1 plus cisplatin, has been investigated in selected patients with expected poor survival outcomes. To expand the indications for neoadjuvant chemotherapy, a clinical trial investigating the efficacy of preoperative S-1 plus oxaliplatin in patients with cStage III (cT3-4N1-3) gastric cancer (JCOG1509) is ongoing in Japan. The addition of immune checkpoint inhibitors to cytotoxic chemotherapy also seems promising and is being investigated in international randomized clinical trials. Although we have to await the final results of these studies, preoperative neoadjuvant chemotherapy is a promising treatment strategy and likely to become standard treatment for locally advanced gastric cancer in Japan.

Topics: Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Drug Combinations; Gastrectomy; Humans; Japan; Neoadjuvant Therapy; Neoplasm Staging; Oxaliplatin; Oxonic Acid; Preoperative Care; Stomach Neoplasms; Tegafur

Apatinib has been proven to significantly prolong the survival of the patients with advanced chemotherapy-refractory gastric cancer. To date, studies on apatinib plus S-1 as first-line palliative therapy for metastatic gastroesophageal junction (GEJ) cancer are rare.. A 61-year-old female patient was admitted with dysphagia, significant loss of body weight, and poor performance status.. Endoscopic biopsy revealed the diagnosis of poorly-differentiated GEJ adenocarcinoma, and the patient was clinically staged as T3NxM1G3 (IVB).. She had received 4 cycles of palliative therapy using oral apatinib (425 mg daily) plus S-1 (40 mg twice daily for 4 weeks, with a 2-week drug-free interval), followed by maintenance low-dose apatinib (250 mg daily) plus S-1 at the same dosage thereafter.. Her progression-free survival was nearly 5 months, and the overall survival was >11 months up to now. The adverse events were tolerable.. Apatinib plus S-1 might be an alternative option for late-stage GEJ cancer. However, high-quality trials are warranted before the recommendation of this therapeutic regimen.

Topics: Adenocarcinoma; Antineoplastic Agents; Drug Combinations; Esophageal Neoplasms; Esophagogastric Junction; Female; Humans; Middle Aged; Oxonic Acid; Pyridines; Stomach Neoplasms; Tegafur

Gastric cancer (GC), particularly unresectable, metastatic, or recurrent GC, has been characterized by unfavorable prognosis. This meta-analysis of clinical randomized phase II trials was conducted to systematically evaluate the efficacy and safety of capecitabine-based versus S-1-based chemotherapy for metastatic or recurrent GC.. We searched PubMed, Embase, Web of Science, and Cochrane Library databases to identify studies eligible for the present analysis. Data were collected from inception to June 20th, 2019. Outcomes included objective response rate (ORR); 6-, 12-, and 18-month progression-free survival (PFS); 1-, 2-, and 3-year overall survival (OS); and adverse events. A meta-analysis was conducted using a random-effects model, and a sensitivity analysis was conducted to examine whether the results of the meta-analysis were robust. Risk ratio (RR) or hazard ratio (HR) with 95% confidence interval (CI) was reported as the main evaluation parameters.. Six eligible studies with 561 subjects were included in the present meta-analysis. There was no significant difference between S-1-based and capecitabine-based chemotherapy in ORR (RR =1.17, 95% CI: 0.95-1.44, P=0.13, I2 =0%); 6-month (HR =0.94, 95% CI: 0.77-1.14, I2 =0%), 12-month (HR =0.89, 95% CI: 0.61-1.31, I2 =0%), and 18-month PFS (HR =1.02, 95% CI: 0.55-1.91, I2 =0%); 1-year (HR =0.99, 95% CI: 0.83-1.18, I2 =0%), 2-year (HR =0.90, 95% CI: 0.58-1.42, I2 =0%), and 3-year OS (HR =1.08, 95% CI: 0.50-2.34, I2 =0%). However, the capecitabine-based chemotherapy had a higher incidence in all grades of hand-foot syndrome (HFS) (RR =3.41, 95% CI: 1.98-5.90, P<0.01, I 2 =39%) and grades 3-4 neutropenia (RR =1.62, 95% CI: 1.05-2.51, P=0.03, I2 =0%).. In terms of efficacy, capecitabine-based chemotherapy and S-1-based chemotherapy had similar short-term outcomes. Regarding safety, we recommend S-1-based chemotherapy for patients with metastatic or recurrent GC prior to capecitabine-based treatment.

Topics: Antimetabolites, Antineoplastic; Capecitabine; Disease-Free Survival; Drug Combinations; Humans; Oxonic Acid; Randomized Controlled Trials as Topic; Stomach Neoplasms; Tegafur

Platinum/S-1 (PS) and platinum/5-fluorouracil (PF) as first-line chemotherapies are extensively used for the treatment of advanced gastric or gastroesophageal junction cancer (AGC); however, there is no definite consensus on which regimen is best. In our meta-analysis, we compared PS with PF in terms of their efficacy and safety in AGC patients.. PubMed, ScienceDirect, Web of Science, Scopus, Ovid MEDLINE, EMBASE, The Cochrane Library, Google Scholar, and CNKI were systematically searched for pertinent literature. We analyzed overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse effects (AEs) as major end points.. A total of 3,225 studies were identified, among which 6 randomized controlled trials, including 1,736 participants, were ultimately included in our analysis. Our results showed that PS and PF were comparable in terms of OS (p = 0.33, 95% confidence interval [CI]: 0.84-1.06), PFS (p = 0.63, 95% CI: 0.87-1.09), ORR (p = 0.38, 95% CI: 0.91-1.28), DCR (p = 0.41, 95% CI: 0.86-1.43), total AEs (p = 0.41, 95% CI: 0.98-1.01), and grade ≥3 AEs (p = 0.58, 95% CI: 0.82-1.41). However, those who received PF had a shorter time to failure (TTF) (p = 0.01, 95% CI: 0.77-0.97), and a significantly higher rate and more severe cases of stomatitis, nausea, and hypokalemia were reported in the PF group.. PF and PS show similar antitumor efficacy (OS, PFS, ORR, and DCR), but patients receiving PS exhibit longer TTF and fewer AEs (stomatitis, nausea, and hypokalemia) than those receiving PF.

Topics: Antineoplastic Agents; Coordination Complexes; Disease-Free Survival; Drug Combinations; Drug Therapy, Combination; Esophagogastric Junction; Fluorouracil; Gastrointestinal Neoplasms; Humans; Neoplasm Staging; Oxonic Acid; Platinum; Proportional Hazards Models; Randomized Controlled Trials as Topic; Stomach Neoplasms; Survival Analysis; Tegafur; Treatment Outcome

Gastric cancer, as one of the increasingly common malignancies, has experienced high morbidity throughout many countries at present. Currently, chemotherapy regimen with more efficacy and safety for advanced gastric cancer (AGC) is needed. We aimed to assess the clinical efficacy and safety of S-1 combined with paclitaxel (PTX) for AGC by performing a systematic review and meta-analysis of the published studies.. All published randomized controlled trials (RCTs) of S-1 combined with PTX for AGC were searched. Studies that included patients with locally advanced or metastases' gastric cancers were included. We searched the databases included Cochrane Library of Clinical Comparative Trials, MEDLINE, Embase, American Society of Clinical Oncology meeting abstracts and China National Knowledge Internet (CNKI) from 2000 to 2018. We searched the database up to January 2018. The first endpoint was overall survival (OS). Other endpoints were progression-free survival (PFS), objective response rate (ORR) and disease control rate (DCR). Safety analyses were also performed.. A total of 7 trials (including 1407 patients, 711 patients in intervention group and 696 patients in control group) were included in the present analysis. S-1 combined with PTX significantly improved the OS [HR = 0.78, 95% CI: 0.60-0.97, P = 0.000],PFS [HR = 0.70, 95% CI: 0.55-0.85, P = 0.000], ORR [RR = 1.30, 95%CI: 1.05-1.60, P = 0.017] and DCR [RR = 1.15, 95%CI: 1.04-1.27, P = 0.008] of patients with AGC. The grade 3 or 4 haematological and non-hematologic toxicities were anemia [RR = 1.71, 95% CI: 1.04-2.79, P = 0.03], neutropenia [RR = 1.65, 95% CI: 1.32-2.06, P < 0.0001] and anorexia [RR = 1.66, 95% CI: 1.05-2.64, P = 0.03] respectively.. S-1 combined with PTX may be a good choice for patients with AGC. S-1 plus PTX experienced more efficacy and safety when compared with S-1 alone or S-1 plus other drugs.

Topics: Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Hematologic Diseases; Humans; Oxonic Acid; Paclitaxel; Stomach Neoplasms; Survival Analysis; Tegafur

Different adjuvant treatments are available for patients with gastric cancer, but conventional meta-analyses performing direct comparisons between two alternative treatments did not have enough power to compare all the adjuvant treatments. Thus, we did a network meta-analysis summarizing the direct and indirect comparisons to identify the optimum treatment.. We systematically searched for RCTs of adjuvant treatments for gastric cancer comparing two or more of the following treatments: surgery alone, radiotherapy with fluoropyrimidine, S-1-based regimens, and XELOX. The treatments offering available indirect evidence to investigate the comparative effectiveness of adjuvant treatments mentioned above were also included. Then we performed a Bayesian network meta-analysis to summarize the direct and indirect comparisons. We estimated hazard ratios with 95% credible intervals (CrI) for OS and DFS.. 11 eligible RCTs (5620 patients) were included in the network meta-analysis. Radiotherapy with fluorouracil (5-FU/RT), S-1-based regimens, and XELOX significantly improved OS as compared with surgery alone [(HR = 0.75 with 95% CrI: 0.63-0.89), (HR = 0.63 with 95% CrI: 0.52-0.76), and (HR = 0.66 with 95% CrI: 0.51-0.85), respectively]. No treatment was clearly superior to others; however, S-1-based regimes and XELOX showed a statistically non-significant trend to better survival as compared with 5-FU/RT.. S-1-based chemotherapy and XELOX are likely to be the most effective adjuvant treatments for patients with resected gastric cancer. 5-FU alone provided little survival benefits as compared with surgery alone. Further clinical trials may be required to investigate S-1-based and XELOX-based adjuvant treatment strategies.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bayes Theorem; Capecitabine; Chemoradiotherapy, Adjuvant; Deoxycytidine; Disease-Free Survival; Drug Combinations; Fluorouracil; Humans; Lymph Node Excision; Network Meta-Analysis; Oxaloacetates; Oxonic Acid; Stomach Neoplasms; Survival Analysis; Tegafur

To review the recent literature regarding treatment of gastric cancer.. Addition of postoperative radiation therapy to perioperative chemotherapy offers no survival benefit. Fluoropyrimidines, in particular 5-fluorouracil (5-FU), are the backbone for gastric cancer chemotherapy. S-1, an oral prodrug of 5-FU, has become the mainstay for gastric cancer chemotherapy in Japan. In a Japanese adjuvant chemotherapy trial, addition of docetaxel to standard S-1 chemotherapy improved disease-free survival; this regimen will become their new standard for adjuvant therapy. Microsatellite instability (MSI) high status is emerging as a favorable prognostic marker in resected gastric cancer and may indicate a group of patients who do not gain additional benefit from treatment with adjuvant chemotherapy. In metastatic gastric cancer, the addition of ramucirumab, an antivascular endothelial growth factor receptor 2-targeted antibody, to first-line chemotherapy did not improve survival over chemotherapy alone. Trifluridine/tipiracil treatment in chemotherapy-refractory gastric cancer improved survival compared to placebo and will emerge as a late-line therapy option. Phase II and III trials indicate activity for the immune checkpoint inhibitors pembrolizumab and nivolumab in chemotherapy-refractory gastric cancer and have led to US regulatory approval for pembrolizumab in chemotherapy-refractory programmed death ligand 1-positive or MSI-high gastric cancer, and approval in Japan for nivolumab in chemotherapy-refractory gastric cancer. However, a phase III trial in advanced gastric cancer failed to show a survival benefit for pembrolizumab over conventional paclitaxel. The poly ADP ribose polymerase inhibitor, olaparib, added to second-line paclitaxel in advanced gastric cancer failed to improve overall survival compared with paclitaxel alone.. Perioperative or postoperative adjuvant chemotherapy without radiation therapy remains the standard of care in gastric cancer. Addition of docetaxel to adjuvant S-1 will likely emerge as a new care standard. Pembrolizumab and nivolumab improve survival and now are treatment options in chemotherapy-refractory gastric cancer, especially for programmed death ligand 1-positive or MSI-high cancers.

Topics: Adenocarcinoma; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Docetaxel; Drug Combinations; Gastrectomy; Humans; Nivolumab; Oxonic Acid; Stomach Neoplasms; Tegafur

Apatinib-targeted therapy is considered a promising treatment option for malignancies. This study systematically evaluated the efficacy and safety of the combination of apatinib and S-1 for the treatment of patients with advanced gastric cancer (GC).. Clinical trials were searched from the PubMed, Cochrane Library, Embase, CNKI, and Wanfang databases. Outcome measures including therapeutic efficacy, quality of life (QoL), and adverse events were extracted and evaluated.. Data from 8 trials including 393 patients with advanced GC were included. The results indicated that, compared with S-1 alone, the combination of apatinib with S-1 significantly improved patient partial response rate (odds ratio [OR] = 1.91, 95% confidence interval [CI] = 1.21-3.02, P = .005), overall response rate (ORR, OR = 2.40, 95% CI = 1.51-3.82, P = .0002), and disease control rate (DCR, OR = 2.78, 95% CI = 1.51-5.10, P = .0010), whereas the rates of complete response (CR, OR = 2.38, 95% CI = 0.93-6.12, P = .07) and stable disease (SD, OR = 0.99, 95% CI = 0.64-1.54, P = .97) and QoL (OR = 1.22, 95% CI = 0.51-2.92, P = .66) did not differ significantly. Moreover, the group receiving the combined therapy had higher rates of hand-foot syndrome (OR = 2.23, 95% CI = 1.19-4.17, P = .01), hypertension (OR = 8.85, 95% CI = 4.07-19.26, P < .00001), albuminuria (OR = 11.25, 95% CI = 3.32-38.06, P = .0001), and hemoglobin reduction (OR = 3.19, 95% CI = 1.32-7.67, P = .010), whereas analysis of other adverse events did not show significant differences (P > .05).. The combination of apatinib and S-1 is more effective for GC treatment than S-1 alone. However, this combined treatment could lead to increased hand-foot syndrome, hypertension, albuminuria, and hemoglobin reduction. Therefore, the benefits and risks should be considered before treatment.

Topics: Antineoplastic Agents; China; Drug Combinations; Drug Therapy, Combination; Humans; Neoplasm Staging; Oxonic Acid; Pyridines; Randomized Controlled Trials as Topic; Stomach Neoplasms; Tegafur; Treatment Outcome

To evaluate the clinical outcomes of S-1 plus cisplatin (SC) for the treatment of patients with advanced gastric cancer (AGC).. A systematic literature search was conducted by searching PubMed, the Cochrane Library, Embase, China Biology Medicine disc (CBMdisc), China National Knowledge Infrastructure (CNKI), and WanFang Database, for all year up to January 2017. Pooled analyses of overall survival (OS), progress-free survival rates, and adverse events were performed.. A total of 8 random controlled trails (RCTs) consisting of 2699 patients with AGC were selected and included in this meta-analysis. The results of our meta-analysis showed that AGC patients who treated with SC regimen receive a similar OS (HR = 1.01, 95%CI: 0.86-1.18, P = .928), PFS (HR = 0.89, 95%CI: 0.72-1.09, P = .263), and overall response rate (HR = 0.88, 95%CI: 0.70-1.11, P = .283). However, SC regimen may increase the risk of 1 to 2 grade (OR = 1.128, 95%CI: 1.075-1.184, P = .000) and 3 to 4 grade (OR = 1.24, 95%CI: 1.01-1.52, P = .039) adverse events.. SC chemotherapy showed no difference in survival compared with 5-FU- and S-1-based other therapy, but has a higher rate of adverse events compared with other chemotherapy regimens.

Topics: Antineoplastic Agents; Cisplatin; Drug Combinations; Humans; Oxonic Acid; Randomized Controlled Trials as Topic; Stomach Neoplasms; Tegafur

We report a case of rhabdomyolysis related to S-1 plus oxaliplatin(SOX)therapy for liver metastasis of gastric cancer. A 76- year-old man who had received SOX therapy for metastatic gastric cancer was admitted to our hospital for a chief complaint of fatigue and weakness. He diagnosed with rhabdomyolysis related to SOX therapy because of his symptoms and because his laboratory studies showed significant elevation of his serum creatine kinase(CK)level. The symptoms disappeared and the CK level normalized following large-volume transfusions. Rhabdomyolysis following SOX therapy is a very rare, but severe adverse event. This is the first detailed case report of rhabdomyolysis related to SOX therapy.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Hepatectomy; Humans; Liver Neoplasms; Male; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Rhabdomyolysis; Stomach Neoplasms; Tegafur

As evidence is inconsistent and based on either isolated Asian or Western studies, we conducted a network meta-analysis (NMA) to examine efficacy and safety of 5-FU (5-fluorouracil), capecitabine and S-1-based first-line treatment of advanced esophagogastric cancer in Asian and Western patients. Medline, EMBASE, CENTRAL and conferences ASCO and ESMO were searched up to January 2016 for randomized-controlled-trials comparing 5-FU, capecitabine or S-1-based regimens with equal chemotherapy backbones. Direct and indirect data for overall survival (OS) and progression-free-survival (PFS) were combined on the Hazard Ratio (HR)-scale using random-effects NMA and calculated as combined HRs and 95%credible intervals (95%CrI). Grade 1-2 and grade 3-4 adverse events were compared with pair-wise meta-analysis. Fifteen studies were identified including capecitabine (n = 945), 5-FU (n = 2,132) or S-1 (n = 1,636). No differences were found in respectively OS and PFS for capecitabine-based versus 5-FU-based regimens (HR = 0.89, 95%CrI = 0.76-1.04 and HR = 0.98, 95%CrI = 0.75-1.32), S-1-based versus 5-FU-based regimens (HR = 0.92, 95%CrI = 0.82-1.04 and HR = 0.88, 95%CrI = 0.70-1.11) and S-1-based versus capecitabine-based regimens (HR = 1.03, 95%CrI = 0.87-1.22 and HR = 0.89, 95%CrI = 0.65-1.20). Effects were similar in Asian and Western subgroups. Toxicity profiles were different but a lower frequency of relevant adverse events was observed with S-1 In conclusion, as efficacy was similar, choosing fluoropyrimidines should be based on their individual toxicity profiles.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Drug Combinations; Esophageal Neoplasms; Female; Fluorouracil; Humans; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Proportional Hazards Models; Publication Bias; Stomach Neoplasms; Tegafur; Treatment Outcome

A 69-year-old man presented to our hospital because of epigastric pain. A type 2 lesion was seen in the lesser curvature of the antrum of the stomach. A moderately differentiated adenocarcinoma(human epidermal growth factor receptor 2-negative) was diagnosed by biopsy. Abdominal computed tomography showed a mass shadow 52mm in diameter in the pyloric region invading the surrounding organs, but no evidence of distant metastasis. Chemotherapy with S-1 and cisplatin(SP therapy)was initiated because of a diagnosis of locally advanced gastric cancer. After 2 courses of chemotherapy, the tumor shrinkage rate was 70%, confirming that treatment was effective. However, severe skin disorders developed, precluding the continuation of chemotherapy. Staging laparoscopy showed no evidence of peritoneal dissemination, but invasion into the superior mesenteric vein was noted. The tumor was resected by pancreaticoduodenectomy with partial resection of the venous wall. Pathological examination of the resected specimens provided a definite diagnosis of neuroendocrine cell carcinoma. As of 1 year and 7 months after surgery, there has been no observation of metastasis or recurrence. SP therapy was suggested to be a useful regimen for preoperative chemotherapy in patients with locally advanced neuroendocrine cell carcinoma.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Neuroendocrine; Cisplatin; Combined Modality Therapy; Drug Combinations; Humans; Male; Oxonic Acid; Stomach Neoplasms; Tegafur; Treatment Outcome

A 69-year-old man, who had undergone distal gastrectomy for duodenal ulcer, was diagnosed with remnant gastric cancer and jejunal mesenteric lymph node metastasis. To improve curability, we planned 2 courses of S-1 and cisplatin therapy. After chemotherapy, primary lesion and lymph node metastases reduced in size drastically. Completion gastrectomy and lymph node dissection were performed with curative intent. The tumor was found to have a pathological complete response(pCR) to chemotherapy on histological examination.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Gastrectomy; Humans; Lymphatic Metastasis; Male; Neoadjuvant Therapy; Oxonic Acid; Peritoneal Neoplasms; Stomach Neoplasms; Tegafur

Nearly 70% of gastric cancer recurrences occur as peritoneal dissemination. Most of the treatment for recurrence of gastric cancer dissemination is chemotherapy; depending on the symptoms and the site of recurrence, palliative bypass surgery may be performed. Intensive treatment is often difficult for elderly patients over 85-years-old. This case was a 91-year-old female who underwent total gastrectomy for gastric cancer(signet-ring cell carcinoma)7years prior. Two years ago, a stenosis due to recurrence was revealed in the small intestine and bypass surgery was performed. At that time, she was 89-years-old, and chemotherapy was continued for 1 year. Six months ago, recurrence was revealed in the esophago-jejuno anastomosis. Since the stenosis was severe, it was possible to resume oral reconstitution by inserting a metallic stent. Chemotherapy(S-1)is currently ongoing. There are few reports of long-term treatment for recurrence of gastric cancer peritoneal dissemination in elderly people over 80 years of age. This report is a case of long-term survival involving multidisciplinary treatments, which improved the quality of life(QOL)over the age of 90 years.

Topics: Aged, 80 and over; Antimetabolites, Antineoplastic; Combined Modality Therapy; Drug Combinations; Female; Gastrectomy; Humans; Intestinal Obstruction; Intestine, Small; Oxonic Acid; Peritoneal Neoplasms; Quality of Life; Recurrence; Stents; Stomach Neoplasms; Tegafur

Peritoneal invasion is more common and has a worse prognosis in gastric cancer than most of other intestinal cancers. Advanced gastric cancers have a poor course in terms of the development of peritoneal carcinomatosis and prognosis, even if the curative resection has been performed. Patients usually die within the first 2 years of the postoperative period mainly due to peritoneal metastasis. It is, therefore, essential to eradicate intraperitoneal free cancer cells to prevent peritoneal recurrences. A standard therapy has not been developed yet for patients with gastric cancer with a positive peritoneal cytology or a gross peritoneal metastasis. Curative resection following neoadjuvant chemotherapy, postoperative oral S-1 chemotherapy, intraoperative intraperitoneal chemotherapy (IPC), and extensive intraoperative peritoneal lavage (EIPL)-IPC are recommended as therapeutic approaches. Although there is a limited number of studies on EIPL, which is a promising and exciting method in this patient population, unexpected results of survival have been demonstrated. We consider that the results of ongoing and further studies would lead to an extensive use of EIPL, which is a simple and easy method which can be applied anywhere and anytime, in patients with advanced gastic cancer and/or peritoneal cytology positive but peritoneal metastasis negative (CY+/P0) gastric cancer.

Topics: Antimetabolites, Antineoplastic; Drug Combinations; Humans; Infusions, Parenteral; Intraoperative Care; Neoadjuvant Therapy; Oxonic Acid; Peritoneal Lavage; Peritoneal Neoplasms; Stomach Neoplasms; Tegafur

A 77-year-old man underwent endoscopic submucosal dissection (ESD) of a type 0-IIc tumor located in the cardiac part of the stomach. The pathological diagnosis of the tumor was poorly differentiated tubular adenocarcinoma with submucosal invasion depth;therefore, radical gastrectomy was also performed. After 1 year and 10 months, liver metastasis was detected because of which partial liver resection was performed. The pathological diagnosis of the tumor was neuroendocrine carcinoma (NEC). The pathology of the ESD specimen was re-examined, and a diagnosis of gastric NEC was made;furthermore, the liver tumor was regarded as metachronous metastasis. Despite the radical excision of the stage IA tumor, metastasis occurred. Chemotherapy with S-1 alone was successfully performed after the liver resection while considering the advanced age of the patient. Follow-up revealed no signs of recurrence at 1 year and 4 months after the treatment, indicating that the S-1 therapy may be considered for treating NEC in elderly and medically compromised patients owing to its mild side effects.

Topics: Adenocarcinoma; Aged; Antimetabolites, Antineoplastic; Carcinoma, Neuroendocrine; Chemotherapy, Adjuvant; Drug Combinations; Endoscopic Mucosal Resection; Humans; Liver Neoplasms; Magnetic Resonance Imaging; Male; Oxonic Acid; Stomach Neoplasms; Tegafur; Time Factors

The Randomized Phase III Study Comparing Oxaliplatin plus S-1 with Cisplatin plus S-1 in Chemotherapy-naïve Patients with Advanced Gastric Cancer (G-SOX) showed the noninferiority of S-1 (an oral fluoropyrimidine-derivative dihydropyrimidine dehydrogenase inhibitor) plus oxaliplatin combination therapy (SOX) to S-1 plus cisplatin therapy (CS) in overall survival [hazard ratio (HR) from proportional hazard model 0.958, 95 % confidence interval (CI) 0.803-1.142; noninferiority margin 1.15]. To further clarify the clinical position of SOX in advanced gastric cancer (AGC), a meta-analysis including information from other reported studies was conducted.. In addition to G-SOX, Japanese phase III clinical trials including S-1 monotherapy were included in the analyses. Individual patient data for SOX (318 patients) and CS (324 patients) from G-SOX, as well as those for S-1 (160 patients) from the Randomized Phase III Study Comparing the Efficacy and Safety of Irinotecan plus S-1 with S-1 Alone as First-line Treatment for Advanced Gastric Cancer (GC0301/TOP-002), were available. Published clinical information for S-1 from other studies (total 705 patients) was also collected. A Weibull distribution was assumed for overall survival time, and parameters for SOX, CS, and S-1 were estimated parametrically. Posterior HR distributions were obtained with a Bayesian approach.. The HR of SOX to S-1 was 0.817 (95 % credible interval 0.704-0.939), and the probability of the HR <1.00 was 99.8 %. The HR of CS to S-1 was 0.871 (95 % credible interval; 0.754-0.998), and the probability of the HR <1.00 was 97.6 %. The HR of SOX to CS in G-SOX was 0.942 (95 % credible interval; 0.789-1.117), and the probability of HR <1.15 was 98.9 %.. This meta-analysis indicates that SOX was superior to S-1 and noninferior to CS in AGC.

Topics: Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cisplatin; Clinical Trials, Phase III as Topic; Drug Combinations; Humans; Irinotecan; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Stomach Neoplasms; Survival Rate; Tegafur

S-1 is first-line therapy for advanced gastric cancer in Asia and is used with increased frequency in Western counties. We conducted a meta-analysis to investigate the efficacy and toxicity of S-1-based therapy compared with 5-fluorouracil (5-FU)/capecitabine-based therapy and S-1-based combination therapy compared with S-1 monotherapy.. MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, American Society of Clinical Oncology meeting abstracts, European Society for Medical Oncology meeting abstracts and ClinicalTrials.gov were searched for randomized clinical trials until May 2015. Data were extracted for overall survival (OS), progression-free-survival (PFS), objective response rate (ORR) and grade 1-2 and grade 3-4 adverse events. Stratified OS data for subgroups were extracted.. S-1 was not different from 5-FU (eight studies, n = 2788) in terms of OS [hazard ratio (HR) 0.93, 95 % confidence interval (CI) 0.85-1.01] and PFS (HR 0.87, 95 % CI 0.73-1.04), whereas ORR was higher (risk ratio 1.43, 95 % CI 1.05-1.96). There was no subgroup difference in efficacy among Asian and Western patients, but in Western patients S-1 was associated with a lower rate of febrile neutropenia, toxicity-related deaths and grade 3-4 stomatitis and mucositis compared with 5-FU. S-1 showed no difference in efficacy compared with capecitabine (three studies, n = 329), but was associated with a lower rate of grade 3-4 neutropenia and grade 1-2 hand-foot syndrome. S-1-combination therapy was superior to S-1 monotherapy (eight studies, n = 1808) in terms of OS (HR 0.76, 95 % CI 0.65-0.90), PFS (HR 0.68, 95 % CI 0.56-0.82) and ORR (risk ratio 1.20, 95 % CI 1.04-1.38) but was more toxic. Survival benefit of S-1 combination therapy over S-1 monotherapy was most pronounced in patients with non-measurable disease, diffuse-type histological features and peritoneal metastasis.. S-1 is effective and tolerable as first-line therapy for advanced gastric cancer in both Asian and Western countries.

Topics: Drug Combinations; Humans; Oxonic Acid; Safety; Stomach Neoplasms; Tegafur; Treatment Outcome

We report a case of advanced gastric cancer that responded completely to S-1 neoadjuvant chemotherapy. An 80-year-old female complained of nausea. A gastroscopy and CT scan revealed advanced gastric cancer with lymph node metastasis (cT4b [diaphragm], cN3a, cM0, cStage III C). S-1 (100 mg/body/day) was administered orally for 14 consecutive days followed by a 7-day interval. After 2 courses of monotherapy, we conducted a total gastrectomy with D2 lymph node dissection. Histological findings revealed that there were no cancer cells in either the primary tumor or the lymph nodes. This meant that the resected lesions were pathologic Grade 3. Our report suggests that S-1 may have a potent therapeutic effect as a neoadjuvant chemotherapy for advanced gastric cancer especially in older patients.

Topics: Aged, 80 and over; Antimetabolites, Antineoplastic; Drug Combinations; Female; Gastrectomy; Humans; Lymph Node Excision; Lymphatic Metastasis; Neoadjuvant Therapy; Oxonic Acid; Prognosis; Stomach Neoplasms; Tegafur

To provide an assessment by meta-analysis of the relationship between the expression variations of 5-fluorouracil metabolic enzymes and clinical outcomes in patients with gastric cancer treated with S-1.. Databases were searched electronically from inception to April 19th, 2015. Studies in gastric cancer patients treated with S-1 investigating the expression variations of 5-fluorouracil metabolic enzymes were included after having been identified systematically. Pooled odds ratios (OR) for the objective response rate (ORR) and median survival ratio were calculated using the Review Manager 5.3 and Stata 12.0 software separately.. A total of 555 patients in 10 studies met our inclusion criteria. There was a significant difference in ORR between patients with high/+ and low/- expression of orotate phosphoribosyl transferase (OPRT) (OR = 8.06; 95% CI, 4.06-16.02; p<0.001) and dihydropyrimidine dehydrogenase (DPD) (OR = 1.95; 95% CI, 1.21-3.13; p = 0.006). There was no significant difference in ORR between different expression levels of thymidylate synthase (TS) and thymidine phosphorylase (TP). Although patients with low/- TS expression, low/- TP expression and high/+ DPD expression showed a trend towards longer survival, no statistical significance was found. The median OS was significantly longer in patients with high/+ expression of OPRT (p = 0.076).. OPRT and DPD expression can be treated as a potential predictive biomarker for S-1 response in gastric cancer patients. Further investigation is warranted.

Topics: Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Drug Combinations; Fluorouracil; Humans; Orotate Phosphoribosyltransferase; Oxonic Acid; Stomach Neoplasms; Tegafur; Thymidine Phosphorylase; Thymidylate Synthase

An 80-year-old man with a local recurrence of gastric cancer was treated with S-1 monotherapy leading to a complete response(CR).The patient was diagnosed with gastric cancer and underwent a distal gastrectomy with lymph node dissection. Pathological findings showed tub2>por1, pT3 (SS), pN2, pStage III A.Five months after surgery, the patient presented with redness of the abdominal skin.Computed tomography (CT) revealed massive tumors in the abdominal cavity with invasion to the abdominal wall. He was administered S-1, 80 mg/body/day for 14 days, followed by a 7-day rest.After 2 courses of treatment, CT showed a dramatic reduction of the tumors. After 6 months, the tumor tissue completely disappeared and he had a CR.Administration of S-1 was continued for 2 years and 6 months.There was no relapse for 3 years after discontinuation.S -1 monotherapy appears to be a feasible and effective therapy for elderly patients with recurrent gastric cancer.

Topics: Aged, 80 and over; Antimetabolites, Antineoplastic; Drug Combinations; Gastrectomy; Humans; Lymphatic Metastasis; Male; Neoplasm Invasiveness; Neoplasm Staging; Oxonic Acid; Recurrence; Remission Induction; Stomach Neoplasms; Tegafur

Recently, Peritoneal Surface Oncology Group International (PSOGI) developed a novel comprehensive treatment consisting of cytoreductive surgery (CRS) and perioperative chemotherapy (POC) for the treatment of peritoneal metastases (PM) from gastric cancer with curative intent. This article reviews the results of this treatment and verifies its indication. In this strategy, peritoneal cancer index (PCI) is determined by laparoscopy, and a peritoneal port is placed. Neoadjuvant bidirectional intraperitoneal/systemic chemotherapy (NIPS) is performed for 3 cycles, and then laparotomy is performed. Cytoreductive surgery with peritonectomy procedures and hyperthermic intraperitoneal chemoperfusion (HIPEC) are performed. Multivariate analyses showed that completeness of cytoreduction, pathologic response to NIPS and PCI level and cytologic status after NIPS, as independent prognostic factors. PCI less than cut-off level after NIPS, negative cytology after NIPS, and positive response to NIPS were identified as the indications for comprehensive treatment. Patients who hold these criteria should be considered as the candidates for CRS and HIPEC.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Cytoreduction Surgical Procedures; Docetaxel; Drug Combinations; Humans; Hyperthermia, Induced; Infusions, Parenteral; Multivariate Analysis; Neoadjuvant Therapy; Oxonic Acid; Peritoneal Neoplasms; Peritoneum; Stomach Neoplasms; Taxoids; Tegafur

Fluoropyrimidine-based regimens are the most common treatments in advanced gastric cancer. We used a Bayesian network meta-analysis to identify the optimal fluoropyrimidine-based chemotherapy by comparing their relative efficacy and safety. We systematically searched databases and extracted data from randomized controlled trials, which compared fluoropyrimidine-based regimens as first-line treatment in AGC. The main outcomes were overall survival (OS), progression-free survival (PFS), overall response rate (ORR), and grade 3 or 4 adverse events (AEs). A total of 12 RCTs of 4026 patients were included in our network meta-analysis. Pooled analysis showed S-1 and capecitabine had a significant OS benefit over 5-Fu, with hazard ratios of 0.90 (95%CI = 0.81-0.99) and 0.88 (95%CI = 0.80-0.96), respectively. The result also exhibited a trend that S-1 and capecitabine prolonged PFS in contrast to 5-Fu, with hazard ratios of 0.84 (95%CI = 0.66-1.02) and 0.84 (95%CI = 0.65-1.03), respectively. Additionally, all the three fluoropyrimidine-based regimens were similar in terms of ORR and grade 3 or 4 AEs. Compared with regimens based on 5-Fu, regimens based on S-1 or capecitabine demonstrated a significant OS improvement without compromise of AEs as first-line treatment in AGC in Asian population. S-1 and capecitabine can be interchangeable according their different emphasis on AEs.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bayes Theorem; Capecitabine; Disease-Free Survival; Drug Combinations; Fluorouracil; Humans; Middle Aged; Network Meta-Analysis; Oxonic Acid; Pyruvates; Stomach Neoplasms; Tegafur

It remains to be seen whether S-1 can be a replacement for infusional fluorouracil (5-FU) for advanced gastric cancer (AGC). The aim of this study was to compare the efficacy and safety of S-1 with 5-FU in AGC.PubMed and Cochrane Library were searched. Randomized controlled trials and meta-analyses comparing S-1 with 5-FU for AGC were eligible. Meta-analysis was performed using RevMan 5.2.Seven trials involving 2443 patients were included. Compared with 5-FU, S-1 showed no significant prolongation of overall survival (OS) (hazard ratio [HR] = 0.91, 95% confidence interval [CI] [0.83-1.01], P = 0.07) and progression-free survival (HR = 0.89, 95% CI [0.70-1.13], P = 0.35), but longer time to treatment failure (HR = 0.74, 95% CI [0.56-0.97], P = 0.03). The objective response rates were comparable (risk ratio [RR] = 1.36, 95% CI [0.95, 1.96], P = 0.10). Regarding treatment-related deaths and hematological toxicities, there was significant heterogeneity between Asian and non-Asian trials, and subgroup analysis was applied. In Asian patients, there was a significant increase in hematological toxicities such as leukopenia (grade 1-4: RR = 1.22, 95% CI [1.08, 1.37], P = 0.001; grade 3-4: RR = 2.21, 95% CI [1.52, 3.21], P < 0.0001), neutropenia (grade 1-4: RR = 1.29, 95% CI [1.11, 1.48], P = 0.0005; grade 3-4: RR = 1.87, 95% CI [1.11, 3.17], P = 0.02), and thrombocytopenia (grade 1-4: RR = 1.71, 95% CI [1.22, 2.41], P = 0.002) in S-1-containing regimens compared with 5-FU-containing regimens, but without significant difference in treatment-related mortality rate (risk difference [RD] = 0.00, 95% CI [-0.01, 0.01], P = 0.68). In non-Asian patients, S-1-containing regimens were, however, associated with significantly fewer treatment-related deaths (RD = -0.02, 95% CI [-0.05, -0.00], P = 0.04), as well as less all grade 1-4 and grade 3-4 hematological toxicities except anemia. There was no significant heterogeneity in nonhematologic toxicities between Asian and non-Asian trials. Lower incidence of grade 1-4 nausea, diarrhea, mucositis, grade 3-4 mucositis, increased creatinine, and decreased calculated creatinine clearance was observed in S-1-containing regimens.S-1 could not improve OS, but increase some hematological toxicities in Asian patients. Therefore, special attention on hematological toxicities should be paid to Asian patients because S-1 is administered on an outpatient basis.

Topics: Antimetabolites, Antineoplastic; Drug Combinations; Fluorouracil; Humans; Neoplasm Staging; Oxonic Acid; Prognosis; Stomach Neoplasms; Tegafur

A globally accepted standard first-line chemotherapy regimen in advanced esophagogastric cancer (AEGC) is not clearly established. We conducted a systematic review to investigate the efficacy and safety of first-line chemotherapy using Network meta-analysis (NMA).. Medline, EMBASE, CENTRAL, and conferences were searched until June 2015 for randomized controlled trials that compared regimens containing: fluoropyrimidine (F), platinum (cisplatin [C] and oxaliplatin [Ox]), taxane (T), anthracycline (A), irinotecan (I), or methotrexate (M). Direct and indirect evidence for overall survival (OS) and progression-free-survival (PFS) were combined using random-effects NMA on the hazard ratio (HR) scale and calculated as combined hazard ratios and 95% credible intervals (CrIs).. The NMA incorporated 17 chemotherapy regimens with 37 direct comparisons between regimens for OS (50 studies, n = 10 249) and 29 direct comparisons for PFS (34 studies, n = 7795). Combining direct and indirect effects showed increased efficacy for fluoropyrimidine noncisplatin doublets (F-doublets) over cisplatin doublets (C-doublets): FI vs CF (combined HR = 0.85, 95% CrI = 0.71 to 0.99), FOx vs CF (combined HR = 0.83, 95% CrI = 0.71 to 0.98) in OS and FOx vs CF (combined HR = 0.82, 95% CrI = 0.66 to 0.99) in PFS. Anthracycline-containing triplets (A-triplets: ACF, AFOx, AFM) and TCF triplet showed no benefit over F-doublets in OS and PFS. The triplet FOxT showed increased PFS vs F-doublets FT (combined HR = 0.61, 95% CrI = 0.38 to 0.99), FI (combined HR = 0.62, 95% CrI = 0.38 to 0.99), and FOx (combined HR = 0.67, 95% CrI = 0.44 to 0.99). Increased grade 3 to 4 toxicity was found for CF vs F-doublets, for ACF vs FI for TCF vs CF, and for FOxT vs FOx.. Based on efficacy and toxicity, F-doublets FOx, FI, and FT are preferred as first-line treatment for AEGC compared with C-doublets, A-triplets, and TCF. FOxT is the most promising triplet.

Topics: Anthracyclines; Antineoplastic Combined Chemotherapy Protocols; Bridged-Ring Compounds; Camptothecin; Capecitabine; Cisplatin; Disease-Free Survival; Drug Combinations; Esophageal Neoplasms; Esophagogastric Junction; Fluorouracil; Humans; Irinotecan; Methotrexate; Network Meta-Analysis; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Randomized Controlled Trials as Topic; Stomach Neoplasms; Survival Rate; Taxoids; Tegafur

The present study was conducted to establish pharmaceutical intervention guidelines to enable hospital pharmacists to provide optimal pharmacotherapy to cancer patients. Many patients who use oral anticancer agents showed favorable drug compliance but insufficient drug adherence. It was demonstrated that in order to improve drug adherence, it is important to conduct interventions tailored to the patients' conditions so as to encourage interest in their medications, as well as to gain their understanding on the necessity and the side effects of their medications. In adjuvant chemotherapy with tegafur/gimeracil/oteracil potassium (S-1) following surgery for stomach cancer, a serum albumin value <3.5 g/dL and a creatinine clearance value <80 mL/min were found to significantly affect S-1 dose reduction or termination of the S-1 intake due to side effects. Furthermore, patients for whom treatment was discontinued or dosage was reduced demonstrated a large reduction in body mass index. When adding insulin to an at-home high-calorie infusion, the insulin retention rate decreased when the number of grams of sugar level per 1 g of sodium bisulfite in the infusion (G/g) was ≤364.6, whereas the insulin retention rate did not decrease when G/g was ≤466.0. Our findings in the present study can serve as highly useful guidelines when pharmacists working in clinical settings conduct pharmaceutical interventions in pharmacotherapy for cancer.

Topics: Administration, Oral; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Drug Combinations; Humans; Insulin; Oxonic Acid; Parenteral Nutrition, Total; Patient Compliance; Practice Guidelines as Topic; Stomach Neoplasms; Sulfates; Tegafur; Terminal Care

A 70-year-old man with cStage III A(cT3N2H0P0CYXM0)advanced gastric cancer in the lesser curvature with esophageal invasion and bulky lymph nodes was treated with S-1/CDDP. After 4 courses of chemotherapy, the tumor and lymph nodes were found to be reduced in a CT examination. Total gastrectomy with lymph node dissection(D2)was performed. Histopathological examination revealed no cancer cells in the stomach or lymph nodes, indicating Grade 3.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Gastrectomy; Humans; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Male; Neoadjuvant Therapy; Neoplasm Grading; Oxonic Acid; Stomach Neoplasms; Tegafur

A 63-year-old man with epigastralgia was referred to our hospital and diagnosed with simultaneous multiple gastric cancers. One lesion was type 2 advanced and the other was type 0- II c early gastric cancer. CT examination revealed 4 regional lymph node metastases. Neoadjuvant chemotherapy(NAC)with docetaxel/CDDP/S-1was administered. After 2 courses of NAC, total gastrectomy with D2(-No. 10), lymphadenectomy was performed. The pathological response to NAC was judged to be Grade 3 for advanced gastric cancer and Grade 0 for early gastric cancer. The patient is alive with no evidence of disease during the 10 months after the operation.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Docetaxel; Drug Combinations; Humans; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neoadjuvant Therapy; Oxonic Acid; Stomach Neoplasms; Taxoids; Tegafur

Gastric cancer patients with positive peritoneal cytology as the only marker of metastatic disease have poor prognoses. There is no universal consensus on the most appropriate treatment regimen for this particular patient group. We reviewed and analyzed published data to determine the optimal treatment regimen for patients with peritoneal cytology-positive gastric adenocarcinomas. Six electronic databases were explored [PubMed, Cochrane (Systematic Reviews and Controlled Trials), PROSPERO, DARE, and EMBASE]. The primary outcome was overall survival with secondary outcomes including patterns of recurrence and treatment-related morbidity. Six studies were included for data extraction. There was no significant heterogeneity between studies. The use of S1 monotherapy was associated with a significant survival benefit (HR 0.48; 95% CI 0.32-0.70; p = 0.0002). Intraoperative intraperitoneal chemotherapy (IIPC) with adjuvant chemotherapy showed a trend toward improvement in overall survival (HR 0.70; 9 % CI 0.47-1.04; p = 0.08). A recent randomized controlled trial examining extensive intraperitoneal lavage (EIPL) with IIPC showed a significant improvement in overall survival (5-year overall survival, 43.8% for EIPL-IPC group compared with 4.6% for IPC group). However, these promising results need to be validated in larger prospective randomized trials.

Topics: Administration, Oral; Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Humans; Intraoperative Period; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Oxonic Acid; Peritoneal Lavage; Stomach Neoplasms; Tegafur; Treatment Outcome

Dissection of the para-aortic lymph nodes (PAN) had once been enthusiastically explored at dedicated centers throughout Japan. Reflecting the results of a randomized trial, however, the current standard surgery for advanced resectable gastric cancer does not include systematic dissection of the PAN. Gastric cancer with PAN metastases, currently considered distant metastases, is classified as Stage IV, and according to the algorithm of the Japanese guidelines, is not indicated for surgery with curative intent. Historical data indicates, however, that a certain proportion of long-term survivors can be introduced among patients with PAN metastasis through D2 + PAN dissection. The Japan Clinical Oncology Group launched a series of phase II trials exploring a strategy employing neoadjuvant chemotherapy followed by D2 + PAN dissection for patients radiologically diagnosed to harbor metastases to the PAN. The campaign was successful, with 57% of these patients surviving for 5 years after two cycles of neoadjuvant S-1/CDDP followed by surgery. This strategy is now the tentative standard, mentioned in the 4th version of the Japanese Gastric Cancer Treatment Guidelines as one of the current clinical questions, and could be replaced by a more powerful combination chemotherapy or treatment employing more or longer cycles of chemotherapy in the future. The relevance of the strategy consisting of neoadjuvant chemotherapy followed by D2 + PAN dissection and its fundamental difference from the concept of conversion therapy are discussed herein with reference to the literature.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Aorta; Cisplatin; Combined Modality Therapy; Drug Combinations; Gastrectomy; Humans; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Neoadjuvant Therapy; Oxonic Acid; Stomach Neoplasms; Tegafur

A 66-year-old man with cStage III B (cT4aN2H0P0M0) advanced gastric cancer in the cardia with esophageal invasion was treated with S-1/CDDP as neoadjuvant chemotherapy. After 3 courses of chemotherapy, a significant reduction in tumor burden was observed. Total gastrectomy and splenectomy with lymph node dissection (D2) were performed. Pathological specimens showed no cancer cells in the stomach and lymph nodes, indicating a pathological complete response.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Humans; Lymphatic Metastasis; Male; Neoadjuvant Therapy; Neoplasm Staging; Oxonic Acid; Stomach Neoplasms; Tegafur

A 64-year-old man with type 3 advanced gastric cancer was referred to our hospital. Abdominal computed tomography (CT)showed thickening of the gastric wall and lymph node metastasis near the stomach, and laparoscopy revealed peritoneal dissemination. After 6 courses of CDDP therapy, lymph node metastasis was no longer detectable on CT scans. A second laparoscopy showed no peritoneal dissemination; therefore, distal partial gastrectomy with D2 lymph node dissection was performed. Histological examination showed no tumor cells in the gastric primary lesion, no metastatic lymph nodes, and no disseminated peritoneal nodules, suggesting pathological complete remission.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Humans; Male; Middle Aged; Neoadjuvant Therapy; Oxonic Acid; Peritoneal Neoplasms; Stomach Neoplasms; Tegafur

Conducting clinical trials to establish evidence of the benefits of adjuvant treatment for resectable esophagogastric junction (EGJ) cancer is difficult because it is a very rare disease compared with gastric or esophageal cancer. In the West, where esophageal cancer occurs more frequently than gastric cancer, a phase III trial (the CROSS trial) demonstrated the efficacy of preoperative chemoradiotherapy using carboplatin plus paclitaxel for patients with esophageal or EGJ cancer. Thus, this preoperative regimen is considered to be the standard adjuvant treatment for resectable EGJ cancer in the West. On the other hand, the Western evidence is not widely accepted in Asia because there are many differences in surgical techniques, particularly in the field of lymph node dissection, between the West and Asia. The standard adjuvant treatment for resectable EGJ cancer in Asia is postoperative chemotherapy using S-1 alone or capecitabine plus oxaliplatin based on the results of two large-scale phase III trials in gastric cancer conducted in East Asia. The incidence of EGJ cancer has recently increased in Japan, and nationwide studies to develop more effective adjuvant treatment for resectable EGJ cancer should be conducted in the near future.

Topics: Antineoplastic Combined Chemotherapy Protocols; Asia; Capecitabine; Carboplatin; Chemoradiotherapy, Adjuvant; Chemotherapy, Adjuvant; Cisplatin; Clinical Trials as Topic; Deoxycytidine; Digestive System Surgical Procedures; Docetaxel; Drug Combinations; Esophageal Neoplasms; Esophagogastric Junction; Europe; Fluorouracil; Humans; Lymph Node Excision; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Paclitaxel; Stomach Neoplasms; Taxoids; Tegafur

To rationally evaluate the effect of S-1 vs capecitabine for the treatment of gastric cancer.. MEDLINE, EMBASE, Cochrane Controlled Trials Register, Google Scholar, and China Journal Full Text Database were accessed to collect clinical randomized controlled trials regarding the effect of S-1 vs capecitabine for the treatment of gastric cancer patients. Statistical analysis was performed by meta-analysis. Four randomized controlled trials met the inclusion criteria.. Compared with capecitabine regimens, the 1-year survival rate in gastric cancer patients was 0.80 (95%CI: 0.52-1.21, P = 0.29). The overall response rate of S-1 vs capecitabine was 0.94 (95%CI: 0.59-1.51, P = 0.93). Compared with capecitabine regimens, the most frequent hematologic toxicities were neutropenia (OR = 0.99, 95%CI: 0.65-1.49, P = 0.94) and thrombocytopenia (OR = 0.72, 95%CI: 0.31-1.67, P = 0.44). The most frequent non-hematologic toxicities included nausea (OR = 0.85, 95%CI: 0.56-1.28, P = 0.43) and hand-foot syndrome (OR = 0.16, 95%CI: 0.10-0.27, P < 0.00001).. The existing studies suggest that S-1 is not more effective than capecitabine in the treatment of gastric cancer patients, but does exhibit less toxicity with regard to hand-foot syndrome.

Topics: Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Chi-Square Distribution; Drug Combinations; Hand-Foot Syndrome; Humans; Odds Ratio; Oxonic Acid; Risk Factors; Stomach Neoplasms; Survival Analysis; Survival Rate; Tegafur; Time Factors; Treatment Outcome

The aim of this study was to compare the efficacy and safety of S-1-based therapy versus non-S-1-based therapy in advanced gastric cancer (AGC) patients.Eligible studies stratifying objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs) in AGC patients were identified from Embase, Pubmed, Cochrane Library, and China National Knowledge Infrastructure databases. The STATA package (version 11.0) was used to pool the data from the eligible studies.Fifteen studies with 2973 AGC cases, of which 1497 (50.4%) received S-1-based therapy and 1476 (49.6%) received non-S-1-based therapy, were identified in the meta-analysis. AGC patients who had received S-1-based therapy had a higher median OS, median PFS, and ORR than those who had received 5-fluorouracil (FU)-based therapy (OS: hazard ratio [HR] 0.89, 95% confidence interval [CI] 0.80-0.98, P = 0.015; PFS: HR 0.88, 95% CI 0.80-0.98, P = 0.016; ORR: OR 1.25, 95% CI 1.08-1.45, P = 0.003, respectively). S-1-based therapy had similar efficacy to capecitabine-based therapy in terms of median OS (HR 1.14, 95% CI 0.91-1.41, P = 0.253), median PFS (HR 1.01, 95% CI 0.82-1.25, P = 0.927), and ORR (OR 0.84, 95% CI 0.63-1.12, P = 0.226). Subgroup analysis for grade 3 to 4 toxicity showed higher incidence of neutropenia (relative risk [RR] = 0.827, P = 0.006), nausea (RR = 0.808, P = 0.040), and lower diarrhea (RR = 1.716, P = 0.012) in 5-FU-based arm, and higher diarrhea (RR = 0.386, P = 0.007) in capecitabine-based arm.S-1-based chemotherapy is favorable to AGC patients with better clinical benefit than 5-FU-based chemotherapy and with equivalent antitumor compare with capecitabine-based therapy.

Topics: Capecitabine; China; Clinical Trials as Topic; Deoxycytidine; Disease-Free Survival; Drug Combinations; Female; Fluorouracil; Humans; Male; Oxonic Acid; Severity of Illness Index; Stomach Neoplasms; Tegafur

There are presented results of recently published large multicenter randomized trials on the effectiveness of different adjuvant therapy regimens after gastrectomy D2 in patients with gastric cancer. It is shown that adjuvant chemotherapy as monotherapy by drug S-1 and polychemotherapy by XELOX improves long-term outcomes of patients with stages 2-3. At the same time the intensification of therapy--additional administration of paclitaxel, the combination FOLFIRI scheme with docetaxel and cisplatin--have not led to a significant increase in survival rate. In regard of the advisability of combination of adjuvant chemotherapy and radiotherapy. The data obtained do not allow to make a define conclusion up to date. Promising areas of research is the use of targeted drugs in adjuvant regimen as well as the search for biomarkers to identify patients at high risk of recurrence and to predict the effectiveness of adjuvant therapy.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Camptothecin; Capecitabine; Chemotherapy, Adjuvant; Cisplatin; Deoxycytidine; Docetaxel; Drug Combinations; Fluorouracil; Gastrectomy; Humans; Leucovorin; Lymph Node Excision; Multicenter Studies as Topic; Oxaloacetates; Oxonic Acid; Paclitaxel; Radiotherapy, Adjuvant; Randomized Controlled Trials as Topic; Stomach Neoplasms; Survival Analysis; Survival Rate; Taxoids; Tegafur; Treatment Outcome

A 61-year-old man was referred to our hospital because of epigastric pain. Upper gastrointestinal endoscopy revealed a type 2 tumor at the gastric antrum, which was diagnosed as gastric adenocarcinoma (tub1) by pathological examination and was HER2 positive 3+ by the IHC method. Abdominal computed tomography revealed multiple metastases to regional lymph nodes (LNs), including bulky nodes at No. 3, 6, and 11p stations. In particular, No. 6 LN was 43 mm in diameter and had invaded to the pancreas. The clinical stage was Ⅲc (T4aN3M0) and neoadjuvant chemotherapy was conducted using S-1/CDDP/trastuzumab. After 2 cycles of chemotherapy, a partial clinical response was obtained and distal gastrectomy with LN dissection (D2 plus No. 16 LN) was performed. The pathological specimens showed no residual cancer cells in the stomach and LNs (Grade 3: pCR). Adjuvant chemotherapy was not administered. The patient is alive 10 months after the surgery with no evidence of recurrence.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Gastrectomy; Humans; Lymphatic Metastasis; Male; Middle Aged; Neoadjuvant Therapy; Oxonic Acid; Receptor, ErbB-2; Stomach Neoplasms; Tegafur; Trastuzumab; Treatment Outcome

An 80-year-old man with type 4 gastric cancer in the mid-gastric region underwent total gastrectomy and D2-No.10 lymph-node dissection (cT4a, N0, M0, cStageⅡB). Several nodules were detected under the left diaphragm, some of which were biopsied. Pathological findings indicated a poorly differentiated adenocarcinoma, pT4a (SE), pN3b, pM1 (P1, CY1), pStage Ⅳ. Systemic chemotherapy was initiated, using a regimen of S-1/docetaxel (DOC). After 6 courses of combination therapy, we switched to S-1 alone, which was continued for 1 year. Eighteen months after the surgery the patient discontinued S-1 treatment and has since survived for 5 years with no obvious cancer recurrence.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Docetaxel; Drug Combinations; Gastrectomy; Humans; Lymph Node Excision; Male; Oxonic Acid; Peritoneal Neoplasms; Stomach Neoplasms; Taxoids; Tegafur; Treatment Outcome

A 78-year-old man with advanced gastric cancer was treated with S-1 and oxaliplatin chemotherapy. He developed hiccups and nausea, and was diagnosed with hyponatremia (serum Na: 120 mEq/L) on day 6 of the first treatment course. Because of his increased urinary Na excretion and relatively high ADH values, he was subsequently diagnosed with chemotherapy-induced syndrome of inappropriate secretion of antidiuretic hormone. The patient recovered after an infusion of hypertonic saline. Although S-1 was restarted, hyponatremia did not recur. We suspected adverse drug reactions to ACE inhibitors and K-sparing diuretics in our case of hyponatremia.

Topics: Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Biopsy; Drug Combinations; Humans; Inappropriate ADH Syndrome; Male; Oxonic Acid; Stomach Neoplasms; Tegafur

Two randomized phase III trials of first-line chemotherapy for advanced gastric cancer (JCOG9205 and JCOG9912) conducted by the Japan Clinical Oncology Group used 5-fluorouracil continuous infusion (5-FUci) as the control arm. New active agents (e.g., S-1, irinotecan, and taxanes) were introduced as second-line chemotherapy in the late 1990s after JCOG9205. This combined analysis evaluated whether patients in the 5-FUci arm of JCOG9912 exhibited better survival after adjusting for baseline factors and also investigated the cause of survival prolongation.. The subjects were patients assigned to the 5-FUci arms who met the eligibility criteria of both JCOG9205 and JCOG9912. Overall survival (OS), time to treatment failure (TTF), and survival after treatment failure in the first-line chemotherapy (OS-TTF) were compared after adjusting baseline characteristics using the Cox proportional hazard model. Second-line chemotherapy details were also reviewed.. The combined analysis included 89 and 230 patients in JCOG9205 and JCOG9912, respectively. After adjusting baseline characteristics, TTF was similar between groups (HR 0.95; 95 % CI, 0.73-1.26). However, both OS (HR, 0.74; 95 % CI, 0.56-0.99) and OS-TTF (HR, 0.76; 95 % CI, 0.57-1.01) were longer in JCOG9912. More patients in JCOG9912 received second-line chemotherapy (83 vs. 52 %) with new drugs (77 vs. 10 %) than in JCOG9205. OS-TTF was substantially prolonged in patients who received second-line chemotherapy (HR, 0.66; 95 % CI, 0.46-0.95).. OS and OS-TTF were longer in JCOG9912 than JCOG9205. Second-line chemotherapy with new drugs is a potential reason for the observed prolongation of survival.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Clinical Trials, Phase III as Topic; Drug Combinations; Female; Fluorouracil; Humans; Infusions, Intravenous; Irinotecan; Male; Middle Aged; Oxonic Acid; Randomized Controlled Trials as Topic; Stomach Neoplasms; Survival Rate; Tegafur; Time Factors; Treatment Failure; Treatment Outcome; Young Adult

This study aimed to derive a more precise estimate of the prognostic significance of S-1-based therapy over S-1 monotherapy in patients with advanced gastric cancer (AGC), including overall survival (OS) time, progression-free survival (PFS) time, objective response rate (ORR), and adverse events (AEs). Studies stratifying OS, PFS, ORR, and AEs in AGC patients in an S-1-based therapy versus an S-1 monotherapy setting were eligible for analysis by systematic computerized PubMed, Embase and Cochrane Library searches. Data from these studies were pooled using STATA package version 11.0. Six studies that investigated outcomes in a total of 913 AGC cases, of which 443 (48.5%) received S-1-based therapy and 470 (51.5%) received S-1 monotherapy, were included in the meta-analysis. Median OS and median PFS were significantly prolonged in AGC patients receiving S-1-based therapy compared with those receiving S-1 monotherapy (hazard ratio [HR] 0.83, 95% confidence interval [CI] 0.71-0.96, P = 0.015, and HR 0.69, 95% CI 0.60-0.80, P = 0.000, respectively). The ORR favored patients with S-1-based therapy (OR 1.65, 95% CI 1.34-2.06, P = 0.000). Higher incidence of grade 3/4 neutropenia was found in patients with S-1-based therapy (P = 0.000). For the Asian population, S-1-based therapy significantly improved OS and PFS and enhanced ORR in comparison to S-1 monotherapy. The safety profile was poorer in patients with S-1-based therapy, but could be considerable between the S-1-based therapy and S-1 monotherapy group. Our conclusion needs to be confirmed via high-quality trials and the results need to be reproduced in other regions and populations.

Topics: Antineoplastic Combined Chemotherapy Protocols; Disease-Free Survival; Drug Combinations; Humans; Oxonic Acid; Stomach Neoplasms; Tegafur

To assess the efficacy and safety of combination therapy based on S-1, a novel oral fluoropyrimidine, vs S-1 monotherapy in advanced gastric cancer (AGC).. We searched PubMed, EMBASE and the Cochrane Library for eligible studies published before March 2013. Our analysis identified four randomized controlled trials involving 790 participants with AGC. The outcome measures were overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and grade 3-4 adverse events.. Meta-analysis showed that S-1-based combination therapy significantly improved OS (HR = 0.77, 95%CI: 0.66-0.91, P = 0.002), PFS (HR = 0.58, 95%CI: 0.46-0.72, P = 0.000) and ORR (OR = 2.23, 95%CI: 1.54-3.21, P = 0.000). Sensitivity analysis further confirmed this association. Lower incidence of grade 3-4 leucopenia (OR = 4.06, 95%CI: 2.11-7.81), neutropenia (OR = 3.94, 95%CI: 2.1-7.81) and diarrhea (OR = 2.41, 95%CI: 1.31-4.44) was observed in patients with S-1 monotherapy.. S-1-based combination therapy is superior to S-1 monotherapy in terms of OS, PFS and ORR. S-1 monotherapy is associated with less toxicity.

Topics: Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Disease Progression; Disease-Free Survival; Drug Combinations; Humans; Odds Ratio; Oxonic Acid; Risk Factors; Stomach Neoplasms; Tegafur; Time Factors; Treatment Outcome

A 66 -year-old man presenting with a chief complaint of upper abdominal pain was diagnosed as having an advanced adenocarcinoma, type 2, of the lower third of the stomach after endoscopy was performed. An abdominal computed tomography( CT)scan revealed 4 lymph node metastases at the infrapyloric nodes(station No. 6)and the nodes around the proximal splenic artery(station No. 11p)and the abdominal aorta(station No. 16a2). The clinical stage was determined to be T3(SS)N2M1(LYM), Stage IV. Gastrectomy with D2 plus para-aortic node dissection was scheduled after 2 courses of S-1 plus cisplatin(CDDP)with curative intent. On day 14 after starting S-1 therapy, the patient complained of severe abdominal pain and peritoneal irritation of acute onset. Because the abdominal CT scan showed a large amount of intra-abdominal free air, we performed an urgent laparotomy with a tentative diagnosis of perforation of the gastric cancer. On laparotomy, we found a perforated malignant ulcer, 5 cm in maximum diameter, in the lesser curvature of the stomach; therefore, distal gastrectomy with D1 plus lymphadenectomy and reconstruction using the Roux-en-Y method were performed. At the end of the surgery, a macroscopic residual tumor remained in the para-aortic lymph node. The postoperative course was uneventful, and the patient was discharged on day 23 after surgery. In the present case, despite the performance of urgent gastrectomy while the patient was receiving strong chemotherapy, perioperative management was successful, with no serious postoperative complication or adverse events as a result of the chemotherapy.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cisplatin; Drug Combinations; Gastrectomy; Humans; Lymph Node Excision; Lymphatic Metastasis; Male; Oxonic Acid; Stomach Neoplasms; Tegafur

An asymptomatic 56-year-old woman, upon medical examination, was diagnosed with advanced adenocarcinoma of the upper third of the stomach. Computed tomography showed that the primary gastric tumor was directly invading the splenic hilum, and there were multiple metastases in the spleen; incurable gastric cancer was confirmed. S-1 plus cisplatin therapy was introduced as the induction regimen, and the main tumor and splenic metastases reduced significantly. Total gastrectomy with splenectomy and D2 lymphadenectomy was performed after 9 courses of chemotherapy. The surgery was completed with no residual tumor, and intraperitoneal washing cytology was negative. Histologically, the primary tumor was classified as Grade 2, reflecting the effect of chemotherapy, and viable metastatic tumors were confirmed in the spleen. S-1-based treatment was continued as adjuvant chemotherapy, and the patient was alive with no evidence of tumor recurrence 39 months after the initiation of chemotherapy. Although metastasis to the spleen from gastric adenocarcinoma has been reported as a rare metastatic pattern with poor prognosis, our patient had a long survival time after gastrectomy following induction chemotherapy.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Female; Gastrectomy; Humans; Induction Chemotherapy; Lymph Node Excision; Lymphatic Metastasis; Middle Aged; Oxonic Acid; Splenic Neoplasms; Stomach Neoplasms; Tegafur

A 79-year-old man presented with a history of vomiting. Laboratory data indicated leukocytosis (26360/μl), and elevated granulocyte-colony stimulating factor (G-CSF) level (155 pg/ml). Upper gastrointestinal endoscopy revealed a type 3 gastric cancer, and subsequent G-CSF immunohistochemical staining of a biopsy specimen was positive. He was therefore diagnosed with a G-CSF-producing gastric cancer. Computed tomography revealed multiple liver metastases. Chemotherapy was initiated, resulting in a partial response for 5 months. G-CSF-producing gastric cancer is rare; thus, we take this opportunity to report our case and to summarize the G-CSF-producing gastric cancer cases reported in Japan.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cisplatin; Drug Combinations; Fatal Outcome; Gastroscopy; Granulocyte Colony-Stimulating Factor; Humans; Irinotecan; Liver Neoplasms; Male; Oxonic Acid; Stomach Neoplasms; Tegafur; Tomography, X-Ray Computed

To compare the efficacy, prognosis, and toxicity of S-1-based with fluorouracil (5-FU)-based chemotherapy in patients with advanced gastric cancer (AGC) as first-line treatment, we performed this meta-analysis of all eligible randomized controlled trials (RCTs). A comprehensive literature search of electronic databases (up to February 20, 2014) was performed. Additionally, abstracts presented at the American Society of Clinical Oncology (ASCO) conferences held between January 2000 and February 2014 were searched to identify relevant trials. Overall response rate (ORR), time to treatment failure (TTF), overall survival (OS), and grade 3 or 4 toxicities were analyzed. Six RCTs with 2,264 patients of AGC were included. Meta-analysis demonstrated that S-1-based therapy was associated with better OS compared with 5-FU-based therapy (hazard ratio (HR) = 0.80, 95 % confidence interval (CI) 0.80-0.99, P = 0.03). Pooled estimate has showed the trend of superiority of S-1-based therapy in the aspect of ORR (odds ratio (OR) = 1.55, 95 % CI 0.87-2.77, P = 0.14) and TTF (HR = 0.73, 95 % CI 0.53-1.00, P = 0.05), but the difference was not significant. The incidence of toxicities of 5-FU-based regimens was significantly higher for thrombocytopenia (OR = 0.60, 95 % CI 0.42-0.88, P = 0.008) and stomatitis (OR = 0.22, 0, 95 % CI 0.05-0.9, P = 0.03). Based on the published studies, S-1-based therapy was superior to 5-FU-based therapy in OS and safety profile as first-line treatment in AGC. It was prone to improving ORR and TTF, though the difference was not significant. More high-quality randomized controlled trials should be performed to provide more information in comparing these two regimens.

Topics: Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Fluorouracil; Humans; Oxonic Acid; Publication Bias; Randomized Controlled Trials as Topic; Stomach Neoplasms; Tegafur; Treatment Failure

Gastric cancer (GC) is often diagnosed at later stages due to the lack of specificity of symptoms associated with the neoplasm, causing high mortality rates worldwide. The first line of adjuvant and neoadjuvant treatment includes cytotoxic fluoropyrimidines and platin-containing compounds which cause the formation of DNA adducts. The clinical outcome with these antineoplastic agents depends mainly on tumor sensitivity, which is conditioned by the expression level of the drug targets and the DNA-repair system enzymes. In addition, some germ line polymorphisms, in genes linked to drug metabolism and response to chemotherapy, have been associated with poor responses and the development of adverse effects, even with fatal outcomes in GC patients. The identification of genomic biomarkers, such as individual gene polymorphisms or differential expression patterns of specific genes, in a patient-by-patient context with potential clinical application is the main focus of current pharmacogenomic research, which aims at developing a rational and personalized therapy (i.e., a therapy that ensures maximum efficacy with no predictable side effects). However, because of the future application of genomic technologies in the clinical setting, it is necessary to establish the prognostic value of these genomic biomarkers with genotype-phenotype association studies and to evaluate their prevalence in the population under treatment. These issues are important for their cost-effectiveness evaluation, which determines the feasibility of using these medical genomic research products for GC treatment in the clinical setting.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Biological Transport; Biomarkers; Biotransformation; Capecitabine; Combined Modality Therapy; Deoxycytidine; Drug Combinations; Drug Resistance, Neoplasm; Enzymes; Ethnicity; Fluorouracil; Gastrectomy; Humans; Mexico; Molecular Targeted Therapy; Organoplatinum Compounds; Oxonic Acid; Patient Selection; Pharmacogenetics; Precision Medicine; Prodrugs; Stomach Neoplasms; Tegafur

An 80-year-old man was diagnosed with advanced gastric cancer and underwent distal gastrectomy. Although the pathological Stage of the cancer was III A, he refused adjuvant chemotherapy. One year later, CT revealed multiple liver metastases. Therefore, he was started with S-1 administration and a complete response was obtained at 10 months after starting S-1 administration. He has maintained a complete response for 22 months after S-1 discontinuation.

Topics: Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Gastrectomy; Humans; Liver Neoplasms; Male; Oxonic Acid; Remission Induction; Stomach Neoplasms; Tegafur; Time Factors

To assess the efficacy and tolerability of S-1-based vs non-S-1-based chemotherapy in advanced gastric cancer (AGC).. We extracted reported endpoints, including overall survival (OS), progression-free survival (PFS), time-to-treatment failure (TTF), objective response rate (ORR) and adverse effects, from randomized controlled trials identified in PubMed, the Cochrane library, Science Direct, EMBASE and American Society of Clinical Oncology meetings. Stata software was used to calculate the pooled values.. Seven randomized controlled trials involving 2176 patients were included in this meta-analysis. Compared to non-S-1-based regimens, the use of S-1-based regimens were associated with an increase in ORR (RR = 1.300; 95%CI: 1.028-1.645); OS (HR = 0.89; 95%CI: 0.81-0.99; P = 0.025), TTF (HR = 0.83; 95%CI: 0.75-0.92; P = 0.000), and a lower risk of febrile neutropenia (RR = 0.225; P = 0.000) and stomatitis (RR = 0.230; P = 0.032). OS, PFS and TTF were prolonged, especially in the Asian population. In subgroup analysis, statistically significant increases in ORR (RR = 1.454; P = 0.029), OS (HR = 0.895; P = 0.041) and TTF (HR = 0.832; P = 0.000) were found when S-1-based chemotherapy was compared to 5-fluorouracil (5-FU)-based chemotherapy. The incidence of leukopenia (RR = 0.584; P = 0.002) and stomatitis (RR = 0.230; P = 0.032) was higher in the 5-FU-based arm. S-1-based regimens had no advantage in ORR, OS, PFS, TTF and grade 3 or 4 adverse events over capecitabine-based regimens.. S-1-based chemotherapy may be a good choice for AGC because of longer survival times, better tolerance and more convenient use.

Topics: Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Chi-Square Distribution; Disease Progression; Disease-Free Survival; Drug Combinations; Humans; Oxonic Acid; Risk Factors; Stomach Neoplasms; Survival Analysis; Tegafur; Time Factors; Treatment Outcome

A 60-year-old man was diagnosed with advanced gastric cancer(Type 3)with multiple liver and lymph node metastases. The clinical stage was determined to be T3(SS), N2, M1, P0, H1, Stage IV, and a chemotherapy regimen of S-1 plus cisplatin (CDDP)was selected for treatment. During 3 courses of chemotherapy, the patient complained of severe abdominal pain, and an urgent laparotomy was performed with a tentative diagnosis of perforated gastric cancer. Surgical findings revealed a 5-mm perforation in the upper part of the anterior wall of the stomach, from the center of the tumor. Although we detected a metastasis only in S6 of the liver, we decided to perform total gastrectomy, D1 lymphadenectomy, and Roux-en-Y reconstruction. Pathological findings demonstrated that cancer cells were replaced by fibrosis, and tumor response after treatment was determined to be Grade 2. No lymph node metastasis was observed. The patient received chemotherapy with S-1 4 weeks after the operation, without any perioperative complications. The patient is alive 12 months after the operation, without any enlargement of the liver metastasis.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Humans; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Stomach Neoplasms; Stomach Rupture; Tegafur

A 67-year-old woman presented with anemia. Computed tomography and upper gastrointestinal endoscopy revealed a primary gastric cancer with tumor embolus in the portal vein, liver metastasis, lymph node metastasis, and pancreatic involvement. Because curative surgery was deemed impossible, we started chemotherapy using S-1 (120 mg/m(2)/day for 3 weeks, followed by discontinuation for 2 weeks) plus cisplatin (80 mg/m(2)/day on days 1 and 8). After 4 courses of chemotherapy, the tumor embolus in the portal vein, liver metastasis, lymph node metastasis, and pancreatic involvement had resolved. Therefore, we performed distal gastrectomy. Histological examination revealed ypT1a, ly0, v0, ypN0 (0/49), ypCY0, ypStage IA, with a two-grade histological change in the main tumor after chemotherapy. Postoperatively, she underwent adjuvant chemotherapy with S-1 for 1 year (120 mg/m(2)/day for 4 weeks, followed by discontinuation for 2 weeks). At the 30-month follow-up after the adjuvant chemotherapy, she had no recurrence.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Female; Gastrectomy; Humans; Liver Neoplasms; Neoadjuvant Therapy; Neoplastic Cells, Circulating; Oxonic Acid; Portal Vein; Stomach Neoplasms; Tegafur

The standard treatment for patients with advanced gastric cancer (AGC) is still a matter of debate. The chemotherapy regimen of paclitaxel (PTX) combined with S-1 has been used to treat AGC or metastatic gastric cancer.We conducted a meta-analysis to compare oral S-1 and infusional 5-fluorouracil (5-FU) to determine which agent was more efficacious and less toxic in combination with PTX. A systematic review with a meta-analysis was performed. PubMed, EmBase, the Cochrane Central Register of Controlled Trials, and the China National Knowledge Infrastructure databases were searched to select randomized controlled trials (RCTs) comparing PTX plus S-1 and PTX plus 5-FU in patients with AGC.Three RCTs were eligible and 352 patients were analyzed. PTX plus S-1 increased the disease control rate (risk ratio [RR] = 1.14, 95% confidence interval [CI] = 1.00-1.30, P = 0.04) and reduced the progressive disease rate (RR = 0.62, 95% CI] = 0.39-0.98, P = 0.04) compared with PTX plus 5-FU. There was a significant decrease in nausea (RR = 0.60, 95% CI = 0.43-0.82, P = 0.001) and vomiting (RR = 0.55, 95% CI = 0.33-0.91, P = 0.02) in patients treated with PTX plus S-1.PTX plus S-1 was associated with almost equivalent safety and a lower progressive disease rate compared with PTX plus 5-FU. PTX plus S-1 is a good alternative strategy for patients who cannot tolerate a continuous intravenous infusion.

Topics: Age Factors; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Disease Progression; Drug Combinations; Fluorouracil; Neoplasm Staging; Oxonic Acid; Risk Factors; Sex Factors; Stomach Neoplasms; Tegafur

Gastric cancer is the fourth most common cancer worldwide and the leading cause of tumor-related death in China. Gastric cancer is a heterogeneous disease and therefore requires different treatments based on the subtype. We describe a patient who had gastric cancer with liver metastases. Biopsy and tumor analysis using the HercepTest revealed a human epidermal growth factor receptor 2 (HER2)-positive adenocarcinoma as confirmed by fluorescence in situ hybridization. The patient was treated with a regimen of trastuzumab, oxaliplatin, and S-1 (six cycles). When positron emission tomography findings suggested that the metastases had resolved, the patient underwent surgery. Histopathologically, no cancer cells were observed in the resected hepatic tissue. The patient underwent tumor resection surgery, during which the tumor and gastric lymph nodes with lesions were removed. The patient has remained disease-free for 3 months. Therefore, trastuzumab may be an effective agent in the chemotherapeutic treatment of liver metastases in patients with HER2-positive gastric adenocarcinoma.

Topics: Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Female; Humans; Liver Neoplasms; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Receptor, ErbB-2; Stomach Neoplasms; Tegafur; Trastuzumab; Treatment Outcome

We report a case of complete response (CR) following induction chemotherapy using S-1 for a patient with early gastric cancer accompanied by multiple synchronous bone metastases. An asymptomatic 70-year-old woman was diagnosed with early gastric cancer by upper gastrointestinal endoscopy during a periodic medical examination. An abdomino-pelvic computed tomography (CT) scan revealed no primary tumor in the stomach and the absence of lymph node or liver metastases. However, osteoplastic changes were detected in the lumbar vertebrae and the ilium. Multiple synchronous bone metastases from early gastric cancer were detected on magnetic resonance imaging, bone scintigraphy, and positron emission tomography- CT. After a regimen consisting of 15 courses of S-1 plus cisplatin (CDDP), and an additional 5 courses of S-1 were administered, clinical CR was confirmed for the bone metastases. Laparoscopic distal gastrectomy with D1 lymphadenectomy was performed for treating the primary gastric cancer 33 months after the initiation of chemotherapy. Pathological CR was also achieved for the primary gastric cancer. Imaging analysis did not show disease progression 48 months after the initiation of chemotherapy. Synchronous bone metastases from early gastric cancer are extremely rare, and a good outcome was achieved in the present case through induction chemotherapy.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Cisplatin; Drug Combinations; Female; Gastrectomy; Humans; Oxonic Acid; Stomach Neoplasms; Tegafur

A 58-year-old man presented with anorexia and weight loss in April 2010. Endoscopic examination revealed a type 3 tumor extending from the gastric cardia to the antrum. Preoperative imaging showed liver metastasis (S8; 2 cm) and direct invasion of the cancer into the pancreas. We administered 4 courses of chemotherapy (DCS) for the unresectable tumor; the impact of the therapy was partial response (PR). We performed total gastrectomy, D2 dissection, splenectomy, distal pancreatectomy, and partial hepatectomy (S8) in April 2011. The patient was treated with 8 courses of adjuvant chemotherapy with S-1. In April 2012, abdominal computed tomography (CT) revealed a solitary recurrent lesion in the liver (S2). After 7 courses of chemotherapy(weekly paclitaxel), abdominal CT and magnetic resonance imaging (MRI) revealed a tumor thrombus in the portal vein extending from P2 to the umbilical portion (UP). We performed left hepatectomy and cholecystectomy due to the absence of new lesions. Histopathological findings revealed that the poorly differentiated adenocarcinoma had metastasized to the liver. Abdominal CT revealed the presence of multiple recurrent metastases in the liver, 4 months after the surgery. The patient died 27 months after the initial surgery and 7 months after the last operation.

Topics: Combined Modality Therapy; Drug Combinations; Humans; Liver Neoplasms; Male; Middle Aged; Oxonic Acid; Paclitaxel; Portal Vein; Stomach Neoplasms; Tegafur; Venous Thrombosis

The patient was a 70-year-old man with a chief complaint of cough.After careful examination, he was diagnosed with pancreatic body cancer with metastasis to the liver and right pleura and with early gastric cancer.He was treated with S-1 and gemcitabine combination chemotherapy.After completing 3 courses, the distant metastasis could no longer be observed. After completing 4 courses, the tumor marker level in the serum was normalized.The pancreatic lesion was restricted by the end of 10 courses, and the pancreas body and tail were resected.After additional chemotherapy with S-1, he was switched to weekly paclitaxel therapy because of peritoneal dissemination.The patient survived for 15 months after surgery.In cases of unresectable pancreatic cancer with distant metastasis, it may be possible to consider the surgical option when chemotherapy is effective.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Deoxycytidine; Drug Combinations; Gemcitabine; Humans; Liver Neoplasms; Male; Neoadjuvant Therapy; Neoplasms, Multiple Primary; Oxonic Acid; Pancreatic Neoplasms; Pleural Neoplasms; Stomach Neoplasms; Tegafur

This is a case report of gastric cancer with a tumor embolus in the portal vein of a 76-year-old male. Both computed tomography (CT) and upper gastrointestinal endoscopy were performed. The diagnosis was gastric cancer with an accompanying tumor embolus in the portal vein, specifically in the superior mesenteric vein. After neoadjuvant chemotherapy, a distal gastrectomy, and thrombectomy were performed. Upon pathological examination, the main tumor was diagnosed as adenocarcinoma, and the embolus was confirmed to extend from the main tumor into the superior mesenteric vein. Upon immunostaining examination, neither the embolus nor main tumor expressed alpha-fetoprotein (AFP), but both expressed carcinoembryonic antigen (CEA). Gastric cancer with a tumor embolus in the portal vein is considered an incurable disease. However, with no other non-curative factor than portal vein embolus, it is possible that gastrectomy with thrombectomy can result in a good prognosis. On the other hand, it is extremely difficult to improve the prognosis of gastric cancer with both tumor embolus in the portal vein and liver metastasis.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Embolism; Gastrectomy; Humans; Male; Neoadjuvant Therapy; Oxonic Acid; Portal Vein; Stomach Neoplasms; Tegafur; Thrombectomy; Tomography, X-Ray Computed

A 50-year-old man was diagnosed with advanced gastric cancer(Borrmann type 3)accompanied with N3.Staging laparoscopy revealed invasion to the transverse mesocolon and positive cytology from peritoneal washing (CY1). After the patient underwent gastrojejunostomy, we administered DCS combination chemotherapy consisting of docetaxel (40 mg/m² intravenously on day 1), cisplatin(60 mg/m² intravenously on day 1), and S-1 (orally 80 mg/m² on days 1 to 14).Four courses of this treatment were provided every 4 weeks, and it resulted in a partial response (PR).We performed curative distal gastrectomy with transverse mesocolon resection and D2 plus 14v lymph node dissection. Cytological analysis of the samples obtained after peritoneal washing showed negative results.Histopathologically, no variable cancer cells remained in the primary lesion, but a few degenerated cancer cells remained in one of the lymph nodes.Pathological features were classified as Grade 3 for the primary lesion and Grade 2 for the lymph node lesions.S -1 and S-1/cisplatin were administered as adjuvant chemotherapy.One year and 6 months after surgery, the patient is alive and free of disease.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Docetaxel; Drug Combinations; Gastrectomy; Humans; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Stomach Neoplasms; Taxoids; Tegafur

We report a case of gastric carcinoma with metastasis to the liver responding to surgery and chemotherapy.The patient was a 74-year-old man with gastric cancer, clinically diagnosed as P0H0M0T3N0.We initially planned to perform an open distal gastrectomy.However, intraoperative findings revealed metastatic tumors in the liver.Therefore, the patient underwent a D1 distal gastrectomy.After surgery, the patient received the following chemotherapy regimens: 1 course of S-1 and 8 courses of a S-1 and cisplatin (CDDP) combination.After 8 courses of S-1 plus CDDP treatment, liver metastases could not be detected by computed tomography (CT), magnetic resonance imaging (MRI), or positron emission tomography (PET). The patient was assessed to have a clinical complete response.Fifty months after surgery, the patient is alive without recurrence.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Drug Combinations; Humans; Liver Neoplasms; Magnetic Resonance Imaging; Male; Multimodal Imaging; Oxonic Acid; Positron-Emission Tomography; Remission Induction; Stomach Neoplasms; Tegafur; Tomography, X-Ray Computed

S-1 (Teysuno(®)) is an oral anticancer agent comprising the 5-fluorouracil (5-FU) prodrug tegafur and targeted modulators, gimeracil and oteracil. S-1 in combination with cisplatin is a recommended first-line treatment for gastrointestinal cancers in Japan and has recently been approved in the EU for the treatment of advanced gastric cancer. This article reviews S-1 pharmacology from an EU perspective. In a randomized, open-label trial in 24 non-Asian countries in patients with advanced gastric cancer, there were no significant differences between S-1 plus cisplatin and 5-FU plus cisplatin groups in median overall survival (OS) [primary endpoint], progression-free survival or overall response rate. In a post hoc analysis of OS, S-1 plus cisplatin was noninferior to 5-FU plus cisplatin. There were no significant between-group differences in patient quality of life, according to the Functional Assessment of Cancer Therapy (Gastric) Trial Outcome Index, except that S-1 plus cisplatin recipients had a significantly longer time to worsening in physical well-being than 5-FU plus cisplatin recipients. Overall, S-1 plus cisplatin was better tolerated than 5-FU plus cisplatin, with significantly lower rates of haematological, some gastrointestinal tract and other adverse events, serious adverse events and deaths resulting from toxicity, along with significantly fewer haematological and renal function abnormalities. Compared with 5-FU, S-1 plus cisplatin recipients had significantly higher rates of hand-foot syndrome and hyperbilirubinaemia, although there were no between-group differences in the proportions of patients with increased liver enzymes. S-1 is a useful alternative to 5-FU for patients with advanced gastric cancer.

Topics: Antimetabolites, Antineoplastic; Disease-Free Survival; Drug Combinations; European Union; Humans; Oxonic Acid; Quality of Life; Randomized Controlled Trials as Topic; Stomach Neoplasms; Survival Rate; Tegafur; Time Factors; Treatment Outcome

We report a case of gastric adenosquamous carcinoma producing granulocyte-colony stimulating factor (G-CSF). A 60- year-old man was admitted to our hospital complaining of upper abdominal pain. Endoscopic examination revealed a large type 5 advanced gastric cancer with bleeding from the low body of stomach to the antrum, accompanied with para-aortic and mesenteric lymph node metastasis. He had marked leukocytosis, and serum levels of G-CSF were elevated. Histological diagnosis of the biopsy specimen was adenosquamous carcinoma producing G-CSF. We attempted combination chemotherapy with docetaxel, cisplatin and S-1(DCS). After 1 course of treatment, the primary lesion was reduced in size. However, the size of the metastatic lymph node was larger. Chemotherapy was not effective enough, and the patient died 3 months after ending chemotherapy.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Biopsy; Carcinoma, Adenosquamous; Cisplatin; Docetaxel; Drug Combinations; Fatal Outcome; Granulocyte Colony-Stimulating Factor; Humans; Male; Oxonic Acid; Stomach Neoplasms; Taxoids; Tegafur; Tomography, X-Ray Computed

A 68-year-old man was introduced to our hospital with right lower abdominal pain. Endoscopic examination and abdominal CT revealed gastric cancer with liver metastasis. We started chemotherapy using S-1(120 mg/body/day), orally administered for 2 weeks followed by a 2-week rest period, and docetaxel(35 mg/m(2)), administered intravenously on day 1 and 15 as 1 course. After 4 courses of chemotherapy, the liver tumor reduced markedly and no new cancerous region was found by examination; therefore total gastrectomy and partial hepatectomy were performed. Histological examination showed an undifferentiated adenocarcinoma remaining as Grade 1b in the resected stomach. A resected specimen of the liver showed necrotic tissue without any cancer cells. This case suggests that S-1/docetaxel chemotherapy may reduce the stage of unresectable liver metastasis from gastric cancer and make a curative operation possible.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Docetaxel; Drug Combinations; Gastrectomy; Hepatectomy; Humans; Liver Neoplasms; Male; Oxonic Acid; Stomach Neoplasms; Taxoids; Tegafur

A 61-year-old female visited our hospital with the complaint of a left cervical hard tumor. Systemic examination revealed advanced gastric carcinoma with nodal involvement of para -aortic and Virchow's lymph nodes. Neoadjuvant chemotherapy with S-1/cisplatin(CDDP)combination therapy was scheduled. Three courses of chemotherapy resulted in marked tumor regression and a reduction of lymph nodes. Total gastrectomy and D2+para-aortic node dissection were performed. The histological examination revealed complete disappearance of cancer cells in the gastric and nodal specimens, confirming a pathological complete response. The patient underwent postoperative adjuvant chemotherapy, and has been alive 5 years postoperatively without recurrence.

Topics: Antineoplastic Combined Chemotherapy Protocols; Aorta; Cisplatin; Drug Combinations; Female; Humans; Lymphatic Metastasis; Middle Aged; Neoadjuvant Therapy; Oxonic Acid; Stomach Neoplasms; Tegafur

We report a curative resection of a case with advanced gastric cancer responding remarkably well to combination chemotherapy of docetaxel, cisplatin and S-1. The patient was a 71-year-old man with gastric cancer of Borrmann type 3 accompanied with N3. Staging laparoscopy revealed peritoneal dissemination. He was administered docetaxel intravenously at 40mg/ m2 on day 1, cisplatin intravenously at 60 mg/m2 on day 1, and S-1 orally at 80 mg/m2 on days 1 to 14. This treatment was repeated every 28 days as one course. According to gastroscope and CT findings, a significant tumor reduction was obtained after 4 courses. After 6 courses, a CT scan revealed partial response of the lymph node metastasis, and the serum CEA value was normalized. Curative total gastrectomy was performed. The histological effect of the primary lesion was judged to be grade 2. Combination chemotherapy of S-1, cisplatin and docetaxel can be effective and feasible for advanced gastric cancer.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Docetaxel; Drug Combinations; Gastrectomy; Humans; Male; Oxonic Acid; Peritoneal Neoplasms; Stomach Neoplasms; Taxoids; Tegafur

Although both oral fluoropyrimidines were reported effective and safe, doubts exist about whether S-1 or capecitabine is more advantageous in advanced gastric carcinoma (AGC). Herein, we performed a meta-analysis to comprehensively compare the efficacy and safety of S-1-based chemotherapy versus capecitabine-based chemotherapy as first-line treatment for AGC.. PubMed/Medline, EmBase, Cochrane library, and China National Knowledge Infrastructure databases were searched for articles comparing S-1-based chemotherapy to capecitabine-based chemotherapy for AGC. Primary outcomes were overall response rate (ORR), time to progression (TTP), overall survival (OS), progression-free probability, and survival probability. Secondary outcomes were toxicities. Fixed-effects model were used and all the results were confirmed by random-effects model.. Five randomized controlled trials and five cohort studies with 821 patients were included. We found equivalent ORR (38.3% vs. 39.1%, odds ratio [OR] 0.92, 95% confidence interval [CI] 0.69-1.24, P = 0.59), TTP (harzad ratio [HR] 0.98, 95% CI 0.82-1.16, P = 0.79), OS (HR 0.99, 95% CI 0.87-1.13, P = 0.91), progression-free probability (3-month OR 1.02, 95% CI 0.62-1.68, P = 0.94; 6-month OR 1.34, 95% CI 0.88-2.04, P = 0.18) and survival probability (0.5-year OR 0.90, 95% CI 0.61-1.31, P =0.57; 1-year OR 0.97, 95% CI 0.70- 1.33, P = 0.84; 2-year OR 1.15, 95% CI 0.61-2.17, P = 0.66). Equivalent grade 3 to 4 hematological and non-hematological toxicities were found except hand-foot syndrome was less prominent in S-1-based chemotherapy (0.3% vs. 5.9%, OR 0.19, 95% CI 0.06-0.56, P = 0.003). There're no significant heterogeneity and publication bias. Cumulative analysis found stable time-dependent trend. Consistent results stratified by study design, age, regimen, cycle, country were observed.. S-1-based chemotherapy was associated with non-inferior antitumor efficacy and better safety profile, compared with capecitabine-based therapy. We recommended S-1 and capecitabine can be used interchangeably for AGC, at least in Asia.

Topics: Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Deoxycytidine; Disease Progression; Drug Combinations; Fluorouracil; Humans; Neoplasm Staging; Odds Ratio; Oxonic Acid; Publication Bias; Stomach Neoplasms; Tegafur; Time Factors; Treatment Outcome

A 72-year-old man with advanced gastric cancer was referred to our hospital. Upper gastrointestinal endoscopy revealed a type 3 tumor in the gastric antrum and pyloric stenosis. Computed tomography( CT) demonstrated that the tumor had directly infiltrated the pancreatic parenchyma and that the paraaortic lymph nodes were enlarged. We judged the tumor to be unresectable and performed gastrojejunostomy. Postoperatively, the patient was treated with 9 courses of combination chemotherapy comprising S-1 and cisplatin( CDDP), and significant tumor reduction was obtained. Therefore, we performed radical distal gastrectomy with D2 lymphadenectomy. Histological examination revealed a complete absence of cancer cells in the stomach and all of the lymph nodes( pathological complete response: pCR). Seven months after surgery, the patient is in good health with no recurrence. This case suggests that aggressive chemotherapy can be a useful treatment to enable radical surgery for unresectable locally advanced gastric cancer.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Gastric Bypass; Humans; Male; Neoplasm Invasiveness; Oxonic Acid; Pancreas; Pyloric Stenosis; Stomach Neoplasms; Tegafur

A 67-year-old woman with complaints of cough and dyspnea was admitted; her chest radiographs and computed tomography (CT) scans revealed pulmonary carcinomatous lymphangitis. Endoscopic examination revealed advanced gastric cancer and the patient was treated with a combination of 40 mg/m2 docetaxel, administered on day 1, and S-1 100 mg/body/day, administered for 14 days followed by a 7-day interval, as 1 course despite her performance status( PS) being grade 3. After 2 courses of chemotherapy, CT showed that the carcinomatous lymphangitis had improved, and the patient was discharged with PS of grade 0. We report that combination chemotherapy with docetaxel and S-1 might be effective for the treatment of advanced gastric cancer with carcinomatous lymphangitis of the lung in patients with a poor systemic condition.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Docetaxel; Drug Combinations; Fatal Outcome; Female; Humans; Lung Neoplasms; Lymphangitis; Oxonic Acid; Stomach Neoplasms; Taxoids; Tegafur

A 67-year-old man with bladder cancer who was treated with transurethral resection of bladder tumour(TUR-Bt)and chemotherapy at the age of 59 years was diagnosed as having urothelial cancer by biopsy 8 years later. Detailed examination revealed the presence of synchronous triple cancer, with hepatocellular cancer and gastric cancer. Subsequently, semi-total gastrectomy, partial hepatectomy(S6), radio frequency ablation(S5, S7), and cholecystectomy were performed. Histologically, the gastric tumor was a moderately differentiated tubular adenocarcinoma, the hepatic tumor was a moderately differentiated hepatocellular carcinoma, the bladder tumor was a transitional cell carcinoma, and the ureteral tumor was an urothelial carcinoma.

Topics: Aged; Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Drug Combinations; Humans; Liver Neoplasms; Male; Neoplasms, Multiple Primary; Oxonic Acid; Stomach Neoplasms; Tegafur; Treatment Outcome; Urinary Bladder Neoplasms; Urologic Neoplasms

Although gastric cancers(GCs)with rhabdoid features are rare, they are known to show a poorer prognosis compared with conventional GCs. Indeed, more than half of reported GCs with rhabdoid features died within 6 months after receiving any kind of initial treatment. Obviously, no effective chemotherapy has been reported. In this study, we present a case of GC with rhabdoid features which showed a better response to a chemotherapy, S-1/CDDP, and lived for over 12 months after the initial chemotherapy. A 75-year-old man was seen in our hospital for epigastralgia. Detailed examinations revealed that he had GC at Stage IV. Consequently, he underwent S-1/CDDP treatment. This treatment produced a good response for 6 months, minimizing the size of the primary tumor and eradicating distant metastases. Re-growth of the primary tumor without uprising distant metastasis was confirmed 8 months after the initialS -1/CDDP treatment, and the patient went through a gastrectomy for curative care. After surgery, a precise pathological examination revealed that the primary tumor possessed a poorly differentiated adenocarcinoma that contained tumor cells with typical rhabdoid features. In the end, the patient died of liver metastasis 13 months after the initial S-1/CDDP chemotherapy.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Drug Combinations; Fatal Outcome; Humans; Male; Neoplasm Staging; Oxonic Acid; Rhabdoid Tumor; Stomach Neoplasms; Tegafur

S-1 plus cisplatin is the standard chemotherapy for recurrent gastric cancer. While depression and delirium are frequent in cancer patients, hypomania during chemotherapy is rare. We describe a rare case of hypomania during S-1 plus cisplatin treatment for recurrent gastric cancer. A 66-year-old woman, with no previous psychiatric disorder, received S-1 plus cisplatin for recurrent gastric cancer. She showed peculiar behavior. Physical examination, urine, blood and imaging findings were normal. There was no gastric cancer progression. During psychiatric consultation, she behaved inappropriately. However, she behaved normally while performing daily activities. She manifested a persistently elevated, expansive or irritable mood, clearly different from her usual non-depressed state, meeting hypomania diagnostic criteria. Her condition did not require chemotherapy discontinuation or additional medication. During the second and subsequent S-1 plus cisplatin cycles, symptoms were stable. Cancer patients often have adjustment disorders, depression and delirium, but rarely hypomania. Our patient showed no significant changes in blood biochemistry and brain and whole body imaging. While S-1 plus cisplatin-induced hypomania cannot be excluded, hypomanic symptoms did not improve during the chemotherapy rest period, nor was there deterioration during subsequent cycles, suggesting drug-induced mania to be unlikely. Possible onset mechanisms include manic defense phenomena, common with stressful life events. There are no reports of recurrent gastric cancer patients experiencing hypomania during S-1 or S-1 plus cisplatin therapy, i.e. our patient represents a rare course. Clinicians should recognize psychosis or mood disorders during gastric cancer treatment. Further accumulation of such rare cases might elucidate pathological mechanisms underlying hypomania in cancer patients.

Topics: Aged; Antineoplastic Agents; Bipolar Disorder; Cisplatin; Drug Combinations; Female; Humans; Neoplasm Recurrence, Local; Oxonic Acid; Prognosis; Review Literature as Topic; Stomach Neoplasms; Tegafur

The patient was a 39-year-old man with type 3 gastric cancer with synchronous multiple liver and lung metastases, who was diagnosed as cStage IV(cT4aN1M1H1). He received induction chemotherapy with S-1 and CDDP. After chemotherapy, the liver and lung metastases had disappeared completely. He underwent total gastrectomy and splenectomy, with D2 nodal dissection. Anastomotic leakage occurred on postoperative day 6, and substantial inflammatory conditions continued for 2 weeks. He died 6 weeks after surgery with multiple liver metastases. This case suggests that elevated inflammatory conditions may cause tumor progression.

Topics: Adult; Anastomotic Leak; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Disease Progression; Drug Combinations; Gastrectomy; Humans; Liver Neoplasms; Lung Neoplasms; Male; Medical Errors; Neoplasm Staging; Oxonic Acid; Splenectomy; Stomach Neoplasms; Tegafur; Treatment Failure

A 52-year-old woman underwent endoscopic submucosal dissection (ESD) for early gastric cancer at the lesser curvature. Microscopic examination revealed tub1, pSM1, ly0, v0, pHM0, and pVM0, which were considered to be relative resection. Four months later, upper gastrointestinal endoscopy showed local recurrence with suspected SM massive tumor infiltration. We performed a laparoscopic distal gastrectomy with lymph node dissection. Postoperative pathology showed tub2, pT4a (SE), pN2, ly0, v0, and fStage IIIb. This indicated that a few remnant cancer cells were stimulated by the local inflammation associated with ESD. ESD is less invasive than open surgery, but strict observation following curative resection is essential to rule out inflammation-mediated recurrence.

Topics: Adenocarcinoma; Antimetabolites, Antineoplastic; Combined Modality Therapy; Drug Combinations; Endoscopy; Female; Gastric Mucosa; Humans; Middle Aged; Neoplasm Invasiveness; Oxonic Acid; Recurrence; Serous Membrane; Stomach Neoplasms; Tegafur

We set out to evaluate the efficacy and safety of S-1-based therapy versus fluorouracil (5-FU)-based therapy in advanced gastric cancer (AGC). Eligible studies were identified from Pubmed, EMBASE, and Cochrane Library. Additionally, abstracts presented at American Society of Clinical Oncology (ASCO) conferences held between January 2000 and November 2009 were searched to identify relevant clinical trials. The outcome included overall survival (OS), overall response rate (ORR), and grade 3/4 advent events. Four randomized controlled trials (one full text and three abstracts) with 2,115 participants in AGC were identified in our analysis(1,065 patients were in the S-1-based group, 1,050 patients were in the 5-FU-based group). Meta-analysis showed there was significant OS benefit in favor of S-1-based therapy (hazard ratio [HR]=0.87, 95% confidence interval [CI]: 0.79 to 0.96). Pooled estimate for ORR showed no significant difference between S-1-based group and 5-FU-based group (OR=1.25, 95%CI: 0.31 to 5.09). Lower incidence of grade 3/4 neutropenia was observed in patients with S-1-based therapy (OR=0.33, 95%CI: 0.25 to 0.44). With regard to grade 3/4 anemia (OR=1.20, 95%CI: 0.74 to 1.96), leucopenia (OR=1.09, 95%CI: 0.43 to 2.74), stomatitis (OR=2.65, 95%CI: 0.12 to 58.89), diarrhea (OR=0.53, 95% CI: 0.00 to 229.10), nausea (OR=1.36, 95%CI: 0.68 to 2.72), and treatment-related deaths (OR=1.84, 95%CI: 0.95 to 3.54), equivalent frequencies were found between groups. S-1-based therapy significantly improved OS in relation to 5-FU-based therapy. ORR and safety profile were considerable between two groups. These results needed to be confirmed by high-quality trials and further studies in the West.

Topics: Antineoplastic Agents; Drug Combinations; Fluorouracil; Humans; Middle Aged; Oxonic Acid; Randomized Controlled Trials as Topic; Stomach Neoplasms; Tegafur

A 62-year-old male was diagnosed as AFP-producing gastric cancer with lymph node metastases and multiple liver metastases. He was treated with S-1 and CDDP combination chemotherapy. At the end of the first course, both primary and metastatic lesions were remarkably decreased in size, and the serum AFP level was also decreased. The chemotherapy was effective against the cancer and led to a partial response (PR) according to the RECIST guideline. Following the nine months of PR, the primary lesion which had once nearly disappeared, emerged again. Because distant lymph node metastases and liver metastases were considered to have disappeared, distal gastrectomy with D2 lymphadenectomy was performed. The patient received S-1 monotherapy for 6 months after the operation. At present the patient has achieved progression-free survival for 1 year and 3 months after the operation. Though AFP-producing gastric cancer is known for its poor prognosis, combination treatment such as operation or hepatic arterial infusion chemotherapy may improve the prognosis in patients with advanced AFP-producing gastric cancer when systemic chemotherapy is effective.

Topics: alpha-Fetoproteins; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Humans; Male; Middle Aged; Oxonic Acid; Stomach Neoplasms; Tegafur; Tomography, X-Ray Computed

We report three cases of advanced gastric cancer successfully treated by combination therapy of S-1 and docetaxel (DOC). We administered S-1 orally at 80 mg/m² on days 1 to 7 and days 15 to 21, and DOC intravenously at 40 mg/m² on day 1 and 15, and evaluation was conducted every two courses. Case 1: A 73-year-old man with gastric cancer of cT4a, accompanied with bulky N2 lymph node metastasis, was treated with two courses of S-1 and DOC. Partial response was confirmed, followed by total gastrectomy, which revealed his histological grade to be 1b. Case 2: A 65-year-old man with gastric cancer of cT4a, accompanied with bulky lymph node metastasis, was treated with two courses of S-1 and DOC. Partial response was confirmed, followed by distal gastrectomy, which revealed his histological grade to be 1b. Case 3: A 76-year-old woman with gastric cancer of cT4b (panc), was treated with four courses of S-1 and DOC. After that, the main tumor was judged to be cT4a, followed by total gastrectomy, which revealed her histological grade to be 1b. Combined S-1 and DOC chemotherapy is an effective regimen for the treatment of unresectable gastric cancer.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Docetaxel; Drug Combinations; Female; Humans; Male; Oxonic Acid; Stomach Neoplasms; Taxoids; Tegafur; Tomography, X-Ray Computed

Gastric cancer is the fourth most common malignancy worldwide with Japan, Korea, Taiwan, China, Mongolia and many countries in South America and eastern Europe, as well as parts of the Middle East, contributing to the majority of cases. In the USA, it was estimated that approximately 10,620 deaths would be caused by gastric cancer in 2010. Gastric cancer is often diagnosed in its advanced stages. Current first-line treatment for advanced gastric cancer (AGC) using triplet combination chemotherapy containing a platinum-based compound, a fluoropyrimidine with an anthracycline (frequently added in Europe) or a taxane (more often used in the USA and elsewhere) has resulted in higher response rates and modest improvement in overall survival compared with doublet combinations. However, triplet combinations can be associated with increased toxicity compared with the doublets and patient selection becomes important. A desirable research strategy is to improve outcomes of patients with AGC by identifying treatments that are effective, convenient and safe. The interest in oral agents compared with intravenous agents is mounting. One oral fluoropyrimidine, S-1, is novel as it combines tegafur, 5-chloro-2,4-dihydroxypyridine and potassium oxonate. S-1 is approved in Japan, China, Taiwan, Korea and Singapore for the treatment of patients with gastric cancer, and more recently has been approved in 27 European countries to treat AGC. Initial clinical trials in the USA and Europe observed diarrhea as the dose-limiting toxicity; however, initial Japanese studies reported myelosuppression as the dose-limiting toxicity. The differing dose tolerance in these two populations is likely due to polymorphisms in the CYP2A6 gene. Based on our review of Phase II and III studies, we conclude that S-1 is a convenient oral fluoropyrimidine that provides safety advantage over intravenous fluorouracil without compromising efficacy against AGC.

Topics: Adenocarcinoma; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Clinical Trials, Phase III as Topic; Deoxycytidine; Drug Combinations; Fluorouracil; Humans; Neoadjuvant Therapy; Neoplasm Staging; Oxonic Acid; Stomach Neoplasms; Tegafur

A59 -year-old woman was referred to our hospital for a close examination and treatment of an advanced gastric carcinoma. A physical examination and CT scan showed that the right cervical and axillar lymph nodes were swelling, and a histopathological examination of the axillar lymph node revealed metastatic growth of the gastric carcinoma (Stage IV). Then, we started S-1/CDDP combination chemotherapy. S-1 (80 mg/m2/day)was orally administered for 3 weeks followed by 2 weeks of rest, and CDDP (60 mg/m2) was administered by drip on day 8. Since the distant metastases were greatly reduced after 6 courses of combination therapy, a distal gastrectomy with lymph nodes dissection (D2) was performed. Histopathological examination of the resected tissues revealed no residual cancer cells, suggesting a pathologically complete response. The clinical course after the operation went well without any complications, and the patient is alive with no evidence of recurrence 1 year after surgery. S-1/CDDP combination chemotherapy appears to be one of the effective treatments for advanced gastric carcinoma.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Drug Combinations; Female; Humans; Lymphatic Metastasis; Middle Aged; Neoplasm Staging; Oxonic Acid; Remission Induction; Stomach Neoplasms; Tegafur; Tomography, X-Ray Computed

A 75-year-old man with type 4 advanced gastric cancer was referred to our hospital. We diagnosed the tumor as cStage III B(cT4a, cN2, cM0)gastric cancer. We selected neoadjuvant S-1 combined with CDDP therapy for him. After 2 courses of chemotherapy, the extension of the gastric wall improved. After an additional 2 courses of chemotherapy, the primary tumor revealed a partial response(PR), judged from a barium meal study and upper GI endoscopic findings, and a total gastrectomy with lymph node dissection was performed. The pathological specimens showed no cancer cells in the gastric wall and lymph nodes, so the histological effect was judged as Grade 3.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Humans; Male; Neoadjuvant Therapy; Oxonic Acid; Stomach Neoplasms; Tegafur

Topics: Combined Modality Therapy; Drug Combinations; Evaluation Studies as Topic; Humans; Molecular Targeted Therapy; Oxonic Acid; Stomach Neoplasms; Tegafur

Cardiothoracic surgeons commonly use the internal thoracic artery (ITA) and the right gastroepiploic artery (RGEA) when performing a coronary artery bypass graft (CABG). Although the development of CABG surgery has enabled long-term survival in patients with coronary artery disease, malignant diseases are more common in older patients. We present the case of a 75-year-old man who had previously undergone CABG with the RGEA and had later developed advanced gastric cancer. We treated this patient with two courses of combination chemotherapy using S-1 and docetaxel as induction therapy, followed by successful tumor resection. Therefore, neoadjuvant chemotherapy was effective for preserving the CABG with the RGEA in a patient with advanced gastric cancer.

Topics: Administration, Oral; Aged; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Coronary Artery Bypass; Coronary Disease; Docetaxel; Drug Combinations; Follow-Up Studies; Gastrectomy; Gastroepiploic Artery; Humans; Infusions, Intravenous; Male; Neoadjuvant Therapy; Neoplasm Staging; Oxonic Acid; Preoperative Care; Risk Assessment; Stomach Neoplasms; Taxoids; Tegafur; Treatment Outcome

We report an 87-year-old woman who was admitted to our hospital due to anemia and extremely elevated serum alkaline phosphatase (ALP) levels. We diagnosed advanced gastric cancer with disseminated carcinomatosis of the bone marrow and multiple bone metastasis. She was immediately treated with low-dose S-1 (50mg/body, p.o., days 1-14) and zoledronic acid hydrate (4mg/body, i.v., day 1) to avoid disseminated intravascular coagulation (DIC). After 1 course of the treatment, she could completely avoid DIC and we found the primary lesion and the metastasis had decreased. Now she is an outpatient and continues treatment without relapse for about 6 months. We consider low-dose S-1 and zoledronic acid hydrate combination therapy to be an effective strategy against advanced gastric cancer with disseminated carcinomatosis of the bone marrow and multiple bone metastasis in very elderly cases.

Topics: Aged, 80 and over; Alkaline Phosphatase; Antimetabolites, Antineoplastic; Bone Marrow Neoplasms; Bone Neoplasms; Carcinoma; Diphosphonates; Disseminated Intravascular Coagulation; Drug Combinations; Female; Humans; Imidazoles; Oxonic Acid; Stomach Neoplasms; Tegafur; Zoledronic Acid

We encountered a case of gastric cancer accompanied with liver metastasis, which had a good response to chemotherapy of S-1. A 68-year-old female was admitted to our hospital due to further examination of gastric tumor detected by an outpatient physician. She was found to have a type-3 gastric cancer in upper gastrointestinal endoscopy and a metastatic tumor of the liver in abdominal CT. Although chemotherapy of S-1 was inducted for the lesions, both the primary and liver tumors were dramatically reduced. We subsequently performed total gastrectomy and partial hepatectomy. Abdominal CT scan at 11 months after the initial operation revealed metachronous liver metastasis. She received combination chemotherapy of S-1 and CDDP. After 5 courses of the combination chemotherapy, the liver tumor disappeared. She has survived for 8 years without a recurrence after the initial operation. There was negative findings of immunostaining with thymidylate synthetase (TS), which was target enzyme for 5-FU at a biopsy sample of the primary gastric tumor before chemotherapy of S-1. TS immunostaining may be a useful marker for S-1 combined therapy for gastric cancer associated with liver metastases.

Topics: Aged; Antimetabolites, Antineoplastic; Drug Combinations; Female; Humans; Liver Neoplasms; Neoadjuvant Therapy; Oxonic Acid; Remission Induction; Stomach Neoplasms; Tegafur; Time Factors; Tomography, X-Ray Computed

A 62-year-old Japanese man presented with a 1-month history of inter-digestive epigastralgia. His family history included a sister with gastric cancer. Gastroendoscopy and gastrography demonstrated a type-2 tumor in the upper region of the stomach. CT scan and fluorodeoxyglucose-positron emission tomography (FDG-PET) scan demonstrated gastric cancer and its metastatic lymph nodes. The patient underwent total gastrectomy with splenectomy and extended lymph node dissection. Although postoperative adjuvant chemotherapy by S-1 was started, the deteriorating condition of the patient prevented drug administration and even eating meals. On the 19th postoperative day (POD), FDG-PET scan of the body demonstrated new uptake in the liver and lymph node around the aorta. Without any sign of infection, leukocytosis developed around the 30th POD. On the 49th POD, remarkable uptake in the whole upper abdomen was detected on FDG-PET scan. Finally, leukocyte count increased to 125,200 and granulocyte colony stimulating factor (G-CSF) was elevated to 28 pg/ml on the 54th POD. The patient died of multiple liver metastases and carcinomatous peritonitis only 56 days after surgery. G-CSF-producing tumor is a rare but aggressive disease, particularly as recurrent tumor. If leukocytosis is detected in relation to a non-lympho hematopoietic malignant tumor, G-CSF-producing tumor should be considered and FDG-PET scan is recommended for early detection. Chemotherapy for G-CSF-producing tumor must be conducted as soon as possible.

Topics: Adenocarcinoma; Antimetabolites, Antineoplastic; Biopsy; Chemotherapy, Adjuvant; Drug Combinations; Fatal Outcome; Fluorodeoxyglucose F18; Gastrectomy; Gastroscopy; Granulocyte Colony-Stimulating Factor; Humans; Leukocytosis; Liver Neoplasms; Lymph Node Excision; Lymphatic Metastasis; Male; Middle Aged; Oxonic Acid; Peritoneal Neoplasms; Positron-Emission Tomography; Radiopharmaceuticals; Splenectomy; Stomach Neoplasms; Tegafur; Time Factors; Tomography, X-Ray Computed; Treatment Outcome

A 66-year-old woman underwent a total gastrectomy for advanced gastric cancer of cardia. The histological diagnosis was moderately-differentiated tubular adenocarcinoma and the pathological Stage was IV: T4 (diaphragm), N2, M0. Microscopically, there were findings of severe lymphatic and venous invasions with intravenous tumor thrombus around the splenic hilum. Immunohistochemical staining confirmed AFP production of the tumor. The risk of recurrence was considered very high and her prognosis very poor. The patient received adjuvant chemotherapy with S-1. There was no finding of recurrence in the series of postoperative follow-up examinations. Previous reports describe the prognosis of AFP producing gastric cancer as very poor. In several cases, however, aggressive treatments for AFP producing gastric cancer may result in a better prognosis. This is a long survival case of AFP producing gastric cancer successfully treated with S-1 after surgery.

Topics: Adenocarcinoma; Aged; alpha-Fetoproteins; Antimetabolites, Antineoplastic; Cardia; Chemotherapy, Adjuvant; Drug Combinations; Female; Humans; Oxonic Acid; Stomach Neoplasms; Tegafur

We experienced a case with multiple liver metastases of gastric cancer that disappeared by S-1 alone. The patient has survived without recurrence after the disappearance of liver metastases.

Topics: Aged; Antimetabolites, Antineoplastic; Drug Combinations; Humans; Liver Neoplasms; Male; Oxonic Acid; Remission Induction; Stomach Neoplasms; Tegafur; Tomography, X-Ray Computed

The present patient was a 53-year-old female diagnosed as gastric cancer with peritoneal dissemination by staging laparoscopy. She was treated with chemotherapy using S-1 (80 mg/body/day) and CDDP (80 mg/body/day, day 8) administered for 3 weeks followed by a drug-free 2 weeks, in five-week courses. Stable disease (SD) was obtained after six courses, and then she underwent second-staging laparoscopy. Because of disappearing peritoneal disseminated nodules both macroscopically and histologically, she underwent curative total gastrectomy with D2 lymph node dissection and reconstruction by the Roux-en Y method. The postoperative pathological findings showed T2 (se) N1M0, stage IIIa and chemotherapy effective evaluation demonstrated Grade 1b. Postoperatively, S-1/CDDP therapy was carried out, after two cycles she suffered from anorexia, and then S-1 only was given. Fourteen months later, peritoneal dissemination developed. Despite changes in the regimen such as docetaxel or CPT-11, she died 23 months after the initial gastrectomy.

Topics: Adenocarcinoma, Scirrhous; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Fatal Outcome; Female; Gastrectomy; Humans; Middle Aged; Neoadjuvant Therapy; Oxonic Acid; Peritoneal Neoplasms; Stomach Neoplasms; Tegafur; Tomography, X-Ray Computed

A 75-year-old woman was referred to our hospital because of locally advanced gastric cancer. Gastrointestinal fiberscopy revealed type 3 advanced gastric cancer in the posterior wall of the gastric cardia extending to the middle body. Abdominal CT scan revealed direct invasion of pancreas and regional lymph node metastases, indicating clinical stage IV (cT4N2H0P0M0). After two courses of S-1/CDDP, neoadjuvant chemotherapy was administered, and total gastrectomy with D2 lymphadectomy was performed. Histological examination revealed no residual cancer cells in the surgically obtained stomach and lymph nodes, suggesting a complete pathological response (Grade 3). She was treated with S-1 for one year after operation and presently, 16 months after operation, she is in good health without recurrence.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Biopsy; Cisplatin; Drug Combinations; Female; Humans; Neoadjuvant Therapy; Neoplasm Staging; Oxonic Acid; Remission Induction; Stomach Neoplasms; Tegafur; Tomography, X-Ray Computed

With the rapid development in cytotoxic agents and molecular targeting drugs, some progress in palliative chemotherapy for advanced gastric cancer has been achieved and the median survival of advanced gastric cancer patients is prolonged to about one year. In this review, we summarized the application of new agents, such as docetaxel, paclitaxel, oxaliplatin, irinotecan, capecitabine, S1 and targeting drugs in the treatment of patients with advanced gastric cancer. We focused on the results of phase III clinical trials and concluded that till now no standard regimens for the treatment of advanced gastric cancer are available. New combination regimens such as docetaxel-cisplatin-fluorouracil (DCF), epirubicin-oxaliplatin-capecitabine (EOX), fluorouracil-leucovorine-oxaliplatin (FLO), irinotecan, leucovorin and 5-FU (ILF), cispaltin plus xeloda, S1 plus cisplatin are considered as new options for the first-line chemotherapy of advanced gastric cancer. Due to uncertain efficacy and safety concerns, the role of molecular targeting agents in the treatment of advanced gastric cancer needs further investigation. It is suggested that neoadjuvant chemotherapy is a suitable choice for locally advanced gastric cancer.

Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Capecitabine; Cisplatin; Clinical Trials, Phase III as Topic; Deoxycytidine; Docetaxel; Doxorubicin; Drug Combinations; Fluorouracil; Gefitinib; Humans; Irinotecan; Methotrexate; Neoadjuvant Therapy; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Paclitaxel; Quinazolines; Stomach Neoplasms; Survival Rate; Taxoids; Tegafur; Trastuzumab

A patient is a 62-year-old man who was presented by epigastralgia. He was pointed out super advanced gastric cancer with paraaortic lymph node metastasis and pancreatic invasion by gastrointestinal endoscopy (GIS) and computed tomography (CT). We diagnosed as cT4N3M0, and started with chemotherapy as follows. S-1 (120 mg/day) was orally administered for 3 weeks followed by 2-week rest as one course, and CDDP (90 mg/body)was administered by intravenous drip on day 8. Partial response was indicated after 6 courses of this procedure. We changed the procedure to S-1 single treatment for 2 weeks followed by 2-week rest. After 12-course of this procedure, he was attacked by brain infarction, the procedure was interrupted for about 8 months. After rehabilitation, an S-1 single treatment was restarted. The main tumor and metastatic lymph node appeared no change before the interruption of S-1 single treatment. So, we considered that complete response was continued. S-1+CDDP and S-1 single regimen appears to be effective for super advanced gastric cancer.

Topics: Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Humans; Male; Middle Aged; Oxonic Acid; Stomach Neoplasms; Tegafur; Treatment Outcome

A 61-year-old male complained of easy fatigue. Gastroscopy revealed a gastric carcinoma. CT showed No.3 and No.7 lymph nodes swelling. Distant metastasis was not found. S-1 (120 mg/day) was administered for 28 days followed by 14- day rest as one course. Total gastrectomy was performed for 2 weeks after the chemotherapy. Pathology revealed no cancer cells in the gastric wall and dissected lymph nodes. The pathological effect was judged as Grade 3. This case suggests that S-1 therapy may be useful for elderly patients and patients with poor renal function.

Topics: Adenocarcinoma; Antimetabolites, Antineoplastic; Drug Combinations; Gastrectomy; Humans; Male; Middle Aged; Oxonic Acid; Stomach Neoplasms; Tegafur

S-1 has been considered to be a key drug in the treatment of advanced gastric cancer in Japan as a standard option of chemotherapy. Interindividual variation in the enzymes of the S-1 metabolic pathway can affect the extent of S-1 metabolism and impact the efficacy of S-1-based chemotherapy. In this review, the role of the "candidate" genetic factors affecting the therapeutic efficacy of S-1 is discussed with a special emphasis on polymorphism and gene expressions involved in the S-1 metabolic pathway, including CYP2A6, thymidylate synthase, thymidine phosphorylase, and orotate phosphoribosyltransferase. The predictive values of these candidates might be overcome with drugs combined with S-1. Pharmacogenetic studies based on a "global" approach by DNA microarray are promising to identify gastric cancer patients with both survival benefit and clinical benefit more accurately than those based on the "candidate" approach, especially for S-1 combination therapy. Large and controlled studies are needed to justify changes in the chemotherapeutic strategies, from "one-size fits all" to "tailor-made."

Topics: Antimetabolites, Antineoplastic; Aryl Hydrocarbon Hydroxylases; Cytochrome P-450 CYP2A6; Drug Combinations; Humans; Orotate Phosphoribosyltransferase; Oxonic Acid; Pharmacogenetics; Stomach Neoplasms; Tegafur; Thymidine Phosphorylase; Thymidylate Synthase

Gastric and gastroesophageal adenocarcinoma (GGA) are significant worldwide health problems. With most patients presenting with advanced disease, palliative chemotherapy plays a significant role in treatment. Results from recent phase III studies of cytotoxic agents in combination therapy, such as docetaxel, oxaliplatin, irinotecan, capecitabine, and S-1, have been encouraging and provide patients with additional therapeutic options. Although these forthcoming regimens have allowed for more flexible patient-tailored therapy, survival continues to be suboptimal. Although still in its infancy, targeted biotherapy, including inhibitors of the vascular endothelial and epidermal growth factor receptors, seems to be promising and its incorporation into the next generation of clinical trials will hopefully improve outcomes and help advance future treatments. This article reviews current active chemotherapeutic regimens and explores the role of novel targeted therapies in advanced GGA.

Topics: Adenocarcinoma; Antimetabolites, Antineoplastic; Antineoplastic Agents, Phytogenic; Camptothecin; Capecitabine; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Deoxycytidine; Docetaxel; Drug Combinations; ErbB Receptors; Esophagogastric Junction; Fluorouracil; Humans; Irinotecan; Oxonic Acid; Radiation-Sensitizing Agents; Stomach Neoplasms; Taxoids; Tegafur; Vascular Endothelial Growth Factor A

S-1 is a potent antitumour drug in gastric cancer. After years of disagreement about the utility of chemotherapy for advanced gastric cancer, several studies have recently demonstrated the efficacy of S-1 in both the adjuvant and primary settings. In this Minireview, the value of S-1 in the treatment of gastric cancer is discussed.

Topics: Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Drug Combinations; Humans; Oxonic Acid; Stomach Neoplasms; Tegafur

Since irinotecan, S-1, docetaxel, and paclitaxel were approved, therapeutic options for chemotherapy in the treatment of gastric cancer have increased. It is suggested that the efficient use of the primary drugs prolongs life in the treatment of progressive colorectal cancer. Also, physicians have discussed ways to take full advantage of the drugs in the treatment of gastric cancer. In first-line treatment in other countries, combination therapy usually includes the administration of two drugs, while in Japan, where therapies based on S-1 have been developed, the most appropriate strategy must be determined after reporting the results of phase III trials in 2007. In the clinic, treatment must be selected on the basis of solid evidence in consideration of the organ dysfunction associated with progressive gastric cancer. The timing of any changes in the treatment should be considered because the cancer easily metastasizes to the peritoneum. Throughout the world, various regimens have been developed that replace cisplatin with oxaliplatin or mainly use oral fluoropyrimidine. Molecular target drugs, now being evaluated in phase II trials, will also be used in the treatment of gastric cancer in the near future. Novel therapies will be developed in Asia and Japan where the incidence of gastric cancer is high.

Topics: Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cisplatin; Clinical Trials, Phase III as Topic; Docetaxel; Drug Administration Schedule; Drug Combinations; Fluorouracil; Humans; Irinotecan; Leucovorin; Methotrexate; Oxonic Acid; Paclitaxel; Stomach Neoplasms; Survival Rate; Taxoids; Tegafur

Topics: Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Chemotherapy, Adjuvant; Cisplatin; Clinical Trials, Phase III as Topic; Docetaxel; Drug Administration Schedule; Drug Combinations; Fluorouracil; Humans; Irinotecan; Neoplasm Staging; Oxonic Acid; Stomach Neoplasms; Taxoids; Tegafur

Gastric cancer is the second most frequent cancer in the world. Approximately 84% of patients with gastric cancer will have advanced disease and median survival of these patients without chemotherapy is only 3-4 months. "Classical" chemotherapy regimens, mainly CF (cisplatin plus infusional 5FU) and ECF (cisplatin plus infusional 5FU plus Epirubicin) obtain responses in 20-40% of the patients and improve quality of life. Nevertheless, duration of these responses is short with very few complete responses. Median time to tumor progression (TTP) with these regimens is only about 4-5 months and median survival does not exceed 7-10 months. Moreover, benefit seems to be limited to patients with good performance status and treatment toxicity and discomfort are not negligible, specially that of regimens with cisplatin or infusional 5FU. Trying to improve these results, the incorporation of new drugs has been explored. Among the new combinations, the more developed ones are those with Docetaxel (DCF), oxaliplatin (EOX, FLO), Capecitabine (EOX, cisplatin-Xeloda) and irinotecan (ILF). We have final results from Phase III trials that suggest that all these regimens could have a role in the treatment of these patients but survival is still very poor and toxicity remains important. It would be interesting to investigate other new combinations and the incorporation of drugs directed against new therapeutic targets in this setting. It would be of utmost interest that these clinical trials would also explore clinical and molecular prognostic and predictive factors.

Topics: Adenocarcinoma; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Capecitabine; Clinical Trials as Topic; Deoxycytidine; Docetaxel; Drug Combinations; Fluorouracil; Humans; Irinotecan; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Stomach Neoplasms; Taxoids; Tegafur; Uracil

Gastroesophageal cancers continue to pose a significant health burden around the world. Advanced gastroesophageal cancer is an incurable condition and more research is desirable. Considerable new and important information, however, has become available.. The number of phase III trials for patients with advanced gastroesophageal cancer is increasing and that is welcome news. Current results suggest that capecitabine can be substituted for 5-fluorouracil and oxaliplatin for cisplatin. Docetaxel, when combined with 5-fluorouracil and cisplatin, prolongs overall survival as well as improves safety, quality of life, and efficacy. S-1, a fourth generation oral fluoropyridine, is especially effective in combination with cisplatin. Dosing of S-1 is different between Western and Asian populations due to differences in metabolism by CYP2A6. Irinotecan should not be used as frontline therapy for advanced gastroesophageal cancer. Biologic agents are currently under investigation.. Safer, more convenient, and more effective chemotherapy combinations are being developed for patients with advanced gastroesophageal cancer; however, considerable challenges exist to select the optimal therapy for an individual patient.

Topics: Adenocarcinoma; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Clinical Trials, Phase III as Topic; Deoxycytidine; Drug Combinations; Epirubicin; Esophageal Neoplasms; Fluorouracil; Humans; Oxonic Acid; Stomach Neoplasms; Tegafur; Treatment Outcome

Two pivotal phase II studies of S-1 in advanced gastric cancer showed response rates of 44% and 49%, and the overall survival time was 207 and 250 days, respectively. The response rate of S-1 exceeded the response rates of other approved drugs, and was comparable to that of combination chemotherapies such as 5-fluorouracil (5-FU) plus cisplatin (CDDP). These data suggested that S-1 could be used as a first-line drug for gastric cancer with a great advantage in quality of life (QOL), because it is an oral drug and can be used at an outpatient clinic. The overall incidences of adverse reactions in the phase II studies were 74.3%, and that of grade 3 or worse were 14.9%. The main adverse reactions were myelosuppression and GI toxicities. As hematological toxicity was more common than other oral fluoropyrimidine derivatives such as UFT, a careful hematological monitoring is necessary. To confirm the survival benefit of S-1 in advanced gastric cancer, a phase III trial of S-1 vs 5-FU vs CDDP plus irinotecan (CPT-11) has been conducted by the Japan Clinical Oncology Group (JCOG), and these results have been awaited. Furthermore, the combination of S-1 with CDDP, CPT-11 or taxane for the treatment of gastric cancer is feasible and active, and phase III studies of S-1 vs several combination therapies including S-1 are also in progress. The effect of S-1 in adjuvant setting is also promising. Currently, a phase III study of surgery alone vs S-1 in patients with a curative resection of gastric cancer has been developed. Further therapeutic benefits are also expected by combining S-1 with other chemotherapeutic agents such as molecular targeted agents.

Topics: Administration, Oral; Anemia; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Chemotherapy, Adjuvant; Cisplatin; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Drug Administration Schedule; Drug Combinations; Humans; Irinotecan; Leukopenia; Neutropenia; Oxonic Acid; Quality of Life; Stomach Neoplasms; Stomatitis; Tegafur

The 5-FU plus cisplatin containing regimen like FP, ECF and DCF, is considered to be the most effective treatment for advanced gastric cancer in the United States, Europe, and Korea. In Japan, oral fluoropyrimidine S-1 (TS-1) is currently considered to be the first candidate as the standard drug for advanced gastric cancer. S-1 based combination therapies with other promising drugs like cisplatin, irinotecan and taxanes, are expected to yield good results. Above all, S-1+CDDP therapy showed a high efficacy and expected to be a standard therapy for advanced gastric cancer. Two large phase III studies, JCOG 9912 5-FU vs S-1 vs CPT-11 +CDDP and S-1 vs S-1+CDDP, are now on going to establish an acceptable frontline standard for patients with AGC. We therefore need to develop new agents and combination chemotherapy regimens to achieve a greater survival benefit in AGC.

Topics: Administration, Oral; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Drug Administration Schedule; Drug Combinations; Humans; Oxonic Acid; Practice Guidelines as Topic; Stomach Neoplasms; Survival Rate; Tegafur

A review of the published literature was undertaken to ascertain the trends in treatment schedules of combination of an oral fluorouracil derivative S-1 with low-dose CDDP (25 mg/m2 or less) for un-resectable and recurrent gastric cancer. The case reports demonstrated as follows: S-1 was given as standard doses of 80-120 mg/body. With regard to CDDP administration, 4 mg/m2 or less was given for 4-consecutive weeks following 2-weeks rest and 6-10 mg/m2 was given for 3-consecutive weeks following 2-weeks rest in the case of 5-day/week CDDP administration. There have been reports of 6-8 mg/m2 CDDP given once or twice a week and weekly CDDP of 10-25 mg/m2 without grade 3 or more adverse events. A phase I study demonstrated the recommend dose of CDDP in the case of 5-day/week was 4 mg/m2 in the regimen of 4-consecutive weeks and 2-weeks rest with a standard dose of S-1. Three phase I studies on weekly low-dose CDDP with S-1 showed the recommend doses were 20-25 mg/m2. S-1+low-dose and a high-dose (30-90 mg/m2) CDDP have come into wide use in Japan. There have been no differences between the case reports and the clinical studies in quantity and quality for both regimens. The unified regimen of S-1+low-dose CDDP as an outpatient based chemotherapy should be developed.

Topics: Ambulatory Care; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Drug Administration Schedule; Drug Combinations; Humans; Maximum Tolerated Dose; Oxonic Acid; Stomach Neoplasms; Survival Rate; Tegafur

The effectiveness of systemic chemotherapy for metastatic gastric cancer has already been established. However, a standard chemotherapy still remains uncertain. New agents such as S-1, CPT-11 and taxanes are markedly improving the response rates for gastric cancer. Including these new drugs, several randomized phase III trials are ongoing in Japan. In the near future, the candidate for standard regimen to treat gastric cancer will be reported. In this article, we described the current state of S-1 +CPT-11 combination chemotherapy for gastric cancer. Among various CPT-11 based chemotherapy, S-1 +CPT-11 appears to be the most effective and less toxic treatment.

Topics: Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Drug Administration Schedule; Drug Combinations; Humans; Irinotecan; Maximum Tolerated Dose; Neoplasm Metastasis; Oxonic Acid; Stomach Neoplasms; Tegafur

The S-1 +biweekly docetaxel (DOC) combination therapy was evaluated for advanced or recurrent gastric cancer patients. This combination therapy was evaluated in vitro using the nude rat-gastric cancer xenograft system. S-1 alone or DOC alone showed antitumor activity, and the antitumor activity was synergistic when two drugs were combined. In clinical settings, the schedule was S-1 80 mg/m2 (day 1-14, orally) and DOC (day 1 and day 15, intravenously) followed by a 2-week rest. In phase I study, the dose of DOC was evaluated, and a recommended dose for phase II was determined as 35 mg/m2. The entry for phase II study was completed, and the preliminary results of 33 patients showed the response rate of 21.2%. The incidence of more than grade 3 adverse effects was 29%(neutropenia, leukocytopenia, anorexia and mucositis). The S-1 +biweekly DOC combination therapy can be a candidate for outpatient chemotherapy for advanced or recurrent gastric cancer.

Topics: Animals; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Docetaxel; Drug Combinations; Humans; Leukopenia; Neoplasm Transplantation; Neutropenia; Oxonic Acid; Quality of Life; Randomized Controlled Trials as Topic; Rats; Rats, Nude; Stomach Neoplasms; Stomatitis; Taxoids; Tegafur

S-1 Combined with Weekly Paclitaxel in Patients with Advanced Gastric Cancer: Masahiro Gotoh, Shin-ichiro Kawabe and Hiroya Takiuchi (Dept. of Gastroenterology, Osaka Medical College) Summary Both paclitaxel and S-1 have been identified as an effective agent for the treatment of gastric cancer. Furthermore, weekly paclitaxel was found to have a better toxicity profile and to be as effective as an equivalently dosed conventional schedule of delivery every 3 weeks. Osaka Gastrointestinal Cancer Chemotherapy Study Group (OGSG) conducted the phase I/II study of weekly paclitaxel combined with S-1. S-1 was given orally at a fixed dosage of 40 mg/m2 bid for 14 consecutive days, followed by a week rest. Paclitaxel was scheduled to be given intravenously on days 1 and 8. The MTD of paclitaxel was presumed to be 60 mg/m2 because 50.0% of patients (2/4) developed DLTs (mainly grade 3 anorexia). Therefore, the RD of paclitaxel was estimated to be 50 mg/m2. This combination treatment was demonstrated to exhibit a tolerable toxicity profile with a high antitumor activity of 48% (14/29) and MST of 417 days. This regimen is investigated in a randomized phase II trial and may yet become a test arm in future phase III trials.

Topics: Administration, Oral; Anemia; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Humans; Infusions, Intravenous; Maximum Tolerated Dose; Oxonic Acid; Paclitaxel; Stomach Neoplasms; Tegafur

A recent development of novel anticancer agents like S-1, CPT-11 or taxanes has improved a therapeutic outcome for advanced gastric cancer, while conventional anticancer agents showed less anticancer effect against gastric cancer. The present main drug in Japan is S-1, which is easily used for outpatient with a high efficacy rate and low toxicity, also shows better effect in combination with other anticancer drugs than S-1 alone. In the present article, we demonstrated significant meaning of additional radiation therapy with anticancer drugs like S-1. With novel anticancer drugs like S-1, we will expose a clinical advantage and appropriateness for chemo-radiation therapy against gastric cancer discussed in the present references according to chemo-radiation therapy. Although chemo-radiation therapy has been recognized as one of the standard therapies for gastric cancer in Western countries, radiation therapy was selected in Japan for palliation therapy of recurrent disease or a terminal cancer to improve patients' QOL. On the other hand, we demonstrated in our trial of chemo-radiation therapy with S-1/low-dose CDDP/radiation (TSLDR), which was applied to initial treatment against highly advanced Stage IV gastric cancer and revealed the usefulness of the regimen in anticancer effect and toxicity. In addition, chemo-radiation therapy including novel anticancer agents like S-1 will be discussed based on various kinds of view points, expecting a better clinical outcome of multimodal therapies against advanced gastric cancer.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Combined Modality Therapy; Drug Administration Schedule; Drug Combinations; Female; Humans; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Pilot Projects; Radiotherapy Dosage; Stomach Neoplasms; Tegafur; Treatment Outcome

Actually there has been no established adjuvant therapy for curable gastric cancer. Thus it is strongly recommended in the guidelines to actively carry out clinical trials. A large scale clinical trial on adjuvant chemotherapy for gastric cancer using S-1 (ACTS-GC) started in 2001. This was the first large trial having the surgery alone as control after 1980. The target population was Stage II, IIIA, IIIB, and the expected hazard ratio was less than 0.70. Between October 2001 and December 2004, for 3 years and 2 months, 1,056 patients were enrolled. Thus it was proven that we should carry out a pivotal study instead of making meta-analysis in the field of gastric cancer. Certainly, the results of this trial will strongly affect the clinical practice in Japan. If the results are negative, the use of adjuvant chemotherapy in practice and in social insurance might be restricted.

Topics: Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Clinical Trials as Topic; Drug Administration Schedule; Drug Combinations; Humans; Meta-Analysis as Topic; Neoplasm Staging; Oxonic Acid; Registries; Stomach Neoplasms; Survival Rate; Tegafur

Therapy for patients with advanced gastric cancer is not satisfactory. The median survival of patients with advanced gastric cancer is approximately 6-9 months and less than 10% of patients survive one year. Despite identification of new classes of agents, such as camptothecins, taxanes, and new platinum analogs, the improvement has been limited and therapy intensive resulting in considerable morbidity. More intensive therapies are challenging not only for the patients and their relatives but also for the health care providers. Oral fluropyrimidines like capecitabine and S-1 have generated considerable interest because of convenience and their activity against gastric carcinoma. S-1 is of significant interest because of many studies in Japan in gastric cancer patients demonstrating its substantial activity as a single agent and in combination with other agents. Furthermore, S-1 represents a fourth generation "designer" drug. It has a component that enhances the cytotoxic activity of tegafur by inhibiting dihydropyrimidine dehydrogenase (DPD) and also has a component that reduces phosphorylation of 5-fluorouracil in the gastrointestinal tract to potentially reduce toxicity. This unique combination is rarely found in an oral agent. In addition, considerable ethnic differences in the tolerated doses of S-1 have been considered related to varying efficiency rates of conversion of tegafur to 5-fluorouracil by the CYP450 enzyme system. The varying efficiency is thought to be due to the presence of certain polymorphisms in the CYP2A6 gene responsible for metabolizing tegafur to 5-fluorouracil. S-1 is under rapid development in the West for gastric carcinoma. Phase I/II studies of the combination of S-1 plus cisplatin have been completed and a global phase III study, accruing rapidly, is comparing S-1 plus cisplatin to 5-fluorouracil plus cisplatin (a reference regimen).

Topics: Administration, Oral; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Drug Administration Schedule; Drug Combinations; Gastrointestinal Neoplasms; Humans; Maximum Tolerated Dose; Multicenter Studies as Topic; Oxonic Acid; Stomach Neoplasms; Tegafur

We performed surgical resections in 6 cases of advanced gastric cancer and 4 cases of colorectal cancer after preoperatively treating them with TS-1 at a daily dose of 80-100 mg/body for 2 weeks, and evaluated whether one can estimate their sensitivity to TS-1 by a pathological examination. Case 1 of type 3 advanced gastric cancer underwent surgery after one week interval following oral administration of TS-1 at a daily dose of 80 mg/body for 2 weeks. Surprisingly, the pathological examination revealed complete disappearance of cancer cells in the resected stomach and no cancer cells in the regional lymphnodes, judged grade 3 in pathological effectiveness. Case 2 of type 2 advanced gastric cancer was treated with TS-1 at a daily dose of 100 mg/body for 2 weeks and underwent surgery after a three-week interval due to the complication of pneumonia. The pathological effectiveness was judged grade 2 in the resected stomach, and no cancer cells were detected in the regional lymphnodes. In both cases, the postoperative course was uneventful, and no adverse effects were detected. In these cases, their high sensitivity to TS-1 was clearly confirmed, and now they have been treated with TS-1 for the postoperative adjuvant chemotherapy, and have undergone regular check-ups at our outpatient clinic in good condition. Recently, we performed the same protocol in 6 cases of advanced gastric cancer including these 2 cases and also in 4 cases of advanced colorectal cancer. This protocol was found useful for evaluating the pathological effect by TS-1. We consider the protocol quite useful and helpful in determining a suitable regimen for postoperative adjuvant chemotherapy.

Topics: Adenocarcinoma; Aged; Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Colorectal Neoplasms; Drug Administration Schedule; Drug Combinations; Female; Gastrectomy; Humans; Infant; Middle Aged; Oxonic Acid; Pilot Projects; Pyridines; Stomach Neoplasms; Tegafur

Lentinan is a beta(1-3) glucan clarified to have a life prolonging effect in non-operable, recurrent gastric cancer patients in combination with chemotherapy. The long lasting issue remaining to be resolved has been the ineffectiveness of Lentinan when administered per-orally. Beta(1-3) glucans possess the particulate size around 100-200 microm in aqueous solution which dampered the absorption through abdominal mucosa. Subsequently the particulate size of Lentinan impaired the immunostimulating potency, to induce reductive form of antigen presenting cells, macrophages and dendritic cells relevant for the polarization of Th1/Th2 balance to Th1. The situation is also the case for the clinical benefit of lentinan to reduce the side effect of chemotherapeutic agents such as TS-1, Gemzar, CDDP, known to be a critical dose limiting factor of these agents and to improve quality of life of the patients. Using the modern nano-technology procedures, Mitherapist, containing 15 mg/dl Lentinan, with a particulate size of 0.2 microm able to pass through mucosal barrier was provided. It was found in randomized double blind clinical testing that Mitherapist is effective against allergy by reducing an antigen specific IgE level through polarization to Th1 biased immune response even by per-oral administration. Per oral administration also exhibited the reduced side effect of chemotherapeutic agents such as TS-1, Gemzar, CDDP and greatly improved quality of life of the cancer patients. The role of hypoxia in local neoplastic tissues will be also discussed.

Topics: Adjuvants, Immunologic; Administration, Oral; Antineoplastic Agents; beta-Glucans; Drug Combinations; Humans; Immunotherapy; Lentinan; Neoplasms; Oxonic Acid; Pyridines; Randomized Controlled Trials as Topic; Stomach Neoplasms; Tegafur

We report an investigation of the therapeutic efficacy and safety of TS-1 single-agent therapy administered as first-line therapy in 23 cases of unresectable advanced gastric cancer treated at our institution. TS-1 was administered at 80 mg-120 mg (divided into two doses) per day for 28 days followed by a 14-day rest interval, making up a single cycle. The response rate for its antitumor efficacy was 39.1%, with partial response in nine cases, no change in seven cases, progressive disease in five cases, and two cases not evaluable (9 5% confidence interval: 19.7%-61.5%). By site, the response rate was 43.5% for primary tumors (10/23), 33.3% for lymph nodes (3/9), and 16.7% for liver metastasis (1/6). In 1 patient, the carcinomatous ascites disappeared,and in 3 patients they decreased remarkably. No significant differences were observed with regard to age (70 and over/under 70) or histological type (differentiated/undifferentiated). The one-year survival rate was 32.8%, and the 50% survival period was 29 9 days. The most common side effect was leucopenia in seven cases (30.4%), followed by decreased hemoglobin, loss of appetite, hepatic dysfunction and the like. Most side effects, however, were mild and did not exceed grade 2; grade 3 side effects were seen only in two cases (8.7%) of leucopenia and two (8.7%) of hepatic dysfunction, a low rate of occurrence. The outpatient follow-up ratio(outpatient period/total treatment period) was high at 69.6%, meaning that first-line single-agent therapy with TS-1 is beneficial in terms not only of efficacy but also in maintaining quality of life.

Topics: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Chemical and Drug Induced Liver Injury; Drug Administration Schedule; Drug Combinations; Female; Humans; Leukopenia; Male; Middle Aged; Oxonic Acid; Pyridines; Quality of Life; Stomach Neoplasms; Survival Rate; Tegafur

A 73-year-old woman came to our hospital because of poor appetite, and careful examination revealed a Borrmann type 2 tumor on the posterior wall of the lower body of the stomach as well as enlarged para aortic-lymph nodes. Surgery was performed in November 2000, but because the para-aortic lymph nodes were densely adherent to the aorta, it was impossible to dissect the lymph nodes from the wall (N3, Stage IV). Postoperatively, a course of TS-1 100 mg/day for 4 weeks and discontinuation for 2 weeks was started. After one course of TS-1, the enlarged para-aortic lymph nodes were no longer seen on abdominal computed tomography (CT). The dose of TS-1 was subsequently reduced to 80 mg/day because of adverse effects. Although the patient is still taking TS-1, she is well with no signs of recurrence 34 months after surgery.

Topics: Adenocarcinoma; Aged; Antimetabolites, Antineoplastic; Aorta, Abdominal; Combined Modality Therapy; Drug Administration Schedule; Drug Combinations; Female; Gastrectomy; Humans; Lymphatic Metastasis; Oxonic Acid; Pyridines; Stomach Neoplasms; Tegafur

We report the case of a 79-year-old female with gastric cancer accompanied by liver metastasis that was successfully treated by TS-1, a novel oral fluoropyrimidine derivative. Abdominal CT scan showed a low-density area in the lateral segment of the liver and lymph node swelling in the right side of the abdominal aorta. One treatment course consisted of 4 weeks of TS-1 administration (100 mg daily) followed by a 2-week break. After 2 courses of this treatment, an abdominal CT scan showed no evidence of liver metastasis and a reduction of lymph nodes metastasis. The serum level of CA19-9 was reduced from 780 U/ml to within a normal range. Grade 1-2 toxicity (nausea and diarrhea) was seen after 2 courses. We conclude that TS-1 may be beneficial in the treatment of the liver metastasis of gastric cancer.

Topics: Administration, Oral; Aged; Antimetabolites, Antineoplastic; Biomarkers, Tumor; CA-19-9 Antigen; Drug Combinations; Humans; Liver Neoplasms; Male; Oxonic Acid; Pyridines; Stomach Neoplasms; Tegafur; Tomography, X-Ray Computed

There is no chemotherapy considered to be standard treatment for advanced gastric cancer worldwide, and there is no consensus as to whether combination or single agent therapy is preferred. In the phase I portion, a dose-escalation study of cisplatin (CDDP) combined with TS-1, new oral dihydropyrimidine dehydrogenase inhibitory fluoropyrimidine, was performed to determine the maximum-tolerated dose (MTD), recommended dose (RD), dose-limiting toxicities (DLTs), and objective response rate (RR) in advanced gastric cancer (AGC). TS-1 was given orally at 40 mg/m2 bid for 21 consecutive days following a 2-week rest. CDDP was planned to be given intravenously on day 8, at a dose of 60, 70, or 80 mg/m2, depending on the DLT. Treatment was repeated every 5 weeks, unless disease progression was observed. In the phase I portion, the MTD of CDDP was presumed to be 70 mg/m2, because 33.3% of patients (2/6) developed DLTs; mainly neutropenia. Therefore, the RD of CDDP was estimated as 60 mg/m2. In the phase II portion, 19 patients including 6 patients of the RD phase I portion were evaluated. The median administered courses was 4 (range: 1-8). The incidence of haematological and non-haematological toxicities (> or = grade 3) was 15.8 and 26.3%, respectively, but all were manageable. The RR was 74% (14/19, 95%) confidence interval: 54.9 (90.6%), and the median survival days were 383. This regimen is considered to be active against AGC with acceptable toxicity. In addition, currently, a randomized phase III study (JCOG 9912) for AGC patients not treated previously with chemotherapy is underway in Japan. It compares three arms: 5-FU alone, TS-1 alone and CPT-11 with CDDP therapy. We also initiated a randomized phase III study comparing TS-1 alone, and with CDDP for AGC. From those two phase III studies, we may be able to evaluate the clinical benefit of TS-1 in combination with CDDP versus TS-1 single, or 5-FU combined with CDDP therapy in terms of survival benefits and improving the QOL for AGC patients.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Drug Administration Schedule; Drug Combinations; Humans; Maximum Tolerated Dose; Oxonic Acid; Pyridines; Stomach Neoplasms; Tegafur

The case reports and clinical trials on combination therapy of a novel oral 5-fluorouracil derivative TS-1 with low-dose cisplatin for gastric cancer were reviewed. In the majority of the case reports, TS-1 was administered at 80-120 mg/body per day for 4 weeks followed by a rest of 2 weeks. However, in several case reports, TS-1 administration was slightly shortened such as 3 weeks administration followed by a rest of 2 weeks. The administration of cisplatin (CDDP) varied: every day, weekly, bi-weekly, and so on; the doses were from 1 to 25 mg/m2. CDDP was mostly given at 5-10 mg/body 5 days per week, mimicking the low-dose FP (5-fluorouracil+ CDDP). In most case reports, combination therapies were undertaken on an inpatient basis due to frequent administration of CDDP, while the weekly or bi-weekly CDDP administration regimens were done on an outpatient basis. The case reports demonstrated high efficacies and few adverse effects of the combination therapy. Several case reports showed unresectable cases could be operated curatively after the combination therapy. There have been three phase I clinical trials, two of which were regimens on an outpatient basis. JFMC 27-9902, an inpatient-basis phase I clinical trial, consisted of TS-1 at 80 mg/m2 every day and CDDP at low-dose for 5 days per a week: the regimen consisted of 4 weeks administration and 2 weeks' rest. The recommended dose of CDDP was determined to be 4 mg/m2 in the JFMC27-9902 regimen. In the modified JFMC27-9902 regimen, CDDP was given twice a week on an outpatient basis. This new phase I/II clinical trial has been under way since 2003 December. In conclusion, TS-1 + low-dose CDDP combination therapy will be done on an outpatient basis in future, and may be examined as a neoadjuvant therapy as well as a conventional form of chemotherapy.

Topics: Administration, Oral; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Clinical Trials, Phase I as Topic; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Humans; Neoplasm Recurrence, Local; Oxonic Acid; Pyridines; Stomach Neoplasms; Survival Rate; Tegafur

The Japanese Foundation for Multidisciplinary Treatment of Cancer (JFMC) has designed and initiated a randomized Phase II clinical trial planned as a first-line of chemotherapy for advanced or recurrent gastric cancer. The trial focuses on two groups and selecting the better of two regimens. The first group was given tailored CPT-11, adjusting individual optimal dosage using toxicity-based grading as an index in combination with TS-1, and the second group was given standard TS-1 treatment. The aim of this tailored dosage regimen for each individual patient is to continue chemotherapy as long as possible, and eventually, to prolong survival. In this trial, subsidiary pharmacokinetics analysis for the tailored arm is also proposed. We would like to introduce the significance and theory of tailored dosage chemotherapy in this paper.

Topics: Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Clinical Trials, Phase II as Topic; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Humans; Irinotecan; Maximum Tolerated Dose; Neoplasm Recurrence, Local; Oxonic Acid; Pyridines; Randomized Controlled Trials as Topic; Stomach Neoplasms; Tegafur

5-FU has been a key chemotherapeutic agent in the treatment of advanced or recurrent gastric cancer. In order to enhance the effect of 5-FU, biochemical modulation or combination chemotherapy has been developed. Although several phase III studies were reported in the 1990s, a standard chemotherapeutic regimen has not been established worldwide. Recently, a newly developed anticancer agent, Paclitaxel, can be clinically used for advanced gastric cancer either as a single agent or in combination with such as 5-FU, cisplatin, and TS-1. It may well further improve the quality of life and prolong the survival of patients with gastric cancer. Further assessment for the well design phase III clinical trials will be necessary to establish the availability of such combination modalities for the treatment of advanced, recurrent gastric cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Administration Schedule; Drug Combinations; Floxuridine; Fluorouracil; Humans; Oxonic Acid; Paclitaxel; Pyridines; Quality of Life; Stomach Neoplasms; Tegafur

The effectiveness of chemotherapy for metastatic gastric cancer has been already revealed. But a standard chemotherapy has not been established yet. New agents such as TS-1, CPT-11 and taxanes are improving the response rates and also the survivals for gastric cancer. Including these new drugs, several randomized phase III trials are ongoing in Japan. In the near future, the candidate for standard resume will be sent abroad. In this article, we described the current state of CPT-11 combined chemotherapy for gastric cancer. Among various CPT-11- combined chemotherapy, CPT-11 + TS-1 is the most effective and less toxic treatment.

Topics: Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cisplatin; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Docetaxel; Drug Administration Schedule; Drug Combinations; Fluorouracil; Humans; Irinotecan; Leucovorin; Mitomycin; Oxonic Acid; Pyridines; Stomach Neoplasms; Taxoids; Tegafur

In the present article, we have summarized the clinical trials on docetaxel and the phase I study of docetaxel and combination therapy. Patients with a performance status (PS) of 0 to 2 received docetaxel at the starting dose of 40 mg/m2 by iv infusion over 1 hour on day 1 and TS-1 at the full dose of 80 mg/m2 daily for two weeks every three weeks. Nine patients were treated with increasing dose levels of docetaxel as follows: (docetaxel/TS-1, mg/m2): 40/80 (level 1), 50/80 (level 2) and 60/80 (level 3), and all the cases were found to be assessable for drug safety, while 7 were assessable for response. The MTD was reached at the 50/80 mg/m2 dose level in three patients out of six, who experienced a dose limiting toxicity (DLT). On the other hand, partial response was achieved in 5 (71.4%) of the 7 patients with evaluable lesions. The drug combination showed a good safety profile, and the responses observed in the study suggest that the drug combination shows a high degree of efficacy in patients with advanced and or recurrent gastric cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; Docetaxel; Drug Administration Schedule; Drug Combinations; Humans; Maximum Tolerated Dose; Neoplasm Recurrence, Local; Oxonic Acid; Pyridines; Stomach Neoplasms; Taxoids; Tegafur

Weekly administration of paclitaxel with a short course of premedication was performed for 8 patients with advanced or recurrent gastric cancer. In this regimen, 500 ml of physiological saline with vitamins was administered in a 3-hour infusion. After 30 minutes of infusion, dexamethasone 10 mg, chlorpheniramine maleate 5 mg, famotidine 20 mg and ramosetron hydrochloride 0.3 mg were administered intravenously. After 30 more minutes of infusion, paclitaxel at a dose of 65 mg/m2 was admixed in the residual normal physiological saline and administered over 2 hours. Administration was continued for 3 weeks with a 1 week rest. Though the partial response rate was 25%, clinical symptoms improved in all patients. Moreover, both hematological and non-hematological toxicities were mild. Weekly administration of paclitaxel with a short course of premedication is an effective and well-tolerated method for patients with advanced or recurrent gastric cancer.

Topics: Aged; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Administration Schedule; Drug Combinations; Female; Fluorouracil; Humans; Infusions, Intravenous; Male; Middle Aged; Neoplasm Recurrence, Local; Oxonic Acid; Paclitaxel; Premedication; Pyridines; Stomach Neoplasms; Tegafur

S-1 (TS-1)-related studies presented at the 74th Japanese Gastric Cancer Congress are reviewed. Of the papers presented at this conference, 35 were related to S-1. In the panel discussion on the therapeutic significance of oral fluoropyrimidines in gastric cancer, 9 papers were related to S-1 (sensitivities to oral fluoropyrimidines, 2 papers; clinical results of treatment with S-1, 5 papers; and combination therapy with S-1, 2 papers). In the general presentations, there were 26 papers on S-1 related-subjects (clinical studies or clinical practice of S-1, 12 papers; case reports, 3 papers; basic studies on animal models of peritoneal metastasis, 2 papers; and combination therapy with S-1, 9 papers). Several studies showed that S-1 was basically as effective against tumors in postmarketing surveillance in clinical practice as in phase II studies at the time of its development, including a report of a patient with complete response to S-1. Some reports suggested the possibility of using S-1 in neoadjuvant chemotherapy and postoperative adjuvant chemotherapy. The usefulness of S-1 in combination chemotherapy was also suggested in several reports. These results indicate that S-1 is a key drug that can be used in first-line treatment of gastric cancer. It will be necessary to accumulate evidence based on data from clinical trials and clinical applications in the future.

Topics: Administration, Oral; Antimetabolites, Antineoplastic; Clinical Trials, Phase II as Topic; Drug Combinations; Fluorouracil; Humans; Japan; Oxonic Acid; Pyridines; Stomach Neoplasms; Tegafur

The current basic and clinical studies of S-1 (TS-1) were reviewed. S-1 is a novel oral dihydropyrimidine dehydrogenase (DPD) inhibitory fluoropyrimidine (DIF) based on a biochemical modulation of 5-fluorouracil (5-FU); S-1 contains tegafur (FF) and two types of enzyme inhibitor, 5-chloro-2,4-dihydroxypyridine (CDHP) and potassium oxonate (Oxo) in a molar ratio of 1:0.4:1. In pharmacokinetic studies, S-1 showed high 5-FU concentration in blood for long periods of time. In a combined analysis of two pivotal late phase II studies in gastric cancer, the overall response rate was 44.6% (45/101), and median survival time and 1-year survival rate were 244 days and 37%, respectively. A postmarketing survey was conducted, and in the interim analysis, tolerability and safety profiles were shown in 3294 patients with gastric cancer. The oral dose form and low incidence of adverse reactions permit treatment on an outpatient basis. To evaluate the survival benefit of S-1 in advanced gastric cancer, a phase III study of S-1 vs 5-FU vs cisplatin (CDDP) plus irinotecan (CPT-11) has been conducted. The effect of S-1 in adjuvant chemotherapy is also promising. Currently, a phase III study of surgery alone vs S-1 in patients with curative resection of gastric cancer is in progress. Further therapeutic benefits are expected to be gained by combining S-1 with other chemotherapeutic agents. Several preliminary results of combination phase I/II studies of S-1 with CDDP or CPT-11 have recently been obtained, and phase II studies are in progress. Thus, S-1 is currently the first candidate as the standard anticancer drug for gastric cancer. Further evaluations by well-controlled clinical trials are still needed.

Topics: Administration, Oral; Antimetabolites, Antineoplastic; Clinical Trials as Topic; Drug Combinations; Fluorouracil; Humans; Oxonic Acid; Pyridines; Quality of Life; Stomach Neoplasms; Tegafur; Treatment Outcome

Topics: Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cisplatin; Colonic Neoplasms; Docetaxel; Drug Administration Schedule; Drug Combinations; Drug Delivery Systems; Fluorouracil; Humans; Irinotecan; Oxonic Acid; Paclitaxel; Pyridines; Stomach Neoplasms; Taxoids; Tegafur

Randomized trials demonstrated the significantly improved survival benefit of 5-fluorouracil (5-FU) based chemotherapy in patients with unresectable advanced gastric cancer (AGC) in comparison with best supportive care (BSC). However there is no chemotherapy considered worldwide to be the standard treatment for AGC and there is no consensus as to whether combination or single agent therapy is preferable. Therefore, 2 large Phase III studies JCOG 9912 5-FU vs TS-1 vs CPT + CDDP and TS-1 vs TS-1 + CDDP are now ongoing to establish an acceptable frontline standard for patients with AGC. We need to develop new agents and combination chemotherapy regimens to achieve greater survival benefit in AGC.

Topics: Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cisplatin; Drug Combinations; Fluorouracil; Humans; Irinotecan; Oxonic Acid; Pyridines; Stomach Neoplasms; Survival Rate; Tegafur

5-FU has been a key chemotherapeutic agent in the treatment of advanced or recurrent gastric cancer. In order to enhance the effect of 5-FU, biochemical modulation or combined chemotherapy has been developed. Although several phase III studies have been reported in 1990's, a standard chemotherapeutic regimen has not been established worldwide. Recently, newly developed anticancer agents such as CPT-11, TS-1, Paclitaxel, or Docetaxel can be clinically used for advanced gastric cancer either single agent or in combination that may further improve the quality of life and prolong the survival of patients with gastric cancer. In Japan, postoperative adjuvant chemotherapy has been actively developed to enhance survival benefit of surgery for patients with gastric cancer. There were a few positive single randomized controlled study showing benefit of adjuvant chemotherapy with a high evidence level. However, all reports of meta-analysis of adjuvant chemotherapy for gastric cancer indicated the survival benefit of adjuvant chemotherapy. At present, a nation-wide randomized controlled study in the postoperative adjuvant setting for gastric cancer using TS-1 (ACTS-GC) is under way that may clarify the effect of postoperative adjuvant chemotherapy in gastric cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cisplatin; Docetaxel; Drug Administration Schedule; Drug Combinations; Humans; Irinotecan; Meta-Analysis as Topic; Neoadjuvant Therapy; Oxonic Acid; Paclitaxel; Pyridines; Stomach Neoplasms; Survival Rate; Taxoids; Tegafur

Topics: Administration, Oral; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials, Phase II as Topic; Dihydrouracil Dehydrogenase (NADP); Drug Combinations; Humans; Oxidoreductases; Oxonic Acid; Pyridines; Stomach Neoplasms; Tegafur; Treatment Outcome

We describe in this paper a therapeutic modality which is based on a self-rescuing concept (SRC) featuring dual activity, i.e., effect-enhancing activity and adverse reaction-reducing activity. We present the theory and practice of S-1, a novel oral fluoropyrimidine anticancer agent designed to enhance anticancer activity and reduce gastrointestinal toxicity through the deliberate combination of the following components: an oral fluoropyrimidine agent, tegafur (FT); a DPD inhibitor (CDHP: 5-chloro-2, 4-dihydroxypyridine) which is about 200-fold more potent than uracil used in UFT; and an ORTC inhibitor (Oxo: potassium oxonate) which is localized in the gastrointestinal tract. We devised a novel oral anticancer agent, S-1, as a combination drug with a molar ratio of 1:0.4:1 for FT, CDHP, and Oxo, respectively. To compare S-1, FT, and UFT in terms of their anticancer activity and adverse reactions, a colon cancer implantation model in rats was used for 4-week consecutive oral administration from the time when the postimplantation tumor weight become about 2 g. The tumor disappeared on day 16 at a given dose of S-1 (as 22.5 mg/kg FT), and the tumor did not reappear for at least three months. Antitumor activity was more marked with S-1 than FT and UFT. Adverse reaction, i.e., stomatitis, depilation, and weight loss, were less frequent in the S-1 group than in the other groups. A clinical pharmacology study examined blood concentrations of 5-FU after twice-a-day administration after meals of S-1 at a dose of 40 mg/m2. Blood concentrations of 5-FU were 60 to 200 ng/ml in all twelve patients examined. Late phase II clinical trials of S-1 were conducted in patients with advanced and recurrent stomach cancers, in the same regimen as for the clinical pharmacology study. It basically consisted in four cycles, each of which comprised 4-week, twice-a-day, consecutive oral administration with a 2-week withdrawal. The overall response rate was 44.6% (45/101). Median survival time (MST) was 224 days. S-1 was given manufacturing approval by the Ministry of Health and Welfare of Japan after a priority review, with indications for advanced and recurrent stomach cancers. A late phase II clinical study of S-1 in patients with advanced/recurrent head and neck cancer was conducted in 59 eligible patients. Objective responses were 4 complete response (CR) and 13 partial response (PR), for a response rate of 28.8% (17/59). MST was 344 days. Grade 4 hemoglobin decrease was observe

Topics: Administration, Oral; Animals; Antimetabolites, Antineoplastic; Clinical Trials as Topic; Colorectal Neoplasms; Drug Combinations; Drug Synergism; Head and Neck Neoplasms; Humans; Oxonic Acid; Pyridines; Rats; Stomach Neoplasms; Tegafur

A 74-year-old female patient underwent total gastrectomy, splenectomy and D2 lymph node dissection for gastric cancer with non-dissectible paraaortic lymph node metastasis. Pathological examination revealed a high level of metastasis of dissected lymph nodes. The patient received daily oral administration of 100 mg TS-1, a novel oral anticancer agent. Each treatment course consisted of a four-week administration followed by two drug-free weeks. A partial response was obtained after the second course and a complete response was observed in the middle of the fourth and after the sixth course. The treatment was stopped because of grade 2 anemia in the middle of the seventh course, but no other adverse effect was observed. Complete response of the treatment persisted for twelve months and the patient has now been in good health without a recurrence for twenty months after surgery. Although the prognosis of gastric cancer with a high level of lymph node metastasis is poor, TS-1 therapy may have a potent efficacy in gastric cancer patients with a high level of lymph node metastasis such as the current case.

Topics: Aged; Antimetabolites, Antineoplastic; Aorta; Drug Combinations; Female; Gastrectomy; Humans; Lymph Node Excision; Lymphatic Metastasis; Oxonic Acid; Pyridines; Remission, Spontaneous; Stomach Neoplasms; Tegafur

Although recent phase II studies have demonstrated high antitumor activity in the treatment of advanced gastric cancer, no significant survival benefit has been clearly demonstrated yet, when compared with 5-FU alone. More recently, a number of new agents including irinotecan and S-1 have demonstrated significant activity against gastric cancer as single agent or in combination with other chemotherapeutic agents. A phase III trial of 5-FU alone versus irinotecan plus cisplatin versus S-1 alone in advanced gastric cancer patients will be initiated in Japan Clinical Oncology Group (JCOG) within a few months. These new regimens have a potential becoming a new standard chemotherapy for the treatment of gastric cancer. The patients with peritoneal dissemination has usually not yet evaluated and explored from clinical study because of risk of toxicity and having no measurable disease. A next randomized phase III trial comparing 5-FU alone with sequential methotrexate and 5-fluorouracil in patients with peritoneal metastasis will be initiated in JCOG next year. The development of molecular biology has demonstrated the molecular mechanisms of chemoresistance or chemosensitivity, as well as a number of molecular targets against cancer cells. To date, many molecular targeted agents are being evaluated in various stages of clinical testing. These advances may provide a possibility of tailor made treatment.

Topics: Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cisplatin; Docetaxel; Drug Administration Schedule; Drug Combinations; Fluorouracil; Humans; Irinotecan; Oxonic Acid; Paclitaxel; Pyridines; Randomized Controlled Trials as Topic; Stomach Neoplasms; Survival Rate; Taxoids; Tegafur

Although gastric carcinoma is an uncommon disease in North America, its incidence is alarmingly high in Asia, South America, Eastern Europe, and countries of the former Soviet Union. Screening for gastric carcinoma is performed only on a limited basis in Japan; in the rest of the world, therefore, patients often present with advanced disease at the time of diagnosis. Chemotherapy, radiotherapy, or both rarely cure patients with unresectable or metastatic carcinoma; therapy thus remains palliative for such patients. Chemotherapy seems to be beneficial, however, and continues to evolve in the treatment of patients with advanced gastric carcinoma. Four small randomized trials demonstrated survival and quality-of-life benefits for patients who received chemotherapy compared with those who received best supportive care. In the past 20 years, several "old" drugs have been studied either alone or in combination to treat this disease; and new active drugs have been identified. Recently, quality of life, convenience, and cost-containment have been emphasized in the treatment of cancer. This has increased interest in oral agents. At present, several promising oral 5-fluorouracil prodrugs are being studied in clinical trials. This article summarizes current developments in the treatment of advanced gastric carcinoma.

Topics: Administration, Oral; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Camptothecin; Capecitabine; Deoxycytidine; Docetaxel; Drug Combinations; Enzyme Inhibitors; Etoposide; Fluorouracil; Humans; Infusions, Intravenous; Irinotecan; Oxonic Acid; Paclitaxel; Pyridines; Randomized Controlled Trials as Topic; Stomach Neoplasms; Taxoids; Tegafur; Uracil

The prognosis of stage III gastric cancer (GC) is not satisfying and the specific chemotherapy regimens for GC of stage IIIC based on the 8th edition of the UICC/AJCC TNM staging system are still inconclusive. Peritoneal recurrence is the common and severe relapse pattern. Nanoparticle albumin-bound paclitaxel (Nab-PTX) is safer and more effective than PTX in the peritoneal metastasis. Clinical trial has demonstrated the safety and efficacy of sintilimab in GC. A combination of Nab-PTX, S-1 and sintilimab could be a promising triplet regimen as adjuvant therapy for GC. The aim of this article is to describe the design of this prospective Dragon-VII trial, conducted to evaluate the safety and efficacy of the combination of Nab-PTX, S-1 and sintilimab.. Lay abstract The prognosis of stage IIIC gastric cancer is poor and the treatment for it is not satisfying. This is a clinical trial that aims to explore a more effective therapy in gastric cancer patients of stage IIIC. Patients with stage IIIC gastric cancer must meet all of the inclusion criteria and none of the exclusion criteria to be eligible for this trial. The eligible patients will be given eight cycles of combinatory therapy of albumin-bound paclitaxel, a chemotherapy (day 1 and day 8), and S-1, another chemotherapy (days 1 to 14), plus sintilimab, a type of immunotherapy called an immune checkpoint inhibitor (day 1) every 3 weeks and then sintilimab maintenance for up to 12 months.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Albumins; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Disease-Free Survival; Drug Administration Schedule; Drug Combinations; Feasibility Studies; Female; Gastrectomy; Humans; Incidence; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Oxonic Acid; Paclitaxel; Peritoneal Neoplasms; Prospective Studies; Stomach Neoplasms; Tegafur; Young Adult

This study aimed to evaluate the feasibility, safety, and efficacy of postoperative adjuvant chemotherapy with docetaxel/cisplatin/S-1 (DCS) following S-1 therapy in patients with stage III gastric cancer after curative gastrectomy.. Patients with stage III gastric cancer who underwent D2 gastrectomy were enrolled. Adjuvant chemotherapy was initiated within 8 weeks of gastrectomy. The first cycle of chemotherapy consisted of S-1 monotherapy (day 1-14), followed by a 7-day rest period. Cycles 2 and 3 consisted of the following: S-1 (day 1-14) administration, followed by a 14-day rest period, and an intravenous infusion of cisplatin and docetaxel on days 1 and 15. After two cycles, S-1 was administered for up to 1 year.. Thirty patients were enrolled between 2014 and 2017. Febrile neutropenia of grade 3 or higher was the most common hematological toxicity with 4 patients (13.3%). Other hematological toxicities of grade 3 or higher were as follows: neutropenia in 3 (10.0%), leukopenia in 3 (10.0%), and anemia in 2 (6.7%) patients. Most frequent non-hematological toxicity of grade 3 was anorexia (n = 4, 13.3%) and general fatigue (n = 3, 10.0%); no grade 4 non-hematological toxicities were observed. Twenty-five patients (83.3%) completed two cycles of DCS treatment and 18 (60.0%) completed subsequent S-1 treatment for 1 year. The relative dose intensity of docetaxel and cisplatin was 0.86 and that of S-1 was 0.88.. The DCS regimen can be acceptable as an adjuvant chemotherapy and offers an effective postoperative treatment option for stage III gastric cancer patients.. UMIN000012785 .. 08/01/2014.

Topics: Adenocarcinoma; Aged; Anemia; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy-Induced Febrile Neutropenia; Chemotherapy, Adjuvant; Cisplatin; Docetaxel; Drug Administration Schedule; Drug Combinations; Fatigue; Feasibility Studies; Female; Humans; Leukopenia; Male; Middle Aged; Neutropenia; Oxonic Acid; Patient Compliance; Stomach Neoplasms; Tegafur

This is a phase 2 study aimed at evaluating the efficacy and safety of TAS-114, a novel deoxyuridine triphosphatase inhibitor, combined with S-1 in patients with advanced gastric cancer (AGC).. Eligible patients had AGC with measurable lesions, according to the Response Evaluation Criteria in Solid Tumors (RECIST, v1.1), with two or more previous chemotherapy regimens including fluoropyrimidines, platinum agents, and taxanes or irinotecan. The primary endpoint was objective response rate (ORR) according to the RECIST, v1.1. Twenty-nine patients were required according to Simon's optimal two-stage design, with one-sided a = 5% and power = 80%. Threshold and expected ORRs were 5% and 25%. Patients received TAS-114 (400 mg/body, twice a day) and S-1 (30 mg/m. Accrual was terminated in June 2018 because meeting the predefined efficacy criteria was considered difficult. ORR and disease control rate were 5.0% [95% confidence interval (CI), 0.1-24.9%] and 70.0% (95% CI, 45.7-88.1%), respectively, for all 20 patients enrolled. Median progression-free survival (PFS) and overall survival were 2.4 months (95% CI, 1.2-3.3 months) and 7.1 months (95% CI, 5.2-9.4 months), respectively. Median PFS in the groups with high and low dUTPase protein expression in the cytoplasm was 2.8 months (95% CI, 1.4-3.9) and 1.6 months (95% CI, 0.6-2.4), respectively [hazard ratio, 0.40 (95% CI, 0.16-1.04), log-rank test two-sided p = 0.047]. Grade 3 or higher treatment-related adverse events included anemia (20%), leucopenia (15%), neutropenia (10%), rash (10%), thrombocytopenia (5%), and lymphopenia (5%) CONCLUSIONS: TAS-114 with S-1 showed only modest antitumor activity with acceptable safety profiles for patients heavily pretreated with AGC.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Female; Humans; Male; Middle Aged; Oxonic Acid; Progression-Free Survival; Proportional Hazards Models; Pyrimidines; Pyrophosphatases; Response Evaluation Criteria in Solid Tumors; Stomach Neoplasms; Sulfonamides; Tegafur; Ubiquitin-Protein Ligases

A regimen of S-1 combined with oxaliplatin (SOX) has been widely used as the first-line regimen for advanced gastric cancer. To further improve the antitumor efficacy for gastric cancer patients with peritoneal metastasis, we added nab-paclitaxel to the established SOX regimen (NSOX). Nab-paclitaxel (nanoparticle albumin-bound paclitaxel) has effective transferability to tumor tissues and strong antitumor effects for peritoneal metastasis. We performed a phase 1 study of this regimen to determine the maximum tolerated dose (MTD) and the recommended dose (RD) in patients with gastric cancer with peritoneal metastasis.. The NSOX regimen involved 21-day cycles with escalated doses of nab-paclitaxel (50 [level 1] to 80 [level 4] mg/m2 on days 1 and 8) and fixed doses of oxaliplatin (100 mg/m2 on day 1) and S-1 (80 mg/m2/day for 2 weeks).. Six patients with gastric cancer with peritoneal metastasis were enrolled. The MTD was determined to be dose level 2, as 2 of 3 patients experienced dose-limiting toxicities (DLTs), grade 4 non-hematological toxicities. One patient experienced acute myocardial infarction, and the other patient developed jejunal perforation. There were no treatment-related deaths. No patients experienced DLTs, so the RD was determined to be dose level 1.. The NSOX regimen was shown to be a tolerable regimen and may be a promising triplet therapy for patients with gastric cancer with peritoneal metastasis.

Topics: Aged; Albumins; Antineoplastic Combined Chemotherapy Protocols; Dose-Response Relationship, Drug; Drug Combinations; Female; Humans; Male; Maximum Tolerated Dose; Middle Aged; Myocardial Infarction; Oxaliplatin; Oxonic Acid; Paclitaxel; Peritoneal Neoplasms; Stomach Neoplasms; Tegafur

A multi-institutional phase II study was conducted to evaluate the efficacy and safety of preoperative docetaxel, cisplatin and S-1 therapy in marginally resectable advanced gastric cancer.. Patients with macroscopic type 4, large macroscopic type 3 and bulky lymph node metastasis received two cycles of preoperative docetaxel, cisplatin and S-1 therapy (docetaxel 40 mg/m2 and cisplatin 60 mg/m2 on day 1, and S-1 80 mg/m2 for 14 days, every 4 weeks). The primary endpoint was the pathological response rate, with an expected value of 65%.. Thirty-one patients were enrolled in this study. The pathological response rate was 54.8%, and it was higher than the threshold value but lower than the expected rate. The R0 resection rate was 93.5%. The frequencies of grade 3-4 toxicities during docetaxel, cisplatin and S-1 therapy were 41.9% for neutropenia, 6.5% for febrile neutropenia and 32.3% for nausea/vomiting. Grade 2 and 3 surgical morbidities occurred in 23.3 and 6.7% of the patients, respectively.. Preoperative docetaxel, cisplatin and S-1 therapy was feasible in terms of chemotherapy-related toxicities and surgical morbidity, but the effect did not achieve the expected value. The association between the pathological response rate and survival will be evaluated in the final analysis of this clinical trial.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Docetaxel; Dose-Response Relationship, Drug; Drug Combinations; Female; Humans; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Postoperative Complications; Preoperative Care; Stomach Neoplasms; Tegafur; Time Factors

Curing locally advanced gastric cancer through surgery alone is difficult. Adjuvant and neoadjuvant chemotherapy bring potential benefits to more patients with gastric cancer based on several clinical trials. According to phase II studies and guidelines, SOX regimen as neoadjuvant chemotherapy is efficient. However, the optimal duration of neoadjuvant chemotherapy has not been established. In this study, we will evaluate the efficacy and safety of different cycles of SOX as neoadjuvant chemotherapy for patients with locally advanced gastric cancer.. RESONANCE-II trial is a prospective, multicenter, randomized, controlled phase III study which will enroll 524 patients in total. Eligible patients will be registered, pre-enrolled and receive three cycles of SOX, after which tumor response evaluations will be carried out. Those who show stable disease or progressive disease will be excluded. Patients showing complete response or partial response will be enrolled and assigned into either group A for another three cycles of SOX (six cycles in total) followed by D2 surgery; or group B for D2 surgery (three cycles in total). The primary endpoint is the rate of pathological complete response and the secondary endpoints are R0 resection rate, three-year disease-free survival, five-year overall survival, and safety.. This study is the first phase III randomized trial to compare the cycles of neoadjuvant chemotherapy using SOX for resectable locally advanced cancer. Based on a total of six to eight cycles of perioperative chemotherapy usually applied in locally advanced gastric cancer, patients in group A can be considered to have completed all perioperative chemotherapy, the results of which may suggest the feasibility of using chemotherapy only before surgery in gastric cancer.. Registered prospectively in the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) with registration number ChiCTR1900023293 on May 21st, 2019.

Topics: Adenocarcinoma; Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Clinical Trials, Phase III as Topic; Drug Combinations; Female; Follow-Up Studies; Humans; Male; Middle Aged; Multicenter Studies as Topic; Neoadjuvant Therapy; Oxaliplatin; Oxonic Acid; Prognosis; Prospective Studies; Randomized Controlled Trials as Topic; Research Design; Stomach Neoplasms; Tegafur; Young Adult

We evaluated the efficacy and safety of first-line S-1 plus cisplatin in combination with cetuximab for Japanese patients with advanced gastric cancer, including gastroesophageal junction adenocarcinoma.. This open-label, single arm, multicenter, phase 2 trial was conducted to assess first-line cetuximab plus S-1 plus cisplatin for advanced gastric cancer. A total of 40 patients from 10 centers were enrolled. Cetuximab was administered weekly, with the initial infusion at 400 mg/m2 and then 250 mg/m2 each subsequent week. S-1 plus cisplatin chemotherapy was concomitantly conducted in a 5-week cycle: S-1 (40-60 mg, adjusted for body surface area) was given twice daily for 3 consecutive weeks, followed by a 2-week rest period, and cisplatin (60 mg/m2) was given on day 8 of each cycle for a maximum of 8 cycles. Treatment continued until the occurrence of radiographically confirmed progressive disease, unacceptable toxicity or withdrawal of consent. The primary endpoint was the best overall response. Secondary endpoints included progression-free survival and safety.. A total of 40 patients were evaluable. One patient (2.5%) had a complete response; 15 patients (37.5%) had a partial response. The observed overall response rate according to the independent review committee was 40.0% (95% confidence interval, 24.9-56.7; P = 0.7043 [one-sided null hypothesis: overall response rate ≤ 43%]); median PFS was 5.6 months (95% confidence intervals, 4.2-8.3). No adverse events leading to death were reported during the study, and no specific safety concerns were observed.. Overall, the addition of cetuximab to S-1 plus cisplatin was well tolerated in patients with advanced gastric cancer but provided no additional clinical benefit in this study. ClinicalTrials.gov identifier: NCT01388790.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cetuximab; Cisplatin; Drug Administration Schedule; Drug Combinations; Female; Humans; Japan; Male; Middle Aged; Oxonic Acid; Remission Induction; Stomach Neoplasms; Tegafur; Treatment Outcome

We conducted a single-arm phase II trial to investigate the short-term efficacy and safety of apatinib combined with oxaliplatin and S-1 in the treatment of unresectable gastric cancer.. Previously untreated patients with unresectable HER-2-negative advanced gastric cancer were selected. All the patients received six cycles of S-1 and oxaliplatin and five cycles of apatinib, which were administered at intervals of three weeks. The surgery was performed after six cycles of drug treatment. The primary endpoints were radical resection (R0) rate and safety. This study was registered with the China Trial Register, number ChiCTR-ONC-17010430  (01/12/2016-01/12/2022).. A total of 39 patients were enrolled. Efficacy evaluation was feasible for 37 patients. One patient achieved complete response (CR, 2.7%), 26 patients achieved partial response (PR, 70.3%), three patients had stable disease (SD, 8.1%) and seven patients had progressive disease (PD, 18.9%). The objective response rate (ORR) was 73.0% and the disease control rate (DCR) was 81.1%. 22 patients underwent surgery, among which 14 patients underwent radical resection (R0), with a R0 resection rate of 63.6%. The 1-year survival rate of the surgical group (22 patients) was 71.1% and the 2-year survival rate was 41.1%. The median survival time was 21 months. The incidence of adverse events (AEs) was 100%. Leucopenia (65.3%) and granulocytopenia (69.2%) were the most common hematological AEs. The most common non-hematological AEs were fatigue (51.3%) and oral mucositis (35.9%).. Apatinib combined with oxaliplatin and S-1 showed good short-term survival and acceptable safety in the conversion therapy of unresectable gastric cancer.

Topics: Adult; Aged; Drug Combinations; Female; Humans; Male; Middle Aged; Oxaliplatin; Oxonic Acid; Pyridines; Stomach Neoplasms; Survival Analysis; Tegafur

Intraperitoneal (IP) chemotherapy is a promising treatment option for gastric cancer (GC) with peritoneal metastasis (PM). Recently, superiority of IP administration of paclitaxel (PTX) combined with S-1 and intravenous PTX over conventional systemic chemotherapy was suggested in a phase III study, although the difference in overall survival did not reach statistical significance in the primary analysis. Thus, attempts to combine IP PTX with other systemic therapies with higher efficacy are warranted. We designed a new regimen combining IP PTX with S-1 plus cisplatin (SP), which is regarded as the standard first-line treatment for metastatic GC in Japan, and subsequently carried out a dose-escalation study.. The combination was a 5-weekly regimen. IP PTX was to be administered on days 1, 8, and 22 with an initial dose of 15 mg/m2 at level 1 and 20 mg/m2 at level 2. S-1 was to be administered orally at a fixed dose of 80 mg/m2 b.i.d. for 21 days followed by a -14-day rest. Cisplatin was to be administered intravenously at a dose of 60 mg/m2 on day 8. Dose-limiting toxicities (DLTs) were defined as grade 4 leukopenia, grade 3 (G3) febrile neutropenia, G3 thrombocytopenia, and G3 nonhematological toxicity.. A total of 9 patients with macroscopic PM were enrolled. No DLTs were observed among the 3 patients at level 1 and 6 patients at level 2. No adverse events or technical problems associated with the IP administration were observed. Consequently, the maximum-tolerated dose was not reached, and the dose for further clinical trials of IP PTX was determined as 20 mg/m2. As for efficacy, peritoneal lavage cytology turned negative after the first course in 4 of 7 patients who had positive cytology before treatment.. The present study determined the dose for further clinical trials of IP PTX to be 20 mg/m2, when combined with the 5-weekly SP regimen.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Female; Humans; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Oxonic Acid; Paclitaxel; Peritoneal Neoplasms; Stomach Neoplasms; Tegafur; Treatment Outcome

Topics: Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Clinical Protocols; Docetaxel; Drug Combinations; Female; Humans; Lymphatic Metastasis; Male; Neoplasm Staging; Oxaliplatin; Oxonic Acid; Postoperative Care; Preoperative Care; Stomach Neoplasms; Tegafur

The KEYNOTE-659 study evaluated the efficacy and safety of pembrolizumab in combination with chemotherapy as the first-line treatment in Japanese patients with advanced gastric/gastroesophageal junction (G/GEJ) cancer. In this paper, we report results from cohort 1 (S-1 plus oxaliplatin [SOX] with pembrolizumab).. This was a non-randomised, multicentre, open-label phase IIb study in patients with advanced programmed death-ligand 1 (PD-L1)-positive, human epidermal growth factor receptor 2-negative G/GEJ tumours. The primary endpoint was the objective response rate (ORR) assessed by blinded independent central review (BICR). Secondary endpoints were duration of response (DOR), disease control rate (DCR), time to response (TTR), progression-free survival (PFS), overall survival (OS) and safety. Exploratory analyses were performed based on the PD-L1 combined positive score (CPS) status.. Fifty-four patients were evaluated. The median follow-up was 10.1 months. ORR and DCR by BICR were 72.2% (95% confidence interval [CI] 58.4-83.5) and 96.3% (95% CI 87.3-99.5), respectively. Median DOR, TTR, PFS and OS were as follows: not reached, 1.5 months, 9.4 months and not reached. The ORR was 73.9% in patients with CPS ≥1 to <10 and 71.0% in those with CPS ≥10. Grade ≥3 treatment-related adverse events (TRAEs) were reported by 57.4% of patients. The most common grade ≥3 TRAEs were decreased platelet count (14.8%), decreased neutrophil count (13.0%), colitis (5.6%) and adrenal insufficiency (5.6%).. SOX with pembrolizumab showed encouraging efficacy and a manageable safety profile for the first-line treatment of advanced G/GEJ cancer.. NCT03382600/JapicCTI-183829.

Topics: Adult; Aged; Antibodies, Monoclonal, Humanized; Antineoplastic Agents, Immunological; Antineoplastic Combined Chemotherapy Protocols; B7-H1 Antigen; Drug Combinations; Esophageal Neoplasms; Esophagogastric Junction; Female; Follow-Up Studies; Humans; Male; Middle Aged; Oxaliplatin; Oxonic Acid; Progression-Free Survival; Receptor, ErbB-2; Remission Induction; Stomach Neoplasms; Tegafur

S-1, a new oral fluorouracil chemotherapeutical drug, has been increasingly used in clinical maintenance after first-line chemotherapy for stage III or IV gastric carcinoma (GC) and colorectal carcinoma (CRC) for its own advantages. XiangshaLiujunzi Decoction (XSLJZD), a classic traditional Chinese medicine (TCM) formula with effects of alleviating the adverse reactions of chemotherapy and improving the quality of life of cancer patients has been gradually confirmed, with no more reports about the maintenance therapy mode of combination of chemotherapeutic drugs and TCM. We designed the study of XSLJZD combined with S-1 in the maintenance therapy of Stage III or IV GC and CRC, and hoped that this research program will go further and comprehensively evaluate its efficacy and safety.. The aim of this study was to determine the efficacy and safety of XSLJZD combined with S-1 in the maintenance therapy of stage III or IV GC and CRC.. This study is an open, single-center, randomized study. Patients with stage III or stage IV GC and CRC will be randomized (1:1) into S-1group, S-1 combined with XSLJZD group for 5 years of maintenance therapy. The primary endpoint was progression-free survival, and secondary end point was overall survival and Quality of Life Assessment (QOLA), which include an improvement in symptoms before and after treatment, Karnofsky Performance Status, and adverse events assessment.. This study will provide meaningful clinical information about the combination of chemotherapeutic drugs S-1 with TCM in the maintenance therapy of stage III or IV GC and CRC.. Chinese Clinical Trial Registry: ChiCTR-INR-16008575.

Topics: Colorectal Neoplasms; Drug Combinations; Drugs, Chinese Herbal; Humans; Maintenance Chemotherapy; Neoplasm Staging; Oxonic Acid; Phytotherapy; Randomized Controlled Trials as Topic; Stomach Neoplasms; Tegafur; Treatment Outcome

Exploring the efficacy and safety of perioperative chemotherapy on patients with AGC at different clinical and pathological stages.. A phase III randomized, multicenter, trial comparing adjuvant (arm A) or perioperative S-1 plus oxaliplatin (SOX, arm B), and perioperative capecitabine plus oxaliplatin (XELOX, arm C) was initiated in T3/4, node + gastric cancer patients (unclear). Each patient received an 8-cycle chemotherapy (3 weeks for one cycle). Group arms B and C received two cycles preoperatively, and six cycles postoperatively. Primary endpoints were R0 resection rate and DFS, and secondary endpoints included OS, ORR, DCR, and safety. This study was registered on Clinicaltrials.gov. NCT01516944.. A total of 749 patients were randomly assigned into groups A, B, and C. Group A received 1460 circles chemotherapy and group B received 1177 circles while group C received 1200 circles. R0 resection rates in the three groups were 81.7%, 88.7%, and 83.1%, respectively. The difference between groups A and B was considered to be statistically significant (P = .018), and no significant difference between groups B and C (P = .051). Hazard ratio were compared between groups B and C and DFS showed 0.72 (0.67-0.77 with 95% CI), P. Compared with PAC, perioperative chemotherapy showed a significant improvement in R0 resection rates and prognosis in AGC patients with higher safety rates. This study was powered to show superiority of perioperative over adjuvant SOX, and noninferiority of SOX to XELOX. Volume measurement, repeated laparoscopic exploration combined with exfoliative cytology can be used as a supplementary method in the clinical staging and efficacy evaluation of AGC.

Topics: Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Chemotherapy, Adjuvant; Confidence Intervals; Disease-Free Survival; Drug Combinations; Female; Humans; Lymph Nodes; Male; Middle Aged; Neoadjuvant Therapy; Oxaliplatin; Oxaloacetates; Oxonic Acid; Prognosis; ROC Curve; Sample Size; Stomach Neoplasms; Tegafur

We conducted a randomized, multicenter, phase III trial to compare S-1 plus docetaxel (DS) with S-1 plus cisplatin (SP) as adjuvant chemotherapy for stage III gastric cancer patients.. Stage III gastric cancer patients who had received curative gastrectomy with D2 lymphadenectomy were randomized into equal groups to receive adjuvant chemotherapy of eight cycles of DS (S-1 70 mg/m2 /day on days 1-14 plus docetaxel 35 mg/m2 on days 1 and 8) every 3 weeks or SP (S-1 70 mg/m2 /day on days 1-14 plus cisplatin 60 mg/m2 on day 1) every 3 weeks. The primary endpoint was 3-year disease-free survival (DFS) rate.. Between November 2010 and July 2013, 153 patients (75 patients to DS and 78 patients to SP) were enrolled from 8 institutions in Korea. After the capecitabine plus oxaliplatin was approved based on the CLASSIC study, itwas decided to close the study early. With a median follow-up duration of 56.9 months, the 3-year DFS rate between two groups was not significantly different (49.14% in DS group vs. 52.5% in SP group). The most common grade 3-4 adverse event was neutropenia (42.7% in DS and 38.5% in SP, p=0.351). SP group had more grade 3-4 anemia (1.3% vs. 11.5%, p=0.037), whereas grade 3-4 hand-foot syndrome (4.1% vs. 0%, p=0.025) and mucositis (10.7% vs. 2.6%, p=0.001) were more common in DS group. Fifty-one patients (68%) in DS group and 52 (66.7%) in SP group finished planned treatment.. Our findings suggest that SP or DS is an effective and tolerable option for patients with curatively resected stage III gastric cancer.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cisplatin; Docetaxel; Dose-Response Relationship, Drug; Drug Combinations; Female; Gastrectomy; Humans; Male; Middle Aged; Oxonic Acid; Republic of Korea; Stomach Neoplasms; Survival Analysis; Tegafur; Treatment Outcome

We carried out a phase II trial to evaluate the feasibility and efficacy of neoadjuvant chemotherapy comprising a single intraperitoneal administration of paclitaxel, followed by intravenous administrations of paclitaxel and cisplatin with S-1 for clinical stage III gastric cancer.. Patients with potentially resectable gastric cancer were eligible. A laparoscopic survey was performed to confirm CY0 and P0. Intraperitoneal paclitaxel (60 mg/m. Twenty patients were enrolled. Planned cycles were completed in all patients. Grade 3/4 leukopenia and grade 3/4 neutropenia were observed in four (20%) and seven (35%) patients, respectively. The overall response rate was 70% (partial response: 14, stable disease: 5, progressive disease: 1). All patients underwent R0 gastrectomy with D2 lymph-node dissection, with no surgery-related deaths. The pathological response rate was 65% (13 of 20). The 3- and 5-year overall survival rates were 90.0% and 77.1%, respectively.. Neoadjuvant chemotherapy including intraperitoneal paclitaxel followed by sequential intravenous paclitaxel and cisplatin with S-1 for resectable advanced gastric cancer is feasible and effective.

Topics: Adenocarcinoma; Administration, Intravenous; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Signet Ring Cell; Chemotherapy, Adjuvant; Cisplatin; Drug Combinations; Feasibility Studies; Female; Follow-Up Studies; Humans; Injections, Intraperitoneal; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Oxonic Acid; Paclitaxel; Stomach Neoplasms; Survival Rate; Tegafur; Young Adult

Two phase 2 trials of oxaliplatin-containing adjuvant therapy for patients with gastric cancer (GC) after D2 gastrectomy were conducted in Japan. The SOXaGC trial evaluated the tolerability and safety of adjuvant therapy with S-1 plus oxaliplatin (SOX), whereas the J-CLASSIC trial evaluated the feasibility of adjuvant therapy with capecitabine plus oxaliplatin (CAPOX). Because both were studies that did not evaluate survival results as study end points, the authors evaluated the survival outcomes for the patients in the two trials.. All 62 and 100 patients in the full analysis set of the SOXaGC and J-CLASSIC trials, respectively, were included in the current study. Their information about survival outcome was collected. The primary end point was relapse-free survival (RFS), and the secondary end point was overall survival (OS).. For the pathologic stage (pStage 2) patients treated with CAPOX, the 3-year RFS rate was 87.8% and the 3-year OS rate was 92.7%. For the pStage 3 patients treated with SOX and CAPOX, the 3-year RFS rates were respectively 70.9% and 67.8% (hazard ratio [HR], 0.93; 95% confidence interval [CI], 0.50-1.72), whereas the 3-year OS rates were respectively 75.7% and 79.3% (HR, 1.10; 95% CI, 0.54-2.26). Subgroup analysis showed significant interactions between the treatment (SOX vs. CAPOX) and both sex (male vs. female; P = 0.024) and histologic type (diffuse vs. other, P = 0.069).. This exploratory analysis demonstrated that SOX and CAPOX are suggested to have similar efficacy for pStage 3 GC patients after D2 gastrectomy. Differences in the treatment effect according to sex and histologic type warrant further evaluation.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Chemotherapy, Adjuvant; Drug Combinations; Female; Follow-Up Studies; Gastrectomy; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Oxaliplatin; Oxonic Acid; Prognosis; Stomach Neoplasms; Survival Rate; Tegafur

Nivolumab is approved as an option for third- or later-line treatment of advanced gastric/gastroesophageal junction (G/GEJ) cancer in several countries after ATTRACTION-2. To further improve the therapeutic efficacy of first-line therapy, exploration of a nivolumab-chemotherapy combination is warranted. In part 1 (phase II) of ATTRACTION-4, the safety and efficacy of nivolumab combined with S-1 plus oxaliplatin (SOX) or capecitabine plus oxaliplatin (CapeOX) as first-line therapy for unresectable advanced or recurrent human epidermal growth factor receptor 2 (HER2)-negative G/GEJ cancer were evaluated.. Patients were randomized (1 : 1) to receive nivolumab (360 mg intravenously every 3 weeks) plus SOX (S-1, 40 mg/m2 orally twice daily for 14 days followed by 7 days off; oxaliplatin, 130 mg/m2 intravenously on day 1 every 3 weeks) or CapeOX (capecitabine, 1000 mg/m2 orally twice daily for 14 days followed by 7 days off; oxaliplatin, 130 mg/m2 intravenously on day 1 every 3 weeks) until disease progression, unacceptable toxicity, or consent withdrawal.. Of 40 randomized patients, 39 (nivolumab plus SOX, 21; nivolumab plus CapeOX, 18) and 38 (21 and 17, respectively) comprised the safety and efficacy populations, respectively. Most frequent (>10%) grade 3/4 treatment-related adverse events were neutropenia (14.3%) in the nivolumab plus SOX group, and neutropenia (16.7%), anemia, peripheral sensory neuropathy, decreased appetite, type 1 diabetes mellitus, and nausea (11.1% each) in the nivolumab plus CapeOX group. No treatment-related death occurred. Objective response rate was 57.1% (95% confidence interval 34.0-78.2) with nivolumab plus SOX and 76.5% (50.1-93.2) with nivolumab plus CapeOX. Median overall survival was not reached (NR) in both groups. Median progression-free survival was 9.7 months (5.8-NR) and 10.6 months (5.6-12.5), respectively.. Nivolumab combined with SOX/CapeOX was well tolerated and demonstrated encouraging efficacy for unresectable advanced or recurrent HER2-negative G/GEJ cancer. ATTRACTION-4 has proceeded to part 2 (phase III) to compare nivolumab plus SOX/CapeOX versus placebo plus SOX/CapeOX.. NCT02746796.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Drug Combinations; Esophagogastric Junction; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Nivolumab; Oxaliplatin; Oxonic Acid; Prognosis; Stomach Neoplasms; Survival Rate; Tegafur

Postoperative adjuvant chemotherapy with S-1 for 1 year (corresponding to eight courses) is standard care for stage II gastric cancer. Whether the duration of S-1 could be shortened to 6 months (corresponding to four courses) without worsening survival is unclear. The aim of this study was to investigate the non-inferiority of four courses of S-1 compared with eight courses of S-1 for patients with stage II gastric cancer.. We did a phase 3, open-label, randomised controlled, non-inferiority trial at 59 hospitals in Japan. Patients aged 20-80 years with stage II adenocarcinoma of the stomach were randomly assigned (1:1) to eight courses or four courses of S-1. Randomisation was done by the Japan Clinical Oncology Group Data Center website, using a minimisation method with a random component using institution, stage (IIA vs IIB), age (<70 years vs ≥70 years), and mode of operation (open gastrectomy with bursectomy vs open gastrectomy without bursectomy vs laparoscopic gastrectomy) as adjustment factors. One course was 80 mg/day per m. Between Feb 16, 2012, and March 19, 2017, 590 patients were enrolled (295 per group). 528 (89%) patients were analysed at the first planned interim analysis in March, 2017, at which time the point estimate of HR for the four-course group compared with the eight-course group was 2·52 (95% CI 1·11-5·77), which exceeded 1·37 and met the prespecified criteria for early termination. Predictive probability for showing non-inferiority at the final analysis was calculated to be 2·9%. The study was stopped for futility. Updated 3-year relapse-free survival analysed in May, 2017, was 93·1% (95% CI 87·8-96·1) for the eight-course group and 89·8% (84·2-93·5) for the four-course group (HR 1·84, 95% CI 0·93-3·63). The most common grade 3-4 adverse event was neutropenia, observed in 46 (16%) patients in the eight-course group and 51 (17%) patients in the four-course group.. S-1 for 1 year should remain as standard adjuvant chemotherapy for stage II gastric cancer.. Japan Agency for Medical Research and Development; the Ministry of Health, Labour and Welfare of Japan; the National Cancer Center Research and Development Fund, Japan.

Topics: Adenocarcinoma; Aged; Antimetabolites, Antineoplastic; Case-Control Studies; Chemotherapy, Adjuvant; Disease-Free Survival; Drug Combinations; Female; Gastrectomy; Humans; Intention to Treat Analysis; Japan; Laparoscopy; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Prospective Studies; Stomach Neoplasms; Survival Analysis; Tegafur

Trastuzumab with S-1 plus cisplatin was proved to be effective for human epidermal growth factor receptor type 2 (HER2)-positive advanced gastric cancer with measurable lesions. However, the efficacy and safety of this regimen in the absence of measurable lesions are unknown.. Patients with HER2-positive gastric cancer without measurable lesions received cisplatin plus trastuzumab intravenously on day 1 and oral S-1 on days 1-14 of a 21-day cycle. The primary end-point was overall survival, and 40 patients were planned to be enrolled.. Fifteen patients were enrolled. The median overall survival was 14.4 months. The 1- and 3-year overall survival rates were 66.7 % and 26.7 %, respectively. Major grade 3-4 adverse events included neutropenia (47%), anemia (40%), diarrhea (20%), nausea (20%), and anorexia (20%).. Trastuzumab with S-1 plus cisplatin might be effective and tolerable for HER2-positive advanced gastric cancer without measurable lesions.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Disease-Free Survival; Drug Combinations; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Receptor, ErbB-2; Stomach Neoplasms; Tegafur; Trastuzumab; Treatment Outcome; Young Adult

Inflammation plays an important role in tumor progression. Predicting survival is remarkably difficult in patients with gastric cancer receiving neoadjuvant chemotherapy. The aim of the present study is to investigate the potential prognostic significance of the platelet-to-lymphocyte ratio in patients with gastric cancer receiving S-1 plus oxaliplatin or oxaliplatin and capecitabine regimen.. Ninety-one patients with gastric cancer treated with neoadjuvant chemotherapy were enrolled in this study and then underwent operation. The optimal cutoff value was calculated using receiver-operating characteristic curve analyses. The optimal cutoff value of platelet-to-lymphocyte ratio was divided into low platelet-to-lymphocyte ratio <162 group and high platelet-to-lymphocyte ratio ≥162 group. Kaplan-Meier method and log-rank test were used to analyze the survival curves. The independent prognostic factors and prognostic value of the platelet-to-lymphocyte ratio were assessed by univariate and multivariate Cox proportional hazards regression model. The toxicity was evaluated according to the National Cancer Institute Common Toxicity Criteria.. Kaplan-Meier analyses revealed that patients with low platelet-to-lymphocyte ratio correlated remarkably with better mean disease-free survival and mean overall survival than those with high platelet-to-lymphocyte ratio (mean disease-free survival 47.33 and 33.62 months, respectively; mean overall survival 51.21 and 36.80 months, respectively). The results demonstrated that platelet-to-lymphocyte ratio had prognostic significance using the cutoff value of 162 on disease-free survival and overall survival, and the mean disease-free survival and overall survival time for patients with low platelet-to-lymphocyte ratio were longer than those with high platelet-to-lymphocyte ratio. Meanwhile, patients with gastric cancer who had lower platelet-to-lymphocyte ratio had longer 1-, 3-, and 5-year rates of disease-free survival and overall survival. Moreover, patients with low platelet-to-lymphocyte ratio had longer mean disease-free survival and overall survival than those with high platelet-to-lymphocyte ratio in receiving S-1 plus oxaliplatin or oxaliplatin and capecitabine regimen.. The preoperative platelet-to-lymphocyte ratio may be a promising and convenient prognostic biomarker for patients gastric cancer receiving S-1 plus oxaliplatin or oxaliplatin and capecitabine regimen neoadjuvant chemotherapy. It may be useful to help the doctors identify the high-risk patients for taking efficient treatment strategy decisions.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Blood Platelets; Capecitabine; Drug Combinations; Female; Follow-Up Studies; Humans; Lymphocytes; Male; Middle Aged; Oxaliplatin; Oxonic Acid; Prognosis; Retrospective Studies; Stomach Neoplasms; Survival Rate; Tegafur

The prognosis of patients with linitis plastica (type 4) and large (≥ 8 cm) ulcero-invasive-type (type 3) gastric cancer is extremely poor, even after extended surgery and adjuvant chemotherapy. Given the promising results of our previous phase II study evaluating neoadjuvant chemotherapy (NAC) with S-1 plus cisplatin (JCOG0210), we performed a phase III study to confirm the efficacy of NAC in these patients, with the safety and surgical results are presented here.. Eligible patients were randomized to gastrectomy plus adjuvant chemotherapy with S-1 (Arm A) or NAC followed by gastrectomy + adjuvant chemotherapy (Arm B). The primary endpoint was the overall survival (OS). This trial is registered at the UMIN Clinical Trials Registry as C000000279.. From February 2007 to July 2013, 300 patients were randomized (Arm A 149, Arm B 151). NAC was completed in 133 patients (88%). Major grade 3/4 adverse events during NAC were neutropenia (29.3%), nausea (5.4%), diarrhea (4.8%), and fatigue (2.7%). Gastrectomy was performed in 147 patients (99%) in Arm A and 139 patients (92%) in Arm B. The operation time was significantly shorter in Arm B than in Arm A (median 255 vs. 240 min, respectively; p = 0.024). There were no significant differences in Grade 2-4 morbidity and mortality (25.2% and 1.3% in Arm A and 15.8% and 0.7% in Arm B, respectively).. NAC for type 4 and large type 3 gastric cancer followed by D2 gastrectomy can be safely performed without increasing the morbidity or mortality.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Drug Combinations; Female; Follow-Up Studies; Gastrectomy; Humans; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Oxonic Acid; Peritoneal Neoplasms; Stomach Neoplasms; Survival Rate; Tegafur; Young Adult

S-1 is a standard postoperative adjuvant chemotherapy for patients with stage II or III gastric cancer in Asia. Neoadjuvant or perioperative strategies dominate in Western countries, and docetaxel has recently shown significant survival benefits when combined with other standard regimens in advanced cancer and perioperative settings.. This randomized phase III study was designed to prove the superiority of postoperative S-1 plus docetaxel over S-1 alone for R0 resection of pathologic stage III gastric cancer. The sample size of 1,100 patients was necessary to detect a 7% increase in 3-year relapse-free survival as the primary end point (hazard ratio, 0.78; 2-sided α = .05; β = .2).. The second interim analysis was conducted when the number of events reached 216 among 915 enrolled patients (median follow-up, 12.5 months). Analysis demonstrated the superiority of S-1 plus docetaxel (66%) to S-1 (50%) for 3-year relapse-free survival (hazard ratio, 0.632; 99.99% CI, 0.400 to 0.998; stratified log-rank test,. Addition of docetaxel to S-1 is effective with few safety concerns in patients with stage III gastric cancer. The present findings may also be applicable in countries in which perioperative adjuvant chemotherapy or chemoradiation is not standard.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Docetaxel; Drug Combinations; Female; Gastrectomy; Humans; Male; Medication Adherence; Middle Aged; Neoplasm Staging; Oxonic Acid; Postoperative Care; Stomach Neoplasms; Tegafur

Postoperative docetaxel plus S-1 (DS) chemotherapy is expected to be the standard therapeutic strategy for pStage III gastric cancer based on the results of the JACCRO GC-07 study. Neoadjuvant chemotherapy (NAC) is thought to have several advantages over adjuvant settings.. This study aimed to compare the efficacies of NAC DS and the surgery-first strategy for advanced gastric cancer patients with D2 gastrectomy.. This was a retrospective, single-institution observational study. Of 171 patients with locally advanced (cStage IIB or III) gastric cancer who underwent curative D2 gastrectomy and received NAC DS and/or S-1 adjuvant chemotherapy between 2011 and 2017, 76 (after propensity score matching for 132 patients who met the eligibility criteria) were enrolled in this study. The 3-year progression-free survival (PFS) rate was used to directly compare efficacies between NAC DS patients and surgery-first patients.. The 3-year PFS rates for the NAC DS group were significantly higher than those for the surgery-first group (80.0 vs. 58.7; p = 0.037), and the progression hazard ratio of the NAC DS group compared with the surgery-first group was 0.394 (95% confidence interval 0.159-0.978; p = 0.045).. The NAC DS group showed a high 3-year PFS compared with the surgery-first group, with standard S-1 postoperative chemotherapy or observation. NAC DS can be expected to be beneficial as the standard therapy for advanced gastric cancer and should be adopted for the test arm of a randomized controlled phase III trial.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Docetaxel; Drug Combinations; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neoadjuvant Therapy; Oxonic Acid; Prognosis; Propensity Score; Retrospective Studies; Stomach Neoplasms; Survival Rate; Tegafur

The importance of definitive radiotherapy for elderly patients with esophageal and esophagogastric-junction cancer is pronounced. However, little is known in terms of the best way to combine radiotherapy with other treatment options. This study aims to compare the efficiency of SIB radiotherapy alone with SIB radiotherapy concurrent and consolidated with S-1 for elderly patients. Comprehensive geriatric assessment is also incorporated in the procedure of treatment.. The study is a two arm, open, randomized multicenter Phase III trial with patients over 70 years old with stage IIA-IVB (UICC 2002, IVB only with metastasis to supraclavicular or celiac lymph nodes) squamous cell carcinoma or adenocarcinoma of esophagus or gastroesophageal junction. A total of 300 patients will be randomized using a 1:1 allocation ratio stratified by disease stage and study site. Patients allocated to the SIB arm will receive definitive SIB radiotherapy (95%PTV/PGTV 50.4Gy/59.92Gy/28f) while those randomized to SIB + S-1 arm will receive definitive SIB radiotherapy concurrent and consolidated with S-1. The primary endpoint of the trial is 1-year overall survival. Secondary objectives include progression-free survival, recurrence-free survival (local-regional and distant), disease failure pattern, toxicity profile as well as quality of life. Besides, detailed radiotherapy protocol and quality assurance procedure have been incorporated into this trial.. The proportion of elderly patients in esophageal cancer is now growing, but there is a lack of evidence in term of treatment standard for this group of patients, which is what we aim to obtain through this prospective phase III study.. clinicaltrials.gov NCT02979691 . Registered November 22, 2016.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Chemoradiotherapy; Drug Combinations; Esophageal Neoplasms; Esophagogastric Junction; Female; Fluorouracil; Humans; Male; Neoplasm Staging; Outcome Assessment, Health Care; Oxonic Acid; Prospective Studies; Radiotherapy, Intensity-Modulated; Stomach Neoplasms; Tegafur

Oxaliplatin plus S-1 (SOX) was a first-line regimen for advanced gastric cancer. The continuous administration of S-1 for 3 weeks can result in unacceptable gastrointestinal and hematological toxicities. Therefore, an alternative regimen (administration of S-1 for 1-week followed by 1-week rest) is warrant for improved tolerability and noninferiority efficacy. We conducted a study to evaluate the efficacy and safety of biweekly SOX as the first-line chemotherapy in patients with metastatic or advanced gastric cancer in China.Patients with metastatic or previously untreated advanced gastric cancer were enrolled. Oxaliplatin was administered intravenously at a dose of 85 mg/m on day 1, while S-1 was administered orally in doses of 80, 100, or 120 mg/day depending on different body surface areas of <1.25 m, 1.25-1.5 m, or >1.5 m respectively; the total dose of S-1 was administered twice daily on days 1-7 followed by a 7-day rest. This schedule was repeated every 2 weeks until disease progressed or intolerable toxicity occurred.Forty-six patients (M/F = 33/13) received biweekly oxaliplatin and S-1 as first-line chemotherapy. A total of 257 treatment cycles were administered and the median number of cycles administered was 6. Thirty-six patients (78.3%) received second-line chemotherapy. The median progression free survival and median overall survival was 4.4 months (95% CI, 3.37-5.36 months) and 10.3 months (95% CI, 8.88-11.3 months), respectively. The 1-year and 2-year survival rate was 41% and 13%. The objective response rate was 30.43%, and the disease control rate was 76.08%. The observed adverse events of Grade 3/4 included were leukocytopenia (13.04%); anemia (13.04%); neutropenia (15.22%); neurological toxicity (2.17%); diarrhea (2.17%).The biweekly SOX regimen as first-line treatment was active and well tolerated in Chinese patients with metastatic or advanced gastric cancer.

Topics: Administration, Intravenous; Adult; Aged; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; China; Disease-Free Survival; Drug Administration Schedule; Drug Combinations; Female; Humans; Male; Middle Aged; Oxaliplatin; Oxonic Acid; Stomach; Stomach Neoplasms; Tegafur; Treatment Outcome

Trastuzumab with cisplatin and fluoropyrimidines improves overall survival (OS) in patients with HER2-positive advanced gastric cancer (AGC). S-1 plus oxaliplatin (SOX) is one of the standard regimens for HER2-negative AGC in Japan. However, few studies have evaluated trastuzumab combined with SOX in patients with HER2-positive AGC.. This was a multicenter, phase II study conducted at 10 institutions in Japan. Patients with HER2-positive AGC received S-1 twice a day on days 1-14 and oxaliplatin and trastuzumab on day 1 of a 21-day cycle. The primary endpoint was the confirmed overall response rate (ORR), and the secondary endpoints were OS, progression-free survival (PFS), and safety. The sample size was 75 to have 90% power with an alpha error of 0.1 (one-sided), expecting an ORR of 65% and threshold of 50%.. From June 2015 to January 2018, 75 patients were enrolled. The ORR was 70.7% [95% confidence interval (CI) 59.0-80.6]. The median OS and PFS were estimated as 18.1 months (95% CI 15.6-26.5) and 8.8 months (95% CI 7.4-12.2), respectively. The major grade 3 or 4 adverse events were sensory neuropathy (16.0%) and neutropenia (10.7%).. Trastuzumab with SOX had promising activity with well-tolerated toxicities for patients with HER2-positive AGC.. UMIN000017602.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Female; Humans; Japan; Male; Middle Aged; Oxaliplatin; Oxonic Acid; Progression-Free Survival; Prospective Studies; Receptor, ErbB-2; Stomach Neoplasms; Survival Rate; Tegafur; Trastuzumab; Treatment Outcome; Young Adult

Oral mucositis is one of the most common reasons for discontinuation of S-1 adjuvant chemotherapy after radical gastrectomy. Some studies suggest that nutritional support with amino acids may improve oral mucositis. We conducted a prospective, randomized clinical trial of patients who underwent adjuvant chemotherapy for gastric cancer to examine whether an oral elemental diet prevents chemotherapy associated oral mucositis and body weight loss.. Patients were randomly assigned to a group consuming Elental. The incidence of oral mucositis was significantly lower in the treatment group (9.1%) than in the control group (27.3%). The median body weight loss in the treatment group was significantly smaller than that in the control group (P = .015). According to Kaplan-Meier estimates the treatment group was significantly associated with high cumulative S-1 continuation rates (log-rank P = .047).. We conclude that the amino-acid-rich elemental diet Elental

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Case-Control Studies; Diarrhea; Drug Combinations; Female; Follow-Up Studies; Food, Formulated; Humans; Incidence; Japan; Male; Middle Aged; Nutritional Support; Oxonic Acid; Pilot Projects; Prognosis; Prospective Studies; Stomach Neoplasms; Stomatitis; Tegafur; Young Adult

The prognosis of patients with locally advanced gastric cancer or esophagogastric junction adenocarcinoma is still dismal. There are no standard treatment strategies for these patients. Multidisciplinary team (MDT) approach is a good choice for making a high-quality decision. Generally, MDT will recommend these patients to receive preoperative chemotherapy or preoperative chemoradiation based on all kinds of treatment guidelines. However, the preferred preoperative treatment is still not established. In order to solve this problem, we carry out this randomized phase III trial of comparing preoperative chemoradiation with preoperative chemotherapy in patients with locally advanced gastric cancer or esophagogastric junction adenocarcinoma.. Eligible patients with locally advanced gastric cancer or esophagogastric junction adenocarcinoma are randomized to receive preoperative chemoradiation or preoperative chemotherapy, followed by surgery and postoperative chemotherapy. In the preoperative chemoradiation arm (Pre-CRT), patients receive two cycles of S-1 and oxaliplatin (SOX), chemoradiation, then followed by surgery and three more cycles of SOX chemotherapy. In the preoperative chemotherapy arm (Pre-CT), patients receive three cycles of SOX, following surgery three more cycles of SOX are given. The primary endpoint of this trial is to verify that preoperative chemoradiation could significantly improve the 3-year disease free survival (DFS) of patients with locally advanced gastric cancer or esophagogastric junction adenocarcinoma compared to preoperative chemotherapy.. The results from this trial will provide important information about whether preoperative chemoradiation could improve survival compared to preoperative chemotherapy among patients with locally advanced gastric cancer or esophagogastric junction adenocarcinoma.. ClinicalTrials.gov Identifier: NCT03013010. First posted January 6, 2017.

Topics: Adenocarcinoma; Adolescent; Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Chemoradiotherapy, Adjuvant; Chemotherapy, Adjuvant; China; Disease-Free Survival; Drug Combinations; Esophageal Neoplasms; Esophagogastric Junction; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neoadjuvant Therapy; Oxaliplatin; Oxonic Acid; Prospective Studies; Stomach Neoplasms; Tegafur; Young Adult

Previous studies have shown sex-related differences in the incidence of adverse events following treatment with fluoropyrimidines, however the mechanism of this difference is unknown. We examined sex-related differences in the safety of S-1 plus oxaliplatin (SOX) and S-1 plus cisplatin (CS) in 663 metastatic gastric cancer patients taking part in a phase III study. The incidences of leukopenia (odds ratio [OR] 1.9; P = .015), neutropenia (OR 2.2; P = .002), nausea (OR 2.0; P = .009), and vomiting (OR 2.8; P < .001) were increased in women versus men treated with SOX, while vomiting (OR 2.9; P < .001) and stomatitis (OR 1.8; P = .043) were increased in women versus men treated with CS. In contrast, male patients treated with CS experienced thrombocytopenia more often (OR 0.51; P = .009). The mean relative dose intensity of S-1 in SOX was 75.4% in women and 81.4% in men (P = .032). No difference in efficacy was observed between women and men undergoing either regimen. Sex-related differences in adverse reactions during SOX and CS treatment were confirmed in this phase III study. Further translational research studies are warranted to pursue the cause of this difference.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Disease-Free Survival; Dose-Response Relationship, Drug; Drug Combinations; Female; Humans; Incidence; Male; Middle Aged; Nausea; Neutropenia; Oxaliplatin; Oxonic Acid; Sex Factors; Stomach Neoplasms; Stomatitis; Tegafur; Thrombocytopenia; Vomiting

Gastric cancer with extensive lymph node metastasis is commonly regarded as unresectable, while preoperative chemotherapy followed by gastrectomy has been tested since 2000 in JCOG (JCOG0001 and JCOG0405). The survivals were quite different between the trials despite the similar eligibility criteria. The aim of this study was to investigate if survival is still better in JCOG0405 after adjusting baseline factors and if there is any subset of patients who benefit more from either treatment.. Eligibility criteria for both trials included histologically proven gastric adenocarcinoma; bulky nodal involvement around the celiac artery and its major branches (bulky N) and/or para-aortic lymph node (PAN); cM0 (except PAN); negative lavage cytology; not linitis plastica type; PS of 0 or 1. Patients received two or three cycles of preoperative chemotherapy of irinotecan plus cisplatin in JCOG0001, or S-1 plus cisplatin in JCOG0405, followed by D3 gastrectomy. Multivariable analysis for overall survival adjusting baseline and treatment factors was performed with the Cox regression model.. After adjusting baseline factors, S-1 plus cisplatin was superior to irinotecan plus cisplatin for overall survival (HR = 0.39: 95% CI 0.22-0.67). The 5-year overall survival was poor for patients with bulky N+/PAN+ (19.2%) compared with bulky N+/PAN- (50.7%) or bulky N-/PAN+ (43.5%).. S-1 plus cisplatin was shown to be a favorable preoperative treatment for gastric cancer with extensive lymph node metastasis by multivariable analysis, while poor prognosis in patients having both bulky N+ and PAN+ may necessitate further treatment improvement.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Drug Combinations; Female; Gastrectomy; Humans; Irinotecan; Lymphatic Metastasis; Male; Middle Aged; Oxonic Acid; Prognosis; Stomach Neoplasms; Survival Rate; Tegafur

Five-weekly S-1 plus cisplatin (SP) therapy is the standard care for advanced gastric or esophagogastric junction cancer (GC/EGJC) in East Asia. However, its efficacy and safety when combined with trastuzumab therapy for human epidermal growth factor receptor 2 (HER2)-positive advanced GC/EGJC remains unclear.. Forty-four patients were enrolled. The response rate, progression-free survival, and overall survival were 61% (95% confidence interval 46-76%), 5.9 months, and 16.5 months respectively. The commonest grade 3 or grade 4 adverse events were neutropenia (30%) and anorexia (25%). A significantly higher response rate (92% vs 43%; P = 0.008) and longer progression-free survival (median 14.5 months vs 4.2 months; P = 0.028) were observed in patients with high (n = 14) compared with low (n = 17) pretreatment serum neuregulin 1 levels.. Five-weekly SP therapy combined with trastuzumab therapy showed a good antitumor response and acceptable toxicity in HER2-positive advanced GC/EGJC. Serum neuregulin 1 might be associated with the efficacy of this treatment regimen.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Cisplatin; Disease-Free Survival; Drug Combinations; Female; Humans; Male; Middle Aged; Oxonic Acid; Receptor, ErbB-2; Stomach Neoplasms; Tegafur; Trastuzumab

We evaluated the safety, tolerability, pharmacokinetics, and tumor response of ramucirumab in combination with one of three platinum/fluoropyrimidine regimens in Japanese patients with chemotherapy-naïve metastatic gastric/gastroesophageal junction cancer.. In this phase 1b study, patients received 8 mg/kg ramucirumab on days 1 and 8 every 3 weeks, following one of three regimens: capecitabine + cisplatin, XP; S-1 + cisplatin, SP; or S-1 + oxaliplatin, SOX. The primary objective was to assess safety and tolerability; the secondary objectives were to evaluate pharmacokinetics and tumor response.. Six patients were treated in each cohort. All regimens were generally well tolerated, although 1 patient in SOX was associated with grade 3 enterocolitis, which was considered a dose-limiting toxicity. Common grade 3 or higher adverse events included neutropenia (1 in XP, 3 in SP, and 2 in SOX), decreased appetite (1 in SP), and hypertension (2 in XP). The mean trough ramucirumab concentrations were consistent across all cohorts, and those of most patients exceeded target levels, which were estimated from previous studies of the approved ramucirumab dose (8 mg/kg every 2 weeks). Among the 11 patients with measurable disease, overall response rate and disease control rate were 45.5% and 100.0%, respectively. Median progression-free survival (95% CI) was 7.6 months (6.0 to not estimable).. Ramucirumab 8 mg/kg on days 1 and 8 every 3 weeks in combination with XP, SP, or SOX was generally well tolerated and demonstrated preliminary anti-tumor activity in chemotherapy-naïve Japanese metastatic gastric/gastroesophageal junction cancer patients.

Topics: Adenocarcinoma; Aged; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents, Immunological; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Cisplatin; Disease-Free Survival; Drug Combinations; Esophagogastric Junction; Female; Humans; Male; Maximum Tolerated Dose; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Ramucirumab; Stomach Neoplasms; Tegafur

To investigate the usefulness of S-1 plus cisplatin alternating with S-1 plus docetaxel as first-line treatment in patients with advanced gastric cancer, we conducted a phase I/II study to determine the maximum tolerated dose and recommended dose, and evaluate efficacy and toxicity.. Patients with histologically confirmed unresectable and recurrent gastric cancer were enrolled in this study. Cisplatin was administered on day 1 and the dose escalated by 10 mg/m from a starting dose of 40 mg/m in the phase I part. S-1 was given orally at 80 mg/m on days 1 to 14 and docetaxel at 40 mg/m on day 22 in combination with S-1 80 mg/m on days 22 to 35. The treatment was repeated every 6 weeks. The primary endpoint of the phase II analysis was the response rate.. Nine patients entered the phase I and 24 the phase II part. Because 50% of patients (3/6) developed dose-limiting toxicities in the phase I part, the maximum tolerated dose of cisplatin was presumed to be 50 mg/m. Therefore, the estimated recommended dose of cisplatin was 40 mg/m; 27 patients received that dose. The response rate was 59.3% (95% confidence interval, 40.8-77.8) and the median follow-up 26.2 months. The median progression-free survival was 7.9 months and the median overall survival 18.6 months. The most common grade 3/4 toxicities were neutropenia (59.3%), leucopenia (37.0%), and anemia (29.6%). These toxicities were tolerable and manageable.. This alternating treatment seems to have promising activity with tolerable toxicities in the first-line treatment of patients with advanced gastric cancer.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Docetaxel; Drug Combinations; Female; Follow-Up Studies; Humans; Lymphatic Metastasis; Male; Maximum Tolerated Dose; Middle Aged; Oxonic Acid; Prognosis; Stomach Neoplasms; Survival Rate; Tegafur

S-1 plus cisplatin is a standard regimen for advanced gastric cancer (AGC) in Asia. The ToGA trial established a fluoropyrimidine plus cisplatin and trastuzumab as a standard treatment for human epidermal growth factor receptor 2 (HER2)-positive AGC. In the HERBIS-1 trial, trastuzumab combined with S-1 plus cisplatin showed promising antitumor activity in patients with HER2-positive AGC. However, cisplatin has several important drawbacks, including vomiting and renal toxicity. These disadvantages of cisplatin are prominent in elderly patients. Therefore, we conducted a prospective phase II study of trastuzumab plus S-1 without cisplatin in elderly patients with HER2-positive AGC.. Patients 65 years or older who had HER2-positive AGC received S-1 orally on days 1-28 of a 42-day cycle and trastuzumab intravenously on day 1 of a 21-day cycle.. A total of 51 patients were enrolled. Two patients were ineligible. The full analysis set thus comprised 49 patients. The median age was 71 years (range 65-85). The confirmed response rate was 40.8% (95% CI 27.1-54.6%), and the null hypothesis was rejected. The median follow-up period was 10.6 months. Median overall survival was 15.8 months. Median progression-free survival was 5.1 months, and time to treatment failure was 4.0 months. Major grade 3 or 4 adverse events included neutropenia (12.0%), anemia (24.0%), diarrhea (10.0%), and anorexia (12.0%). There was one treatment-related death.. Trastuzumab in combination with S-1 alone demonstrated promising antitumor activity and manageable toxic effects as well as promising survival results in elderly patients with HER2-positive AGC.. UMIN000007368.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Disease-Free Survival; Drug Combinations; Female; Humans; Male; Oxonic Acid; Prospective Studies; Receptor, ErbB-2; Stomach Neoplasms; Tegafur; Trastuzumab

Recent gastric cancer clinical trials have aimed to establish the efficacy of combination therapy over monotherapy, however, the role for genomic biomarkers in these trials has remained largely unexplored. Here, using the NanoString expression platform, we analyzed 105 gastric tumors from a randomized phase III Japanese clinical trial (GC0301/TOP002) testing the efficacy of irinotecan plus S-1(IRI-S) versus S-1 therapy. We found that previously established proliferative subtype signatures, were associated with older patients (>65 years) and liver metastasis while mesenchymal subtype signatures were associated with younger patients (≤65 years) and peritoneal metastasis. Genes associated with tumor microenvironment (CD4, CD14, ADAMTS1, CCL5, CXCL12, CCL19), therapeutic implications (DPYD) and oncogenic signaling (Wnt5A, PTRF) were significantly associated with patient age, histology, tumor status, measurable lesions and metastasis. We identified Wnt5A downregulation as a candidate predictor of improved progression free survival (>8 weeks) in S-1 but not in IRI-S treatment. Although statistical significance was not achieved, mesenchymal subtype showed a trend for treatment interaction with IRI-S for efficacy. These findings highlight promising genomic markers that could be useful predictors of chemotherapy efficacy for better prognosis and survival outcome in gastric cancer.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Drug Combinations; Female; Humans; Irinotecan; Liver Neoplasms; Male; Middle Aged; Neoplasm Recurrence, Local; Oxonic Acid; Stomach Neoplasms; Tegafur; Wnt-5a Protein

This study investigated the efficacy and safety of S-1 versus capecitabine in elderly patients with metastatic gastric cancer (MGC), and examined the association between cytochrome P450 2A6 (CYP2A6) polymorphisms and treatment outcomes.. MGC patients 70-85 years old with Eastern Cooperative Oncology Group (ECOG) performance status 0-2 or 65-70 years old with ECOG PS 2 were randomized to receive S-1 40 mg/m, twice daily, or capecitabine 1250 mg/m, twice daily, on days 1-14 every 3 weeks.. From May 2007 up to July 2010, 107 patients were enrolled. G3/4 neutropenia developed in 3.8% of each arm, and the most common G3/4 nonhematological toxicities were anorexia and fatigue. Vomiting and tearing were more frequent with S-1 and hand-foot syndrome with capecitabine. The primary endpoint, the overall response rate, was 26.4% (14/53, 95% confidence interval: 14.5-38.3%) in S-1 and 24.1% (13/54, 95% confidence interval: 12.7-35.5%) in capecitabine, both of which exceeded the null hypothesis response rate of 10%. The median time to progression (TTP; 3.2 vs. 3.4 months, P=0.813) and overall survival (OS; 8.5 vs. 10.3 months, P=0.691) were similar in both arms. CYP2A6 polymorphisms were associated with S-1 efficacy. In the S-1 arm only, patients with CYP2A6 variant/variant alleles had worse TTP and OS than those with wild/wild or wild/variant alleles, and in multivariate analysis, the CYP2A6 genotype was predictive for TTP and OS.. Both S-1 and capecitabine were active and tolerable for elderly MGC patients. The CYP2A6 genotyping might guide treatment selection.

Topics: Activities of Daily Living; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Capecitabine; Cytochrome P-450 CYP2A6; Drug Administration Schedule; Drug Combinations; Female; Humans; Male; Oxonic Acid; Pharmacogenomic Variants; Polymorphism, Single Nucleotide; Random Allocation; Stomach Neoplasms; Survival Analysis; Tegafur; Treatment Outcome

The ideal treatment strategy of patients with locally advanced gastric adenocarcinoma is unclear. The aim of this study is to evaluate the efficacy and feasibility of preoperative chemoradiation in these patients.. All patients underwent laparoscopic exploration or exploratory laparotomy before chemoradiation. Patients received one cycle of S-1 and oxalipatin followed by concurrent radiation and chemotherapy, then underwent another cycle of S-1 and oxalipatin. Surgery was performed 6-8 weeks after completing radiochemotherapy. The rate of curative gastrectomy and survival were investigated. This trial was registered with ClinicalTrial.gov, number NCT02024217.. From April 2012 to August 2014, 40 patients were enrolled in the trial, and 36 patients were assessable. The most common hematologic toxic effects were leukopenia (80.6%), neutropenia (69.4%), and thrombocytopenia (50%); the most common nonhematologic toxic effects were anorexia (50%), nausea (22.3%), and vomiting (13.9%). There were no treatment related deaths. A total of 33 patients underwent second exploratory laparotomy after preoperative chemoradiation, and 24 (67%) patients received curative gastrectomy. The rates of pathological complete response (pCR) were 13.9%. The medial survival time (MST) was 30.3 months.. Preoperative chemoradiation may be an effective treatment strategy among patients with locally advanced gastric adenocarcinoma.

Topics: Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy, Adjuvant; Drug Combinations; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Preoperative Care; Stomach Neoplasms; Tegafur; Treatment Outcome

This phase I/II clinical trial investigated S-1 administered with intensity-modulated radiotherapy (IMRT) as adjuvant therapy for node-positive gastric cancer. Patients had undergone radical resection and D1/D2 lymph node dissection.. In phase I, patients received adjuvant chemoradiotherapy of IMRT (45 Gy in 25 fractions) with concurrent S-1 administered on a dose-escalation schedule to determine the recommended dose (RD). In phase II, the safety and efficacy of the RD of S-1 combined with IMRT were assessed.. We consecutively enrolled 73 patients (56 men; median age, 53 years; range, 29-73 years) and the phase I portion of the study included 27 patients. The RD of S-1 administered concomitantly with IMRT was 80 mg m. S-1 combined with IMRT adjuvant chemoradiotherapy is safe and efficacious for advanced gastric cancer.

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Chemoradiotherapy, Adjuvant; Disease-Free Survival; Drug Combinations; Female; Gastrectomy; Humans; Lymph Node Excision; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Recurrence, Local; Oxonic Acid; Radiotherapy, Intensity-Modulated; Stomach Neoplasms; Survival Rate; Tegafur

Trastuzumab when combined with fluoropyrimidine and cisplatin was proven to improve survival in patients with human epidermal growth factor receptor 2 (HER2)-positive gastric cancer (GC) in the ToGA study. The safety and efficacy of trastuzumab in combination with docetaxel and S-1 have not yet been evaluated.. This study was a multicenter, phase II study. Patients with chemotherapy-naïve HER2-positive advanced or metastatic GC were eligible. Trastuzumab was administered intravenously on day 1 of the first cycle at 8 and 6 mg/kg in subsequent cycles. Docetaxel was administered intravenously at 40 mg/m. A total of 23 patients were enrolled. Median PFS was 6.7 months (95% CI 4.1-10.1). The response rate (RR) was 39.1%. Median overall survival (OS) and time to treatment failure (TTF) were 17.5 and 4.4 months, respectively. Major grade 3-4 adverse events were neutropenia (39.1%), leukopenia (30.4%), and febrile neutropenia (8.7%).. Trastuzumab in combination with docetaxel and S-1 showed effective antitumor activity and manageable toxicities as first-line treatment for patients with HER2-positive GC.

Topics: Aged; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Docetaxel; Drug Combinations; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Oxonic Acid; Progression-Free Survival; Prospective Studies; Receptor, ErbB-2; Stomach Neoplasms; Tegafur; Trastuzumab

Fluoropyrimidine and platinum combination is the standard treatment for advanced or recurrent gastric cancer (AGC). However, fluoropyrimidine monotherapy is commonly used for elderly patients with AGC because of its good tolerability.. In this multicenter retrospective study, we collected clinical data of AGC patients aged 70 years or older, treated with S-1 alone or S-1 plus cisplatin (SP) as the first-line treatment between January 2009 and December 2011. Propensity score matched cohorts (PSMC) were used for reducing the confounding effects to compare efficacy and safety between the two treatment groups. Cox regression analysis was performed to clarify the prognostic factors.. PSMC (n = 109 in each group) were selected from among 444 eligible patients (S-1 group, 210; SP group, 234); the S-1 group included more patients deemed unfit for intensive chemotherapy than the SP group (e.g., higher age, poorer PS, poor renal function). In the PSMC, patients' characteristics were comparable between groups, except the male ratio (S-1 group, 64.2%; SP group, 77.1%; p = 0.04). No significant differences were observed in either overall survival [hazard ratio (HR) 0.93, p = 0.63] or progression-free survival (HR 1.09, p = 0.61). Severe adverse events (AEs) and hospitalization due to AEs were more frequent in the SP group than in the S-1 group (p < 0.001 each).. Our findings do not support the survival benefit of SP over S-1 in elderly patients with AGC. We are now conducting a prospective comparative study to optimize treatment strategy and explore applicability of the geriatric assessment for these patients.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Disease-Free Survival; Drug Combinations; Female; Humans; Male; Multivariate Analysis; Oxonic Acid; Propensity Score; Stomach Neoplasms; Tegafur; Treatment Outcome

Some patients develop recurrence after curative resection and adjuvant chemotherapy. S-1, an oral fluoropyrimidine, is one of the standard regimens in adjuvant chemotherapy, and is also used in first-line treatment for advanced/metastatic gastric cancer. It is controversial as to whether the same treatment strategy can be applied for patients who develop recurrence after adjuvant chemotherapy and those who did not receive adjuvant chemotherapy. To investigate this issue, we compared the outcomes of patients who developed recurrences after treatment with or without adjuvant chemotherapy using the results of the Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer (ACTS-GC).. Patients who had confirmed recurrence in the ACTS-GC trial were analyzed. We defined 2 independent cohorts. Cohort 1 patients were divided by whether they received adjuvant chemotherapy (adjuvant S-1 group and surgery-only group). Cohort 2 patients were divided by whether they received a regimen including S-1 (IS) or not including S-1 (NIS) after recurrence.. A total of 375 patients experienced recurrence (160 in the adjuvant S-1 group and 215 in the surgery-only group). In cohort 1, the median time from recurrence to death (TFRD) was 11.4 months (95% confidence interval [CI], 8.4-13.9) in the adjuvant S-1 group and 11.3 months (95% CI, 9.7-13.1) in the surgery-only group (hazard ratio [HR], 1.05; 95% CI, 0.84-1.31). In cohort 2, 292 patients received chemotherapy after recurrence and were divided into the IS (n = 189) or the NIS group (n = 103). The median TFRD was 13.9 months (95% CI, 12.7-15.6) in the IS group and 8.1 months (95% CI, 6.6-9.7) in the NIS group (HR, 0.59; 95% CI, 0.45-0.76), and there was no significant interaction between the adjuvant S-1 group and surgery-only group.. Adjuvant chemotherapy with S-1 prolonged overall survival without influencing the TFRD. The same treatment strategy may be applied for patients who develop recurrence after adjuvant chemotherapy and those who did not receive adjuvant chemotherapy.. NCT00152217 . First Posted on September 9, 2005.

Topics: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Combined Modality Therapy; Drug Combinations; Female; Humans; Male; Middle Aged; Neoplasm Grading; Neoplasm Recurrence, Local; Neoplasm Staging; Oxonic Acid; Retreatment; Stomach Neoplasms; Survival Analysis; Tegafur; Treatment Outcome

Endostar is a new vascular epithelial inhibitor, which is reported to be effective in treating liver metastasis from gastric cancer. However, the optimal therapeutic regimen of Endostar remains unclear. Thus, our study aimed to examine the efficacy and safety of Endostar continuous intravenous infusion combined with S-1 and oxaliplatin (SOX) chemotherapy in treating such patients.. A total of sixty patients with liver metastasis from gastric cancer admitted in our department were enrolled. The experimental group (n = 30) was treated with Endostar continuous intravenous infusion combined with SOX regimen chemotherapy, and the control group (n = 30) received SOX regimen chemotherapy alone. All patients received at least two cycles of treatment. The objective effective rate (ORR), disease control rate (DCR), progression-free survival (PFS), and adverse reactions were recorded and compared.. The ORR of the experimental group and control group was 63.3% and 43.3% (P = 0.046), respectively. The DCR of the experimental group and the control group was 86.7% and 73.3% (P = 0.034). The median PFS in the experimental group was longer than that in the control group (15.3 months vs. 12 months). There was no significant difference in the incidence of common adverse reactions such as gastrointestinal reaction, bone marrow suppression, and cardiac toxicity between the two groups. No death was observed in the study period.. Continuous infusion of Endostar combined with SOX chemotherapy could be recommended for the treatment of liver metastasis from gastric cancer due to its high effective rate, and Endostar did not increase the incidence of adverse reactions.

Topics: Adult; Aged; Angiogenesis Inhibitors; Antineoplastic Combined Chemotherapy Protocols; Disease-Free Survival; Drug Combinations; Endostatins; Female; Humans; Infusions, Intravenous; Liver Neoplasms; Male; Middle Aged; Neoplasm Staging; Oxaliplatin; Oxonic Acid; Recombinant Proteins; Stomach Neoplasms; Tegafur; Treatment Outcome

Upfront surgery and subsequent S-1 chemotherapy is frequently selected for peritoneal cytology-positive (CY1) gastric cancer patients without other distant metastases (CY1-only). The objective of this study was to confirm the efficacy of this strategy in clinical practice and to identify the risk factors associated with survival.. Overall survival (OS) and recurrence-free survival (RFS) were examined in 36 CY1-only patients who underwent macroscopic curative resection followed by postoperative S-1 chemotherapy between January 2000 and June 2015. Univariate and multivariate analyses were performed using a Cox proportional hazards model to identify risk factors.. The median OS was 22.3 months (95% confidence interval 18.7-31.0). When the OS was compared by a log-rank test, significant differences were observed in the status of lymph node metastasis of pathological N3b (pN3b). Moreover, the univariate and multivariate analyses demonstrated that the status of pN3b was a significant independent risk factor for OS and RFS. The median OS in patients with pathological N0-N3a (pN0-N3a) was 31.0 months, while that in patients with pN3b was 18.2 months (P = 0.002). The median RFS in patients with pN0-N3a was 16.4 months, while that in patients with pN3b was 7.9 months (P = 0.007).. The present study confirmed the efficacy of postoperative S-1 chemotherapy for CY1-only gastric cancer patients who received upfront surgery. This strategy might be recommended as clinical practice for patients with CY1 disease but a more effective treatment should be established for CY1-positive patients, especially for those who are diagnosed with CY1 and pN3b disease.

Topics: Aged; Disease-Free Survival; Drug Combinations; Female; Gastrectomy; Humans; Lymphatic Metastasis; Male; Middle Aged; Oxonic Acid; Peritoneal Lavage; Peritoneal Neoplasms; Postoperative Care; Proportional Hazards Models; Risk Factors; Stomach Neoplasms; Survival Analysis; Tegafur; Treatment Outcome

Neoadjuvant chemotherapy (NAC) is a promising method of improving the survival of resectable gastric cancer. Cisplatin/S-1 (CS) and docetaxel/cisplatin/S-1 (DCS) are both effective against metastatic gastric cancer. This report clarified the impact of these regimens on early endpoints, including the pathological responses, chemotherapy-related toxicities, and surgical results.. Patients with M0 and either T4 or T3 in case of junctional cancer or scirrhous type received two or four courses of cisplatin (60 mg/m2 at day 8)/S-1 (80 mg/m2 for 21 days with 1 week rest) or docetaxel (40 mg/m2 at day 1)/cisplatin (60 mg/m2 at day 1)/S-1 (80 mg/m2 for 14 days with 2 weeks rest) as NAC. Patients then underwent D2 gastrectomy and adjuvant S-1 chemotherapy for 1 year. The primary endpoint was the 3-year overall survival.. Between October 2011 and September 2014, 132 patients were assigned to receive CS (n = 66; 33 in 2 courses and 33 in 4 courses) or DCS (n = 66; 33 in 2 courses and 33 in 4 courses). The respective major grade 3 or 4 hematological toxicities (CS/DCS) were leukocytopenia (14.1%/26.2%), neutropenia (29.7%/47.7%), anemia (14.1%/12.3%), and platelet reduction (3.1%/1.5%). The rate of pathological response, defined as a complete response or < 10% residual cancer remaining, was 19.4% in the CS group and 15.4% in the DCS group, and 15.6% in the two-course group and 19.0% in the 4-course group. The R0 resection rate was 72.7% in the CS group and 81.8% in the DCS group and 80.3% in the two-course group and the 74.2% in the four-course group. No treatment-related deaths were observed.. Our results do not support three-drug therapy with a taxane over two-drug therapy, or any further treatment beyond two cycles as an attractive candidate for the test arm of NAC.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Docetaxel; Drug Combinations; Female; Humans; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Grading; Neoplasm Staging; Oxonic Acid; Stomach Neoplasms; Taxoids; Tegafur

The aim of this study was to identify biomarkers for predicting the efficacy of docetaxel, cisplatin, and S-1 (DCS) therapy for advanced gastric cancer using microarrays of biopsy specimens before chemotherapy.. Nineteen samples were taken from 19 patients with unresectable metastatic gastric cancer who received DCS as a first-line therapy. Laser capture microdissection was performed, and total cellular RNA was extracted from each microdissected sample. Whole-gene expression was analyzed by microarray, and the difference in mRNA expression observed with the microarrays was confirmed by quantitative real-time PCR. Immunohistochemical staining was performed using clinical tissue sections obtained by endoscopic biopsy.. Eleven patients were identified as early responders and 8 patients as nonresponders to DCS therapy. Twenty-nine genes showed significant differences in relative expression ratios between tumor and normal tissues. A classifier set of 29 genes had high accuracy (94.7%) for distinguishing gene expression between 11 early responders and 8 nonresponders. Decreasing the size of the classifier set to 4 genes (PDGFB, PCGF3, CISH, and ANXA5) increased the accuracy to 100%. Expression levels by real-time PCR for validation were well correlated with those 4 genes in microarrays.. The genes identified may serve as efficient biomarkers for personalized cancer-targeted therapy.

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Docetaxel; Dose-Response Relationship, Drug; Drug Combinations; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Male; Microarray Analysis; Middle Aged; Molecular Targeted Therapy; Neoplasm Metastasis; Oxonic Acid; Prognosis; Stomach Neoplasms; Survival Analysis; Taxoids; Tegafur; Treatment Outcome

Although S-1 based chemotherapy for patients with advanced gastric cancer has generally been accepted in Japan, discontinuations of treatment have been reported due to grade 3 or more adverse events. The present randomized phase II study was conducted to test whether alternate-day administration of S-1 would be comparably efficient and reduce adverse events compared with conventional daily administration in the first-line chemotherapy for advanced gastric cancer.. The 6-month PFS rate of the alternate-day administration group was 20.9% and failed to show significant difference from the pre-specified threshold at 15% (p = 0.117), whereas that of the daily administration group was 39.1% and significantly higher than the threshold (p = 0.001). The hazard ratio of the alternate-day administration group compared with the daily administration group was 1.753 (95% confidence interval (CI) 1.15-2.68, p = 0.010). With regard to OS, the hazard ratio of the alternate-day administration group compared with the daily administration group was 1.487 (95% CI 0.97-2.29, p = 0.072). The median TTF were 4.2 and 2.8 months in the daily and alternate-day administration group, respectively (p = 0.007).. The alternate-day administration of S-1 was not recommended as the first-line therapy for patients with advanced gastric cancer.

Topics: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Disease-Free Survival; Drug Administration Schedule; Drug Combinations; Female; Humans; Japan; Male; Middle Aged; Oxonic Acid; Stomach Neoplasms; Tegafur; Treatment Outcome

Gastrectomy with D2 lymphadenectomy plus postoperative chemotherapy is the standard treatment for resectable locally advanced gastric cancer in Japan. However, the prognosis of patients with serosa-positive tumors remains unsatisfactory because of peritoneal recurrence. This study aimed to investigate the validity of neoadjuvant therapy with docetaxel, cisplatin, and S-1 (DCS) in patients with locally advanced gastric cancer. Thirty patients with locally advanced gastric cancer underwent neoadjuvant DCS therapy at Dokkyo Medical University Hospital between June 2013 and October 2015. Gastrectomy and D2 lymphadenectomy were performed after two cycles of preoperative DCS therapy. The clinical responses of the primary gastric tumors based on endoscopic findings were partial response in 17 patients (57%) and stable disease in 13 patients (43%). Analysis of pathological response in the primary gastric lesions showed grade 1a in five patients (17%), grade 1b in nine patients (30%), grade 2 in 11 patients (37%), and grade 3 in five patients (17%). Twenty-four patients (80%) remained alive after a median follow-up period of 31 months. The 2- and 3-year overall survival rates in all patients were 89 and 70%, respectively. The 2-year overall survival rate in pathological responders (grade 1b-3) was 96%, compared with 50% in pathological non-responders (grade 1a) (P = 0.00187). Pathological responders had a significantly higher survival rate than non-responders. These results indicate that neoadjuvant DCS therapy may improve the prognosis in patients with serosa-positive locally advanced gastric cancer.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Docetaxel; Drug Combinations; Female; Gastrectomy; Humans; Male; Middle Aged; Neoadjuvant Therapy; Oxonic Acid; Stomach Neoplasms; Survival Analysis; Survival Rate; Taxoids; Tegafur; Treatment Outcome

We compared continuous versus stop-and-go chemotherapy after disease stabilisation with induction chemotherapy in the first-line treatment of metastatic gastric cancer (MGC).. MGC patients who achieved disease control after 6 cycles of S-1/oxaliplatin (SOX) were randomised to receive either continuous SOX until progression (continuous arm) or to have a chemotherapy-free interval followed by SOX reintroduction at progression (stop-and-go arm). The primary end-point was overall survival (OS).. Of the 250 patients enrolled, 247 participated in the induction phase. Of these, 121 patients were randomised to the continuous arm (n = 59) or the stop-and-go arm (n = 62). Progression-free survival (PFS) was significantly longer in the continuous arm than in the stop-and-go arm (10.5 versus 7.2 months; hazard ratio [HR] 0.55, 95% CI, 0.37-0.81; P = 0.002). Duration of disease control (DDC) and OS, however, were comparable between the two arms: median DDC, 10.5 versus 11.3 months, HR 0.92 (95% CI, 0.62-1.36; P = 0.674); median OS, 22.6 versus 22.7 months, HR 0.78 (95% CI, 0.50-1.23; P = 0.284). Adverse events including grade ≥3 fatigue (28.8% versus 8.1%; P = 0.003) and sensory neuropathy (25.4% versus 9.7%; P = 0.022) occurred more frequently in the continuous arm than in the stop-and-go arm. Quality of life (QOL) including global health status, physical/role functioning and other symptom scores significantly favoured the stop-and-go arm.. Compared with the stop-and-go strategy, maintenance chemotherapy improved PFS but not DDC and OS and had a negative impact on QOL, suggesting the stop-and-go strategy may be an appropriate option in MGC patients following induction chemotherapy.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Disease-Free Survival; Drug Administration Schedule; Drug Combinations; Female; Humans; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Prospective Studies; Quality of Life; Stomach Neoplasms; Tegafur

Peritoneal cytology positive for carcinoma cells (CY+) is an independent poor prognostic factor in gastric cancer, and patients with CY+ are diagnosed with stage IV disease. However, there is no standard treatment strategy for CY+ gastric cancer, whereas combination chemotherapy with fluoropyrimidine and platinum has been established as the standard treatment for unresectable advanced gastric cancer or after R2 resection. Herein, we assessed whether adding cisplatin to S-1 (SP) could improve the outcome of CY+ gastric cancer patients, as compared to S-1 monotherapy.. This retrospective study was conducted at a single Japanese institute between June 2005 and March 2014. Patients diagnosed with CY+ advanced gastric cancer and treated with S-1-based therapy were enrolled. Patients with incurable factors other than CY+ were excluded.. Forty-four patients were enrolled; 25 and 19 were administered S-1 and SP, respectively. The 2-year survival rates were 52.0% [95% confidence interval (CI), 31.2-69.2%] and 52.6% (28.7-71.9%) in the S-1 and SP groups, respectively. The median overall survival (OS) and progression-free survival (PFS) were 28.2 and 15.6 months in the S-1 group and 24.0 and 18.8 months in the SP group, respectively; they were not significantly different. The relative dose intensities were 0.79 (S-1) in the S-1 group and 0.69 (S-1)/0.70 (cisplatin) in the SP group.. Adding cisplatin to long-term S-1 monotherapy did not significantly improve the outcome of CY+ advanced gastric cancer patients.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Disease-Free Survival; Drug Combinations; Female; Humans; Male; Middle Aged; Oxonic Acid; Peritoneal Neoplasms; Retrospective Studies; Stomach Neoplasms; Survival Rate; Tegafur; Treatment Outcome

The effect of histology-based treatment regimen on diffuse gastric adenocarcinoma has not been evaluated in clinical trials. This international phase III trial evaluated the efficacy and safety of S-1 (a contemporary oral fluoropyrimidine)/cisplatin versus 5-fluorouracil (5-FU)/cisplatin in chemotherapy-naïve patients with diffuse-type adenocarcinoma involving the gastroesophageal junction or stomach.. Eligibility criteria included untreated, measurable, advanced diffuse adenocarcinoma confirmed by central pathology and performance status of 0-1. Patients were randomized (2 : 1) to receive S-1/cisplatin or 5-FU/cisplatin. Primary end point was overall survival (OS), and secondary end points were progression-free survival, time to treatment failure, overall response rate, and safety. A multivariable analysis was also carried out.. Overall, 361 patients were randomized (S-1/cisplatin, n = 239; 5-FU/cisplatin, n = 122); half (51%) were men, and median age was 56.0 years. In each group, median number of treatment cycles per patient was 4 (range, S-1/cisplatin: 1-20; 5-FU/cisplatin: 1-30), and dose intensity was >95%. OS was not different in the two groups {median OS with S-1/cisplatin, 7.5 [95% confidence interval (CI): 6.7, 9.3]; 5-FU/cisplatin, 6.6 [95% CI: 5.7, 8.1] months; hazard ratio, 0.99 [95% CI: 0.76, 1.28]; P = 0.9312}. Overall response rate was significantly higher in the S-1/cisplatin than 5-FU/cisplatin group (34.7% versus 19.8%; P = 0.01), but progression-free survival and time to treatment failure were not different. Safety was similar between the 2 groups; however, fewer patients treated with S-1/cisplatin than 5-FU/cisplatin had ≥1 grade 3/4 treatment-emergent adverse event or ≥1 adverse event resulting in treatment discontinuation. One treatment-related death occurred in each group. Slow accrual led to early termination.. These data suggest that S-1/cisplatin and 5-FU/cisplatin are similar in efficacy and safety in untreated patients with advanced diffuse adenocarcinoma of the gastroesophageal junction or stomach. The primary end point was not met.. NCT01285557.

Topics: Adenocarcinoma; Administration, Oral; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Esophagogastric Junction; Female; Fluorouracil; Humans; Infusions, Intravenous; Male; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Stomach Neoplasms; Survival Analysis; Tegafur

This research aimed to investigate the efficacy of S-1 plus oxaliplatin (SOX) as perioperative chemotherapy for locally advanced gastric cancer. We enrolled 102 patients with preoperative clinical stage T3-4N×M0 gastric cancer who were then randomly assigned to receive SOX as either perioperative chemotherapy (group A, 50 patients) or postoperative adjuvant chemotherapy (group B, 52 patients). Short-term curative efficacy and adverse effects of perioperative chemotherapy were analyzed. The rates of R0 resection, surgical complications, combined multiple organ resection, overall survival (OS), and disease-free survival (DFS) were compared between the groups. Results showed an overall response rate in group A of 42%, with a disease control rate of 94% and a tumor down-staging rate of 50%. An R0 resection rate of 90% was achieved in group A, which was significantly higher than that in group B (75%). No surgical mortality was observed, and the differences in surgical complications and combined multiple organ resection rates between the groups were not significant. The postoperative pathological examination of 4 patients in group A did not show any cancer cells in the tumor bed, resulting in a histological complete remission rate of 8%. The average OS and DFS for group A patients were 17.928 and 16.134 months, respectively, which were both longer than that of group B patients. However, the differences were not significant. In all, our results shows that in locally advanced gastric carcinoma, SOX perioperative chemotherapy is effective and results in a significantly improved R0 resection rate compared to postoperative SOX administration. Perioperative SOX does not cause additional surgical complications and has low adverse reaction rates; moreover, it appears to prolong survival.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Disease-Free Survival; Drug Combinations; Female; Humans; Male; Middle Aged; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Postoperative Complications; Prospective Studies; Stomach Neoplasms; Survival Rate; Tegafur; Treatment Outcome

We conducted a phase II trial to investigate the efficacy and safety of neoadjuvant chemotherapy (NAC) comprising S-1 and cisplatin (CDDP) followed by extensive resection in the management of resectable locally advanced gastric cancer with lymph node (LN) metastases.. Patients with LN metastases from stage II or III gastric cancer received S-1 and CDDP, as NAC criteria for LN metastases were the involvement of ≥4 nodes <2 cm or ≥1 nodes ≥2 cm as confirmed by a total body computed tomography scan. All patients underwent extensive resection including D2 gastrectomy. The primary endpoint was complete resection rate and the secondary endpoints were 3-year relapse-free and overall survival.. Fifty patients were assessable for the analysis. The complete resection rate was 87.8%. Three-year relapse-free survival was 44.9% and 3-year overall survival rate was 48.0%.. NAC with S-1 and CDDP is safe and may improve the complete resection rate in patients with metastatic LN gastric cancer. This suggests that LN metastases would provide good target lesions in future clinical trials of NAC.

Topics: Adult; Aged; Antineoplastic Agents; Cisplatin; Drug Combinations; Female; Humans; Lymphatic Metastasis; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Oxonic Acid; Stomach Neoplasms; Tegafur

The association between progression type and survival has been reported in breast cancer, but remains unclear in advanced gastric cancer (AGC). Here, this association was assessed using data obtained from an earlier randomized phase III study demonstrating the non-inferiority of S-1 plus oxaliplatin (SOX) to S-1 plus cisplatin (CS) on progression-free survival and overall survival (OS) in the first-line treatment of AGC.. A Cox regression model including two time-dependent covariates, progression with new lesions and with no new lesions, was used to determine their effect on OS in each treatment group. When both types of progression were detected simultaneously, this was categorized as progression with new lesions.. Progression with and with no new lesions was identified in 91 and 167 patients, respectively, in the SOX group (333 patients) and 95 and 147 patients, respectively, in the CS group (330 patients). The association between progression type and OS was similar in both treatment groups; both progression types were strong poor prognostic factors, particularly progression with new lesions [hazard ratio (HR), 7.26; 95% confidence interval (CI), 4.89-10.80 in SOX and HR, 5.78; 95% CI, 4.13-8.08 in CS] compared to no new lesions (HR, 4.66; 95% CI, 3.21-6.77 in SOX and HR, 2.71; 95% CI, 1.95-3.75 in CS).. Progression accompanied by new lesions had a strong negative impact on OS in patients treated with S-1 and platinum for AGC.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Disease Progression; Disease-Free Survival; Drug Combinations; Female; Humans; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Proportional Hazards Models; Stomach Neoplasms; Tegafur

The first one-arm phase II trial aimed to evaluate and predict efficacy and safety of S-1 plus oral leucovorin (S-1/LV) as first-line chemotherapy for patients with advanced gastric cancer (AGC), using S-1 pharmacogenetic pathway approach.. A total of 39 patients orally took S-1 at conventional dose and LV simultaneously at a dose of 25 mg twice daily for a week, within a 2-week cycle. The primary endpoint was overall response rate (ORR), while the secondary endpoints were progression-free survival (PFS), time to failure (TTF), overall survival (OS), disease control rate (DCR), and adverse events (AEs). Peripheral blood was sampled prospectively for baseline expression of dihydropyrimidine dehydrogenase (DPD), orotate phosphoribosyltransferase (OPRT), thymidine phosphorylase (TP), and thymidylate synthase (TS), CYP2A6 gene polymorphisms, and 5-FU pharmacokinetics.. Two-week, oral S-1/LV regimen demonstrated promising efficacy and safety as first-line chemotherapy for AGC. CLINICALTRIALS.. NCT02090153.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cytochrome P-450 CYP2A6; Disease-Free Survival; Drug Combinations; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Orotate Phosphoribosyltransferase; Oxonic Acid; Pharmacogenomic Testing; Stomach Neoplasms; Tegafur

We conducted a phase II study to evaluate the efficacy and safety of perioperative S-1 plus docetaxel in locally advanced gastric cancer (LAGC) and to investigate the association between CYP2A6 genotype and outcome.. Patients with LAGC [clinical stage III-IV (M0) by the Japanese staging system] received three cycles of pre- and postoperative chemotherapy (S-1 40 mg/m(2) twice daily on days 1-14; intravenous docetaxel 35 mg/m(2) on days 1 and 8, every 3 weeks) followed by gastrectomy with D2 dissection. We also performed a pharmacokinetic and CYP2A6 genotyping study (*1, *4, *7, *9, *10) for S-1.. From October 2006 to June 2008, 44 patients entered the study. 43 eligible patients completed preoperative chemotherapy and 40 completed postoperative chemotherapy. The most common G3/4 toxicities during pre- and postoperative chemotherapy were neutropenia, stomatitis, and abdominal pain. The clinical response rate by RECIST was 74.4 % (95 % CI, 61.4-87.4 %), and the R0 resection rate was 97.7 %. Clinical downstaging in T or N occurred in 41.9 % of patients. The 3-year progression-free survival (PFS) rate was 62.8 % and 5-year overall survival (OS) rate was 69.6 %. PFS and OS differed significantly according to clinical response, clinical downstaging, and CYP2A6 genotype. Patients with CYP2A6 variant/variant genotypes had a higher tegafur C max and worse survival than those with wild/wild or wild/variant genotypes.. Perioperative S-1 plus docetaxel is active with a manageable toxicity in patients with LAGC receiving D2 surgery. Clinical tumor response, clinical downstaging, and CYP2A6 genotype may predict efficacy.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cytochrome P-450 CYP2A6; Disease-Free Survival; Docetaxel; Drug Combinations; Female; Gastrectomy; Humans; Male; Middle Aged; Oxonic Acid; Perioperative Care; Pharmacogenetics; Postoperative Care; Stomach Neoplasms; Survival Rate; Taxoids; Tegafur; Treatment Outcome

Although the docetaxel, 5-fluorouracil, and cisplatin triplet has yielded significant improvements in time to progression, overall survival, and overall response rate, the high incidence of severe adverse events limits the use of the docetaxel, 5-fluorouracil, and cisplatin triplet. To overcome this limitation, we evaluated the efficacy and safety of the combination of docetaxel, oxaliplatin, and S-1 for the treatment of metastatic gastric cancer.. Chemotherapy-naive patients with pathologically proven unresectable recurrent or metastatic gastric adenocarcinoma were assessed for eligibility. Docetaxel at 52.5 mg/m(2) and oxaliplatin at 105 mg/m(2) were administered intravenously on day 1, and S-1 was administered orally at 80 mg/m(2) on days 1-14 of every 21-day cycle.. Forty-four patients (median age 54.5 years) were enrolled. All patients had metastatic disease. A total of 340 cycles of chemotherapy were administered (median of eight cycles per patient; range 1-36 cycles). Toxicities were evaluated in 43 patients, and the responses were evaluated in 40 patients. Major toxicities included grade 3/4 neutropenia (37.2 %) and leukopenia (27.9 %). The overall response rate was 54.5 % [95 % confidence interval (CI) 40.1-68.3 %] in the intention-to-treat population. The median progression-free survival and overall survival were 7.6 months (95 % CI 6.2-9.0 months) and 12.0 months (95 % CI 6.9-17.2 months), respectively.. These data suggest that the docetaxel, oxaliplatin, and S-1 combination regimen is effective and relatively well tolerable, and it seems to have potential to be a reasonable therapeutic strategy in patients with metastatic or recurrent gastric cancer.

Topics: Adenocarcinoma; Administration, Intravenous; Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Disease-Free Survival; Docetaxel; Drug Combinations; Female; Humans; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Stomach Neoplasms; Taxoids; Tegafur; Treatment Outcome

Although postoperative adjuvant chemotherapy with S-1, an oral fluoropyrimidine, has become a standard of care for gastric cancer in Japan, nonresponders may suffer from the cost and adverse reactions without clinical benefit. This multicenter exploratory phase II trial was conducted to see whether a chemosensitivity test, the collagen gel droplet embedded culture drug sensitivity test (CD-DST), can adequately select patients for chemotherapy.. The CD-DST using four different concentrations of 5-fluorouracil was conducted with resected specimens from preregistered patients who underwent gastrectomy with D2 or more extensive lymphadenectomy. Patients who were histopathologically confirmed to have stage II or greater disease without distant metastasis were eligible for final enrollment. All patients underwent protocol-specified adjuvant chemotherapy with S-1. Three-year relapse-free survival was compared between patients determined as sensitive by the CD-DST (responders) and those deemed insensitive (nonresponders). Appropriate cutoff values for in vitro growth inhibition were defined when the hazard ratio for relapse in responders and the log-rank P values were at their minimum.. Of the 311 patients enrolled, 14 were ineligible and 27 failed to start the protocol treatment. The CD-DST failed in 64 other patients, and survival analyses were conducted with the remaining 206 patients (39 stage II disease, 155 stage III disease, and 12 stage IV disease). The outcome of patients who were determined to be responders was significantly superior to that of nonresponders regardless of the 5-fluorouracil concentrations, although no differences in clinicopathologic characteristics were observed between the two groups, except for age.. The CD-DST identified those who benefit from adjuvant chemotherapy. It deserves further evaluation in the setting of a prospective randomized trial. ClinicalTrials.gov identifier: NCT00287755.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Disease-Free Survival; Drug Combinations; Drug Resistance, Neoplasm; Drug Screening Assays, Antitumor; Female; Fluorouracil; Gastrectomy; Gene Expression Regulation, Neoplastic; Humans; Male; Middle Aged; Oxonic Acid; Stomach Neoplasms; Tegafur; Treatment Outcome

This randomized phase II study compared weekly administration of paclitaxel (wPTX) with the best available 5-fluorouracil (5-FU) regimen as second-line treatment for advanced gastric cancer patients with severe peritoneal metastasis refractory to fluoropyrimidine.. In the best available 5-FU arm, continuous infusion of 5-FU (800 mg/m(2)/day, days 1-5, every 4 weeks) was given to patients with prior chemotherapy including bolus 5-FU, and methotrexate and 5-FU sequential bolus injection (methotrexate at 100 mg/m(2) followed by bolus 5-FU at 600 mg/m(2) with leucovorin, weekly) was given to those who had previously received continuous infusion of 5-FU or oral administration of fluoropyrimidine. In the wPTX arm, paclitaxel (80 mg/m(2)) was administered on days 1, 8, and 15, every 4 weeks. This study adopted a screening design (one-sided α = 30 %) with the primary end point of overall survival.. One hundred patients were randomized to the 5-FU arm (n = 49) or the wPTX arm (n = 51). Although the median survival time was 7.7 months in both arms, the 2-year survival rates were 2.9 % in the 5-FU arm and 9.1 % in the wPTX arm [hazard ratio 0.89 (95 % confidence interval 0.57-1.38), one-sided p = 0.298}. The median progression-free survival was longer with wPTX than with 5-FU [3.7 months vs 2.4 months; hazard ratio 0.58 (95 % confidence interval 0.38-0.88), one-sided p = 0.005]. The incidences of grade 4 neutropenia, grade 3/4 febrile neutropenia, diarrhea, and treatment-related death were 6 %, 4 %, 10 %, and 2 %, respectively, in the 5-FU arm and 2 %, 0 %, 0 %, and 0 %, respectively, in the wPTX arm.. As second-line chemotherapy, wPTX appears feasible and promising. This regimen can be included in a test arm in future phase III trials for treatment of advanced gastric cancer with severe peritoneal metastasis.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Capecitabine; Drug Combinations; Female; Fluorouracil; Follow-Up Studies; Humans; Irinotecan; Leucovorin; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Oxonic Acid; Paclitaxel; Peritoneal Neoplasms; Prognosis; Stomach Neoplasms; Survival Rate; Tegafur

A randomized phase III study of Japanese patients with advanced gastric cancer, the G-SOX trial, revealed that S-1 and oxaliplatin (SOX) combination therapy was noninferior to S-1 and cisplatin (CS) combination therapy. However, it is unclear whether the efficacy and safety in elderly patients were different between the two regimens.. A total of 685 patients registered in the G-SOX trial were classified as elderly (70 years or older) or not elderly (younger than 70 years), and 663 patients (SOX therapy, elderly 113 of 333 patients, 34 %; CS therapy, elderly 99 of 330 patients, 30 %) and 673 patients (SOX therapy, elderly 114 of 338 patients, 34 %; CS therapy, elderly 101 of 335 patients, 30 %) were analyzed for efficacy and safety, respectively. Treatment delivery of SOX was also compared between elderly and nonelderly groups.. No differences in efficacy were identified between the elderly and nonelderly groups for either regimen. In the elderly groups, SOX therapy showed better trends in progression-free survival (hazard ratio 0.805, 95 % confidence interval 0.588-1.102) and overall survival (hazard ratio 0.857, 95 % confidence interval 0.629-1.167) compared with CS therapy, although there were no significant differences. Grade 3 or worse adverse events were less frequent in the elderly group receiving SOX than in the elderly group receiving CS except for the low incidence of sensory neuropathy (5.3 % vs 0 %), neutropenia (25.4 % vs 42.6 %), anemia (21.1 % vs 42.6 %), febrile neutropenia (1.8 % vs 10.9 %), increased creatinine level (0.9 % vs 3.0 %), and hyponatremia (7.9 % vs 18.8 %).. SOX is an effective and feasible therapy in both nonelderly and elderly patients with advanced gastric cancer. In elderly patients, SOX demonstrated favorable efficacy and safety compared with CS.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Female; Follow-Up Studies; Humans; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Peritoneal Neoplasms; Prognosis; Safety; Stomach Neoplasms; Survival Rate; Tegafur

This study aimed to investigate the safety and efficacy of S-l combined with cisplatin plus concurrent chemoradiotherapy (SCCC) versus cisplatin plus concurrent chemoradiotherapy (CCC) for Chinese patients with advanced gastric cancer (AGC).. Between April 2008 and June 2010, 144 eligible patients with AGC were included and divided randomly into 2 groups. Seventy-two patients in the SCCC group received with S-1 on days 1-14 of a 21-day cycle, 24-h cisplatin infusion (70 mg/m(2) on day 1) every 4 weeks for 2 cycles, and concurrent chemoradiotherapy (30-Gy radiotherapy over 4 weeks) beginning on day 1. The other 72 patients in the CCC group were administered cisplatin and concurrent chemoradiotherapy as for SCCC. The primary outcome was overall survival. Secondary outcomes were progression-free survival and adverse events.. The median overall survival durations were 11.7 months (range 1.7-29.7 months) and 9.5 months (range 1.2-25.4 months) in SCCC and CCC groups, respectively (P = 0.041). The median progression-free survival durations were 10.6 months for SCCC (range 1.3-24.7 months) and 8.8 months (range 0.7-22.3 months) for CCC (P = 0.046). The toxicity profile was similar in both groups.. In summary, SCCC showed more promising safety and efficacy than CCC in Chinese patients with AGC. In addition, the toxicities were also acceptable in both groups.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Asian People; Chemoradiotherapy; Cisplatin; Disease-Free Survival; Drug Combinations; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Oxonic Acid; Stomach Neoplasms; Tegafur; Treatment Outcome; Young Adult

Preoperative chemotherapy is a promising strategy for downstaging advanced gastric cancer before radical resection, although severe adverse events can occur and clinical outcomes are often unsatisfactory. To identify predictive biomarkers of drug sensitivity, we used a well-designed functional apoptosis assay and assessed the correlations between chemosensitivity and clinical outcomes.. Drug sensitivity to docetaxel, cisplatin, and 5-fluorouracil was examined in 11 gastric cancer cell lines. BCL2-homology domain 3 (BH3) profiling was performed and assessed for correlations with drug sensitivity. Immunohistochemical staining of clinical gastric cancer specimens was performed before preoperative chemotherapy, and correlations with histopathological responses and clinical outcomes were assessed.. BIM (BCL2L11)-BH3 profiling results correlated with docetaxel sensitivity and BAK protein expression, whose knockdown caused docetaxel resistance. The BAK expression indexes of 69 gastric cancer specimens before preoperative chemotherapy (including docetaxel treatment) were determined by multiplying numerical values describing the degrees of BAK positivity and staining intensity observed. Patients whose specimens showed good chemotherapeutic histopathological responses had higher BAK indexes than those with poor responses. Patients with BAK index values ≥3 showed improved progression-free survival (HR, 2.664; 95 % CI, 1.352-5.248; P = 0.005) and overall survival (HR, 3.390; 95 % CI, 1.549-7.422; P = 0.002).. BH3 profiling clearly showed that BIM expression, which depends on BAK expression, correlated with docetaxel sensitivity. BAK expression in gastric cancer is thus predictive of chemotherapeutic responses to docetaxel and clinical prognosis in patients treated with preoperative chemotherapy.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; bcl-2 Homologous Antagonist-Killer Protein; Biomarkers, Tumor; Cisplatin; Docetaxel; Drug Combinations; Female; Follow-Up Studies; Gastrectomy; Humans; Immunoenzyme Techniques; Male; Middle Aged; Neoplasm Staging; Non-Randomized Controlled Trials as Topic; Oxonic Acid; Peptide Fragments; Prognosis; Proto-Oncogene Proteins; Stomach Neoplasms; Survival Rate; Taxoids; Tegafur; Young Adult

The aim of this study was to explore whether a combination of S-1 and paclitaxel offers any benefit over paclitaxel alone to patients pretreated by S-1.. Gastric cancer patients who developed progression during S-1-based first-line chemotherapy or had recurrence during postoperative adjuvant chemotherapy by S-1 were randomly assigned to receive second-line treatment either by weekly administration of paclitaxel at 80 mg/m(2) three times every 4 weeks or daily oral S-1 (80 mg/m(2)) for 2 weeks plus paclitaxel (50 mg/m(2)) given on days 1 and 8, every 3 weeks (S-1 plus paclitaxel). The primary endpoint was progression-free survival (PFS) at 4 months after the initiation of treatment.. A total of 78 patients were eligible for efficacy analyses-40 were assigned to the paclitaxel group and 38 to the S-1 plus paclitaxel group. PFS at 4 months was similar between the groups (50 % for paclitaxel vs 55 % for S-1 plus paclitaxel, P = 0.641). There were no differences between the groups either in progression-free survival (4.6 vs 4.6 months, respectively, P = 0.526), overall survival (10.0 vs 10.0 months, respectively, P = 0.464), or overall response rate (27 vs 22 %, respectively, P = 0.767). The incidences of grade 3 or 4 hematological and non-hematological toxicities were also equivalent between the two groups (25 vs 26 % and 24 vs 26 %, respectively).. No benefit of S-1 administration beyond progression was shown when paclitaxel was selected as the key drug for second-line chemotherapy.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Disease-Free Survival; Drug Combinations; Female; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Oxonic Acid; Paclitaxel; Prospective Studies; Retreatment; Stomach Neoplasms; Survival Rate; Tegafur

A multi-center phase II study was conducted to evaluate the safety and efficacy of neoadjuvant chemotherapy (NAC) with S-1 plus cisplatin for advanced gastric cancer.. The eligibility criteria were clinical T3/T4 or N2, not Stage IV. Patients received two 35-day cycles of S-1 plus cisplatin, and then underwent D2 gastrectomy. The primary endpoint was 3-year progression free survival (PFS). Secondary endpoints were ratio of R0 resection, response rate, adverse events, and overall survival. A sample size of 49 was determined to have 80% power for detecting 15% improvement in the 3-year PFS over 55% at a one-sided alpha of 0.1.. Among 53 patients enrolled, 44 patients completed two cycles of NAC (83%), and 48 patients underwent R0 resection (91%). Postoperative complications occurred in 13 patients (26%). A pathological response was confirmed in 24 patients (45%), including four complete responses. The 3-year PFS was 50.7%, while the 3-year OS was 74.9%.. Although the observed 3-year PFS rate was worse than expected, NAC with S1 plus cisplatin was safe and led to a high rate of R0 resection. A randomized controlled trial is needed to make conclusions about the effectiveness of NAC in Japanese patients undergoing D2 resection.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cisplatin; Disease-Free Survival; Drug Administration Schedule; Drug Combinations; Female; Gastrectomy; Humans; Kaplan-Meier Estimate; Lymphatic Metastasis; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Neoplasm Staging; Oxonic Acid; Stomach Neoplasms; Tegafur; Treatment Outcome

Although leucovorin enhances the efficacy of fluorouracil, the anti-tumour activity of S-1 and leucovorin and their combination with oxaliplatin for patients with advanced gastric cancer is unknown. We compared the activity and safety of S-1 plus leucovorin, S-1 plus leucovorin and oxaliplatin, and S-1 plus cisplatin as first-line chemotherapy for advanced gastric cancer.. In this multicentre, randomised, open-label, phase 2 trial, we recruited chemotherapy-naive patients with unresectable or recurrent gastric cancer with measurable lesions aged 20 years or older from 25 general hospitals and specialist centres in Japan. Patients were randomly assigned (1:1:1) centrally to receive S-1 plus leucovorin (S-1 40-60 mg orally plus oral leucovorin 25 mg twice a day for 1 week, every 2 weeks), S-1 plus leucovorin and oxaliplatin (S-1 plus leucovorin and intravenous oxaliplatin 85 mg/m(2) on day 1, every 2 weeks), or S-1 plus cisplatin (S-1 40-60 mg orally twice a day for 3 weeks, plus intravenous cisplatin 60 mg/m(2) on day 8, every 5 weeks). Randomisation was done with the minimisation method using performance status (0 vs 1) and tumour stage (stage IV vs recurrent) as stratification factors. The primary endpoint was independently reviewed overall response in the full analysis set. This trial is registered with Japic CTI, number 111635.. Between Oct 20, 2011, and Dec 17, 2012, we enrolled and randomly assigned 145 patients: 49 patients were assigned to S-1 plus leucovorin, 47 to S-1 plus leucovorin and oxaliplatin, and 49 to S-1 plus cisplatin. An objective response assessed by the independent review committee was achieved in 20 (43% [95% CI 28·3-57·8]) of the 47 patients in the S-1 plus leucovorin group, 31 (66% [50·7-79·1]) of the 47 patients in the S-1 plus leucovorin and oxaliplatin group, and 22 (46% [31·4-60·8]) of the 48 patients in the S-1 plus cisplatin group (Fisher's exact test, p=0·84 for S-1 plus leucovorin vs S-1 plus cisplatin, p=0·063 for S-1 plus leucovorin and oxaliplatin vs S-1 plus cisplatin, and p=0·038 for S-1 plus leucovorin and oxaliplatin vs S-1 plus leucovorin). The most common grade 3-4 adverse events were neutropenia (three [6%] of 48 patients in the S-1 plus leucovorin group vs 12 [26%] of 47 patients in the S-1 plus leucovorin and oxaliplatin group vs 17 [35%] of 49 patients in the S-1 plus cisplatin group), decreased appetite (six [13%] vs 14 [30%] vs 12 [24%]), anaemia (five [10%] vs seven [15%] vs 13 [27%]), and hyponatraemia (two [4%] vs two [4%] vs nine [18%]).. S-1 plus leucovorin and oxaliplatin was more active than S-1 plus leucovorin or S-1 plus cisplatin with acceptable toxic effects for patients with advanced gastric cancer. A phase 3 trial comparing S-1 plus leucovorin and oxaliplatin with S-1 plus cisplatin is underway.. Taiho Pharmaceutical.

Topics: Adenocarcinoma; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Disease-Free Survival; Drug Combinations; Feeding and Eating Disorders; Female; Humans; Hyponatremia; Leucovorin; Male; Middle Aged; Neoplasm Recurrence, Local; Neutropenia; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Stomach Neoplasms; Survival Rate; Tegafur; Treatment Outcome

Surgery is the only possible curative treatment for gastric cancer. However, the high recurrence rate makes gastric cancer difficult to cure by surgery alone. The present study was conducted to evaluate the clinical outcomes and toxicity of adjuvant treatment, including S-1/cisplatin chemotherapy followed by radiotherapy with concurrent S-1.. Patients with radically D2-resected adenocarcinoma of the stomach of stage IB-IV (M0) were eligible. Patients were treated with S-1 (40-60 mg depending on the patient's body surface area) twice daily for 3 weeks and cisplatin (60 mg/m(2)) intravenously on day 1 every 5 weeks. Patients received CRT (45 Gy of radiation at 1.8 Gy/day, 5 days per week, for 5 weeks with the same dose of S-1 during radiation) followed by two additional cycles of S-1/cisplatin. The primary endpoint was the 3-year disease-free survival (DFS) rate; the secondary endpoints were the 3-year overall survival rate and toxicities.. Until May 2012, 46 patients were enrolled, and 34 (73.9%) completed the planned treatment. The median age was 53 years (range: 31-69 years), and the numbers of patients with stage IB, II, III and IV disease were 0, 17, 25 and 4, respectively. Main grade 3-4 toxicities were as follows: neutropenia (28.2%), nausea (17.4%), vomiting (8.7%) and anorexia (15.2%). At the time of analysis, after a median follow-up period of 56.5 months (3.03-74.0 months), 16 recurrence events and 15 deaths were reported. The estimated 3-year DFS and survival rates were 65.2 and 76.1%, respectively. The most common site of recurrence was the peritoneum (n = 12).. The results of this phase II study show that intensified adjuvant treatment with S-1/cisplatin chemotherapy and S-1-based chemoradiotherapy was tolerable and effective in reducing disease recurrence. The addition of radiotherapy to chemotherapy may be effective in D2-resected gastric cancer. Although the data here are promising, a randomized trial is needed between patients treated with the current regimen and an appropriate comparator arm.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Chemotherapy, Adjuvant; Cisplatin; Disease-Free Survival; Drug Combinations; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Oxonic Acid; Stomach Neoplasms; Survival Rate; Tegafur

We evaluated the efficacy and safety of 5-weekly S-1 and cisplatin combined with trastuzumab, a monoclonal antibody against human epidermal growth factor receptor type 2 (HER2) for HER2-positive advanced gastric cancer (AGC).. This phase II study treatment consisted of S-1 (80-120 mg per day) orally on day 1-21, cisplatin (60 mg/m(2)) intravenously on day 8, and trastuzumab (8 mg/kg on day 1 of the first cycle, followed by 6 mg/kg every 3 weeks) intravenously. The primary end point was 1-year survival rate. The secondary end points included overall survival, progression-free survival (PFS), response rate (RR), and safety.. A total 22 patients from seven centers were enrolled. In the 20 patients evaluable for analysis, the 1-year survival rate was 70 % (95 % confidence interval (CI) 49.9-90.1 %), and median survival time, PFS, and RR were 15.3, 7.5 months and 41.2 %, respectively. Major grade 3/4 adverse events were neutropenia (30 %), anorexia (30 %), leukopenia (25 %), fatigue (20 %), and anemia (15 %).. Five-weekly S-1 and cisplatin combined with trastuzumab showed effective with favorable safety profile in patients with HER2-positive AGC.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Disease-Free Survival; Drug Combinations; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Oxonic Acid; Prospective Studies; Receptor, ErbB-2; Response Evaluation Criteria in Solid Tumors; Stomach Neoplasms; Tegafur; Trastuzumab

Gastric cancer is a common and heterogeneous disease; however, global standard and biomarkers for selecting chemotherapy regimens have not been established. This study was designed retrospectively to identify molecular biomarkers for irinotecan plus S-1 (IRI-S) and S-1 therapy from subset analyses in GC0301/TOP-002, a randomised phase III trial for advanced gastric cancer.. Paraffin-embedded primary tumour specimens were collected from 126 of 326 randomised patients in GC0301/TOP-002. The mRNA was measured for thymidylate synthase, dihydropyrimidine dehydrogenase, topoisomerase I, excision repair cross-complementing gene 1 (ERCC1) and thymidine phosphorylase; categorised into low and high to analyse their association with efficacy end points.. There was no significant difference in each mRNA between S-1 and IRI-S groups, whereas there were differences among some clinical characteristics. Multivariate analyses for overall survival showed that mRNA levels were not correlated with prognosis. By comparison, between IRI-S and S-1 arms, low thymidylate synthase, low ERCC1 and high thymidine phosphorylase were associated with better prognosis for IRI-S versus S-1 (hazard ratio = 0.653, 0.702 and 0.709, respectively; P < 0.15 for each interaction).. Low thymidylate synthase, low ERCC1 and high thymidine phosphorylase are candidates for predictive biomarkers for first-line treatment in advanced gastric cancer by IRI-S. Further study is warranted to confirm these results in other clinical trials and cohort studies.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Camptothecin; Dihydrouracil Dehydrogenase (NADP); DNA Topoisomerases, Type I; DNA-Binding Proteins; Drug Combinations; Endonucleases; Female; Humans; Irinotecan; Male; Middle Aged; Oxonic Acid; Prognosis; Retrospective Studies; RNA, Messenger; Stomach Neoplasms; Tegafur; Thymidine Phosphorylase; Thymidylate Synthase

It was unclear whether the transhiatal approach and D2 total gastrectomy after neoadjuvant chemotherapy (NAC) for adenocarcinoma of the esophago-gastric (AEG) junction are as feasible and safe as D2 gastrectomy following NAC.. We clarified the short-term surgical results in AEG and non-AEG patients in a subset analysis of the COMPASS trial.. Eighty-three patients, 24 with AEG and 59 with non-AEG, were registered in the study. Among 24 patients with AEG, 5 were classified to have Siewert type I, 11 to have type II and 8 to have type III. The tumor progression, completion of NAC, and clinical and pathological responses were similar between the groups. Twenty-four AEG and 51 non-AEG patients proceeded to surgery. The extent of dissection (D1/D2) was 3/21 in the AEG and 3/48 in the non-AEG patients. The R0 resection rate was 69% in the non-AEG and 88% in the AEG patients. Neither grade 3b/4 morbidity nor surgical mortality was observed in either group.. The transhiatal approach and D2 total gastrectomy after NAC seem to be as safe and feasible as D2 gastrectomy for non-AEG cancer.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cisplatin; Dissection; Drug Combinations; Esophagogastric Junction; Feasibility Studies; Female; Gastrectomy; Humans; Male; Margins of Excision; Middle Aged; Neoadjuvant Therapy; Neoplasm, Residual; Oxonic Acid; Paclitaxel; Stomach Neoplasms; Tegafur

The prognosis for stage III gastric cancer is unsatisfactory by D2 gastrectomy and S-1 adjuvant chemotherapy. Both S-1 plus cisplatin (SC) and paclitaxel plus cisplatin (PC) are promising regimens as neoadjuvant chemotherapy; however, the optimal duration remains unclear.. In this 2×2 randomised phase II trial, stage III gastric cancer patients, those with a prognosis corresponding to stage III, and macroscopically resectable stage IV cases were randomised to two or four courses of S-1 (80 mg/m(2) for 21 d with 1 week rest)/cisplatin (60 mg/m(2) at day 8) or PC (80 and 25 mg/m(2), respectively, on days 1, 8, and 15 with 1 week rest) as neoadjuvant chemotherapy. The primary end-point was the 3-year overall survival (OS).. Between October 2009 and July 2011, 83 patients received 2 courses of SC (n=21), 4 courses of SC (n=20), 2 courses of PC (n=21) and 4 courses of PC (n=21). The 3-year OS was 60.9% for SC and 64.3% for PC and 64.3% for the two courses and 61.0% for the four courses. Subset analyses demonstrated no subgroup which showed any potential survival benefit by PC in comparison to SC or by four courses as in comparison to two courses.. Two courses of SC as neoadjuvant chemotherapy are recommended as a test arm of a future phase III study for patients with locally advanced gastric cancer.. UMIN-000002595.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Drug Administration Schedule; Drug Combinations; Female; Gastrectomy; Humans; Male; Middle Aged; Neoadjuvant Therapy; Oxonic Acid; Paclitaxel; Stomach Neoplasms; Survival Analysis; Tegafur

Lentinan (LNT) is a purified β-1, 3-glucan that augments immune responses. The present study was conducted to assess the efficacy of LNT in combination with S-1 as a first-line treatment for unresectable or recurrent gastric cancer.. Eligible patients were randomly assigned to receive S-1 alone or S-1 plus LNT. The primary end-point was overall survival (OS). Secondary end-points were time-to-treatment failure (TTF), overall response rate (ORR), safety, quality of life (QOL), and biomarker. The percentages of LNT-binding monocytes in peripheral blood prior to treatment were analysed for the biomarker assessment.. One hundred and fifty-four and 155 patients were randomly assigned to receive S-1 alone or S-1 plus LNT, respectively. The median OS was 13.8 and 9.9 months (P = 0.208), the median TTF was 4.3 and 2.6 months (P < 0.001), the ORR was 22.3% and 18.7% for the S-1 and S-1 plus LNT groups, respectively. The incidences of haematologic and non-haematologic adverse events were similar, and no significant changes in QOL scores were observed during the treatment in both groups. In a subpopulation of patients with LNT-binding monocytes ≥2%, patients who received more than two cycles of chemotherapy showed a longer survival time in the S-1 plus LNT group.. OS did not improve and TTF was significantly worse in the S-1 plus LNT group as compared with the S-1-only group. This study showed no efficacy of LNT when combined with S-1 treatment in patients with unresectable or recurrent gastric cancer.. UMIN 000000574.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Drug Combinations; Female; Humans; Lentinan; Male; Middle Aged; Monocytes; Oxonic Acid; Quality of Life; Stomach Neoplasms; Tegafur

The efficacy of 5-fluorouracil (5FU)-based therapy, which remains the cornerstone of gastrointestinal cancer treatment, depends upon the expression of enzymes involved in pyrimidine metabolism, including thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), thymidine phosphorylase (TP), and orotate phosphoribosyltransferase (OPRT). We analyzed the expression of these genes in patients enrolled in the Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer (ACTS-GC) and their possible roles as biomarkers for treatment outcomes.. Formalin-fixed, paraffin-embedded specimens were available for 829 of a total of 1,059 (78.3 %) patients. TS, DPD, TP, and OPRT expression was measured by RT-PCR in manually microdissected tumor specimens and normalized to the reference gene, β-actin. The expression level of each gene was categorized as low or high using cutoffs at the 33.3rd, 50th, or 66.7th percentiles.. The hazard ratio (HR) for overall survival (OS) after S-1 treatment versus surgery alone was significantly lower in high (>66.7th percentile; HR = 0.370; 95 % CI 0.221-0.619) compared to low (<66.7th percentile; HR = 0.757; 95 % CI 0.563-1.018) TS expression groups (P = 0.015). Similarly, the HR for OS after S-1 therapy versus surgery alone was significantly lower in high (>33.3rd percentile; HR = 0.520, 95 % CI 0.376-0.720) compared to low (<33.3rd percentile; HR = 0.848, 95 % CI 0.563-1.276) DPD expression groups (P = 0.065). There was no interaction between TP or OPRT expression and OS.. This large biomarker study showed that high TS and DPD gene expression in tumors was associated with enhanced benefit from postoperative adjuvant S-1 treatment in gastric cancer. There was no interaction between TP and OPRT expression and S-1 treatment.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Dihydrouracil Dehydrogenase (NADP); Drug Combinations; Female; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Orotate Phosphoribosyltransferase; Oxonic Acid; Retrospective Studies; Stomach Neoplasms; Tegafur; Thymidine Phosphorylase; Thymidylate Synthase

We evaluated the efficacy and safety of S-1 plus oxaliplatin (SOX) as an alternative to cisplatin plus S-1 (CS) in first-line chemotherapy for advanced gastric cancer (AGC).. In this randomized, open-label, multicenter phase III study, patients were randomly assigned to receive SOX (80-120 mg/day S-1 for 2 weeks with 100 mg/m(2) oxaliplatin on day 1, every 3 weeks) or CS (S-1 for 3 weeks with 60 mg/m(2) cisplatin on day 8, every 5 weeks). The primary end points were noninferiority in progression-free survival (PFS) and relative efficacy in overall survival (OS) for SOX using adjusted hazard ratios (HRs) with stratification factors; performance status and unresectable or recurrent (+adjuvant chemotherapy) disease.. Overall, 685 patients were randomized from January 2010 to October 2011. In per-protocol population, SOX (n = 318) was noninferior to CS (n = 324) in PFS [median, 5.5 versus 5.4 months; HR 1.004, 95% confidence interval (CI) 0.840-1.199; predefined noninferiority margin 1.30]. The median OS for SOX and CS were 14.1 and 13.1 months, respectively (HR 0.958 with 95% CI 0.803-1.142). In the intention-to-treat population (SOX, n = 339; CS, n = 337), the HRs in PFS and OS were 0.979 (95% CI 0.821-1.167) and 0.934 (95% CI 0.786-1.108), respectively. The most common ≥grade 3 adverse events (SOX versus CS) were neutropenia (19.5% versus 41.8%), anemia (15.1% versus 32.5%), hyponatremia (4.4% versus 13.4%), febrile neutropenia (0.9% versus 6.9%), and sensory neuropathy (4.7% versus 0%).. SOX is as effective as CS for AGC with favorable safety profile, therefore SOX can replace CS.. JapicCTI-101021.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Disease-Free Survival; Drug Administration Schedule; Drug Combinations; Female; Humans; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Stomach Neoplasms; Tegafur; Young Adult

The aim of this phase I study was to adjust the dose of cisplatin as adjuvant combination chemotherapy with S-1 in an outpatient setting for gastric cancer.. The first course was initiated with S-1 monotherapy on days 1-28. From the second to the sixth course, S-1 was administered on days 1-28 and cisplatin was added on days 1, 15, and 29. The dose level of cisplatin was escalated as follows: 20 mg/m(2) (level 1); 25 mg/m(2) (level 2); 30 mg/m(2) (level 3). Dose-limiting toxicity was a delay factor of the start of the next course due to incomplete recovery.. The maximum tolerated and recommended doses were confirmed as level 3 and level 2, respectively.. Although further clinical trials are recommended to evaluate efficacy, this combination of S-1 plus cisplatin regimen is expected to become a standard adjuvant treatment for gastric cancer in the outpatient setting.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cisplatin; Drug Administration Schedule; Drug Combinations; Female; Humans; Male; Maximum Tolerated Dose; Medication Adherence; Middle Aged; Outpatients; Oxonic Acid; Stomach Neoplasms; Tegafur; Treatment Outcome

Patient-reported outcomes (PRO) of health-related quality of life (HRQoL) and time to worsening of clinical benefit parameters were evaluated as secondary end points in the phase 3 first-line advanced gastric cancer study (FLAGS) trial of cisplatin/S-1 versus cisplatin/5-fluorouracil (5-FU) in patients with previously untreated advanced gastric cancer.. The primary PRO end point was the Trial Outcome Index of the Functional Assessment of Cancer Therapy-Gastric (FACT-Ga). FACT-Ga was completed at the beginning of the first 4 cycles, cycle 6, and then every 3 cycles thereafter. The Chemotherapy Convenience and Satisfaction Questionnaire (CCSQ) was administered before the first 4 cycles; clinical benefit parameters (performance status, weight loss, and anorexia) were assessed at baseline, prior to study drug administration on day 1 of each cycle after cycle 1, and at the end of study treatment.. Compliance to questionnaire fulfillment was more than 80 % through cycle 9. Significantly, fewer patients treated with cisplatin/S-1 reported worsened physical well-being (PWB) scores (45.1 versus 51.7 %, p = 0.044) and experienced significantly longer time to worsening in PWB scores, with a median of 4.5 months (95 % confidence interval (CI), 3.1-5.1) compared to 3.0 months (2.8-4.6) with cisplatin/5-FU (CF) (p = 0.01). Patients receiving cisplatin/S-1 also reported significantly higher best and worst score of PWB as well as CCSQ scores and a longer median time to worsening in clinical benefit parameters.. Differences in secondary end points of PWB, CCSQ scores, and clinical benefit parameters favoring the cisplatin/S-1 arm provide further evidence for considering this combination a standard therapeutic option for first-line treatment of advanced gastric cancer.

Topics: Adenocarcinoma; Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Esophageal Neoplasms; Female; Fluorouracil; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Prognosis; Quality of Life; Stomach Neoplasms; Survival Rate; Tegafur; Young Adult

The optimal second-line regimen for treating advanced gastric cancer (AGC) remains unclear. While irinotecan (CPT-11) plus cisplatin (CDDP) combination therapy and CPT-11 monotherapy have been explored in the second-line setting, the superiority of second-line platinum-based therapies for AGC patients initially treated with S-1 monotherapy has not yet been evaluated; therefore, we aimed to examine the survival benefit of CPT-11/CDDP combination over CPT-11 monotherapy.. AGC patients showing progression after S-1 monotherapy for advanced cancer or recurrence within 6 months after completion of S-1 adjuvant therapy were randomly allocated to CPT-11/CDDP (CPT-11, 60 mg/m(2); CDDP, 30 mg/m(2), q2w) or CPT-11 (150 mg/m(2), q2w).. Sixty-eight advanced and 95 recurrent cases were evaluated. The median overall survivals were 13.9 (95% confidence interval [CI]: 10.8-17.6) and 12.7 (95% CI: 10.3-17.2) months for CPT-11/CDDP and CPT-11, respectively (hazard ratio: 0.834; 95% CI: 0.596-1.167, P = 0.288). No significant differences were observed in the secondary end-points, including progression-free survival (4.6 [95% CI: 3.4-5.9] versus 4.1 [95% CI: 3.3-4.9]months) and response rate (16.9% [95% CI: 8.8-28.3] versus 15.4% [95% CI: 7.6-26.5]). The incidences of grade 3-4 anaemia (16% versus 4%) and elevated serum lactate dehydrogenase levels (5% versus 0%) were higher for CPT-11/CDDP than for CPT-11. Exploratory subgroup analysis revealed that CPT-11/CDDP was significantly more effective for intestinal-type AGC, compared with CPT-11 (overall survival: 15.8 versus 14.0 months; P = 0.019).. No survival benefit was observed upon adding CDDP to CPT-11 after S-1 monotherapy failure.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Chemotherapy, Adjuvant; Cisplatin; Disease Progression; Drug Combinations; Drug Resistance, Neoplasm; Female; Humans; Irinotecan; Male; Middle Aged; Oxonic Acid; Stomach Neoplasms; Tegafur; Treatment Failure

S-1 is an oral 5-fluorouracil agent containing tegafur, 5-chloro-2, 4-dihydroxypyridine (CDHP), and potassium oxonate. This study explored the pharmacokinetics of S-1 and pharmacokinetic changes after gastric surgery in patients with resectable gastric cancer who received pre- and postoperative S-1 plus docetaxel. Serial blood was drawn before and after gastrectomy from 37 patients for pharmacokinetic analysis. The pharmacokinetics of tegafur, 5-fluorouracil, and CDHP were analyzed by noncompartmental analysis (NCA) methods and by modeling. In modeling analysis, CHDP concentrations were incorporated in the model as a time-varying covariate that inhibits the clearance of 5-fluorouracil following an inhibitory Emax model. In NCA, the pharmacokinetics of tegafur and 5-FU before and after gastric surgery were similar, although average maximum concentrations of 5-FU were decreased with statistical significance after gastrectomy. Median Tmax of tegafur was shorter after surgery without statistical significance. In modeling analysis, tegafur was best fitted by mixed zero and first-order absorption. The only difference in the final pharmacokinetic model around gastrectomy was the presence of an absorption lag of 0.23 hours before surgery. Incorporation of CDHP concentrations significantly improved the model. Although some pharmacokinetic results showed statistically significant changes after gastrectomy, these differences seem to be too small to have any clinical implication.

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Drug Combinations; Female; Gastrectomy; Humans; Male; Middle Aged; Models, Biological; Oxonic Acid; Pyridines; Stomach Neoplasms; Tegafur

We aimed to assess the efficacy and safety of S-1 combined with cisplatin (SC) over cisplatin alone (C) for the treatment of advanced gastric cancer in China. Between July 2009 and June 2011, 72 eligible patients with advanced gastric cancer were selected and divided randomly into two groups. Thirty-six patients received SC, with S-1 on days 1 through 14 of a 21-day cycle and cisplatin (60 mg/m on day 1) every 4 weeks for two cycles. The other 36 patients were administered only cisplatin (in the same manner as SC). The primary outcome was overall survival. The secondary outcomes were progression-free survival and adverse events. The 2-year overall response rate was 51.5 and 42.3% for the SC and C groups, respectively, and the difference was statistically significant, whereas the median overall survival was 9.4 months (range, 1.9-24.4 months) and 7.6 months (range, 1.7-21.4 months), respectively (P=0.039). The median progression-free survival was 7.7 months for SC (range, 1.8-19.4 months), whereas it was 6.5 months (range, 1.5-16.4 months) for C (P=0.047). The toxicity profile was similar in both groups. In summary, we have shown that S-1 combined with cisplatin is more effective, with acceptable toxicity in comparison with cisplatin alone in Chinese patients with advanced gastric cancer. Chinese Clinical Trials Register: ChiCTR-TRC-13003993.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Female; Humans; Male; Middle Aged; Oxonic Acid; Pilot Projects; Stomach Neoplasms; Tegafur

Paclitaxel and S-1 are both effective antitumor chemotherapeutic agents for advanced gastric cancer. However, the continuous administration of S-1 for 3 weeks or more can result in unacceptable toxicities, particularly hematological toxicities. Therefore, an alternative treatment schedule (1-week administration followed by 1-week rest) is warrant for testing in order to allow continuation of the therapy. We evaluate the efficacy and safety of biweekly S-1 and paclitaxel (SPA) as first-line chemotherapy in patients with metastatic or advanced gastric cancer.. Patients with previously untreated advanced or relapsed gastric cancer who had measurable lesion(s) were enrolled. Paclitaxel was administered intravenously at a dose of 120 mg/m(2) on day 1 and oral S-1 was given twice daily (BSA < 1.25 m(2), 80 mg/day; 1.25 ≤ BSA < 1.50 m(2), 100 mg/day; 1.50 m(2) ≤ BSA, 120 mg/day) on days 1-7 followed by a drug-free interval of 1 week every 14-day cycle.. Forty-four patients (M/F = 33/11) were enrolled. A total of 277 chemotherapy cycles were administered, with a median of six cycles per patient (range 1-12), and 19 (43.2 %) patients received up to seven cycles. The assessed overall response rate was 38.6 with 38.6 % partial response in 17 patients, 45.4 % stable disease in 20 patients, and 13.6 % progressive disease in six patients. Thirty-four patients (77.3 %) received second-line chemotherapy. The estimated median progression-free survival and median overall survival times were, respectively, 5.2 months (95 % CI 4.08-6.39 months) and 12.2 months (95 % CI 8.81-15.60 months). The major hematological toxicities were included grade 3 leucocytopenia in two patients (4.5 %), grade 3 neutropenia in 14 patients (40.9 %), and grade 4 neutropenia in four patients (9.0 %). Two patients (4.5 %) suffered grade 1 febrile neutropenia. All grade of the non-hematological toxicities, such as nausea, vomiting, alopecia, and diarrhea, held the proportion of 54.5 % (grade 3/4, 4.5 %), 31.8, 95.4, and 18.1 % (grade 3/4, 2.2 %), respectively.. Biweekly S-1 and paclitaxel (SPA regimen) combination therapy had promising activity with acceptable adverse toxicities. SPA regimen was easily implemented, and more patients received second-line chemotherapy. It deserved to conduct a well-designed randomized phase III study to compare this regimen with S-1-based combination treatment.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Drug Administration Schedule; Drug Combinations; Female; Humans; Male; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Paclitaxel; Prospective Studies; Stomach Neoplasms; Tegafur; Young Adult

Postoperative chemoradiotherapy (CRT) with concurrent 5-fluorouracil is the standard care for gastric cancer patients after curative surgery. The previous studies revealed that the subgroup of patients with high recurrence risk would benefit most from adjuvant CRT. S-1, a novel oral fluorouracil, has showed very effective in metastatic gastric cancer and became the standard option for gastric cancer with D2 dissection. The safety and dosage of S-1 combined with postoperative radiotherapy have not yet been evaluated. This study is to determine the maximum tolerate dose (MTD) and dose-limiting toxicity (DLT) of S-1 given concurrently with postoperative high-dose radiotherapy in gastric cancer. Patients with more advanced stage (pT4 and/or pN+) after R0 resection were recruited. Eligible patients received one cycle standard SOX (S-1 plus oxaliplatin) chemotherapy, then S-1 monotherapy with concurrent radiotherapy for 6 weeks, followed by additional three cycles of SOX. During the concurrent CRT, S-1 was administered on every radiotherapy treatment day according to a predefined dose-escalation schedule. Radiotherapy (3D-RT or IMRT) was given to a total dose of 50.4 Gy in 28 fractions. DLT was defined as grade 3 or 4 hematologic and non-hematologic toxicity. From March 2011 to October 2012, 21 patients were enrolled at five dose levels: 40 (n = 3), 50 (n = 3), 60 (n = 6), 70 (n = 6) and 80 mg/m(2)/day (n = 3). D2-dissection was performed in 18 patients (85.7 %) and 15 patients (71.4 %) had stage III disease. The most common dose-related toxicity was anorexia, nausea and vomiting, fatigue and leucopenia. DLT was occurred in one patient at 60 mg/m(2)/day (grade 3 fatigue), one patient at 70 mg/m(2)/day (grade 3 vomiting and anorexia), two patients at 80 mg/m(2)/day (one with grade 3 vomiting and anorexia; another with grade 3 febrile leucopenia). Four patients did not complete CRT as planned. Overall, this phase I study demonstrated that postoperative CRT with daily S-1 was feasible in gastric cancer and the MTD of S-1 concurrent with radiotherapy was 70 mg/m(2)/day. This S-1-based postoperative CRT will be investigated in a multicenter phase III study in West China.

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy, Adjuvant; Combined Modality Therapy; Drug Combinations; Female; Fluorouracil; Humans; Male; Maximum Tolerated Dose; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Postoperative Care; Stomach Neoplasms; Tegafur

We carried out a phase II trial to evaluate the feasibility, efficacy, and tolerability of perioperative chemotherapy including single intraperitoneal(IP) administration of paclitaxel(PTX) followed by intravenous(IV) administrations of PTX with S-1 in a neoadjuvant setting for serosa-positive gastric cancer.. Patients with cT4a gastric cancer were enrolled. A laparoscopic survey was performed before study inclusion for the confirmation of serosal invasion, negative lavage cytology, and negative peritoneal metastasis. IP PTX (80 mg/m(2)) was administered, followed by systemic chemotherapy. Surgery was performed after the completion of chemotherapy. The primary endpoint was the treatment completion rate.. 37 patients were recruited. The treatment completion rate was 67.6% (25/37; 90% CI, 52.8-80.1%), which was significantly higher than 50%; we set this as a threshold value (P = 2.4% [one-sided]). 14 patients had target lesions; of these, 10 showed a partial response (71.4%), three had stable disease (21.4%), and one had progressive disease(7.2%). The response rate was 71.4% (10/14). All patients underwent gastrectomy with D2 lymph node dissection. The 3- and 5-year OS rates were 78.0 and 74.9%, respectively.. Perioperative chemotherapy including neoadjuvant IP PTX followed by sequential IV PTX with S-1 for serosa-positive gastric cancer is feasible, safe, and efficient.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Drug Combinations; Feasibility Studies; Female; Gastrectomy; Humans; Infusions, Intraventricular; Infusions, Parenteral; Injections, Intraperitoneal; Male; Middle Aged; Neoadjuvant Therapy; Oxonic Acid; Paclitaxel; Serous Membrane; Stomach Neoplasms; Tegafur; Treatment Outcome

This open-label, randomized phase II trial was performed to compare the efficacy and safety of nimotuzumab plus S-1 and cisplatin (NCS) versus S-1 and cisplatin (CS) alone in patients with untreated unresectable or metastatic gastric cancer in the first-line setting. Eligible participants were randomly assigned (1:1) to receive either NCS or CS. The treatment consisted of 3-week cycles of twice-daily S-1 40 mg/m² (on days 1-14) and intravenous cisplatin 30 mg/m² (on days 1, 2), with or without weekly nimotuzumab (200 mg/m²). The primary endpoint was objective response rate (ORR). The second endpoint included progression-free survival (PFS), overall survival (OS), safety and association between efficacy and tumor epidermal growth factor receptor (EGFR) expression. Between October, 2009, and February, 2012, we enrolled 62 patients in Cancer Hospital Chinese Academy of Medical Sciences (CAMS). The ORR for 31 patients allocated NCS was 54.8% compared with 58.1% for 31 patients who were allocated to receive CS alone (P = 0.798). Median PFS for patients in CS arm was significantly improved than that in NCS arm [7.2 months vs. 4.8 months HR = 2.136 (95% CI 1.193-3.826), P = 0.011]. There was also a trend toward better overall survival for patients in CS arm compared with NCS arm [14.3 months vs. 10.2 months; HR = 1.776 (95% CI 0.972-3.246), P = 0.062]. In the EGFR 2+/3+ subgroup, adding nimotuzumab also failed to show additional benefit than chemotherapy alone. Both groups were well tolerated. Less than 10% of patients in both arms developed grade 3/4 toxicity. Combination of nimotuzumab and S-1-cisplatin provided no additional benefit than chemotherapy alone in the first-line treatment of unresectable or metastatic gastric cancer.

Topics: Adult; Aged; Antibodies, Monoclonal, Humanized; Antimetabolites, Antineoplastic; Antineoplastic Agents; Cisplatin; Disease-Free Survival; Drug Combinations; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Oxonic Acid; Prospective Studies; Stomach Neoplasms; Tegafur; Young Adult

The use of trastuzumab, a monoclonal antibody targeting the HER2 protein, in combination with 5-fluorouracil/platinum-based chemotherapy improves survival in patients with HER2-positive advanced gastric cancer. In addition, TS-one (S-1)/platinum is also used as a standard of care in Asian countries. However, little is known about the combination of S-1/cisplatin chemotherapy and trastuzumab in patients with HER2-positive advanced gastric/gastroesophageal junction (GEJ) cancer.. We conducted a single-arm, two-stage, open-label, multicenter phase II study. Trastuzumab was administered intravenously on day 1 of the first cycle at 8 mg/kg and 6 mg/kg on day 1 of subsequent cycles. Cisplatin was administered intravenously at 60 mg/m(2) on day 1 of each cycle after trastuzumab. S-1 was administered orally [based on body surface area (BSA)] twice a day for 14 days in a 3-weekly cycle. Patients with BSA of <1.25 received a total of 80 mg of S-1, those with BSA ≥1.5 received 120 mg, and the remaining received 100 mg daily in two divided doses.. All evaluable patients experienced tumor reduction during the trial. The primary end point (overall survival rate) was 59.3 %, with a clinical benefit rate of 66.7 %. Median progression-free survival was 7.4 months; 62.6 % patients were free from disease progression at 6 months. Median overall survival was 14.6 months, and the median time to treatment failure was 6.0 months.. The combination of trastuzumab with S-1 and cisplatin demonstrated good activity, was generally well tolerated, and is a feasible treatment option in the first-line treatment of HER2-positive advanced gastric/GEJ cancers.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; ErbB Receptors; Feasibility Studies; Female; Humans; Male; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Stomach Neoplasms; Tegafur; Trastuzumab

We previously reported that a triplet combination of docetaxel, cisplatin, and S-1 (DCS) is active against metastatic gastric cancer with a very high response rate of 87.1 % in a phase II study. Recently, the efficacy of trastuzumab (T-mab) for the treatment of HER2-positive gastric cancer has been reported. Therefore, we investigated the feasibility and preliminary efficacy of DCS + T-mab (DCS-T) for unresectable HER2-positive metastatic gastric cancer.. Patients received oral S-1 (40 mg/m(2) b.i.d.) on days 1-14, intravenous cisplatin (60 mg/m(2)), docetaxel (50 mg/m(2)), and T-mab (8 mg/kg in the first cycle and 6 mg/kg in the second cycle and thereafter) on day 8 every 3 weeks.. The study included 16 patients: median age, 60 (34-76) years; males/females, 11:5; intestinal-type/diffuse-type histology, 11:5; and HER2 3+/2+(FISH+), 13:3. The completion rate until the third cycle was 87.5 % (14/16) (95 %CI 71.3-103.7 %). Adverse events of grade 3/4 severity during the first 3 cycles were: leukopenia/neutropenia, 50.0:75.0 %; febrile neutropenia, 12.5 %; diarrhea, 12.5 %; and stomatitis, 12.5 %. All of these side effects were manageable and well controlled. There were no treatment-related deaths. The overall response rate was 93.8 % (15/16), and the response rate in patients with measurable lesions was 100 % (15/15). The median cycle to response was only 1 (1-3 cycles). Non-curative factors disappeared in 56.3 % (9/16) of patients, and conversion surgery (R0 resection) was performed in all these cases. Pathological response rates in primary and metastatic lesions were 88.9 % (8/9) and 100 % (9/9), respectively. The median PFS and OS were not reached during the median follow-up time of 18.3 months ranged from 11.0 to 34.3 months.. DCS-T was feasible in patients with unresectable HER2-positive metastatic gastric cancer. The observed response was very promising and warrants further investigation.. UMIN000005603.

Topics: Adult; Aged; Antibodies, Monoclonal, Humanized; Cisplatin; Docetaxel; Drug Combinations; ErbB Receptors; Feasibility Studies; Female; Humans; Male; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Stomach Neoplasms; Taxoids; Tegafur; Trastuzumab

In Japan, S-1 plus cisplatin has been used as first-line therapy for advanced gastric cancer (AGC). Patients with no response to first-line treatment with S-1 often receive a taxane-alone or irinotecan-alone as second-line treatment. However, second-line treatment with S-1 plus irinotecan is widely used in patients with AGC resistant to first-line S-1-based chemotherapy. The goal of this trial was to determine whether the consecutive use of S-1 plus irinotecan improves survival when compared with irinotecan-alone as second-line treatment for AGC.. Patients who had disease progression during first-line S-1-based chemotherapy were randomly assigned to receive S-1 plus irinotecan or irinotecan-alone. The S-1 plus irinotecan group received oral S-1 (40-60 mg/m(2)) on days 1-14 and intravenous irinotecan (150 mg/m(2)) on day 1 of a 21-day cycle. The irinotecan-alone group received the same dose of irinotecan intravenously on day 1 of a 14-day cycle. The primary end point was overall survival (OS).. From February 2008 to May 2011, a total of 304 patients were enrolled. The median OS was 8.8 months in the S-1 plus irinotecan group and 9.5 months in the irinotecan-alone group. This difference was not significant (hazard ratio for death, 0.99; 95% confidence interval 0.78-1.25; P = 0.92). Grade 3 or higher toxicities were more common in the S-1 plus irinotecan group than in the irinotecan-alone group.. The consecutive use of S-1 plus irinotecan is not recommended as second-line treatment in patients who are refractory to S-1-based first-line chemotherapy. ClinicalTrials.gov ID: NCT00639327.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Disease-Free Survival; Drug Administration Schedule; Drug Combinations; Drug Resistance, Neoplasm; Female; Humans; Irinotecan; Male; Middle Aged; Oxonic Acid; Stomach Neoplasms; Tegafur; Treatment Outcome; Young Adult

Five-weekly S-1 plus cisplatin (SP5) is one of the standard first-line regimens for advanced gastric cancer (GC), proven in a Japanese phase III study. To enhance the dose intensity of cisplatin, 3-weekly S-1 plus cisplatin (SP3) was developed.. This multicenter, randomized, open-label, phase III study evaluated whether SP3 (S-1 80 mg/m(2)/day on days 1-14 and cisplatin 60 mg/m(2) on day 1) was noninferior/superior to SP5 (S-1 80-120 mg/day on days 1-21 and cisplatin 60 mg/m(2) on day 1 or 8) in terms of progression-free survival (PFS). Chemotherapy-naive patients with metastatic, recurrent gastric or gastroesophageal junction adenocarcinoma were randomized 1 : 1 to receive either SP3 or SP5. The trial is registered at ClinicalTrials.gov (NCT00915382).. Between February 2009 and January 2012, 625 patients were randomized at 42 sites in Korea and Japan. With a median follow-up duration of 32.4 months (range, 13.3-48.6 months) in surviving patients, SP3 was not only noninferior but also superior to SP5 in terms of PFS [median 5.5 versus 4.9 months; hazard ratio (HR) = 0.82; 95% confidence interval (CI) 0.68-0.99; P = 0.0418 for superiority). There was no difference in overall survival (OS) between the groups (median 14.1 versus 13.9 months; HR = 0.99; 95% CI 0.81-1.21; P = 0.9068). In patients with measurable disease, the response rates were 60% in the SP3 arm and 50% in the SP5 arm (P = 0.065). Both regimens were generally well tolerated, but grade 3 or higher anemia (19% versus 9%) and neutropenia (39% versus 9%) were more frequent in SP3.. SP3 is superior to SP5 in terms of PFS. However, since the improvement in PFS was only slight and there was no difference in OS, both SP3 and SP5 can be recommended as first-line treatments for patients with advanced GC.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Administration Schedule; Drug Combinations; Follow-Up Studies; Humans; Lymphatic Metastasis; Neoplasm Recurrence, Local; Neoplasm Staging; Oxonic Acid; Prognosis; Stomach Neoplasms; Survival Rate; Tegafur

Pre-operative chemotherapy with S-1 plus cisplatin is considered to be acceptable as one of the standard treatment options for gastric cancer patients with extensive lymph node metastases in Japan. Addition of trastuzumab to chemotherapy is shown to be effective for HER2-positive advanced gastric cancer patients, and we have commenced a randomized Phase II trial in March 2015 to evaluate S-1 plus cisplatin plus trastuzumab compared with S-1 plus cisplatin alone in the neoadjuvant setting for HER2-positive gastric cancer patients with ELM, which are followed by adjuvant chemotherapy with S-1 for 1 year. A total of 130 patients will be accrued from 41 Japanese institutions over 3 years. The primary endpoint is overall survival. The secondary endpoints are progression-free survival, response rate of pre-operative chemotherapy, proportion of patients with R0 resection, proportion of patients who complete the pre-operative chemotherapy and surgery, proportion of patients who complete the protocol treatment including post-operative chemotherapy, pathological response rate and adverse events. This trial has been registered in the UMIN Clinical Trials Registry as UMIN 000016920.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cisplatin; Disease-Free Survival; Drug Combinations; Esophageal Neoplasms; Esophagogastric Junction; Female; Humans; Japan; Kaplan-Meier Estimate; Lymphatic Metastasis; Male; Middle Aged; Neoadjuvant Therapy; Oxonic Acid; Patient Selection; Receptor, ErbB-2; Stomach Neoplasms; Tegafur; Trastuzumab; Treatment Outcome

The safety and efficacy of S-1 plus cisplatin in Chinese advanced gastric cancer patients in first line setting is unknown. In this pilot study, patients with advanced gastric or gastro-esophageal junction adenocarcinoma were enrolled and randomly assigned in a 1:1 ratio to receive S-1 plus cisplatin (CS group) or 5-FU plus cisplatin (CF group). The primary endpoint was time to progression (TTP). Secondary end points included overall survival (OS) and safety. This study was registered on ClinicalTrials. Gov, number NCT01198392. A total of 236 patients were enrolled. Median TTP was 5.51 months in CS group compared with 4.62 months in CF group [hazard ratio (HR) 1.028, 95% confidential interval (CI) 0.758-1.394, p = 0.859]. Median OS was 10.00 months and 10.46 months in CS and CF groups (HR 1.046, 95%CI 0.709-1.543, p = 0.820), respectively. The most common adverse events in both groups were anemia, leukopenia, neutropenia, nausea, thrombocytopenia, vomiting, anorexia and diarrhea. We find that S-1 plus cisplatin is an effective and tolerable option for advanced gastric or gastro-esophageal junction adenocarcinoma patients in China.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Disease-Free Survival; Drug Combinations; Esophagogastric Junction; Female; Fluorouracil; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Oxonic Acid; Pilot Projects; Stomach Neoplasms; Tegafur

Sorafenib inhibits several receptor tyrosine kinases involved in tumor progression and angiogenesis. S-1, an oral fluorouracil antitumor drug, plus cisplatin (CDDP) is the standard regimen for advanced gastric adenocarcinoma (AGC) in Japan. The purpose of this phase I study was to evaluate the safety, pharmacokinetics, and preliminary efficacy of sorafenib in combination with S-1 plus CDDP.. Patients with histologically confirmed previously untreated AGC were evaluated for eligibility and treated with sorafenib (400 mg bid, days 1-35), S-1 (40 mg/m(2) bid, days 1-21), and CDDP (60 mg/m(2), day 8). Treatment was continued until disease progression or unacceptable toxicity. Pharmacokinetics for sorafenib, 5-FU, and CDDP were investigated in cycle 1.. Thirteen patients were enrolled and received at least one dose of the study treatment. No specific or serious adverse event was newly reported in this study. Five patients had partial response and 8 had stable disease as the best response. Pharmacokinetic analysis showed no significant differences in the exposures of sorafenib when administered alone or in combination with S-1 and CDDP.. The present phase I study demonstrates the acceptable toxicity and preliminary efficacy of combined treatment with S-1, CDDP, and sorafenib.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Female; Fluorouracil; Humans; Male; Middle Aged; Niacinamide; Oxonic Acid; Patient Compliance; Phenylurea Compounds; Sorafenib; Stomach Neoplasms; Tegafur; Treatment Outcome

This phase I, dose-finding study evaluated the maximum tolerated dose (MTD), safety, pharmacokinetics, and antitumor activity of sunitinib plus S-1/cisplatin in Japanese patients with advanced/metastatic gastric cancer.. Patients received oral sunitinib on a continuous daily dosing (CDD) or 2-weeks-on/2-weeks-off schedule (Schedule 2/2; 25 mg/day or 37.5 mg/day), plus S-1 (80-120 mg/day)/cisplatin 60 mg/m(2).. Twenty-seven patients received treatment, including 26 patients treated per protocol (sunitinib 25 mg/day CDD schedule, n = 4; sunitinib 25 mg/day Schedule 2/2, n = 16 [dose-limiting toxicity (DLT) cohort, n = 6 plus expansion cohort, n = 10]; sunitinib 37.5 mg/day Schedule 2/2, n = 6). One patient erroneously self-administered sunitinib 12.5 mg/day and was excluded from the analyses. The MTD was sunitinib 25 mg/day on Schedule 2/2. DLTs were reported for: 2/4 patients given sunitinib 25 mg/day on the CDD schedule; 1/6 patients administered sunitinib 25 mg/day on Schedule 2/2 (grade [G] 3 neutropenic infection, G4 thrombocytopenia, and S-1 dose interruption ≥5 days), and 3/6 patients given sunitinib 37.5 mg/day on Schedule 2/2. Results below are for the overall MTD cohort (n = 16). The most frequently reported G3/4 adverse events were neutropenia (93.8 %) and leukopenia (75.0 %). The objective response rate was 37.5 %; six additional patients experienced no disease progression for ≥24 weeks. Median progression-free survival was 12.5 months. No pharmacokinetic drug-drug interactions were observed between sunitinib/S-1/cisplatin and S-1/cisplatin.. The MTD of sunitinib was 25 mg/day on Schedule 2/2 combined with cisplatin/S-1 in patients with advanced/metastatic gastric cancer. This regimen had a manageable safety profile and preliminary antitumor activity.

Topics: Adult; Aged; Angiogenesis Inhibitors; Antineoplastic Combined Chemotherapy Protocols; Asian People; Cisplatin; Drug Combinations; Female; Humans; Indoles; Male; Maximum Tolerated Dose; Middle Aged; Oxonic Acid; Pyrroles; Stomach Neoplasms; Sunitinib; Tegafur; Treatment Outcome

We have previously reported the superior feasibility and safety of adjuvant S-1 plus docetaxel in patients with stage III gastric cancer during a prospective phase II study. We report 3-year follow-up data on patients enrolled in this study.. Fifty-three patients with histologically confirmed stage III gastric cancer who underwent gastrectomy with D2 lymphadenectomy were enrolled into this study. They received oral S-1 (80 mg/m(2)/day) for 2 consecutive weeks and intravenous docetaxel (40 mg/m(2)) on day 1, repeated every 3 weeks (one cycle). Treatment was initiated within 45 days after surgery and repeated for four cycles, followed by S-1 monotherapy (4 weeks on, 2 weeks off) until 1 year after surgery. Three-year overall survival (OS) and disease-free survival (DFS) were evaluated.. The OS rate at 3 years was 78.4 % [95 % confidence interval (CI), 67.9-90.6 %] and the DFS rate at 3 years was 66.2 % (95 % CI, 54.4-80.7 %). Subgroup analyses according to disease stage showed a 3-year OS and DFS rate of 85.7 % (95 % CI, 74.9-98.1 %) and 70.8 % (95 % CI, 57.1-87.8 %) for stage IIIA, and 62.5 % (95 % CI, 42.8-91.4 %) and 56.2 % (95 % CI, 36.5-86.7 %) for stage IIIB, respectively.. On the basis of 3-year follow-up data, postoperative adjuvant therapy with S-1 plus docetaxel yielded promising OS and DFS in stage IIIA gastric cancer patients who had undergone D2 gastrectomy. We believe that this regimen is a candidate for future phase III trials studying the optimal adjuvant chemotherapy regimen for stage III gastric cancer.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Combined Modality Therapy; Docetaxel; Drug Combinations; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Oxonic Acid; Prognosis; Prospective Studies; Salvage Therapy; Stomach Neoplasms; Survival Rate; Taxoids; Tegafur; Time Factors

S-1 is an oral anticancer drug widely used in postoperative adjuvant therapy for patients in Japan with stage II/III gastric cancer. Candidates for more intense adjuvant treatments need to be identified, particularly among patients with stage III cancer.. Univariate and multivariate analyses were conducted for patients with stage II/III gastric cancer who underwent surgery and received S-1 postoperatively between 2000 and 2010.. Factors indicating poor prognosis identified by univariate analysis include male sex (P = 0.022), age ≥67 years (P = 0.021), intestinal-type histology (P = 0.049), lymph node ratio ≥16.7 % (P < 0.0001), open surgery (P = 0.039), as well as the 13th JGCA stage (P < 0.0001) and the 14th JGCA/7th International Union Against Cancer (UICC) stage (P < 0.0001). Multivariate analysis revealed that lymph node ratio ≥16.7 % and intestinal-type histology were significant as predictors of prognosis, independent from the pathological stages. Based on these and other findings, stage IIIC cancer on the 14th JGCA/7th UICC stage system in combination with the lymph node ratio could identify patients with extremely high risk for recurrence. Our current findings suggest that lymph node ratio ≥16.7 % in combination with the new staging system could be a useful prognostic indicator in advanced gastric cancer. Because these high-risk patients cannot be identified preoperatively by any diagnostic tool, further improvement in postoperative adjuvant therapy is warranted.

Topics: Adenocarcinoma; Aged; Chemotherapy, Adjuvant; Drug Combinations; Female; Humans; Japan; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Multivariate Analysis; Neoplasm Staging; Oxonic Acid; Prognosis; Stomach Neoplasms; Tegafur; Treatment Outcome

The prognosis for stage 3 gastric cancer is not satisfactory, even with S-1 adjuvant chemotherapy. A randomized phase II trial was conducted to compare two and four courses of neoadjuvant S-1/cisplatin (SC) and paclitaxel/cisplatin (PC) using a two-by-two factorial design for locally advanced gastric cancer. The primary endpoint was overall survival. We clarified the impact of these regimens on the secondary endpoints, including the clinical and pathological responses, chemotherapy-related toxicities, and surgical results.. Patients received S-1 (80 mg/m(2) for 21 days with 1 week's rest)/cisplatin (60 mg/m(2) at day 8) or paclitaxel/cisplatin (80 and 25 mg/m(2), respectively, on days 1, 8, and 15 with 1 week's rest) as neoadjuvant chemotherapy.. Eighty-three patients were assigned to arm A (two courses of SC, n = 21), arm B (four courses of SC, n = 20), arm C (two courses of PC, n = 21), and arm D (four courses of PC, n = 21). Pathological response rate was 43 % in arm A, 40 % in arm B, 29 % in arm C, and 38 % in arm D. Pathological complete response was only observed in arms B (10 %) and D (10 %). Most bone marrow toxicities, nausea, vomiting, alopecia, and fatigue were slightly higher but acceptable in arms B and D. Grade 3/4 surgical morbidities were not commonly observed in all four arms.. Pathological complete response could be induced by four courses of neoadjuvant chemotherapy without a marked increase of toxicities, regardless of a SC or PC regimen.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Oxonic Acid; Paclitaxel; Prognosis; Stomach Neoplasms; Survival Rate; Tegafur; Young Adult

S-1 plus weekly split-dose cisplatin demonstrated promising results in previous phase I and II studies for advanced gastric cancer (AGC) patients.. In this randomized phase II study, the efficacy and safety of S-1 plus weekly split-dose cisplatin (SWP, S-1 daily oral dose of 80-120 mg according to body surface area on days 1-14, and cisplatin 20 mg/m(2) i.v. on days 1 and 8 every 3 weeks) were compared with those of S-1 plus standard-dose cisplatin (SP) as first-line chemotherapy for AGC patients. The primary endpoint was 1-year survival rate.. Patients were randomized into two groups: 18 in the SWP arm and 19 in the SP arm. This trial was terminated early because of low patient enrollment. The 1-year survival rate was 61 % [95 % confidence interval (CI), 36-86 %] and 53 % (95 % CI, 30-75 %) in the SWP and SP arms, respectively. However, the median survival time was 12.3 months (9.9-14.6 months) and 15.7 months (4.0-27.4 months), respectively (P = 0.064). Progression-free survival was significantly shorter in the SWP arm than in the SP arm (P = 0.047). Toxicity tended to be milder in the SWP arm than in the SP arm. For approximately 40 % of patients in the SWP arm, cisplatin was omitted on day 8 and treatment delayed because of prolonged myelosuppression.. No clear benefits of adding cisplatin to S-1 in the SWP arm were demonstrated in this study. At this point, split-dose cisplatin combined with S-1 cannot be recommended for use in clinical practice.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Docetaxel; Drug Combinations; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Oxonic Acid; Prognosis; Stomach Neoplasms; Survival Rate; Taxoids; Tegafur; Young Adult

The Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer established oral S-1 administration for 1 year as the standard postoperative adjuvant chemotherapy for gastric cancer in Japan. We conducted a multicenter cooperative prospective study comparing daily and alternate-day S-1 administration as postoperative adjuvant therapy for gastric cancer.. Patients with Stage II or III gastric cancer who underwent curative surgery were randomly assigned to receive standard daily S-1 administration [group A: 80-120 mg/day S-1 depending on body surface area (BSA); days 1-28 every 6 weeks for 1 year] or alternate-day administration (group B: 80-120 mg/day S-1 depending on BSA; alternate days for 15 months). Treatment completion rate was the primary endpoint, and relative dose intensity and safety, overall survival, and relapse-free survival (RFS) were secondary endpoints.. Seventy-three patients were enrolled. The treatment completion rate was 72.2 % in group A and 91.8 % in group B; the relative dose intensity was 67.5 % in group A and 81.2 % in group B; and compliance was better in group B. Digestive system adverse effects were less frequent in group B than in group A. Median follow-up time was 2.8 years; 3-year survival rate was 69.6 % in group A and 87.3 % in group B; and 3-year RFS rate was 76.4 % in group A and 73.1 % in group B.. Our data show improved compliance and fewer adverse effects with alternate-day S-1 administration, which appears to be a more sustainable option for adjuvant chemotherapy for Stage II or III gastric cancer.

Topics: Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Disease-Free Survival; Drug Administration Schedule; Drug Combinations; Feasibility Studies; Female; Follow-Up Studies; Humans; Male; Medication Adherence; Middle Aged; Neoplasm Staging; Oxonic Acid; Prospective Studies; Stomach Neoplasms; Survival Rate; Tegafur; Treatment Outcome

Neoadjuvant chemotherapy may improve outcomes in gastric cancer. Tumor responses can be evaluated with RECIST, Japanese Classification of Gastric Carcinoma (JCGC), and histological criteria. These approaches have not yet been compared.. We analyzed two phase II trials of neoadjuvant chemotherapy using S-1 plus cisplatin. JCOG0210 included patients with linitis plastica and large ulcero-invasive tumors, whereas JCOG0405 comprised those with para-aortic or bulky lymph node metastases. Radiologic evaluations were conducted using RECIST in JCOG0405 and JCGC criteria in JCOG0210, because the latter included many patients without measurable lesions. A histological responder was defined as a patient in whom one third or more of the tumor was affected. The hazard ratios (HR) for death between responders and non-responders and response rate differences between short- and long-term survivors were estimated.. In JCOG0210 (n = 49), HR was 0.54 in JCGC responders (P = 0.059) and 0.40 in histological responders (P = 0.005). The difference in response rates between short- and long-term survivors using histological criteria (34 %, P = 0.023) was greater than that using JCGC criteria (24 %, P = 0.15). In JCOG0405 (n = 51), HR was 0.67 in RECIST responders (P = 0.35) and 0.39 in histological responders (P = 0.030). In short- and long-term survivors, respectively, RECIST response rates were 62  and 67 % (P = 0.77), whereas histological response rates were 33  and 63 % (P = 0.048).. Histological criteria showed higher response assessment validity than RECIST or JCGC criteria and yielded the best surrogate endpoint for overall survival.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Female; Humans; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Invasiveness; Neoplasm Metastasis; Oxonic Acid; Proportional Hazards Models; Stomach Neoplasms; Survival Rate; Tegafur; Time Factors; Treatment Outcome

S-1+cisplatin (CDDP) is the standard treatment for advanced gastric cancer (AGC) in Japan and Korea. However, the usefulness of S-1 based chemotherapy for elderly patients is unclear. Therefore, we conducted a multicenter phase II study of S-1 monotherapy for AGC in elderly patients.. Chemotherapy-naïve patients aged over 75 years with AGC were enrolled. The starting dose of S-1 was determined on the basis of body surface area and modified according to the creatinine clearance value. S-1 was administered twice a day during a 4-week period followed by a 2-week rest period.. Thirty-five patients were enrolled. The response rate (RR) was 14.3% and the median overall survival was 14.6 months. Grade 3 or more severe adverse events consisted of anaemia (3%), neutropaenia (3%), anorexia (3%), and fatigue (6%). There were no treatment-related deaths.. Our study indicates that S-1 monotherapy is safe and well tolerated in chemotherapy-naïve elderly patients with AGC, but exerts limited activity when given using a tailor-made dosing strategy based on renal function.

Topics: Age Factors; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Drug Administration Schedule; Drug Combinations; Female; Follow-Up Studies; Humans; Male; Neoplasm Recurrence, Local; Neoplasm Staging; Oxonic Acid; Prognosis; Stomach Neoplasms; Survival Rate; Tegafur

The combination of docetaxel and S-1 (DS) therapy is effective in patients with unresectable gastric cancer and is expected to be a regimen in neoadjuvant setting for advanced gastric cancer. This study was held to evaluate the efficacy and safety of DS followed by surgery.. Patients with resectable gastric cancer received 2 courses of docetaxel 40 mg/m(2) on days 1, 15 and S-1 40 mg/m(2) bid orally on days 1-7, 15-21 every 4 weeks, followed by standard radical gastrectomy. Primary end point was the pathological response rate: rate of tumors in which one-third or more parts were affected.. Fourteen patients were enrolled. Thirteen (92.8 %) patients completed two courses of chemotherapy. Grade 3 adverse events were neutropenia in 3 (21.4 %) patients, anemia in 1 (6.2 %) patient and diarrhea in 1 (6.2 %) patient. There were no grade 4 adverse event and febrile neutropenia. All patients underwent R0 resection, and pathological response was found in 50.0 % of patients. There were no major surgical complications and no treatment-related mortality.. The neoadjuvant chemotherapy with DS was effective for patients with locally advanced gastric cancer with manageable toxicities. Further study to confirm the usefulness of this regimen is needed.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cohort Studies; Docetaxel; Drug Combinations; Feasibility Studies; Female; Humans; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Oxonic Acid; Prospective Studies; Stomach Neoplasms; Taxoids; Tegafur

We conducted a multicenter phase II trial to assess the suitability of three types of chemotherapy (docetaxel plus S-1, irinotecan plus S-1, or S-1 alone) for patients with advanced gastric cancer by means of the collagen gel droplet embedded culture-drug sensitivity test (CD-DST). To our knowledge, this is the first multicenter clinical trial that has employed CD-DST to choose anticancer agents for the treatment of advanced gastric cancer.. Subjects (n = 64) were patients with advanced or recurrent gastric cancer. Patients were allocated to one of the treatment regimens on the basis of CD-DST results. Outcome of the patients was compared between the groups deemed chemosensitive or chemoresistant by the CD-DST.. Thirty-three patients showed high sensitivity (T/C ratio <60 %) to at least one type of anticancer agent (sensitive group), and 31 showed low sensitivity (T/C ratio ≥60 %) to all agents (resistant group). Specifically, the 1-year survival rate was significantly higher in the sensitive group (78.5 %; 95 % CI, 67.2-94.7 %) than in the resistant group (54.7 %; 95 % CI, 38.7-74.3 %; P = 0.019), whereas time to progression (TTP) was significantly longer in the sensitive group (59.8 %; 95 % CI, 48.2-81.7 %) than in the resistant group (30.0 %; 95 % CI 13.6-46.4 %; P = 0.023). Median survival time was also significantly longer in the sensitive group (15.5 months; 95 % CI, 12.8-18.2) than in the resistant group (12.5 months; 95 % CI, 10.2-14.9; P = 0.038).. CD-DST predicts the outcome of patients undergoing chemotherapy for advanced gastric cancer, presumably through evaluating chemosensitivity.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cisplatin; Collagen; Docetaxel; Drug Combinations; Drug Resistance, Neoplasm; Female; Humans; Irinotecan; Male; Middle Aged; Neoplasm Recurrence, Local; Oxonic Acid; Stomach Neoplasms; Taxoids; Tegafur; Treatment Outcome

Cisplatin plus 5-fluorouracil has been globally accepted as a standard regimen for the treatment for advanced gastric cancer. However, cisplatin has several disadvantages, including renal toxicity and the need for admission. S-1 plus cisplatin has become a standard treatment for advanced gastric cancer in East Asia. This phase III study was designed to evaluate the potential benefits of adding docetaxel to S-1 without a platinum compound in patients with advanced gastric cancer.. Patients were randomly assigned to receive docetaxel plus S-1 or S-1 alone. The docetaxel plus S-1 group received docetaxel on day 1 and oral S-1 on days 1-14 of a 21-day cycle. The S-1 alone group received oral S-1 on days 1-28 of a 42-day cycle. The primary end point was overall survival.. Of the 639 patients enrolled, 635 were eligible for analysis. The median overall survival was 12.5 months in the docetaxel plus S-1 group and 10.8 months in the S-1 alone group (p = 0.032). The median progression-free survival was 5.3 months in the docetaxel plus S-1 group and 4.2 months in the S-1 alone group (p = 0.001). As for adverse events, neutropenia was more frequent in the docetaxel plus S-1 group, but remained manageable.. As first-line treatment for advanced gastric cancer, docetaxel plus S-1 significantly improves median overall and progression-free survival as compared with S-1 alone. (ClinicalTrials.gov number: NCT00287768).

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Docetaxel; Drug Combinations; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Neoplasm Staging; Oxonic Acid; Prognosis; Prospective Studies; Stomach Neoplasms; Survival Rate; Taxoids; Tegafur; Young Adult

In patients with highly advanced gastric cancer, the recurrence rate remains high and the prognosis disappointing. We previously reported a phase I study of a neoadjuvant chemoradiotherapy of S-1 plus weekly cisplatin. Although adequate safety and efficacy were reported, myelosuppression was frequently observed, leading to treatment delay in several cases. To decrease toxicity and improve efficacy, we planned a phase I study with a modified chemotherapy regimen with biweekly cisplatin.. Patients with advanced gastric cancer and lymph node metastasis who were treated by our institution between 2011 and 2012 were eligible for inclusion. The initial chemoradiotherapy schedule consisted of 6 weeks of S-1 orally administered on days 1-15 with an escalating dose of cisplatin administered on days 1 and 15. The starting dose (level 1) of cisplatin was 15 mg/m(2), the second dose (level 2) was 20 mg/m(2), and the third dose (level 3) was 25 mg/m(2). Radiation of 40 Gy was administered in 20 fractions. After initial chemoradiotherapy, one cycle of combination chemotherapy with S-1 plus cisplatin was delivered. The second cycle was 42 days in duration and included S-1 administered on days 1-29 plus biweekly cisplatin administered on days 1, 15, and 29. After neoadjuvant treatment, a curative gastrectomy with extended (D2) lymph node dissection was planned.. Nine patients were enrolled. At level 3, one patient had dose-limiting grade 3 diarrhea. Another patient experienced grade 3 nausea and intended to discontinue the treatment. Overall, because 2 of 3 patients experienced dose-limiting toxicity at level 3, we confirmed level 3 (Cisplatin 25 mg/m(2)) as the maximum tolerated dose and level 2 (Cisplatin 20 mg/m(2)) as the recommended dose (RD). The response rate was 78%, and 8 patients underwent curative gastrectomy. Resected specimens showed a histological response in 6 patients (75%), including one with a pathological complete response.. In this phase I trial, RD of cisplatin was identified as 20 mg/m(2). Generally, S-1 plus biweekly cisplatin can be given safely with concurrent radiation. We have initiated a multicenter phase II trial to further confirm the efficacy and safety of this approach.. UMIN000008941.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Cisplatin; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Humans; Lymphatic Metastasis; Male; Maximum Tolerated Dose; Middle Aged; Neoadjuvant Therapy; Oxonic Acid; Radiotherapy Dosage; Stomach Neoplasms; Tegafur; Treatment Outcome

S-1, an oral fluoropyrimidine, plus cisplatin (SP) is a standard regimen for advanced gastric cancer (AGC) in East Asia. To date, no studies have evaluated the efficacy and safety of trastuzumab combined with SP in patients with human epidermal growth factor receptor type 2 (HER2)-positive AGC.. Patients with HER2-positive AGC received S-1 (80-120 mg per day) orally on days 1-14, cisplatin (60 mg m(-2)) intravenously on day 1, and trastuzumab (course 1, 8 mg kg(-1); course 2 onward, 6 mg kg(-1)) intravenously on day 1 of a 21-day cycle. The primary end point was response rate (RR); secondary end points included overall survival (OS), progression-free survival (PFS), time to treatment failure (TTF), and adverse events.. A total of 56 patients were enrolled. In the full analysis set of 53 patients, the confirmed RR was 68% (95% confidence interval (CI)=54-80%), and the disease control rate was 94% (95% CI=84-99%). Median OS, PFS, and TTF were estimated as 16.0, 7.8, and 5.7 months, respectively. Major grade 3 or 4 adverse events included neutropaenia (36%), anorexia (23%), and anaemia (15%).. Trastuzumab in combination with SP showed promising antitumour activity and manageable toxic effects in patients with HER2-positive AGC.

Topics: Adult; Aged; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Disease-Free Survival; Drug Combinations; Female; Humans; Male; Middle Aged; Oxonic Acid; Receptor, ErbB-2; Stomach Neoplasms; Tegafur; Trastuzumab

S-1-based regimens are commonly used for advanced gastric cancer (AGC) in Japan. We performed this trial to evaluate the efficacy and safety of S-1 plus irinotecan (SIri) and S-1 plus paclitaxel (SPac) as first-line treatments for AGC in order to select the optimal regimen for a subsequent phase III trial.. Patients with previously untreated, locally advanced or metastatic measurable gastric adenocarcinoma were randomly assigned to receive SIri (irinotecan 80 mg/m(2) was administered intravenously (i.v.) on day 1 and 15, while 40 mg/m(2) S-1 was orally administered twice daily for three weeks from days 1-21 followed by a two-week pause) or SPac (paclitaxel 50 mg/m(2) was administered i.v. on day 1 and 8, while 40 mg/m(2) S-1 was orally administered twice daily for two weeks from day 1-14 followed by a one-week pause) regimen. The primary end-point was the overall response rate (ORR), and the secondary end-points were progression-free survival (PFS), overall survival (OS), and toxicity.. A total of 102 patients were enrolled. The ORR was 33.3% for SIri and 31.4% for SPac, which did not achieved the predicted ORR in either group. PFS and OS were 5.7 and 12.4 months for SIri, 4.6 and 11.9 months for SPac respectively. No treatment-related deaths occurred during the study. Although grade 3/4 neutropenia and anemia were more frequent in the Siri group, both regimens were well-tolerated.. Both regimens were well-tolerated in patients with AGC, but we conclude that neither regimen was optimal for a phase III trial.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Disease-Free Survival; Drug Administration Schedule; Drug Combinations; Female; Humans; Irinotecan; Male; Middle Aged; Oxonic Acid; Paclitaxel; Prospective Studies; Stomach Neoplasms; Tegafur

Accuracy of the radiologic diagnosis of gastric cancer staging after neoadjuvant chemotherapy remains unclear.. Patients enrolled in the COMPASS trial, a randomized phase II study comparing two and four courses of S-1 plus cisplatin and paclitaxel and cisplatin followed by gastrectomy, were examined. The radiologic stage was determined by using thin-slice computed tomography (CT) or multidetector low CT by following Habermann's method.. A total of 75 patients registered in the COMPASS study who underwent surgical resection were examined in this study. The radiologic T and pathologic T stages were not significantly correlated (p = 0.221). The radiologic accuracy and rates of underdiagnosis and overdiagnosis were 42.7, 10.7, and 46.7%, respectively. When patients were stratified according to the pathologic response of the primary tumor, the correlation was not significant in either the responders (n = 32, p = 0.410) or the nonresponders (n = 43, p = 0.742). The radiologic accuracy was 37.5% in the responders and 42.7% in the nonresponders. The radiologic N and pathologic N stages were significantly correlated (p = 0.000). The radiologic accuracy and rates of underdiagnosis and overdiagnosis were 44, 29.3, and 26.7%, respectively. When stratifying the patients with measurable lymph nodes according only to the radiologic response, the correlation was significant in the nonresponders (n = 23, p = 0.035) but not in the responders (n = 28, p = 0.634). The radiologic accuracy was 39.3% in the responders and 52.1% in the nonresponders.. Restaging using CT after neoadjuvant chemotherapy for gastric cancer is considered to be inaccurate and unreliable. In particular, the radiologic T-staging determined after neoadjuvant chemotherapy should not be considered in clinical decision-making.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Cohort Studies; Combined Modality Therapy; Drug Combinations; Female; Follow-Up Studies; Gastrectomy; Humans; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Oxonic Acid; Paclitaxel; Prognosis; Radiographic Image Interpretation, Computer-Assisted; Stomach Neoplasms; Survival Rate; Tegafur; Tomography, X-Ray Computed

We conducted a phase II trial to evaluate the efficacy and safety of preoperative chemotherapy with docetaxel (DTX) plus S-1 for resectable advanced gastric cancer.. A total of 47 patients from 14 centers were centrally registered. Patients received DTX (35 mg/m(2)) on days 1 and 15, and daily oral administration of S-1 (80 mg/m(2)/day) for days 1-14 every 4 weeks for two courses, followed by gastrectomy with D2 lymphadenectomy. The primary endpoint was pathological response rate (pRR). This study was registered in the UMIN clinical trial registry (UMIN000000875).. The primary endpoint pRR was 47 % (90 % confidence interval (CI), 34-60 %; p < 0.0001). The response rate to preoperative chemotherapy using Response Evaluation Criteria in Solid Tumors (RECIST) was 34 %. Forty-six patients (98 %) underwent surgery, and curative resection was performed in 44 patients. Thirty-seven patients completed the protocol treatment. The most common toxicities of neoadjuvant chemotherapy were grade 3/4 neutropenia (42 %), febrile neutropenia (4 %), grade 2 anorexia (21 %), and fatigue (15 %). Treatment-related death and operative mortality was not observed in this study.. The combination of docetaxel and S-1 was well tolerated. This is promising as a preoperative chemotherapy regimen for patients with potentially resectable advanced gastric cancer.

Topics: Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Docetaxel; Drug Combinations; Female; Follow-Up Studies; Gastrectomy; Humans; Lymph Node Excision; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Oxonic Acid; Preoperative Care; Prognosis; Stomach Neoplasms; Survival Rate; Taxoids; Tegafur

This randomized phase II study was performed to compare the efficacy and safety of oxaliplatin combined with S-1 (OXS regimen) with S-1 alone in the management of advanced gastric cancer (AGC). Ninety-four patients were 1:1 randomly assigned to S-1 on days 1-14 of a 3-week cycle or S-1 on days 1-14 plus oxaliplatin (130 mg/m(2) i.v.) on day 1 of the 3-week cycle. S-1 was orally administered in a fixed quantity according to body surface area. The median survival time with OXS versus S-1 monotherapy was 14·0 versus 11·0 months (P = 0·03), progression-free survival was 6·5 versus 4·0 months (P = 0·02), and the 1-year survival rate was 63·8% versus 48·9%, respectively. The response rate was significantly higher for OXS than for S-1 monotherapy (51·1% vs. 27·7%, P = 0·03). OXS was well tolerated with no treatment-related death. In conclusion, the OXS regimen evidenced a relatively high efficacy and was well tolerated as a first-line therapy for AGC patients.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Disease-Free Survival; Drug Combinations; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Proportional Hazards Models; Stomach Neoplasms; Tegafur

Locally advanced gastric cancer with extensive regional and/or para-aortic lymph node (PAN) metastases is typically unresectable and associated with poor outcomes. This study investigated the safety and efficacy of S-1 plus cisplatin followed by extended surgery with PAN dissection for gastric cancer with extensive lymph node metastasis.. Patients with gastric cancer with bulky lymph node metastasis along the coeliac artery and its branches and/or PAN metastasis received two or three 28-day cycles of S-1 plus cisplatin, followed by gastrectomy with D2 plus PAN dissection. The primary endpoint was the percentage of complete resections with clear margins in the primary tumour (R0 resection). A target sample size of 50 with one-sided α of 0.105 and β of approximately 0.2 corresponded to an expected R0 rate of 65 per cent and a threshold of 50 per cent.. Between February 2005 and June 2007, 53 patients were enrolled, of whom 51 were eligible. The R0 resection rate was 82 per cent. Clinical and pathological response rates were 65 and 51 per cent respectively. The 3- and 5-year overall survival rates were 59 and 53 per cent respectively. During chemotherapy, grade 3/4 neutropenia occurred in 19 per cent and grade 3/4 non-haematological adverse events in 15.4 per cent. The incidence of grade 3/4 adverse events related to surgery was 12 per cent. There were no reoperations or treatment-related deaths.. For locally advanced gastric cancer with extensive lymph node metastasis, 4-weekly S-1 plus cisplatin followed by surgery including PAN dissection was safe and effective for some patients. Further investigation of this treatment strategy is warranted.

Topics: Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cisplatin; Drug Combinations; Female; Gastrectomy; Humans; Kaplan-Meier Estimate; Lymph Node Excision; Lymphatic Metastasis; Male; Middle Aged; Neutropenia; Oxonic Acid; Postoperative Complications; Stomach Neoplasms; Tegafur; Treatment Outcome

The feasibility and safety of D2 surgery following neoadjuvant chemotherapy (NAC) has not been fully evaluated in patients with gastric cancer. Moreover, risk factor for surgical complications after D2 gastrectomy following NAC is also unknown. The purpose of the present study was to identify risk factors of postoperative complications after D2 surgery following NAC.. This study was conducted as an exploratory analysis of a prospective, randomized Phase II trial of NAC. The surgical complications were assessed and classified according to the Clavien-Dindo classification. A uni- and multivariate logistic regression analyses were performed to identify risk factors for morbidity.. Among 83 patients who were registered to the Phase II trial, 69 patients received the NAC and D2 gastrectomy. Postoperative complications were identified in 18 patients and the overall morbidity rate was 26.1 %. The results of univariate and multivariate analyses of various factors for overall operative morbidity, creatinine clearance (CCr) ≤ 60 ml/min (P = 0.016) was identified as sole significant independent risk factor for overall morbidity. Occurrence of pancreatic fistula was significantly higher in the patients with a low CCr than in those with a high CCr.. Low CCr was a significant risk factor for surgical complications in D2 gastrectomy after NAC. Careful attention is required for these patients.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Creatinine; Drug Combinations; Feasibility Studies; Female; Follow-Up Studies; Gastrectomy; Humans; Lymph Node Excision; Lymphatic Metastasis; Male; Middle Aged; Morbidity; Neoadjuvant Therapy; Neoplasm Staging; Oxonic Acid; Peritoneal Neoplasms; Postoperative Complications; Prognosis; Prospective Studies; Risk Factors; Stomach Neoplasms; Tegafur

To compare the short-term efficacy and safety profile of the S-1 + irinotecan + oxaliplatin (TIROX) and docetaxel + cisplatin + flurouracil (DCF) anticancer regimens in patients with advanced gastric cancer.. Patients with recurrent or metastatic gastric cancer diagnosed by pathology were randomly divided into two groups to receive six cycles of either the TIROX regimen (21-day cycle) or the DCF regimen (21-day cycle). After six chemotherapy cycles, the short-term efficacy was evaluated according to the Response Evaluation Criteria in Solid Tumors guidelines and adverse reactions were recorded according to National Cancer Institute Common Toxicity Criteria 2.0 standards.. A total of 60 patients were enrolled in the study. The response rate (complete response + partial response) was significantly higher in the TIROX group (18/30 patients; 60.0%) compared with the DCF group (10/30 patients; 33.3%). The rates of grade III-IV leucopenia and neurotoxicity were significantly higher in the TIROX group than the DCF group.. The TIROX regimen was effective for the treatment of advanced gastric cancer, but it was associated with leucopenia and neurotoxicity.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cisplatin; Docetaxel; Drug Administration Schedule; Drug Combinations; Female; Fluorouracil; Humans; Irinotecan; Leukopenia; Lymphatic Metastasis; Male; Middle Aged; Neurotoxicity Syndromes; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Prospective Studies; Recurrence; Stomach Neoplasms; Taxoids; Tegafur; Treatment Outcome

The prognosis for locally advanced gastric cancer is poor despite advances in adjuvant chemotherapy. We did the Stomach cancer Adjuvant Multi-Institutional group Trial (SAMIT) to assess the superiority of sequential treatment (paclitaxel then tegafur and uracil [UFT] or paclitaxel then S-1) compared with monotherapy (UFT or S-1) and also the non-inferiority of UFT compared with S-1.. We did this randomised phase 3 trial with a two-by-two factorial design at 230 hospitals in Japan. We enrolled patients aged 20-80 years with T4a or T4b gastric cancer, who had had D2 dissection and a ECOG performance score of 0-1. Patients were randomly assigned to one of four treatment groups with minimisation for tumour size, lymph node metastasis, and study site. Patients received UFT only (267 mg/m(2) per day), S-1 only (80 mg/m(2) per day) for 14 days, with a 7-day rest period or three courses of intermittent weekly paclitaxel (80 mg/m(2)) followed by either UFT, or S-1. Treatment lasted 48 weeks in monotherapy groups and 49 weeks in the sequential treatment groups. The primary endpoint was disease-free survival assessed by intention to treat. We assessed whether UFT was non-inferior to S-1 with a non-inferiority margin of 1·33. This trial was registered at UMIN Clinical Trials Registry, number C000000082.. We randomly assigned 1495 patients between Aug 3, 2004, and Sept 29, 2009. 374 patients were assigned to receive UFT alone, 374 to receive S-1 alone, 374 to received paclitaxel then UFT, and 373 to receive paclitaxel then S-1. We included 1433 patients in the primary analysis after at least 3 years of follow-up (359, 364, 355, and 355 in each group respectively). Protocol treatment was completed by 215 (60%) patients in the UFT group, 224 (62%) in the S-1 group, 242 (68%) in the paclitaxel then UFT group, and 250 (70%) in the paclitaxel then S-1 group. 3-year disease-free survival for monotherapy was 54·0% (95% CI 50·2-57·6) and that of sequential treatment was 57·2% (53·4-60·8; hazard ratio [HR] 0·92, 95% CI 0·80-1·07, p=0·273). 3-year disease-free survival for the UFT group was 53·0% (95% CI 49·2-56·6) and that of the S-1 group was 58·2% (54·4-61·8; HR 0·81, 95% CI 0·70-0·93, p=0·0048; pnon-inferiority=0·151). The most common grade 3-4 haematological adverse event was neutropenia (41 [11%] of 359 patients in the UFT group, 48 [13%] of 363 in the S-1 group, 46 [13%] of 355 in the paclitaxel then UFT group, and 83 [23%] of 356 in the paclitaxel then S-1 group). The most common grade 3-4 non-haematological adverse event was anorexia (21 [6%], 24 [7%], seven [2%], and 18 [5%], respectively).. Sequential treatment did not improve disease-free survival, and UFT was not non-inferior to S-1 (and S-1 was superior to UFT), therefore S-1 monotherapy should remain the standard treatment for locally advanced gastric cancer in Japan.. Epidemiological and Clinical Research Information Network.

Topics: Adenocarcinoma; Aged; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Disease-Free Survival; Drug Combinations; Female; Humans; Intention to Treat Analysis; Male; Middle Aged; Neoplasm Staging; Neutropenia; Oxonic Acid; Paclitaxel; Stomach Neoplasms; Survival Rate; Tegafur; Uracil

The treatment choice of advanced gastric carcinoma after failure from first-line therapy is quite limited. To evaluate the efficacy and toxicity of S-1 monotherapy in patients with advanced gastric cancer after failure of first line cisplatin and fluorouracil combination (CF). S-1 monotherapy as a second line treatment was given to the patients who had failed to CF combination in SC-101 study. The efficacy and toxicity of S-1 monotherapy were evaluated exploratory. The results indicated that forty-one patients received S-1 as a second line therapy after disease progression. The overall response rate and disease control rate were 14.6% and 41.5%, respectively. The median progression free survival (PFS) was 5.1 months (range: 2.9~6.2 month). The median overall survival time was 6.4 months. The survival rates at 6 month and 1 year were 56% and 7.3%, respectively. Grade 3/4 adverse events were uncommonly occurred, including anemia (2.4%), neutropenia (2.4%), thrombocytopenia (4.9%) and rash (2.4%). There were no unexpected or life-threatening toxicities. Only one patient experienced dose reduction due to grade 3 rash. In conclusion, S-1 monotherapy provided a mild response rate and overall survival, and a favorable toxicity profile in the second line setting after the first line failure to cisplatin and fluorouracil combination.

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Disease-Free Survival; Drug Combinations; Female; Fluorouracil; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Oxonic Acid; Salvage Therapy; Stomach Neoplasms; Tegafur

Second-line chemotherapy is now considered a standard therapy option in patients with advanced gastric cancer (AGC) who failed from first-line chemotherapy. Single agents, such as irinotecan, docetaxel or paclitaxel, provided an overall response rate of about 10 %. However, the efficacy was not satisfactory. The authors conducted a phase II study to investigate biweekly regimen of S-1 plus paclitaxel in Chinese AGC in second-line setting, with response rate as the primary end point.. Patients with AGC failed from first-line chemotherapy with fluoropyrimidine/platinum who had measurable lesions were enrolled. Paclitaxel was administered intravenously on day 1 at a dose of 120 mg/m(2), and oral S-1 was administered twice a day from days 1 to 7, followed by a 7-day drug-free interval.. A total of 30 patients with pretreated AGC were accrued. No complete responses were observed. Partial responses were documented in 10 (33.3 %) patients. Ten (33.3 %) patients had stable disease. The median progression-free survival was 3.6 months and the overall survival was 7.2 months. The main toxicity was bone marrow suppression. The most frequent grade 3/4 hematological toxicities were neutropenia and anemia, which were observed in 8 (26.7 %) and 6 (20 %) patients, respectively. The most common grade 3/4 non-hematological toxicity was neuropathy, which was reported in 4 (13.3 %) patients.. Biweekly S-1 plus paclitaxel showed promising activity with acceptable toxicities as second-line chemotherapy in pretreated patients with AGC. This regimen deserves further investigation in a phase III trial.

Topics: Administration, Oral; Adult; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Asian People; Disease-Free Survival; Drug Administration Schedule; Drug Combinations; Female; Fluorouracil; Humans; Injections, Intravenous; Male; Middle Aged; Neutropenia; Oxonic Acid; Paclitaxel; Platinum; Stomach Neoplasms; Tegafur; Treatment Outcome

The treatment choice of advanced gastric carcinoma after failure from first-line therapy is quite limited. To evaluate the efficacy and toxicity of S-1 monotherapy in patients with advanced gastric cancer after failure of first line cisplatin and fluorouracil combination (CF). S-1 monotherapy as a second line treatment was given to the patients who had failed to CF combination in SC-101 study. The efficacy and toxicity of S-1 monotherapy were evaluated exploratory. The results indicated that forty-one patients received S-1 as a second line therapy after disease progression. The overall response rate and disease control rate were 14.6% and 41.5%, respectively. The median progression free survival (PFS) was 5.1 months (ange: 2.9~6.2 month). The median overall survival time was 6.4 months. The survival rates at 6 month and 1 year were 56% and 7.3%, respectively. Grade 3/4 adverse events were uncommonly occurred, including anemia (2.4%), neutropenia (2.4%), thrombocytopenia (4.9%) and rash (2.4%). There were no unexpected or life-threatening toxicities. Only one patient experienced dose reduction due to grade 3 rash. In conclusion, S-1 monotherapy provided a mild response rate and overall survival, and a favorable toxicity profile in the second line setting after the first line failure to cisplatin and fluorouracil combination.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Agents; Cisplatin; Disease-Free Survival; Drug Combinations; Female; Fluorouracil; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Oxonic Acid; Salvage Therapy; Stomach Neoplasms; Tegafur

The present study evaluated the efficacy of lafutidine, a histamine H2 receptor antagonist, for reducing gastrointestinal toxicities during adjuvant chemotherapy using oral fluorouracil anticancer drugs for gastric cancer.. Patients with stage II (T1 cases excluded) or stage III gastric adenocarcinoma who underwent gastrectomy with D2 lymphadenectomy achieving R0 resection from 2011 to 2013 were prospectively enrolled in the study. Patients were randomly assigned to either S-1 treatment or S-1 plus lafutidine treatment. Quality of life and gastrointestinal toxicity were evaluated before chemotherapy and at 2, 4, and 6 weeks after the beginning of treatment.. The incidence of diarrhea during chemotherapy was significantly lower in the S-1 plus lafutidine group than in the group treated with S-1 alone (10% vs. 83%, respectively; p=0.002). The grades of diarrhea and nausea during chemotherapy were also significantly lower compared to those before chemotherapy in patients receiving S-1 plus lafutidine than in those administered S-1 alone. The rate of patients requiring a dose reduction or interruption of S-1 was significantly lower in the S-1 plus lafutidine group than in the group treated with S-1 alone (30% vs. 83%, respectively; p=0.027).. Lafutidine might be useful not only for preventing gastrointestinal toxicities during adjuvant chemotherapy for gastric cancer, but also for improving compliance with taking oral fluorouracil anticancer drugs. However, this indication needs to be confirmed in a larger, prospective, randomized, controlled trial.

Topics: Acetamides; Adenocarcinoma; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Diarrhea; Drug Combinations; Female; Fluorouracil; Gastrectomy; Gastrointestinal Tract; Histamine H2 Antagonists; Humans; Lymph Node Excision; Male; Middle Aged; Nausea; Oxonic Acid; Piperidines; Prospective Studies; Pyridines; Quality of Life; Stomach Neoplasms; Tegafur

We designed a phase I/II trial of intraperitoneal (IP) docetaxel plus S-1 to determine the maximum tolerated dose (MTD) and recommended dose (RD) and to evaluate its efficacy and safety in gastric cancer patients with peritoneal carcinomatosis (PC).. Patients with PC confirmed by laparoscopy or laparotomy received IP docetaxel on days 1 and 15 and S-1 (80 mg/m(2)) on days 1-14 every 4 weeks.. In the phase I part (n = 12), each cohort received escalating doses of docetaxel (35-50 mg/m(2)); the MTD was determined to be 50 mg/m(2) and the RD was determined to be 45 mg/m(2). Dose-limiting toxicities included grade 3 febrile neutropenia and grade 3 diarrhea. In the phase II part (n = 27), the median number of courses was 4 (range 2-11). The 1-year overall survival (OS) rate was 70 % (95 % confidence interval 53-87 %). The overall response rate was 22 % and peritoneal cytology turned negative in 18 of 22 (81 %) patients. The most frequent grade 3/4 toxicities included anorexia (19 %), neutropenia (7 %), and leukopenia (7 %).. IP docetaxel plus S-1 is active and safety in gastric cancer patients with PC.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Docetaxel; Dose-Response Relationship, Drug; Drug Combinations; Female; Humans; Male; Maximum Tolerated Dose; Middle Aged; Oxonic Acid; Peritoneal Neoplasms; Stomach Neoplasms; Survival Rate; Taxoids; Tegafur; Treatment Outcome

To report the results of a safety analysis from a phase II trial comparing administration of weekly paclitaxel plus S-1 (TS) versus paclitaxel plus 5-fluorouracil (5-FU)/calcium folinate (LV) (TLF) as first-line therapy for advanced gastric cancer.. Patients (n = 240) with previously untreated advanced gastric cancer were randomly assigned to receive either TS or TLF in a 28-day cycle for six cycles.. The clinical features of both sets of patients were similar, with the exception of the incidence of prior chemotherapy (P>0·05). Most treatment-related adverse events occurred at similar rates in both treatment arms. However, patients receiving TS experienced an increase in all-grade especially grade 3/4 neutropenia, with an incidence of 43·7% in the TS arm and 16·3% in the TLF arm, respectively (P<0·05). Other severe adverse events were infrequent and not significantly different between the groups.. The safety and tolerance of weekly paclitaxel plus S-1 or 5-FU/LV is well in untreated advanced gastric cancer patients.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Oxonic Acid; Paclitaxel; Stomach Neoplasms; Tegafur; Young Adult

The prognosis of patients with gastric cancer with peritoneal metastasis is extremely poor. This phase 2 study evaluated the benefits and tolerability of weekly intravenous and intraperitoneal paclitaxel (PTX) treatment combined with oral S-1 in patients with gastric cancer who had macroscopic peritoneal metastasis.. Patients with gastric cancer who had primary tumors with macroscopic peritoneal metastasis were enrolled. PTX was administered intravenously at 50 mg/m2 and intraperitoneally at 20 mg/m2 on days 1 and 8, respectively. S-1 was administered at 80 mg/m2 per day for 14 consecutive days, followed by 7 days of rest. The primary endpoint was the 1-year overall survival (OS) rate. The secondary endpoints were the response rate, efficacy against malignant ascites, and safety.. Thirty-five patients were enrolled. The median number of treatment courses was 11 (range, 2-35). The 1-year OS rate was 77.1% (95% confidence interval, 60.5-88.1). The overall response rate was 71% in 7 patients with target lesions. Malignant ascites disappeared or decreased in 15 of 22 (68%) patients. The frequent grade 3/4 toxic effects were neutropenia (34%), leukopenia (23%), and anemia (9%).. Combination chemotherapy consisting of intravenous and intraperitoneal PTX with S-1 is well-tolerated and effective in patients with gastric cancer who have macroscopic peritoneal metastasis.

Topics: Administration, Intravenous; Adult; Aged; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Female; Humans; Infusions, Parenteral; Male; Middle Aged; Oxonic Acid; Paclitaxel; Peritoneal Neoplasms; Prognosis; Stomach Neoplasms; Survival Rate; Tegafur

This study aimed to compare the efficacy and toxicity of weekly paclitaxel plus S-1 with weekly paclitaxel plus 5-fluorouracil in treating advanced gastric cancer as first line regimen. The primary end-point was disease control rate (DCR).. Patients with advanced or recurrent gastric cancer were randomly assigned to an experimental arm or a control arm. The experimental arm's dosage schedule was paclitaxel 60 mg/m2 (intravenous infusion) on days 1, 8 and 15 and S-1 80-120 mg/d (oral administration) on days 1-14. Control arm patients were given the same paclitaxel, combined with 5-fluorouracil 500 mg/m2 (continuous intravenous infusion) on days 1-5; and leucovorin 20 mg/m2 (intravenous infusion) on days 1-5. All schedules were repeated every 28 d.. A total of 240 patients were enrolled and equally randomised into two arms. The overall response rate and DCR of the experimental arm was non-inferior to that of the control arm both in the per-protocol set and the full analysis set. The secondary end-point median progression-free survival (PFS) of the experimental and control arms was 153 and 129 d, with the hazard ratio of 0.641 (95% CI: 0.473-0.868, P = 0.004). The hazard ratio of the time to treatment failure of the two arms was 1.449 (95% CI: 0.705-2.980, P = 0.229). The six-month PFS rates of both arms were similar (31.3% versus 31.8%, P = 0.94). Cox regression analysis indicated that only treatment regimen and age were independent predictive factors for PFS. The most common adverse events were haematological and gastrointestinal. The rates of grade 3-4 adverse events were not significantly different between the two study arms and were mostly lower than 5%.. Weekly paclitaxel combined with S-1 is an active and well-tolerated regimen, supporting the view that S-1 can be an alternative for infusional 5-fluorouracil for advanced gastric cancer.

Topics: Administration, Oral; Adolescent; Adult; Aged; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Drug Administration Schedule; Drug Combinations; Female; Fluorouracil; Humans; Infusions, Intravenous; Kaplan-Meier Estimate; Leucovorin; Leukopenia; Male; Middle Aged; Multivariate Analysis; Nausea; Oxonic Acid; Paclitaxel; Stomach Neoplasms; Tegafur; Treatment Outcome; Young Adult

In Japan, CPT-11 is often used to treat unresectable gastric cancer in the second-line setting. However, evidence regarding benefit of second-line chemotherapy remains sparse, especially after failing S-1.. A phase II study to evaluate the efficacy and safety of weekly administration of CPT-11 at a dose of 100 mg/m(2) after failing a S-1-containing first-line treatment was planned with response rate as a primary end point. UGT1A1*6, *27, and *28 genotyping were performed in all cases, and those found to have either homozygous for *28, homozygous for *6, heterozygous for both *6 and *28, and heterozygous for *27 were rendered ineligible for the phase II trial.. Two patients of homozygous for *28, two patients of homozygous for *6, and one patient of heterozygous for *27 were found among 39 recruited patients. The median number of courses delivered was 3 courses. The overall response rate was 15.4 % and disease control rate was 65.4 %. The median time to treatment failure was 87.5 days and median overall survival was 268 days. Twenty-two (73 %) of 30 valuable patients experienced protocol-specified skip of treatment and 8 (30 %) of patients could continue treatment with dose reduction. ≥G3 neutropenia was found in 30 % and ≥G3 anorexia and diarrhea were found in 23 and 17 %, respectively.. Weekly CPT-11 at 100 mg/m(2) showed moderate response among gastric cancer patients who were refractory to S-1, but the disease control rate seemed meaningful. Even after selection of patients by UGT1A1 polymorphism of *6, *27, and *28, severe toxic events could not be prevented completely.

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Antineoplastic Agents, Phytogenic; Camptothecin; Dose-Response Relationship, Drug; Drug Combinations; Female; Genotype; Glucuronosyltransferase; Humans; Irinotecan; Male; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Polymorphism, Genetic; Stomach Neoplasms; Survival Rate; Tegafur; Time Factors; Treatment Outcome

Since the best chemotherapy regimen for each patient with advanced gastric cancer is uncertain, we aimed to identify molecular prognostic or predictive biomarkers from biopsy specimens in JCOG9912, a randomized phase III trial for advanced gastric cancer.. Endoscopic biopsy specimens from primary lesions were collected in 445 of 704 randomized patients in JCOG9912. We measured the mRNA expression of excision repair cross-complementing group 1 (ERCC1), thymidylate synthase, dihydropyrimidine dehydrogenase, and five other genes, then, categorized them into low and high groups relative to the median, and examined whether gene expression was associated with efficacy end point.. Multivariate analyses showed that high ERCC1 expression [HR 1.37; 95% confidence interval (CI) 1.08-1.75; P = 0.010], performance status ≥ 1 (HR 1.45; 95% CI 1.13-1.86; P = 0.004), and number of metastatic sites ≥ 2 (HR 1.66; 95% CI 1.28-1.86; P < 0.001) were associated with a poor prognosis, and recurrent disease (versus unresectable; HR 0.75; 95% CI 0.56-1.00; P = 0.049) was associated with a favorable prognosis. None of these molecular factors were a predictive marker for choosing irinotecan plus cisplatin or 5-fluorouracil rather than S-1.. These correlative analyses suggest that ERCC1 is an independent prognostic factor for overall survival in the first-line treatment of gastric cancer.. C000000062, www.umin.ac.jp.

Topics: Antimetabolites, Antineoplastic; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Camptothecin; Cisplatin; Dihydrouracil Dehydrogenase (NADP); DNA-Binding Proteins; Drug Combinations; Endonucleases; Female; Fluorouracil; Gene Expression; Humans; Irinotecan; Male; Oxonic Acid; Prognosis; RNA, Messenger; Stomach Neoplasms; Survival; Tegafur; Thymidylate Synthase; Vascular Endothelial Growth Factor A

The aim of developing oral fluorouracil (5-FU) is to provide a more convenient administration route with similar efficacy and the best achievable tolerance. S-1, a novel oral fluoropyrimidine, was specifically designed to overcome the limitations of intravenous fluoropyrimidine therapies.. A multicentre, randomised phase 3 trial was undertaken to compare S-1/cisplatin (CS) with infusional 5-FU/cisplatin (CF) in 1053 patients with untreated, advanced gastric/gastroesophageal adenocarcinoma. This report discusses a post-hoc noninferiority overall survival (OS) and safety analyses.. Results (1029 treated; CS = 521/CF = 508) revealed OS in CS (8.6 months) was statistically noninferior to CF (7.9 months) [hazard ratio (HR) = 0.92 (two-sided 95% confidence interval (CI), 0.80-1.05)] for any margin equal to or greater than 1.05. Statistically significant safety advantages for the CS arm were observed [G3/4 neutropenia (CS, 18.6%; CF, 40.0%), febrile neutropenia (CS, 1.7%; CF, 6.9%), G3/4 stomatitis (CS, 1.3%; CF, 13.6%), diarrhoea (all grades: CS, 29.2%; CF, 38.4%) and renal adverse events (all grades: CS, 18.8%; CF, 33.5%)]. Hand-foot syndrome, infrequently reported, was mainly grade 1/2 in both arms. Treatment-related deaths were significantly lower in the CS arm than the CF arm (2.5% and 4.9%, respectively; P<0.047).. CS is noninferior to CF with a better safety profile and provides a new treatment option for patients with advanced gastric carcinoma.

Topics: Adenocarcinoma; Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Disease Progression; Drug Combinations; Esophageal Neoplasms; Female; Fluorouracil; Humans; Male; Middle Aged; Neoadjuvant Therapy; Oxonic Acid; Stomach Neoplasms; Tegafur; Young Adult

Adjuvant chemotherapy trial of TS-1 for gastric cancer study demonstrated that postoperative S-1 chemotherapy for 1 year improved overall survival of locally advanced gastric cancer (LAGC) patients. The goals of this study were to evaluate the feasibility and efficacy of neoadjuvant docetaxel, oxaliplatin, and S-1 (DOS) chemotherapy followed by surgery and adjuvant S-1 chemotherapy.. In this single-center, open-label, phase II study, patients with potentially resectable adenocarcinoma of the stomach or gastroesophageal junction were eligible. For neoadjuvant chemotherapy, docetaxel 50 mg/m(2) on day (D) 1, oxaliplatin 100 mg/m(2) on D1, and S-1 40 mg/m(2) bid orally on D1-14 were administrated every 3 weeks for three cycles. After DOS chemotherapy, gastrectomy was performed, and then, adjuvant S-1 40 mg/m(2) bid was given on D1-28 every 6 weeks for 1 year. The primary endpoints were the proportion of patients who did not experience grade 3 or 4 toxicities (except grade 3 neutropenia) and R0 resection rates.. A total of 41 patients were enrolled. All patients completed three planned cycles of neoadjuvant chemotherapy without disease progression. Eighteen patients (43.9 %) did not experience any grade 3-4 toxicity (except grade 3 neutropenia) during the neoadjuvant chemotherapy. All patients underwent surgery, and R0 resection was achieved in 40 patients (97.6 %).. Neoadjuvant DOS chemotherapy could be performed safely with a high R0 resection rate in LAGC patients. A phase III trial is currently underway.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Disease Progression; Docetaxel; Drug Combinations; Esophageal Neoplasms; Esophagogastric Junction; Female; Humans; Male; Middle Aged; Neoadjuvant Therapy; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Stomach Neoplasms; Taxoids; Tegafur; Treatment Outcome

We conducted a phase I study of S-1 combined with irinotecan and oxaliplatin (TIROX) to determine the maximum-tolerated dose (MTD) and recommended dose (RD) and to assess its safety, pharmacokinetics, pharmacogenetics, and preliminary efficacy in patients with metastatic colorectal cancer (MCRC) or metastatic gastric cancer (MGC).. Patients received escalating doses of S-1 (30-40 mg/m² b.i.d.) orally on days 1-14, an escalating dose of intravenous irinotecan (120-150 mg/m²) on day 1, and a fixed dose of intravenous oxaliplatin (85 mg/m²) on day 1 every 3 weeks.. Twenty-three patients (10 MCRC, 13 MGC; 13 chemonaive, 10 previously treated for metastatic disease) were treated across six dose levels. Because only one patient experienced a dose-limiting toxicity of grade 3 anorexia at the highest dose level (S-1 40 mg/m² b.i.d., irinotecan 150 mg/m², and oxaliplatin 85 mg/m²) (n = 8), the MTD was not obtained, and this level was established as the RD. With a median of 10 cycles per patient, the most common grade 3 or 4 adverse events included neutropenia (43 %), diarrhea (13 %), and nausea (13 %). In 22 efficacy-evaluable patients, the objective tumor response rate was 59.1 % (75 % for both MCRC and MGC in the first-line setting) and the disease control rate was 100 %. The exploratory pharmacokinetic/pharmacogenetic study showed that CYP2A6 variants (*4, *7, *9) are associated with a lower metabolic ratio of S-1 (exposure ratio of 5-fluorouracil to tegafur).. The new triplet TIROX regimen has shown promising antitumor activity and a favorable toxicity profile in patients with MCRC and MGC.

Topics: Adult; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Aryl Hydrocarbon Hydroxylases; Camptothecin; Cohort Studies; Colorectal Neoplasms; Cytochrome P-450 CYP2A6; Dose-Response Relationship, Drug; Drug Combinations; Female; Follow-Up Studies; Half-Life; Humans; Irinotecan; Male; Middle Aged; Neoplasm Metastasis; Neutropenia; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Polymorphism, Genetic; Stomach Neoplasms; Survival Analysis; Tegafur

This study aimed to determine whether combination S-1 plus cisplatin (CDDP) therapy, the most widely used therapy for Japanese patients with advanced gastric cancer, and the novel oral antiangiogenic agent TSU-68 could contribute to gastric cancer treatment.. Ninety-three patients with chemotherapy-naïve unresectable or recurrent advanced gastric cancers were randomised into two groups: TSU-68 plus S-1/CDDP (group A) and S-1/CDDP (group B) groups. Both patient groups received identical S-1 and CDDP dosages. TSU-68 was orally administered for 35 consecutive days. Group B patients received S-1 orally twice daily for three consecutive weeks, followed by intravenous CDDP on day 8. The primary endpoint was progression-free survival (PFS).. Median PFS periods were 208 and 213 days in groups A and B, respectively (P=0.427). Median survival periods for groups A and B were 497.0 and 463.5 days, respectively (P=0.219). No statistically significant differences were noted for PFS, survival or the adverse event (AE) incidence rate. All AEs were expected according to previous reports for TSU-68, TS-1, and CDDP.. Combination therapy involving TSU-68, S-1, and CDDP was safe and well tolerated in patients with chemotherapy-naïve unresectable or recurrent advanced gastric cancers. However, factors related to therapeutic efficacy should be investigated further.

Topics: Aged; Angiogenesis Inhibitors; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Disease-Free Survival; Drug Combinations; Female; Humans; Indoles; Male; Middle Aged; Oxindoles; Oxonic Acid; Propionates; Pyrroles; Stomach Neoplasms; Survival Rate; Tegafur

The effectiveness of specific regimens of adjuvant therapy for gastric cancer has not been verified by large clinical trials. Recently, several large trials attempted to verify the effectiveness of adjuvant therapy. The Adjuvant Chemotherapy Trial of TS-1 for Gastric Cancer in Japan, a randomized controlled trial of adjuvant S-1 therapy for resected gastric cancer, demonstrated significant improvement in overall and relapse-free survival, compared to surgery alone. To evaluate value for money of S-1 therapy, cost-effective analysis was carried out.. The analysis was carried out from a payer's perspective. As an economic measure, cost per quality-adjusted life-year (QALY) gained was estimated. Overall survival was estimated by the Kaplan-Meier method, up to 5-year observation. Beyond this period, it was simulated by the modified Boag model. Utility score is derived from interviews with sampled patients using a time trade-off method. Costs were estimated from trial data during observation, while in the period beyond observation they were estimated using simulation results. To explore uncertainty of the results, qualitative and stochastic sensitivity analyses were done.. Adjuvant S-1 therapy gained 1.24 QALYs per patient and increased costs by $3,722 per patient for over lifetime (3% discount rate for both effect and costs). The incremental cost-effectiveness ratio (95% confidence intervals) for over lifetime was estimated to be $3,016 ($1,441, $8,840) per QALY. The sensitivity analyses showed the robustness of these results.. Adjuvant S-1 therapy for curatively resected gastric cancer is likely cost-effective. This therapy can be accepted for wide use in Japan.

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Combined Modality Therapy; Cost-Benefit Analysis; Drug Combinations; Female; Humans; Japan; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Quality-Adjusted Life Years; Stomach Neoplasms; Tegafur; Treatment Outcome

Regimens of standard-dose cisplatin have usually been administered as inpatient chemotherapy in Japan. This prospective study evaluated the feasibility of outpatient chemotherapy with standard-dose cisplatin in Japanese patients with advanced gastric cancer.. Advanced gastric cancer patients received an S-1 + cisplatin regimen (S-1: 80-120 mg days 1-21; cisplatin: 60 mg/m(2) day 8, every 4-5 weeks), either as outpatient chemotherapy with oral hydration on days 9-10, or as inpatient chemotherapy with intravenous hydration on days 9-10, based on the results of an oral hydration test during days 1-7 of the first cycle. The primary endpoint was the completion rate of two cycles in the outpatient group.. A total of 36 patients were enrolled: 32 were allocated to the outpatient group and 4 to the inpatient group. The completion rate of two cycles in the outpatient group was 78% [90% confidence interval (CI): 63-89]. The median of the total number of treatment cycles of S-1 + cisplatin and the median progression-free survival in the outpatient group were 5 (range 1-11) and 10.6 months (95% CI 4.2-16.9), respectively. Although seven patients in the outpatient group discontinued treatment, mainly owing to gastrointestinal toxicity, most of them could continue S-1 + cisplatin by switching to inpatient chemotherapy from the next cycle.. Outpatient chemotherapy with S-1 + cisplatin in advanced gastric cancer patients can be safely and effectively administered in Japan with appropriate patient selection and supportive treatment.

Topics: Adult; Aged; Ambulatory Care; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Disease-Free Survival; Drug Combinations; Feasibility Studies; Female; Humans; Japan; Male; Middle Aged; Oxonic Acid; Patient Selection; Prospective Studies; Stomach Neoplasms; Tegafur; Treatment Outcome

The factors that affect the 6-month continuation of adjuvant chemotherapy with S-1 have not been fully evaluated. The objective of this retrospective study was to clarify the risk factors for 6-month continuation of S-1 adjuvant chemotherapy.. The study selected patients who underwent curative D2 surgery for gastric cancer, were diagnosed with stage 2 or 3 disease, had a serum creatinine level of ≤ 1.2 mg/dl, and received adjuvant S-1 between June 2002 and March 2011.. One hundred of these patients were eligible for the present study. A comparison of 6-month continuation of S-1 stratified by various clinical factors, using the log-rank test, revealed a marginally significant difference in creatinine clearance (CCr) between those patients who continued for 6 months and those who did not. A CCr of 60 ml/min was regarded as the critical point. Uni- and multivariate Cox's proportional hazard analyses demonstrated that CCr was the only significant independent factor for the prediction of 6-month continuation. The 6-month continuation rate was 72.9 % in the patients with CCr ≥ 60 ml/min, and 40.0 % in patients with CCr <60 ml/min (P = 0.015). Adverse events occurred more frequently and earlier in the patients with CCr <60 ml/min than in those with CCr ≥ 60 ml/min.. CCr <60 ml/min was a significant risk factor for 6-month continuation of S-1 adjuvant chemotherapy, even though the renal function was judged as normal by the serum creatinine level. Careful attention is therefore required for S-1 continuation in patients with CCr <60 ml/min.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Creatinine; Drug Combinations; Female; Humans; Male; Middle Aged; Oxonic Acid; Patient Compliance; Predictive Value of Tests; Proportional Hazards Models; Retrospective Studies; Risk Factors; Stomach Neoplasms; Survival Rate; Tegafur

The aim of this study was to evaluate the efficacy and toxicity of low dose of docetaxel in combination with standard dose of S-1 for patients with advanced or recurrent gastric cancer and to investigate whether the protein expression level of dihydropyrimidine dehydrogenase is a predictive factor of toxicities or responses.. Between March 2010 and December 2011, 61 patients from the Department of Medical Oncology of Shanghai Zhong Shan Hospital, Fudan University, were enrolled in the study. Patients with advanced or recurrent gastric adenocarcinoma were treated with docetaxel of 40 mg/m(2) intravenously on day 1 and S-1 of 80 mg/m(2) orally on days 1-14 every 3 weeks as first-line chemotherapy. The chemotherapeutic effects were evaluated following every 3 cycles of chemotherapy using the Response Evaluation Criteria In Solid Tumors (RECIST). The serum of peripheral blood was obtained at the start of the study and at each evaluation point to analyze the protein expression level of DPD, which was estimated using an enzyme-linked immunosorbent assay. All the patients were followed-up until the time of progression, death, or the censor time, to calculate progression-free survival and overall survival (OS) time.. In total, 61 patients [median age 60 years (range 28-76 years)] received a total of 318 treatment cycles [median 5 (range 2-9)], and 94 cycles of single S-1 maintenance treatment. One complete response (CR) and 25 partial responses (PR) were observed, with an overall response rate of 42.6%. A total of 29 patients (47.5%) had stable disease (SD) and 6 patients (9.8%) had progressive disease (PD). The disease control rate (DCR, CR + PR + SD) was 90.2%. Median overall survival was 13.0 months [95% confidence interval (CI) 10.76-15.24 months], and median PFS was 6.0 months (95% CI 4.61-7.39 months). Progression-free survival was far longer in peritoneal metastatic patients than that in patients with other metastases (7.3 ± 2. 6 vs. 5.4 ± 2.8 months; P < 0.05); however, this was not the case for OS. Grade 3-4 neutropenia was well controlled and grade 4 non-hematologic toxicities did not occur. Baseline expression level of DPD was not associated with efficacy. Lower expression level of DPD was correlated with high grade of toxicities (P < 0.05).. This combination of standard dose of S-1 and low dose of docetaxel is effective and well tolerated in patients with advanced or recurrent gastric cancer. Peritoneal metastasis is treated more effectively by this regimen than other forms of metastases. Baseline DPD expression level in the serum is associated with toxicity, but not tumor response.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Dihydrouracil Dehydrogenase (NADP); Docetaxel; Dose-Response Relationship, Drug; Drug Combinations; Enzyme-Linked Immunosorbent Assay; Female; Gene Expression Regulation, Neoplastic; Humans; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Oxonic Acid; Peritoneal Neoplasms; Stomach Neoplasms; Survival Rate; Taxoids; Tegafur; Treatment Outcome

S-1 and cisplatin combination therapy is a standard regimen for patients with advanced gastric cancer in Japan. The primary objective of this study was to determine the maximum tolerated dose and dose-limiting toxicities of a triplet regimen adding paclitaxel to S-1 and cisplatin combination therapy.. Patients with previously untreated metastatic or recurrent gastric cancer were enrolled. Patients received S-1 (40 mg/m(2) p.o., twice daily, on days 1-21 every 35 days), cisplatin (30 mg/m(2) divided, on days 1 and 15) and paclitaxel (divided on days 1 and 15). The starting dose of paclitaxel was 50 mg/m(2) (level 1); the dose was escalated to 60 (level 2), 70 (level 3) and 80 mg/m(2) (level 4) in a stepwise fashion. Dose-limiting toxicity was determined during the first treatment cycle.. Eighteen patients enrolled. During the first cycle, no dose-limiting toxicity was observed at dose levels 1 and 2. At dose level 3, one of the six patients had dose-limiting toxicity (one patient had grade 4 neutropenia) and at dose level 4, one of the six patients had dose-limiting toxicity (one patient had febrile neutropenia, hypoalbuminemia and fatigue of grade 3). The maximum tolerated dose was not reached at level 4; however, grade 3 hyponatremia and hypokalemia in two of the six patients occurred during the second treatment course at level 4. From the point of view of safety in the outpatient setting, the recommended dose of paclitaxel was determined at 70 mg/m(2). The overall response rate was 50%.. The recommended dose of paclitaxel added to S-1 (80 mg/m(2) days 1-21) plus cisplatin (30 mg/m(2) days 1 and 15) was 70 mg/m(2) on days 1 and 15 of a 5-week cycle.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Administration Schedule; Drug Combinations; Fatigue; Female; Humans; Hypoalbuminemia; Hypokalemia; Hyponatremia; Male; Middle Aged; Neoplasm Staging; Neutropenia; Oxonic Acid; Paclitaxel; Stomach Neoplasms; Tegafur; Treatment Outcome

The combination of docetaxel, cisplatin, and S-1 (DCS) chemotherapy is expected to be a promising regimen for advanced gastric cancer. This study was performed to evaluate the efficacy and safety of neoadjuvant DCS chemotherapy for locally advanced resectable gastric cancer.. Patients with locally advanced gastric cancer received 2 courses of preoperative chemotherapy with S-1 (40 mg/m(2) b.i.d.) on days 1-14 and docetaxel (60 mg/m(2)) plus cisplatin (60 mg/m(2)) on day 8 every 3 weeks, followed by standard curative surgery within 4-8 weeks. The primary endpoint was R0 resectability. Expression of damage DNA binding protein complex subunit 2 (DDB2)/excision repair cross-complementing 1 (ERCC1) in the pretreated tumor tissues was examined by immunohistochemistry.. A total of 43 patients received neoadjuvant chemotherapy. The response rate was 74.4%, and disease control ratio was 100%. Grade 4 neutropenia developed in 53.5% of patients and febrile neutropenia in 16.3%. Non-hematological grade 3/4 adverse events were anorexia (23.3%), nausea (14.0%), and diarrhea (23.3%), but these were generally transient and manageable. The proportion of R0 resections in the 43 eligible patients was 90.7%, and a pathological response was found in 65.9% of patients. There were no treatment-related deaths and no major surgical complications. The accuracy of the combination of DDB2 and ERCC1 expression for predicting chemoresistance was 82.5%.. Preoperative treatment with DCS combination for locally advanced gastric cancer demonstrated a sufficient R0 resection rate and a good pathological response with manageable toxicities. The DDB2/ERCC1-high phenotype, as determined by immunohistochemistry, may be useful predictor of resistance to DCS chemotherapy.

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Biomarkers; Cisplatin; Combined Modality Therapy; DNA Repair; DNA-Binding Proteins; Docetaxel; Drug Administration Schedule; Drug Combinations; Drug Resistance, Neoplasm; Endonucleases; Endosonography; Female; Follow-Up Studies; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Neoadjuvant Therapy; Oxonic Acid; Stomach Neoplasms; Survival Analysis; Taxoids; Tegafur; Tomography, X-Ray Computed; Treatment Outcome

Peritoneal dissemination is the most frequent and life-threatening mode of metastasis and recurrence in patients with gastric cancer. A multicenter phase II study was designed to evaluate the efficacy and tolerability of S-1 and docetaxel combination chemotherapy regimen for the treatment of advanced or recurrent gastric cancer patients with peritoneal dissemination.. Nineteen patients with histologically confirmed unresectable or recurrent gastric cancer with peritoneal dissemination were enrolled. Oral S-1 at 80 mg/m(2)/day was administered twice daily for 2 weeks, followed by 1 drug-free week. Docetaxel infusion at 40 mg/m(2) was performed on day 1, simultaneous with S-1 administration. The primary endpoints were overall survival (OS) and time to progression (TTP). The secondary endpoints were the response rates and safety status.. Patients received a median of 4 cycles of the S-1 and docetaxel regimen (range 1-43). The disease control rate was 73.7 % (14/19). Median overall survival was 459 days (15.3 months), while median time to progression was 212 days (7.1 months). Neutropenia was the most common type of toxicity (n = 7, 36.8 %).. Combination chemotherapy with S-1 and docetaxel is a tolerable and effective treatment for advanced or recurrent gastric cancer patients with peritoneal dissemination.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Docetaxel; Drug Combinations; Female; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Oxonic Acid; Peritoneum; Stomach Neoplasms; Taxoids; Tegafur

This randomized phase II study was conducted to compare the efficacy and safety of paclitaxel with S-1 (PS) vs. S-1 in patients with advanced gastric cancer (AGC).. Eighty-two (82) patients were 1:1 randomly assigned to oral S-1 (daily for 2 weeks, every 4 weeks' cycle) or S-1 (daily for 2 weeks, every 4 weeks' cycle) plus paclitaxel (on day 1, 8 and 15 of a 4 weeks' cycle). S-1 was orally administered with a fixed quantity according to body surface area (BSA), while paclitaxel was given 60 mg/m(2) i.v. daily through an implanted catheter. The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), overall responsible rates and safety.. The median OS with PS versus S-1 monotherapy was 14.0 versus 11.0 months (P = 0.02), survival at 12 months was 61.0 % in the PS group and 46.3 % in the S-1 group. Median PFS was also significantly longer in the PS group (6.0 months) than in the S-1 group (4.0 months). The overall response rate was determined in 82 evaluable patients, and was significantly higher (P = 0.04) with PS (19 patients, 46.3 %) than with S-1 monotherapy (10 patients, 24.4 %). PS was well tolerated with no treatment-related deaths, all were grade 3-4 gastrointestinal toxicities, including anorexia, nausea, and diarrhea developed in less than 10 % of the patients.. Combination chemotherapy of paclitaxel with S-1 is well tolerated and active in AGC patients. Further investigation with comparative trials is needed for confirmation.

Topics: Adenocarcinoma; Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Feasibility Studies; Female; Follow-Up Studies; Humans; Liver Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Paclitaxel; Peritoneal Neoplasms; Prognosis; Stomach Neoplasms; Survival Rate; Tegafur; Young Adult

This study assessed the toxicity and activity of biweekly docetaxel and S-1 combination therapy in elderly patients with advanced gastric cancer.. One-hundred and thirteen patients were enrolled: 35 were 75 years old or more. The objective response rate, toxicity, progression-free survival (PFS), and overall survival (OS) were compared.. Dose reduction was significantly frequent in the elderly group (24/35 versus 25/78, p<0.001). The overall response rate was 54.9%. Out of these, 18 (15.9%) underwent gastrectomy (13 R0 gastrectomy). The median OS was 17.3 months and the median PFS was 8.0 months. Neutropenia was the most frequently observed hematological toxicity at grade 3 and 4 (34.5%), followed by leukopenia (24.8%). Most non-hematological toxicities were of grade 1 or 2. There were no significant differences in overall response rate, median OS, median PFS, or toxicities between the two groups.. This combination offers favourable survival benefits with controllable tolerance for therapy of AGC in the elderly.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Disease-Free Survival; Docetaxel; Drug Combinations; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Oxonic Acid; Proportional Hazards Models; Stomach Neoplasms; Taxoids; Tegafur

We conducted a phase II study to evaluate the safety and efficacy of preoperative chemotherapy with S-1 + cisplatin followed by gastrectomy in patients with linitis plastica (type 4) or large ulcero-invasive-type (type 3) gastric cancer.. Eligibility criteria included histologically proven adenocarcinoma of the stomach; clinically resectable gastric cancer of type 4 or type 3. Patients received two 28-day courses of preoperative chemotherapy of S-1 (80-120 mg/body, p.o., days 1-21) and cisplatin (CDDP; 60 mg/m(2), i.v., day 8). Primary endpoints were completion of protocol treatment and incidence of treatment-related death (TRD).. Among the 49 eligible patients with the median age of 61 years, 36 completed the protocol treatment comprising two courses of preoperative chemotherapy and R0/1 resection (73.5% completion, 80% CI, 63.7-81.7%). One TRD was observed during the first course of chemotherapy. Median survival and 3-year overall survival were 17.3 months and 24.5%, respectively.. Preoperative chemotherapy with S-1 + CDDP followed by gastrectomy is a safe and promising treatment for type 4 and large type 3 gastric cancers. Based on the results of this study, we are now conducting a phase III study (JCOG0501) to confirm the superiority of this treatment.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Administration Schedule; Drug Combinations; Female; Gastrectomy; Humans; Kaplan-Meier Estimate; Linitis Plastica; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Invasiveness; Neoplasm Staging; Oxonic Acid; Stomach Neoplasms; Stomach Ulcer; Tegafur; Treatment Outcome

Palliative chemotherapy has been shown to have a survival benefit for patients with recurrent or metastatic gastric cancer. 5-fluorouracil (5-FU) and cisplatin have been widely used in a variety of combinations. We conducted a phase II study of combination chemotherapy with new agents, S-1 and oxaliplatin (SOx), in advanced gastric cancer patients in an effort to evaluate the efficacy and toxicity of this regimen.. Histologically confirmed recurrent or metastatic gastric cancer were treated by the oral administration of S-1 80 mg/m(2)/day on days 1-28, and oxaliplatin 85 mg/m(2) administered as a 90-min intravenous infusion on days 1, 15, and 29. Treatment courses were repeated every 6 weeks. Patients received a maximum of four cycles.. From Feb 2006 to May 2008, 41 patients were enrolled in this study. The ratio of males to females was 28 to 13. The median patient age was 61 years (range, 36-74 years), and 85.4% (35/41) of the patients had a performance status (ECOG) of 1. The median number of chemotherapy cycles administered was 3 (range, 1-4). According to the results of our Intent-to-Treat analysis, 22 patients (53.7%) achieved a partial response (95% CI, 38-70%). 15 patients (36.6%) evidenced a stable disease, and 1 patient (2.4%) progressed during the course of the treatment. 3 patients were lost to follow-up prior to evaluation. The median time to progression and overall survival time were 4.6 months (95% CI, 3.4-5.8 months) and 7.8 months (95% CI, 6.9-8.7 months) from the start of the chemotherapy, respectively. A total of 114 cycles were assessed for toxicity. The major hematologic toxicities included grade 2 anemia (41.2%), grade 1-2 neutropenia (28.1%), and grade 1 thrombocytopenia (23.7%). Only 1 cycle of neutropenic fever occurred. The non-hematological toxicities observed were grade 3 vomiting (12.2%) and grade 3 diarrhea (4.9%). No treatment-related deaths occurred in our patient population during the study period.. The SOx regimen evidenced a relatively high response rate and was well tolerated as a first-line therapy for advanced gastric cancer.

Topics: Adenocarcinoma; Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chi-Square Distribution; Drug Administration Schedule; Drug Combinations; Female; Humans; Infusions, Intravenous; Kaplan-Meier Estimate; Male; Middle Aged; Neoplasm Recurrence, Local; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Prospective Studies; Republic of Korea; Stomach Neoplasms; Tegafur; Time Factors; Treatment Outcome

Although its efficacy is unproven, 5-fluorouracil plus cisplatin (FP) is used to prevent postoperative relapse in gastric cancer. We investigated the safety and feasibility of S-1 plus cisplatin (SP) vs. FP for stage IIIB-IV (M0) gastric cancer.. Following curative resection, 41 stage IIIB-IV (M0) gastric cancer patients were assigned to SP (eight 14-day cycles of S-1 [40 mg/m(2) twice daily] plus cisplatin [60 mg/m(2) day 1] administered every 3 weeks) or FP (six 3-day cycles of FU [1 g/m(2) per day] plus cisplatin [80 mg/m(2) day 1] every 4 weeks). Doses were reduced based on predefined criteria.. Patient characteristics were balanced between the two arms. In total, 124 cycles of SP (N = 20, median = 7, range 1-8) and 113 cycles of FP (N = 21, median 6, range 1-6) were administered. The median relative dose intensity per patient was 75% (49.99-100%) for S-1, 100% (75-100%) for cisplatin in SP, and 100% (64-100%) for 5-FU, 100% (60-100%) for cisplatin in FP. The relative dose intensity of FP was stable, while that of SP decreased during treatment. After median follow-up of 7.9 months (3.8-14.55), the median RFS was not reached. Relapse occurred in two (10%) patients on SP and five (23.8%) in the FP arm (P = 0.24). The incidence of grade 3-4 granulocytopenia was 36.8% with SP and 14.3% with FP. Grade 3-4 non-hematologic toxicities included fatigue (5.2% with SP vs. 4.8% with FP), vomiting (10.5% with SP vs. 0% with FP), and infection (5.2% with SP vs. 0% FP).. S-1 plus cisplatin was feasible and tolerable as adjuvant treatment for stage IIIB-IV (M0) gastric cancer. However, because of decreased relative dose intensity during treatment, further study is warranted to determine optimal dosage and combination.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Chi-Square Distribution; Cisplatin; Disease-Free Survival; Drug Combinations; Feasibility Studies; Female; Fluorouracil; Gastrectomy; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Pilot Projects; Republic of Korea; Stomach Neoplasms; Tegafur; Time Factors; Treatment Outcome

To improve the poor prognosis in patients with stage IV (StIV) gastric cancer (GC), we conducted a multicenter phase II study of preoperative S-1 plus cisplatin followed by gastrectomy and postoperative S-1 for StIV GC (the protocol is registered at the clinical trial site of the National Cancer Institute; KYUH-UHA-GC03-01, NCT00088816).. Eligibility criteria included histologically proven StIVGC. Patients received S-1 (80 mg/m(2)/day, days 1-21) plus cisplatin (60 mg/m(2) on day 8) for 2 courses. After preoperative chemotherapy (CTx), radical gastrectomy was performed. Postoperative S-1 (80 mg/m(2)/day, days 1-14) was administered every 3 weeks for 1 year.. Fifty-one patients were enrolled and all patients were followed for more than 2 years. The 2-year overall survival and progression-free survival rates were 43.1% (95% confidence interval [CI] 29.4-56.1%) and 33.3% (95% CI 20.9-46.2%), respectively. Preoperative chemotherapy was accomplished in 44 patients (86.3%). These 44 patients underwent surgery and R0 resection was achieved in 26. The rate of R0 resection for GC with a single StIV factor (n = 24) was 79.2% and that for GC with multiple StIV factors (n = 27) was 25.9%. All patients with cancer cells in peritoneal washings (cytology [Cy] 1) alone (n = 12) became Cy0 after preoperative chemotherapy. Postoperative chemotherapy was completed in 11 patients, including 8 with Cy1 alone. No treatment-related death was recorded. Recurrences were observed in 14 patients after R0 resection. The most frequent recurrence site was the peritoneum. Patients who underwent R0 resection and those with Cy1 alone had a better survival.. This perioperative treatment was safe and feasible for StIVGC but failed to show a survival benefit. In patients with StIVGC with Cy1 alone this treatment resulted in a better prognosis.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Disease-Free Survival; Drug Combinations; Feasibility Studies; Female; Gastrectomy; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Oxonic Acid; Prognosis; Prospective Studies; Stomach Neoplasms; Survival Rate; Tegafur; Treatment Outcome

The feasibility of a 3-week combination of S-1 and cisplatin as an adjuvant chemotherapy for patients with curatively resected gastric cancer was investigated.. Korean patients with stage II-IV (M0) gastric adenocarcinoma who underwent a gastrectomy with D2 lymph node resection were enrolled. The S-1 was administered orally at 80 mg/m(2) divided into two daily doses for 14 days, while the cisplatin was administered at 60 mg/m(2) intravenously over 2 h every 21 days. The patients received a maximum of six cycles.. From January 2006 to July 2010, 74 patients were included in this study. The median patient age was 56 years (range, 22-71), and 51.4% (38/74) of the patients had a performance status of 0. The median number of chemotherapy cycles administered was 6 (range, 1-6). The median relative dose intensity was 86.4% for S-1 and 80.0% for cisplatin. With a median follow-up duration of 13.9 months, the median relapse-free survival (RFS) and overall survival (OS) have not yet been reached. Fifteen relapses (20.3%) were documented. Plus, the estimated RFS rate was 60.5% at 3 years. The treatments were generally well tolerated. The most frequently observed grade 3-4 hematological toxicity was neutropenia (35.1%), and only 1 cycle of neutropenic fever occurred. The most frequently observed grade 3-4 non-hematological toxicities were nausea (4.1%) and asthenia (4.1%), and all the other grade 3-4 non-hematological toxicities were observed in less than 3% of the patients.. Postoperative adjuvant S-1 plus cisplatin for 18 weeks was found to be feasible for patients with stage II-IV (M0) gastric adenocarcinoma following complete surgical resection.

Topics: Adult; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cisplatin; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Female; Humans; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Pilot Projects; Stomach Neoplasms; Survival Analysis; Tegafur; Young Adult

It is unclear whether S-1 plus cisplatin is effective for patients with recurrent gastric cancer after adjuvant S-1 chemotherapy.. We retrospectively evaluated the efficacy of S-1 plus cisplatin in patients whose gastric cancer recurred after adjuvant S-1 chemotherapy.. In the 52 patients evaluated, the median duration of adjuvant S-1 chemotherapy was 8.1 months, and the median recurrence-free interval (RFI) since the last administration of adjuvant S-1 was 6.4 months. Among the 36 patients with measurable lesions, 7 achieved a complete or partial response, and 13 were evaluated as having stable disease, for an overall response rate of 19.4% and a disease control rate of 55.6%. For all patients, the median progression-free survival (PFS) was 4.8 months, and the median overall survival (OS) was 12.2 months. Compared with patients with an RFI of <6 months (n = 25), patients with an RFI of ≥6 months (n = 27) had a significantly higher response rate (5.0 vs. 37.5%, respectively), longer PFS (2.3 vs. 6.2 months, respectively), and longer overall survival (7.3 vs. 16.6 months, respectively). According to a multivariate Cox model including performance status (PS) and reason for discontinuation of adjuvant S-1, an RFI of 6 months was still significantly associated with PFS and OS.. S-1 plus cisplatin is effective for patients with gastric cancer that recurs after adjuvant S-1 chemotherapy, especially for those with an RFI of ≥6 months.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cisplatin; Disease-Free Survival; Drug Combinations; Female; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Oxonic Acid; Proportional Hazards Models; Retrospective Studies; Stomach Neoplasms; Tegafur; Treatment Outcome

Current advances in chemotherapy provide opportunities for stage IV gastric cancer patients with distant metastasis to undergo potentially curable resection. There are, however, few data on gastrectomy as a secondary surgery aimed at rendering such patients cancer-free.. We investigated stage IV gastric cancer patients who underwent surgery with curative intent after S-1-based chemotherapy between 2000 and 2008. Twenty-eight patients from 12 hospitals were enrolled in this study. Factors indicating that the tumors were incurable included clinical stage T4 in 9 patients, para-aortic node metastasis in 15, peritoneal metastasis in 7, and liver metastasis in 4.. Of the 28 laparotomy patients, 26 underwent complete resection with no residual tumor, obtaining a complete resection rate of 92.9%. There were no in-hospital deaths or reoperations. In four patients, the primary tumor showed pathological complete response. The 1-, 3-, and 5-year overall survival rates after secondary gastrectomy were 82.1, 45.9, and 34.4%, respectively, with a median survival time of 29 months. Univariate analysis revealed histological tumor length, clinical depth of tumor invasion, number of metastatic nodes, pathological depth of tumor invasion, and pathological response to be the factors influencing patient survival after secondary surgery. On multivariate analysis, histological tumor length (5.0 cm or larger) was the only significant prognostic factor (relative risk 3.23, P = 0.028).. Secondary gastrectomy following S-1-based chemotherapy was a safe and effective treatment for stage IV gastric cancer. Primary tumor size is an indicator for the appropriate selection of patients for this treatment.

Topics: Adenocarcinoma; Aged; Antimetabolites, Antineoplastic; Drug Combinations; Female; Gastrectomy; Humans; Laparotomy; Male; Multivariate Analysis; Oxonic Acid; Prognosis; Retrospective Studies; Stomach Neoplasms; Survival Rate; Tegafur; Treatment Outcome

This randomized Phase II trial will compare the outcome of neoadjuvant chemotherapy using two and four courses of S-1 plus cisplatin or S-1 plus cisplatin plus docetaxel by a two-by-two factorial design for patients with macroscopically resectable serosa-positive gastric cancer. After neoadjuvant chemotherapy, patients will receive D2 gastrectomy followed by S-1 chemotherapy for 1 year postoperatively. The primary endpoint is the 3-year overall survival. The sample size is 120 for the two hypotheses: the superiority of four courses compared with two courses and the superiority of S-1 plus cisplatin plus docetaxel compared with S-1 plus cisplatin. This trial will be able to define the more suitable number of cycles and better regimen of neoadjuvant chemotherapy for gastric cancer.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cisplatin; Combined Modality Therapy; Docetaxel; Drug Combinations; Gastrectomy; Humans; Neoadjuvant Therapy; Oxonic Acid; Stomach Neoplasms; Taxoids; Tegafur

The aim of this study was to evaluate the efficacy and feasibility of preoperative chemotherapy with S-1 plus cisplatin in patients with initially unresectable locally advanced gastric cancer.. We enrolled patients with initially unresectable locally advanced gastric cancer because of severe lymph node metastases or invasion of adjacent structures. Preoperative chemotherapy consisted of S-1 at 80 mg/m(2) divided in two daily doses for 21 days and cisplatin at 60 mg/m(2) intravenously on day 8, repeated every 35 days. If a tumor decreased in size, patients received 1 or 2 more courses. Surgery involved radical resection with D2 lymphadenectomy.. Between December 2000 and December 2007, 27 patients were enrolled on the study. No CR was obtained, but PR was seen in 17 cases, and the response rate was 63.0%. Thirteen patients (48.1%) had R0 resections. There were no treatment related deaths. The median overall survival time (MST) and the 3-year overall survival (OS) of all patients were 31.4 months and 31.0%, respectively. Among the 13 patients who underwent curative resection, the median disease-free survival (DFS) and the 3-year DFS were 17.4 months and 23.1%, respectively. The MST and the 3-year OS were 50.1 months and 53.8%, respectively. The most common site of initial recurrence after the R0 resection was the para-aortic lymph nodes.. Preoperative S-1 plus cisplatin can be safely delivered to patients undergoing radical gastrectomy. This regimen is promising as neoadjuvant chemotherapy for resectable gastric cancer. For initially unresectable locally advanced gastric cancer, new trials using more effective regimens along with extended lymph node dissection are necessary.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Disease-Free Survival; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Female; Follow-Up Studies; Gastrectomy; Humans; Immunohistochemistry; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Invasiveness; Neoplasm Staging; Oxonic Acid; Premedication; Risk Assessment; Stomach Neoplasms; Survival Analysis; Tegafur; Treatment Outcome

Doses and schedules of the combination of S-1 and cisplatin for the treatment of advanced gastric cancer (AGC) have not been standardized. We therefore evaluated the efficacy and feasibility of a 3-week schedule of S-1 and cisplatin in patients with AGC, as well as assessing factors prognostic of patient outcomes.. A total of 159 patients with AGC were treated with S-1 (40 mg/m(2) bid on days 1-14) and cisplatin (60 mg/m(2) IV on day 1) between January 2004 and December 2008.. Median follow-up duration was 20.0 months (range, 11.4-48.5 months), during which time 129 patients (81.1%) died. Patients received a median 6 cycles of chemotherapy (range, 1-19 cycles). Among the 59 patients with measurable disease, 1 achieved a complete response (1.7%) and 24 (40.7%) had partial responses, giving an overall response rate of 42.4% (95% CI, 23.0-61.8%). The median progression-free survival (PFS) was 5.8 months (95% CI, 4.8-6.9 months), and the median overall survival (OS) was 11.3 months (95% CI, 9.6-13.0 months). Multivariate analysis showed that initial metastasis, bone metastasis, and liver metastasis were independent prognostic factors for reduced PFS, whereas poor performance status, initial metastasis, and bone metastasis were prognostic for reduced OS. Application of a previous prognostic model showed that observed PFS and OS survival curves for patients in various risk groups differed significantly (P < 0.001 each).. A 3-week regimen of S-1 plus cisplatin was active and well tolerated as first-line treatment in patients with AGC. Disease status and bone metastasis were the most important prognostic factors.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Cisplatin; Disease-Free Survival; Drug Administration Schedule; Drug Combinations; Female; Follow-Up Studies; Humans; Liver Neoplasms; Male; Middle Aged; Multivariate Analysis; Oxonic Acid; Prognosis; Retrospective Studies; Stomach Neoplasms; Tegafur; Treatment Outcome

The standard treatment for T4 locally advanced gastric cancer is gastrectomy with D2 lymph node dissection followed by adjuvant chemotherapy with S-1 for 12 months; however, prognostic outcome in Stage IIIb has been insufficient. It is expected that survival is improved by preoperative treatment with a triplet regimen of docetaxel, cisplatin and S-1 (divided DCS therapy). A multicenter Phase II study has been conducted to evaluate the safety and efficacy of two courses of preoperative chemotherapy followed by gastrectomy. Fifty-five patients are required for this study. The primary endpoint of the study is pathological response rate of primary lesions. Secondary endpoints are overall survival, disease-free survival, R0 resection rate and adverse events.

Topics: Adenocarcinoma; Adult; Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cisplatin; Disease-Free Survival; Docetaxel; Drug Administration Schedule; Drug Combinations; Feasibility Studies; Female; Gastrectomy; Humans; Infusions, Intravenous; Lymph Node Excision; Lymphatic Metastasis; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Oxonic Acid; Patient Selection; Stomach Neoplasms; Survival Analysis; Taxoids; Tegafur; Treatment Outcome

S-1 or capecitabine plus oxaliplatin are considered active and tolerable in gastric cancer patients. We conducted a randomized phase II trial in gastric cancer patients to compare the activity and safety of these combinations.. The patients received S-1 at 80 mg/m2 for 14 days, followed by a 7-day rest period within a 3-week schedule in the S-1/oxaliplatin (SOX) arm, and capecitabine at 2000 mg/m2 for 14 days, followed by a 7-day rest period within a 3-week schedule in the capecitabine/oxaliplatin (CAPOX) arm. Oxaliplatin 130 mg/m2 was administered every 3 weeks in both arms.. One hundred twenty-nine patients were randomly assigned to SOX (N=65) or CAPOX (N=64). The median time to progression and the overall survival were 6.2 and 12.4 months with SOX, respectively; and 7.2 and 13.3 months with CAPOX, respectively. The overall response rates were 40% and 44% for SOX and CAPOX, respectively. The most frequent grade 3 or 4 toxicities were thrombocytopenia (15.4%) for SOX and neutropenia (18.8%) for CAPOX. The median time to 10% deteriorations in global health scores was similar in both arms (SOX, 4.3 months, CAPOX, 4.9 months).. Both the SOX and CAPOX regimens were equally active and well tolerated in advanced gastric cancer patients.

Topics: Adenocarcinoma; Adult; Aged; Algorithms; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Deoxycytidine; Disease Progression; Drug Combinations; Female; Fluorouracil; Humans; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Stomach Neoplasms; Tegafur; Treatment Outcome; Young Adult

The purpose of this study was twofold: (1) to compare S-1 with infusional 5-fluorouracil (FU) to determine which would be a better partner of paclitaxel (PTX), and (2) to compare a concurrent strategy with a sequential one, the latter strategy being the one that is widely used in Japanese general practice.. The 161 eligible patients were randomized into four arms to receive the following regimens: A (sequential), intravenous 5-FU at 800 mg/m(2) for 5 days every 4 weeks followed by weekly PTX at 80 mg/m(2); B (sequential), S-1 at 80 mg/m(2) for 4 weeks and 2-week rest followed by PTX; C (concurrent), intravenous 5-FU at 600 mg/m(2) for 5 days and weekly PTX at 80 mg/m(2) every 4 weeks; and D (concurrent), S-1 for 14 days and PTX at 50 mg/m(2) on days 1 and 8 every 3 weeks. The primary endpoint was the overall survival (OS) rate at 10 months.. The ten-month OS rates in arms A, B, C, and D were 63, 65, 61, and 73%, respectively. The OS was best in the concurrent S-1/PTX arm, with a mean survival time of 15.4 months, but no significant difference was observed between the four arms. Response rates were higher in the concurrent arms than in the sequential arms.. Our study did not show sufficient prolongation of survival with the concurrent strategy to proceed to a phase-III trial; however, the sequential arms showed survival comparable to that in the concurrent arms, with less toxicity. In patients who are ineligible for cisplatin (CDDP), sequential treatment starting with S-1 and proceeding to PTX would be a good alternative strategy, considering quality of life (QOL) and the cost-benefits of an oral agent as first-line treatment.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Female; Fluorouracil; Humans; Infusions, Parenteral; Male; Middle Aged; Oxonic Acid; Paclitaxel; Patient Compliance; Stomach Neoplasms; Tegafur; Treatment Outcome

The aim of this phase I study was to investigate the optimal dose of S-1 and oxaliplatin with concurrent radiotherapy in a preoperative setting for locally advanced gastric cancer.. Twelve patients with histologically confirmed clinical stage T2N+ or T3-T4 gastric adenocarcinoma received dose level -1 (oral S-1 at 60 mg/m(2)/day + oxaliplatin 40 mg/m(2) intravenously on days 1, 8, 15 and 22) or dose level 1 (S-1 80 mg/m(2)/day + oxaliplatin 40 mg/m(2)), with concurrent radiotherapy at daily fractions of 1.8 Gy 5 days per week, to a total dose of 41.4 Gy. Surgical resection, including D2 dissection, was performed within 4 weeks after the last day of chemotherapy.. Chemoradiotherapy was generally well tolerated, with the most common dose-related grade 1 or 2 adverse events being anemia, nausea, vomiting, anorexia and abdominal pain. Two DLTs (prolonged thrombocytopenia and stomach perforation) were observed at dose level 1 (n = 6) and resulted in dose de-escalation to level -1. The recommended dose for future study is dose level -1, at which 1 of 6 patients developed grade 3 vomiting and anorexia. R0 resection was possible in 11 patients. Pathologic down-staging was observed in 6 patients, including one complete response. No clinically relevant postoperative complications occurred.. The activity of preoperative concurrent chemoradiotherapy with S-1 (60 mg/m(2)/day for 28 consecutive days) and oxaliplatin (40 mg/m(2) on days 1, 8, 15 and 22) will be explored more extensively in a phase II study in patients with locally advanced GC.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Dose-Response Relationship, Drug; Drug Combinations; Female; Humans; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Stomach Neoplasms; Tegafur; Treatment Outcome

This randomized Phase III trial will evaluate whether perioperative nutrition enriched with eicosapentaenoic acid can prevent body weight loss after total gastrectomy for gastric cancer. The patients who enroll in this study will be randomly assigned to Group A: no supplementation with oral nutrients (standard diet) or Group B: standard diet with eicosapentaenoic acid-enriched supplementation for 7 days before surgery and for 21 days after surgery. For both groups, patients will undergo total gastrectomy with Roux-en Y reconstruction. The extent of dissection will principally follow the third edition of the Gastric Cancer Treatment Guideline published by the Japanese Gastric Cancer Association. When patients are diagnosed with pathological Stage II or III disease, adjuvant chemotherapy with S-1 will be initiated within 6 weeks after surgery and administered for 1 year. The primary endpoint will be the body weight loss at 1 and 3 months after surgery (double primary endpoints). The secondary endpoints will be the relative performance of the supplement, loss of lean body mass at 1 and 3 months after surgery, the lowest serum albumin level, quality of life, the incidence of surgical morbidity and mortality, and the incidence of surgical site infection.

Topics: Adult; Aged; Anastomosis, Roux-en-Y; Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Dietary Supplements; Drug Combinations; Eicosapentaenoic Acid; Female; Gastrectomy; Humans; Japan; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Perioperative Period; Practice Guidelines as Topic; Quality of Life; Research Design; Stomach Neoplasms; Tegafur; Time Factors; Treatment Outcome; Weight Loss

The standard of care for gastric cancer with peritoneal metastasis is chemotherapy. However, there is no chemotherapy regimen with a sufficient level of evidence, and thus S-1 plus cisplatin (CDDP), which is regarded as the standard regimen for advanced metastatic gastric cancer, is widely applied. Meanwhile the efficacy of intraperitoneal (IP) administration of taxanes has been verified, and the novel multidisciplinary treatment combining chemotherapy and surgery is now being tested. We developed a combination chemotherapy regimen of S-1, weekly intravenous and IP paclitaxel (PTX), and determined the recommended dose of IP PTX to be 20 mg/m2 in our phase I study. In our phase II study, the median survival time (MST) of 40 patients enrolled was 23.6 months, and peritoneal cytology turned negative for 86% of 28 patients. Moreover, we performed gastrectomy on 52 patients after disappearance or obvious shrinkage of peritoneal metastasis, and the MST was 34.9 months. The multidisciplinary treatment combining IP-containing chemotherapy and surgery is safe and effective for gastric cancer patients with peritoneal metastasis. We have just started a phase III trial (PHOENIX-GC trial) comparing our IP regimen versus S-1 plus CDDP.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Drug Combinations; Gastrectomy; Humans; Injections, Intraperitoneal; Injections, Intravenous; Middle Aged; Oxonic Acid; Peritoneal Neoplasms; Stomach Neoplasms; Tegafur

A Phase II trial was initiated in Japan to evaluate the efficacy and safety of preoperative chemotherapy with docetaxel, cisplatin and S-1 for gastric cancer with extensive lymph node metastasis. Patients are eligible to participate in the study if they have para-aortic lymph node metastases (stations no. 16a2/16b1) and/or a bulky lymph node (≥3 cm × 1 or ≥1.5 cm × 2) along the celiac, splenic, common or proper hepatic arteries or the superior mesenteric vein, while patients with other distant metastases are ineligible. A total of 50 patients will be enrolled over 2.5 years. The primary endpoint is the response rate of the preoperative chemotherapy, which will be assessed based on the Response Evaluation Criteria in Solid Tumors ver. 1.0. The secondary endpoints are %3-year survival, %5-year survival, proportion of patients with R0 resection, proportion of patients who complete the preoperative chemotherapy and surgery, proportion of patients who complete the protocol treatment, pathological response rate and adverse events. This trial was registered at the UMIN Clinical Trials Registry (www.umin.ac.jp/ctr/) as UMIN000006069.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Aorta; Chemotherapy, Adjuvant; Cisplatin; Docetaxel; Drug Combinations; Female; Gastrectomy; Humans; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Oxonic Acid; Stomach Neoplasms; Survival Analysis; Taxoids; Tegafur; Treatment Outcome

In gastric cancer patients who have positive results for peritoneal lavage cytology the disease is defined as CY1, and classified as stage IV, and this population has generally suffered a dismal outcome. For this population, we had conducted a phase II trial, with the 2-year survival rate as the primary endpoint, to test the strategy of D2 dissection followed by chemotherapy with single-agent S-1 (1 M tegafur-0.4 M gimestat-1 M otastat potassium). Forty-eight patients were enrolled, of whom 47 were found to have been eligible for analysis. The 2-year survival rate of 46 % exceeded our expectations.. Further follow up was conducted to confirm whether radical surgery could be recommended for the CY1 population.. The 5-year overall and relapse-free survival rates were 26 and 21 %, respectively.. Gastrectomy with curative intent could be considered for patients with CY1 disease provided they are scheduled to receive effective postoperative chemotherapy.

Topics: Aged; Antimetabolites, Antineoplastic; Drug Combinations; Follow-Up Studies; Gastrectomy; Humans; Oxonic Acid; Peritoneal Cavity; Peritoneal Lavage; Stomach Neoplasms; Survival Rate; Tegafur

A combination of S-1 and cisplatin has been shown to be effective with acceptable safety for the first-line treatment of far-advanced gastric cancer in Japan. This is the first randomised phase II trial to compare S-1+paclitaxel with S-1+cisplatin in this setting.. Patients with unresectable and/or recurrent advanced gastric cancer were randomly assigned to receive one of the two regimens: S-1 (40 mg m(-2) twice daily) on days 1-14 plus paclitaxel (60 mg m(-2)) on days 1, 8, and 15 of a 4-week cycle (S-1+paclitaxel) or S-1 (40 mg m(-2) twice daily) on days 1-21 plus cisplatin (60 mg m(-2)) on day 8 of a 5-week cycle (S-1+cisplatin). The primary end point was the response rate (RR). Secondary end points included progression-free survival (PFS), overall survival (OS), and safety.. A total of 83 patients were eligible for safety and efficacy analyses. In the S-1+paclitaxel and S-1+cisplatin groups, RRs (52.3% vs 48.7%; P=0.74) and median PFS (9 vs 6 months; P=0.50) were similar. The median OS was similar in the S-1+paclitaxel and S-1+cisplatin groups (16 vs 17 months; P=0.84). The incidence of grade 3 or higher haematological toxicity was 19.0% with S-1+paclitaxel and 19.5% with S-1+cisplatin. The incidence of grade 3 or higher non-haematological toxicity was 14.2% with S-1+paclitaxel and 17.1% with S-1+cisplatin.. S-1+paclitaxel was suggested to be a feasible and effective non-platinum-based regimen for chemotherapy in patients with advanced gastric cancer. Our results should be confirmed in multicenter, phase III-controlled clinical trials.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Disease-Free Survival; Drug Combinations; Female; Humans; Male; Middle Aged; Oxonic Acid; Paclitaxel; Stomach Neoplasms; Tegafur

This study was performed to determine the recommended dose (RD) and dose-limiting toxicity (DLT) associated with epirubicin, oxaliplatin, and S-1 (EOS) combination therapy in patients with previously untreated advanced gastric cancer (AGC).. Previously untreated patients with histologically proven metastatic AGC, with an ECOG performance status of 0-2, were enrolled in this study. A fixed dose of epirubicin (50 mg/m(2)) and oxaliplatin (130 mg/m(2)) was intravenously administered on day 1 of treatment, followed by oral S-1 administration twice daily on days 1-14. The S-1 dose was escalated according to the following schedule: level I, 35 mg/m(2); level II, 40 mg/m(2); level III, 45 mg/m(2); Level IV, 50 mg/m(2). Each cycle was repeated every 21 days. DLTs were evaluated during the first two cycles of treatment.. Nineteen patients with a median age of 53 years (range, 40-71 years) were enrolled in this study. One case of DLT (grade 4 neutropenia lasting more than 5 days) developed from among the six dose level II patients, while 2 DLTs (grade 3 diarrhea and nausea) were observed among the 4 dose level III patients. Based on these results, dose level II was determined as the RD. Of the 13 patients with measurable lesions, eight achieved partial response, three showed stable disease, and the objective response rate was 61.5 % (95 % confidence interval (CI), 13.3-66.6 %). The median progression-free survival and overall survival of all patients was 6.8 months (95 % CI, 1.4-9.5 months) and 13.3 months (95 % CI, 1.9-24.6 months), respectively.. The RD of the EOS regimen in patients with previously untreated AGC was 50 mg/m(2) of epirubicin and 130 mg/m(2) of oxaliplatin on day 1, with administration of 40 mg/m(2) of S-1 twice a day on days 1-14 for each 21-day cycle. The EOS regimen described produced promising results.

Topics: Adenocarcinoma; Administration, Oral; Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Disease-Free Survival; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Epirubicin; Female; Humans; Injections, Intravenous; Kaplan-Meier Estimate; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Prospective Studies; Stomach Neoplasms; Tegafur; Young Adult

On the basis of international clinical trials, capecitabine plus cisplatin (XP) as a first-line treatment of advanced gastric cancer is considered a global standard regimen. However, the usefulness of XP as compared with S-1 plus cisplatin (SP), which is considered standard therapy in Japan, has not yet been assessed.. This is a multicenter randomized phase II trial to elucidate the efficacy of XP as compared with SP for first-line treatment of advanced gastric cancer. Patients with unresectable metastatic or recurrent gastric cancer, 20-74 years of age and human epidermal growth factor 2 (HER2)-negative status, will be assigned in a 1:1 ratio to receive either S-1 40 mg/m2 bid for 21 days plus cisplatin 60 mg/m2 (day 8) every 5-week cycle or capecitabine 1000 mg/m2 bid for 14 days plus cisplatin 80 mg/m2 (day 1) every 3-week cycle. Patients will be also asked to the analysis of tumor tissues for translational investigations. The Primary endpoint is progression-free survival and secondary endpoints are overall survival, time to treatment failure, tumor response rate and safety. These comparisons will also be evaluated in terms of biomarkers. Planned sample size is 100 (50 in each arm), which is appropriate for this trial.. Fluoropyrimidine plus cisplatin combination is the standard regimen of the first line treatment for advanced gastric cancer. Both S-1 and capecitabine are the prodrug of 5-FU but differ from their process of metabolism. Result of this trial and translational research will provide the important clues to prepare the individualized therapy for advanced gastric cancer in the near future.. ClinicalTrials.gov Identifier NCT01406249.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Cisplatin; Deoxycytidine; Drug Combinations; Fluorouracil; Humans; Middle Aged; Neoplasm Staging; Oxonic Acid; Stomach Neoplasms; Tegafur; Young Adult

The aim of this study was to evaluate the safety and efficacy of vaccination with human leukocyte antigen (HLA)-A24-restricted human vascular endothelial growth factor receptor 1 (VEGFR1)-1084 and VEGFR2-169 combined with chemotherapy in patients with advanced gastric cancer. HLA-A 2402-positive patients with advanced or recurrent adenocarcinoma of the stomach were vaccinated with VEGFR1-1084 and VEGFR2-169 combined with S-1 and cisplatin. The study included 22 patients (median age 60.5 years) who received at least one cycle of the combination therapy. No severe adverse effects caused by the vaccine therapy were observed except for an inflammatory reaction at the site of injection in 6 patients. Twelve patients (55%) showed partial response and 10 had stable disease after two cycles of the combination therapy. The disease control rate (partial response and stable disease) was 100% after two cycles. The median time to progression was 9.6 months and median overall survival was 14.2 months. VEGFR1-1084-specific cytotoxic T lymphocyte (CTL) response was induced in 18 (82%) of the 22 patients and VEGFR2-169-specific CTL response was induced in 18 (82%) of the 22 patients. Patients showing CTL response to VEGFR2-169 peptide had significantly better prognosis than those without, as demonstrated by the overall survival (OS) and time to progression (TTP) (OS, p=0.028, TTP, p=0.006). The combination therapy was well tolerated and highly effective in advanced or recurrent gastric cancer. Substantial specific CTL for both peptides was frequently induced even under chemotherapy. Thus, cancer vaccination combined with standard chemotherapy warrants further analysis as a promising strategy for the treatment of advanced cancer.

Topics: Adenocarcinoma; Aged; Cancer Vaccines; Cisplatin; Combined Modality Therapy; Drug Combinations; Female; HLA-A24 Antigen; Humans; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Prognosis; Stomach Neoplasms; T-Lymphocytes, Cytotoxic; Tegafur; Vaccines, Subunit; Vascular Endothelial Growth Factor Receptor-1; Vascular Endothelial Growth Factor Receptor-2

Surgery alone is no longer an adequate standard of care for patients with resectable gastric cancer. Thus, research efforts should focus on which regimens are the most effective for patients with recurrent gastric cancer after combined treatment with surgery and perioperative or adjuvant chemotherapy.. Patients with histologically confirmed and measurable advanced gastric cancer who showed a relapse even after fluoropyrimidine and/or cisplatin-based adjuvant chemotherapy received docetaxel (35 mg/m(2)) intravenously on day 1 and 8 plus oxaliplatin (100 mg/m(2)) intravenously on day 1 every 3 weeks until disease progression or unacceptable toxicity.. A total of 34 patients with relapsed advanced gastric cancer who had received adjuvant chemotherapy with fluoropyrimidine and/or cisplatin for a median of 6 months (range, 1-48 months) were enrolled in this trial; 22 (64.7 %) patients had been exposed to both agents. Their median age was 58 years (range, 50-68 years). The overall response rate was 55.9 % (95 % confidence interval (CI), 38.3-73.5 %), including 1 complete response and 18 partial responses. At a median follow-up duration of 28.5 months (range, 9.2-50.7 months), the median progression-free survival for all patients was 5.3 months (95 % CI, 4.4-6.1 months) and the median overall survival was 13.8 months (95 % CI, 11.1-16.4 months). The most common grade 3 or 4 hematologic and nonhematologic toxicities were neutropenia (47.1 %) and diarrhea (17.6 %), respectively. Five patients (14.7 %) experienced febrile neutropenia.. Docetaxel and oxaliplatin combination chemotherapy was active and tolerable in patients with recurrent gastric cancer after fluoropyrimidine and/or cisplatin-based adjuvant chemotherapy.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Chemotherapy, Adjuvant; Cisplatin; Combined Modality Therapy; Deoxycytidine; Disease-Free Survival; Docetaxel; Drug Combinations; Female; Fluorouracil; Follow-Up Studies; Humans; Korea; Male; Middle Aged; Neoplasm Recurrence, Local; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Stomach Neoplasms; Survival Rate; Taxoids; Tegafur; Treatment Outcome

To evaluate the efficacy and safety profile and to explore the role of docetaxel, S-1 plus cisplatin (DCS) or oxaliplatin (DOS) in the treatment of advanced gastric cancer.. A total of 45 patients with advanced gastric cancer were recruited. They received DCS or DOS at the discretion of investigators. Docetaxel was given intravenously at the dose of 60 mg/m² at d1, S-1 60 mg×m⁻²×d⁻¹ or 80 - 120 mg/d according to individual patient's area of body surface orally from d1 to d14 and cisplatin 30 mg/m² at d1, d2 or oxaliplatin 111 - 127 (median: 117) mg/m ²at d2. Each cycle was for 21 days.. Forty-three patients received ≥ 1 complete cycle of DCS/DOS with a median cycle number of 5(range: 1 - 8). Among 42 patients evaluated for efficacy, the outcomes were partial response (n = 28), stable disease (n = 9) and progression (n = 5). The response rate was 66.7%. Progression-free survival (PFS) of 32 patients on chemotherapy alone was 7.1 months and the median overall survival (OS) was not reached. The most common grade 3/4 adverse effects included neutropenia (46.5%), thrombocytopenia (9.3%), vomiting (9.3%), nausea (7.0%) and diarrhea (4.7%). Ten of fourteen patients with advanced unresectable gastric cancer without clinically detectable distant metastases underwent surgical resection after a median of 4 (2-6) cycles of DCS or DOS and 9 (64.3%) had R0 resection.. DCS/DOS is effective for advanced gastric cancer and in the setting of neoadjuvant chemotherapy. And the toxicities of DCS/DOS are manageable.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Docetaxel; Drug Combinations; Female; Humans; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Platinum; Stomach Neoplasms; Taxoids; Tegafur; Treatment Outcome

The present study analyzed the expression of phosphorylated AMP-activated protein kinase (pAMPK), Fyn kinase, and pyruvate dehydrogenase kinase-1 (PDK-1) and their impact on the survival of patients with resected gastric cancer who received cisplatin-based adjuvant chemotherapy.. Korean patients with stage II-IV (M0) gastric adenocarcinoma who underwent a gastrectomy with D2 lymph node resection and received a combination regimen of cisplatin and S-1 were enrolled. Immunohistochemistry was carried out to determine the expression of pAMPK, Fyn kinase, and PDK-1 in operative specimens of gastric cancer. The expression was divided into two groups according to the intensity score (negative: 0 or 1+ and positive: 2+ or 3+).. From January 2006 to July 2010, 73 tumor samples obtained from 74 patients were analyzed. Forty patients were included in the pAMPK-positive group, while 33 patients were included in the pAMPK-negative group. Meanwhile, positive Fyn kinase expression was observed in only 10 patients (13.7 %), and there was no or very weak PDK-1 staining. The clinicopathologic characteristics were similar between the two groups according to the expression of pAMPK. With a median follow-up duration of 26.5 months (2.6-73.2), the estimated 3-year relapse-free survival (RFS) and overall survival rates were 55.0 and 78.4 %, respectively. In a multivariate analysis adjusted for age, sex, Lauren classification, and stage, the pAMPK-negative group was significantly associated with improved RFS (Hazard ratio = 0.459, 95 % CI 0.109-0.711, P = 0.043).. A low expression of pAMPK was found to be correlated with better RFS in patients with resected gastric cancer treated with adjuvant cisplatin-based chemotherapy.

Topics: Adenocarcinoma; Adult; Aged; AMP-Activated Protein Kinases; Antineoplastic Combined Chemotherapy Protocols; Asian People; Chemotherapy, Adjuvant; Cisplatin; Disease-Free Survival; Drug Combinations; Female; Follow-Up Studies; Gastrectomy; Gene Expression Regulation, Neoplastic; Humans; Korea; Lymph Node Excision; Male; Middle Aged; Multivariate Analysis; Neoplasm Staging; Oxonic Acid; Phosphorylation; Pilot Projects; Prognosis; Stomach Neoplasms; Survival Rate; Tegafur; Young Adult

A preliminary study with the aim of evaluating the safety and efficacy of a single intraperitoneal administration of paclitaxel, combined with intravenous administration of paclitaxel plus S-1, was carried out in gastric cancer patients with peritoneal metastasis.. Paclitaxel was administered intraperitoneally at 80 mg/m(2). After one to two weeks, S-1 was administered at 80 mg/m(2)/day for 14 consecutive days, followed by seven days' rest. Paclitaxel was administered intravenously at 50 mg/m(2) on days 1 and 8. The safety, pharmacokinetic analysis and efficacy of this therapy were investigated.. Fifteen patients were enrolled in this study. The toxic effects of the intraperitoneal chemotherapy were mild. The toxic effects with the systemic chemotherapy were acceptable. The ratio of (AUC peri)/(AUC pla) was 1065:1 in the pharmacokinetic analysis. The one-year overall survival rate was 10/15 (66.7%).. A single intraperitoneal administration of paclitaxel combined with intravenous administration of paclitaxel plus S-1 is a well-tolerated and feasible treatment for patients with gastric cancer with peritoneal metastasis.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Drug Administration Schedule; Drug Combinations; Humans; Middle Aged; Oxonic Acid; Paclitaxel; Peritoneal Neoplasms; Stomach Neoplasms; Tegafur; Young Adult

To establish a safe, long-term regimen of docetaxel (DOC) and cisplatin (CDDP) in an outpatient setting for gastric cancer refractory to S-1 adjuvant chemotherapy, a dose-escalating phase I study was conducted. Cohorts of patients were treated with escalating doses of DOC (starting at 20 mg/m² per week with 5 mg/m² increments) and a fixed dose of CDDP (25 mg/m²). Drugs were administered on days 1, 8, and 15. A cycle of this treatment was 28 days. In total, 52 courses were performed, and the mean number of courses was 5.3. Two of the four patients at dose level 3 showed dose-limiting toxicities (grade 4 neutropenia, and grade 3 anorexia and dehydration). The recommended dose (RD) of DOC was therefore defined as 25 mg/m². There is a need for a phase II clinical trial using this regimen in patients with S-1-refractory stage II/III gastric cancer.

Topics: Aged; Anorexia; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cisplatin; Cohort Studies; Dehydration; Docetaxel; Dose-Response Relationship, Drug; Drug Combinations; Drug Resistance, Neoplasm; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasm Staging; Neutropenia; Oxonic Acid; Stomach Neoplasms; Taxoids; Tegafur

Triplet combination chemotherapy has the potential to improve the prognosis of patients with unresectable gastric cancer. We conducted a phase I trial of triplet combination chemotherapy consisting of paclitaxel, cisplatin, and S-1 (PCS) for unresectable gastric cancer.. Patients with metastatic or incurable disease were enrolled. S-1 was administered on days 1-14. Paclitaxel and cisplatin were infused on days 1 and 15. The starting doses of paclitaxel and cisplatin were 100 and 20 mg/m(2), respectively. Dose levels of paclitaxel and cisplatin were escalated as follows: 120 and 20 mg/m(2), respectively (level 2); 120 and 30 mg/m(2), respectively (level 3). End-points: Dose-limiting toxicities included grade 3 nausea, vomiting, and general fatigue, and grade 4 febrile neutropenia. The maximum tolerated dose and recommended dose were established at level 3 and level 2, respectively.. Although further clinical trials are recommended to more thoroughly evaluate safety and efficacy, PCS appears to be an excellent candidate for a standard treatment strategy for unresectable gastric cancer.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Dose-Response Relationship, Drug; Drug Combinations; Female; Humans; Male; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Paclitaxel; Stomach Neoplasms; Tegafur; Treatment Outcome

To evaluate the efficacy and safety of weekly paclitaxel combined with S-1 or fluorouracil in the first line treatment of advanced gastric carcinoma.. Two hundred and forty patients with untreated advanced gastric carcinoma were randomized into two arms, patients in the experimental arm were given paclitaxel and S-1, while those in the control arm received paclitaxel and fluorouracil. The regimen of experimental arm was paclitaxel 60 mg/m(2) by intravenous infusion, day 1, 8, 15; S-1 80 - 120 mg/day given by oral administration, day 1 - 14. The regimen of control arm was fluorouracil 500 mg/m(2) by intravenous infusion continuously, day 1 - 5; CF 20 mg/m(2) by intravenous infusion, day 1 - 5. The regimens in both arms were repeated every 28 days. The efficacy and safety of both arms were assessed.. Two hundred and twenty-eight patients were analyzed in the full analysis set, and 192 patients were analyzed in per-protocol set (experimental arm 100 patients, control arm 92 patients). The overall response rates of experimental and control arms were 50.0% and 28.3% (P = 0.002), and the disease control rates were 82.0% and 70.7% (P = 0.064), respectively. The primary endpoints of experimental arm were non-inferior to that of the control arm. The secondary endpoint of experimental arm in terms of median progression free survival was significantly better than that of control arm (5 months versus 4 months, P = 0.006). The experimental arm had a higher incidence of grade III-IV bone marrow suppression than the control arm, but the incidence of fever in both arms was not significantly different.. Oral administration of S-1 is an alternative option of venous infusional fluorouracil. Weekly paclitaxel combined with S-1 is a safe regimen and has a promising efficacy.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Diarrhea; Disease-Free Survival; Drug Combinations; Female; Fluorouracil; Follow-Up Studies; Humans; Leukopenia; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Paclitaxel; Prospective Studies; Remission Induction; Stomach Neoplasms; Survival Rate; Tegafur

The present study was conducted to evaluate the efficacy and safety of a combination regimen of S-1, paclitaxel plus cisplatin in patients with advanced gastric cancer.. Patients with previously untreated metastatic or recurrent, measurable gastric cancer received intravenous paclitaxel 80 mg/m² plus cisplatin 30 mg/m² on days 1, 8 and S-1 35 mg/m² orally twice daily on days 1-14 based on a 3-week cycle.. Forty-four patients were enrolled in the current study, among whom 38 were assessable for efficacy and all assessable for toxicity. Two complete response and 24 partial responses were confirmed, giving an overall response rate of 59.1%. At a median follow-up of 11.4 months, the median time to progression and median overall survival was 9.4 (95% CI 6.8-12.1) months and 11.2 (95% CI 7.6-14.8) months, respectively. Grade 3/4 neutropenia occurred in 45 events (20.9%) and febrile neutropenia was observed in five events (2.3%). The common non-hematologic toxicity was nausea (grade 1/2, 27.2%) and diarrhea (grade 1/2, 9.0%).. The combination of S-1, paclitaxel and cisplatin was found to be well tolerated and effective in patients with advanced gastric cancer.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Disease Progression; Drug Combinations; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Oxonic Acid; Paclitaxel; Prospective Studies; Stomach Neoplasms; Survival; Tegafur; Treatment Outcome

To evaluate the efficacy, safety and pharmacokinetic profiles of S-1, which composed of tegafur (FT, a prodrug of 5-FU), 5-chloro-2,4-dihydroxypyridine and potassium oxonate (Oxo), in Taiwanese advanced gastric cancer (AGC) patients.. Patients with chemo-naïve, histologically confirmed AGC were eligible. S-1 was given orally at dose of 40, 50 or 60 mg, twice daily for patients with body surface <1.25, 1.25-1.5 and >1.5 m(2), respectively, on day 1-28 every 42 days/cycle.. Thirty-four patients were included. On intent-to-treat analysis, the overall response rate, median progression-free and overall survival were 35.3% [95% confidence interval (CI): 19.2-51.3%], 2.9 (95% CI: 2.4-5.8) months and 9.8 (95% CI: 6.1-NA) months, respectively. The most common grade 3-4 toxicities were anemia 23.5% and neutropenia 11.8%. There were two treatment-related mortality, which occurred in patients with suboptimal renal function underestimated by serum creatinine level at study entry. Single-dose pharmacokinetic study showed trend toward lower AUC(5-FU), and higher AUC(FT) and AUC(Oxo) comparing to most Western reports.. The efficacy, toxicity and pharmacokinetic profiles of S-1 in current study are compatible with those from other Asian populations. Accurate renal function assessment and more closely monitoring is mandatory for S-1 therapy in patients with low body mass. Literature review suggests that, besides AUC(5-FU), AUC(Oxo) may also attribute to the difference in the compliance to S-1 between Asian and Caucasian populations.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Asian People; Drug Combinations; Female; Humans; Male; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Stomach Neoplasms; Taiwan; Tegafur

We evaluated the efficacy and toxicity of biweekly S-1 and docetaxel combination therapy in patients with advanced gastric cancer.. Patients with histologically proven, unresectable advanced or recurrent gastric cancer, a performance status (PS) of 0-2 and no prior chemotherapy history were eligible for inclusion (n = 45). Patients received a total of 215 treatment courses (median, 4; range, 2-12) of S-1 oral administration twice daily for 1 week followed by a drug-free interval of 1 week. Docetaxel (40 mg/m(2)) was administered intravenously on days 1 and 15.. We observed 25 partial responses (55.6%) and one complete response (2.2%), resulting in an overall response rate of 57.8%. Twenty-four patients (53.3%) received second-line chemotherapy. Five patients (11.1%) underwent R0 gastrectomy during the course of the study. The median overall survival time was 15.3 months, the median time to progression was 6.9 months, and the median duration of response in 26 patients was 8.0 months. Neutropenia was the most frequently observed (40.4%) haematological toxicity at grades 3 and 4 and leucopenia was the second most common (29.8%). There were no treatment-related deaths.. S-1 plus docetaxel combination therapy in an outpatient setting provided promising activity with acceptable adverse toxicities.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Disease-Free Survival; Docetaxel; Drug Administration Schedule; Drug Combinations; Female; Humans; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Oxonic Acid; Stomach Neoplasms; Survival Rate; Taxoids; Tegafur

To evaluate the feasibility of S-1 plus cisplatin as adjuvant chemotherapy for stage III gastric cancer after curative resection.. Japanese patients with stage III gastric cancer who underwent gastrectomy with D2 lymph node resection were enrolled. Treatment consisted of 3 cycles of S-1 (80 mg/m(2)/day, b.i.d.) for 21 days followed by a 14-day rest, and cisplatin (60 mg/m(2) iv) on day 8. After that, S-1 monotherapy was given on days 1-28 every 6 weeks until 1-year postsurgery. After protocol amendment, the first chemotherapy cycle consisted of S-1 monotherapy; cisplatin was added to cycles 2, 3, and 4, followed by S-1 monotherapy up to 1-year postsurgery. The primary endpoint was the completion rate of three cycles of S-1 plus cisplatin.. A total of 63 enrolled patients have been evaluated. Grade 3/4 toxicities included neutropenia (40%), anorexia (28%), and febrile neutropenia (4%) before protocol amendment (n = 25), and neutropenia (37%), anorexia (8%), and febrile neutropenia (3%) after amendment implementation (n = 38). Excluding ineligible cases, treatment completion rates were 57% (12/21) before and 81% (30/37) after the protocol amendment.. The amended S-1 plus cisplatin is more feasible than the original protocol because of early dose reduction of S-1 prior to cisplatin addition and greater recovery time from surgery prior to cisplatin. This treatment should be considered as a feasible experimental arm for the next postoperative adjuvant phase III trial.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cisplatin; Drug Combinations; Feasibility Studies; Female; Humans; Male; Middle Aged; Oxonic Acid; Patient Compliance; Stomach Neoplasms; Tegafur

The aim of this study was to investigate the efficacy and safety of S-1/irinotecan/oxaliplatin (TIROX) in metastatic gastric cancer (MGC) and the association between treatment outcome and uridine diphosphate-glucuronosyltransferase (UGT) 1A polymorphisms.. Patients with previously untreated MGC received S-1 40 mg/m(2) b.i.d. on days 1-14 and irinotecan 150 mg/m(2) plus oxaliplatin 85 mg/m(2) on day 1 every 3 weeks.. Forty-four patients were enrolled. In intent-to-treat analysis, the objective response rate was 75%, including the complete response (CR) rate of 14%. The median time to progression and overall survival was 10.2 and 17.6 months, respectively. Ten (26%) of the 39 patients with primary gastric tumor showed biopsy-confirmed gastric CR. Grade 3/4 neutropenia developed in 66% of patients and grade 3 febrile neutropenia in 16%. The most common grade 3 nonhematologic toxic effects were abdominal pain (18%), anorexia (16%), and diarrhea (14%). UGT1A polymorphisms were associated with significantly higher incidence of grade 4 leukopenia (UGT1A1*6), neutropenia (UGT1A1*6, UGT1A6*2, and UGT1A7*3), grade 3/4 febrile neutropenia (UGT1A1*6), and grade 3 abdominal pain (UGT1A1*6).. The TIROX regimen induced marked tumor reduction and promising survival with a manageable toxicity profile in MGC patients. UGT1A genotype may be predictive of TIROX toxicity.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Drug Combinations; Female; Glucuronosyltransferase; Humans; Irinotecan; Male; Middle Aged; Neoplasm Metastasis; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Polymorphism, Genetic; Stomach Neoplasms; Tegafur; Treatment Outcome

This single-arm, phase II clinical study evaluated the efficacy and safety of sequential treatment with S-1 followed by cisplatin in patients with advanced or recurrent gastric cancer.. Fifty patients with histologically confirmed advanced or recurrent gastric cancer and an Eastern Cooperative Oncology Group performance status of 0-2 who had measurable and/or assessable lesions and gave written informed consent were enrolled. S-1 (40 mg/m(2), bid) was administered on days 1-21, and cisplatin (70 mg/m(2)) was given as an intravenous infusion on day 22 of a 35-day cycle. Treatment was continued until disease progression or intolerable adverse events. Cisplatin was administered for 6 cycles. Adverse events were assessed according to Common Terminology Criteria of Adverse Events version 3.0, and efficacy was evaluated according to the Response Evaluation Criteria in Solid Tumors version 1.0 for patients with measurable lesions and by the criteria of the Japanese Research Society for Gastric Cancer for all patients.. Efficacy could be evaluated in 49 of the 50 enrolled patients. The median age was 62 years. Lesions were measurable in 38 patients and assessable in 11. The response rate was 44.7% in patients with measurable lesions and 40.8% overall. The progression-free survival and overall survival were, respectively, 233 days (7.8 months) and 574 days (19.0 months) in patients with measurable lesions and 192 days (6.4 months) and 402 days (13.4 months) overall. Serious adverse events (grade 3 or higher) included neutropenia (24.5%), anemia (20.4%), and anorexia (20.4%) and were safely managed.. The safety and effectiveness of sequential treatment with S-1 followed by cisplatin every 35 days is equivalent to that reported for conventional chemotherapeutic regimens in patients with advanced or recurrent gastric cancer.

Topics: Adenocarcinoma; Adult; Aged; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Oxonic Acid; Patient Compliance; Stomach Neoplasms; Survival Analysis; Tegafur; Treatment Outcome

This phase II trial first describes the combination chemotherapy of biweekly irinotecan plus S-1 (biweekly IRIS) for pretreated advanced gastric cancer (AGC) patients.. Patients who had previously been treated with greater than or equal to one regimen were enrolled. They received S-1 35 mg/m(2) twice daily on days 1-14 and irinotecan 150 mg/m(2) on days 1 and 15, every 4 weeks. The primary endpoint was overall survival (OS).. Among the 38 patients enrolled, 18 patients were treated as second line, and the remaining 20 patients were enrolled as third- or fourth line. A total of 208 cycles were administered with the median being four cycles (range 1-16). The median OS was 8.7 months [95% confidence interval (CI) 7.5-10.3], and the median progression-free survival was 6.3 months (95% CI 5.3-7.3). Low serum albumin (<3.5 mg/dL) was an independent adverse prognosticator for survival. Overall response rate was 17% (95% CI 4-30%). The major grade 3/4 toxicities were neutropenia (26%) and diarrhea (18%).. Biweekly IRIS showed the moderate activity as salvage treatment in AGC. Considering high neutropenia and gastrointestinal toxicity, patient selection should be warranted; serum albumin may be a predictive factor for treatment decision.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Diarrhea; Disease-Free Survival; Drug Combinations; Female; Humans; Irinotecan; Male; Middle Aged; Neutropenia; Oxonic Acid; Patient Selection; Salvage Therapy; Serum Albumin; Stomach Neoplasms; Survival; Tegafur; Treatment Outcome

Irinotecan hydrochloride and S-1, an oral fluoropyrimidine, have shown antitumor activity against advanced gastric cancer as single agents in phase I/II studies. The combination of irinotecan and S-1 (IRI-S) is also active against advanced gastric cancer. This study was conducted to compare the efficacy and safety of IRI-S versus S-1 monotherapy in patients with advanced or recurrent gastric cancer.. Patients were randomly assigned to oral S-1 (80 mg/m² daily for 28 days every 6 weeks) or oral S-1 (80 mg/m² daily for 21 days every 5 weeks) plus irinotecan (80 mg/m² by intravenous infusion on days 1 and 15 every 5 weeks) (IRI-S). The primary endpoint was overall survival. Secondary endpoints included the time to treatment failure, 1- and 2-year survival rates, response rate, and safety.. The median survival time with IRI-S versus S-1 monotherapy was 12.8 versus 10.5 months (P = 0.233), time to treatment failure was 4.5 versus 3.6 months (P = 0.157), and the 1-year survival rate was 52.0 versus 44.9%, respectively. The response rate was significantly higher for IRI-S than for S-1 monotherapy (41.5 vs. 26.9%, P = 0.035). Neutropenia and diarrhea occurred more frequently with IRI-S, but were manageable. Patients treated with IRI-S received more courses of therapy at a relative dose intensity similar to that of S-1 monotherapy.. Although IRI-S achieved longer median survival than S-1 monotherapy and was well tolerated, it did not show significant superiority in this study.

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Disease Progression; Drug Combinations; Female; Follow-Up Studies; Humans; Irinotecan; Male; Middle Aged; Neoplasm Recurrence, Local; Oxonic Acid; Stomach Neoplasms; Tegafur; Treatment Outcome; Young Adult

Intraperitoneal administration of taxanes revealed excellent anti-tumor effect for peritoneal metastasis of gastric cancer in some experimental models. The aim of this study is to determine maximum tolerated dose (MTD), dose limiting toxicity (DLT) and recommended dose (RD) of intraperitoneally infused paclitaxel (PTX) with S-1 as a phase I study.. Eighteen patients with advanced gastric cancer in addition to confirmed peritoneal metastasis using laparoscopy were enrolled in this study. The regimen consists of oral administration of S-1 (Dose 80 mg: BSA<1.25 m(2), 100 mg: 1.251.5 m(2)) for 14 days and intraperitoneal infusion of PTX (Dose escalation: level I: 40, II: 60, III: 80, level IV: 90, V: 100 mg/m(2)) at day 1 and 14. PTX concentrations in serum and ascites were determined at 4, 8, 12, 24, 48 hours after the infusion, which was repeated twice every 4 weeks.. The number of patients were as follows: Level I: 3, Level II: 6, Level III: 3, Level IV: 3, Level V: 3. Grade 3 leukocytopenia was confirmed in 1 (Level II) and 2 (Level V). MTD is 90 mg/m(2), RD is 80 mg/m(2) and DLT is Grade 3 leukocytopenia. The average serum PTX concentrations remained in optimal range except for all 3 of level V patients. In all cohorts, the PTX concentrations in the ascites were approximately 1000 folds higher than those in serum for 48 hours after the infusion.. MTD and RD were PTX 90 mg/m(2), 80 mg/m(2), respectively. These findings were supported by pharmocokinetics of PTX.

Topics: Adenocarcinoma; Aged; Antineoplastic Agents, Phytogenic; Ascitic Fluid; Drug Combinations; Female; Humans; Infusions, Parenteral; Male; Maximum Tolerated Dose; Middle Aged; Oxonic Acid; Paclitaxel; Peritoneal Neoplasms; Stomach Neoplasms; Tegafur

The pharmacokinetics of irinotecan vary markedly between individuals. This study sought to compare tailored irinotecan and S-1 therapy with S-1 monotherapy for the treatment of patients with advanced/recurrent gastric cancer. Patients with advanced/recurrent gastric cancer were randomized to receive tailored irinotecan and S-1 (arm A) therapy or S-1 therapy alone (arm B). Arm A received S-1 (80-120 mg/m(2)/day) for 14 days, with irinotecan on days 1 and 15. The initial irinotecan dose of 75 mg/m(2) (level 0) was adjusted for toxicity during an earlier course. In arm B, S-1 (80-120 mg/day) was administered alone for 28 days, followed by 14 days without therapy. Ninety-five patients were randomized (48 patients to arm A and 47 patients to arm B). The response rate of the primary tumor (Japanese criteria) was 25.0% in arm A (12 of 48 patients) and 14.9% in arm B (seven of 47 patients), whereas the response rates according to Response Evaluation Criteria In Solid Tumors were 27.8% (10 of 36) versus 21.9% (seven of 32). Hematological toxicity, anorexia, and diarrhea were significantly more common in arm A, but both arms had similar grades 3-4 toxicities. These findings suggest the usefulness of tailored irinotecan and S-1 therapy for gastric cancer.

Topics: Adult; Aged; Ambulatory Care; Antimetabolites, Antineoplastic; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Blood Cell Count; Camptothecin; Dose-Response Relationship, Drug; Drug Combinations; Female; Humans; Irinotecan; Male; Middle Aged; Neoplasm Recurrence, Local; Oxonic Acid; Stomach Neoplasms; Tegafur; Treatment Outcome; Young Adult

The purpose of this study was to compare 2 weekly docetaxel-based regimens as first-line treatments for advanced gastric cancer and to investigate the expression of secreted protein acidic and rich in cysteine (SPARC) and its abilities to predict treatment-related clinical outcomes.. Patients were randomly selected to receive 3 weekly cycles of docetaxel (35 mg/m(2) on days 1 and 8) plus S-1 (35 mg/m(2) each twice daily on days 1-14) (DS), or docetaxel plus cisplatin (35 mg/m(2) each on days 1 and 8) (DC). Endpoints included overall response rate (primary), survival, toxicity, and quality of life (secondary). SPARC expression in prechemotherapy specimens of primary gastric tumors was evaluated via immunohistochemical analysis.. Eighty patients were enrolled in the study. Confirmed overall response rates were 46% (95% confidence interval, 30%-62%) for DS and 24% (95% confidence interval, 11%-38%) for DC via intent-to-treat analysis. Median progression-free survival was 7.3 and 4.9 months and overall survival was 16.0 and 8.3 months for DS and DC, respectively. The most common grade ≥ 3 toxicity was neutropenia. Grade ≥ 3 mucositis (18%) and hand-foot syndrome (8%) were the toxicities most associated with DS, whereas anorexia (20%) and lethargy (20%) were more common with DC. High SPARC expression was related to early progression (hazard ratio, 3.67; P = .042) and poor overall survival (hazard ratio, 2.01; P = .010) in docetaxel chemotherapy on multivariate analysis.. The outcomes in this study favored DS over DC for further phase 3 study. The findings suggest that split-dose weekly docetaxel alleviates hematological toxicity without compromising efficacy, and that SPARC expression may help individualize therapy in advanced gastric cancer.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Docetaxel; Drug Administration Schedule; Drug Combinations; Female; Humans; Male; Middle Aged; Osteonectin; Oxonic Acid; Stomach Neoplasms; Taxoids; Tegafur

To carry out a phase II multi-center study on the efficacy and safety of triple combination therapy with paclitaxel, S-1, and cisplatin in patients with unresectable/metastatic gastric cancer.. A total of 63 patients from 8 institutions were included in this study. Paclitaxel (160 mg/m²) was administered by infusion for 3 h on the first day. S-1 (70 mg/m²/day) was administered orally for 14 consecutive days from the first day. Cisplatin (60 mg/m²) was administered intravenously over 24 h on day 14 of every 28-day cycle.. All 63 patients were assessed for clinical efficacy and safety. A total of 259 cycles of treatment were administered (median 4, range 1-10). Grade 3-4 toxicities included neutropenia in 30.2%, thrombocytopenia in 12.7%, and anemia in 11.1%. There was no grade 3-4 non-hematological toxicity or treatment-related death. Complete response was observed in 6 patients and partial response in 34 patients. The overall response rate was 63.5%. The median progression-free survival and response duration were 8.0 and 8.8 months, respectively, and median survival time was 15 months.. Triple combination therapy with paclitaxel, S-1, and cisplatin showed promising safety and efficacy profiles with the potential to become a standard regimen for unresectable/metastatic gastric cancer.

Topics: Adult; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Disease-Free Survival; Drug Combinations; Female; Humans; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Neutropenia; Oxonic Acid; Paclitaxel; Stomach Neoplasms; Survival Rate; Tegafur; Thrombocytopenia; Treatment Outcome

The aim of this prospective study was to evaluate the feasibility and safety of adjuvant S-1 plus docetaxel in patients with stage III gastric cancer.. We enrolled 53 patients with pathological stage III gastric cancer who underwent D2 gastrectomy. They received oral S-1 (80 mg/m(2)/day) administration for 2 consecutive weeks and intravenous docetaxel (40 mg/m(2)) on day 1, repeated every 3 weeks (1 cycle). The treatment was started within 45 days after surgery and repeated for 4 cycles, followed by S-1 monotherapy (4 weeks on, 2 weeks off) until 1 year after surgery. The feasibility of the 4 cycles of chemotherapy, followed by S-1 administration, was evaluated.. A total of 42 patients (79.2%, 95% CI 65.9-82.9) tolerated the planned 4 cycles of treatment with S-1 and docetaxel, and 34 patients (64.2%, 95% CI 49.8-76.9) completed subsequent S-1 monotherapy for 1 year. Grade 4 neutropenia was observed in 28% and grade 3 febrile neutropenia in 9% of the patients, while grade 3 nonhematological toxicities were relatively low.. Adjuvant S-1 plus docetaxel therapy is feasible and has only moderate toxicity in stage III gastric cancer patients. We believe that this regimen will be a candidate for future phase III trials seeking the optimal adjuvant chemotherapy for stage III gastric cancer patients.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Docetaxel; Drug Administration Schedule; Drug Combinations; Feasibility Studies; Female; Gastrectomy; Humans; Infusions, Intravenous; Lymph Node Excision; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Prospective Studies; Stomach Neoplasms; Taxoids; Tegafur; Treatment Outcome

The prognosis for advanced gastric cancer is poor, with surgery as the only treatment for resectable advanced gastric cancer. Therefore, treatment options that might improve the prognosis are needed. To that end, neoadjuvant chemoradiotherapy with S-1 and cisplatin (CDDP) was investigated.. The chemotherapy schedule included one cycle repeated after 6 weeks. S-1 was administered orally every day on days 1-21 and CDDP was infused on days 1, 8 and 15. Radiation therapy was started concurrently with chemotherapy and repeated daily on days 1-5, 8-12, 15-19, and 22-26.. A total of 10 patients were recruited. The first four patients were entered into level 1 (CDDP, 20 mg/m²). The next six patients were entered into level 0 (15 mg/m²), because of dose-limiting toxicity (delaying the second course of chemotherapy in two patients) that had been observed at level 1. The maximum tolerated dose (MTD) of CDDP was 20 mg/m². Seven patients underwent surgery and all had an R0 (no residual tumor) resection without surgical complications.. Neoadjuvant chemoradiotherapy with S-1 and CDDP may cause surgery to be delayed, but shows promise for resectable advanced gastric cancer.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cisplatin; Drug Combinations; Female; Humans; Male; Middle Aged; Oxonic Acid; Stomach Neoplasms; Tegafur

The first planned interim analysis (median follow-up, 3 years) of the Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer confirmed that the oral fluoropyrimidine derivative S-1 significantly improved overall survival, the primary end point. The results were therefore opened at the recommendation of an independent data and safety monitoring committee. We report 5-year follow-up data on patients enrolled onto the ACTS-GC study.. Patients with histologically confirmed stage II or III gastric cancer who underwent gastrectomy with D2 lymphadenectomy were randomly assigned to receive S-1 after surgery or surgery only. S-1 (80 to 120 mg per day) was given for 4 weeks, followed by 2 weeks of rest. This 6-week cycle was repeated for 1 year. The primary end point was overall survival, and the secondary end points were relapse-free survival and safety.. The overall survival rate at 5 years was 71.7% in the S-1 group and 61.1% in the surgery-only group (hazard ratio [HR], 0.669; 95% CI, 0.540 to 0.828). The relapse-free survival rate at 5 years was 65.4% in the S-1 group and 53.1% in the surgery-only group (HR, 0.653; 95% CI, 0.537 to 0.793). Subgroup analyses according to principal demographic factors such as sex, age, disease stage, and histologic type showed no interaction between treatment and any characteristic.. On the basis of 5-year follow-up data, postoperative adjuvant therapy with S-1 was confirmed to improve overall survival and relapse-free survival in patients with stage II or III gastric cancer who had undergone D2 gastrectomy.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Drug Combinations; Gastrectomy; Humans; Middle Aged; Neoplasm Staging; Oxonic Acid; Stomach Neoplasms; Tegafur

This is a randomized phase II trial to evaluate non-inferiority of progression-free surviva(l PFS) by comparing S-1 and S-1/PSK for advanced or recurrent gastric cancer. Sample size was calculated to be 120. However, the trial was terminated because of slow accrual. This exploratory analysis was done by collecting the minimum data.. Only 8 patients were enrolled. Four patients were randomly assigned to S-1 and the others to S-1/PSK. Performance status was 0 in all 8 patients. Median age was 64. Median overall survival was 13.7 months in all 8 patients, 8 . 9 months in S-1 group, and 13 . 7 months in S-1/PSK group.. When considering PS 0 in 8 patients enrolled, an overall survival was comparable to that observed in S-1 group of other phase III trials. Standard chemotherapy for advanced gastric cancer was changed to S-1/CDDP by SPIRITS phase III trial which was presented just after this trial was initiated, which would be a major cause of slow accrual. When conducting phase III trial, we should carefully determine design and standard arm by considering on-going phase III trial.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Female; Humans; Male; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Proteoglycans; Recurrence; Stomach Neoplasms; Tegafur

To evaluate the effects and safety of combination chemotherapy with oxaliplatin (L-OHP) and S-1 (SOX regimen) in older patients with advanced gastric cardiac adenocarcinoma (GCA).. Seventy patients with advanced GCA were classified according to age into an older group (≥ 75 years) and a control group (< 75 years). The SOX regimen was administered to the two groups as follows: S-1 (40 mg/m² po bid) on days 1 to 14 followed by a 7-d off period, plus L-OHP (65 mg/m² iv) for 2 h on days 1 and 8 of a 21-d cycle. This regimen was repeated for four to six cycles. Response and swallow statuses were evaluated after two cycles (6 wk). Effects and toxicity were evaluated four weeks after chemotherapy was completed.. The response rate was 65.6% (21/32) in the older group and 68.4% (26/38) in the control group (χ² = 0.062 and P = 0.804). Improvement in swallowing was 78.1% (25/32) in the older group and 76.3% (29/38) in the control group (χ² = 0.032 and P = 0.857). Efficacy was 68.8% (22/32) in the older group and 65.8% (25/38) in the control group (χ² = 0.069 and P = 0.793). Toxicities were reversible and similar in both groups (P > 0.05).. The SOX regimen is an effective, safe and well-tolerated regimen for older patients with advanced GCA.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Agents; Drug Combinations; Female; Humans; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Stomach Neoplasms; Tegafur; Treatment Outcome

We aimed to determine the maximum-tolerated dose (MTD) of S-1 when given with oxaliplatin, to evaluate S-1 pharmacokinetics, and to determine the efficacy and safety of this regimen as a first-line treatment for advanced gastric cancer (AGC).. Oxaliplatin was fixed at a dose of 130 mg/m2 on day 1 (D1). S-1 was administered from D1 to D14 of a 3-week cycle, and escalated by 10 mg/m2 per day from 70 mg/m2 per day up to 100 mg/m2 per day. Pharmacokinetic analyses were performed following a single dose of S-1 on D-5 and D1 of the first cycle.. In phase I (n=18), MTD was not defined. In phase II (n=47) with the planned maximum dose, partial response was achieved in 26 patients (55.3%) and stable disease in 14 patients (29.8%). The median time to progression was 6.6 months (95% CI 4.0-9.2 months) and the median overall survival was 12.5 months (95% CI 9.2-15.9 months). Frequent grade 3/4 toxicities included thrombocytopenia (39%), neutropenia (28%), anemia (17%), and leukopenia (13%). There was one grade 5 febrile neutropenia during the first cycle.. The pharmacokinetics of S-1 was not influenced by oxaliplatin. S-1/Oxaliplatin combination therapy is highly active against AGC and has a favorable toxicity profile.

Topics: Adult; Anemia; Antineoplastic Combined Chemotherapy Protocols; Area Under Curve; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Female; Humans; Leukopenia; Male; Metabolic Clearance Rate; Middle Aged; Nausea; Neutropenia; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Stomach Neoplasms; Survival Analysis; Tegafur; Thrombocytopenia; Treatment Outcome; Vomiting

A phase III trial of S-1 plus cisplatin (SP) versus S-1 alone, for first-line treatment of advanced gastric cancer (SPIRITS trial), has shown that overall survival was better in patients treated with SP than with S-1 alone. In the present retrospective biomarker study, we aimed to develop a methodology to identify the patients with advanced gastric cancer who would respond better to S-1 alone than SP. We studied 120 patients who received S-1 alone or SP for first-line chemotherapy for advanced gastric cancer, and quantitatively evaluated mRNA levels of thymidylate synthase (TS), thymidine phosphorylase (TP), orotate phosphoribosyltransferase (OPRT), dihydropyrimidine dehydrogenase, vascular endothelial growth factor-A, and epidermal growth factor receptor in paraffin-embedded specimens of primary tumors. Multivariate survival analysis in patients who received S-1 monotherapy (66 patients) demonstrated that low TP expression (hazard ratio: 2.55 (95% CI: (1.33 to 4.89)), low TS (2.71 (1.36 to 5.37)), and high OPRT (0.33 (0.13 to 0.86)) were significant predictors of long overall survival. In patients with lower expression of both TP and TS (n = 23) than their cutoff values, the S-1 alone group (n = 15) had longer overall survival than the SP group (n = 8; median overall survival, 18.2 months vs. 9.4 months), whereas the frequency of overall adverse events in the S-1 alone group tended to be lower than that in SP group. Our results suggest that these biomarkers are useful for selection of patients with advanced gastric cancer in whom treatment with S-1 alone will yield survival benefit.

Topics: Adenocarcinoma; Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Enzymes; Female; Fluorouracil; Humans; Male; Middle Aged; Oxonic Acid; Stomach Neoplasms; Survival Analysis; Tegafur; Treatment Outcome

A phase II study to evaluate the efficacy and tolerability of weekly i.v. and i.p. paclitaxel (PTX) combined with S-1 was carried out in gastric cancer patients with peritoneal metastasis.. Gastric cancer patients with peritoneal dissemination and/or cancer cells on peritoneal cytology were enrolled. PTX was administered i.v. at 50 mg/m(2) and i.p. at 20 mg/m(2) on days 1 and 8. S-1 was administered at 80 mg/m(2)/day for 14 consecutive days, followed by 7 days rest. The primary end point was the 1-year overall survival (OS) rate. Secondary end points were the response rate, efficacy against malignant ascites and safety.. Forty patients were enrolled, including 21 with primary tumors with peritoneal dissemination, 13 with peritoneal recurrence and six with positive peritoneal cytology only. The median number of courses was 7 (range 1-23). The 1-year OS rate was 78% (95% confidence interval 65% to 90%). The overall response rate was 56% in 18 patients with target lesions. Malignant ascites disappeared or decreased in 13 of 21 (62%) patients. The frequent grade 3/4 toxic effects included neutropenia (38%), leukopenia (18%) and anemia (10%).. Combination chemotherapy of i.v. and i.p. PTX with S-1 is well tolerated and active in gastric cancer patients with peritoneal metastasis.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Female; Humans; Injections, Intraperitoneal; Kaplan-Meier Estimate; Male; Middle Aged; Oxonic Acid; Paclitaxel; Peritoneal Neoplasms; Stomach Neoplasms; Tegafur

This prospective multicenter phase II study was carried out to investigate the efficacy, safety and pharmacokinetics of S-1 monotherapy in elderly patients over 75 years of age, with unresectable advanced or recurrent gastric cancer.. Patients had measurable or evaluable lesions according to the Japanese Classification of Gastric Carcinoma. S-1 (25-60 mg determined by the body surface area and creatinine clearance) was given orally, twice daily. A course of treatment consisted of 4-week administration followed by a 2-week rest period, and the patients received repeated courses.. Thirty-three patients were enrolled. Pharmacokinetics of S-1 was studied in six patients, and the maximum plasma concentrations of respective metabolites after S-1 administration were found to be similar to those reported for younger cancer patients. The overall response rate in 33 patients was 21.2% (95% CI, 10.7-37.8%), and median progression-free survival was 3.9 months, with a median overall survival of 15.7 months. Frequently noted adverse events include leukopenia, neutropenia, anemia, anorexia, and fatigue. As for serious adverse events, relatively higher frequencies of anemia (9%) and anorexia (12%) of grade 3 severity were found, but there were no grade 4 episodes.. The results suggest that S-1 monotherapy is safe and useful for elderly patients with unresectable advanced or recurrent gastric cancer when the dose is selected with caution, taking into account renal function.

Topics: Aged; Aged, 80 and over; Anorexia; Antimetabolites, Antineoplastic; Drug Combinations; Fatigue; Female; Humans; Leukopenia; Male; Metabolic Clearance Rate; Neutropenia; Oxonic Acid; Prospective Studies; Stomach Neoplasms; Survival Analysis; Tegafur; Treatment Outcome

The efficacy and safety of oxaliplatin combined with S-1 (SOX regimen) for unresectable advanced or recurrent gastric cancer were investigated.. Oxaliplatin was administered i.v. (100 mg/m(2)) on day 1, while S-1 was administered orally (80 mg/m(2)/day, b.i.d.) for 14 days followed by a 7-day rest. This schedule was repeated every 3 weeks.. Among 55 patients enrolled, one patient received oxaliplatin for the other study, and three patients were considered unsuitable against the inclusion criteria. Accordingly, 51 patients were assessable for efficacy. The response rate was 59%, and the disease control rate was 84%. The median progression-free survival time was 6.5 months, the 1-year survival rate was 71%, and the median survival time was 16.5 months. In 54 patients assessed for safety, the major grade 3/4 toxic effects were neutropenia (22%), thrombocytopenia (13%), anemia (9%), anorexia (6%), fatigue (6%), and sensory neuropathy (4%).. These findings indicate that SOX regimen with oxaliplatin at a dose of 100 mg/m(2) is feasible and shows promising efficacy against advanced gastric cancer.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Female; Follow-Up Studies; Humans; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Recurrence, Local; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Peritoneal Neoplasms; Stomach Neoplasms; Survival Rate; Tegafur; Treatment Outcome

In this study, we compared the pharmacokinetic profiles of 5-fluorouracil (5-FU), tegafur, 5-chloro-2,4-dihydroxypyridine (CDHP) and potassium oxonate (Oxo) after administration of S-1 at 35 or 40 mg/m(2) bid for 28 consecutive days, in Cycles 1 and 3, in patients with advanced gastric cancer.. Three patients were enrolled for each dosage. S-1 dosage was assigned based on body surface area (BSA), which is different from the Japanese dosing system. The median daily dose per BSA was 76 mg/m(2), ranging from 70 to 88 mg/m(2).. Plasma levels of 5-FU, tegafur, CDHP and Oxo at 4 h post-dose reached steady-state on day 8. The estimated steady-state level was dependent on S-1 dosage. There were no intercyclic differences of pre-dose and 4 h post-dose levels between Cycles 1 and 3, implying no cumulative effect of S-1 was shown probably due to 2-week drug-resting period. Pharmacokinetic profiles on day 28 were similar to previous Japanese report. C(max) and AUC(0-48 h) values of each S-1 component increased depending on S-1 dosage. Pharmacokinetic parameters were not correlated with tumor response or toxicity.. We suggest that these pharmacokinetic profiles of Asian population could provide a basis for schedule optimization and for additional studies on interaction with other antitumor drugs.

Topics: Adenocarcinoma; Adult; Aged; Antimetabolites, Antineoplastic; Dose-Response Relationship, Drug; Drug Combinations; Female; Humans; Korea; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Stomach Neoplasms; Tegafur; Treatment Outcome

We evaluated the activity and toxicity of docetaxel, cisplatin, and S-1 (DCS) combination chemotherapy in patients with unresectable metastatic gastric cancer.. Patients with histologically proven, unresectable metastatic gastric adenocarcinoma, performance status (PS) 0-2, and no prior chemotherapy were eligible. Patients received oral S-1 (40 mg/m(2) b.i.d.) on days 1-14 and intravenous cisplatin (60 mg/m(2)) and docetaxel (60 mg/m(2)) on day 8 every 3 weeks.. Thirty-four patients were enrolled between March 2005 and April 2007. Three patients were considered ineligible and did not receive the DSC therapy. Clinical characteristics were as follows: median age, 63 years (range, 44-77); PS, 0/1/2: 23/8/0; women/men, 8/23; and well-differentiated/undifferentiated adenocarcinoma, 10/21. The objective response rate was 87.1% with 1 complete response (3.2%) and 26 partial responses (83.9%) in 31 assessable patients. Four had stable disease (12.9%) but none had progressive disease. Of these 27 responders, 8 (25.8%) achieved downstaging and 7 (22.6%) underwent curative surgery. The median survival time and progression-free survival were 687 days [confidence interval (95% CI), 600.0-1,138.1] and 226 days (95% CI, 182.5-379.3), respectively. Most common grade 3/4 hematologic toxicity was neutropenia (77.4%). Most common grade 3 nonhematologic toxicities included anorexia (35.5%) and nausea (32.3%). All treatment-related toxicities resolved, and no toxic deaths were observed.. DCS combination chemotherapy is highly active against unresectable metastatic gastric cancer and can be given safely with proper management of adverse events. Further studies of this combination are warranted.

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Docetaxel; Dose-Response Relationship, Drug; Drug Combinations; Female; Granulocyte Colony-Stimulating Factor; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Metastasis; Neutropenia; Oxonic Acid; Stomach Neoplasms; Survival Analysis; Taxoids; Tegafur; Treatment Outcome

Combination chemotherapy of S-1 and cisplatin has shown promising activity against advanced gastric cancer, but the schedules and dose intensities of S-1 and cisplatin have not been consistent in several clinical trials. We investigated the efficacy and toxicity of 3-weekly S-1/cisplatin chemotherapy as first-line treatment in metastatic or relapsed gastric cancer (MRGC). Forty-six patients with MRGC were prospectively enrolled. S-1 (80 mg/m(2)/day; days 1-14) and cisplatin (60 mg/m(2); day 1) were administrated every 3 weeks. Among 46 patients who received chemotherapy, one achieved a complete response and 21 achieved a partial response, resulting in an overall response rate (RR) of 48%. Thirteen patients (28%) had stable disease and eight patients (17%) had progressive disease. After a median follow-up duration of 48.3 weeks, the median progression-free survival (PFS) and overall survival (OS) were 21.1 weeks and 68.3 weeks, respectively. Patients with good Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1 had prolonged PFS and OS compared with patients with ECOG PS of 2. Common hematologic toxicities were anemia (93%), leucopenia (61%), and neutropenia (61%). However, grade 3/4 anemia, leucopenia, and neutropenia developed in only 11, 9, and 24% of patients, respectively. Grade 3/4 non-hematologic toxicities included anorexia (22%), fatigue (13%), nausea (7%), and diarrhea (7%). No treatment-related mortality occurred. Three-weekly S-1/cisplatin chemotherapy was active and well-tolerated in MRGC patients.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Disease-Free Survival; Drug Administration Schedule; Drug Combinations; Fatigue; Follow-Up Studies; Gastrointestinal Diseases; Hematologic Diseases; Humans; Kaplan-Meier Estimate; Middle Aged; Oxonic Acid; Proportional Hazards Models; Prospective Studies; Stomach Neoplasms; Tegafur; Treatment Outcome

Patients with advanced gastric or gastroesophageal adenocarcinoma need more efficacious and safer treatments than established today. S-1, a contemporary oral fluoropyrimidine, can provide that advantage.. This study was conducted in 24 countries and 146 centers. One thousand fifty-three patients were stratified (center, number of metastatic sites, prior adjuvant therapy, and measurable cancer) and randomly assigned. Patients received either S-1 at 50 mg/m(2) divided in two daily doses for 21 days and cisplatin at 75 mg/m(2) intravenously on day 1, repeated every 28 days (527 patients) or infusional fluorouracil at 1,000 mg/m(2)/24 hours for 120 hours and cisplatin at 100 mg/m(2) intravenously on day 1, repeated every 28 days (526 patients). The primary end point was superiority in overall survival (OS) from cisplatin/S-1 compared with cisplatin/infusional fluorouracil in patients with advanced, untreated gastric, or gastroesophageal adenocarcinoma. The secondary end points were response rate, progression-free survival, time to treatment failure, and safety.. The median OS was 8.6 months in the cisplatin/S-1 arm and 7.9 months in the cisplatin/infusional fluorouracil arm (HR, 0.92; 95% CI, 0.80 to 1.05; P = .20). Significant safety advantages were observed in the cisplatin/S-1 arm compared with the cisplatin/infusional fluorouracil arm for the rates of grade 3/4 neutropenia (32.3% v 63.6%), complicated neutropenia (5.0% v 14.4%), stomatitis (1.3% v 13.6%), hypokalemia (3.6% v 10.8%), and treatment-related deaths (2.5% v 4.9%; P < .05).. Cisplatin/S-1 did not prolong OS of patients with advanced gastric or gastroesophageal adenocarcinoma compared with cisplatin/infusional fluorouracil, but it did result in a significantly improved safety profile.

Topics: Adenocarcinoma; Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Esophageal Neoplasms; Female; Fluorouracil; Humans; Male; Middle Aged; Oxonic Acid; Stomach Neoplasms; Survival Analysis; Tegafur; Treatment Outcome; Young Adult

This randomized Phase II trial compares neoadjuvant chemotherapy of two or four courses of S-1 (1 M tegafur-0.4 M gimestat-1 M ostat potassium) plus cisplatin or paclitaxel plus cisplatin by a two-by-two factorial design for patients with macroscopically resectable locally advanced gastric cancer. The primary endpoint is the 3-year overall survival. The sample size is 60-80 in a total for two hypotheses of the superiority of four courses to two courses and the superiority of paclitaxel plus cisplatin to S-1 plus cisplatin. In both arms, S-1 is strongly recommended post-operatively for at least 6 months but no adjuvant chemotherapy is permitted other than S-1 until recurrence. This trial could appraise more suitable cycles and regimen as neoadjuvant chemotherapy for gastric cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Digestive System Surgical Procedures; Drug Combinations; Humans; Neoadjuvant Therapy; Oxonic Acid; Paclitaxel; Stomach Neoplasms; Tegafur

We have previously reported the molecular detection of peritoneal micrometastases in patients with gastric cancer by quantifying carcinoembryonic antigen (CEA) mRNA in the peritoneal washes. Patients with CEA mRNA exceeding a cutoff value have a significant risk for developing peritoneal carcinomatosis, but optimal treatment for this population remains unknown.. CEA mRNA (+) patients with gastric cancer were treated postoperatively with S-1 monotherapy. Overall survival, the primary endpoint of this phase II trial, was compared with the historical control, which is comprised of CEA mRNA (+) patients who were not given postoperative chemotherapy.. A total of 32 patients with CEA mRNA (+) gastric cancer were enrolled. Twelve patients (37.5%) relapsed; ten showed peritoneal relapse. Three-year survival was similar between the study population and the historical control (67.3% vs. 67.1%, respectively).. S-1 monotherapy, which significantly reduced risk for recurrence in stage II/III gastric carcinoma in another phase III trial, seems not to be as effective in eradicating free cancer cells in the abdominal cavity.

Topics: Adenocarcinoma; Antimetabolites, Antineoplastic; Carcinoembryonic Antigen; Chemotherapy, Adjuvant; Disease-Free Survival; Drug Combinations; Female; Humans; Kaplan-Meier Estimate; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Peritoneal Lavage; Peritoneal Neoplasms; Reverse Transcriptase Polymerase Chain Reaction; Risk Assessment; Stomach Neoplasms; Tegafur

Gastric cancer with cancer cells on peritoneal cytology has very poor prognosis because of the existence of simultaneous peritoneal metastasis. Here we performed a dose-escalation study of intraperitoneal docetaxel (DTX) combined with S-1 to determine the maximum-tolerated dose (MTD) and recommended dose (RD) in gastric cancer with peritoneal dissemination.. Twelve gastric cancer patients with positive cytology were enrolled in this study. Peritoneal lavage specimens were obtained under local anesthesia or staging laparoscopy before treatment and the combination chemotherapy was applied in patients with positive cytology. DTX was administered on day 1 intraperitoneally with initial dose of 40 mg/m(2), stepped up to 50 or 60 mg/m(2). S-1 was administered at a fixed dose of 80 mg/m(2)/day on days 1-14, followed by 7 days of rest. After two cycles of the combination chemotherapy, staging laparoscopy was performed to evaluate the effect of the chemotherapy. Simultaneous gastrectomy was performed in cases without peritoneal deposits at staging laparoscopy.. The MTD of intraperitoneal DTX was not determined and the RD was defined as 60 mg/m(2) because dose-limiting toxicity occurred in only one patient at level II (DTX: 50 mg/m(2)). Out of twelve patients given the combination chemotherapy, nine had cytologically negative peritoneal lavage and had no peritoneal metastases at surgery after chemotherapy.. The combined chemotherapy of S-1 plus intraperitoneal DTX was revealed to be safe and may be effective for gastric cancer with peritoneal dissemination.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Docetaxel; Dose-Response Relationship, Drug; Drug Combinations; Feasibility Studies; Female; Humans; Infusions, Parenteral; Male; Middle Aged; Oxonic Acid; Peritoneal Neoplasms; Remission Induction; Stomach Neoplasms; Taxoids; Tegafur

Clinically serosa-positive (T3-4) gastric cancer has a poor prognosis. This phase II trial explored the feasibility and safety of preoperative chemotherapy followed by D2 or D3 gastrectomy in this type of gastric cancer.. Patients with T3-4 gastric cancer received one course of S-1 (80mg/m(2) daily for 3 weeks) and cisplatin (60mg/m(2) on day 8) chemotherapy and then underwent D2 or D3 gastrectomy with curative intent. Primary endpoint was toxicities.. Of 50 patients enrolled, 49 were eligible and received the treatment protocol. Chemotherapy-related toxicities were mild; grade 3 neutropenia in 2 patients, anorexia in 3, and nausea in 2, and no grade 4 toxicities. Clinical response was achieved in 13 of 34 evaluable patients. Of the 49 patients, 39 underwent D2 or D3 dissection. There was no surgical mortality. Operative morbidity occurred in 5 of 49 patients, including pancreatic fistula in 1 and abdominal abscess in 2.. This multi-modality treatment seems to be feasible and safe for T3-4 gastric cancer.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Drug Combinations; Female; Gastrectomy; Humans; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Preoperative Care; Stomach Neoplasms; Tegafur; Treatment Outcome

Irinotecan and S-1, an oral fluoropyrimidine composed of tegafur, gimeracil, and oteracil potassium, have demonstrated antitumor activity against advanced gastric cancer. We performed a phase 1/2 study to determine the recommended dose, antitumor activity, and safety of a combination of S-1 and irinotecan in patients with advanced gastric cancer.. Patients with previously untreated advanced gastric cancer were enrolled. Patients received irinotecan intravenously on days 1 and 15 plus oral S-1 twice daily on days 1-14 of a 28-day cycle. In the phase 1 part, the dose of irinotecan was escalated from 100 mg/m(2) to 125 mg/m(2) and then to 150 mg/m(2).. A total of 24 patients were enrolled. Overall, the median number of treatment cycles per patient was 5.9, and 92% of the patients completed at least two cycles. The overall response rate was 54.2% (13 of 24). The response rates in differentiated and undifferentiated cancer were 56.3% (nine of 16) and 50.0% (four of eight), respectively. Median survival time was 581 days. The maximum tolerated dose of irinotecan was not reached at the highest level. However, grade 4 neutropenia occurred at 125 mg/m(2). We concluded that the recommended dose of irinotecan for the present regimen was 125 mg/m(2).. Treatment with S-1+irinotecan is considered effective in patients with advanced gastric cancer who have not previously received chemotherapy. A combination of irinotecan and S-1 was well tolerated in patients with advanced gastric cancer and could be given on an outpatient basis.

Topics: Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Drug Combinations; Female; Humans; Irinotecan; Male; Middle Aged; Oxonic Acid; Stomach Neoplasms; Tegafur; Young Adult

S-1 plus cisplatin is standard treatment for advanced gastric cancer in Japan. Triplet therapy with docetaxel, cisplatin and fluoropyrimidine showed a survival benefit over doublet therapy, but was associated with substantial toxicities. We investigated the maximum tolerated dose of combination chemotherapy with divided-dose docetaxel added to standard-dose S-1 plus cisplatin in advanced gastric cancer patients.. Patients with advanced gastric cancer, naive to chemotherapy or not refractory to fluoropyrimidine, were enrolled. Fixed doses of S-1 (40 mg/m(2) twice daily for 3 weeks) and cisplatin (60 mg/m(2) on day 1) were administered with increasing docetaxel dose levels of 20 mg/m(2) (dose level 1), 25 mg/m(2) (dose level 2) and 30 mg/m(2) (dose level 3) on days 1, 8 and 15, or 40 mg/m(2) (dose level 4) on days 1 and 15 of a 5-week cycle. Treatment cycles were repeated until disease progression, patient's refusal or unacceptable toxicity occurred.. Fifteen patients were enrolled. During the first cycle, no dose-limiting toxicity was observed at dose levels 1 and 2. At dose level 3, grade 3 febrile neutropenia was seen in one patient. At dose level 4, grade 3 infection and grade 3 abdominal pain were observed. Thus, dose level 4 was determined to be the maximum tolerated dose. The response rate was 54% (7/13), and median progression-free survival and overall survival were 243 and 383 days, respectively.. The recommended dose of docetaxel added to standard-dose S-1 (80 mg/m(2) days 1-21) plus cisplatin (60 mg/m(2) day 1) was 40 mg/m(2) on days 1 and 15 of a 5-week cycle.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Docetaxel; Drug Combinations; Female; Humans; Japan; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Male; Maximum Tolerated Dose; Middle Aged; Oxonic Acid; Peritoneal Neoplasms; Stomach Neoplasms; Survival Rate; Taxoids; Tegafur; Treatment Outcome

A multicenter phase II study was conducted to evaluate the efficacy and safety of a combination regimen of weekly paclitaxel plus S-1 in patients with advanced gastric cancer.. Patients with previously untreated metastatic or recurrent gastric cancer received intravenous paclitaxel 50 mg/m(2) on days 1, 8, and 15, plus oral S-1 40 mg/m(2) b.i.d. on days 1 to 14 followed by 2 weeks off, in a 28-day cycle.. A total of 54 patients were registered. All of them had measurable disease and were determined to be eligible for the present study. Two complete responses and 23 partial responses were confirmed, giving an overall response rate of 46.3%. At a final follow up of 3 years, the median progression-free survival and median overall survival were 6.0 and 14.3 months, respectively. Grade 3 neutropenia occurred in 14 patients, and grade 4 in 1 patient (total, 27.8%). The most serious nonhematological toxicity was diarrhea, where grade 3 occurred in 5 patients (9.3%). There were no treatment-related deaths.. A combination of weekly paclitaxel plus S-1 was found to be well tolerated and effective in patients with advanced gastric cancer. Further investigation with comparative trials is needed for confirmation.

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Antineoplastic Agents, Phytogenic; Confidence Intervals; Disease Progression; Drug Combinations; Female; Humans; Japan; Kaplan-Meier Estimate; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Oxonic Acid; Paclitaxel; Stomach Neoplasms; Tegafur

There is a great need for effective outpatient chemotherapy for advanced gastric cancer in patients with good performance status. The present pilot study evaluated the use of combination chemotherapy with S-1 and fractional CDDP for unresectable-recurrent gastric cancer in an outpatient setting.. A total of 41 patients with unresectable or recurrent gastric cancer were treated with this combination chemotherapy. S-1 was administered orally every day on days 1-28 and CDDP was infused on days 1, 15, and 29.. Thirty-six patients had measurable lesions and 19 patients had partial responses, resulting in an overall response rate of 52.8%. The median survival time was 494 days. There was no grade 4 haematological toxicity, no grade 3 or more non-haematological toxicity, and no treatment-related death.. This combination chemotherapy has no serious toxicities in patients with unresectable and recurrent gastric cancer and can be used effectively in an outpatient setting.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Female; Humans; Male; Middle Aged; Outpatients; Oxonic Acid; Pilot Projects; Stomach Neoplasms; Tegafur; Young Adult

Although S-1 is effective against advanced gastric cancer (AGC), its efficacy in elderly patients has not yet been investigated sufficiently. We assessed the efficacy and safety of S-1 monotherapy in elderly patients with AGC.. We conducted a retrospective review of the data of 153 patients with unresectable/recurrent gastric adenocarcinoma who received S-1 monotherapy as first-line chemotherapy at our institution. S-1 was administered orally twice daily at the dose of 40 mg/m², on days 1-28, every 6 weeks. We categorized the patients into three groups, the young (≤65 years old), the middle-aged (66-75 years old), and the elderly (≥76 years old); and the drug toxicity, objective responses, progression-free survivals, and overall survivals were compared among the three groups.. The incidence of leukopenia of grade 3 or greater in the three groups was 7%, 5%, and 13%, and that of anemia was 9%, 18%, and 27%, respectively. In regard to nonhematological toxicities, the incidence of nausea of grade 3 or greater was 3%, 5%, and 13%; that of fatigue was 5%, 11%, and 20%; and that of anorexia was 5%, 6%, and 27%, respectively. As for the treatment efficacy, the objective response rates, median progressionfree survivals, and overall survivals in the young, middle-aged, and elderly groups were 53%, 46%, and 33%; 7.8, 5.6, and 3.9 months; and 16.9, 17.1; and 7.7 months, respectively.. Although S-1 monotherapy showed moderate efficacy in elderly (≥76 years) patients with AGC, patients in this age group showed higher incidences of severe toxicities than the younger patients.

Topics: Adenocarcinoma; Administration, Oral; Age Factors; Aged; Aged, 80 and over; Anemia; Anorexia; Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Drug Administration Schedule; Drug Combinations; Fatigue; Female; Humans; Leukopenia; Male; Middle Aged; Nausea; Neoplasm Recurrence, Local; Oxonic Acid; Retrospective Studies; Stomach Neoplasms; Survival Analysis; Tegafur; Treatment Outcome

The efficacy and the toxicity of oral fluorouracil derivative S-1 plus low-dose cisplatin in unresectable or recurrent gastric cancer were evaluated by a phase II study.. S-1 was administered orally for 28 days following 14 days' rest at 80-120 mg/body/day, depending on body surface area. During administration of S-1, cisplatin was given twice a week at the recommended dose (10 mg/m(2)), which was determined by a phase I study. Data from 34 patients in phase II and 8 patients treated with the recommended dose of cisplatin in phase I were analyzed. The primary endpoint was objective response.. The response rate was 47.1%. The median survival time was 11.0 months and the median progression-free survival was 6.9 months. The grade 3/4 toxicities observed in 10% or more of the treated patients were neutropenia (16.7%), anemia (16.7%) and anorexia (11.9%). The serum concentration of cisplatin was 794 ± 341 ng/ml at day 25 of the first course.. S-1 plus low-dose cisplatin may be a clinically useful regimen for unresectable or recurrent gastric cancer because of its infrequent adverse events in spite of considerable efficacy and its convenience of no hydration and no hospitalization.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Disease-Free Survival; Drug Administration Schedule; Drug Combinations; Female; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Oxonic Acid; Stomach Neoplasms; Tegafur; Treatment Outcome

This study was conducted to evaluate the safety and efficacy of S-1 and paclitaxel combination therapy for patients with advanced gastric cancer.. Eligible patients had previously untreated advanced or relapsed gastric cancer with measurable lesion(s) and an ECOG PS of 0-2. Treatment consisted of S-1 35 mg/m(2) p.o. b.i.d. on days 1-14 followed by a 7-day off plus paclitaxel 70 mg/m(2) i.v. on days 1 and 8 of a 21-day cycle.. Fifty-six patients (M/F = 37/19) were enrolled. The median age was 59 years. The median number of cycles administered was six (range 1-18). Out of the 53 patients evaluated, there was 1 (1.9%) CR, 20 (37.7%) confirmed PRs, 5 (9.4%) unconfirmed PRs, 21 (39.6%) SDs, and 6 (11.3%) PDs. The objective tumor response was 39.6%. The median time to progression was 29 weeks. The median survival was 51 weeks. All 56 patients were assessed for treatment safety. The treatment was well tolerated with grade 3/4 neutropenia in 20%/13%, grade 3 febrile neutropenia in 7%, grade 2/3 diarrhea in 9%/4%, vomiting in 11%/0%, stomatitis in 4%/4%, and neuropathy in 4%/0% of patients.. S-1 and paclitaxel combination treatment is an effective regimen with a favorable toxicity profile in patients with advanced gastric cancer.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Drug Administration Schedule; Drug Combinations; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Oxonic Acid; Paclitaxel; Prospective Studies; Stomach Neoplasms; Tegafur

Anemia is a unique side effect in Korean gastric cancer patients after S-1 monotherapy. We studied gastric cancer patients from a phase II trial of S-1 monotherapy with a 2-week treatment and 1-week rest schedule. Patients from a phase II trial of S-1 monotherapy with a 4-week treatment and 2-week rest were used as a reference group. The patients were categorized into two groups based on the degree of hemoglobin reduction per cycle of S-1: the mild reduction group (MRG DeltaHb/cycle < or =1.0) or severe reduction group (SRG DeltaHb/cycle >1.0). DeltaHb/cycle was calculated from maximum reduction of hemoglobin per one cycle of the treatment. Microarray-CGH was performed using a 17K cDNA microarray containing 15,723 unique genes. We selected genes with copy number variation defined as amplification (log2R/G >0.68) or deletion (log2R/G <-0.68), and a genetic aberration frequency difference of > or =30% between the MRG and the SRG. There were no differences in clinical factors, S-1 treatment-related factors (dose, dose intensity), toxicity, S-1 metabolism-related gene copy numbers (CYP2A6, DPD), or progression-free survival between the MRG and the SRG. Three genes were selected from microarray-CGH and logistic regression model: logit LN(Z) = (1.321) + (1.038 x PTX1) + (0.211 x MYO5A) + (0.516 x ZNF664). In the SRG, all 3 genes showed a trend of higher copy numbers than the MRG. There were no common anemia-related genes identified from different chemotherapy schedule of S-1 monotherapy. The logistics obtained from 3 genes predicted the hemoglobin reduction with an accuracy of 78%. The AUC was 0.744 for the final regression model. The combined copy number changes of the 3 genes can be developed into a biomarker in predicting S-1 treatment-related anemia.

Topics: Adult; Aged; Anemia; Antimetabolites, Antineoplastic; Disease-Free Survival; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Female; Gene Dosage; Hemoglobins; Humans; Male; Middle Aged; Oxonic Acid; Stomach Neoplasms; Survival Rate; Tegafur; Treatment Outcome

We conducted this study to evaluate the efficacy of S-1 combination chemotherapy as second-line treatment for advanced/recurrent gastric cancer that was resistant to S-1 based chemotherapy as first-line treatment.. We evaluated patients included in phase II.III clinical trials, that is SPIRITS trial(S-1 vs CDDP +S-1), GC0301/TOP-002(S-1 vs CPT-11+S-1), OGSG0002(S-1+CPT-11)and OGSG0105(S-1+paclitaxel). Eligibility criteria at first-line included; pathologically proven gastric cancer, adequate bone marrow, hepatic, and renal functions, PS 0-2, no prior therapy, life expectancy estimated > or =12 weeks, age 20-75 years and written informed consent. Endpoints were as follows; )PFS in first-line and second-line, )Time to Second Progression(TSP), 3) OS.. Sixty-six patients were evaluable in this study. We classified these patients into 4 groups according to the protocol. A)S-1 alone in first-line and S-1 combination in second-line(n=7), B)S-1 alone in first-line and other drugs in second-line(n=13), C)S-1 combination in first-line and another S-1 combination in second-line(n=33), D) S-1 combination in first-line and other drugs in second-line(n=13). We compared S-1 combination group(A+C)to other drugs group(B+D)in second-line. In first-line, PFS was 157.5 days in group(A+C)and 130 days in group(B +D)(p=0.2749). In second-line, PFS, TSP and OS were as follows; 72.5, 256.5, 473 days in group(A+C)and 56, 201.5, 398.5 days(PFS; p=0.0806, TSP: p=0.0718, OS: p=0.0204)in group(B+D), respectively. With regards to adverse events, group(A+C)in first-line showed higher frequency in grade 3/4 leukopenia(10%), febrile neutropenia(5%)and grade 3 diarrhea(10%)than group(B+D). In second-line, group(B+D)showed grade 3/4 leukopenia (12%)and neutropenia(8%)than group(A+C). There were no treatment-related deaths.. These results indicate that S-1 combination chemotherapy is efficient as second-line for advanced/recurrent gastric cancer that got resistant to S-1 based chemotherapy as first-line.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Female; Humans; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Recurrence; Salvage Therapy; Stomach Neoplasms; Survival Rate; Tegafur

A dose-escalation study of weekly intraperitoneal paclitaxel (PTX) combined with S-1 and intravenous PTX was performed to determine the maximum-tolerated dose (MTD) and recommended dose (RD) in gastric cancer patients.. Nine gastric cancer patients with peritoneal dissemination and/or cancer cells on peritoneal cytology were enrolled. PTX was administered intravenously on days 1 and 8 at a fixed dose of 50 mg/m(2), and intraperitoneally with an initial dose of 20 mg/m(2), stepped up to 30 or 40 mg/m(2). S-1 was administered at a fixed dose of 80 mg/m(2)/day for 14 consecutive days, followed by 7 days of rest. A pharmacokinetic study of PTX was also performed.. The MTD was determined to be 30 mg/m(2), as 2 of 3 patients developed dose-limiting toxicities, grade 3 febrile neutropenia and diarrhea. Therefore, the RD was determined to be 20 mg/m(2). The intraperitoneal and serum PTX concentration remained effective for over 72 and 48 h, respectively.. Combined chemotherapy of S-1 plus weekly intravenous and intraperitoneal PTX was shown to be a safe regimen that should be further explored in clinical trials.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Female; Humans; Infusions, Intravenous; Injections, Intraperitoneal; Lymphatic Metastasis; Male; Maximum Tolerated Dose; Middle Aged; Neoplasm Staging; Oxonic Acid; Paclitaxel; Peritoneal Neoplasms; Stomach Neoplasms; Tegafur; Tissue Distribution; Treatment Outcome

Patients with gastric cancer who have positive cytologic results for cancer cells in peritoneal washings (CY1) have poor outcomes, even in the absence of other distant metastases. A standard treatment for such patients remains to be established.. We conducted a phase II trial with the 2-year survival rate as the primary endpoint. Patients who had gastric cancer with CY1 status but no other residual disease received postoperative chemotherapy with S-1 (1M tegafur-0.4M gimestat-1M otastat potassium) at a daily dose of 80mg/m(2) for 4 weeks, followed by 2 weeks of rest. This cycle was continued until disease progression or intolerable adverse events. D2 dissection was the recommended surgical procedure; splenectomy could be omitted at the discretion of the surgeon. Accrual of 50 patients was planned, and a 2-year survival rate of more than 36% was needed to exceed the historical control.. Forty-eight patients were enrolled, among whom 47 were assessable for survival and 46 for adverse reactions. Median overall survival was 705 days, and progression-free survival was 376 days. The 2-year survival rate was 47%. Median time to treatment failure was 288 days. Neutropenia was the commonest > or = grade 3 toxicity (6 patients), and anorexia was the most frequent > or = grade 2 non-hematologic toxicity (10 patients).. Gastrectomy followed by S-1 monotherapy resulted in survival that surpassed historical data and can serve as an active control treatment for future trials in patients who have gastric cancer with CY1 status in the Far East.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Disease Progression; Drug Combinations; Female; Gastrectomy; Humans; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Peritoneal Cavity; Pyridines; Stomach Neoplasms; Survival Rate; Tegafur; Treatment Outcome

The prognosis of scirrhous gastric cancer remains poor despite extended surgery or adjuvant or neoadjuvant chemotherapy. A pilot study of S-1 (TS-1; Taiho Pharmaceutical, Tokyo, Japan), an oral 5-fluorouracil derivative, for neoadjuvant chemotherapy unexpectedly showed good response and a promising effect on survival. Therefore, the Japan Clinical Oncology Group conducted a phase II trial to confirm the efficacy of S-1 for neoadjuvant chemotherapy against resectable scirrhous gastric cancer.. Patients were eligible if they had typical scirrhous gastric cancer invading more than half of the stomach, and resectable disease confirmed by laparoscopic staging. The treatment schedule consisted of two courses (each, 4-week administration and 2-week withdrawal) of S-1 (100-120 mg/body per day), followed by radical surgery.. Fifty-five eligible patients were registered. Three completed only one course of the neoadjuvant chemotherapy, whereas 52 completed two courses. Toxicity was acceptable, with a few grade 3 (5.5%) events, but no grade 4 adverse events. The response rate was 32.6% in 43 evaluable patients. Of the 55 patients, 2 refused operation, 1 developed lung metastasis, and 52 underwent laparotomy. The curative resection rate was 80.8%, with acceptable morbidity and no mortality. The survival curve at 2 years' follow up showed a better survival rate than that of the historical controls, but did not reach the expected survival rate.. S-1 neoadjuvant chemotherapy appeared feasible and showed positive effects against scirrhous gastric cancer; however, the survival rate with S-1 did not reach the expected rate required when selecting an agent for a phase III trial to confirm the effectiveness of neoadjuvant chemotherapy against scirrhous gastric cancer.

Topics: Adenocarcinoma, Scirrhous; Adult; Aged; Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Combined Modality Therapy; Drug Combinations; Feasibility Studies; Humans; Japan; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Oxonic Acid; Prognosis; Stomach Neoplasms; Survival Rate; Tegafur; Treatment Outcome

The combination of 5-fluorouracil (5-FU) and cisplatin (CDDP) has been reported to be active against metastatic gastric cancer (MGC) and great synergy has been shown in vivo and in vitro when 5-FU precedes CDDP. The sequential combination of S-1 (tegafur, oxonic acid, 5-chloro-2,4-dihydroxypyridine) followed by CDDP for MGC was investigated. A phase I trial applying increasing doses of oral administration of S-1 (65-80 mg/m(2)) for 21 days and increasing doses of CDDP (60-80 mg/m(2)) on day 22 every 35 days was conducted in order to determine the maximum tolerated dose (MTD) and recommended phase II dose. Patients with metastatic or recurrent gastric cancer, no prior chemotherapy, measurable disease, ECOG performance status less than 3 and adequate organ functions were eligible for the study. Three patients were treated at each dose level with escalation based on toxicity. Fifteen patients were included and evaluated for dose-limiting toxicity (DLT) and MTD. DLT included NCICTC grade 3 anorexia and fatigue in patients treated at S-1 80 mg/m(2) and CDDP 80 mg/m(2) (dose level 5). The other toxicities, grade 3 or higher, included neutropenia (grade 3) and nausea/vomiting (grade 3). Non-hematological toxicities were grade 1/2 and included diarrhea, nausea and stomatitis. There was no treatment-related mortality. Therefore, the recommended dose was a combination of S-1 at 80 mg/m(2) and CDDP at 70 mg/m(2). This sequential administration of S-1 and CDDP every 35 days is tolerable and warrants a phase II trial. A multicenter phase II study is currently under way.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Female; Humans; Male; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Stomach Neoplasms; Tegafur

S-1 is a fourth-generation oral fluoropyrimidine that was developed to mimic the effects achieved with protracted continuous infusion of 5-fluorouracil (5-FU). This phase II study evaluated the efficacy and safety of S-1 salvage chemotherapy in patients with paclitaxel- and cisplatin-refractory gastric cancer. The primary end point was progression-free survival; secondary end points were overall survival, safety, and clinical benefit.. Patients were eligible for the study if they had histologically documented gastric adenocarcinoma previously treated with paclitaxel and cisplatin, age > or = 18 years, Eastern Clinical Oncology Group performance status < or =2, adequate organ function, and no evidence of gastrointestinal obstruction or passage disturbance. Patients were treated with a dose of S-1 based on body surface area (BSA) as follows: BSA < 1.25 m(2), 80 mg/day; 1.25 < or = BSA < 1.5 m(2), 100 mg/day; BSA > or= 1.5 m(2), 120 mg/day. The total dose was divided in two and administered twice daily for 4 weeks followed by a 2-week rest period.. Of the 53 patients enrolled in this study, 49 were evaluable. A total of 190 chemotherapy cycles were administered, and the median number of cycles was 2. Five patients (9.4%) had a partial response, and 18 (34%) had stable disease. Median progression-free survival and overall survival were 4.9 and 10.4 months, respectively. Grade 3/4 hematological toxicities included neutropenia in six patients (11%) but no cases of febrile neutropenia were found. Most of the non-hematological toxicities were diarrhea, asthenia, and mucositis, but none reached grade 3 or grade 4 in severity. Improvement of pain was observed in 17 patients (32.1%).. S-1 monotherapy provides active and safe salvage chemotherapy for patients with advanced gastric cancer who have been previously treated with paclitaxel and cisplatin.

Topics: Adenocarcinoma; Adult; Aged; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Cisplatin; Disease-Free Survival; Drug Combinations; Female; Fever; Humans; Male; Middle Aged; Neutropenia; Oxonic Acid; Paclitaxel; Pain; Salvage Therapy; Severity of Illness Index; Stomach Neoplasms; Survival Rate; Tegafur; Treatment Outcome

We performed preoperative chemotherapy with combined docetaxel, cisplatin and S-1 (DCS therapy) for treatment of advanced gastric cancer with para-aortic lymph node metastases. The aim of this study was to determine the maximum tolerated dose (MTD) and the dose-limiting toxicities. Furthermore, we evaluated the feasibility of DCS therapy in a preoperative setting, and also examined the pathological response. Fifteen patients received intravenous docetaxel and cisplatin (30, 35 or 40 mg/m2, each dose escalation was reciprocal) on days 1 and 15 and oral S-1 (40 mg/m2 twice daily) on days 1-14 every 4 weeks. After one cycle of chemotherapy, toxicities were evaluated and after two cycles of chemotherapy, patients who were judged to be candidates for curative resection underwent gastrectomy with D2 lymphadenectomy plus para-aortic lymph node dissection. The MTD of this combination was presumed to be at dose level 3 (docetaxel 40 mg/m2 and cisplatin 35 mg/m2). The dose-limiting toxicities were grade 4 neutropenia in one patient, grade 3 febrile neutropenia in two patients and grade 3 diarrhoea in two patients. Thirteen of the 15 patients received complete resection and there was no operation-related death. Good pathological responses were observed in 12 cases with lesions in the lymph nodes (complete response, n = 4; partial response, n = 8) and 11 patients with primary stomach lesions (complete response, n = 2; partial response, n = 9). This preoperative DCS therapy was considered feasible and provided a high pathological response rate in gastric cancer patients with para-aortic lymph node metastases.

Topics: Aged; Antimetabolites, Antineoplastic; Antineoplastic Agents; Cisplatin; Docetaxel; Drug Combinations; Drug Therapy, Combination; Female; Humans; Liver; Liver Neoplasms; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Oxonic Acid; Stomach; Stomach Neoplasms; Taxoids; Tegafur; Treatment Outcome

This phase II study evaluated the toxicity and efficacy of a novel dosing schedule of docetaxel and S-1 as treatment for advanced gastric cancer.. Patients with measurable advanced or recurrent gastric cancer and no prior exposure to the investigational drugs were treated with intravenous docetaxel 35 mg/m(2) on days 1 and 15, and oral S-1 80 mg/m(2)/day on days 1-14 every 4 weeks. The primary endpoint was objective response.. Thirty-five eligible patients were enrolled and received a total of 151 cycles of treatment (median 3, range 1-19). One complete response and 13 partial responses were observed, with an overall response rate of 40% (95% CI: 24-56%). Median progression-free survival and median overall survival times were 4.5 and 14.2 months, respectively. The most common grade 3-4 toxicities were neutropenia (23%) and leukocytopenia (15%).. Biweekly docetaxel combined with S-1 is active in advanced or recurrent gastric cancer, and can be administered with proper management of adverse events in an outpatient clinic.

Topics: Adenocarcinoma; Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Docetaxel; Drug Combinations; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Oxonic Acid; Prognosis; Stomach Neoplasms; Survival Rate; Taxoids; Tegafur; Treatment Outcome; Young Adult

S-1, an oral fluoropyrimidine, contains tegafur, which is converted to 5-fluorouracil mainly by CYP2A6. We evaluated the association between CYP2A6 polymorphisms and treatment outcome in metastatic gastric cancer patients treated with S-1 plus docetaxel.. Chemonaive patients received S-1 40 mg/m(2) twice daily on days 1-14 and docetaxel 35 mg/m(2) on days 1 and 8 of a 3-week cycle. We analyzed the wild-type (W) allele (CYP2A6*1) and four variant (V) alleles that abolish or reduce enzyme activity (CYP2A6*4, *7, *9 and *10). A total of 50 patients were enrolled.. The genotype frequencies were as follows: W/W (n=14, 28%), W/V (n=26, 52%) and V/V (n=0, 20%). Patients having fewer variant alleles had significantly better response rates (W/W vs W/V vs V/V=79 vs 65 vs 30%; p=0.04) and median progression-free survival (W/W vs W/V vs V/V=8.1 vs 6.9 vs 3.1 months; p=0.0009).. Our findings showed that the CYP2A6 genotype correlated with the treatment efficacy of S-1-based chemotherapy in previously untreated metastatic gastric cancer patients.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Aryl Hydrocarbon Hydroxylases; Cytochrome P-450 CYP2A6; Docetaxel; Drug Combinations; Female; Genome-Wide Association Study; Humans; Male; Middle Aged; Oxonic Acid; Pilot Projects; Polymorphism, Genetic; Stomach Neoplasms; Taxoids; Tegafur; Treatment Outcome; Young Adult

From July, 2007 to June, 2008, we prospectively investigated the influence of Hange-shashin-to on the therapeutic and adverse effects of chemotherapy and the changes in quality of life(QOL)scores of the patients with metastatic gastric and colorectal cancer. Twenty patients receiving S-1/Irinotecan (CPT-11) therapy were randomly allocated into group A (with Hange-shashin-to) and B (without Hange-shashin-to). While the anti-tumor effects did not differ significantly between these two groups, severe side effects of more than grade 3 occurred less frequently in group A. Our results suggested that the decrease in QOL scores on day 15 might be alleviated in group A, compared to group B. Therefore, Hange-shashin-to can be one of the useful supportive medicines in the combination therapy of S-1/CPT- 11.

Topics: Aged; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colorectal Neoplasms; Drug Combinations; Drugs, Chinese Herbal; Female; Humans; Irinotecan; Male; Middle Aged; Oxonic Acid; Quality of Life; Stomach Neoplasms; Tegafur

The best chemotherapy regimen for metastatic gastric cancer is uncertain, but promising findings have been reported with irinotecan plus cisplatin and S-1 (tegafur, 5-chloro-2,4-dihydropyrimidine, and potassium oxonate). We aimed to investigate the superiority of irinotecan plus cisplatin and non-inferiority of S-1 compared with fluorouracil, with respect to overall survival, in patients with metastatic gastric cancer.. We undertook a phase 3 open label randomised trial in 34 institutions in Japan. We enrolled patients aged 20-75 years or younger, who had histologically proven gastric adenocarcinoma, and randomly assigned them by minimisation to receive either: a continuous infusion of fluorouracil (800 mg/m(2) per day, on days 1-5) every 4 weeks (n=234); intravenous irinotecan (70 mg/m(2), on days 1 and 15) and cisplatin (80 mg/m(2), on day 1) every 4 weeks (n=236); or oral S-1 (40 mg/m(2), twice a day, on days 1-28) every 6 weeks (n=234). The primary endpoint was overall survival. Analyses were done by intention to treat. This study is registered with Clinicaltrials.gov, number NCT00142350, and with UMIN-CTR, number C000000062.. All randomised patients were included in the primary analysis. Median overall survival was 10.8 months (IQR 5.7-17.8) for individuals assigned fluorouracil, 12.3 months (8.1-19.5) for those allocated irinotecan plus cisplatin (hazard ratio 0.85 [95% CI 0.70-1.04]; p=0.0552), and 11.4 months (6.4-21.3) for those assigned S-1 (0.83 [0.68-1.01]; p=0.0005 for non-inferiority). Three treatment-related deaths occurred in the irinotecan plus cisplatin group and one was recorded in the S-1 group.. S-1 is non-inferior to fluorouracil and, in view of the convenience of an oral administration, could replace intravenous fluorouracil for treatment of unresectable or recurrent gastric cancer, at least in Asia. Irinotecan plus cisplatin is not superior to fluorouracil in this setting.

Topics: Adenocarcinoma; Administration, Oral; Adult; Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cisplatin; Disease-Free Survival; Drug Administration Schedule; Drug Combinations; Female; Fluorouracil; Humans; Infusions, Intravenous; Irinotecan; Japan; Male; Middle Aged; Oxonic Acid; Proportional Hazards Models; Risk Assessment; Stomach Neoplasms; Tegafur; Time Factors; Treatment Outcome; Young Adult

We aimed to examine the safety and antitumor effects of a combination of S-1 and paclitaxel in patients with unresectable or recurrent gastric cancer in a phase I/II setting.. The study was designed as a phase I/II clinical trial. In phase I portion, the dose of paclitaxel was escalated to estimate the maximum-tolerated dose (MTD) and recommended dose (RD) of paclitaxel with fixed dose of S-1. S-1 (daily dose, 80 mg/m(2)) was given orally on days 1-21 every 35-day cycle (rest on days 22-35). Paclitaxel was administered intravenously on days 1, 8 and 15, at an initial dose of 40 mg/m(2), stepping up to 70 mg/m(2) in 10-mg/m(2) increment. Dose-limiting toxicity (DLT) was defined as grade 4 hematological toxicity, grade 3 or higher nonhematological toxicity, and treatment discontinuation due to adverse reactions during the first course of treatment. In phase II portion, the efficacy and toxicity at the RD of paclitaxel with S-1 were assessed.. The MTD of paclitaxel was estimated to be 60 mg/m(2), because >33.3% of patients (2/3) developed DLTs. DLT included postponement of treatment due to grade 2 neutropenia, and grade 3 stomatitis, anorexia, and nausea. Therefore, the RD of paclitaxel was estimated to be 50 mg/m(2). In the phase II portion, 22 patients were evaluated with 50 mg/m(2) paclitaxel and 80 mg/m(2) S-1 in a 35-day cycle. The response rate was 54.5% (95% CI, 32.2-75.6%). The median survival time was 283 days (95% CI, 218-508 days). The median number of treatment courses was 4 (range 1-10), indicating that this regimen could be given repeatedly.. This phase I/II trial of combination therapy with S-1 and paclitaxel in patients with unresectable or recurrent gastric cancer showed that this regimen has substantial antitumor activity and can be given safely.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Female; Humans; Kaplan-Meier Estimate; Male; Maximum Tolerated Dose; Middle Aged; Neoplasm Recurrence, Local; Oxonic Acid; Paclitaxel; Stomach Neoplasms; Tegafur

To determine the dose-limiting toxicity (DLT) and activity of combination with docetaxel and S-1 on unresectable gastric cancer.. Docetaxel was administered intravenously on day 1 and S-1 was administered orally on days 1-14, every 3 weeks. Doses of each drug in phase I study were docetaxel 60-75 mg/m(2) and S-1 60-80 mg/m(2). A phase II study was conducted with the recommended dose (RD) based on phase I.. Sixty-five patients (median age 54 years) were enrolled. The DLTs were neutropenia with fever or stomatitis. The RD was docetaxel 75 mg/m(2) and S-1 60 mg/m(2). Two patients (aged 66 and 64 years) developed septic shock during the initial part of phase II study. A phase I study at lower dose (docetaxel 60 mg/m(2) and S-1 80 mg/m(2)) was conducted for patients older than 60 years, and this dose was determined as the RD for these patients. In the phase II study, frequent grade 3/4 toxicities were neutropenia (47%) and febrile neutropenia (26%). The overall response rate was 50% (95% CI, 35-66%) and median survival was 15.3 months (95% CI, 10.0-20.6 months).. Combination with docetaxel and S-1 was active against advanced gastric cancer and gave manageable toxicities.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Docetaxel; Drug Combinations; Female; Humans; Male; Maximum Tolerated Dose; Middle Aged; Oxonic Acid; Recurrence; Stomach Neoplasms; Taxoids; Tegafur

The primary objectives of this study were to estimate the maximum-tolerated dose (MTD) of docetaxel in combination with a fixed dose of S-1 and to determine the recommended dose (RD).. Patients with histologically proven gastric carcinoma with metastatic or locally advanced inoperable disease were eligible. Patients received intravenous docetaxel starting at 40 mg/m(2) (dose level 1), and stepwise dose increases to 50, 60, and 70 mg/m(2) were planned for successive patient cohorts (dose levels 2, 3, and 4, respectively) over 1 h on day 1 and oral S-1 administered at a fixed dose of 40 mg/m(2) twice daily on days 1-14, both drugs every 21 days.. A total of 13 patients were enrolled into this trial. All three patients at dose level 3 developed dose-limiting toxicities (DLT), and this level was declared to be the MTD. Hence, level 2 (docetaxel 50 mg/m(2)) was declared to be the RD for the next study. As 9 of the 13 enrolled patients responded to treatment, the overall objective response rate was 69.2% (95% CI, 44.1-94.3%). The median time to progression was 8.38 months (range 1.44-8.51) and the overall survival duration was 9.9 months (range 0.62-11.57). The most common grade 3/4 toxicity of docetaxel plus S-1 was neutropenia, which was tolerable and manageable.. This regimen showed encouraging activity and a manageable safety profile in advanced gastric carcinoma and could be used in further randomized studies.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Docetaxel; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Female; Humans; Male; Maximum Tolerated Dose; Middle Aged; Oxonic Acid; Prospective Studies; Stomach Neoplasms; Taxoids; Tegafur; Treatment Outcome

S-1 is an oral fluoropyrimidine consisting of the 5-fluorouracil prodrug tegafur combined with two modulating substances, gimeracil and potassium oxonate. On the basis of the potential additive effect between mitomycin C (MMC) and 5-fluorouracil as a continuous infusion, we conducted a phase II study to assess the efficacy and tolerability of the combination of S-1 and MMC as second-line chemotherapy for advanced gastric cancer (AGC). Patients with measurable AGC, progressive after one prior chemotherapy for metastatic disease, received MMC (7 mg/m2) on day 1 and S-1 (40 mg/m2) twice daily as an intermittent regimen of 4 weeks of treatment followed by a 2-week rest. Treatment was repeated every 6 weeks. The primary objective was the response rate. For 43 patients registered, 42 patients were treated with MMC plus S-1. A total of 121 chemotherapy cycles were delivered (median: 2; range: 1-6). The patients' median age was 53 years (range: 31-75) and nine (21%) had an Eastern Cooperative Oncology Group performance status of 2. In an intent-to-treat analysis, nine patients (21%) achieved an objective response, which was maintained for 4.1 months. The median progression-free and overall survivals were 3.4 months (95% confidence interval: 2.3-4.5) and 8.0 months (95% confidence interval: 6.1-9.9), respectively. Although fatigue was the most frequently encountered toxicity safety profiles were generally predictable and manageable. One patient developed hemolytic anemia, which was resolved spontaneously. Grade > or = 2 hand-foot syndrome was observed in only three patients. Second-line chemotherapy with MMC and S-1 is an active and tolerable regimen for AGC patients with good performance status.

Topics: Adult; Aged; Anemia, Hemolytic; Antineoplastic Combined Chemotherapy Protocols; Disease Progression; Disease-Free Survival; Drug Combinations; Fatigue; Female; Humans; Infusions, Intravenous; Male; Middle Aged; Mitomycin; Neoplasm Metastasis; Oxonic Acid; Stomach Neoplasms; Survival Rate; Tegafur; Treatment Outcome

A phase II study of weekly paclitaxel combined with S-1, a novel oral fluoropyrimidine, was performed to evaluate the efficacy and tolerability in unresectable or metastatic gastric cancer.. Twenty-nine patients with unresectable and/or metastatic gastric cancer were enrolled in the study. Paclitaxel 50 mg/m(2) was administered on days 1 and 8. S-1 was administered orally at 40 mg/m(2) b.i.d. for 14 consecutive days, followed by a 1-week rest. The primary endpoint was the response rate. Secondary endpoints were safety and overall survival.. The overall response rate in 29 patients was 48.3%, differentiated 36.4% and undifferentiated 55.6%. The median survival time was 13.9 months. Grade 3 or higher toxicity was observed in neutropenia (3.4%), diarrhea (3.4%), bilirubin (3.4%) and neuropathy (3.4%).. Combination chemotherapy of weekly paclitaxel and S-1 demonstrated tolerable toxicity and efficacy. This regimen will be one of the initial treatment options for unresectable or metastatic gastric cancer.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Female; Humans; Male; Middle Aged; Oxonic Acid; Paclitaxel; Stomach Neoplasms; Tegafur; Treatment Outcome

Study rationale, objectives, design, methods, and statistical considerations of an ongoing phase III study comparing S-1 alone versus the S-1/docetaxel combination are reviewed. This study is a prospective, multicenter, multinational, nonblinded, randomized, phase III study of subjects with advanced gastric cancer. Subjects are to be randomly assigned to 3-week cycles of Treatment Arm A (docetaxel and S-1) or 6-week cycles of Treatment Arm B (S-1 only). The primary objective of the study is to compare median overall survival of the test arm (docetaxel and S-1) to the control arm (S-1 only) in subjects with advanced or recurrent gastric cancer. The secondary objectives of the study are to assess the time-to-tumor progression (TTP), defined as time from randomization to date of first documentation of progressive disease (PD), to determine the clinical response (RR), defined as the sum of complete response (CR) and partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST), and to evaluate the safety of the two regimens. A total of 628 subjects (314 in each treatment arm) will be enrolled. Subject enrollment began in September 2005 and lasts approximately 3 years. We have already enrolled 556 patients (88.5%: Japan, 346 cases; Korea, 210 cases) from 103 centers (Japan, 86 centers; Korea, 17 centers) between December 2005 and February 2008. We are expecting full enrollment at the end of August 2008. The JACCRO GC-03 study is now ongoing. After 2 years follow-up from full enrollment, in 2010 we will report the final results of this study.

Topics: Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Docetaxel; Drug Combinations; Humans; Oxonic Acid; Stomach Neoplasms; Survival Rate; Taxoids; Tegafur

This randomised multicentre phase II study was conducted to investigate the activity and safety of two oral fluoropyrimidines, capecitabine or S-1, in elderly patients with advanced gastric cancer (AGC). Elderly (>or=65 years) chemo-naive patients with AGC were randomly assigned to receive capecitabine 1250 mg m(-2) two times daily on days 1-14 every 3 weeks or S-1 40-60 mg two times daily according to body surface area on days 1-28 every 6 weeks. Ninety-six patients were enrolled and 91 patients were randomised to capecitabine (N=46) or S-1 (N=45). Overall response rate, the primary end point, was 27.2% (95% CI, 14.1-40.4, 12 of 44 assessable patients) with capecitabine and 28.9% (95% CI, 15.6-42.1, 13 of 45) with S-1. Median times to progression and overall survival in the capecitabine arm (4.7 and 9.5 months, respectively) were similar to those in the S-1 arm (4.2 and 8.2 months, respectively). The incidence of grade 3-4 granulocytopenia was 6.8% with capecitabine and 4.8% with S-1. Grade 3-4 nonhaematologic toxicities were: asthenia (9.1% with capecitabine vs 7.1% with S-1), anorexia (6.8 vs 9.5%), diarrhoea (2.3 vs 0%), and hand-foot syndrome (6.8 vs 0%). Both capecitabine and S-1 monotherapies were active and tolerable as first-line treatment for elderly patients with AGC.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Bone Neoplasms; Capecitabine; Deoxycytidine; Drug Combinations; Feasibility Studies; Female; Fluorouracil; Humans; Liver Neoplasms; Lymphatic Metastasis; Male; Neoplasm Recurrence, Local; Oxonic Acid; Peritoneal Neoplasms; Prognosis; Stomach Neoplasms; Survival Rate; Tegafur; Treatment Outcome

It has been shown that T-cell dysfunction, including apoptosis of peripheral blood T cells, commonly occurs in patients receiving chemotherapy. In order to evaluate whether concomitant administration of the oral biological response modifier protein-bound polysaccharide K (PSK) could induce anti-apoptotic effects in patients treated with the anti-cancer drug, S-1, peripheral blood T cells were analyzed for induction of apoptosis, caspase-3 activities and expression of proapoptotic protein Bax and anti-apoptotic protein Bcl-2 in patients with curatively resected stage III gastric cancer, who were randomly assigned to postoperative adjuvant therapy with S-1 alone (n = 10) or S-1 combined with PSK (n = 10).. T-cell apoptosis 5 weeks after adjuvant therapy was significantly higher in the S-1 group (24.1 +/- 5.0%) than in the S-1 + PSK group (19.1 +/- 3.9%). S-1 induced T-cell apoptosis and concomitantly elevated caspase-3 activities and Bax expression in peripheral blood T cells. In addition, PSK partially prevented the T-cell apoptosis induced by S-1.. PSK could partially prevent the T-cell apoptosis induced by S-1.

Topics: Aged; Antibiotics, Antineoplastic; Antimetabolites, Antineoplastic; Apoptosis; bcl-2-Associated X Protein; Caspases; Chemotherapy, Adjuvant; Drug Combinations; Drug Therapy, Combination; Female; Flow Cytometry; Humans; Male; Oxonic Acid; Proteoglycans; Proto-Oncogene Proteins c-bcl-2; Stomach Neoplasms; T-Lymphocytes; Tegafur

This dose-escalation study of a combination of docetaxel, cisplatin and S-1 investigated the dose-limiting toxicity (DLT), maximum-tolerated dose (MTD), recommended dose (RD) and antitumor activity in advanced gastric cancer.. Patients received docetaxel (40 mg/m(2)), cisplatin (DIV on day 1) and S-1 (40 mg/m(2) p.o., twice daily, on days 1-14 every 28 days). The starting dose of cisplatin was 60 mg/m(2) (level 1); the dose was escalated to 70 (level 2) and 80 mg/m(2) (level 3) in a stepwise fashion.. Fourteen patients were enrolled. The MTD of cisplatin was 80 mg/m(2) (level 3). DLT was grade 3 diarrhea, febrile neutropenia and delayed resumption of treatment. The RD of cisplatin was considered to be 70 mg/m(2) (level 2). DLT was liver dysfunction, occurring in only 1 patient at level 2. The response rate was 69.2% (9/13).. For combined treatment with docetaxel, cisplatin and S-1 in patients with advanced gastric cancer, RD were docetaxel 40 mg/m(2), cisplatin 70 mg/m(2) and S-1 80 mg/m(2)/day. This regimen yields a high rate of tumor response and can be administered safely. Phase II studies of this regimen are under way.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Docetaxel; Dose-Response Relationship, Drug; Drug Combinations; Female; Humans; Male; Maximum Tolerated Dose; Middle Aged; Oxonic Acid; Stomach Neoplasms; Taxoids; Tegafur

Since 2000, we have introduced pre-operative chemotherapy including intra-peritoneal chemotherapy to patients with positive cytology and with no non-curative factors except peritoneum. Since 2006, we have started phase I trial with S-1 and intra-peritoneal chemotherapy with docetaxel to improve the efficacy and safety of the pre-operative regimen for advanced gastric cancer with peritoneal dissemination. The combination therapy with local and systemic chemotherapy is a promising regimen for gastric cancer with peritoneal dissemination.

Topics: Antineoplastic Combined Chemotherapy Protocols; Docetaxel; Dose-Response Relationship, Drug; Drug Combinations; Female; Humans; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Oxonic Acid; Peritoneal Neoplasms; Stomach Neoplasms; Survival Rate; Taxoids; Tegafur

The prognosis of advanced gastric cancer patients complicated with positive lavage cytology is poor, similar with that of peritoneal dissemination. For these diseases, we had reported the usefulness of intraperitoneal chemotherapy with cisplatin. Recently, systemic chemotherapy with S-1 and cisplatin is effective even for gastric cancer with peritoneal dissemination. Therefore, we compared the combination chemotherapy of S-1 and intraperitoneal cisplatin (IP group) with systemic S-1 plus cisplatin chemotherapy (IV group) for positive lavage cytology without peritoneal dissemination (P0CY1) gastric cancer. In this trial, 8 patients were enrolled after gastrectomy. Four were IP group and another 4 were IV group. The average chemotherapy courses for IV group and IP group are 3.5 times and 4.8 times, respectively. There was no difference in prognosis. Grade 3/4 events occurred for IV group and IP group were 3 patients and only 1 patient, respectively. The combination chemotherapy of S-1 and intraperitoneal cisplatin was found to be well tolerated and effective in patients with advanced gastric cancer with P0CY1.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Female; Gastric Lavage; Humans; Infusions, Intravenous; Infusions, Parenteral; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Peritoneal Neoplasms; Stomach Neoplasms; Tegafur

The prognosis of patients with T3 gastric cancer is poor, even if a curative resection is performed. Novel combination neo-adjuvant chemotherapy has been introduced for T3 gastric cancer patients. This pilot study involving 5 patients was performed between December 2002 and March 2003. They were diagnosed with gastric cancer with serosal invasion (T3) without P1 and CY1 by staging laparoscopy. We selected a combined chemotherapy with both paclitaxel and S-1. Paclitaxel at 60 mg/m2 was administered intraperitoneally on days 1 and 8, and S-1 at 80 mg/m2 was administered orally for 14 days followed by a 7-day-rest, as one course. After one course of this therapy, surgery was performed. The plasma concentration of paclitaxel was measured in two patients. Toxicites were generally mild, and no serious adverse reactions were observed. The plasma concentration of paclitaxel was about 100 ng/mL in the period of 1-6 hours after the administration. After one course, four patients underwent a total gastrectomy and one distal gastrectomy. The final histological stagings were included one stage IB, one stage II, one stage IIIA, one stage IIIB, and one stage IV. Three patients died at 10, 11, and 16 months after the initial treatment, and two have survived for 64 and 62 months. As the intraperitoneal administration of paclitaxel and oral S-1 was well-tolerated, further studies should be conducted involving T3 gastric cancer patients.

Topics: Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Humans; Injections, Intraperitoneal; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Oxonic Acid; Paclitaxel; Pilot Projects; Stomach Neoplasms; Tegafur

Randomized phase III study of S-1 alone versus S-1 plus Lentinan (LNT) in advanced or recurrent gastric cancer started in February 2007 conducted by the Japanese Foundation for Multidisciplinary Treatment of Cancer. The objective of this study is to evaluate the superiority of S-1/LNT to S-1 alone. The primary end point is to compare over all survival between both treatment groups. Secondary end points include time to treatment failure, the grade and rate of the adverse events, the evaluation of quality of life (QOL), response rate evaluated by RECIST and immunological parameters. QOL is evaluated by Japanese version of FACT-BRM questionnaire. Immunological parameters include serum complements (CH50, C3) and beta-1, 3 binding monocytes. The sample size is estimated at 150 patients per arm. Registration period is 2 years with 2-year follow-up. This study has a chance to prove the efficacy of the non-specific biological response modifier. We will have to cooperate in order to make this study a success.

Topics: Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Humans; Immunotherapy; Lentinan; Neoplasm Staging; Oxonic Acid; Recurrence; Stomach Neoplasms; Survival Rate; Tegafur

To define the maximum-tolerated dose (MTD) of S-1, given daily for 2 weeks followed by a 1-week rest, with a fixed dose of cisplatin on the initial day, and to determine the activity and safety of this regimen at the recommended dose (RD) when used as first line treatment of advanced gastric cancer (AGC).. Cisplatin was fixed at a dose of 60 mg/m2 on day 1 (D1) and the starting dose of S-1 was 60 mg/m2/day (30 mg/m2 bid) (level I) on D1 to D14, every 3 weeks. The dose of S-1 was increased by 5 mg/m2 bid up to 100 mg/m2/day (level V) unless the MTD was achieved.. Sixty-two eligible patients were enrolled. MTD was set at level V with two of three patients developing grade 3 diarrhea or febrile neutropenia. The RD was determined at level IV (90 mg/m2/day). After the first 20 patients were enrolled in phase II, the protocol was amended; the S-1 dose was reduced to 80 mg/m2/day (N=23) because of poor bone marrow recovery. The objective response was observed in 20 of 42 evaluable patients (48%). SD was achieved in 15 (36%). The median PFS was 5.3 months (95% CI, 4.6-6.0 months) with a median OS of 10.0 months (95% CI, 5.1-14.8 months). Grade 3-4 toxicities included neutropenia (33%), anemia (31%), and anorexia (24%).. The 3-week combination of cisplatin plus S-1 is active against AGC with favorable toxicitiy profiles. The phase II schedule or doses may need further refinements.

Topics: Adult; Aged; Anemia; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Diarrhea; Drug Administration Schedule; Drug Combinations; Female; Fever; Humans; Male; Maximum Tolerated Dose; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Neutropenia; Oxonic Acid; Stomach Neoplasms; Tegafur

The results of a pilot study using S-1/low-dose cisplatin/radiotherapy led us to hypothesize that the initial chemoradiotherapy regimen would induce a 70% efficacy rate with a 10% pathologic complete response rate.. Only patients with unresectable or incurable advanced gastric cancer were eligible. The patients received induction S-1 and cisplatin therapy with radiotherapy followed by chemotherapy alone.. Of the 30 patients recruited and assessed, 29 were eligible for clinical evaluation of measurable lesions. The response rate was 65.5%, with 19 with a partial response, 8 with no change, and 2 with progressive disease of 29 patients. Of the 30 patients recruited, 10 (33.3%) underwent stomach resection and D2 LN dissections. The pathologic complete response rate was 13.3% (4 patients), and the R0 resection rate was 100% (10 patients). The survival analysis showed a median survival time of 25 months. Grade 3 toxicity occurred in 66.7% for leukocytopenia, 33.3% for thrombocytopenia, 23.3% for nausea and appetite loss, and 6.7% for anemia, diarrhea, and renal dysfunction. Although all the patients had been hospitalized with a poor performance status with a giant tumor, 97% (29 of 30) could be discharged after the first cycle, resulting in an improvement in quality of life.. Chemoradiotherapy could be a powerful regimen for controlling tumor progression in advanced gastric cancer, improving patients' quality of life with tolerable toxicity. A complete histologic response rate of >10% would be expected, even for large tumors with metastatic lesions.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Drug Combinations; Female; Humans; Male; Middle Aged; Oxonic Acid; Postoperative Complications; Quality of Life; Remission Induction; Stomach; Stomach Neoplasms; Survival Analysis; Tegafur

A pre-clinical study demonstrated that paclitaxel induced thymidine phosphorylase in the tumor tissues. The combination of paclitaxel and doxifluridine is expected to exert extra anti-tumor effects. We evaluated the efficacy of this combination in patients with unresectable or recurrent gastric cancer who had been previously treated with S-1.. Registration was started to enroll 35 patients with advanced/recurrent gastric cancer, who were selected among those with measurable lesions fitting to response evaluation criteria in solid tumors, and with resistant to S-1 treatment. This regimen is consisted of paclitaxel, 80 mg/m(2), iv on days 1 and 8; and doxifluridine, 600 mg/m(2), po on days 1-14. The treatment was repeated every three weeks. Primary endpoint was response rate (RR); and secondary endpoints were overall survival (OS), progression free survival (PFS) and onset rate of adverse events.. From September 2003 to March 2005, 35 patients were registered: including 28 men; 7 women; median age of 66 years (range, 49-75 years); and performance status (PS) levels were, zero with 21 and one with 14 patients. In 33 eligible patients, except two, clinical usefulness was evaluated resulting in RR of 18.2% (partial response, 6; stable disease, 15; progressive disease, 10; and not evaluable, 2 patients). Median survival time was 321 days and median PFS was 119 days. Severe adverse events were found in three patients to discontinue the present treatment.. The combination of paclitaxel and doxifluridine might be a treatment of choice as a second line chemotherapy for patient undergone S-1 treatment.

Topics: Adenocarcinoma; Aged; Anemia; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Disease-Free Survival; Drug Combinations; Drug Resistance, Neoplasm; Female; Floxuridine; Humans; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Recurrence, Local; Neutropenia; Oxonic Acid; Paclitaxel; Peritoneal Neoplasms; Stomach Neoplasms; Survival Rate; Tegafur; Thrombocytopenia

Phase I/II clinical trials of S-1 plus cisplatin for advanced gastric cancer have yielded good responses and the treatment was well tolerated. In this S-1 Plus cisplatin versus S-1 In RCT In the Treatment for Stomach cancer (SPIRITS) trial, we aimed to verify that overall survival was better in patients with advanced gastric cancer treated with S-1 plus cisplatin than with S-1 alone.. In this phase III trial, chemotherapy-naive patients with advanced gastric cancer were enrolled between March 26, 2002, and Nov 30, 2004, at 38 centres in Japan, and randomly assigned to S-1 plus cisplatin or S-1 alone. In patients assigned to S-1 plus cisplatin, S-1 (40-60 mg depending on patient's body surface area) was given orally, twice daily for 3 consecutive weeks, and 60 mg/m(2) cisplatin was given intravenously on day 8, followed by a 2-week rest period, within a 5-week cycle. Those assigned to S-1 alone received the same dose of S-1 twice daily for 4 consecutive weeks, followed by a 2-week rest period, within a 6-week cycle. The primary endpoint was overall survival. Secondary endpoints were progression-free survival, proportions of responders, and safety. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00150670.. 305 patients were enrolled; seven patients were ineligible or withdrew consent, therefore, 148 patients were assigned to S-1 plus cisplatin and 150 patients were assigned to S-1 alone. Median overall survival was significantly longer in patients assigned to S-1 plus cisplatin (13.0 months [IQR 7.6-21.9]) than in those assigned to S-1 alone (11.0 months [5.6-19.8]; hazard ratio for death, 0.77; 95% CI 0.61-0.98; p=0.04). Progression-free survival was significantly longer in patients assigned to S-1 plus cisplatin than in those assigned to S-1 alone (median progression-free survival 6.0 months [3.3-12.9] vs 4.0 months [2.1-6.8]; p<0.0001). Additionally, of 87 patients assigned S-1 plus cisplatin who had target tumours, one patient had a complete response and 46 patients had partial responses, ie, a total of 54% (range 43-65). Of 106 patients assigned S-1 alone who had target tumours, one patient had a complete response and 32 had partial responses, ie, a total of 31% (23-41). We recorded more grade 3 or 4 adverse events including leucopenia, neutropenia, anaemia, nausea, and anorexia, in the group assigned to S-1 plus cisplatin than in the group assigned to S-1 alone. There were no treatment-related deaths in either group.. S-1 plus cisplatin holds promise of becoming a standard first-line treatment for patients with advanced gastric cancer.

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Antineoplastic Agents; Cisplatin; Drug Administration Schedule; Drug Combinations; Female; Humans; Japan; Male; Middle Aged; Oxonic Acid; Stomach Neoplasms; Survival Rate; Tegafur; Treatment Outcome

Although the prognosis in patients with pancreatic cancer has been poor, we recently reported unusually high response rate and survival benefit of S-1 treatment in patients with pancreatic cancer. The aim of this study was to reveal genetic background of this unique activity of S-1 against pancreatic cancer. S-1 is a novel oral fluoropyrimidine derivative consisting of Tegafur (FT) and dihydropyrimidine dehydrogenase (DPD) inhibitor (5-chloro-2,4-dihydroxypyridine; CDHP). Accordingly, intratumoral DPD mRNA expression level was measured to reveal whether the level in pancreatic cancer was different from other GI cancer and whether it was relevant to chemosensitivity.. Thirty-three recurrent pancreatic cancer patients treated with S-1 were studied. We obtained 15 responders and 13 non-responders according to the change of serum CA19-9. The mRNA was extracted from paraffin-embedded surgical specimens using laser captured microdissection, and relative expression levels of each DPD/beta-actin were measured using a quantitative reverse transcription polymerase chain reaction (RT-PCR) (Taqman) system. Forty-four colorectal cancer patients and 20 gastric cancer patients treated with S-1 were enrolled as control groups. Thymidylate synthase (TS) mRNA expression levels were also measured.. Intratumoral DPD mRNA expression level was significantly higher in pancreatic cancer than that in colorectal cancer (P = 0.0003; median level, 1.38 vs. 0.44) and gastric cancer (P = 0.0061; 1.38 vs. 0.82). No difference in TS mRNA expression levels was observed among cancer types. DPD expression among responded pancreatic cancer was significantly lower than non-responded. (P = 0.012, Mann-Whitney U test).. Intratumoral DPD mRNA expression level in pancreatic cancer was significantly higher than the other malignancies. This result may elucidate possible reasons for the high effectiveness of S-1 in pancreatic cancer.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; CA-19-9 Antigen; Cisplatin; Colorectal Neoplasms; Dihydrouracil Dehydrogenase (NADP); Drug Combinations; Female; Humans; Male; Middle Aged; Neoplasm Proteins; Oxonic Acid; Pancreatic Neoplasms; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; RNA, Neoplasm; Stomach Neoplasms; Tegafur; Treatment Outcome

This Phase II study assessed the activity and safety of biweekly paclitaxel and oral S-1 as treatment for unresectable and recurrent gastric cancer. The maximum tolerated dose for this regimen had been established previously in a Phase I study performed in Japanese patients.. Chemotherapy was performed using two anticancer agents, S-1 and paclitaxel. Oral S-1 (80 mg/m(2)) was administered twice a day after meals for two consecutive weeks from Day 1 to 14, followed by a 2 week recovery period; paclitaxel (120 mg/m(2)) was administered intravenously, biweekly, on Days 1 and 15. The patient received cycles of this regimen every 4 weeks (q 28-day cycles). The primary end point was the response rate according to the Response Evaluation Criteria in Solid Tumors.. A total of 39 patients (median age, 65 years) were enrolled; 13 other patients were screened, but found to be ineligible. All patients had unresectable and recurrent gastric cancer. The most common treatment-related Grade 3/4 adverse events were neutropenia (37.5%), appetite loss, diarrhea, decreased sodium (each 5%), and anemia, increased alanine aminotransferase, general fatigue, and dizziness (each 2.5%). Almost all the patients experienced alopecia. Intent-to-treat analysis showed a response rate of 43.6%. With a median follow-up of 14 months (range 8-21 months), median survival was 256 days and the median time to progression was 4 months.. A combination regimen of biweekly paclitaxel and oral S-1 was well tolerated and showed promising activity against unresectable and recurrent gastric cancer.

Topics: Adenocarcinoma; Aged; Alopecia; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Disease Progression; Disease-Free Survival; Drug Combinations; Female; Gastrointestinal Diseases; Humans; Hyponatremia; Kaplan-Meier Estimate; Male; Middle Aged; Neutropenia; Oxonic Acid; Paclitaxel; Stomach Neoplasms; Survival Analysis; Tegafur

We designed a phase I/II trial of S-1 combined with weekly docetaxel to determine the maximum tolerated dose (MTD) and recommended dose (RD) and to evaluate the efficacy and toxicity in metastatic gastric carcinoma (MGC). Patients with measurable disease received S-1 orally b.i.d. on days 1-14 and docetaxel intravenously on days 1 and 8 every 3 weeks. In phase I (n=30), each cohort received escalating doses of S-1 (30-45 mg m(-2) b.i.d.) and docetaxel (25-40 mg m(-2)); MTD was 45 mg m(-2) b.i.d. S-1/35 mg m(-2) docetaxel and RD was 40 mg m(-2) b.i.d. S-1/35 mg m(-2) docetaxel. Dose-limiting toxicities included grade 3 elevated liver enzymes, gastric perforation, grade 3 diarrhoea/fatigue, febrile neutropenia with grade 3 anorexia/fatigue, and neutropenic infection with grade 3 stomatitis/anorexia. In phase II (n=52), the overall response rate was 66.7% (95% confidence interval (CI): 53.8-79.6%) and the median time to progression and overall survival were 6.5 months (95% CI: 4.9-8.1) and 13.7 months (95% CI: 9.9-17.5), respectively. The most common grade 3/4 toxicity was neutropenia (29.4%), and febrile neutropenia/neutropenic infection occurred in 19.6% of patients. Non-haematological toxicities were generally mild. There was one treatment-related death due to pneumonitis. S-1 combined with weekly docetaxel is active in MGC with moderate toxicities.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Docetaxel; Drug Combinations; Female; Humans; Male; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Stomach Neoplasms; Taxoids; Tegafur

A dose-escalation study was conducted for postoperative patients with stage IV gastric cancer to determine the recommended dose of daily intravenous cisplatin combined with a fixed dose of TS-1. TS-1 was administered orally twice daily for 2 weeks followed by a 1-week rest. The dose of TS-1 was based on the body surface area (BSA) as follows: 80 mg/day for BSA less than 1.25, 100 mg/day for BSA 1.25 to less than 1.50, and 120 mg/day for BSA 1.5 or more. Three dose levels of cisplatin (2, 4, 6 mg/m(2)) were studied, and two courses were performed. Cisplatin was infused on day 1-5 and 8-12 for 30 minutes. The National Cancer Institute common toxicity criteria (NCI-CTC Version 3) were used to evaluate the grade of toxicity. Three patients enrolled in each level. Dose escalation was performed when dose-limiting toxicities (DLT) were seen in 0/3, and 3 more cases of the same level were added when DLTs were seen 1-2/3. Maximum-tolerated dose (MTD) were determined when DLTs were seen in 3 cases. DLTs were not recorded during the administration of CDDP up to 4 mg/m(2). However, DLTs were seen 3/3 at level 3. From these results, cisplatin of 4 mg/m(2)was determined to be the recommended dose (RD) in this protocol for postoperative stage IV gastric carcinoma.

Topics: Administration, Oral; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Administration Schedule; Drug Combinations; Female; Gastrectomy; Humans; Male; Maximum Tolerated Dose; Middle Aged; Neoplasm Staging; Oxonic Acid; Postoperative Period; Stomach Neoplasms; Tegafur

This study describes the first phase II study of S-1, a novel oral fluoropyrimidine, in a non-Japanese Asian population with advanced gastric cancer. S-1 was administered twice daily for 28 days every 6 weeks. A pharmacokinetic study was performed on day 28 of cycles 1 and 3. Genomic DNA from peripheral mononuclear cells was analyzed using a cDNA microarray-based comparative genomic hybridization (CGH) method. Thirty-one patients were initially given a dose of 35 mg/m(2) twice daily (bid) (group 1); then, the protocol was amended by increasing the dose to 40 mg/m(2) bid for an additional 31 patients (group 2) because of good tolerability to S-1. The overall response rate was 19.3% (95% confidence interval, 9.2%-29.5%). Over a median follow-up duration of 265 days, the median time to progression and overall survival time were 126 and 264 days, respectively. The 1-year survival rate was 34%. There was no grade 4 toxicity and the major adverse event was anemia. Pharmacokinetic parameters were similar to those of the previous Japanese reports. Microarray CGH identified 18 genes with copy number changes that were associated with hemoglobin reduction with S-1 treatment. A logistic regression analysis, integrating one clinical parameter (initial hemoglobin level) combined with three genetic copy number variations (HIST1H2BL, C10orf127, and XPNPEP2), provided a predictive model for the development of severe hemoglobin reduction. In conclusion, this study showed the feasibility of using S-1 at 35 mg/m(2) bid in gastric cancer. We suggest that the pharmacogenomic markers identified in this study may be potential candidates for predicting anemia after S-1 treatment.

Topics: Adenocarcinoma; Adult; Aged; Antimetabolites, Antineoplastic; Area Under Curve; Asian People; Body Surface Area; DNA, Neoplasm; Drug Combinations; Drug Evaluation; Feasibility Studies; Female; Follow-Up Studies; Hemoglobins; Humans; Logistic Models; Male; Middle Aged; Nucleic Acid Hybridization; Oligonucleotide Array Sequence Analysis; Oxonic Acid; Pharmacogenetics; Predictive Value of Tests; Stomach Neoplasms; Survival Analysis; Tegafur; Treatment Outcome

We previously conducted a phase I/II study of irinotecan (CPT-11) combined with S-1 as first-line chemotherapy for metastatic advanced gastric cancer. In the present study,second-line chemotherapy was given to 32 of 44 patients whose disease became refractory to this first-line treatment. Overall survival time of the patients given second-line chemotherapy was significantly longer than that of patients not given such therapy (444 days vs. 230 days, p = 0.013). The response rate to second-line chemotherapy was 13% (4/32). Survival time of patients who responded to second-line chemotherapy was significantly longer than that of non-responders. Second-line chemotherapy may produce a better clinical response in patients who have progressive disease during first-line chemotherapy. Overall survival time and time to progression after second-line chemotherapy did not significantly differ between patients who received second-line chemotherapy regimens including S-1 and those who received regimens not including S-1.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cisplatin; Drug Administration Schedule; Drug Combinations; Female; Humans; Irinotecan; Male; Middle Aged; Oxonic Acid; Paclitaxel; Retrospective Studies; Stomach Neoplasms; Survival Rate; Tegafur

A randomized phase II clinical trial is being conducted for patients with advanced or recurrent gastric cancer, in order to select the most promising treatment for subsequent evaluation in a large-scale phase III trial. We compare four chemotherapeutic treatments, which include two sequential and two combination regimens using paclitaxel with 5-fluorouracil or S-1, an oral fluorouracil derivative. The primary endpoint is 10-month overall survival rate, while the secondary endpoints are adverse events, time to treatment failure and progression-free survival. A Bayesian method is used to provide a statistical rule for monitoring the trial. Forty patients per treatment regimen (160 in total) were randomized into one of the four regimens using a centralized dynamic method.

Topics: Aged; Antimetabolites, Antineoplastic; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Fluorouracil; Humans; Neoplasm Recurrence, Local; Oxonic Acid; Paclitaxel; Stomach Neoplasms; Tegafur

Systemic chemotherapy for gastric cancer is often associated with treatment-related toxicity, which is particularly severe in patients with a poor performance status. In this paper, we describe the first study to evaluate S-1 monotherapy as an option for advanced gastric cancer patients who are not candidates for combination chemotherapy due to poor clinical condition. Fifty-two patients with Eastern Cooperative Oncology Group (ECOG) performance scale 2-3, whose general condition had made use of combination chemotherapy impossible, were enrolled. S-1 was administered to 30 patients as second- or third-line therapy. The initial dose of S-1 was 35 mg m(-2), administered b.i.d for 14 days every 3 weeks. With a median follow-up period of 33 weeks, the median progression-free survival, and overall survival were 11 weeks (95% CI, 8-14) and 33 weeks (95% CI, 19-47), respectively. The overall 1-year survival rate was 29% by intent-to-treat analysis. The overall response rate was 12% (95% CI, 3-21), and the percentage of stable disease was 35%, resulting in the disease control rate of 47% (95% CI, 32-60). Significant drug-related toxicity included grade 3 diarrhoea (14%), anorexia (14%), fatigue (10%), neutropenia (10%), and leucopenia (6%). In conclusion, this study indicated the modest activity of S-1 in gastric cancer patients with poor performance status.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Disease Progression; Drug Administration Schedule; Drug Combinations; Feasibility Studies; Female; Follow-Up Studies; Humans; Male; Middle Aged; Oxonic Acid; Prognosis; Stomach Neoplasms; Survival Analysis; Tegafur; Time Factors; Treatment Outcome

We have reported that vascular endothelial growth factor (VEGF) expression in gastric cancers might be a selective marker between 5-fluorouracil (5-FU) and a combination of 5-FU plus cisplatin (CDDP). In this study, the relationship between VEGF expression and effects of S-1 with and without CDDP is investigated.. The subjects were 44 patients treated with S-1 (40 mg/m2, twice daily, days 1-28, repeated every 6 weeks) and 24 patients treated with S-1 plus CDDP (S-1 40 mg/m2, twice daily, days 1-21, CDDP, 60 or 70 mg/m2, day 8, repeated every 5 weeks). VEGF expression in pretreatment endoscopic biopsy samples was assessed immunohistochemically.. Median survival times (MST) of the patients treated with S-1 and S-1 plus CDDP were 344 and 388 days. Among evaluable patients, the response rates of patients with VEGF (+) and (-) tumors to S-1 were 40% (6/15) and 54% (13/24), and to S-1 plus CDDP, 79% (15/19) and 80% (4/5). While the survival of patients with VEGF (-) tumors was slightly longer than those with VEGF (+) tumors in the S-1 group (MST, 425 versus 308 days, P = 0.42), patients with VEGF (+) tumors survived remarkably longer than those with VEGF (-) tumors in the S-1 plus CDDP group (MST, 570 versus 333 days, P = 0.19).. Similarly to our previous study, it is suggested that the effects of adding CDDP to S-1 might be more remarkable in gastric cancer patients with VEGF (+) tumors than in those with VEGF (-) tumors. These results should be confirmed in a large phase III study.

Topics: Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Cisplatin; Drug Combinations; Fluorouracil; Humans; Immunohistochemistry; Middle Aged; Oxonic Acid; Stomach Neoplasms; Tegafur; Vascular Endothelial Growth Factor A

The effect of gastrectomy on pharmacokinetics after S-1 administration was investigated.. A dose of 40 mg/m(2) of S-1 was administered orally twice daily for 7 days (80 mg/m(2)/day) preoperatively in ten patients with resectable gastric cancer, and the same dose of S-1 was administered for 28 consecutive days after gastrectomy. Plasma concentrations of tegafur, gimeracil, and oteracil potassium, all the components of S-1, and 5-FU were measured on pre- and postoperative days. Concentrations of 5-FU in tumor and normal tissues were also determined.. At day 4 from the initial preoperative administration of S-1, the AUC of 5-FU was 1,055 +/- 304 ng h/ml. At day 18, day 28, and day 42 after gastrectomy, it was 1,012 +/- 331, 1,070 +/- 403, and 946 +/- 226 ng h/ml, respectively. No significant differences for plasma 5-FU were observed between pre- and postoperative days. In the resected tumor tissues, concentrations of 5-FU were 242 +/- 83 ng/g around 4.5 h and 91.7 +/- 37.0 ng/g around 20 h after the final administration, respectively.. Gastrectomy does not affect on pharmacokinetics of 5-FU derived from S-1 regardless of partial or total gastrectomy, indicating that S-1 can be a useful drug in postoperative adjuvant chemotherapy for gastric cancer.

Topics: Administration, Oral; Aged; Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Drug Combinations; Female; Fluorouracil; Gastrectomy; Humans; Male; Middle Aged; Oxonic Acid; Pyridines; Stomach Neoplasms; Tegafur

The aim of this dose escalation study was to determine the maximum-tolerated dose (MTD), dose-limiting toxicities (DLTs) and preliminary efficacy of docetaxel, S-1 and cisplatin combination chemotherapy in patients with unresectable metastatic gastric cancer. Seventeen patients received oral S-1 (40 mg m(-2) bid) on days 1-14, intravenous cisplatin (60 mg m(-2)) and docetaxel (60, 70 or 80 mg m(-2) depending on DLT) on day 8 every 3 weeks. The MTD of this combination was presumed to be docetaxel 70 mg m(-2). At this dose level, 40% of the patients (two of five) developed grade 4 neutropenia and 20% (one of five) exhibited grade 3 nausea during the first course. Therefore, the recommended dose of docetaxel was defined as 60 mg m(-2). The DLT was neutropenia. The response rate (RR) was 88.2% (15 of 17), consisting of one complete response and 14 partial responses. There were two stable diseases but no progressive disease. Of these 15 responders, four (23.5%) with high VEGF expression showed rapid tumour regression and achieved downstaging, leading to subsequent curative gastrectomy. Three of these have been disease free for about 3 years, suggesting a complete cure. In conclusion, this regimen was tolerable and showed a quite high RR, with an appreciable downstaging rate in metastatic gastric cancer.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Docetaxel; Drug Combinations; Female; Humans; Immunoenzyme Techniques; Intestinal Neoplasms; Male; Maximum Tolerated Dose; Middle Aged; Oxonic Acid; Stomach Neoplasms; Taxoids; Tegafur; Vascular Endothelial Growth Factor A

Advanced gastric cancer can respond to S-1, an oral fluoropyrimidine. We tested S-1 as adjuvant chemotherapy in patients with curatively resected gastric cancer.. Patients in Japan with stage II or III gastric cancer who underwent gastrectomy with extended (D2) lymph-node dissection were randomly assigned to undergo surgery followed by adjuvant therapy with S-1 or to undergo surgery only. In the S-1 group, administration of S-1 was started within 6 weeks after surgery and continued for 1 year. The treatment regimen consisted of 6-week cycles in which, in principle, 80 mg of oral S-1 per square meter of body-surface area per day was given for 4 weeks and no chemotherapy was given for the following 2 weeks. The primary end point was overall survival.. We randomly assigned 529 patients to the S-1 group and 530 patients to the surgery-only group between October 2001 and December 2004. The trial was stopped on the recommendation of the independent data and safety monitoring committee, because the first interim analysis, performed 1 year after enrollment was completed, showed that the S-1 group had a higher rate of overall survival than the surgery-only group (P=0.002). Analysis of follow-up data showed that the 3-year overall survival rate was 80.1% in the S-1 group and 70.1% in the surgery-only group. The hazard ratio for death in the S-1 group, as compared with the surgery-only group, was 0.68 (95% confidence interval, 0.52 to 0.87; P=0.003). Adverse events of grade 3 or grade 4 (defined according to the Common Toxicity Criteria of the National Cancer Institute) that were relatively common in the S-1 group were anorexia (6.0%), nausea (3.7%), and diarrhea (3.1%).. S-1 is an effective adjuvant treatment for East Asian patients who have undergone a D2 dissection for locally advanced gastric cancer. (ClinicalTrials.gov number, NCT00152217 [ClinicalTrials.gov].).

Topics: Aged; Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Disease-Free Survival; Drug Combinations; Female; Follow-Up Studies; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Recurrence, Local; Neoplasm Staging; Oxonic Acid; Stomach Neoplasms; Survival Rate; Tegafur

A phase I/II study of a combination of S-1 and weekly paclitaxel was conducted to determine the maximum tolerated dose (MTD), recommended dose (RD), dose-limiting toxicities (DLTs) and objective response rate (RR) in patients with advanced or recurrent gastric cancer.. S-1 was administered orally at a fixed dose of 80 mg/m(2) per day on days 1-14. Paclitaxel was injected intravenously on days 1, 8, and 15, starting with a dose of 50 mg/m(2). The dose was increased in a stepwise manner.. In phase I, level 2 (60 mg/m(2)) was considered the MTD, because 2 of 3 patients in level 2 developed DLTs (grade 3 neutropenia and anemia, and grade 4 diarrhea and stomatitis). Therefore, the RD was determined to be level 1 (50 mg/m(2)). In phase II, efficacy and safety were assessed in 18 patients treated with the RD. The RR was 64.7% and the median survival time was 13.5 months. The most severe toxicities were grade 3 leukopenia (5.5%) and grade 3 neutropenia (5.5%).. Our study showed that S-1 combined with 50 mg/m(2) paclitaxel is effective and safe in patients with advanced or recurrent gastric cancer.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Dose-Response Relationship, Drug; Drug Combinations; Female; Humans; Male; Maximum Tolerated Dose; Middle Aged; Oxonic Acid; Paclitaxel; Stomach Neoplasms; Tegafur

We conducted a Phase I study to evaluate the safety and efficacy of a combination of S-1 with semi-weekly low-dose cisplatin in patients with unresectable/recurrent gastric cancer to determine the recommended dose (RD) for a subsequent Phase II study.. S-1 was administered orally at 80-120 mg/body/day based on body surface area. One cycle consisted of the consecutive administration of S-1 for 28 days followed by 14 days rest. Three dose levels, 7.5, 10, and 15 mg/m(2)/day, were set for cisplatin, which was administered twice-a-week for 4 weeks followed by 2 weeks of rest in each cycle. Dose-limiting toxicity (DLT) data were continually monitored to enable decisions regarding cisplatin dose escalation and deescalation based on a new dose-finding algorithm using a continual reassessment method (CRM). The CRM target toxicity level to estimate the RD was set at 20%.. Eight and five patients were treated at cisplatin dose levels of 10 and 15 mg/m(2)/day, respectively. Two DLTs occurred at both dose levels. On the basis of this data, the CRM estimated the RD to be 10 mg/m(2)/day of cisplatin. Three patients of eight patients treated with 10 mg/m(2)/day of cisplatin exhibited a confirmed partial response during the treatment period.. For future trials examining the safety and efficacy of daily S-1 with semi-weekly cisplatin in patients with unresectable/recurrent gastric cancer, we found a cisplatin RD of 10 mg/m(2)/day.

Topics: Administration, Oral; Adult; Aged; Algorithms; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Cisplatin; Drug Administration Schedule; Drug Combinations; Female; Humans; Injections, Intravenous; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Recurrence, Local; Oxonic Acid; Patient Selection; Research Design; Stomach Neoplasms; Tegafur; Treatment Outcome

An early detection and treatment of gastric cancer with peritoneal dissemination are rather difficult so that a clinical trial has been neglected. Therefore, we introduced a pre-operative peritoneal lavage diagnosis for gastric cancer patients with serosa-invaded tumors. Neoadjuvant chemotherapy was introduced to patients with positive cytology and with no non-curative factors except peritoneum. The neoadjuvant chemotherapy followed by surgery was done safely. The patients with the disappearance of CY and P factors due to neoadjuvant chemotherapy had a better prognosis than those with positive results of CY or R However, many of the patients with negative results from peritoneum eventually suffered a peritoneal recurrence. We started another protocol study with S-1 and an intra-peritoneal chemotherapy using docetaxel. The efficacy in the protocol result will be expected.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Docetaxel; Drug Combinations; Female; Fluorouracil; Follow-Up Studies; Humans; Male; Middle Aged; Neoadjuvant Therapy; Oxonic Acid; Peritoneal Neoplasms; Stomach Neoplasms; Survival Rate; Taxoids; Tegafur

To determine the safety profile and activity of IP docetaxel combined with S-1 for patients with peritoneal dissemination of gastric cancer, a multi-centric phase I/II study has started. Patients with histologically confirmed peritoneal dissemination by laparoscopy or laparotomy were eligible to participate in this study, but the patients with a large amount of malignant ascites were excluded. In phase I part, the patients received variable doses of intraperitoneal docetaxel on day 1 and day 15 and 80 mg/m2 of daily oral S-1 on days 1-14 every 4 weeks. Phase I part determines the dose-limiting toxicity (DLT), maximum-tolerated dose (MTD) and recommended dose (RD), and phase II part evaluates a safe successful execution. The response rate of peritoneal dissemination was explored as the secondary endpoint. After 2 cycles, peritoneal tumor response was assessed according to the new criteria of Society for the Study of Peritoneal Dissemination in Gastric Cancer. The response criteria included the following: a decrease in ascites and change in cytology negative; at least a 50% decrease in the sum of the longest diameter of peritoneal tumor using photographs of peritoneal lesions taken to confirm an objective response before and after the treatment.

Topics: Antineoplastic Combined Chemotherapy Protocols; Docetaxel; Drug Combinations; Humans; Infusions, Parenteral; Oxonic Acid; Peritoneal Neoplasms; Stomach Neoplasms; Taxoids; Tegafur

To investigate the efficacy and safety of the combination therapy of irinotecan (CPT-11) plus S-1 in patients with advanced gastric cancer at the dose recommended by a previous phase I study.. A total of 23 patients received 80 mg/m(2) of CPT-11 on days 1 and 15, and S-1 at a dose level set on the basis of the body surface area (BSA): 40 (BSA <1.25 m(2)), 50 (BSA > or =1.25 to <1.5 m(2)) or 60 mg (BSA > or =1.5 m(2)) b.i.d. was given from days 1-21.. The overall response rate was 47.8% (11 of 23, 95% confidence interval, CI: 27.4-68.2%). The median time to progression (TTP) was 210 days (95% CI: 145-322 days) and the median survival time was 394 days (95% CI: 241-484 days). The incidence of grade 3 or 4 hematological and non-hematological toxicity was 17.4 and 8.7%. The most common hematological toxicity was anemia and the most common non-hematological toxicity was diarrhea.. The combination therapy of CPT-11 and S-1 provided prolonged TTP with low toxicity, and the results warrant a further phase III study to define the efficacy in improvement of survival in patients with advanced gastric cancer.

Topics: Adult; Aged; Anemia; Antimetabolites, Antineoplastic; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Diarrhea; Disease-Free Survival; Drug Administration Schedule; Drug Combinations; Female; Humans; Irinotecan; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Stomach Neoplasms; Survival Analysis; Tegafur; Treatment Outcome

The aim of the current study was to determine the maximum tolerated dose (MTD) and the dose limiting toxicity (DLT) of a combination of paclitaxel and S-1 in patients with advanced gastric cancer. Fifteen patients were enrolled. The dose for S-1 was set at 80 mg/m2/day (days 1-14), while the dose for paclitaxel increased by 10 mg/m2 for every three patients, with a starting dose of 100 mg/m2 and was given biweekly on day 1 and 15. There was no severe toxicity (grade 4) recorded in patients receiving up to 120 mg/m2 of paclitaxel. Leukopenia/neutrophilia with grade 1 to 3 occurred in six patients up to level 3. At 130 mg/m2 of paclitaxel, grade 4 leukocytopenia and neutropenia events and grade 3 diarrhea developed in one out of three patients. One patient in another group of three patients that were enrolled at level 3, developed grade 4 granulocytopenia with fever (a body temperature higher than 38 degrees C) and grade 3 leukocytopenia. Eight patients, out of a total of 15, showed a partial response, resulting in an objective response rate of 53%. Five patients received gastrectomy. Median survival time was 428 days and the 1 year survival rate was 53%. Biweekly paclitaxel/S-1 combination chemotherapy could be safely used for the treatment of advanced gastric cancer. The recommended doses for a phase II study with paclitaxel and S-1 are 120 mg/m2 and 80 mg/m2, respectively.

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Female; Humans; Male; Maximum Tolerated Dose; Middle Aged; Oxonic Acid; Paclitaxel; Pyridines; Stomach Neoplasms; Tegafur

The safety of chemotherapy combining TS-1 and weekly paclitaxel for the treatment of unresectable and recurrent gastric cancer was evaluated in this study. Paclitaxel was administered by intravenous drip infusion at a starting dose (level 1) of 50 mg/m2 on days 1, 8, and 15. TS-1 was administered orally at a dose of 40 mg/m2twice a day for 2 weeks (days 1-14) followed by 2 weeks rest. A total of 9 patients were enrolled in this study. Two out of 6 patients treated with level 1 suffered from leukocytopenia and neutropenia, which were determined as dose-limiting toxicity (DLT). Three patients were treated with level 2, in which the dose of paclitaxel was increased up to 60 mg/m2. One of 3 patients suffered from grade 3 diarrhea and one patient from grade 4 leukocytopenia, eutrocytopenia, anemia, and stomatitis, which were determined as DLT. According to these results,level 1 of this regimen was recommended as a safe treatment for gastric cancer patients. A phase II study will be performed to evaluate the efficacy of the combination chemotherapy.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Female; Humans; Leukopenia; Male; Middle Aged; Neutropenia; Oxonic Acid; Paclitaxel; Pyridines; Stomach Neoplasms; Tegafur

S-1 plus cisplatin is considered highly active in Japanese gastric cancer patients. We conducted a phase II multi-institutional trial, in the West, in patients with untreated advanced gastric or gastroesophageal junction adenocarcinoma to evaluate activity and safety of this combination.. Patients received cisplatin intravenously at 75 mg/m2 on day 1 and S-1 orally at 25 mg/m2/dose bid (50 mg/m2/d) on days 1 to 21, repeated every 28 days. Patients with histologic proof of gastric or gastroesophageal junction adenocarcinoma with a Karnofsky performance status (KPS) of > or = 70% and near-normal organ function were eligible. All patients provided a written informed consent. To observe a 45% confirmed overall response rate (ORR), 41 assessable patients were needed.. All 47 patients were assessed for safety and survival, and 41 patients were assessed for ORR. The median age was 56 years and median KPS was 80%. The median number of chemotherapy cycles was four. The confirmed ORR was 51% (95% CI, 35% to 67%) and it was 49% by an independent review. At the 6-month interval, 71% of patients were alive, with a median survival time of 10.9 months. Frequent grade 3 or 4 toxicities included fatigue (26%), neutropenia (26%), vomiting (17%), diarrhea (15%), and nausea (15%); however, stomatitis (2%) and febrile neutropenia (2%) were uncommon. There was one (2%) treatment-related death.. S-1 plus cisplatin is active against gastric cancer and has a favorable toxicity profile. A global phase III study of S-1 plus cisplatin versus fluorouracil plus cisplatin currently is accruing patients.

Topics: Adenocarcinoma; Adult; Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Administration Schedule; Drug Combinations; Esophagogastric Junction; Female; Humans; Male; Middle Aged; Oxonic Acid; Pyridines; Stomach Neoplasms; Survival Analysis; Tegafur; Treatment Outcome

A dose-escalation study of irinotecan (CPT-11) combined with S-1, an oral dihydropyrimidine dehydrogenase inhibitory fluoropyrimidine, was performed to determine the maximum-tolerated dose (MTD), recommended dose (RD), dose-limiting toxicities (DLTs), and objective response rate (RR) in advanced gastric cancer (AGC). S-1 was administered orally at 80 mg m-2 day-1 from day 1 to 14 of a 28-day cycle and CPT-11 was given intravenously on day 1 and 8 at an initial dose of 70 mg m-2 day-1, stepping up to 100 mg m-2. The treatment was repeated every 4 weeks, unless disease progression was observed. In the phase I portion, the MTD of CPT-11 was presumed to be 100 mg m-2, because 66.6% of patients (two of three) developed DLTs. All three patients at the initial RD of CPT-11 (90 mg m-2) experienced grade 4 haematological or grade 3 nonhaematological toxicities at second course, followed by the dose reduction of CPT-11 from the third course. Considering safety and the ability to continue treatment, the final RD was determined to be 80 mg m-2. In the phase II portion, 42 patients including seven patients in the final RD phase I portion were evaluated. The median treatment course was five (range: 1-13). The incidences of severe (grade 3-4) haematological and nonhaematological toxicities were 19 and 10%, respectively, but all were manageable. The RR was 62% (26 of 42, 95% confidence interval: 47.2-76.6%), and the median survival time was 444 days. Our phase I/II trial showed S-1 combined with CPT-11 is effective for AGC and is well tolerated, with acceptable toxicity.

Topics: Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Disease Progression; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Female; Humans; Injections, Intravenous; Irinotecan; Male; Maximum Tolerated Dose; Middle Aged; Neoplasm Staging; Oxonic Acid; Safety; Stomach Neoplasms; Survival Rate; Tegafur; Time Factors; Treatment Outcome

To evaluate the efficacy and toxicity of docetaxel in combination with a novel oral 5-fluorouracil analogue S-1 for patients with advanced or recurrent gastric cancer.. Patients with advanced or recurrent adenocarcinoma of the stomach and up to one previous chemotherapy regimen were treated with i.v. docetaxel 40 mg/m2 on day 1 and oral S-1 80 mg/m2/d on days 1 to 14 every 3 weeks.. Forty-eight patients (median age, 65 years; range, 25-75 years) received a total of 272 treatment cycles (median, 4; range, 1-17). No complete responses and 27 partial responses were observed for an overall response rate of 56.3% [95% confidence interval (95% CI), 38-66%]. Eighteen patients (37.5%) had stable disease and three patients (6.3%) had progressive disease as best response. The tumor control rate (complete response + partial response + stable disease) was 93.8% (95% CI, 83-98%). Median overall survival was 14.3 months (95% CI, 10.7-20.3 months) and median time to tumor progression was 7.3 months (95% CI, 4.3-10.0 months). The most common grade 3 to 4 hematologic toxicities were neutropenia (58.3%), leukopenia (41.7%), febrile neutropenia (8.3%), and anemia (8.3%). The most common grade 3 nonhematologic toxicities included anorexia (14.6%), stomatitis (8.3%), and nausea (6.3%). No grade 4 nonhematologic toxicities were reported and all treatment-related toxicities were resolved.. Docetaxel/S-1 combination is highly active and well tolerated in advanced or recurrent gastric cancer. Further investigation in randomized studies is warranted.

Topics: Adenocarcinoma; Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Disease Progression; Docetaxel; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Injections, Intravenous; Kaplan-Meier Estimate; Male; Middle Aged; Neoplasm Recurrence, Local; Oxonic Acid; Stomach Neoplasms; Survival Rate; Taxoids; Tegafur; Treatment Outcome

The aims of this phase I/II study of docetaxel and S-1 were to determine the dose-limiting toxicity (DLT), maximum-tolerated dose (MTD), and recommended dose (RD) in the phase I part and to explore the tumour response, survival and safety in the phase II part. Patients with histologically- or cytologically confirmed unresectable or recurrent gastric cancer were eligible. Treatment consisted of intravenous docetaxel on day 1 (starting dose 50 mg m(-2)) and oral S-1 at a fixed dose of 40 mg m(-2) twice daily on days 1-14, every 4 weeks up to six cycles. Nine patients took part in the phase I portion of the study. The MTD of docetaxel was determined to be 50 mg m(-2), with the DLTs of grade 3 infection associated with grade 3 neutropenia and grade 4 neutropenia during S-1 administration. The RD of docetaxel was 40 mg m(-2) in combination with S-1 40 mg m(-2) b.i.d. The efficacy and safety of this regimen was therefore assessed in 46 patients with at least one measurable lesion. The overall response rate and estimated median overall survival were 46% (95% CI, 31-61%) and 14.0 months (8.3-17.3 months), respectively. The most common grade 3/4 toxicity was neutropenia (67% of patients), which was predictable and manageable. This regimen showed promising activity with moderate toxicities in advanced gastric cancer.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Docetaxel; Dose-Response Relationship, Drug; Drug Combinations; Female; Humans; Male; Maximum Tolerated Dose; Oxonic Acid; Stomach Neoplasms; Survival Analysis; Survival Rate; Taxoids; Tegafur; Treatment Outcome

In this randomized multicenter Phase III study, patients with curatively resected Stage II/IIIA gastric cancer were assigned to postoperative adjuvant therapy with an oral fluoropyrimidine S-1 alone (2 weeks of treatment and 1 week of rest for 6 months, followed by 2 weeks of treatment and 2 weeks of rest for 6 months) or S-1 combined with an oral biological response modifier PSK (the same regimen of S-1 plus daily PSK for 12 months). The main objective was to evaluate the survival benefit and quality of life (QOL) of combined therapy. The primary end points were the time to relapse and the duration of survival after surgery, i.e. the rates of disease-free survival and overall survival at 3 and 5 years. The secondary end points were the relations of survival rates to drug compliance, QOL, adverse events, postoperative complications, relapse status, and the preoperative expression of immune or tumor markers. The sample size was 140 per treatment arm.

Topics: Adenocarcinoma; Administration, Oral; Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Disease-Free Survival; Drug Administration Schedule; Drug Combinations; Gastrectomy; Humans; Immunologic Factors; Immunotherapy; Middle Aged; Neoplasm Staging; Oxonic Acid; Proteoglycans; Quality of Life; Stomach Neoplasms; Survival Rate; Tegafur

We developed a combination chemotherapy, comprising weekly dosing of iv cisplatin (days 1 and 8) combined with a fixed dose (70 mg/m2/day) of S-1 (days 1-14) for patients with metastatic gastric cancer. The treatment was repeated every 3 weeks. Twenty patients were studied. Dose-limiting toxicities of grade 3 diarrhea and stomatitis were observed in one patient at the dose of cisplatin 20 mg/m2. Grade 2 gastrointestinal adverse reactions, such as nausea and anorexia, were seen in approximately half of patients at this dose level within the first two treatment cycles. This was the maximum acceptable level. The overall response rate in 18 patients evaluated was 61%. The median survival was 11 months, despite including 11 pre-treated patients. S-1 given with weekly cisplatin was a feasible and promising combination regimen for an outpatient setting.

Topics: Administration, Oral; Adult; Aged; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Diarrhea; Drug Administration Schedule; Drug Combinations; Female; Humans; Infusions, Intravenous; Male; Maximum Tolerated Dose; Middle Aged; Oxonic Acid; Stomach Neoplasms; Stomatitis; Survival Rate; Tegafur

We reported the results of phase I study with CPT-11 and S-1 (IRIS) in advanced gastric cancer (AGC) patients at ASCO 2002. Now I present an outline of this phase I/II trial. A combined treatment of IRIS (CPT-11 + S-1) was given to the AGC patients who had not received prior chemotherapy. S-1 was orally administered twice a day for 14 days, and CPT-11 was administered as a 90-minute intravenous infusion on days 1 and 15. This schedule was repeated every 4 weeks. Fifteen patients were registered in this phase I study and 9 patients were added in this phase II study. Non-hematological toxicities were almost classified as grade 2 or lower, except for grade 3 nausea and grade 3 dermatitis of level 2. These adverse events were manageable by administering anti-emetic drugs and a drug rest. As for hematological toxicities, grade 4 neutropenia occurred with one patient at level 1 and level 2 in phase I. And grade 4 neutropenia occurred with four patients at level 2 in phase II. However, they recovered after the drug rest, and we could continue the administration based on the standard dose modifications. These side effects were tolerable, and the overall response rate was 54.2%. MST of this regimen is 581 days. The IRIS treatment is effective and tolerable for outpatient treatments.

Topics: Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Capsules; Diarrhea; Drug Administration Schedule; Drug Combinations; Humans; Infusions, Intravenous; Irinotecan; Middle Aged; Nausea; Oxonic Acid; Quality of Life; Stomach Neoplasms; Survival Rate; Tegafur

In the present article, we have summarized the phase I/II clinical trials on combination therapy of S-1 and docetaxel. With result of the phase I study, patients were treated with intravenous infusion of 40 mg/m2 docetaxel on day 1 and oral S-1 80 mg/m2/day on days 1 to 14 every 3 weeks. Forty eight patients received a total of 272 treatment cycles. No complete responses (CRs) and 27 partial responses (PRs) were observed for an overall response rate (CR+PR) of 56.2% (95% CI, 38-66%). Eighteen patients (37.5%) had stable disease (SD), and 3 patients (6.2%) had progressive disease (PD) as best response. The tumor control rate (CR+PR+SD) was 93.8% (95% CI, 83-98%). The median overall survival was 14.3 months (95% CI: 10.7-20.3 months) and the median time to tumor progression was 7.3 months (95% CI: 4.2-10.7 months). The most common grade 3-4 hematologic toxicities were neutropenia 58.3%, leukopenia 41.7%, febrile neutropenia 8.3%, and anemia 8.3%. The most common grade 3 nonhematologic toxicities were anorexia 14.6%, stomatitis 8.3%, nausea 6.3%, diarrhea 4.2%, constipation 4.2%, and vomiting 2.1%. No grade 4 nonhematologic toxicities were reported, and all treatment-related toxicities were resolved. The mechanisms underlying these synergistic effects of S-1 and docetaxel were examined by expression and activity analyses of 5-FU metabolic enzymes. The expressions of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) were decreased and that of orotate phosphorybosyl transferase (OPRT) was increased in mRNA, protein level and activity assay after the treatment with docetaxel and 5-FU in the TMK-1 gastric cancer cell. These findings strongly indicate that the combination chemotherapy of docetaxel and S-1 is effective against gastric carcinomas and therefore is a good candidate as a standard chemotherapeutic strategy in treating these tumors.

Topics: Adult; Aged; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Docetaxel; Drug Administration Schedule; Drug Combinations; Humans; Infusions, Intravenous; Leukopenia; Middle Aged; Neoplasm Recurrence, Local; Neutropenia; Oxonic Acid; Stomach Neoplasms; Survival Rate; Taxoids; Tegafur

In the present article, we report the results of phase I/II combination chemotherapy study of biweekly paclitaxel and S-1 administration in patients with advanced gastric cancer. In the phase I study, we could determine the recommended dose for the phase II study with paclitaxel and S-1 to be 120 mg/m2 and 80 mg/m2, respectively. The side effect was not so severe. The overall response was 53%. In conclusion, biweekly paclitaxel and S-1 administration can be safely combined for the treatment of advanced gastric cancer. This combined therapy represents a novel and active treatment regimen with low toxicity and can be defined as safe and effective. Now we are analyzing the result of the phase II study.

Topics: Administration, Oral; Adult; Aged; Alopecia; Antineoplastic Combined Chemotherapy Protocols; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Female; Humans; Infusions, Intravenous; Leukopenia; Male; Maximum Tolerated Dose; Middle Aged; Oxonic Acid; Paclitaxel; Quality of Life; Stomach Neoplasms; Tegafur

Lentinan (LNT) is a beta-glucan known to have a life-prolonging effect in combination with chemotherapy for patients with unresectable or recurrent gastric cancer. Thus, a multi-center trial of chemo-immunotherapy using S-1 combined with LNT may benefit patients with unresectable or recurrent gastric cancer with acceptable toxicity. With such a regimen, the median survival time in 32 patients was 559 days. Regardless of change to second-line chemotherapy, the mean period of using S-1+LNT for patients with long NC above 400 days was 725 days. In subset analyses, the survival period of the patients with G/L ratio of equal to or less than 2 was significantly better than that of the higher one (p<0.0001). The incidence of hematological toxicity (grade 3 leukopenia and thrombocytopenia) was 6.3% (2/32), and non-hematological toxicity (grade 2 dysgeusia) was 6.3% (2/32), while no grade 4 toxicity was observed. S-1 and LNT combination immunotherapy was carried out safely with high QOL and allowed a prolonged administration. S-1+LNT regimen may prolong NC periods in patients with unresectable or recurrent gastric cancer.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Drug Administration Schedule; Drug Combinations; Female; Humans; Lentinan; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Oxonic Acid; Quality of Life; Stomach Neoplasms; Survival Rate; Tegafur

Both paclitaxel and S-1 are effective against gastric cancer, but the optimal regimen for combined chemotherapy with these drugs remains unclear. This phase I/II study was designed to determine the maximum tolerated dose (MTD), recommended dose (RD), dose-limiting toxicity (DLT), and objective response rate of paclitaxel in combination with S-1. S-1 was administered orally at a fixed dose of 80 mg m-2 day-1 from days 1 to 14 of a 28-day cycle. Paclitaxel was given intravenously on days 1, 8, and 15, starting with a dose of 40 mg m-2 day-1. The dose was increased in a stepwise manner to 70 mg m-2. Treatment was repeated every 4 weeks unless disease progression was confirmed. In the phase I portion, 17 patients were enrolled. The MTD of paclitaxel was estimated to be 70 mg m-2 because 40% of the patients given this dose level (two of five) had DLT. The RD was determined to be 60 mg m-2. In the phase II portion, 24 patients, including five with assessable disease who received the RD in the phase I portion, were evaluated. The median number of treatment courses was six (range: 1-17). The incidence of the worst-grade toxicity in patients given the RD was 28 and 8%, respectively. All toxic effects were manageable. The response rate was 54.1%, and the median survival time was 15.5 months. Our phase I/II trial showed that S-1 combined with paclitaxel is effective and well tolerated in patients with advanced gastric cancer.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Disease Progression; Drug Combinations; Female; Humans; Intestinal Neoplasms; Male; Maximum Tolerated Dose; Middle Aged; Neoplasm Recurrence, Local; Oxonic Acid; Paclitaxel; Stomach Neoplasms; Survival Rate; Tegafur; Treatment Outcome

The combination of a new oral dihydropyrimidine dehydrogenase-inhibitory fluoropyrimidine (S-1) and cisplatin (CDDP) is one of the most active chemotherapy regimens for gastric cancer. However, the optimum schedule for this combination has not yet been determined. This study was conducted to establish the maximum tolerated dose (MTD) and the recommended dose of CDDP when combined with 2-week S-1 administration, and to observe the safety and efficacy of the regimen as treatment for patients with advanced gastric cancer.. S-1 was administered orally at a dose of 80 mg/m2 per day for 2 weeks, followed by a 2-week rest. CDDP was administered intravenously on day 8 of each course; the initial dose of CDDP was 60 mg/m2 and it was increased in 10-mg/m2 increments. Treatment was repeated every 4 weeks unless disease progression was observed.. Eleven patients were enrolled. The main toxicities were leucopenia, neutropenia, nausea, and anorexia. These toxicities were not severe, and were reversible and manageable. The MTD for CDDP was established as 80 mg/m2, as 2 of 5 (40%) patients developed dose-limiting toxicity (DLT) at this level. Therefore, the recommended dose of CDDP was determined to be 70 mg/m2. All 11 patients were evaluable for a response: 8 achieved a partial response and 1 had stable disease. The overall response rate was 73%.. This regimen is considered to be generally well-tolerated and has substantial antitumor activity.

Topics: Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Administration Schedule; Drug Combinations; Female; Humans; Infusions, Intravenous; Male; Maximum Tolerated Dose; Middle Aged; Oxonic Acid; Pyridines; Stomach Neoplasms; Tegafur

Although combination therapy of S-1 and cisplatin (CDDP) has excellent efficacy against gastric cancer, the effect of the treatment on survival has been unclear. The aim of this study was to evaluate the long-term outcome of this combination therapy.. Sixty-three patients with advanced or recurrent gastric cancer were treated with S-1, with or without CDDP, as first-line chemotherapy, and the clinical results were compared retrospectively. S-1 was administered orally at a standard dose of 80 mg/m(2). In the treatment of the S-1 group, S-1 was given for 28 consecutive days, followed by a 14-day rest. In the treatment of the S-1/CDDP group, S-1 was given for 21 consecutive days, followed by a 14-day rest, and CDDP, at 60 mg/m(2), was infused on day 8.. The incidence of adverse reactions of more than grade 3 was 22.5% in the S-1 group and 43.5% in the S-1/CDDP group, and the treatment compliance was better in the S-1 group. The overall response rate was 25.9% in the S-1 group, and 36.8% in the S-1/CDDP group. The combination of S-1 with CDDP had better effects on the primary lesion and on differentiated-type carcinoma than S-1 alone. However, there was no difference in survival between the two patient groups. The median survival time after the initiation of treatment in the S-1 group was 322 days, and that in the S-1/CDDP group was 319 days.. Our results suggest that the combination of CDDP with S-1 does not improve the long-term outcome of S-1 therapy.

Topics: Administration, Oral; Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Female; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Oxonic Acid; Patient Compliance; Pyridines; Stomach Neoplasms; Survival Analysis; Tegafur; Treatment Outcome

This is a phase I study to determine the maximum tolerated dose (MTD) and toxicity of a combination of TS-1 and weekly cisplatin (CDDP) in advanced gastric cancer patients. TS-1 was administered orally twice daily after meals, at a standard dose of 80 mg/m2. One course consisted of 21 days' consecutive administration followed by 14 days' rest. Cisplatin (CDDP) was injected intravenously on days 8, 15 and 22 using the following dose levels: dose level 1 20 mg/m2, dose level 2 25 mg/m2, and dose level 3 30 mg/m2. Twelve patients were entered in this trial. One of the 6 patients at dose level 3 had neutropenia NCI-CTC grade 3, while another patient at dose level 3 suffered from DLT (liver function grade 3. The maximal tolerable dose (MTD) was not reached using dose level 3. Partial responses were seen in 5 (62.5%) of 8 patients with evaluable lesions. At level 2 (25 mg/m2), the response rate was 100%. We recommended dose level 2 for phase II trials from the standpoint of toxicity and response rate.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Administration Schedule; Drug Combinations; Humans; Maximum Tolerated Dose; Middle Aged; Nausea; Oxonic Acid; Pyridines; Stomach Neoplasms; Tegafur

We designed an outpatient regimen consisting of fractional cisplatin in combination with S-1, a novel oral fluoropyrimidine derivative for the treatment of recurrent or advanced gastric cancer and conducted a phase I study to determine the dose limiting toxicities (DLTs) and recommended dose (RD).. Escalating dosages of cisplatin (15, 20, and 25 mg/m(2), as levels 1, 2, and 3, respectively) were administered over 2 h on days 1, 8, and 15, with a fixed dose of S-1 for 3 consecutive weeks (days 1-21), repeated every 5 weeks. National Cancer Institute common toxicity criteria(NCI-CTC) grade 2 toxicities required treatment delay. Primary first cycle DLTs were defined as NCI-CTC grade 3 or 4 toxicities (except for hemoglobin levels, nausea, and vomiting).. Nine patients were initially enrolled, and DLTs did not appear; however, one level-3 patient experienced grade 3 anemia. An additional three patients were enrolled in level 3 to confirm the toxicity profiles, and none experienced DLTs. Toxicity evaluations throughout a total of 62 cycles revealed that grade 1 or 2 hematological toxicities were common, although mostly transient, with recovery without specific treatment. One patient each in levels 1 and 3 required hospitalization due to grade 3 toxicities in the later cycles. Mean dose intensities for S-1 and cisplatin were both more than 91%. There were no treatment-related deaths. The preliminary response rate was 44%.. It was concluded that the RD of cisplatin in this regimen was 25 mg/m(2) (level 3). S-1 in combination with fractional cisplatin is a promising regimen that allows repeated drug administration, in an outpatient setting, for advanced or recurrent gastric cancers. A phase II study of the RD is now under way.

Topics: Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Dose-Response Relationship, Drug; Drug Combinations; Female; Humans; Infusions, Intravenous; Male; Maximum Tolerated Dose; Middle Aged; Neoplasm Recurrence, Local; Oxonic Acid; Pyridines; Stomach Neoplasms; Tegafur

A phase I study of weekly intravenous paclitaxel combined with a fixed dose of S-1, a dihydropyrimidine-dehydrogenase-inhibitory oral fluoropyrimidine, was conducted for patients with advanced or recurrent gastric cancer (ARGC). Endpoints of this study were to examine the toxicity profile OF this regimen and to determine the recommended dose (rd) of paclitaxel.. S-1 was fixed at a dose of 80 mg/m(2) per day and was administered for 2 weeks (days 1--14) followed by a 2-week rest. Two dose levels of paclitaxel (level 1: 60 mg/m(2), level 0: 50 mg/m(2)) were studied. Paclitaxel was infused over 1 h on days 1, 8, and 15. Plasma sampling was performed to characterize the pharmacokinetics and pharmacodynamics of paclitaxel in some patients. Fifteen patients were enrolled (6 patients in level 1, and 9 patients in level 0). Dose-limiting toxicities were defined as grade 4 hematological (including grade 3 febrile neutropenia) and grade 3 non-hematological (except anorexia, nausea, vomiting and depilation) toxicities.. Three of 6 patients in level 1 developed grade 4 neutropenia or grade 3 febrile neutropenia, and 1 of them also showed grade 3 diarrhea, which settled the maximum-tolerated dose at this level. At level 0, 2 of 9 patients developed grade 4 neutropenia or grade 3 febrile neutropenia, and the RD of paclitaxel for this protocol was set at this level. Pharmacologic studies demonstrated the persistence of significant serum paclitaxel levels over 24 h after drug administration at both levels. Objective responses according to Response Evaluation Criteria in Solid Tumors were observed in 3 of 6 patients who had measurable disease.. A combination of S-1 and weekly paclitaxel was feasible and well tolerated, and is suggested to produce a worthwhile response in ARGC. These results warrant further investigation, and a phase II study has already been started.

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Drug Administration Schedule; Drug Combinations; Feasibility Studies; Female; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Oxonic Acid; Paclitaxel; Pyridines; Stomach Neoplasms; Tegafur; Treatment Outcome

A dose-escalation study of irinotecan (CPT-11) combined with S-1, a novel oral fluoropyrimidine, was performed to determine the maximum-tolerated dose (MTD), recommended dose (RD) and dose-limiting toxicities (DLTs) in advanced gastric cancer.. S-1 was administered orally at 80 mg/m(2)/day for 21 consecutive days followed by a 2 week rest. CPT-11 was given intravenously on days 1 and 15 of each course, at an initial dose of 40 mg/m(2)/day, stepping up to 60, 80, 100 or 120 mg/m(2)/day depending on the DLT. Courses were repeated every 5 weeks, unless disease progression or severe toxicity was observed. At a level of the RD, five patients were added to conduct a pharmacokinetic (PK) study.. A total of 24 patients were entered in this study. The MTD of CPT-11 was considered to be 100 mg/m(2), because 50% of the patients (3/6) developed DLTs, diarrhea and rash. Therefore, the RD of CPT-11 was set at the dose immediately below 80 mg/m(2). The overall response rate (RR) by the criteria of the Japanese Research Society of Gastric Cancer was 58.3% (14/24) and the RR at the RD was 66.7% (6/9), suggesting promising clinical efficacy. There were no significant differences between the PK parameters of S-1 on days 10 and 15.. S-1 with CPT-11 can be combined safely without CPT-11 effect on S-1 PK data and holds promise as an effective regimen for advanced gastric cancer.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Drug Combinations; Female; Humans; Irinotecan; Male; Maximum Tolerated Dose; Middle Aged; Neoplasm Staging; Oxonic Acid; Pyridines; Stomach Neoplasms; Survival Rate; Tegafur; Treatment Outcome

The conversion rate of tegafur (a component of S-1) to fluorouracil (FU) differs in Asians and whites because of polymorphic differences in the CYP2A6 gene. S-1 with cisplatin is considered highly active in Japanese gastric cancer patients. Therefore, we initiated a phase I pharmacokinetic study of this combination in our gastric cancer patients.. Patients received cisplatin intravenously on day 1 and S-1 orally, twice daily, on days 1 to 21 every 28 days. At level 1, the S-1 dose was 25 mg/m2/dose (50 mg/m2/d), but it was increased by 5 mg/m2/dose for the next level. Cisplatin was administered at 75 mg/m2 (for levels 1 and 2) but was then reduced to 60 mg/m2 (level 1A). At every level, a cohort of three patients, which could be expanded to six patients, was studied. Maximum-tolerated dose (MTD) was determined based on the dose-limiting toxicity (DLT) in the first cycle. Patients with histologic proof of gastric adenocarcinoma and near-normal organ function were studied.. Sixteen patients were enrolled. No DLTs occurred at level 1. However, DLTs occurred at levels 2 and 1A. The area under the curve for FU correlated significantly with DLT (P = .006) and grade 3 to 4 diarrhea (P = .004). Six partial responses were confirmed, including three at the MTD.. At the established MTD of S-1 plus cisplatin, the S-1 dose (50 mg/m2/d for 21 days) is lower in our study than in the Japanese study (80 mg/m2/d for 21 days). A multi-institutional phase II study of this active combination is currently accruing patients.

Topics: Adenocarcinoma; Administration, Oral; Adult; Antineoplastic Combined Chemotherapy Protocols; Area Under Curve; Cisplatin; Drug Combinations; Female; Humans; Infusions, Intravenous; Male; Maximum Tolerated Dose; Middle Aged; Oxonic Acid; Pyridines; Stomach Neoplasms; Tegafur; Treatment Outcome

Paclitaxel, S1 and their combined sequential administration is proposed to be examined installing UFT as an active control of adjuvant chemotherapy for curatively resected T3-4 gastric cancer in a multicenter Phase III trial. The primary endpoint is disease-free survival and the secondary endpoints are incidence of adverse events, overall survival and compliance. The sample size is 370 per treatment arm (1480 in total) for two hypotheses of the superiority of sequential use of paclitaxel followed by oral fluoropyrimidines to fluoropyrimidines (UFT/S1) alone and the non-inferiority of S1 to UFT to be tested by two-by-two factorial design. Abdominal CT or US is performed every 3 months in the first 2 years and every 6 months thereafter for 3 years in total to ensure recurrence data collection. This trial could appraise sequential combination therapy and efficacy of new drugs as adjuvant for gastric cancer treatment.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Disease-Free Survival; Drug Administration Schedule; Drug Combinations; Endpoint Determination; Humans; Middle Aged; Oxonic Acid; Paclitaxel; Pyridines; Pyrimidines; Stomach Neoplasms; Tegafur; Uracil

A dose-escalation study of weekly paclitaxel combined with S-1, a novel oral fluoropyrimidine, was performed to determine the maximum tolerated dose (MTD), the recommended dose (RD) and the dose-limiting toxicities (DLTs) in advanced gastric cancer.. Twelve patients were enrolled. S-1 was given orally at a fixed dosage of 40 mg/m(2) b.i.d. for 14 consecutive days, followed by a 1-week rest. Paclitaxel was scheduled to be given intravenously on days 1 and 8 at a dose of 50, 60, 70 or 80 mg/m(2), depending on the DLTs. Treatment was repeated every 3 weeks. A pharmacokinetic study was conducted in an additional 5 patients on days 7 and 8 during the first course given at the RD.. The MTD of paclitaxel was presumed to be 60 mg/m(2), because 50.0% of patients (2/4) developed DLTs (mainly grade 3 anorexia). DLT was observed in 1 out of 8 patients at a dose of 50 mg/m(2). Therefore, the RD of paclitaxel was estimated to be 50 mg/m(2). The preliminary response rate was 62.5% (5/8) at the RD. There were no significant pharmacokinetic interactions between S-1 and paclitaxel. An adequate plasma paclitaxel concentration for an antineoplastic effect was achieved with weekly doses of 50 mg/m(2).. Weekly paclitaxel combined with S-1 was demonstrated to exhibit a tolerable toxicity profile with therapeutic plasma concentration at the dose of 50 mg/m(2). This regimen could represent a novel and low toxic combination for advanced gastric cancer.

Topics: Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Dose-Response Relationship, Drug; Drug Combinations; Female; Humans; Male; Maximum Tolerated Dose; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Paclitaxel; Pyridines; Risk; Stomach Neoplasms; Tegafur; Time Factors; Treatment Outcome

The safety of chemotherapy combining TS-1 and pirarubicin (THP) for treatment of recurrent or locally advanced gastric cancer was evaluated. THP was administered by intravenous drip infusion at a dose of 14 mg/m2 every other week. TS-1 was administered orally at a dose of 40 mg/m2 twice a day for 2 weeks followed by 2 weeks of rest (level 1), for 3 weeks followed by 2 weeks of rest (level 2), and for 4 weeks followed by 2 weeks of rest (level 3). Three patients were treated with the level 1 schedule. One patient with peritoneal dissemination received 22 courses of the treatment, and benefited from a long-term NC. However the remaining 2 cases were diagnosed as PD after 4 courses and were withdrawn from further treatment. Two patients in this group suffered from grade 2 adverse events according to the NCI-CTC. Only 1 patient who had liver metastasis was treated at level 2. Fourteen courses were administered, and a PR was achieved while grade 2 adverse events were observed. One of 3 patients who were treated with level 3 had grade 3 adverse events. Consequently, 3 more cases were added to this dose level, and no additional grade 3 adverse events were observed, while grade 2 adverse events were seen in 4 cases. Urinary urgency had completely disappeared in 1 patient with peritoneal recurrence. Myelosuppression, which was the main observed adverse event, was well controlled and of brief duration. The response, including alleviation of clinical symptoms, was confirmed in 3 of 5 chemo-naive patients.

Topics: Adult; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Doxorubicin; Drug Administration Schedule; Drug Combinations; Female; Humans; Leukopenia; Liver; Male; Middle Aged; Nausea; Neoplasm Recurrence, Local; Oxonic Acid; Pyridines; Stomach Neoplasms; Tegafur; Vomiting, Anticipatory

A phase I/II clinical trial has been planned to evaluate the safety and efficacy of combination therapy of S-1 with low-dose cisplatin in patients with unresectable or recurrent gastric cancer. A new statistically as well as clinically deliberated study design is applied to determine the maximal benefits of combination chemotherapy. This trial uses a 'continual reassessment method' for evaluating toxicity and a "two-stage method" for assessing the response rate to determine the combination that achieves adequate tumor response without toxicity in a high proportion of patients. Three specialized institutions will recruit 10-16 patients for the phase I part of the trial, and 14 institutions, in conjunction with the three specialized ones, will enroll 42 patients for the phase II part. The goal of this trial is to establish a useful chemotherapeutic treatment in an outpatient setting.

Topics: Administration, Oral; Adult; Aged; Ambulatory Care; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Female; Humans; Leukopenia; Male; Middle Aged; Neoplasm Recurrence, Local; Neutropenia; Oxonic Acid; Pyridines; Stomach Neoplasms; Tegafur; Thrombocytopenia

We conducted a feasibility study using S-1, a novel oral derivative of 5-fluorouracil, as postoperative adjuvant chemotherapy for curatively resected gastric cancer patients.. Adjuvant chemotherapy consisted of eight courses (4-week administration and 2-week withdrawal) of S-1, at 80-120 mg/body per day. Forty-one patients from 11 institutions were enrolled in this pilot study, from November 1999 to October 2000.. Thirty-five patients were eligible. In 7 patients, S-1 administration was discontinued due to recurrence. Among the 28 patients without recurrence, the planned eight courses of S-1 were administered to 17 patients (60.7%). In 4 patients, S-1 administration was discontinued due to subjective symptoms, such as anorexia, in the first course. Adverse reactions such as neutropenia, leukopenia, elevated total bilirubin, anorexia, general fatigue, diarrhea, nausea, and stomatitis were seen in more than half of the patients. Although grade 3 neutropenia (29.3%), leukopenia (9.8%), and diarrhea (9.8%) were observed, no grade 4 adverse effects appeared. Compared with the treatment of unresectable or recurrent gastric cancer with S-1, the incidence of adverse reactions in the adjuvant setting was slightly higher, probably due to the influence of gastrectomy.. Except for the early development of anorexia, most likely due to adverse effects of surgery, postoperative administration of S-1 for 1 year seems feasible as adjuvant chemotherapy for gastric cancer.

Topics: Adenocarcinoma; Adult; Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Combined Modality Therapy; Drug Combinations; Feasibility Studies; Female; Humans; Incidence; Male; Middle Aged; Oxonic Acid; Pyridines; Safety; Stomach Neoplasms; Tegafur

The oral fluoropyrimidine S-1, which consists of a mixture of a 5-fluorouracil (5-FU) prodrug (tegafur), a dihydropyrimidine dehydrogenase inhibitor [5-chloro-2,4-dihydroxypyrimidine (CDHP)], and an inhibitor of orotate phosphoribosyltransferase [potassium oxonate (oxonic acid)], was developed to increase the feasibility and therapeutic index of 5-FU administered orally. The principal objective of this study was to assess the feasibility of administering S-1 on a once-daily-for-28-day schedule every 5 weeks, determine the maximum tolerated dose, characterize the pharmacokinetics of S-1, and seek evidence of anticancer activity.. Patients with advanced solid malignancies were treated with escalating doses of S-1 on a once-daily oral schedule for 28 days every 5 weeks. The maximum tolerated dose was defined as the highest dose in which fewer than two of the first six new patients experienced dose-limiting toxicity. The pharmacokinetic profiles of the tegafur, CDHP, and oxonic acid constituents were characterized.. Twenty patients were treated with 72 courses of S-1 at three dose levels ranging from 50 to 70 mg/m(2)/day. Diarrhea, which was often associated with abdominal discomfort and cramping, was the principal dose-limiting toxicity of S-1 on this protracted schedule. Nausea, vomiting, mucositis, fatigue, and cutaneous effects were also observed but were rarely severe. Myelosuppression was modest and uncommon. A partial response and a 49% reduction in tumor size were observed in patients with fluoropyrimidine- and irinotecan-resistant colorectal carcinoma. The pharmacokinetic data suggested potent inhibition of 5-FU clearance by CHDP, with resultant 5-FU exposure at least 10-fold higher than that reported from equitoxic doses of tegafur modulated by uracil in the oral fluoropyrimidine UFT.. The recommended dose for Phase II studies of S-1 administered once daily for 28 consecutive days every 5 weeks is 50 mg/m(2)/day. The pharmacokinetic data indicate substantial modulation of 5-FU clearance by CDHP. Based on these pharmacokinetic data, the predictable toxicity profile of S-1, and the low incidence of severe adverse effects at the recommended Phase II dose, evaluations of S-1 on this schedule are warranted in malignancies that are sensitive to the fluoropyrimidines.

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Area Under Curve; Colorectal Neoplasms; Dose-Response Relationship, Drug; Drug Combinations; Enzyme Inhibitors; Female; Follow-Up Studies; Humans; Lung Neoplasms; Male; Maximum Tolerated Dose; Middle Aged; Orotate Phosphoribosyltransferase; Oxonic Acid; Pyridines; Pyrimidines; Stomach Neoplasms; Tegafur; Time Factors

A randomized phase II clinical trial has been designed and started in the Japanese Foundation for Multidisciplinary Treatment of Cancer (JFMC) to select the better regimen between tailored CPT-11 + S-1 and the standard S-1 treatment for advanced or recurrent gastric cancer as the first line chemotherapy. Selection of the better treatment for general clinical practice in this clinical trial will lead to a more precise assignment of a promising regimen for a future phase III randomized trial, placing continuous 5-FU infusion as the reference arm. In this trial, subsidiary pharmacokinetic analysis for the tailored dose arm is also proposed. In order to continue chemotherapy for a long time and to obtain longer survival, our study design for the tailored therapy could be exploited, especially in the field of general clinical practice.

Topics: Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Drug Combinations; Female; Humans; Irinotecan; Male; Neoplasm Recurrence, Local; Oxonic Acid; Pyridines; Stomach Neoplasms; Tegafur

The predictive values of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) gene expressions were retrospectively evaluated in patients with gastric cancer treated by a regimen containing S-1. The study population consisted of 53 patients registered into different two phase II studies for metastatic gastric cancer; 27 patients treated by S-1-alone study: 26 patients treated with S-1 combined with irinotecan (CPT-11). TS and DPD gene expressions in primary tumours were measured by the real-time reverse transcription PCR method. There was no statistical difference in DPD gene expression in terms of response in cases treated with S-1 alone and those treated with S-1 plus CPT-11. TS mRNA of responding tumours was lower than that of nonresponding ones when treated with S-1 (P<0.005). In the S-1-alone group, taking TS cutoff as the median values, the response rate in the low TS group was 50%, but only 8% in the high TS group (P<0.05). Patients with low TS gene expression survived longer than those with high TS gene expression (P<0.0001). However, there was no statistically significant difference in response rate and survival between patients with low TS tumours and those with high TS tumours, when the cutoff was taken as the median value of TS gene expression in the group treated with S-1 plus CPT-11. In conclusion, treatment effects of S-1 monotherapy for gastric cancer were determined by the status of TS gene expression, regardless of DPD gene expression. TS predictive power was overcome by CPT-11 combination therapy with S-1.

Topics: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Dihydrouracil Dehydrogenase (NADP); Drug Combinations; Female; Gene Expression Profiling; Humans; Male; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Predictive Value of Tests; Prognosis; Pyridines; Stomach Neoplasms; Tegafur; Thymidylate Synthase; Treatment Outcome

There is no chemotherapy considered to be standard treatment for advanced gastric cancer worldwide, and there is no consensus as to whether combination or single agent therapy is preferred. In the phase I portion, a dose-escalation study of cisplatin (CDDP) combined with TS-1, new oral dihydropyrimidine dehydrogenase inhibitory fluoropyrimidine, was performed to determine the maximum-tolerated dose (MTD), recommended dose (RD), dose-limiting toxicities (DLTs), and objective response rate (RR) in advanced gastric cancer (AGC). TS-1 was given orally at 40 mg/m2 bid for 21 consecutive days following a 2-week rest. CDDP was planned to be given intravenously on day 8, at a dose of 60, 70, or 80 mg/m2, depending on the DLT. Treatment was repeated every 5 weeks, unless disease progression was observed. In the phase I portion, the MTD of CDDP was presumed to be 70 mg/m2, because 33.3% of patients (2/6) developed DLTs; mainly neutropenia. Therefore, the RD of CDDP was estimated as 60 mg/m2. In the phase II portion, 19 patients including 6 patients of the RD phase I portion were evaluated. The median administered courses was 4 (range: 1-8). The incidence of haematological and non-haematological toxicities (> or = grade 3) was 15.8 and 26.3%, respectively, but all were manageable. The RR was 74% (14/19, 95%) confidence interval: 54.9 (90.6%), and the median survival days were 383. This regimen is considered to be active against AGC with acceptable toxicity. In addition, currently, a randomized phase III study (JCOG 9912) for AGC patients not treated previously with chemotherapy is underway in Japan. It compares three arms: 5-FU alone, TS-1 alone and CPT-11 with CDDP therapy. We also initiated a randomized phase III study comparing TS-1 alone, and with CDDP for AGC. From those two phase III studies, we may be able to evaluate the clinical benefit of TS-1 in combination with CDDP versus TS-1 single, or 5-FU combined with CDDP therapy in terms of survival benefits and improving the QOL for AGC patients.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Drug Administration Schedule; Drug Combinations; Humans; Maximum Tolerated Dose; Oxonic Acid; Pyridines; Stomach Neoplasms; Tegafur

The Japanese Foundation for Multidisciplinary Treatment of Cancer (JFMC) has designed and initiated a randomized Phase II clinical trial planned as a first-line of chemotherapy for advanced or recurrent gastric cancer. The trial focuses on two groups and selecting the better of two regimens. The first group was given tailored CPT-11, adjusting individual optimal dosage using toxicity-based grading as an index in combination with TS-1, and the second group was given standard TS-1 treatment. The aim of this tailored dosage regimen for each individual patient is to continue chemotherapy as long as possible, and eventually, to prolong survival. In this trial, subsidiary pharmacokinetics analysis for the tailored arm is also proposed. We would like to introduce the significance and theory of tailored dosage chemotherapy in this paper.

Topics: Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Clinical Trials, Phase II as Topic; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Humans; Irinotecan; Maximum Tolerated Dose; Neoplasm Recurrence, Local; Oxonic Acid; Pyridines; Randomized Controlled Trials as Topic; Stomach Neoplasms; Tegafur

S-1 is a new oral fluorinated pyrimidine derivate, in which the oral 5-fluorouracil (5-FU) prodrug, tegafur, was combined with two 5-FU-modulating substances, 5-chloro-2,4-dihydroxypyridine (gimeracil), and potassium oxonate (oteracil), at a molar ratio of 1:0.4:1. The final mechanism of action is exerted by 5-FU. The present study is the first European phase II trial of S-1 in gastric cancer. The primary study objectives were the safety, toxicity and activity of S-1 in non-pretreated patients with gastric cancer. The secondary objective was the duration of response. Patients had to have histologically- or cytologically-verified metastatic or locally advanced, unresectable gastric cancer; S-1 was administered orally twice daily at 40, then 35 mg/m(2) for 28 days every 5 weeks. The starting dose of 40 mg/m(2) was found to be intolerable due to significant non-haematological toxicity, and this dose was rapidly reduced to 35 mg/m(2) twice daily. Of the 7 patients enrolled at the 40 mg/m(2) level, only 3 were evaluable. At 35 mg/m(2), a response rate of 26.1% (95% Confidence Interval (CI) 12.0-45.1%) in 23 enrolled patients, and 31.6% (C.I. 14.7-53.0%) in 19 evaluable patients according to an independent radiology review, was found. The median duration of response at 35 mg/m(2) (6 patients) was 223 days (range, 108-828 days), and of stable disease was 111 days (range 68-411 days). S-1 can be administered with an acceptable safety and toxicity in European patients at a dose of 35 mg/m(2) days 1 - 28 every 5 weeks and is associated with a moderate response rate similar to the results achieved with other fluoropyrimidines.

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Cohort Studies; Drug Combinations; Female; Humans; Male; Middle Aged; Oxonic Acid; Pyridines; Stomach Neoplasms; Tegafur; Treatment Outcome

Several chemotherapy regimens used against advanced gastric cancer have been studied extensively over the decades in an attempt to further improve the prognosis of patients. To date, no standard chemotherapeutic regimens have been established worldwide. S-1 (TS-1), a combination of ftorafur and two modulators, gimestat (CDHP) and oxonic acid, in a molar ratio of 1:0.4:1, has been widely used in Japan for the treatment of advanced gastric cancer, and much attention has been paid to attempts to increase its antitumor effect by combining it with other chemotherapeutic drugs. We treated 12 patients with advanced gastric cancer with 80 mg/m2 of S-1 for 21 days and 60 mg/m2 of cisplatin (CDDP) on day 8 every 5 weeks. The treatment was continued until disease progression, unacceptable toxicity, or the patient's refusal. Eight out of 12 evaluable patients achieved a partial response (PR), with a response rate of 66.7%. The incidence of grade 3 or 4 adverse effects, including myelosuppression and gastrointestinal toxicities, was 16.6%. None of the patients treated with this regimen died of adverse effects and none required hospitalization for the toxicity. We conclude that the combination of S-1 and CDDP seems to have a high therapeutic index, enhancing the antitumor effect of S-1 while maintaining modest adverse effects, thus suggesting the possible use of this combination based at the outpatient clinic (apart from a short stay in hospital during the infusion of CDDP with hydration). Further study with a large number of patients may be needed to confirm the combination of S-1 and CDDP to be an appropriate first-line chemotherapy for gastric cancer.

Topics: Adenocarcinoma; Adult; Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Digestive System Surgical Procedures; Drug Combinations; Drug Evaluation; Female; Humans; Japan; Liver Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Oxonic Acid; Peritoneal Neoplasms; Pyridines; Severity of Illness Index; Stomach Neoplasms; Survival Analysis; Tegafur; Treatment Outcome

The response rate of advanced or recurrent gastric cancer to S-1 (TS-1) is 46.5%, which is higher than the response rate of this type of cancer to any other anticancer agent. However, the incidence of adverse reactions to this drug has also been reported to be as high as 83.2%. According to a postmarketing survey, adverse reactions to this drug begin to appear 2-3 weeks after the start of drug administration. With these findings in mind, we recently devised a new dosing regimen for the drug, by which the drug is administered for 2-week periods separated by 1-week drug-free intervals (the 2-week regimen). The aim of this retrospective study was to evaluate the efficacy and feasibility of the 2-week regimen in comparison with a 4-week dosing regimen with a 2-week interval between sessions (the 4-week regimen) as the historical control.. The subjects were 27 patients with advanced or recurrent gastric cancer who received S-1 therapy at our center between September 1999 and November 2001. Of these patients, 14 who received the 4-week regimen before January 2001 served as historical controls, and the results in these patients were compared with those of the remaining 13 patients, who received the 2-week regimen after February 2001. Patient backgrounds, adverse reactions, compliance, and efficacy were investigated retrospectively.. The incidence of adverse reactions tended to be lower in the 2-week-regimen group (77%) than in the 4-week-regimen group (93%). The percentage of patients who received the drug for 6 months in complete compliance with the dosing schedule, as calculated by the Kaplan-Meier method, was 85% in the 2-week-regimen group and 40% in the 4-week-regimen group. The response rate to the drug was 23% in the 2-week-regimen group and 21% in the 4-week-regimen group.. These results suggest that this 2-week regimen may mitigate adverse reactions and prolong the medication period.

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Feasibility Studies; Female; Fluorouracil; Follow-Up Studies; Humans; Japan; Male; Middle Aged; Neoplasm Recurrence, Local; Oxonic Acid; Patient Compliance; Pyridines; Retrospective Studies; Severity of Illness Index; Stomach Neoplasms; Tegafur; Time Factors; Treatment Outcome

We have developed a clinical pathway to enable the safe continuous administration of S-1 (TS-1) in ambulatory care for patients with advanced gastric cancer. The S-1 clinical pathway includes a pathway for clinicians, a pathway for patients, and such assist tools as a medication diary, an explanatory document containing instructions relating to patient compliance, a table of associations between adverse reactions and prodromes, and general principles for dose reduction and withdrawal. These pathways and assist tools will improve the patient's perception of adverse reactions, thereby contributing to early discovery and rapid action against adverse events. The S-1 clinical pathway has been used with ten patients. S-1 administration has been continued in seven patients. In four of the seven patients, continued administration on the occurrence of adverse reactions was made possible by the use of appropriate measures such as drug withdrawal or dose reduction. It was confirmed that the S-1 clinical pathway was a useful tool for cancer chemotherapy in ambulatory care.

Topics: Adult; Aged; Ambulatory Care; Antimetabolites, Antineoplastic; Critical Pathways; Disease Progression; Drug Combinations; Female; Humans; Japan; Male; Medical Records; Middle Aged; Oxonic Acid; Pyridines; Quality Assurance, Health Care; Safety Management; Self Administration; Stomach Neoplasms; Tegafur; Treatment Outcome; Withholding Treatment

A previous phase II study showed that S-1 (TS-1) was effective for advanced gastric cancers and had mild toxicity. The present study aimed to evaluate the efficacy and feasibility of this novel anticancer drug combined with low-dose cisplatin (CDDP).. Fifteen patients with unresectable and recurrent gastric cancer were enrolled. S-1 was administered orally twice daily after meals, at a standard dose of 80 mg/m2 per day according to the late phase II trial protocol. One course consisted of 28 days' consecutive administration followed by 14 days' rest. Five or 10 mg CDDP was infused three times each week (days 1, 3, 5) during S-1 administration on hospitalization, and once each week (day 1) at the outpatient clinic. Patients' backgrounds, response rates, response durations, and time to progression were investigated.. None of the 15 patients had a complete response and 8 had a partial response. Therefore, the overall response rate was 53% (8/15). For site efficacy, the response rate was 50% (5/10) for the primary lesion, 50% (3/6) for liver metastasis, and 39% (5/13) for lymph node metastasis. The median response duration of the 8 responders was 4 months, and the time to progression was 3.3 months. Adverse reactions appeared in 60% (9/15). The incidence of adverse reactions of grades 3 and 4 was 13% (2/15) and 0%, respectively. As for hematological toxicity, grade 3 leukopenia was observed in 2 patients (2/15), but decreased hemoglobin level and thrombocytopenia did not appear. Although gastrointestinal adverse reactions appeared in 40% (6/15), all reactions were grades 1 and 2. Because of the mild toxicity, most patients were treated at the outpatient clinic.. Combination chemotherapy of S-1 and low-dose CDDP is expected to be a useful chemotherapy for advanced gastric cancer.

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Digestive System Surgical Procedures; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Female; Follow-Up Studies; Humans; Incidence; Japan; Liver Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Peritoneal Neoplasms; Pyridines; Retrospective Studies; Severity of Illness Index; Stomach Neoplasms; Tegafur; Time Factors; Tomography, X-Ray Computed; Treatment Outcome; Ultrasonography, Interventional

In the present study, in order to evaluate the feasibility of personalized chemotherapy, a prospective randomized pilot study was performed in 30 advanced or recurrent gastric cancer patients. As we have demonstrated previously, the expressions of mRNA from tumor biopsy samples for seven molecular markers, i.e., dihydropyrimidine dehydrogenase (DPD), glutathione S-transferase (GST)-pi, beta-tubulin (tub), O6-methylguanine-DNA methyltransferase (MGMT), multiple drug-resistant protein (MRP)-1, NADPH/quinone oxidoreductase (NQO)-1, and cytochrome p450 (P450), were examined by reverse transcription-polymerase chain reaction (RT-PCR) analysis and therapy was recommended in a flow chart that depended on the level of expression of these predictive molecular markers. We chose 12 therapeutic plans, including best supportive care (BSC). We treated 15 patients according to the gene expression profiles, and the remaining 15 patients (controls) were treated without recommended regimens, and the therapy was continued after the expression profiles were checked. Interestingly, 11 of 26 lesions (42.3%) responded after treatment given according to gene expression analysis; however, no clinical response was detected in the control group. The prediction of the response, including resistance, was successful in 75.9% by the gene expression profiles. Moreover, the survival of the patients with the recommended treatment was better than that of patients without a recommended protocol. These results indicate that personalized treatment may be beneficial for gastric cancer chemotherapy and further randomized trials should be carried out in the future.

Topics: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Cisplatin; Dose-Response Relationship, Drug; Drug Combinations; Drug Hypersensitivity; Drug Resistance, Neoplasm; Drug Therapy; Female; Gene Expression; Gene Expression Profiling; Humans; Japan; Male; Middle Aged; Neoplasm Recurrence, Local; Oxonic Acid; Pilot Projects; Predictive Value of Tests; Prospective Studies; Pyridines; Stomach Neoplasms; Survival Analysis; Tegafur; Treatment Outcome

This study was designed to investigate the role of thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), and thymidine phosphorylase (TP) in tumor progression and sensitivity to 5-fluorouracil (5-FU).. A total of 275 tumor samples from 275 patients with gastric cancer were utilized in this study. TS activity was determined in 130 samples by 5-fluorodeoxyuridine monophosphate binding assay. DPD activity was measured in 140 samples by radioenzymatic assay, and TP protein level was determined in 157 samples by an enzyme-linked immunosorbent assay (ELISA) system. These parameters were compared with several clinicopathologic factors and sensitivity to 5-FU determined by in-vitro ATP assay. The antitumor activities of 5-FU, uracil plus tegafur (UFT), and 1M tegafur--0.4 M 5-chloro-2,4-dihydroxypyridine--1 M potassium oxonate (S-1 [TS-1]) were also compared, using three human gastric cancer xenografts in nude mice.. There was no correlation between either TS or TP and sensitivity to 5-FU. However, a weak inverse correlation was found between DPD activity and sensitivity to 5-FU. High DPD activity in tumor resulted in poor prognosis, especially in patients who received 5-FU-based adjuvant chemotherapy. Although TP was significantly correlated with depth of tumor invasion and with lymphatic and venous invasions, TP alone had no impact on survival. On the other hand, TS, as well as peritoneal, hepatic, and lymph node metastases, was selected as an independent prognostic factor in gastric cancer. In the animal model, there was no significant difference in antitumor activities among the drugs in a tumor with low DPD activity. However, S-1 showed superior antitumor activity to 5-FU or UFT in tumors with high DPD activity.. DPD is considered to be a most important predictive factor of 5-FU sensitivity. The use of DPD inhibitory fluoropyrimidines is strongly recommended for tumors with high DPD activity.

Topics: Adult; Aged; Aged, 80 and over; Animals; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Combined Modality Therapy; Dihydrouracil Dehydrogenase (NADP); Drug Combinations; Female; Fluorouracil; Gastrectomy; Humans; Japan; Liver Neoplasms; Lymphatic Metastasis; Male; Mice; Mice, Inbred BALB C; Middle Aged; Multivariate Analysis; Neoplasm Staging; Oxidoreductases; Oxonic Acid; Peritoneal Neoplasms; Predictive Value of Tests; Pyridines; Retrospective Studies; Statistics as Topic; Stomach Neoplasms; Survival Analysis; Tegafur; Thymidine Phosphorylase; Thymidylate Synthase; Treatment Outcome; Uracil

TS-1, an anticancer, antimetabolis agent, has shown clinically superior antitumor activity against unresectable advanced or recurrent gastric cancer (UARG). A biological response modifier, lentinan (LNT) prolonged the survival period of patients with UARG when combined with tegafur (FT). To assess the efficacy, the safety and prognostic factors of chemo-immunotherapy using TS-1, a FT derivative, and LNT, we conducted a multi-institutional pilot study in patients with UARG. Patients were treated with TS-1 at 80 mg/m2/day (bid) for 4-weeks, and LNT was given at 2 mg/body (i.v.) in a week, followed by a 2-week rest for 4 cycles. Twenty-two patients were entered from 4 institutes and 19 patients were eligible. The median survival time in eligible patients was 400 days. The incidence of hematological toxicity (grade 2 leukopenia), and non-hematological toxicity (grade 3 nausea or fatigue) was 5.3% (1/19) and no grade 4 toxicity was observed. The response ratio was 37.5% in 8 patients who had been administered the planned dose of TS-1. In subset analyses, the survival period of the patients with normal (< 500 micrograms/ml) serum immunosuppressive acidic protein level was significantly (p < 0.0001) better than that of the higher one. The survival period for those patients whose granulocytes/lymphocytes ratio was not more than 2 tended to be better. From the prolonged survival periods, chemo-immunotherapy using TS-1 combined with LNT would seem to have a benefit against UARG, and reduced toxicity. Future clinical trials are warranted to confirm its potency.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Drug Administration Schedule; Drug Combinations; Female; Humans; Lentinan; Male; Middle Aged; Neoplasm Recurrence, Local; Oxonic Acid; Pilot Projects; Pyridines; Stomach Neoplasms; Survival Rate; Tegafur

The efficacy and safety of the oral fluoropyrimidine TS-1, which contains a dihydropyrimidine dehydrogenase (DPD) inhibitor, were examined in fifty-five patients with gastric cancer. The patients were divided into 28 with measurable cancer lesions (TUM group) and 27 without them (ADJ group). The total number of courses was 164 (mean: 5.9 courses) in the TUM group and 146 (mean; 5.4 courses) in the ADJ group. The response rate in the TUM group, excluding three patients who could not be evaluated because of incomplete administration, was 40% (CR: 4, PR: 6, NC: 6, PD: 9). Among responders, the mean number of courses to response was 2.2 and the median survival time (MST) was 21.7 months. In terms of safety, adverse reactions appeared in forty-five patients (82%) and the incidence was higher in the ADJ group. Major toxicities were leukopenia (38%), anorexia (27%), increased total bilirubin concentration (25%) and diarrhea (24%). Adverse reaction of grade 3 was found in only three patients (5.5%) and there were no drug-related deaths. In conclusion, TS-1 is safe and effective if attention is given to biweekly examinations for the development of adverse reactions.

Topics: Administration, Oral; Adult; Aged; Anorexia; Antimetabolites, Antineoplastic; Bilirubin; Drug Administration Schedule; Drug Combinations; Female; Humans; Leukopenia; Male; Middle Aged; Neoplasm Recurrence, Local; Oxonic Acid; Postoperative Period; Pyridines; Stomach Neoplasms; Tegafur

A dose-escalation study was conducted for patients with metastatic gastric cancer to determine the recommended dose of weekly intravenous (i.v.) cisplatin combined with a fixed dose of a new oral dihydropyrimidine dehydrogenase-inhibitory fluoropyrimidine, S-1, on an outpatient basis. Secondary endpoints were to define the toxicity profile and to determine tumour responses. S-1 was fixed at a dose of 70 mg/m(2)/day and was administered for 2 weeks followed by a 1-week rest. Three dose levels of cisplatin (10, 15 and 20 mg/m(2)) were studied. Cisplatin was infused over 30 min on days 1 and 8. 20 patients were enrolled. No dose-limiting toxicities (DLTs) were recorded during the administration of cisplatin up to 20 mg/m(2), except for grade 3 diarrhoea and stomatitis in one patient at dose level 3. No grade 4 adverse events occurred. However, grade 2 gastrointestinal adverse reactions, such as nausea and anorexia, were seen in 7 of 13 patients at dose level 3 within the first two treatment cycles. This was determined to be the maximum acceptable level that would not negate the advantages observed with use of an oral drug such as S-1. An objective tumour response was seen at all dose levels, and the overall response rate in the 18 patients evaluated was 61%. A higher response rate of 78% was observed in 9 patients who had received no prior chemotherapy. Oral S-1 with weekly cisplatin is a feasible and promising combination regimen that is appropriate for an outpatient setting. A randomised phase II study comparing this combination with S-1 alone in chemo-nai;ve patients is warranted.

Topics: Adult; Aged; Ambulatory Care; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Humans; Infusions, Intravenous; Middle Aged; Oxonic Acid; Pyridines; Stomach Neoplasms; Tegafur

We performed a critical evaluation of neoadjuvant chemotherapy (NAC) with TS-1 and cisplatin (CDDP) for advanced gastric cancer patients. Since October 2000, 37 patients with far advanced or non-curative resectable gastric cancer received NAC, together with TS-1 and CDDP after informed consent was obtained. TS-1 (80 mg/m2/day) was administrated for 21 consecutive days followed by 14 days rest as one course, and CDDP (50 mg/m2) was infused over 2 hours on day 8. After at least 2 courses of treatment, the patients underwent gastrectomy with lymphadenectomy. The median number of courses administered was 3 (range 2-7), and 6 cases were treated on an outpatient basis only. The overall response rate was 62.2% (no CR, but 23 PR), and the individual response rates were 67.6% for the primary lesion, 90.5% for lymph node metastasis including para-aortic region, 50.0% for liver metastasis and 14.3% for peritoneal dissemination, respectively. Toxicities were generally mild, no treatment-related death and no serious adverse reactions were observed. There were only 2 grade 4 anemia (5.4%), and leucopenia, neutropenia, anemia, thrombocytopenia of grade 3 were observed in one (2.7%), 3 (8.1%), 6 (16.2%), and 2 (5.4%) patients respectively at hematological toxicity. Appetite loss and diarrhea of grade 3 were observed in only one (2.7%) patient at nonhematological toxicity. Twenty-four cases had undergone surgical treatment, and resection was performed in all cases. Seventeen of the 24 (70.8%) patients underwent curative resection. There was no major morbidity following surgery. The patients were favorable both for operation time (229 min) and bleeding volume (365 ml). The mean duration of hospitalization after surgery was 23.5 days and the only complications were one leakage, ileus and 2 pancreatitis. Two-year survival rate was 46.8% and MST was 523 days. In conclusion, a combination of TS-1 and CDDP for NAC appears to be an effective treatment modality for far advanced gastric cancer patients in view of toxicities, antitumor effects and QOL of the patients.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Administration Schedule; Drug Combinations; Female; Gastrectomy; Humans; Lymph Node Excision; Lymphatic Metastasis; Male; Middle Aged; Neoadjuvant Therapy; Oxonic Acid; Pyridines; Stomach Neoplasms; Survival Rate; Tegafur

Irinotecan plus intravenous 5-fluorouracil with leucovorin is effective against gastrointestinal cancer. S-1 is an oral fluoropyrimidine derivative combining tegafur with the modulators 5-chloro-2,4-dihydroxypyrimidine (a potent dihydropyrimidine dehydrogenase inhibitor), and potassium oxonate (an orotate phosphoribosyl transferase inhibitor), in a molar ratio of 1 : 0.4 : 1. S-1 has a high response rate, of about 40%, in advanced gastric cancer. A phase I study was conducted to assess the maximum tolerated dose and the recommended dose of the combination of irinotecan and S-1.. Irinotecan was given intravenously over the course of 90 min on day 1 and S-1 was given orally from days 1 to 14 of a 21-day cycle. The dose of S-1 was 80 mg/m2 per day, given in two divided doses. The dose of irinotecan was escalated in a stepwise fashion from 100 mg/m2 (level 1; n = 3), to 125 mg/m2 (level 2; n = 3), and 150 mg/m2 (level 3; n = 6).. Dose-limiting toxicity did not occur during cycle 1, and the recommended dose for phase II studies was determined to be level 3, which was associated with grade 3 diarrhea in one patient, and with refusal to continue treatment because of prolonged fatigue in two patients. Grade 3 neutropenia developed in one of three patients at level 1 and level 2, and in two of six during cycle 1 of level 3. The recommended dose was determined to be 150 mg/m2 of irinotecan on day 1 and 80 mg/m2 per day of S-1 on days 1 to 14 of a 21-day cycle. Five of seven patients with measurable lesions had a partial response.. A combination of irinotecan and S-1 can be recommended for further phase II studies in patients with gastric cancer.

Topics: Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Drug Combinations; Fatigue; Female; Humans; Infusions, Intravenous; Irinotecan; Male; Maximum Tolerated Dose; Middle Aged; Neutropenia; Oxonic Acid; Pyridines; Stomach Neoplasms; Tegafur

A dose-escalation study of cisplatin (CDDP) combined with S-1, a new oral dihydropyrimidine dehydrogenase inhibitory fluoropyrimidine, was performed to determine the maximum-tolerated dose (MTD), recommended dose (RD), dose-limiting toxicities (DLTs), and objective response rate (RR) in advanced gastric cancer (AGC). S-1 was given orally at 40 mg m(-2) b.i.d. for 21 consecutive days following a 2-week rest. CDDP was planned to be given intravenously on day 8, at a dose of 60, 70, or 80 mg m(-2) depending on the DLT. Treatment was repeated every 5 weeks, unless disease progression was observed. In the phase I portion, the MTD of CDDP was presumed to be 70 mg m(-2), because 33.3% of patients (2/6) developed DLTs, mainly neutropenia. Therefore, the RD of CDDP was estimated as 60 mg m(-2). In the phase II portion, 19 patients including six patients of the RD phase I portion were evaluated. The median administered courses was four (range: 1-8). The incidences of severe (grades 3-4) haematological and nonhaematological toxicities were 15.8 and 26.3%, respectively, but all were manageable. The RR was 74% (14/19, 95% confidence interval: 54.9-90.6%), and the median survival day was 383. This regimen is considered to be active against AGC with acceptable toxicity.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Dihydrouracil Dehydrogenase (NADP); Dose-Response Relationship, Drug; Drug Combinations; Female; Humans; Male; Maximum Tolerated Dose; Middle Aged; Neoplasm Staging; Oxonic Acid; Pyridines; Stomach Neoplasms; Tegafur; Treatment Outcome

The prognosis for patients with advanced gastric cancer remains poor. Peritoneal metastasis is the most frequent cause of death in patients with gastric cancer, but the most appropriate treatment for patients with disseminated gastric cancer remains uncertain. S-1 is a newly developed oral fluoropyrimidine derivative with unusually high activity against several tumor types. The aim of this study was to evaluate the feasibility and efficacy of S-1 for the treatment of patients with disseminated gastric cancer. A total of 31 patients with primary or recurrent gastric cancer with peritoneal dissemination were entered into this study. One course of this single-drug therapy consisted of S-1 (80-120 mg) twice daily for 28 days, followed by a 2-week period of no treatment. These treatments were repeated until disease progression or patient refusal. With a median follow-up period in survivors of 293 days, the median survival time was 357 days. Toxicities were mild and no patient withdrew from treatment before disease progression. Grade 3 hematotoxicity was observed in only one patient. S-1 showed promising activity against gastric cancer with peritoneal dissemination and acceptable toxicity. Further evaluation of S-1 treatment is warranted in this disease.

Topics: Administration, Oral; Adult; Aged; Drug Administration Schedule; Drug Combinations; Female; Humans; Male; Middle Aged; Oxonic Acid; Peritoneal Neoplasms; Pilot Projects; Pyridines; Stomach Neoplasms; Survivors; Tegafur; Time Factors; Treatment Outcome

TS-1 is a novel oral fluoropyrimidine anticancer agent and show synergism with CDDP. The objectives of this study were to determine the clinical toxicities, antitumor effect, survival duration, and a recommended dosage schedule in combination with TS-1 and CDDP. Patients with measurable, locally advanced or metastatic gastric cancer were candidates for the study. Three patients were assigned to one of four levels of treatment, as follows. At first, TS-1 was administered orally twice a day for 14 consecutive days followed by 14 days rest and a 24-h infusion of CDDP (70 mg/m2) was administered on day 8 of 28 every 4 weeks. Next, duration of S1 administration was increased in increments of 25% and in increments of 50%. At last, only the dose of CDDP was increased in increments of 10 mg/m2. The first three patients did not have over grade 3 hematologic and nonhematological toxicity during any course. Grade 4 neutropenia occurred during the second course in two patients consecutively in increments of 50% of TS-1. Neutropenia was considered as a dose limiting toxicity. Nonhematologic side effects generally were mild. The overall response rate including all levels was 90.9%. Three complete responses (27.3%) and 8 partial responses (63.6%) were observed among the 11 patients. At first schedule, CR was two of three patients, and PR by the other (overall response rate, 100%). Survival rate of all cases in eight months were 100%. In conclusion, a combination of TS-1 and CDDP chemotherapy showed favorable antitumor activity and less adverse reaction compared to results reported with other chemotherapy. Administration of TS-1 for 14 days followed by 14 days rest, plus CDDP (70 mg/m2) on day 8 every 4 weeks would be recommended in the view of high responsibility and low adverse reaction.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Administration Schedule; Drug Combinations; Female; Humans; Male; Middle Aged; Oxonic Acid; Pilot Projects; Pyridines; Stomach Neoplasms; Survival Analysis; Tegafur

Eighteen patients with far advanced and recurrent gastric cancer with peritoneal dissemination were treated with a novel oral anticancer drug, TS-1, and assessed according to clinical effect. TS-1 was administered at a dose of 80-120 mg/day. One course consisted of consecutive administration of TS-1 for 28 days followed by 14 days rest. The 1- and 2-year survival rates and median survival time after administration of TS-1 were 63.2%, 23.7% and 437 days, respectively. Eight patients (44.4%) survived for 1 year or more. Adverse reactions consisted of reduction in hemoglobin level and hyperbilirubinemia at grades 3 and 4, which were observed in 3 patients and 1 patient, respectively. TS-1 is a promising drug for gastric cancer with peritoneal dissemination.

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Drug Administration Schedule; Drug Combinations; Female; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Oxonic Acid; Peritoneal Neoplasms; Pyridines; Stomach Neoplasms; Survival Rate; Tegafur

In the present study, we demonstrate the treatment results of TS-1 on 22 gastric carcinoma patients (15 far advanced and 7 recurrent patients) from June 1999 to December 2000. TS-1 was administered at 75 mg/m2/day, twice daily per body for 28 days followed by a 14-day interval (1 cycle). Successful treatment was obtained in from 1 to 11 cycles, and we obtained 9 (47.4%) partial responses (PR), 7 stable disease (NC) and progressive disease (PD) among 19 evaluable patients. PR was obtained in 7 (58.3%) out of 12 primary lesions of the stomach. We also obtained 1 CR of liver metastasis and 4 PR of 9 distant lymph node metastases (44.4%). Moreover, malignant ascites disappeared in 4 (57.1%) out of 7 cases and PR was obtained in 3 (50%) out of 6 measurable cases of peritoneal disease. In addition, two patients had hydronephrosis which improved after 1 cycle of TS-1 treatment. The adverse effects observed were grade 3 bone marrow suppression in three cases, severe diarrhea in one case, one case of liver dysfunction and a few cases of nausea and vomiting. These results indicate that the oral tegafur compound, TS-1, is a new therapeutic tools for advanced and recurrent gastric carcinomas, especially peritoneal disease.

Topics: Administration, Oral; Adult; Aged; Antimetabolites, Antineoplastic; Drug Administration Schedule; Drug Combinations; Female; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Oxonic Acid; Pyridines; Stomach Neoplasms; Tegafur

TS-1, a novel oral formation of 5-fluorouracil, consists of tegafur (5-FU), CDHP and Oxo. Low-dose cisplatin (CDDP) and TS-1 was evaluated in 12 patients with advanced or recurrent gastric cancer. CDDP was given biweekly at a dose of 15 mg/m2 infused for 30 minutes, and 80 mg/body of TS-1 was orally administered as many times as possible. The response rate was 41.7%. Median survival time was 13.3 months. In one case, an adverse reaction of grade 3 leucopenia was observed. Thus, thought it is necessary to watch for leucopenia, this chemotherapy could well be effective for patients with advanced or recurrent gastric cancer.

Topics: Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Administration Schedule; Drug Combinations; Female; Humans; Infusions, Intravenous; Male; Middle Aged; Oxonic Acid; Pilot Projects; Pyridines; Stomach Neoplasms; Survival Rate; Tegafur

To assess the efficacy and safety of S-1, a novel oral fluoropyrimidine derivative, we conducted a multicenter late phase II study in patients with advanced gastric cancer.. Fifty-one patients who had received no previous chemotherapy were enrolled. Fifty patients were eligible for efficacy and safety analyses. The overall response was evaluated for the 43 patients who had metastatic lesions. S-1 was administered orally after breakfast and dinner for 28 days, followed by a 14-day break. The dosages were assigned according to the patients' body surface area (BSA): BSA <1.25 m(2), 40 mg; 1.25-1.5 m(2), 50 mg, and BSA > or =1.5 m(2), 60 mg, twice daily.. The overall response to treatment was evaluated as partial response in 19 of the 43 patients (44%; 95% confidence interval 30-59%). The median survival time in all patients was 207 days with 1- and 2-year survival rates of 36.0 and 14.0%, respectively. Grade 3 adverse reactions included decreased hemoglobin values in 2 patients, leukopenia, neutropenia and diarrhea in 1 patient each. No other grade 4 or unexpected adverse reactions were seen.. S-1 is effective against advanced gastric cancer. This oral treatment is suitable for outpatients because of its mild toxicity. Further therapeutic benefits are likely to be obtained by combining S-1 with other chemotherapeutic agents.

Topics: Administration, Oral; Adult; Aged; Antimetabolites, Antineoplastic; Drug Administration Schedule; Drug Combinations; Female; Fluorouracil; Humans; Male; Middle Aged; Oxonic Acid; Pyridines; Stomach Neoplasms; Tegafur; Treatment Outcome

Many reports have demonstrated that thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) are biomarkers for the response and prognosis of patients treated with 5-fluorouracil (5-FU)-based chemotherapy. A newly developed orally administered drug, fluoropyrimidine (S-1), has been developed with clinical efficacy when combined with an inhibitor of DPD. In this study, the relationship between immunoreactivity to TS and DPD in biopsy specimens and the effects of chemotherapy was investigated in 41 patients treated with S-1 therapy for advanced gastric cancer. Response rates were 54% (13/24) in TS(+) and 53% (9/17) in TS(-) patients (p=0.938), and those of DPD(+) and (-) patients were 61% (11/18) and 48% (11/23) (p=0.397), respectively. The median survival time of all the subjects was 253 days. There was no significant difference in median survival time between TS(+) patients (284 days) and (-) patients (189 days: p=0.670). The 18 DPD(+) patients had median survival times slightly longer (338 days) than the 23 patients with DPD(-) (207 days: p=0.206). This study indicates that S-1 may be effective in the treatment of gastric cancer patients, regardless of intratumoral TS and DPD immunoreactivity status. Further studies are needed to confirm these results with larger numbers of patients.

Topics: Adult; Aged; Antibody Specificity; Antimetabolites, Antineoplastic; Dihydrouracil Dehydrogenase (NADP); Drug Combinations; Female; Humans; Immunohistochemistry; Male; Middle Aged; Oxidoreductases; Oxonic Acid; Pyridines; Stomach Neoplasms; Survival Analysis; Tegafur; Thymidylate Synthase; Treatment Outcome

In developing a new anticancer agent, it is most important to balance the antitumor activity and toxicity of the agent. S-1 was designed to achieve high activity and low toxicity. In it tegafur, a prodrug of 5-FU, is combined with two classes of modulators. CDHP, an inhibitor of 5-FU degradation in the liver, and Oxo, an inhibitor of 5-FU phosphoribosylation in the digestive tract. In both early and late Phase II studies, S-1 was effective against advanced or recurrent gastrointestinal cancer. Toxicities were generally mild, and there were no toxic deaths.

Topics: Administration, Oral; Antimetabolites, Antineoplastic; Colonic Neoplasms; Drug Administration Schedule; Drug Combinations; Female; Humans; Male; Middle Aged; Oxonic Acid; Pyridines; Rectal Neoplasms; Remission Induction; Stomach Neoplasms; Tegafur

S-1 is a novel oral fluorouracil antitumor drug that combines three pharmacological agents: tegafur (FT), which is a prodrug of 5-fluorouracil (5-FU); 5-chloro-2,4-dihydroxypyridine (CDHP), which inhibits dihydropyrimidine dehydrogenase (DPD) activity; and potassium oxonate (Oxo), which reduces gastrointestinal toxicity. Phase I and early Phase II clinical trials have already been completed. On the basis of the results of these trials, 80 mg/m2/day, given daily in two divided doses after breakfast and supper, a 28-day consecutive oral regimen is recommended. In this study, we investigated the pharmacokinetics of 5-FU, intact FT, CDHP, and Oxo, after administration of S-1, at a standard dose of 80 mg/m2/day, in advanced cancer patients. Twelve patients were recruited to the study; 5 patients with gastric cancer, 4 with colorectal cancer, and 3 with breast cancer. Among them, analysis was conducted on 12 patients for single administration and on 10 patients for consecutive administration. The initial dose of S-1 for each patient was determined according to his/her body surface area (BSA) as follows: for BSA < 1.25 m2, 80 mg/body/day; for 1.25 m2 < or = BSA < 1.5 m2, 100 mg/day; and for 1.5 m2 < or = BSA, 120 mg/day. For single administration, half of the standard dose was used. For 28-day consecutive administration, the standard dose was given daily in two divided doses. The average single dose per BSA was 35.9 mg/m2 (31.7-39.7 mg/m2). Pharmacokinetic parameters of plasma 5-FU were as follows: Cmax, 128.5 +/- 41.5 ng/ml; Tmax, 3.5 +/- 1.7 h; AUC(0-14), 723.9 +/- 272.7 ng x h/ml; and T(1/2), 1.9 +/- 0.4 h. In the 28-day consecutive regimen, there were no fluctuations in pharmacokinetics nor any drug accumulation. Because the pharmacokinetics of orally administered S-1 is almost similar to that of continuous i.v. infusion of 5-FU, we concluded that S-1 may improve patients' quality of life.

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Breast Neoplasms; Colorectal Neoplasms; Drug Combinations; Drug Evaluation; Female; Humans; Male; Middle Aged; Neoplasms; Oxonic Acid; Pyridines; Stomach Neoplasms; Tegafur

S-1 is a novel oral anticancer drug, composed of tegafur (FT), gimestat (CDHP) and otastat potassium (Oxo) in a molar ratio of 1:0.4:1, based on the biochemical modulation of 5-fluorouracil (5-FU). CDHP inhibits dihydropyrimidine dehydrogenase (DPD), an enzyme which degrades 5-FU, and maintains prolonged 5-FU concentrations in the blood and tumours. Oxo is distributed in the gastrointestinal tract at a high concentration after oral administration and alleviates gastrointestinal toxicity due to 5-FU. S-1 improves the tumour-selective toxicity of 5-FU by the actions of two modulators, CDHP and Oxo. We conducted a late phase II clinical trial of S-1 as an open trial in patients with advanced gastric cancer, to confirm its antitumour effect and adverse reactions. 51 patients with advanced gastric cancer were enrolled in the trial. S-1 was administered orally twice daily after meals, at a standard dose of 80 mg/m2/day. One course consisted of consecutive administration for 28 days and 14 days' rest. Administration was repeated over four courses. A complete response was obtained in 1 patient and partial responses in 24 patients, producing a response rate of 49% (25/51) (95% confidence interval (CI) 35.9-62.3%). The incidence of adverse reactions was 78% (40/51) and that of adverse reactions of grades 3 and 4 was 20%. Adverse reactions of grades 3 and 4 included a decrease in the haematocrit, leucopenia, granulocytopenia, diarrhoea, malaise and proteinuria. No serious unexpected adverse reactions were observed. In conclusion, S-1 was effective and well tolerated in patients with advanced gastric cancer.

Topics: Administration, Oral; Adult; Aged; Antimetabolites, Antineoplastic; Drug Combinations; Female; Humans; Male; Middle Aged; Oxonic Acid; Pyridines; Stomach Neoplasms; Survival Analysis; Tegafur; Treatment Outcome

To investigate the efficacy and safety of additional S-1 chemotherapy to S-1 plus oxaliplatin (SOX) regimen chemotherapy for Stage III gastric carcinoma (GC) after radical resection.. A total of 161 patients who were pathologically diagnosed as Stage III GC after D2 gastrectomy and received SOX regimen adjuvant chemotherapy between January 2012 and April 2016 were included in this retrospective study. SOX regimen postoperative chemotherapy was composed of Oxaliplatin and S-1, administrated every 3 weeks for 8 scheduled courses. After SOX chemotherapy, 76 patients preferred additional chemotherapy with S-1 (the ACT group), while additional S-1 chemotherapy was not given to the other 85 patients (control group). The ACT with S-1 was administrated every 3 weeks for 8 scheduled courses. Treatment was terminated in case of life-threatening adverse events or tumor progression, or patients' demand for termination. Progression-free survival (PFS), overall survival (OS), and adverse events were analyzed.. Additional S-1 chemotherapy may be helpful for improving the disease progression and survival for patients with Stage III GC after radical resection with an acceptable safety profile.

Topics: Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Female; Humans; Male; Middle Aged; Neoplasm Staging; Oxaliplatin; Oxonic Acid; Progression-Free Survival; Retrospective Studies; Stomach Neoplasms; Tegafur

Gastric cancer with para-aortic node (PAN) metastasis has a chance to be cured with multidisciplinary treatment of D2 and PAN dissection (PAND) following neoadjuvant chemotherapy (NAC), but its prognosis remains unsatisfactory. To establish a better multidisciplinary treatment, a better surrogate endpoint is needed. The present study focused on a pathological complete response at the PANs alone as a new surrogate endpoint and evaluated its prognostic value.. The study examined patients who received radical gastrectomy with D2 and PAND after NAC for gastric cancer with PAN metastasis from 2004 to 2015. The study compared five methods of evaluating the response to NAC: RECIST, clinical disappearance of PANs (cPAN), histological response of the primary tumor defined by Japanese Classification of Gastric Carcinoma (JCGC histological criteria) and Becker's criteria, and pathological disappearance of PANs (pPAN). The efficacy of these methods was compared using the hazard ratio (HR) for death between responders and non-responders.. Thirty-two patients were analyzed. The respective HR and 5-year overall survival rates of responders and non-responders were 1.316 and 49.1% vs. 60.0% by RECIST, 1.106 and 52.9% vs. 52.5% by cPAN, 0.246 and 71.3% vs. 28.6% by JCGC histological criteria, 0.239 and 76.2% vs. 36.8% by Becker's criteria, and 0.074 and 81.0% vs. 0.0% by pPAN.. A pathological complete response at the PANs had the lowest HR and clearly differentiated the survival, suggesting it might be a good surrogate endpoint for identifying future candidates for NAC in multidisciplinary treatment for gastric cancer with PAN metastasis.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Aorta; Biomarkers; Capecitabine; Cisplatin; Docetaxel; Drug Combinations; Female; Gastrectomy; Humans; Irinotecan; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neoadjuvant Therapy; Oxaliplatin; Oxonic Acid; Proportional Hazards Models; Response Evaluation Criteria in Solid Tumors; Retrospective Studies; Stomach Neoplasms; Survival Rate; Tegafur; Trastuzumab

To investigate the safety and efficacy of camrelizumab in combination with nab-paclitaxel plus S-1 for the treatment of gastric cancer with serosal invasion.. Two hundred patients with gastric cancer with serosal invasion who received neoadjuvant therapy from January 2012 to December 2020 were retrospectively analyzed. According to the different neoadjuvant therapy regimens, the patients were divided into the following three groups: the SOX group (S-1 + oxaliplatin) (72 patients), SAP group (S-1 + nab-paclitaxel) (95 patients) and C-SAP group (camrelizumab + S-1 + nab-paclitaxel) (33 patients).. The pathological response (TRG 1a/1b) in the C-SAP group (39.4%) was not significantly different from that in the SAP group (26.3%) and was significantly higher than that in the SOX group (18.1%). The rate of ypT0 in the C-SAP group (24.2%) was higher than that in the SAP group (6.3%) and the SOX group (5.6%). The rate of ypN0 in the C-SAP group (66.7%) was also higher than that in the SAP group (38.9%) and the SOX group (36.1%). The rate of pCR in the C-SAP group (21.2%) was higher than that in the SAP group (5.3%) and the SOX group (2.8%). The use of an anti-PD-1 monoclonal antibody was an independent protective factor for TRG grade (1a/1b). The use of camrelizumab did not increase postoperative complications or the adverse effects of neoadjuvant therapy.. Camrelizumab combined with nab-paclitaxel plus S-1 could significantly improve the rate of tumor regression grade (TRG 1a/1b) and the rate of pCR in gastric cancer with serosal invasion.

Topics: Adenocarcinoma; Adult; Aged; Albumins; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Female; Humans; Male; Middle Aged; Neoadjuvant Therapy; Oxonic Acid; Paclitaxel; Retrospective Studies; Stomach Neoplasms; Tegafur; Treatment Outcome

Oxaliplatin-based chemotherapy is associated with hepatic sinusoidal obstruction syndrome (SOS).. We analyzed patients from two prospective trials, in which capecitabine/oxaliplatin (XELOX, 8 cycles; n=51) and S-1/oxaliplatin [SOX, continuous (SOX-C, n=50), or intermittent (discontinuation after cycle 6 and restart on progression, SOX-I, n=50)] were administered. We compared severity (splenomegaly, thrombocytopenia, liver enzyme levels, and hepatic parenchymal heterogeneity), clinical significance (delay or dose-reduction of chemotherapy), and reversibility of SOS (splenomegaly and thrombocytopenia after stopping chemotherapy) between SOX and XELOX in gastric cancer patients.. SOX was more likely to be associated with splenomegaly, thrombocytopenia, hyperbilirubinemia, and hepatic parenchymal heterogeneity than XELOX. Splenomegaly was partially reversible after stopping chemotherapy in both regimens, but recovery rate was lower in SOX. Proportion of delayed or dose-reduced chemotherapy cycles due to thrombocytopenia was significantly higher in SOX-C than in XELOX.. S-1 combination is more likely to worsen oxaliplatin-induced hepatic sinusoidal injuries than capecitabine in gastric cancer patients.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Biomarkers; Capecitabine; Disease Management; Drug Combinations; Female; Hepatic Veno-Occlusive Disease; Humans; Incidence; Liver Function Tests; Male; Middle Aged; Oxaliplatin; Oxonic Acid; Retrospective Studies; Spleen; Splenectomy; Stomach Neoplasms; Tegafur; Treatment Outcome

The Japanese Gastric Cancer Treatment Guidelines recommend S-1 and S-1 plus docetaxel as postoperative chemotherapy for pathological stage II and III gastric cancer (GC). There is currently no strategy for using chemotherapy to treat high-risk recurrent pathological stage II/III. Previous studies reported that the several nutritional, immunological, and inflammatory markers examined the association with clinical outcomes after surgery for GC.. Ninety patients with GC (stage II, n = 48; stage III, n = 42) for whom gastrectomy was performed at our institution between November 2009 and September 2018 were examined. Nutritional, immunological, and inflammatory markers were calculated from blood samples within 1 week before surgery.. The prognostic nutritional index (PNI) status correlated with the pathological stage and disease recurrence after surgery (p = 0.015 and p < 0.0001, respectively). Thirty-three patients had disease recurrence after gastrectomy (stage II, n = 11; stage III, n = 22). The PNI was significantly lower in the recurrent group than in the non-recurrent group (p = 0.0003). The PNI correlated with overall survival and recurrence-free survival after gastrectomy (p = 0.0021 and p = 0.0001, respectively). A multivariate analysis identified the PNI as an independent prognostic factor (p = 0.006).. The PNI may be useful for predicting the outcomes of patients with pathological stage II/III GC and may contribute to the selection of an appropriate adjuvant chemotherapy regimen.

Topics: Aged; Aged, 80 and over; Chemotherapy, Adjuvant; Docetaxel; Drug Combinations; Female; Gastrectomy; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Nutrition Assessment; Oxonic Acid; Practice Guidelines as Topic; Prognosis; Retrospective Studies; Stomach Neoplasms; Survival Analysis; Tegafur; Treatment Outcome

Adjuvant tegafur-gimeracil-oteracil (S-1) is commonly used for gastric cancer in Asia, and tegafur-uracil (UFT) is another oral fluoropyrimidine when S-1 is unavailable. The real-world data of adjuvant UFT has less been investigated.. Patients with pathological stage II-IIIB (except T1) gastric cancer receiving adjuvant UFT or S-1 monotherapy after D2 gastrectomy were included. Usage of UFT or S-1 was based on reimbursement policy of the Taiwanese healthcare system. The characteristics, chemotherapy completion rates, and 5-year recurrence-free survival (RFS) and overall survival (OS), were compared between these two groups.. From 2005 to 2016, 86 eligible patients were included. Most tumor characteristics were similar between the UFT group (n = 37; age 59.1 ± 13.9 years) and S-1 group (n = 49; age 56.3 ± 10.7 years), except there were significantly more Borrmann type III/IV (86.5% versus 67.3%; p = 0.047) and T4 (56.8% versus 10.2%; p < 0.001) lesions in the UFT group than in the S-1 group. The chemotherapy complete rates were similar in the two groups. The 5-year RFS was 56.1% in the UFT group and 59.6% in the S-1 group (p = 0.71), and the 5-year OS was 78.3% in the UFT group and 73.1% in the S-1 group (p = 0.48). The hazard ratio of adjuvant chemotherapy (S-1 versus UFT) on RFS was 1.25 (95% confidence interval = 0.53-2.94) when Borrmann type and T and N stages were adjusted.. This small cohort study showed adjuvant UFT, and S-1 monotherapy had a comparable long-term outcome for pathological stage II-IIIB gastric cancer following D2 gastrectomy.

Topics: Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cohort Studies; Disease-Free Survival; Drug Combinations; Female; Humans; Middle Aged; Neoplasm Staging; Oxonic Acid; Prognosis; Stomach Neoplasms; Tegafur; Treatment Outcome; Uracil

Advanced gastric cancer (AGC) patients are not tolerant to the toxicities of traditional chemotherapy and its second-line therapeutic regimens are limited. The aim of the present study is to evaluate the efficacy and safety of apatinib combined with S-1 as the second-line therapy for AGC patients.Patients with AGC were enrolled in this study. Patients received oral apatinib (250 mg to 500 mg once daily) and S-1(40 mg/m2 twice daily) on days 1-14. Each cycle was 28 days and one course of treatment consisted of 2 cycles. Clinical efficacy and adverse events (AEs) were observed. Kaplan-Meier method was used for survival analysis.From November 2015 to December 2017, 58 AGC patients who failed first-line chemotherapy were enrolled and assessed retrospectively. According to the Response Evaluation Criteria in Solid Tumors (RECIST) standard, all patients were evaluable for response. None achieved CR, and 10 (17.2%) achieved PR (95% CI 7.2%-27.3%). SD was observed in 58.6% (34/58) of patients (95% CI 45.6%-71.7%) and NR in 24.1% (14/58) of patients (95% CI 12.8%-35.5%). The objective response rate (ORR) and the disease control rate (DCR) were 17.2% and 75.8% respectively. The median progression-free survival (PFS) and median overall survival (OS) were 143.1 days (95% CI 121.7-164.5) and 211.6 days (95% CI 162.9-219.7) respectively. The multivariate analysis showed that the ECOG PS was the independent factor of PFS and OS for AGC patients (PFS: HR = 3.565, 95% CI: 2.25-5.65, P < .001; OS: HR = 3.676, 95% CI: 2.29-5.89, P < .001). The main AEs were fatigue (72.4%), hypertension (46.6%), and leukopenia (48.3%).Apatinib combined with S-1 showed promising efficiency and was well tolerated as the second-line therapy for AGC patients. ECOG PS was the independent factor of PFS and OS for AGC patients. AEs were moderate and controllable, and leukopenia or hypertension was predictable factors for the PFS and OS of AGC patients.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Drug Therapy, Combination; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Multivariate Analysis; Oxonic Acid; Progression-Free Survival; Pyridines; Response Evaluation Criteria in Solid Tumors; Retrospective Studies; Stomach Neoplasms; Tegafur; Young Adult

For the past 20 years, S-1 has been used in the treatment of many types of cancer. However, the clinical importance of myocardial dysfunction attributed to S-1 remains to be unclear. Thus, in this study, we report on a patient with myocardial dysfunction associated with S-1.S-1 postoperative chemotherapy for gastric cancer was included as a treatment for a 65-year-old man. On day 8, S-1 treatment was discontinued after the patient developed an oral ulcer. He was then admitted to the hospital because of diarrhea caused by S-1. At approximately the same time, he developed dyspnea, and his chest X-rays revealed perihilar vascular engorgement and cardiac enlargement. Although his brain natriuretic peptide was 595.8 pg/mL, troponin I and creatine phosphokinase were unremarkable. Electrocardiograms showed no change in atrial fibrillations or new ST-T wave change. As per his transthoracic echocardiogram, noted were expansion of the left ventricle, global hypokinesis, and reduced left ventricular ejection fraction (approximately 40%). The patient was then diagnosed with S-1-related myocardial dysfunction. Furosemide, human atrial natriuretic peptide, dobutamine, enalapril, spironolactone, and bisoprolol were administered. Thirteen days after being diagnosed with heart failure, his symptoms disappeared, his echocardiogram showed that the left ventricular ejection fraction had increased to 65%, and the cardiothoracic ratio improved to 47% according to his chest X-rays.S-1-related myocardial dysfunction may be reversible, as it can improve after approximately 2 weeks.

Topics: Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Cardiotoxicity; Drug Combinations; Humans; Male; Oxonic Acid; Pyridines; Stomach Neoplasms; Tegafur

We report the case of a 36‒year‒old man who was treated with S‒1 plus oxaliplatin(SOX)therapy for gastric cancer with disseminated intravascular coagulation(DIC). The patient visited our hospital for the treatment of an unresectable type 4 advanced gastric cancer. He had respiratory distress at the first visit. A chest CT scan revealed ground‒glass shadows as well as interstitial and septal thickening diffusely located in both the lungs, which suggested cancerous lymphangiopathy. Moreover, based on blood test results, DIC was diagnosed. After the administration of SOX in combination with recombinant human soluble thrombomodulin, the patient recovered from DIC, and the values of the tumor markers(CEA and CA19‒9) were normalized. After more than 14 months post treatment, the patient has survived without relapse. There are several reports that chemotherapy for gastric cancer is effective for DIC; however, there are no reports on regimens using oxaliplatin. Regimens using this drug may improve the prognosis of gastric cancer complicated by disseminated myelocarcinomatosis and DIC.

Topics: Adult; Disseminated Intravascular Coagulation; Drug Combinations; Humans; Male; Neoplasm Recurrence, Local; Oxaliplatin; Oxonic Acid; Stomach Neoplasms; Tegafur; Thrombomodulin

This study aimed to evaluate the prognostic significance of PLA2G2A expression in patients with locally advanced gastric cancer (GC).. PLA2G2A expression levels in cancerous tissue specimens and adjacent normal mucosa obtained from 134 patients with stage II/III GC who received adjuvant chemotherapy with S-1 after curative resection were measured using real-time quantitative polymerase chain reaction. Subsequently, the associations of PLA2G2A expression with clinicopathological features and survival were evaluated.. No association was observed between clinicopathological features and PLA2G2A expression levels. Overall survival was significantly longer in patients with high PLA2G2A expression levels (p=0.022). Multivariate analysis revealed that PLA2G2A expression was a significant, independent prognostic factor (hazard ratio=0.136; 95% confidence interval=0.0185-0.992; p=0.049).. PLA2G2A mRNA expression may serve as a useful prognostic marker in patients with locally advanced GC who receive curative surgery and adjuvant chemotherapy with S-1.

Topics: Aged; Antineoplastic Agents; Chemotherapy, Adjuvant; Drug Combinations; Female; Gastrectomy; Gastric Mucosa; Group II Phospholipases A2; Humans; Male; Neoplasm Staging; Oxonic Acid; Prognosis; RNA, Messenger; Stomach; Stomach Neoplasms; Tegafur

Adjuvant chemotherapy has changed the paradigm in resectable gastric cancer. S-1 is an oral chemotherapeutic with promising efficacy in Asia. However, comparisons with close observation or platinum-based doublets post D2 gastrectomy have been less reported, notably on real-world experiences.. We retrospectively evaluated patients with D2-dissected stage IB-III gastric cancer who received S-1 (S-1, n = 67), platinum-based doublets (P, n = 145) and surgery with close observation (OBS, n = 221) from Jan 2008 to Oct 2018. A propensity score matching was used to compare for recurrence-free (RFS) and overall survivals (OS) in patients who had a locally-advanced disease (T3-4 or lymph node-positive). Adverse reactions, dosage, and associated factors for S-1 are also discussed.. In a median follow-up time of 51.9 months, adjuvant S-1 monotherapy was associated with an intermediate survival as compared with P and OBS (median RFS/OS: S-1 vs. P, 20.9/35.8 vs. 31.2/50.5 months, HR = 1.76/2.14, p = 0.021/0.008; S-1 vs. OBS, 24.4/40.2 vs. 20.7/27.0 months, HR = 0.62/0.55, p = 0.041/0.024). The survival differences were more prominent in patients with N2-3 diseases. S-1 was well-tolerated with a relative dose intensity of 73.6%, a median duration of 8.3 months and associated with less adverse reactions as compared with P. S-1 monotherapy was selected by physicians based on age, lymph node stage, serum carcinoembryonic antigen and disease stage.. Adjuvant S-1 correlated with intermediate survival outcomes between OBS and P but conferred fewer adverse reactions as compared with P. Patients with a moderate risk of recurrence had comparable survivals when treated with S-1 while platinum-based doublets were favored in advanced cases. The study provides additional information about adjuvant S-1 in patients with selected risk of recurrence.

Topics: Aged; Chemotherapy, Adjuvant; Drug Combinations; Humans; Middle Aged; Oxonic Acid; Propensity Score; Pyridines; Retrospective Studies; Stomach Neoplasms; Tegafur

S-1 plus oxaliplatin (SOX) is an established treatment for advanced gastric cancer. S-1 adherence is the key to successful SOX treatment. This study focused on S-1 adherence by evaluating real-world adherence to S-1 and investigating factors related to decreased S-1 adherence. This study included cases treated between August 1, 2014 and October 12, 2016 at the Cancer Institute Hospital of the Japanese Foundation for Cancer Research. The S-1 adherence rate per cycle was defined as the number of times a patient took S-1/28. In this study, adherence to S-1 was assessed through pill counts and by asking the patient about the reason for non-adherence at a pharmaceutical outpatient clinic. Univariate and multivariate analyses were performed to investigate factors influencing lower adherence. This analysis included 116 patients evaluated for adherence to S-1 on SOX treatment. The median rate of adherence to S-1 was 92.8% in the first cycle and 90.5% in the seventh cycle. The median relative dose intensity of S-1 was 84.6%. In terms of reasons for nonadherence, patients most commonly cited nausea/vomiting (43.7%), diarrhea (20.8%), missed dose (11.8%), and fever (8.1%). Logistic regression analysis was performed using the most appropriate regression equation, and a significant association was detected with 1 factor, number of combined drugs ≥5 (odds ratio (OR) = 2.50; 95% confidence interval (CI), 1.04-6.03, p = 0.04). Eliminating unnecessary concomitant medications helps maintain proper adherence to S-1 in SOX treatment.

Topics: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Diarrhea; Drug Combinations; Female; Humans; Logistic Models; Male; Medication Adherence; Middle Aged; Motivation; Nausea; Odds Ratio; Oxaliplatin; Oxonic Acid; Polypharmacy; Prescription Drugs; Stomach Neoplasms; Tegafur; Young Adult

We investigated whether the expression of L-type amino acid transporter 1 (LAT-1) in clinical gastric cancer (GC) patients could predict patient therapeutic response to postoperative adjuvant chemotherapy.. Immunohistochemistry was used to investigate LAT-1, CD98, and phosphorylated-mammalian target of rapamycin (p-mTOR) expression in 111 GC patients. To clarify whether LAT-1 influences the therapeutic effects of chemotherapy, the correlation between disease-free survival rates and LAT-1 was determined in 2 groups: 59 patients who did not undergo postoperative adjuvant chemotherapy and 52 patients who did undergo postoperative adjuvant chemotherapy.. LAT-1 was significantly correlated with CD98 and p-mTOR expressions. We did not find any statistically significant correlation between LAT-1 and recurrence in the nontreated group. In contrast, a significant association was found between LAT-1 expression and disease-free survival in the chemotherapy group. Moreover, multivariate regression analysis demonstrated that LAT-1 was an independent predictor of disease-free survival in the postoperative adjuvant chemotherapy group (p = 0.012).. Our findings demonstrate that LAT-1 is a useful predictive marker for a successful postoperative adjuvant chemotherapy treatment.

Topics: Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Chemotherapy, Adjuvant; Disease-Free Survival; Drug Combinations; Drug Resistance, Neoplasm; Female; Fluorouracil; Fusion Regulatory Protein-1; Humans; Immunohistochemistry; Large Neutral Amino Acid-Transporter 1; Male; Middle Aged; Neoplasm Recurrence, Local; Oxonic Acid; Phosphorylation; Prognosis; Prospective Studies; Stomach Neoplasms; Tegafur; TOR Serine-Threonine Kinases

It is elusive which subtypes of immune cells are pivotal in cancer progression and prognosis in gastric cancer (GC). The aim of this study is to clarify clinical impact of immature myeloid-derived immune cells in patients with GC who underwent curative gastrectomy with curative lymphadenectomy and treated with S-1 (tegafur/gimeracil/oteracil) postoperatively.. The prognostic impact of recruited CD33+ immature myeloid-derived cells were clinicopathologically analyzed in curatively resected stage II and III GC. Correlation of preoperative peripheral leukocyte fractions with recruited CD33+ immature cells was also assessed.. Patients with high CD33+ cell counts in primary tumor showed dramatically worse prognosis (5-y recurrence-free survival 29.0%) than that of the counterparts (79.4%). High CD33+ cell counts independently predicted poor prognosis in stage II/III (hazard ratio, 4.34; P < 0.001). In analyses of each stage, high CD33+ cell count was pivotally associated with poor prognosis in both stages. There was no significant correlation of each peripheral leukocyte fraction with CD33+ cell recruitment. Of note, high CD33+ cell count was significantly correlated with hematogenous recurrence.. Recruitment of CD33+ immature myeloid cells critically predict hematogenous recurrences in curatively resected advanced GC. These results give rational to focusing on CD33+ myeloid-derived cells as a novel approach to tackle advanced GC.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Disease-Free Survival; Drug Combinations; Female; Gastrectomy; Humans; Lymph Node Excision; Male; Middle Aged; Myeloid-Derived Suppressor Cells; Neoplasm Recurrence, Local; Neoplasm Staging; Oxonic Acid; Prognosis; Sialic Acid Binding Ig-like Lectin 3; Stomach; Stomach Neoplasms; Tegafur

Gastric cancer (GC) patients with positive peritoneal lavage cytology (CY1) and/or localized peritoneum metastasis (P1a) are defined as stage IV in the 15th edition of the Japanese Classification of Gastric Cancer. In Japan, the most common treatment for patients with CY1 and/or P1a is gastrectomy followed by postoperative chemotherapy.. Subjects in this multi-institutional retrospective study were GC patients with CY1 and/or P1a who received surgical resection that leaves no macroscopically visible disease. Patients were selected from 34 institutions in Japan between 2007 and 2012. Selection criteria included adenocarcinoma, no distant metastasis except CY1 and P1a, and no prior treatment for GC before surgery.. Among 824 patients registered, 506 were identified as eligible, with a background of P0CY1, P1aCY0, or P1aCY1 (72.5%, 16.0%, and 11.5% of subjects, respectively). Sixty-two patients had not received postoperative chemotherapy (no-Cx), whereas 444 patients had received postoperative chemotherapy: S-1 monotherapy (S-1; n = 267, 52.7%), cisplatin plus S-1 (CS; n = 114, 22.5%), and others (n = 63, 12.6%). Overall survival (OS) was 29.5, 24.7, 25.4 and 9.9 months in the S-1, CS, 'others', and no-Cx groups, respectively [CS vs. S-1: hazard ratio (HR) 1.15, 95% confidence interval (CI) 0.89-1.50; p = 0.275]. In multivariate analysis, OS was similar between the S-1 and CS groups (CS vs. S-1: HR 1.19, 95% CI 0.92-1.55; p = 0.18).. Postoperative chemotherapy after gastrectomy that leaves no macroscopically visible disease may have some survival benefits for GC patients with CY1 and/or P1a. In contrast, S-1 plus cisplatin seems to have no additional benefit over S-1 treatment alone.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Disease-Free Survival; Drug Combinations; Female; Gastrectomy; Humans; Japan; Male; Middle Aged; Neoplasm Recurrence, Local; Oxonic Acid; Peritoneal Cavity; Peritoneal Lavage; Peritoneal Neoplasms; Postoperative Period; Retrospective Studies; Stomach Neoplasms; Survival Rate; Tegafur; Young Adult

Little is known about the changes in prognostic factors after adjuvant S-1 monotherapy has become widespread as a standard of care for patients with gastric cancer (GC) in East Asia. The present study compared prognostic factors of patients with stage II/III GC treated with or without S-1 adjuvant to formulate appropriate risk stratification strategies.. We designed a large multicenter dataset and retrospectively analyzed 847 patients with GC stage II or III, who underwent curative gastrectomy between 2010 and 2014. Clinicopathological features and prognostic factors were compared between the two patient groups: surgery-alone (n = 266) and S-1 adjuvant (n = 581).. There were no significant differences in pathological tumor depths, nodal status, and disease stages between groups. Recurrence-free survival was significantly longer in the S-1 adjuvant group. For the surgery-alone group, independent prognostic factors were (in order of hazard ratio): (1) invasive growth, (2) high preoperative carcinoembryonic antigen levels, (3) total gastrectomy. For the S-1 adjuvant group, macroscopic tumor size (≥50 mm) was identified as another independent prognostic factor next only to pN2/3. There was overlap between the survival curves of patients with tumor size  ≥50 mm in both groups. After receiving adjuvant S-1 monotherapy,  ≥50 mm patients had significantly higher prevalence of peritoneal and lymph node metastasis as initial recurrences compared with  <50 mm patients.. Adjuvant S-1 monotherapy may alter listing of adverse prognostic factors of stage II and III patients. Macroscopic tumor size  ≥50 mm may serve as an important determinant for risk stratification to identify patients who require more intensive treatment.

Topics: Aged; Aged, 80 and over; Drug Combinations; Female; Gastrectomy; Humans; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Prognosis; Retrospective Studies; Stomach Neoplasms; Tegafur

Jumonji domain-containing protein 2A (JMJD2A) of the JMJD2 family of histone lysine demethylases has been implicated in tumorigenesis. However, its expression and role in gastric cancer (GC) drug resistance remain unknown. Here, we investigated the role of JMJD2A in GC chemotherapeutic susceptibility and its clinical relevance in GC.. We selected 12 relevant genes from previously identified gene signatures that can predict GC susceptibility to docetaxel, cisplatin, and S-1 (DCS) therapy. Each gene was knocked down using siRNA in GC cell lines, and cell viability assays were performed. JMJD2A expression in GC cell lines and tissues was assessed using qRT-PCR and immunohistochemistry, respectively. A JMJD2A downstream target related to drug susceptibility was examined using whole-gene expression array and immunoprecipitation.. Among the 12 candidate genes, down-regulation of JMJD2A showed the maximum effect on GC susceptibility to anti-cancer drugs and increased the IC. Our results indicate that JMJD2A is a novel epigenetic factor affecting GC chemotherapeutic susceptibility, and JMJD2A/CCDC8 is a potential GC therapeutic target.

Topics: Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Biomarkers, Tumor; Carrier Proteins; Cell Proliferation; Cisplatin; Docetaxel; Drug Combinations; Gene Expression Regulation, Neoplastic; Humans; Jumonji Domain-Containing Histone Demethylases; Oxonic Acid; Prognosis; Stomach Neoplasms; Tegafur; Tumor Cells, Cultured

S-1 plus oxaliplatin appears effective in chemo-naïve patients with advanced gastric cancer. However, comprehensive safety and efficacy data for S-1 plus oxaliplatin is limited for patients with impaired renal function.. We retrospectively extracted data from advanced gastric cancer patients with normal renal function (normal group, CLcr ≥ 60 ml/min), who were treated with standard doses of S-1 (80 mg/m2) plus oxaliplatin (100 mg/m2), and patients with impaired renal function (impaired group, CLcr < 60 ml/min) who were treated with standard or reduced doses of S-1 (60 mg/m2 or 40 mg/m2) plus standard doses of oxaliplatin. Treatment efficacy and safety between the groups were compared.. Data from 100 normal patients and 42 patients with impaired renal function were extracted. Baseline characteristics differed significantly between the two groups, including age (median, 64 vs 72 years, P < 0.0001) and body surface area (median, 1.68 vs 1.51 m2, P < 0.0001). In the impaired group, 66.6% (28/42) started with a reduced dose. Within the impaired group, more patients had a reduced initial S-1 dose when CLcr <50 ml/min (77.3%). The median progression-free and overall survival between the normal and impaired groups was 6.1 vs 5.7 months (P = 0.698) and 16.1 vs 18.5 months (P = 0.638), respectively.. S-1 plus oxaliplatin in advanced gastric cancer patients with impaired renal function appears safe and has demonstrated efficacy given appropriate dose modification.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Creatinine; Dose-Response Relationship, Drug; Drug Combinations; Female; Humans; Male; Middle Aged; Oxaliplatin; Oxonic Acid; Renal Insufficiency; Retrospective Studies; Stomach Neoplasms; Tegafur; Treatment Outcome

Epstein-Barr virus (EBV)-associated gastric cancer (GC) is associated with a high degree of DNA methylation. However, the association between chemotherapy susceptibility and tumor DNA methylation in advanced diseases remains unclear. The comprehensive DNA methylation status of GC cells obtained from an advanced EBV-associated GC (EBVGC) case, in which complete response to S-1 plus cisplatin chemotherapy was achieved, was analyzed using a DNA methylation microarray. We compared DNA methylation of GC cells with public data and identified genes with higher methylation in EBVGC cell lines than in normal gastric cells, and genes in which methylation was increased by EBV. Of these genes, ABCG2, AHNAK2, BCL2, FZD1, and TP73 are associated with published evidence for resistance to 5-fluorouracil and cisplatin. Silencing of these genes may be associated with hypersensitivity to chemotherapy.

Topics: Antineoplastic Agents; ATP Binding Cassette Transporter, Subfamily G, Member 2; Cell Line; Cisplatin; Cytoskeletal Proteins; DNA Methylation; DNA, Neoplasm; Drug Combinations; Drug Resistance, Neoplasm; Fluorouracil; Frizzled Receptors; Gene Silencing; Herpesvirus 4, Human; Humans; Male; Middle Aged; Neoplasm Proteins; Oligonucleotide Array Sequence Analysis; Oxonic Acid; Promoter Regions, Genetic; Proto-Oncogene Proteins c-bcl-2; Stomach Neoplasms; Tegafur; Tumor Protein p73

The enzymes gamma-glutamyl hydrolase (GGH) and folylpolyglutamate synthetase (FPGS) regulate intracellular folate concentrations needed for cell proliferation, DNA synthesis, and repair. High GGH expression affects 5-FU thymidylate synthase (TS) inhibition and is a risk factor for various malignancies. Here, the clinical significance of GGH and FPGS expression was investigated in Stage II/III gastric cancer patients undergoing postoperative adjuvant chemotherapy with S-1.. Surgical specimens of cancer tissue and adjacent normal mucosa, obtained from 253 patients with previously untreated gastric cancer, were examined. GGH and FPGS mRNA expression was measured by qPCR to evaluate their clinicopathological significance in gastric cancer patients after curative resection.. While FPGS expression showed no significant differences between the cancerous and normal samples, GGH expression was higher in cancer tissue than in adjacent normal mucosa. High GGH expression was correlated with age, histological type, and vascular invasion. Overall survival (OS) of patients with high GGH mRNA expression was significantly poorer than of patients with low GGH expression. Multivariate analysis showed that high GGH expression was an independent prognostic factor of OS (HR: 2.58, 95% CI 1.29-5.16). Patients who received S-1 adjuvant treatment showed a significantly poor OS between high GGH/low FPGS and low GGH/high FPGS. Patients without adjuvant treatment showed no significant difference.. GGH expression was significantly higher in gastric cancer tissue than in adjacent normal mucosa. High GGH and low FPGS expression is a useful independent predictor of poor outcomes in stage II/III gastric cancer patients undergoing postoperative adjuvant chemotherapy with S-1.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Chemotherapy, Adjuvant; Drug Combinations; Female; gamma-Glutamyl Hydrolase; Gastric Mucosa; Gene Expression; Humans; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Peptide Synthases; RNA, Messenger; Stomach Neoplasms; Tegafur

New chemotherapeutic regimens such as S-1 plus docetaxel, S-1 plus oxaliplatin and capecitabine plus oxaliplatin are reported to be effective and safe as postoperative adjuvant chemotherapy (PAC) for advanced gastric cancer (GC) patients. Although the use of these PACs is increasing, it is still unclear how to choose the best regimen for advanced GC patients. Therefore, we aimed to investigate which clinical characteristics are associated with recurrence after curative surgery in patients receiving S-1 as PAC. Thirty-nine patients who received a PAC regimen with S-1 for more than 1 year after curative surgery for advanced GC were enrolled. Univariate and multivariate analyses using the Cox proportional hazard model were performed to detect clinical characteristics that correlated with recurrence. Patients were divided into two groups, recurrence, and non-recurrence, and receiver operating characteristic (ROC) curve analysis was used to identify the cut-off values. Kaplan-Meier analysis and the log-rank test were used for comparison of relapse-free survival (RFS). Fifteen patients had a recurrence after surgery (38.5%, 15/39). Multivariate analysis using clinical characteristics revealed that preoperative C-reactive protein (CRP) (>0.3/≤0.3, mg/dL) (HR 10.73;95% C.I., 1.824-63.14;P=0.009) was significantly associated with recurrence. Kaplan-Meier analysis and the log-rank test demonstrated that preoperative CRP (>0.3/≤0.3, mg/dL) was also significantly associated with RFS (P<0.001). Therefore, preoperative CRP is significantly associated with recurrence and RFS after curative surgery in advanced GC patients receiving S-1 as PAC.

Topics: Antineoplastic Combined Chemotherapy Protocols; C-Reactive Protein; Chemotherapy, Adjuvant; Drug Combinations; Humans; Neoplasm Recurrence, Local; Neoplasm Staging; Oxonic Acid; Prognosis; Retrospective Studies; Stomach Neoplasms; Tegafur

Capecitabine plus oxaliplatin (XELOX) as adjuvant therapy for gastric cancer (GC) reduces cancer recurrence and improves survival. S-1 plus oxaliplatin (SOX) is well-tolerated and effective against advanced GC, and also be used widely in adjuvant treatment. However, data comparing SOX and XELOX as adjuvant treatments are lacking.. Data on treatment modalities, adverse events, recurrence and metastasis were collected from 180 patients with stage II and III GC, who received SOX or XELOX after D2 gastrectomy between January 2012 and December 2015, and analyzed retrospectively. The primary endpoint was 3-year disease-free survival (DFS) rate.. Median follow was 52.9 months; 3-year DFS rate and overall survival (OS) rate were 75.2% and 67.6% (P = 0.359) and 81.2% and 83.3% (P = 0.77) in the SOX and XELOX groups, respectively. There was no significant difference in peritoneal metastasis rates in the SOX and XELOX groups (8.6% vs 15%, respectively; P = 0.232). Compound recurrent disease was associated with significantly shorter OS. Multivariate analysis identified metastatic lymph node ratio (LNR) as an independent prognostic factor for OS (P = 0.036; hazard ratio = 2.875; 95% confidence interval, 1.069-7.729); the LNR ≥17% group had inferior 3-year OS rate to the LNR <17% group (P = 0.001). The incidence of grades 3 and 4 adverse events was similar in both groups; however, grade ≥2 hand-foot syndrome was significantly less frequent in the SOX group (P = 0.01).. SOX has similar survival benefits to XELOX and is well-tolerated in Chinese patients with GC following D2 gastrectomy.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Chemotherapy, Adjuvant; Drug Combinations; Female; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Oxaliplatin; Oxonic Acid; Retrospective Studies; Stomach Neoplasms; Survival Rate; Tegafur

This study aimed to explore novel microRNAs in plasma for predicting chemoresistance in adjuvant chemotherapy for patients with gastric cancer (GC). We used the Toray 3D-Gene microRNA array-based approach to compare preoperative plasma microRNA levels between GC patients with and without recurrences after curative gastrectomy. All patients underwent adjuvant chemotherapy with S-1, an oral fluoropyrimidine. Of 2566 candidates, six candidate microRNAs (miR-1229-3p, 1249-5p, 762, 711, 1268a and 1260b), which were highly expressed in the preoperative plasma of patients with subsequent recurrences, were selected. In a large-scale validation analysis by quantitative RT-PCR, we focused on high plasma levels of miR-1229-3p, which was an independent poor prognostic factor for recurrence free survival (P = 0.009, HR = 3.71). Overexpression of miR-1229-3p in GC cells induced significant chemoresistance to 5-fluorouracil (5-FU), up-regulation of thymidylate synthase (TS) and dihydroprimidine dehydrogenase (DPD) and down-regulation of SLC22A7 both in vitro and in vivo. Intraperitoneal injection of miR-1229-3p in mice induced significant chemoresistance to 5-FU, accompanied by high levels of miR-1229-3p in plasma and tumor tissue. These findings suggest that plasma miR-1229-3p might be a clinically useful biomarker for predicting chemoresistance to S-1 and selecting other or combined intensive chemotherapy regimens in GC patients.

Topics: Animals; Biomarkers, Tumor; Cell Line, Tumor; Cell Movement; Cell Survival; Disease-Free Survival; Drug Combinations; Drug Resistance, Neoplasm; Female; Fluorouracil; Gastrectomy; Humans; Male; Mice; Mice, Inbred BALB C; Mice, Nude; MicroRNAs; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Organic Anion Transporters, Sodium-Independent; Oxonic Acid; Prognosis; Proportional Hazards Models; Stomach Neoplasms; Tegafur

This study aimed to investigate the impact of postoperative complications (PCs) in patients with pathological stage (pStage) II or III gastric cancer (GC) who received adjuvant chemotherapy with S-1 after curative surgery.. Altogether, data for 226 patients were examined retrospectively. The relationship between PCs and clinicopathological features and survival were examined.. Recurrence-free survival was significantly worse in the group with PCs than in the PC-negative group. On multivariate analysis, having PCs of grade 2 or more was an independent risk factor for recurrence (hazard ratio=1.721; 95% confidence intervaI=1.014-2.920; p=0.044). In addition, for each pStage analysis, having PCs of grade 2 or more was a risk factor for recurrence even in patients with pStage II GC.. PC of grade 2 or more was an independent risk factor for recurrence in patients with pStage II GC who received adjuvant chemotherapy with S-1 after curative gastrectomy. Thus, for patients with PCs, even for those with pStage II GC, more effective adjuvant chemotherapy, such as S-1 plus docetaxel, may be needed.

Topics: Chemotherapy, Adjuvant; Drug Combinations; Female; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Oxonic Acid; Postoperative Complications; Prognosis; Stomach Neoplasms; Tegafur

Studies to identify predictive biomarkers of adjuvant chemotherapy with S-1 after gastrectomy in Stage II/III gastric cancer patients have been done; however, more clarity and understanding are needed. Our aim in the present study was to identify biomarkers predicting benefit due to S-1 adjuvant chemotherapy using comprehensive gene expression analysis.. We retrospectively analyzed 102 patients receiving adjuvant chemotherapy with S-1 and 46 patients not receiving S-1 adjuvant chemotherapy after gastrectomy for gastric cancer treatment between January 2014 and December 2016. Hierarchical clustering analysis was performed based on the gene expression data obtained using cDNA microarray. Differentially expressed genes (DEGs) were identified using thresholds of absolute fold changes of > 4.0 and a false discovery rate P value of < 0.01. Gene Ontology (GO) analysis and GO network visualization were performed using the ClueGO app in Cytoscape.. Hierarchical clustering analysis in patients treated with S-1 adjuvant chemotherapy revealed two clusters with favorable and unfavorable survival outcomes. We identified 147 upregulated DEGs and 192 downregulated DEGs in the favorable outcome group. GO analysis to identify significantly upregulated genes showed enrichment in immune-related genes and GO terms. Upregulation of these immune-related genes was not associated with survival in patients not receiving S-1 adjuvant chemotherapy.. The upregulation and enrichment of immune-related genes and GO terms may be predictive biomarkers in patients who would benefit from adjuvant S-1 chemotherapy to treat Stage II/III gastric cancer.

Topics: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Biomarkers, Tumor; Chemotherapy, Adjuvant; Drug Combinations; Female; Follow-Up Studies; Gene Expression Profiling; Humans; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Retrospective Studies; Stomach Neoplasms; Survival Rate; Tegafur; Young Adult

Several factors are known to be significantly associated with a low completion rate of 1-year adjuvant S-1 monotherapy for gastric cancer. The present study investigated whether or not the specialties of physicians conducting adjuvant S-1 monotherapy affect the completion rate.. A total of 437 patients who underwent curative gastrectomy followed by adjuvant S-1 monotherapy for pathological stage II or III gastric cancer between 2008 and 2013 were retrospectively analyzed. Factors affecting completion of adjuvant S-1 monotherapy, including the physicians (medical oncologists or surgeons) administering S-1, were evaluated by a multivariate analysis. The relationship between patient factors and physicians was analyzed regarding the cumulative incidence of discontinuation. The number of times the dose was reduced, the schedule changed, or administration was suspended or delayed in patients completing adjuvant S-1 monotherapy was also counted.. The multivariate analysis showed that old age (≥ 65 years old), excess body weight loss (≥ 15%), and surgeons were independently associated with discontinuation. In older patients, the cumulative incidence of discontinuation by medical oncologists was significantly lower than that by surgeons. Medical oncologists ensured that older patients continued S-1 by frequent suspension or a delay in each course.. Medical oncologists may facilitate completion of adjuvant S-1 monotherapy.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Drug Combinations; Female; Humans; Incidence; Male; Middle Aged; Neoplasm Staging; Oncologists; Oxonic Acid; Patient Compliance; Retrospective Studies; Stomach Neoplasms; Surgeons; Tegafur; Time Factors; Withholding Treatment

A 78-year-old man diagnosed with advanced gastric cancer and para-aortic lymph node metastases at clinical stage cT3 (SS)N1M1(LYN), Stage Ⅳwas treated with S-1/docetaxel(S-1/DTX)therapy. Eight months later, lymph node metastases resolved on abdominal CT, and the primary lesion appeared scarred when viewed by upper gastrointestinal endoscopy; this was considered to be a complete response(CR). S-1/DTX therapy was administered for a total of 16 courses, followed by 13 courses ofS -1 therapy. During the treatment, CR was maintained. Though chemotherapy was completed 2 years and 2 months after its initiation, the patient's serum CEA level was found to be elevated. As the serum CEA level gradually increased, S-1/DTX therapy was resumed. Three months after chemotherapy was restarted, PET-CT revealed multiple bone metastases. The chemotherapy protocol was changed to paclitaxel/ramucirumab therapy followed by nivolumab therapy. Disease control was difficult, and the patient died 9 months after reinstituting chemotherapy(3 years and 8 months after the first chemo- therapy). This case report summarizes our treatment ofa patient with advanced gastric cancer using S-1/DTX therapy for an extended period of time.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Docetaxel; Drug Combinations; Humans; Lymph Nodes; Lymphatic Metastasis; Male; Oxonic Acid; Positron Emission Tomography Computed Tomography; Stomach Neoplasms; Tegafur

Case 1: A 59-year-old man was diagnosed with type 3 gastric cancer cStage Ⅲ(MU, Gre, tub2>por, cT4aN2M0)induced by gastric perforation. The first surgery involving resection of the lesser curvature of stomach lymph node was judged to be difficult, and eventually exploratory laparotomy was performed. He received 3 courses of chemotherapy using S-1 plus oxaliplatin(SOX)(S-1 120mg/m2/day, day 1-14, oxaliplatin 100 mg/m2, day 1, followed by 7 days of rest). He subsequently underwent curative laparotomy gastrectomy plus D2(-No. 10)lymph node dissection, and Roux-en-Y reconstruction. Histological type was judged to be Grade 3. Case 2: A 69-year-old man was diagnosed with type 2 esophageal gastric junctional cancer,(GE, Less, tub2, cT4aN3M1[LYM])of cStage Ⅳ. He received 6 courses of chemotherapy using trastuzu- mab plus S-1 plus oxaliplatin(HER plus SOX)(trastuzumab 8mg/kg[2nd course 6mg/kg], day 1, S-1 120mg/m2/day, day 1-14, oxaliplatin 100mg/m2[5th course 80 mg/m2], on day 1, followed by 7 days of rest). He subsequently underwent laparotomy of the lower esophageal total gastrectomy plus D2(-No. 10, +No. 16, No. 110)lymph node dissection, and Roux-en-Y reconstruction as conversion surgery. Histological type was Grade 3. Both were impressive cases suggesting the usefulness of SOX therapy as a multidisciplinary treatment strategy for advanced gastric cancer.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Gastrectomy; Humans; Male; Middle Aged; Oxaliplatin; Oxonic Acid; Stomach Neoplasms; Tegafur

An 82-year-old woman presented with a dull feeling in her stomach and anemia. The gastroscopy and abdominal CT scan showed a progressive gastric tumor with multiple liver metastases, and a biopsy specimen revealed moderately differentiated tubular adenocarcinoma. A subtotal gastrectomy with D1 plus lymph node dissection was performed. The final diagnosis was as follows: H1, P0, CY0, M1, pT3, pN2, and fStageⅣ. We considered her age, and postoperative chemotherapy with of an oral anticancer drug, S-1, was initiated at a daily dose of 100 mg, with a 2-week administration and 1-week suspension schedule. The multiple liver metastases obviously reduced in size(PR)by 3 months, and the CT scan revealed complete response(CR)by 8 months after beginning S-1 administration. However, grade 2 anorexia and general malaise developed, so the S-1 administration was changed to a daily dose of 80 mg, with a 2-week administration and 2-week suspension schedule. However, an adverse event of nausea appeared again, and the patient needed a 2-month discontinuation. Therefore, S-1 administration was changed to alternate-day administration, at a daily dose of 100 mg. Subsequently, no side effects were observed, and we continued the S-1 administration for 4 years. She has maintained a complete response(CR) for 10 years, with no obvious cancer recurrence.

Topics: Aged, 80 and over; Antimetabolites, Antineoplastic; Drug Combinations; Female; Gastrectomy; Humans; Liver Neoplasms; Lymphatic Metastasis; Neoplasm Recurrence, Local; Oxonic Acid; Stomach Neoplasms; Tegafur

A 4-week administration of tegafur/gimeracil/oteracil (S-1) followed by a 2-week rest is the standard adjuvant chemotherapy for surgically resected advanced gastric cancer. This study aimed to evaluate the oncological feasibility of a 2-week S-1 administration followed by a 1-week rest, which is frequently applied in clinical practice to reduce toxicity and improve drug adherence.. We retrospectively enrolled patients with stage II/III gastric cancer who received S-1 adjuvant chemotherapy following radical gastrectomy from 2006 to 2016 in three institutions. Two-week and 4-week regimen cohorts were compared for relative dose intensity (RDI) as a primary outcome, and treatment completion rate, adverse event incidence, overall survival (OS), and relapse-free survival (RFS) as secondary outcomes. Confounders were adjusted for using propensity score matching (PSM).. One hundred and thirty-four patients received the 2-week regimen and 121 patients received the 4-week regimen. Ninety-five patients were extracted from each group after PSM. The RDIs of S-1 in the 2-week and 4-week cohorts were 73.5 and 69.9%, respectively (p = 0.35), which were not significantly different. The treatment completion rate (54.7 vs. 53.7%, p = 1.0), incidence of grade ≥3 adverse events (7.4 vs. 12.6%, p = 0.33), 3-year OS (76.4 vs. 82.7%, p = 0.78), and 3-year RFS (71.3 vs. 73.4%, p = 0.70) did not significantly differ between both cohorts.. The 2-week S-1 adjuvant chemotherapy could not improve drug adherence in terms of RDI, but its relapse rates were not significantly different compared with those of the 4-week regimen. The 2-week regimen might be considered as an option depending on the patient's status.

Topics: Aged; Chemotherapy, Adjuvant; Drug Combinations; Female; Gastrectomy; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Oxonic Acid; Propensity Score; Retrospective Studies; Stomach Neoplasms; Tegafur; Treatment Outcome

CDO1 is a presumed tumor suppressor gene in human cancers, the expression of which is silenced by promoter DNA methylation. Moreover, CDO1 harbors functionally oncogenic aspects through modification of mitochondrial membrane potential. We recently proposed that this oncogenic feature allows for the prediction of the efficacy of postoperative chemotherapy in colon cancer. The present study aims to elucidate the efficacy of prediction of success of postoperative chemotherapy in advanced gastric cancer to improve the treatment strategy of patients.. Forced expression of CDO1 in gastric cancer cell lines was assessed using the JC-1 assay. Promoter DNA methylation was investigated in quantitative TaqMan methylation-specific polymerase chain reaction in 321 pathological stage II/III advanced gastric cancer cases treated by curative gastrectomy with or without postoperative chemotherapy.. (1) Forced expression of CDO1 led to increased mitochondrial membrane potential, accompanied by augmented survival in gastric cancer cells under anaerobic conditions. These results suggest that CDO1-expressing cancer cells survive more easily in anaerobic lesions which are inaccessible to anticancer drugs. (2) Intriguingly, in cases with the highest CDO1 methylation (ranging from 15% to 40%), patients with postoperative chemotherapy showed significantly better survival than those with no postoperative chemotherapy. (3) A robust prognostic difference was observed that was explained by differential recurrences of distant metastasis (P = 0.0031), followed by lymph node (P = 0.0142) and peritoneal dissemination (P = 0.0472).. The oncogenic aspects of CDO1 can be of use to determine patients with gastric cancer who will likely respond to treatment of invisible systemic dissemination by postoperative adjuvant chemotherapy.

Topics: Age Factors; Aged; Aged, 80 and over; Antineoplastic Agents; Biomarkers, Tumor; Cell Line, Tumor; Chemotherapy, Adjuvant; Cysteine Dioxygenase; DNA Methylation; Drug Combinations; Drug Resistance, Neoplasm; Epigenesis, Genetic; Female; Follow-Up Studies; Gastrectomy; Humans; Kaplan-Meier Estimate; Male; Neoplasm Recurrence, Local; Neoplasm Staging; Oxonic Acid; Prognosis; Promoter Regions, Genetic; Retrospective Studies; Risk Factors; Stomach; Stomach Neoplasms; Tegafur

Glioma-associated oncogene 1 (GLI1) is an important transcription factor in the hedgehog signalling pathway and tumour formation. We evaluated the clinical significance of GLI1 expression as a prognostic factor in patients with locally advanced gastric cancer (GC).. GLI1 expression levels were measured by quantitative real-time polymerase chain reaction analysis of cancerous and adjacent normal mucosa specimens obtained from 142 patients with Stage II/III GC administered adjuvant chemotherapy with S-1 after curative resection. The associations of GLI1 expression with clinicopathological features and survival were evaluated.. Clinicopathological features and GLI1 expression showed no association. Overall survival was significantly poorer in the high compared to the low GLI1 expression group (p=0.04). Multivariate analysis revealed that GLI1 expression was a significant independent prognostic factor [p=0.019, hazard ratio (HR)=1.94, 95% confidence interval (CI)=1.70-3.38].. GLI1 expression may be a useful prognostic marker in patients with locally advanced GC.

Topics: Aged; Aged, 80 and over; Biomarkers, Tumor; Disease-Free Survival; Drug Combinations; Female; Gene Expression Regulation, Neoplastic; Humans; Male; Neoplasm Staging; Oxonic Acid; Prognosis; Stomach Neoplasms; Tegafur; Zinc Finger Protein GLI1

The patient was a 65-year-old man who developed dyspnea after 6 courses of S-1 and oxaliplatin(SOX)chemotherapy for advanced stomach cancer. The chemotherapy regimen consisted of SOX chemotherapy. The patient developed hypoxemia, and chest radiography revealed ground-glass opacity in both lungs. Bronchoscopy and DLST led to a diagnosis of druginduced lung injury caused by S-1. Although steroid pulse therapy was administered, the patient's condition deteriorated rapidly and was ultimately fatal. Based on the clinical course and histopathological findings, a DAD-type lung disorder was diagnosed. This description of a DAD-type drug-induced lung injury caused by S-1, for which histopathological findings were available in the early stages, is clinically valuable. We report this case along with a review of the relevant literature.

Topics: Aged; Biopsy; Drug Combinations; Humans; Lung; Lung Injury; Male; Oxonic Acid; Stomach Neoplasms; Tegafur

After undergoing an upper gastrointestinal endoscopy, a 74-year-old woman with anemia was diagnosed with advanced lower gastric cancer. We performed laparotomy and identified the tumor as unresectable because of the direct invasion to the pancreas. S-1 was administered at 60mg/day for 2 weeks followed by 1-week discontinuation. After 6 weeks, we changed the schedule to the same dosage of S-1 for 1 week followed by 2-week discontinuation. CT and endoscopic findings showed complete response after 64weeks of S-1 administration. Since then, S-1 has been maintained at 60mg/day intermittently for 14 days in 7 weeks accordingto the patient's condition. The patient is currently doingwell with a complete response for more than 5 years.

Topics: Aged; Antimetabolites, Antineoplastic; Drug Combinations; Female; Humans; Oxonic Acid; Remission Induction; Stomach Neoplasms; Tegafur

Some postoperative gastric cancer patients have to terminate systemic intravenous chemotherapy early due to adverse drug reactions. We performed a retrospective study to explore the efficacy and feasibility of sequential therapy.We retrospectively analyzed 55 postoperative gastric cancer patients (Group A) who received sequential therapy (intravenous chemotherapy and S-1) and 53 patients (Group B) who received intravenous chemotherapy from January 2012 to December 2013 in our hospital. The therapeutic effect (including 1-year, 5-year tumor recurrence and survival rate) and the incidence of adverse reactions were analyzed.When death and survival for more than 5 years was regarded as the end point of follow-up, the mean follow-up period was 40.6 months (34.7-46.4) in Group A and 39.2 months (33.0-45.3) in Group B. The 1-year tumor recurrence after the operation was 23.6% (13/55, Group A) and 28.3% (15/53, Group B). The 5-year tumor recurrence was 45.5% (25/55, Group A) and 49.1% (26/53, Group B). There was no significant difference in the 1- and 5-year tumor recurrence rates between these two groups (P > .05). The 1-year survival rates of Group A and Group B were 81.8% (45/55) and 79.2% (42/53), respectively, and the 5-year survival rates of Group A and Group B were 47.3% (26/55) and 45.3% (24/53), respectively. No significant difference was observed between these two treatments at either the 1- or 5-year survival benefit (P > .05). However, the patients in Group A had a lower incidence of gastrointestinal reactions (such as nausea and vomiting), leukopenia and liver function damage (P < .05). We also found that patients who underwent sequential therapy might show lower levels of adverse reactions.Our retrospective study provided some evidence to suggest that sequential treatment is effective and safe for postoperative gastric cancer patients who are intolerant to intravenous chemotherapy.

Topics: Administration, Oral; Adult; Aged; Chemotherapy, Adjuvant; Drug Combinations; Feasibility Studies; Female; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Oxonic Acid; Postoperative Period; Retrospective Studies; Stomach Neoplasms; Survival Analysis; Tegafur

The KIAA1199 gene has been associated with cancer-cell proliferation, but its functions remain poorly studied. Here, we examined the clinical significance of the KIAA1199 mRNA levels in locally advanced gastric cancer (GC). Materials and Methods/Results: Using samples from 254 patients with stage II/III GC, we found significantly higher KIAA1199 levels in cancerous tissues compared to adjacent normal mucosa (ANM). There was no significant relationship between KIAA1199 expression and clinical features. Although overall survival rates (OSR) of patients, who underwent surgery did not correlate with KIAA1199 expression, patients who underwent adjuvant chemotherapy with S-1 and had high KIAA1199 levels displayed significantly lower OSR. KIAA1199 knock down (KIAA1199-KD) suppressed proliferation, invasiveness, and sensitivity of GC cells to 5-fluorouracil (5-FU).. KIAA1199 expression appears to be a promising prognostic marker in patients with locally advanced GC, who underwent postoperative adjuvant chemotherapy with S-1. KIAA1199 may represent a novel target for GC pharmacotherapy.

Topics: Aged; Cell Line, Tumor; Cell Proliferation; Chemotherapy, Adjuvant; Digestive System Surgical Procedures; Drug Combinations; Female; Gene Expression Regulation, Neoplastic; Humans; Hyaluronoglucosaminidase; Male; Middle Aged; Neoplasm Invasiveness; Oxonic Acid; Prognosis; Stomach Neoplasms; Survival Analysis; Tegafur; Up-Regulation

We sought to assess the prognostic significance of lymph node ratio (LNR) and N stage in patients undergoing D2 gastrectomy and adjuvant chemotherapy, S-1, and XELOX and to compare the efficacy of them according to LNRs and N stages to evaluate the clinical impact of using LNRs compared with using N staging.. Patients undergoing D2 gastrectomy with adequate lymph node dissection and adjuvant chemotherapy for stage II/III gastric cancer between Mar 2011 and Dec 2016 were analysed. Of the 477 patients enrolled, 331 received S-1 and 146 received XELOX. LNR groups were segregated as 0, 0-0.1, 0.1-0.25, and > 0.25 (LNR0, 1, 2, and 3, respectively). Propensity score matching (PSM) was used to minimise potential selection bias and compare DFS and OS stratified by LNRs and N stages in the two treatment groups.. After PSM, the sample size of each group was 110 patients, and variables were well balanced. All patients had more than 15 examined lymph nodes (median 51, range 16~124). In multivariate analysis, LNR (> 0.25) and N stage (N3) showed independent prognostic value in OS and DFS, but LNR (> 0.25) showed better prognostic value. In subgroup analysis, the LNR3 group showed better 5-year DFS (20% vs 54%; HR 0.29; p = 0.004) and 5-year OS (26% vs 67%; HR 0.28; p = 0.020) in the XELOX group. The N3 group showed better 5-year DFS (38% vs 66%; HR 0.40; p = 0.004) and 5-year OS (47% vs 71%; HR 0.45; p = 0.019) in the XELOX group. Stage IIIC showed better 5-year DFS (22% vs 57%; HR 0.32; p = 0.004) and 5-year OS (27% vs 68%; HR 0.32; p = 0.009) in the XELOX group. The LNR3 group within N3 patients showed better 5-year DFS (21% vs 55%; HR 0.31; p = 0.004) and 5-year OS (27% vs 68%; HR 0.34; p = 0.018) in the XELOX group.. LNR showed better prognostic value than N staging. LNR3, N3 and stage IIIC groups showed the superior efficacy of XELOX to that of S-1. And the LNR3 group within N3 patients showed more survival benefit from XELOX. LNR > 0.25, N3 stage and stage IIIC were the discriminant factors for selecting XELOX over S-1.. Not applicable (retrospective study).

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Chemotherapy, Adjuvant; Drug Combinations; Female; Humans; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Oxaliplatin; Oxonic Acid; Retrospective Studies; Stomach Neoplasms; Tegafur; Young Adult

Neoadjuvant chemotherapy(NAC)with S-1 plus CDDP(SP)followed by gastrectomy has been used for the treatment of patients with locally advanced gastric cancer. We examined the number of treatment courses, histologic effects, ypStage, and prognosis to estimate the utility and define the best treatment course of SP NAC. The patients were divided into 1 course(A: 54 cases), 2 courses(B: 50 cases), and incomplete first course(C: 12 cases). The rates of Grade 2 or more in histological effect were 24.1% in group A, 34.0% in B, and 0% in C. Four patients achieved pathological CR(1 case in group A and 3 cases in group B). The pathological response by NAC was more effective in group B than in group A. In down-staging cases by NAC, survival curves were obtained according to ypStage. The 5-year survival rates in R0 cases were 67.0%in the effective therapeutic group and 51.0%in the non-effective group; the results being significantly different. According to the number of therapeutic courses of NAC, the 5-year survival rates were 57.9% in group A, 65.2% in group B, and 20.0% in group C, demonstrating a significantly better prognosis in group B. Although the pathological response appeared in 1 course, it was significant in 2 courses of NAC. The results indicate that the completion of at least 2 courses of NAC are necessary in locally advanced gastric cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Humans; Neoadjuvant Therapy; Neoplasm Staging; Oxonic Acid; Stomach Neoplasms; Tegafur

Gastroscopy ofa 79-year-old man complaining ofanemia showed a type 3 tumor at the lesser curvature ofthe gastric body. A biopsy revealed poorly differentiated HER2-negative adenocarcinoma. Abdominal CT showed the tumor at the lesser curvature ofthe gastric body, multiple lymph nodes with a maximum diameter of 25mm at the lesser curvature, and a mass measuring 50mm with ring enhancement on S6 ofthe liver. The clinical diagnosis was cT4aN2M1(Hep), cStage Ⅳ. He was treated with chemotherapy comprising 4 courses ofS -1 plus oxaliplatin. Although the tumor had shrunk remarkably, chemotherapy was discontinued because of anorexia. Therefore, we performed total gastrectomy and hepatic partial resection(S6). The final staging was ypT3N0M0, ypStage ⅡA. We achieved R0 resection, and he has shown no recurrence without adjuvant chemotherapy for 3 years.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Gastrectomy; Humans; Liver Neoplasms; Male; Neoplasm Recurrence, Local; Oxaliplatin; Oxonic Acid; Stomach Neoplasms; Tegafur

Although the S-1 plus CDDP(SP)regimen is the standard treatment for advanced gastric cancer, hydration and admission have been recommended after cisplatin has been administered. In this study, short hydration(SH)method was used and SP was administered in outpatient settings. We evaluated renal toxicity of cisplatin in the SH-SP regimen at our hospital.. Eleven of 16 patients(5 underwent only 1 course and so were excluded)received the SH-SP regimen between January 2012 and January 2018 to present and were included. Serum creatinine(Cr)and estimated glomerular filtration rate(eGFR)were used to assess renalfunction.. Median course was 5. Rate of 5-course accomplishment was 72.7%. Grade 1 Cr elevation was observed in only 3 patients and there was no severe renal disorder.. The SHSP regimen could be administered in outpatient settings and was considered safe as it did not cause renal toxicity.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Humans; Kidney Diseases; Outpatients; Oxonic Acid; Stomach Neoplasms; Tegafur

A 78-year-old man presented with anemia, with a hemoglobin level of 6.7 g/dL, during follow-up for angina pectoris and paroxysmal atrial fibrillation. Upper gastrointestinal endoscopy revealed type 2 advanced gastric cancer(por), and abdominal computed tomography(CT)showed multiple lymph node metastases. He was diagnosed with advanced gastric cancer, cStage Ⅲ(cT3N1M0). He received neoadjuvant chemotherapy in 3 courses of SOX(80mg/m / 2/day of S-1 on days 1-14 and 7 days of rest, and 100mg/m2 of oxaliplatin on day 1). Grade 1 thrombocytopenia was observed, but it resolved without any other major side effects. Upper gastrointestinal endoscopy revealed a marked reduction in the primary lesion, and abdominal CT showed a significant reduction in the metastatic lymph node. We performed laparoscopic distal gastrectomy(D2+No. 14v)for advanced gastric cancer ycT1N(+)M0, ycStage ⅡA. Histological assessment revealed no evidence of residual tumor cells in the primary tumor or lymph nodes, and the histologic response was classified as Grade 3, pathological complete response(pCR). We report a case in which pCR was obtained by SOX therapy administered as neoadjuvant chemotherapy for advanced gastric cancer.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Gastrectomy; Humans; Male; Neoadjuvant Therapy; Oxaliplatin; Oxonic Acid; Stomach Neoplasms; Tegafur

We report a case of advanced gastric cancer with right gastroepiploic vein tumor thrombus treated using preoperative S-1 plus cisplatin(CDDP)in which pathological complete response was achieved. A 78-year-old man was diagnosed with type 2 gastric cancer located at the greater curvature of the antrum, accompanied by right gastroepiploic vein tumor thrombus. Four courses of S-1 plus CDDP were administered as neoadjuvant chemotherapy. After 2 courses, computed tomography(CT) revealed the disappearance of the tumor in the right gastroepiploic vein thrombus. Distal gastrectomy with D2 lymphadenec- tomy was performed, and the diagnosis was pathological complete response(CR). Eight courses of S-1(100mg/day on days 1-28, followed by 2 weeks of rest)were administered as adjuvant chemotherapy. During the 1-year postoperative follow up, the patient showed no recurrence. An S-1 plus CDDP regimen can be a useful preoperative chemotherapy option for advanced gastric cancer with tumor vein thrombus.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Gastrectomy; Humans; Lymphatic Metastasis; Male; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Oxonic Acid; Stomach Neoplasms; Tegafur; Thrombosis

In Japan, S-1 adjuvant chemotherapy for 1 year is the standard of care for the treatment of stage II and III patients under 80 years old with gastric cancer after curative operation. However, the feasibility of S-1 chemotherapy in patients over 80 years old has not yet been elucidated.. To clarify the current treatment situation and feasibility of S-1 treatment in patients over 80 years old, a questionnaire survey of the patients treated from January 2011 to December 2012 was conducted at 58 member institutions of the Stomach Cancer Study Group of the JCOG (Japan Clinical Oncology Group).. Gastrectomy was performed in 15,573 patients of all ages, and 1,660 (10.7%) patients were over 80 years of age. Of these elderly patients, 661 (4.2%) were diagnosed as stage II and III. While S-1 adjuvant chemotherapy was recommended to 248 (37.5%) of the stageII/III patients, only 99 (15.0%) of them actually received S-1. Interestingly, the creatinine clearance rate was between 30 and 80 mL/min in 87 (87.9%) of the patients suggesting that S-1 dose modification should be considered. Moreover, S-1 compliance was poor in patients with more than 15% body weight loss.. In general practice, surgery alone can be regarded as the standard of care for stage II and III gastric cancer patients over 80 years old. The feasibility and efficacy of S-1 adjuvant chemotherapy should be elucidated in a randomized control trial considering the vulnerabilities of the elderly.

Topics: Aged, 80 and over; Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Drug Combinations; Female; Gastrectomy; Humans; Male; Oxonic Acid; Practice Patterns, Physicians'; Stomach Neoplasms; Surveys and Questionnaires; Tegafur

We investigated early tumor shrinkage (ETS) and depth of response (DpR) using data from the G-SOX study comparing S-1 plus oxaliplatin with S-1 plus cisplatin as the first-line treatment for advanced gastric cancer (AGC).. ETS was determined as % decrease in the sum of the longest diameters of the target lesions at the first evaluation of week 6 compared to baseline. DpR was the maximum % shrinkage during the study treatment. The impact of ETS (cutoff value 20%) and DpR (continuous value) on progression-free survival (PFS) and overall survival (OS) were assessed by the log-rank test and Cox regression analysis including prognostic factors obtained in the G-SOX study; ECOG performance status, baseline sum of tumor diameters, disease status (recurrent/unresectable), and histology (diffuse/intestinal).. Among 685 patients enrolled in the G-SOX study, 632 patients who had the first tumor evaluation were analyzed. Patients with ETS ≥ 20% had longer PFS (median 4.5 vs. 2.8 months, p < 0.0001) and OS (median 14.8 vs. 10.5 months, p < 0.0001) than those with ETS < 20%. Adjusted hazard ratios of ETS < 20 vs. ≥ 20% were 0.606 (95% confidence interval (CI) 0.506-0.725) for PFS and 0.589 (95% CI 0.492-0.704) for OS. DpR was also significantly associated with PFS and OS (both p < 0.0001). These results were similar between the SOX and CS groups.. In AGC patients receiving the first-line therapy, ETS and DpR might be predictors for PFS and OS.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Clinical Trials, Phase III as Topic; Drug Combinations; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Multicenter Studies as Topic; Oxaliplatin; Oxonic Acid; Progression-Free Survival; Proportional Hazards Models; Randomized Controlled Trials as Topic; Retrospective Studies; Stomach Neoplasms; Tegafur; Young Adult

To study the prognostic factors of gastric cancer (GC) patients who were classified with stage III disease according to the newest TNM classification.. This study retrospectively enrolled 279 patients who underwent radical gastrectomy from January 2012 to December 2014 at our hospital and who were diagnosed with stage III GC according to the new 8th edition of the TNM classification. The patient data that were collected included age, sex, pathological parameters, survival, lymph node ratio, neo-adjuvant chemotherapy with oxaliplatin and S-1, and operation type. The characteristics, survival, and prognostic factors of the patients were analyzed by univariate and multivariate analyses.. The median OS of the patients after curative surgery was 19 months, and the 3-year survival rate (3-YSR) was 25.3%. A univariate analysis showed that tumor location (P = 0.01), neo-adjuvant chemotherapy (P = 0.005), pathological T stage (P = 0.002), pathological N stage (P < 0.001), lymph node ratio (LNR) (P < 0.001), and operation type (P = 0.032) were significantly associated with overall survival. A multivariate analysis revealed that neo-adjuvant chemotherapy (P = 0.009), pathological T stage (P = 0.012), and LNR (P < 0.001) were independent prognostic factors.. Neo-adjuvant chemotherapy, pathological T stage, and LNR were independent prognostic factors for the overall survival of patients with stage III GC. The neo-adjuvant chemotherapy with oxaliplatin and S-1 can be used for the patients to improve their survival.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Drug Combinations; Female; Gastrectomy; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Oxaliplatin; Oxonic Acid; Prognosis; Retrospective Studies; Stomach Neoplasms; Tegafur

We have assessed the combination of DC-CIK with S-1 plus cisplatin chemotherapy in advanced gastric cancer (AGC) and the role of mutational analysis of circulating tumor DNA (ctDNA) and T-cell receptor (TCR) repertoire in predicting clinical outcomes.. Consecutive patients (. The DC-CIK infusions were well tolerated with no serious adverse events. The disease control rates (CR. DC-CIK combined with S-1 plus cisplatin provided a favorable PFS and OS in patients with AGC and the combination therapy was safe with tolerable toxicities. Clinical efficacy correlated with decreases in ctDNA mutational profiles and restored TCR repertoire.

Topics: Aged; Antimetabolites, Antineoplastic; Biomarkers; Combined Modality Therapy; Cytokine-Induced Killer Cells; Dendritic Cells; Drug Combinations; Female; Humans; Immunotherapy; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Oxonic Acid; Prospective Studies; Retreatment; Stomach Neoplasms; Tegafur; Treatment Outcome

Discontinuation of postoperative S-1 adjuvant monotherapy is a frequent problem in the management of patients with gastric cancer.. A total of 355 stage II/III gastric cancer patients who underwent gastrectomy and adjuvant S-1 were retrospectively analyzed using a multicenter dataset. We randomly assigned patients into either discovery or validation cohort in a 2:1 ratio. In the discovery cohort, 29 parameters were assessed as candidate factors to predict discontinuation of S-1 adjuvant within 6 months. A scoring system was designed using independent risk factors identified by the multivariate analysis. Reproducibility was tested in the validation cohort.. Overall, 92 patients (25.9%) discontinued the treatment within 6 months because of adverse effects. Age, preoperative urea nitrogen (UN) and the preoperative albumin-to-bilirubin index (ALBI) showed the highest area under the curve (AUC) for the discontinuation of S-1 adjuvant within 6 months in each category: body status, blood tests and indices. In the multivariate analysis, age ≥ 64 years, preoperative UN ≥ 15.2 mg/dl and preoperative ALBI ≥ -0.265 were identified as independent risk factors. A scoring scale consisting of these three factors was developed for the prediction of drug discontinuation and demonstrated a greater AUC (0.728) than that of each of the three constituents. The time to treatment discontinuation decreased incrementally as the risk score increased. The reproducible findings were confirmed in the validation cohort.. We identified risk factors and developed a scoring scale to predict S-1 adjuvant monotherapy discontinuation in patients with stage II/III gastric cancer.

Topics: Age Factors; Aged; Antimetabolites, Antineoplastic; Bilirubin; Blood Urea Nitrogen; Chemotherapy, Adjuvant; Drug Combinations; Female; Gastrectomy; Humans; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Prognosis; Random Allocation; Reproducibility of Results; Retrospective Studies; Risk Assessment; Risk Factors; Serum Albumin; Stomach Neoplasms; Tegafur

S-1-based regimens have been shown to be as effective as other fluoropyrimidine-based regimens with a better safety profile in patients with advanced esophagogastric adenocarcinoma. However, real-world data on S-1 in European patients with advanced esophagogastric adenocarcinoma are lacking. The Safety Compliance Observatory on Oral fluoroPyrimidines (SCOOP) study evaluated safety and relative dose intensities for patients treated with S-1-based regimens for advanced esophagogastric adenocarcinoma as part of daily practice.. Overall, data for 125 patients with advanced esophagogastric adenocarcinoma were collected at 21 centers in five countries in Europe. Demographics, treatment, and adverse-event data were recorded over a planned treatment of six cycles.. Most patients (87%) received combination treatment of S-1 plus a platinum compound. Adverse events related to S-1 treatment were mostly grade 1 or 2 while reported grade 3-4 serious adverse events related to S-1 occurred in 12 patients and were most often grade 3 neutropenia (n = 4, 3.2%) or diarrhea (n = 5, 4%). The most common adverse events of any grade that were attributable to S-1 treatment included neutropenia, anemia, thrombocytopenia, diarrhea, nausea, vomiting, and fatigue. No patients experienced mucositis, dehydration, or febrile neutropenia, whereas 2% (3/125) of patients experienced hand-foot syndrome.. The overall relative dose intensity was 70%. In a real-world setting, patients with advanced esophagogastric adenocarcinoma tolerated S-1 treatment well with high compliance rates. The SCOOP study provides valuable information on S-1 relative dose intensity that can be used for treatment decision making.

Topics: Adenocarcinoma; Administration, Oral; Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Dose-Response Relationship, Drug; Drug Combinations; Esophageal Neoplasms; Esophagogastric Junction; Europe; Female; Humans; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Stomach Neoplasms; Tegafur; Treatment Outcome

Adjuvant S-1 monotherapy prolongs the survival of patients with pathological stage II or III gastric cancer undergoing D2 gastrectomy. This therapeutic regimen is standard in Japan. Unfortunately, some patients who undergo this treatment suffer from recurrent disease. However, information regarding the timing and site-specific trends of recurrence is insufficient.. Among 396 patients who underwent D2 gastrectomy followed by adjuvant S-1 monotherapy between 2008 and 2012, 122 experienced a recurrence. We retrospectively determined the timing and sites of recurrence.. The median RFS of the 122 patients was 19.5 months, and their 1-, 3- and 5-year RFS rates were 67.2%, 23.0% and 5.7%, respectively. There were no significant differences in RFS among disease substages. Local recurrence, lymph node involvement and peritoneal and hematogenous metastases were found in 6, 25, 63 and 42 patients, respectively. Approximately 10% of patients presented with contemporaneous sites of recurrence. Local recurrence and lymph node metastasis plateaued 3 years after gastrectomy. Peritoneal and hematogenous metastasis increased within 5 years after surgery. In patients with hematogenous metastasis, the number of liver metastases plateaued but increased in others.. In patients with recurrent disease who underwent D2 gastrectomy followed by adjuvant S-1 monotherapy, 80% of recurrences occur within 3 years after gastrectomy. The timing of recurrence is not significantly different among substages. Although the rates of local recurrence and lymph node and liver metastasis plateau after 3 years, peritoneal and the other hematogenous metastases increase within 5 years.

Topics: Aged; Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Drug Combinations; Female; Gastrectomy; Humans; Japan; Liver Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Oxonic Acid; Retrospective Studies; Stomach Neoplasms; Survival Rate; Tegafur; Time Factors

We report a case of recurrent gastric cancer that was successfully treated by S-1 chemotherapy.An 81-year-old woman with advanced gastric cancer[L Less, Type 2, cT4a(SE), cN0H0P0M0, cStageⅡB]underwent distal gastrectomy.Abdominal CT performed 6 months after surgery revealed a low-density area in the liver.She was diagnosed with liver metastasis and started receiving S-1 chemotherapy.The liver metastasis achieved complete response, so S-1 chemotherapy was discontinued 12 months after recurrence.Abdominal CT performed 9 months after the discontinuation of S-1 chemotherapy revealed multiple low-density areas in the liver.She started receiving S-1 chemotherapy again, but S-1 chemotherapy was discontinued because of side effects after 2 courses.The patient died 24 months after receiving S-1 chemotherapy.

Topics: Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Female; Humans; Liver Neoplasms; Neoplasm Recurrence, Local; Oxonic Acid; Stomach Neoplasms; Tegafur

The effectiveness of steroid rotation from dexamethasone to prednisolone for hiccups caused by dexamethasone for antiemetic chemotherapy has been reported overseas, but has not been reported in Japan. The effectiveness of steroid rotation in Japanese individuals is unclear because ethnic differences and variations in glucocorticoid receptors affect sensitivity to dexamethasone. We report a case of the effectiveness of steroid rotation in a Japanese patient with hiccups caused by dexamethasone for antiemetic chemotherapy. A 74-year-old man was diagnosed as having stage IV gastric cancer. Chemotherapy was initiated using S-1 (80 mg/d on Days 1-21) and cisplatin (80 mg on Day 8), with dexamethasone (8 mg/d on Day 8 intravenously and on Days 9-11 orally) as antiemetic. Severe hiccups developed on Day 10 and resolved on Day 11 by the 1st cycle of chemotherapy. Subcutaneous injection of atropine by the 5th cycle and ingestion of Syakuyakukanzouto (Glycyrrhiza extract) by the 6th cycle did not effectively relieve the hiccups. By the 7th cycle, the hiccups resolved after the dose of dexamethasone was decreased from 8 mg/d to 4 mg/d but recurred by the 8th cycle. We then changed to prednisolone 30 mg/d from dexamethasone 4 mg/d by the 9th cycle; the hiccups completely resolved thereafter. Steroid rotation from dexamethasone to prednisolone completely controlled the hiccups, with no further recurrence. No emetic episodes occurred during chemotherapy. Therefore, this demonstrates the effectiveness of steroid rotation in a Japanese patient with hiccups caused by dexamethasone for antiemetic chemotherapy.

Topics: Aged; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Asian People; Cisplatin; Dexamethasone; Drug Combinations; Hiccup; Humans; Male; Oxonic Acid; Prednisolone; Receptors, Glucocorticoid; Stomach Neoplasms; Tegafur

This study aimed to identify biomarkers for predicting the prognosis of advanced gastric cancer patients who received docetaxel, cisplatin, and S-1 (DCS).. Gene expression profiles were obtained from the Gene Expression Omnibus database (GSE31811). Gene-Ontology-enrichment and KEGG-pathway analysis were used for evaluating the biological functions of differentially-expressed genes. Protein-protein interaction (PPI) network and Kaplan-Meier survival analyses were employed to assess the prognostic values of hub genes.. A total of 1,486 differentially expressed genes (DEGs) were identified, including 13 up-regulated and 1,473 down-regulated genes. KEGG pathways such as metabolic pathways, cell adhesion molecules (CAMs), PI3K-Akt signaling pathway and pathways in cancer were significantly represented. In the PPI network, the top ten hub genes ranked by degree were GNG7, PLCB1, CALML5, FGFR4, GRB2, JAK3, ADCY7, ADCY9, GNAS and KDR. Five DEGs, including ANTXR1, EFNA5, GAMT, E2F2 and NRCAM, were associated with relapse-free survival and overall survival.. ANTXR1, EFNA5, GAMT, E2F2 and NRCAM are potential biomarkers and therapeutic targets for DCS treatment in GC.

Topics: Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Cisplatin; Clinical Decision-Making; Computational Biology; Databases, Genetic; Docetaxel; Drug Combinations; Drug Resistance, Neoplasm; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Gene Regulatory Networks; Humans; Oxonic Acid; Precision Medicine; Protein Interaction Maps; Stomach Neoplasms; Tegafur; Transcriptome; Treatment Outcome

Gastric cancer with portal vein tumor thrombosis (GC-PVTT) is a rare condition with a very poor prognosis. A 64-year-old man with GC-PVTT was admitted to our hospital. His carcinoembryonic antigen level was slightly elevated (17.4 ng/ml). Upper gastrointestinal endoscopy showed a type-2 gastric lesion (45 mm × 40 mm) in the gastric antrum. The PVTT originated from the main gastric tumor and continued to the superior mesenteric vein. Fluorodeoxyglucose-positron emission tomography showed high uptake both by the main tumor and PVTT. A distal gastrectomy with D2 lymphadenectomy was performed with simultaneous removal of the PVTT. Pathological examination showed a poorly differentiated adenocarcinoma with neuroendocrine differentiation. Adjuvant chemotherapy with S-1 was administered for 1 year. The patient survived for >5 years with no recurrence. Surgical gastrectomy and complete removal of the PVTT followed by S-1 chemotherapy could be a treatment option that offers improved long-term survival for patients with GC-PVTT.

Topics: Adenocarcinoma; Chemotherapy, Adjuvant; Combined Modality Therapy; Disease-Free Survival; Drug Combinations; Gastrectomy; Humans; Male; Middle Aged; Oxonic Acid; Portal Vein; Stomach Neoplasms; Tegafur; Venous Thrombosis

This study aimed to evaluate whether the timing of initiating postoperative chemotherapy with S-1 monotherapy affects gastric cancer patients' prognosis.. A multi-institution dataset identified patients with pStage II or III gastric cancer who received S-1 monotherapy for over 6 months after curative resection between 2010 and 2014. Patients were divided into three groups based on the timing of S-1 monotherapy initiation. Prognostic factors for relapse-free survival (RFS) were investigated.. We classified 401 patients into groups as follows: S-1 administered within 6 weeks (n = 247), between 6 and 8 weeks (n = 95), and after 8 weeks (n = 59). The RFS times were not significantly different in the within 6 weeks group and the between 6 and 8 weeks group, but the after 8 weeks group had a shorter RFS time compared with the other two groups (within 6 weeks group vs. after 8 weeks group; P = 0.0044). By disease stage, this trend was the same. The multivariable analysis showed that a larger tumor size (≥ 50 mm), pStage III, and the after 8 weeks group were independent prognostic factors for RFS (after 8 weeks group: hazard ratio, 2.05; P = 0.0069). The prevalence of hematogenous metastasis as the initial recurrence site increased by delayed initiation of S-1. A forest plot revealed that delayed administration after 8 weeks was associated with a greater risk of recurrence in most subgroups.. Postoperative chemotherapy with S-1 monotherapy for gastric cancer is recommended to begin within 8 weeks after surgery.

Topics: Aged; Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Disease-Free Survival; Drug Combinations; Female; Humans; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Postoperative Period; Prognosis; Retrospective Studies; Stomach Neoplasms; Tegafur; Time Factors

S-1 is an oral anticancer drug composed of tegafur (FT), which is a prodrug of 5-FU, 5-chloro-2,4-dihydroxypyridine (CDHP), and potassium oxonate. Recently, some studies have been reported on watering eyes caused by S-1. However, the mechanism of watering eyes caused by S-1 is still unclear. The aim of this study was to investigate the correlation between tears and plasma concentrations of FT, 5-FU, and CDHP, which are components and active modulator of S-1.. Total of eight patients were enrolled. All the FT, 5-FU and CDHP were detected both in plasma and in tears, and their PK parameters were measured. There was a positive correlation between the concentrations of FT, 5-FU and CDHP in the plasma and those in the tears on day 1 and day 14 (correlation coefficients r, right eye/left eye: r = 0.882/0.878, 0.877/0.890, and 0.885/0.878, respectively).. There was a positive correlation between the concentrations of FT, 5-FU and CDHP in the plasma and those in the tears. The result is expected to facilitate the further investigation into the causes of watering eyes and the establishment of the effective methods for the prevention and the treatment.

Topics: Adult; Aged; Drug Combinations; Female; Fluorouracil; Humans; Male; Middle Aged; Oxonic Acid; Plasma; Prospective Studies; Pyridines; Stomach Neoplasms; Tears; Tegafur; Tissue Distribution

S-1 monotherapy is one of the standard adjuvant treatments for patients with stage II and III gastric cancers. Early recurrence after S-1 adjuvant therapy has a poor prognosis. This study aimed to clarify the treatment outcomes of systemic chemotherapy and explore encouraging regimens.. This was a multicenter retrospective study. Among gastric cancer patients who underwent curative gastrectomy followed by adjuvant S-1 monotherapy, patients who experienced a recurrence while receiving adjuvant therapy or within 6 months after completion and started systemic chemotherapy at four institutions between 2005 and 2015 were eligible.. A total of 112 patients were included. The main treatment regimens were weekly paclitaxel (n = 38, 34%), irinotecan plus cisplatin (n = 31, 28%), capecitabine plus cisplatin (n = 7, 6%), and irinotecan monotherapy (n = 6, 5%). For all patients, median progression-free survival and overall survival were 3.7 and 11.4 months, respectively. Among 77 patients with measurable lesions, the overall response and disease control rates were 24.7% and 62.3%, respectively. Multivariate analyses for overall survival showed that Eastern Cooperative Oncology Group performance status 2 [hazard ratio (HR) 3.71; 95% confidence interval (CI) 1.78-7.73] and undifferentiated histological type (HR 2.04; 95% CI 1.35-3.44) were independent prognostic factors, and treatment regimens were not prognostic. Exploratory comparisons did not show statistically significant differences between treatment regimens.. This study of the largest number of patients with early recurrence after S-1 adjuvant monotherapy demonstrated that the prognosis for patients treated by all regimens was similar and poor.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cisplatin; Drug Combinations; Female; Humans; Irinotecan; Male; Middle Aged; Neoplasm Recurrence, Local; Oxonic Acid; Prognosis; Retrospective Studies; Stomach Neoplasms; Survival Rate; Tegafur

A 68-year-old female patient presented with advanced gastric cancer and multiple hepatic tumors. Upper GI endoscopy showed a type 3 lesion in the posterior wall of the gastric body. Abdominal computed tomography revealed multiple liver metastases, and staging laparoscopy identified peritoneal dissemination. She was diagnosed with clinical Stage Ⅳ gastric cancer(cT3N2M1H1). She received 3 courses of combined chemotherapy containing S-1 and cisplatin. The therapeutic response was PR. We performed total gastrectomy with D2 lymph node dissection and splenectomy. Histopathological examination revealed no residual cancer cells, indicating pCR. She continued S-1 adjuvant chemotherapy and has remained free from recurrence for 18 months.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Female; Gastrectomy; Humans; Neoplasm Recurrence, Local; Oxonic Acid; Stomach Neoplasms; Tegafur

A 77-year-old woman was admitted to our hospital with complaints of lumbago. Based on MRI, bone marrow biopsy, and upper endoscopy, she was diagnosed as having advanced gastric cancer accompanied by bone marrow metastasis and multiple bone metastases. She underwent combination chemotherapycontaining S-1 and docetaxel(TXT). However, during the first course of chemotherapy, she developed Grade 4 neutropenia and sepsis, and her ADL worsened. The anticancer agent doses were reduced drasticallyto 40% of the initial dose from the next course of chemotherapy. She was able to continue treatment without developing severe adverse events, and the disease did not progress for 11 months. However, during the 6 course of chemotherapy, she developed Grade 4 neutropenia and sepsis again, and it became difficult to continue treatment. Subsequent S-1 monotherapywas not efficacious, and she died 17 months after diagnosis. From the view of persistence and efficacy, we believe that low-dose combination chemotherapycontaining S-1 and TXT maybe a suitable regimen for advanced gastric cancer with bone marrow metastasis.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Bone Marrow Neoplasms; Docetaxel; Drug Combinations; Female; Humans; Oxonic Acid; Stomach Neoplasms; Tegafur

The MAGIC trial has shown perioperative chemotherapy does significantly improve overall survival of patients with gastric and esophagogastric junction carcinoma. The approach to evaluate the effectiveness of adjuvant chemotherapy is urgent in clinical practice.. Totally, 264 patients with locally advanced gastric carcinoma (including esophagogastric junction carcinoma) treaded by perioperiate chemotherapy (SOX or XELOX) from May 2012 to December 2017 in our cancer center were included. Tumor response was evaluated by tumor regression grade (TRG, Mandard system) and Response Evaluation Criteria in Solid Tumor (RECIST v1.1). The clinical characteristics and the effect on survival were analyzed.. Univariate analysis showed TRG was correlated to tumor size, Lauren classification, grade of differentiation, histological type, postsurgical T category (ypT), postsurgical N category (ypN), vascular invasion or lymphatic invasion and so on. However, only Lauren classification and ypT were independent factors for TRG. On contrary to RECIST, TRG was founded to be a prognostic factor for DFS and OS on univariate analysis. Cox proportional hazards were established to evaluate the relationship among TRG, clinical-pathological factors and survival. On multivariate analysis, the chemotherapy cycle, Lauren classification, vascular invasion or lymphatic invasion, ypN and postsurgical pathologic stage were independent factors for OS and DFS, while TRG were negatively correlated to survival.. TRG seems to be a promising prognostic indicator and it predicts the prognosis of patients with locally advanced gastric cancer after adjuvant chemotherapy more reasonably in comparisons to RECIST v1.1.

Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Carcinoma, Signet Ring Cell; Chemotherapy, Adjuvant; Drug Combinations; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Grading; Oxaliplatin; Oxonic Acid; Retrospective Studies; Stomach Neoplasms; Survival Rate; Tegafur; Young Adult

There is no standard first-line chemotherapy for advanced gastric cancer with severe peritoneal metastasis. Although fluoropyrimidine is often used, its efficacy is limited, and it remains unclear whether combination therapy with platinum improves clinical outcomes.. This retrospective study involved patients at six Japanese academic hospitals between 2010 and 2016. Patients with advanced gastric cancer and severe peritoneal metastasis were included if they had massive ascites and/or inadequate oral intake requiring intravenous nutritional support. We then compared the efficacy and safety of fluoropyrimidine monotherapy with those of fluoropyrimidine/platinum combination therapy.. Compared with the combination therapy group (n = 64), the monotherapy group (n = 65) had worse general health (more patients with elderly age, performance status > 2, and having both massive ascites and inadequate oral intake). Both overall survival (9.0 vs 5.0 months, p < 0.01) and progression-free survival (4.3 vs 2.3 months, p < 0.01) were significantly longer in the combination group, and the significance remained after adjusting for prognostic variables (hazard ratios of 0.47 and 0.41, respectively; p < 0.01). Improvements in ascites and oral intake were also greater in the combination group. Although neutropenia (grade ≥ 3) occurred more frequently with combination therapy, both treatments in this study were tolerable.. Combination therapy with fluoropyrimidine and platinum might be more effective than monotherapy with fluoropyrimidine and was tolerable for patients with advanced gastric cancer and severe peritoneal metastasis.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Ascites; Cisplatin; Drug Combinations; Female; Fluorouracil; Humans; Leucovorin; Male; Malnutrition; Methotrexate; Middle Aged; Neutropenia; Organoplatinum Compounds; Oxonic Acid; Peritoneal Neoplasms; Progression-Free Survival; Pyridines; Retrospective Studies; Stomach Neoplasms; Tegafur; Treatment Outcome; Withholding Treatment; Young Adult

A 76-year-old female patient was diagnosed with inoperable gastric cancer with distant lymph node metastasis(cT3N2M1 [LYM], cStage Ⅳ), for which she received S-1 chemotherapy(orally administered on days 1-14 ofa 28-day courses). The patient received a total of4 2 treatment courses. After an initial phase of stable disease due to chemotherapy, she eventually showed progressive disease. S-1 chemotherapy was discontinued. Because ofher social background, she decided against any further chemotherapy. After 1 year, she underwent metallic stent insertion through the gastric cancer, which enabled her to consume food. She is currently alive as of 5 years and 3 months from the date of first diagnosis.

Topics: Aged; Drug Combinations; Female; Humans; Lymph Nodes; Lymphatic Metastasis; Oxonic Acid; Stomach Neoplasms; Tegafur

Currently, radical surgery with D2 lymphadenectomy has become the standard operation mode of patients in East Asian countries who suffer from resectable gastric cancer. Our target is to compare the efficacy of postoperative adjuvant chemotherapy with S-1 versus SOX/XELOX regimens for gastric cancer after D2 resection.. We selected 186 patients with gastric cancer who underwent D2 resection in Hangzhou First People's Hospital and Hangzhou Cancer Hospital from June 2014 to June 2017. All patients were followed up for more than 3 years. The primary endpoint was disease-free survival (DFS), and the secondary endpoints were overall survival (OS) and toxicity.. The 3-year DFS of monotherapy group and combined group were, respectively, 50.7% and 64.0%, while the 3-year OS were, respectively, 62.7% and 71.2%. The 3-year DFS and OS of the combined group were higher than the monotherapy group, but the differences had no statistical significance (3-year DFS: P = 0.071; 3-year OS: P = 0.224). Subgroup analysis showed that the DFS of patients with stage III gastric cancer in monotherapy group was significantly lower than the combined group, with the difference that had statistical significance (P = 0.030), while there was no significant difference in OS (P = 0.186). Most toxic and side effects seen in both groups had no significant differences, while the incidence of hand-foot syndrome and peripheral neurotoxicity in combined group was significantly higher than that in the monotherapy group (P < 0.001).. For patients with advanced gastric cancer who underwent D2 resection, compared with S-1 regimen, there is prolonged disease-free survival trend with SOX/XELOX regimen, while there is no significant overall survival benefit.

Topics: Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Chemotherapy, Adjuvant; China; Cohort Studies; Disease-Free Survival; Drug Combinations; Female; Gastrectomy; Hand-Foot Syndrome; Humans; Incidence; Male; Middle Aged; Outcome and Process Assessment, Health Care; Oxaloacetates; Oxonic Acid; Paraneoplastic Polyneuropathy; Stomach Neoplasms; Tegafur

Surgical resection with S-1 adjuvant chemotherapy (AC) is the standard of care for stage II-III gastric cancer (GC). However, it is unclear if time to initiation and duration of S-1 AC impact on survival.. A multi-institutional GC database identified 498 patients who were treated with S-1 AC after D2 or more extended radical surgery for stage II-III gastric cancer. Patients were divided into four groups according to the interval between surgery and initiation of AC and the duration of AC as follows: group A (n = 226), who received AC earlier (≤6 weeks) and for longer (≥6 months) after surgery; group B (n = 160), who received AC later (>6 weeks) and for longer after surgery; group C (n = 46), who received AC earlier but for a shorter period (<6 months) after surgery; and group D (n = 66), who received AC later and for a shorter period after surgery. Prognostic factors for overall survival (OS) were investigated using multivariate analysis.. The 5-year OS was 69.5%. Pathological stage II disease (hazard ratio (HR), 0.334; 95% confidence interval (CI), 0.215-0.499), with an OS of 85.8% versus 60.5% for stage III disease, as well as a longer duration (≥6 months) of S-1 (HR, 0.498; 95% CI, 0.355-0.706), with an OS of 74.3% versus 53.0% for a shorter duration (<6 months) of S-1, were identified as significant prognostic factors for long-term survival. Time to initiation was not associated with OS.. A duration of S-1 AC of ≥6 months, but not time to initiation within 6 weeks, impacts on OS in stage II-III gastric cancer.

Topics: Adenocarcinoma; Chemotherapy, Adjuvant; Disease-Free Survival; Drug Combinations; Female; Humans; Kaplan-Meier Estimate; Male; Oxonic Acid; Prognosis; Proportional Hazards Models; Retrospective Studies; Stomach Neoplasms; Tegafur

Although S-1 chemotherapy is used widely as postoperative adjuvant chemotherapy for gastric cancer, some patients experience diarrhea during treatment. The patient was a 39-year-old woman who underwent distal gastrectomy for gastric cancer and who had started S-1 chemotherapy as postoperative adjuvant chemotherapy 1 week before her presentation. She experienced severe diarrhea immediately after starting the course of S-1 tablets. Capsule endoscopy revealed severe S-1-induced enteritis with extensive mucosal injury in the ileum and red intestinal fluid due to the oozing of blood in the ileum. After reducing the dosage of S-1, her diarrhea became milder, and she was able to continue S-1 chemotherapy.

Topics: Adult; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Capsule Endoscopy; Chemotherapy, Adjuvant; Diarrhea; Drug Combinations; Enteritis; Female; Gastrectomy; Humans; Oxonic Acid; Severity of Illness Index; Stomach Neoplasms; Tegafur

Although, gastric cancer is one of the most common cancers worldwide, alpha-fetoprotein (AFP) producing human epidermal growth factor receptor 2 (HER2) positive gastric cancers are rare. AFP producing gastric cancer has a poor prognosis and an appropriate treatment option has not been established to date. A 75-year-old woman with AFP- producing gastric cancer was treated with S-1, an oral fluoropyrimidine derivative, chemotherapy after distal gastrectomy. Recurrence of gastric cancer was observed after 18 months and immunohistochemistry analysis showed AFP and HER2 positive gastric cancer. The patient received combination therapy containing capecitabine, cisplatin, and trastuzumab. Computed tomography scans showed regression of the lymph node metastasis. The patient's quality of life substantially improved after the treatment. Thus, the present case suggests that AFP and HER2 positive gastric cancer can be effectively treated with, capecitabine, cisplatin, and trastuzumab combination therapy.

Topics: Aged; alpha-Fetoproteins; Antimetabolites, Antineoplastic; Antineoplastic Agents, Immunological; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Cisplatin; Drug Combinations; Female; Humans; Lymphatic Metastasis; Neoplasm Recurrence, Local; Oxonic Acid; Quality of Life; Receptor, ErbB-2; Stomach Neoplasms; Tegafur; Trastuzumab; Treatment Outcome

Limited information exists regarding beneficial effects of Helicobacter pylori. To examine the effect in advanced gastric cancer, we compared survival for patients treated with surgery-only or adjuvant chemotherapy on the basis of H. pylori infection status.. A cohort of 491 patients who underwent R0 resection for locally advanced gastric cancer between 2000 and 2009 at 12 institutions in northern Japan was included. H. pylori infection status, was assessed from paraffin-embedded formalin-fixed samples. Overall survival (OS) and disease-free survival (DFS) in surgery-only (Surgery) and adjuvant chemotherapy (S-1) groups were analyzed. A propensity score matching was employed to correct for confounding factors by indication.. H. pylori infection was positive in 175 patients and negative in 316 patients. H. pylori-positive patients showed significantly better survival than H. pylori-negative patients in both OS (hazard ratio [HR] 0.593, 95% confidence interval [CI] 0.417-0.843; P = 0.003]) and DFS (HR 0.679, 95%CI 0.492-0.937; P = 0.018). Propensity score matching further confirmed that S-1 was virtually only effective when tumors were H. pylori-positive.. The favorable outcome of H. pylori-positive patients implies that the host immune system is modulated by H. pylori enhancing the chemotherapeutic efficacy.

Topics: Aged; Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Cohort Studies; Drug Combinations; Female; Follow-Up Studies; Helicobacter Infections; Helicobacter pylori; Humans; Male; Oxonic Acid; Prognosis; Stomach Neoplasms; Survival Rate; Tegafur

A phase 3 trial of S-1, leucovorin (LV), and oxaliplatin for treating gastric cancer is now underway. However, the antitumor efficacy of the combination has not yet been examined in an in vivo preclinical study. This study examined the antitumor efficacy of combination therapy consisting of S-1, LV, and oxaliplatin against 4 human gastric cancer xenografts: NUGC-4, St-40, SC-2, and SC-4.. The antitumor efficacy was evaluated using human gastric cancer xenograft-bearing nude mice. S-1 and LV were administered orally once daily on days 1-7 at doses of 6.9 and 10 mg/kg, respectively. Oxaliplatin was administered intravenously at a dose of 8.3 mg/kg on day 1. The tumor volume was measured on day 15, and the relative tumor volume (RTV) was calculated.. In all 4 xenograft models, S-1 alone and oxaliplatin alone, but not LV alone, had significant antitumor activities (p < 0.001). Combination therapy consisting of S-1 and LV resulted in a significantly smaller RTV than S-1 alone (p < 0.001). Combination therapy consisting of S-1 and oxaliplatin also resulted in a significantly smaller RTV than either S-1 alone (p < 0.001) or oxaliplatin alone (p < 0.001). Furthermore, combination therapy consisting of S-1, LV, and oxaliplatin resulted in the highest antitumor activity in these models (p < 0.001 vs. S-1 + LV; p < 0.001 or p = 0.003 vs. S-1 + oxaliplatin).. Combination therapy consisting of S-1, LV, and oxaliplatin administered according to a 1-week-on/1-week-off schedule may be useful for the treatment of patients with gastric cancer.

Topics: Animals; Antineoplastic Agents; Cell Line, Tumor; Drug Combinations; Drug Therapy, Combination; Humans; Leucovorin; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Stomach Neoplasms; Tegafur; Transplantation, Heterologous

After curative resection of gastric cancer with D2 lymph node dissection, postoperative adjuvant chemotherapy with S-1 or capecitabine plus oxaliplatin (XELOX) is considered to be standard therapy in Eastern countries. This study aimed to compare the efficacies of adjuvant S-1 and XELOX chemotherapy for gastric cancer patients after D2 dissection based on disease-free survival (DFS).. This retrospective observational study was conducted at 29 tertiary hospitals in Korea. Of 1898 patients who underwent curative resection and received adjuvant chemotherapy for gastric cancer between February 2012 and December 2013, 1088 patients who met the eligibility criteria were enrolled in the study. After propensity score-matching, the 3-year disease-free survival rate (DFS) was used to compare efficacies directly between adjuvant XELOX and S-1 chemotherapies for patients with stage 2 or 3 gastric cancer after D2 gastrectomy.. The 3-year DFS rates for the S-1 and XELOX groups did not differ significantly among disease stages 2A, 2B, and 3A (all p > 0.05). However, the survival rates for the S-1 group were significantly lower than for the XELOX group for stage 3B (65.8% vs. 68.6%; p = 0.019) and stage 3C (48.4% vs. 66.7%; p = 0.002) gastric cancer. The hazard ratios (HRs) of S-1 chemotherapy for recurrence compared with XELOX for stages 3B and 3C were respectively 2.030 [95% confidence interval (CI), 1.110-3.715; p = 0.022] and 2.732 (95% CI 1.427-5.234; p = 0.002).. Adjuvant XELOX chemotherapy was more effective than S-1 for patients with stage 3B or 3C gastric cancer after D2 lymph node dissection.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Chemotherapy, Adjuvant; Deoxycytidine; Disease-Free Survival; Drug Combinations; Female; Fluorouracil; Humans; Lymph Node Excision; Male; Middle Aged; Neoplasm Staging; Oxaloacetates; Oxonic Acid; Retrospective Studies; Stomach Neoplasms; Tegafur

A 70's man presenting with a chief complaint of stomachache was found to have advanced gastric cancer with a deep ulcer and some lymph-node metastases. We decided performing a curative operation after 2 courses of S-1 plus cisplatin. On the first course day 13 of chemotherapy, he complained of severe epigastralgia, and we diagnosed as generalized peritonitis due to perforation of gastric cancer. We performed an urgent laparoscopic operation, which made perforation simple closure and omentopexy. Curative distal gastrectomy with D2 lymph node dissection was successfully performed on postoperative day 16.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Gastrectomy; Humans; Male; Oxonic Acid; Stomach Diseases; Stomach Neoplasms; Tegafur

S-1 and cisplatin therapy (SP therapy) is widely used as the first-line of advanced/recurrent gastric cancer. However, severe neutropenia is often observed (40%) during this therapy. Therefore, the risk management of neutropenia is important. From September 2014 to April 2017, we investigated 76 patients who underwent SP therapy as primary treatment for advanced/recurrent gastric cancer at Ogaki Municipal Hospital. Risk factors for grade 3/4 neutropenia were examined by univariate and multivariate analyses. In SP therapy, 19 patients (25%) experienced grade 3/4 neutropenia. The results of multivariate analysis of factors with p <0.05 in the univariate analysis indicated that less than 10.6 g/dL of the haemoglobin value before the course at the lowest neutrophil count (odds ratio: 7.900; 95% CI: 1.280-48.60; p = 0.026), more than six courses of the total course (odds ratio: 9.13; 95% CI: 2.13-39.1; p = 0.003), and less than 3140 m2 neutrophil counts (odds ratio: 5.33; 95% CI: 1.47-19.3; p = 0.011) before chemotherapy were risk factors of grade 3/4 neutropenia. A low haemoglobin value before the course at the lowest neutrophil count was revealed as a risk factor causing severe neutropenia in SP therapy.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Female; Hemoglobins; Humans; Leukocyte Count; Male; Middle Aged; Neoplasm Recurrence, Local; Neutropenia; Neutrophils; Oxonic Acid; Risk Factors; Stomach Neoplasms; Tegafur

There are few reports of long-term outcomes of gastric cancer patients with sarcopenia. The purpose of this study was to assess the impact of sarcopenia on long-term outcomes in gastric cancer patients who underwent curative resection.. A total of 951 patients aged 65 years or older who underwent R0 resection for gastric cancer were investigated. Sarcopenia was defined as a decreased arm muscle area < 38.05 cm. Of 951 patients, 111 (11.7%) were diagnosed with sarcopenia. Reduced surgery was performed significantly more frequently in patients with sarcopenia (p = 0.006). The incidence of eligible patients who received adjuvant chemotherapy was significantly lower in patients with sarcopenia than in those without sarcopenia (p = 0.030). Mortality due to gastric cancer and aging-associated multiple organ failure rates without obvious diseases were higher in patients with sarcopenia (p = 0.036 and p < 0.001, respectively). Overall survival (OS) and cause-specific survival (CSS) were significantly worse in patients with sarcopenia (p < 0.001 and p = 0.005, respectively). Multivariate analysis for OS and CSS revealed that sarcopenia was an independent prognostic factor in gastric cancer patients (p < 0.001 and p = 0.043, respectively).. Sarcopenia is related to poor survival in gastric cancer patients and appears to be a significant negative prognostic factor in patients with gastric cancer who underwent curative resection.

Topics: Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Cause of Death; Chemotherapy, Adjuvant; Drug Combinations; Female; Humans; Male; Multiple Organ Failure; Neoplasm Staging; Oxonic Acid; Postoperative Complications; Preoperative Period; Prognosis; Sarcopenia; Stomach Neoplasms; Survival Rate; Tegafur; Time Factors; Treatment Outcome

A 55-year-old man underwent distal gastrectomy and D2 lymph node dissection for type 2 gastric cancer of the antrum. One year later, CEA elevation was discovered, and contrast-enhanced abdominal computed tomography(CT)revealed a 40 mm mass in the liver(S8), which was judged to be a metastatic recurrence of the gastric cancer.S -1 plus CDDP was administered in 5 courses, followed by regular treatment with S-1 alone.Two years after the recurrence was diagnosed, the patient's CEA level was found to be normal, and CT revealed almost total scarring.After 2 more years, there was still no sign of recurrence, so, with the patient's consent, we discontinued the chemotherapy.Eight years after the gastrectomy, a 10mm nodular shadow was observed in the left lower lung lobe, and resection was performed.Despite the earlier diagnosis of gastric adenocarcinoma, this mass was considered a primary lung adenocarcinoma, and the patient died of small-cell lung cancer 11 years and 8 months after the gastrectomy.It is notable that the liver metastasis in this case responded to the S-1 plus CDDP and S-1 therapies, and this response is considered in light of the literature.

Topics: Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Gastrectomy; Humans; Liver Neoplasms; Male; Middle Aged; Oxonic Acid; Recurrence; Stomach Neoplasms; Tegafur

We report a case of Stage IV gastric cancer showing pathological complete response(pCR)after neo-adjuvant chemotherapy( NAC)using S-1 and oxaliplatin(SOX).A woman 73-year-old was diagnosed as harming type 3 Stage IV gastric cancer with para-aortic lymph node(PAN)metastasis.She underwent 4 courses of NAC with SOX regimen.After the treatment, both the primary tumor and the metastatic PAN decreased in size remarkably.She underwent distal gastrectomy with D2 plus PAN dissection with curative intent.Pathological diagnosis revealed complete disappearance of cancer cells in both the primary lesion of the stomach and all dissected lymph nodes, confirming pCR.She is alive without recurrence 4 months after surgery.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Female; Gastrectomy; Humans; Neoadjuvant Therapy; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Stomach Neoplasms; Tegafur

A 49-year-old man was diagnosed with advanced gastric cancer, with a chief complaint of epigastric discomfort. Computed tomography revealed multiple liver metastases. S-1 plus cisplatin therapy was administered as first-line chemotherapy, and after 4courses, the liver metastases markedly reduced. Total gastrectomy with D2 lymphadenectomy and a needle biopsy of segment 2 of the liver were performed. Histopathological examination revealed no viable cancer cells in the resected stomach, lymph nodes, or liver tissue. The primary tumor was defined as Grade 3 by histopathological examination. Adjuvant chemotherapy with S-1 was administered for 1 year. The patient is alive without recurrence more than 6 years after surgery.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Gastrectomy; Humans; Liver Neoplasms; Male; Middle Aged; Oxonic Acid; Stomach Neoplasms; Tegafur

A 27-year-old woman was diagnosed with gastric cancer complicated peritoneal dissemination and direct invasion to pancreas via staging laparoscopy. After systemic chemotherapy using regimen of S-1/CDDP for 2courses, the tumor did not increase in size and peritoneal dissemination did not progress. The patient subsequently underwent distal gastrectomy as a curative surgery. The histological diagnosis was ypT4bN1M0, ypStage III B. The patient was treated with DOC/CDDP for 6 courses after surgery as adjuvant therapy. At present 6 years after surgery, the patient is alive without tumor recurrence.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Female; Humans; Oxonic Acid; Peritoneal Neoplasms; Prognosis; Stomach Neoplasms; Tegafur

The patient is a 51-year-old man.Upper gastrointestinal endoscopy revealed gigantic type 3 gastric cancer.Enhanced abdominal CT demonstrated a gigantic mass of 15×7 cm in the stomach, and a large number of peritoneal dissemination with moderate amount of ascites.The patient was diagnosed with cT4aN3bM1(peritoneal dissemination), Stage IV gastric cancer(JPN ver8)and was treated by chemotherapy with docetaxel(40mg/m / 2 day 1)plus cisplatin(60mg/m2 day 1)plus S-1(80mg/m2 day 1-14).After 7 courses of chemotherapy, peritoneal dissemination was disappeared.The patient received total gastrectomy and D2 lymphadenectomy as a conversion surgery.The pathological findings revealed a T0N0M0, stage 0; the tumor was determined to be Grade 3 owing to the chemotherapeutic effect.Without postoperative adjuvant therapy, the patient is alive without recurrence at the 5 years follow-up after operation.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Docetaxel; Drug Combinations; Gastrectomy; Humans; Male; Middle Aged; Neoadjuvant Therapy; Oxonic Acid; Stomach Neoplasms; Taxoids; Tegafur

A57 -year-old man was diagnosed with advanced gastric cancer(adenocarcinoma[tub2/por1])with multiple(S3, S4, S5, S6, S8)liver and para-aortic lymph node metastases. The tumor was classified as cT4a, N3, M1, HEP, cStage IV, and the patient received chemotherapy with S-1 plus CDDP(SP). After 10 courses of SP, a CT scan revealed that the primary tumor and the metastases disappeared. The patient presented with cCR and underwent distal gastrectomy, D2 lymph node dissection, partial hepatic resection, and cholecystectomy. The histological diagnosis was classified as ypT0N0M0,(ypStage 0), pCR, and pathological Grade 3.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Digestive System Surgical Procedures; Drug Combinations; Humans; Liver Neoplasms; Male; Middle Aged; Neoadjuvant Therapy; Oxonic Acid; Stomach Neoplasms; Tegafur

One-year adjuvant S-1 monotherapy following D2 gastrectomy has been the Japanese treatment standard for pathological stage II or III gastric cancer since the Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer (ACTS-GC) was concluded in 2007. Trial patients were selected according to the 13th edition of the Japanese classification (JC-13). The JC-13 and the TNM classification underwent major revisions in 2010 (JC-14/TNM-7). However, neither the recent therapeutic results for patients with stage II/III disease defined by the current system nor comparisons with the ACTS-GC-results have been reported.. The 390 study patients had pathological stage II/III gastric cancer defined by the JC-14/TNM-7 and treated with S-1 following D2 gastrectomy between 2008 and 2012. The completion rate of 1-year S-1, first relapse site, and stage-specific survival according to the JC-14/TNM-7, JC-13, and TNM-6 were examined and the results compared with those of the ACTS-GC.. The completion rate for 1-year S-1 (69.5%) was slightly higher than in the ACTS-GC. The recurrence pattern was almost identical. The 5-year overall survival rates of pathological IIA, IIB, IIIA, IIIB, and IIIC in the JC-14/TNM-7 were 96.0, 85.5, 81.8, 72.0, and 51.1%, respectively. Their 5-year overall and relapse-free survival rates by the JC-13 and TNM-6 systems were favorable as compared to those of ACTS-GC patients for all substages.. Survival outcome shown in this study of patients treated with 1-year adjuvant S-1 after D2 gastrectomy at a high-volume cancer hospital will provide a reference for future adjuvant trials targeting JC-14/TNM-7 stage II/III disease.

Topics: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Drug Combinations; Gastrectomy; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Oxonic Acid; Patient Compliance; Retrospective Studies; Stomach Neoplasms; Survival Rate; Tegafur

The clinical significance of postoperative neutrophil lymphocyte ratio (NLR) remains unclear. The aim of this study was to examine the impact of postoperative NLR on prediction for postoperative recurrence of gastric cancer.. A retrospective analysis was performed on data from 170 patients with Stage II/III gastric cancer who underwent surgery followed by adjuvant chemotherapy using S-1 between 2006 and 2015. Postoperative NLR was calculated every 6 months and the data at the time of recurrence or last survival were used for analysis.. Postoperative NLR was associated with Prognostic nutritional index (PNI) and modified Glasgow Prognostic Score (mGPS). In multivariate analysis, we found that elevated CA19-9, CEA and NLR were independent predictive markers. The patients with low values of both NLR and CEA after surgery had the most favorable prognosis.. The postoperative NLR might be one of the surrogate markers for recurrence after curative surgery for patients with Stage II/III gastric cancer.

Topics: Aged; Antimetabolites, Antineoplastic; Biomarkers, Tumor; Chemotherapy, Adjuvant; Combined Modality Therapy; Disease-Free Survival; Drug Combinations; Female; Humans; Leukocyte Count; Lymphocytes; Male; Middle Aged; Neoplasm Recurrence, Local; Neutrophils; Nutrition Assessment; Oxonic Acid; Postoperative Period; Prognosis; Retrospective Studies; Stomach Neoplasms; Tegafur

The aim of this study was to compare the efficacies of the XELOX and DOS regimens as preoperative chemotherapy in patients with locally advanced gastric cancer.. All cases of locally advanced gastric cancer treated with the XELOX or DOS regimen were reviewed retrospectively. Propensity score matching (PSM) was carried out to reduce selection bias based on age, gender, location, Lauren type, carcinoembryonic antigen level, clinical tumor stage, and clinical node stage.. From January 2010 to December 2016, 248 patients were matched; 159 of them received the XELOX regimen and 89 the DOS regimen. The response rates in the XELOX and DOS groups were 34.5 and 38.1%, respectively (P = 0.823). After four cycles of chemotherapy, 111 patients (69.8%) in the XELOX group and 65 patients (73.0%) in the DOS group underwent radical surgery (P = 0.485). The median progression-free survival (33.0 months vs. 18.7 months, P = 0.0356) and the median overall survival (43.8 months vs. 29.1 months, P = 0.0003) were longer for patients who received the DOS regimen than for those who received the XELOX regimen. The occurrence of grade 3 to 4 toxicity was similar in the two groups.. For locally advanced gastric cancer patients, the DOS regimen showed more benefit than the XELOX regimen as preoperative chemotherapy, without any added toxicity effects.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Chemotherapy, Adjuvant; Deoxycytidine; Docetaxel; Drug Combinations; Female; Fluorouracil; Humans; Male; Middle Aged; Oxaliplatin; Oxaloacetates; Oxonic Acid; Propensity Score; Retrospective Studies; Stomach Neoplasms; Tegafur

A 70-year-old man was diagnosed with advanced gastric cancer based on esophagogastroduodenoscopy(EGD). Abdominal computed tomography(CT)showed swelling of the lymph nodes and invasion to the liver and pancreas. The patient was treated using combined docetaxel, cisplatin, and S-1(DCS)chemotherapy. After 2 courses of treatment, the primary tumor and lymph node metastases continued to grow. The patient was treated using secondary chemotherapy with irinotecan (CPT-11). After 1 course of treatment, the primary tumor and regional lymph nodes reduced in size. We performed curative total gastrectomy with D2 lymph node dissection. There has been no recurrence for 15 months after adjuvant chemotherapy with capecitabine and oxaliplatin(CapeOX). Therefore, CPT-11 therapy is a possible option for the management of advanced gastric cancer after DCS therapy.

Topics: Aged; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cisplatin; Docetaxel; Drug Combinations; Gastrectomy; Humans; Irinotecan; Male; Oxonic Acid; Stomach Neoplasms; Taxoids; Tegafur; Treatment Outcome

A preliminary study evaluating the feasibility of single intraperitoneal (IP) administration of paclitaxel followed by paclitaxel and cisplatin with S-1 (PCS) systemic chemotherapy for cytology-positive (CY1) gastric cancer.. Staging laparoscopy was performed to confirm CY1 and P0 status. Initially, patients received IP paclitaxel. Beginning 7 days later PCS was given every 3 weeks followed by second-look laparoscopy.. Nine patients were enrolled. The toxic effects of IP and systemic chemotherapy were acceptable. After chemotherapy, 8 patients converted from CY1P0 to CY0P0 and 1 patient from CY1P0 to CY1P1. Gastrectomy was performed on 8 patients except for the CY1P1 patient. Four patients were alive without recurrence. The 2-year overall and progression-free survival rates were 76% and 65%, respectively.. Combination chemotherapy with IP paclitaxel and sequential PCS is safe and may be effective for CY1 gastric cancer.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Feasibility Studies; Female; Follow-Up Studies; Humans; Injections, Intraperitoneal; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Recurrence, Local; Oxonic Acid; Paclitaxel; Peritoneal Neoplasms; Prognosis; Prospective Studies; Stomach Neoplasms; Survival Rate; Tegafur

Topics: Antineoplastic Combined Chemotherapy Protocols; Cyclobutanes; Disease Progression; Disease-Free Survival; Drug Combinations; Humans; Neoplastic Cells, Circulating; Organoplatinum Compounds; Oxonic Acid; Prognosis; Remission Induction; Retrospective Studies; Stomach Neoplasms; Tegafur

A 59-year-old woman was diagnosed with advanced gastric cancer with para-aortic and Virchow's lymph node metastases (L, Less, type 2, tub1, cT3N2H0P0M1[LYM: #16, Virchow's]). Four courses of S-1(80mg/m / 2, days 1-21)and CDDP(60mg/ m2, day 8)were administered. After the chemotherapy, CT showed that the primary tumor and para-aortic and Virchow's lymph nodes had reduced in size. The clinical stage was ycT3N1H0P0M0, stage III A. The patient underwent distalgastrectomy, D2 dissection, and sampling of the para-aortic lymph nodes(#16b1lat, #16a2int). The pathological diagnosis was L, less, type 1, por1/2, pT2N2H0P0M0CY0, pStage III B. The patient was treated with S-1(80mg/m2, days 1-28)as adjuvant chemotherapy. After 3 courses had been administered(6 months after the resection), swelling of a para-aortic lymph node (#16b1int)was detected using CT. Based on the diagnosis of recurrence in the lymph node, weekly paclitaxel(80mg/m2, days 1, 8, and 15)was administered. After receiving 9 courses of weekly paclitaxel, the swelling of the lymph node disappeared, and the response evaluation was complete response. She discontinued the chemotherapy 5 years and 9 months after the surgery. To date, she has survived more than 6 years after surgery without recurrence. We report a long-surviving patient with advanced gastric cancer with para-aortic lymph node metastasis who received combined modality therapy.

Topics: Antineoplastic Combined Chemotherapy Protocols; Aorta; Cisplatin; Combined Modality Therapy; Drug Combinations; Female; Humans; Lymphatic Metastasis; Middle Aged; Oxonic Acid; Stomach Neoplasms; Tegafur; Time Factors

This study aimed to retrospectively evaluate the efficacy and safety of capecitabine plus oxaliplatin(CapeOX)for heavily pretreated advanced gastric cancer(AGC)refractory to S-1, cisplatin, irinotecan, and taxanes.. Twelve patients with AGC refractory to S-1, cisplatin, irinotecan, and taxanes were enrolled in this study.Treatment comprised capecitabine(1,000mg/m / 2 twice a day on days 1-14)and oxaliplatin(130mg/m2 on day 1).Cycles were repeated at 3- week intervals.. The overall response rate was 16.7%, and the disease control rate at 6 weeks was 75.0%. The progression free survival was 3.1 months, and the overall survival was 8.3 months after initiation of CapeOX therapy. The most common hematological toxicity was grade 3 neutropenia(50%).Peripheral neuropathy of Grade 1 or 2 was found in 50%of cases, but no Grade 3 or 4 neuropathy was found.. CapeOX showed some activities as salvage therapy for heavily pretreated AGC patients.We suggest that CapeOX therapy should be considered a treatment option for pretreated AGC with good performance status.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Cisplatin; Drug Combinations; Drug Resistance, Neoplasm; Female; Humans; Irinotecan; Male; Middle Aged; Oxaliplatin; Oxonic Acid; Salvage Therapy; Stomach Neoplasms; Taxoids; Tegafur; Treatment Outcome

We report the case of a 72-year-old female who underwent laparoscopic total gastrectomy for gastric cancer. The pathological diagnosis was pT3, N1, M0, pStage II B. She received adjuvant chemotherapy with the TS-1®combination OD tablet, beginning 48 days after gastrectomy. The first course was stopped at day 7 because of neutropenia. The dose was decreased, a second course was started, and the patient completed her second course without neutropenia. After completion of the second course, we discovered that she had taken generic drugs(NKS-1®combination OD tablet)during the second course. She was enrolled in a clinical trial in which the administration of generic drugs was not permitted, as per the protocol. Beginning with the third course, we once again treated her with TS-1, and we observed a return of neutropenia in every subsequent course. We decreased the dose of TS-1 and changed the administration schedule each time. She exhibited no neutropenia only when using the generic S-1 formulation. It is possible that the anti-tumor effect of the generic S-1 formulation, and its associated adverse events, are not identical to the innovator formulation.

Topics: Aged; Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Drug Combinations; Drugs, Generic; Female; Gastrectomy; Humans; Neutropenia; Oxonic Acid; Stomach Neoplasms; Tegafur

The neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR) are associated with poor prognoses in patients with gastric cancer; however, few studies have focused on the dynamic changes in these ratios during the treatment of patients with gastric cancer. Here, we assessed the clinical utility of changes in these ratios as prognostic indicators in patients with stage II or III gastric cancer who received adjuvant chemotherapy.. We retrospectively reviewed 100 patients who received S-1 adjuvant chemotherapy at ≥70% of the relative dose intensity, and their NLRs and PLRs were evaluated at different times: prior to gastrectomy and upon commencement and termination of adjuvant chemotherapy. To assure the clinical utility of the changes in NLR and PLR as prognostic indicators, other clinical factors were assessed as well.. Disease recurred in 35 patients as follows: lymph node metastasis (17 patients, 17.0%), peritoneal metastasis (12 patients, 12.0%), and hematogenous metastasis (6 patients, 6.0%); 24 patients died. An increase in the NLR during adjuvant chemotherapy with S-1 was identified as an independent indicator associated with overall survival (hazard ratio [HR] 6.736, 95% confidence interval [CI] 2.420-18.748; P < 0.001), and relapse-free survival (HR 5.309, 95% CI 2.585-10.901; P < 0.001).. An increase in the NLR during S-1 adjuvant chemotherapy may be a useful prognostic indicator in patients with stage II or III gastric cancer.

Topics: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Drug Combinations; Female; Gastrectomy; Humans; Lymphocyte Count; Male; Middle Aged; Neoplasm Staging; Neutrophils; Oxonic Acid; Prognosis; Stomach Neoplasms; Survival Analysis; Tegafur; Treatment Outcome

Case 1: A 74-year-old man underwent total gastrectomy for gastric cancer, but peritoneal dissemination(P1c)was con- firmed intraoperatively in July 2011. Postoperatively, S-1/docetaxel(DTX)combination chemotherapy was administered; after 32 courses of treatment, S-1 was continued as monotherapy. However, in November 2013, CT scan showed a portal vein tumor. We modified the chemotherapy regimen, but he died 3 years and 7 months after the operation. Case 2: A 77-year-old man underwent distal gastrectomy for gastric cancer with peritoneal dissemination(P1b)in September 2013. He was treated with S-1/DTX/trastuzumab(Tmab)combination chemotherapy. After 5 courses of treatment, S-1was continued as monotherapy until October 2015. He has since survived without recurrence. Case 3: A 75-year-old woman was diagnosed with gastric cancer with peritoneal dissemination(P1c)by laparotomy in September 2014. She was treated with S-1/DTX combination chemotherapy. After 23 courses of treatment, chemotherapy was discontinued according to the patient's wish. She died 2 years and 6 months after the surgery. We suggest S-1/DTX combination chemotherapy as an option for advanced gastric cancer with peritoneal dissemination.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Docetaxel; Drug Combinations; Female; Gastrectomy; Humans; Male; Neoplasm Recurrence, Local; Oxonic Acid; Peritoneal Neoplasms; Stomach Neoplasms; Tegafur

We encountered a case of type 4 gastric cancer with esophageal invasion that responded to neoadjuvant chemotherapy containing S-1 and oxaliplatin(SOX)followed by surgery, which could be curative resection. A 46-year-old man was referred to our hospital because of abnormal upper gastrointestinal series findings. He was diagnosed with type 4 advanced gastric cancer with esophageal invasion, cT4b(diaphragm)N2M0, Stage ⅢC, and 3 courses of neoadjuvant SOX therapy were administered. Adverse events were minor. After NAC, the primary lesion and lymph nodes showed marked reductions on CT; total gastrectomy and subtotal thoracic esophagectomy were performed. The pathological response to NAC was evaluated as Grade 2 in the primary tumor and Grade 3 in the lymph node; overall, NAC showed considerable antitumor effects. The final diagnosis was ypT3N0M0P0CY0H0, StageⅡA, and was judged as curatively resected. Currently, we are continuing to administer adjuvant chemotherapy containing S-1.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Esophagus; Gastrectomy; Humans; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Invasiveness; Oxaliplatin; Oxonic Acid; Stomach Neoplasms; Tegafur

Case 1: A 75-year-old man underwent distal gastrectomy with Billroth Ⅰ reconstruction and resection of the involved transverse mesocolon. Microscopic examination revealed adenocarcinoma(tub2, tub1), pT4b(SI)N3M0, pStageⅢc. Adjuvant chemotherapy with S-1 was performed for 6 months after the operation. One year later, CT revealed a localized dissemination in the transverse mesocolon; therefore, we performed transverse colectomy. Adjuvant chemotherapy with PTX was performed, and the patient remains free from recurrence 7 years after the initialoperation. Case 2: A 65-year-old man was diagnosed with gastric scirrhous carcinoma by esophagogastroduodenoscopy. CT and colonoscopy showed a tumorous lesion in the pelvis(Schnitzler's metastasis). Neo-adjuvant chemotherapy with S-1 plus CDDP was performed. After 6 courses, CT and endoscopy showed shrinkage of the tumors, and no other distant metastasis was detected by PET-CT. We performed totalgastrectomy(D2), splenectomy, and low anterior resection of the rectum simultaneously. Microscopic examination revealed adenocarcinoma(tub2, por2, sig), pT4a(SE)N0, and the histological response was Grade 1a. S-1 was administered, and the patient has had no recurrence in the 1 year 6 months after the operation. Dissemination of gastric cancer tends to be difficult to treat and has a poor prognosis. However, in some cases, the proper combination of chemotherapy and surgery might be beneficial for long survival.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Drug Combinations; Gastrectomy; Humans; Male; Neoplasm Recurrence, Local; Oxonic Acid; Positron Emission Tomography Computed Tomography; Stomach Neoplasms; Tegafur

Here, we report a long-term survival case treated with docetaxel and S-1 combination therapy(DS therapy)for peritoneal dissemination of gastric cancer. A 58-year-old man was diagnosed with gastric cancer in 2006. Distal gastrectomy, D2 dissec- tion, and RY reconstruction were performed. The pathological diagnosis was gastric cancer, por2, pT3(SS), pN3a(8/27), pStage ⅢB. S -1 monotherapy was administered as an adjuvant chemotherapy for 1 year from 3 months after surgery. Five years after surgery, peritoneal dissemination and bladder recurrence caused rectal stenosis and hydronephrosis. We performed ileostomy and left nephrostomy. DS therapy was started 5 years and 2 months after the initial surgery. A complete clinical remission was observed 2 years and 10 months after starting DS therapy(23 courses). Multiple lymph node metastasis and bone metastasis were confirmed at 5 years and 5 months(57 courses). Even though irinotecan monotherapy was performed for five courses, the bone and lymph node metastasis increased at 5 years and 9 months after starting DS therapy, and the patient died at 69 years of age. DS therapy may be a useful option for peritoneal metastasis of gastric cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; Docetaxel; Drug Combinations; Gastrectomy; Humans; Male; Middle Aged; Oxonic Acid; Peritoneal Neoplasms; Stomach Neoplasms; Tegafur

The aim of this study was to investigate the efficacy and safety of S-1 plus low-dose cisplatin for stage IIIB and stage IIIC gastric cancer patients after D2 gastrectomy.. The study group comprised of 52 patients. In the first cycle, S-1 (80 mg/m. Overall survival was 47.0 months for stage IIIB patients and 24.0 months for stage IIIC (p=0.038). Disease-free survival was 17.0 and 16.0 months respectively (p=0.739). Grade 3 or 4 adverse events occurred in 20 patients (38.5%). Multivariate analysis identified stage IIIC as independent prognostic factor for survival.. Our treatment was manageable and safe for stage IIIB or stage IIIC patients. Stage IIIC gastric cancer portends an especially poor prognosis following D2 gastrectomy.

Topics: Aged; Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Cisplatin; Combined Modality Therapy; Disease-Free Survival; Drug Combinations; Female; Humans; Male; Middle Aged; Multivariate Analysis; Oxonic Acid; Prognosis; Proportional Hazards Models; Stomach Neoplasms; Tegafur; Treatment Outcome

To evaluate the efficacy of conversion surgery following S-1 plus cisplatin (CS) or oxaliplatin (SOX) chemotherapy.. We retrospectively analyzed clinicopathological and survival data of 74 patients with unresectable gastric cancer receiving CS or SOX.. Fifty-five and nineteen patients received CS and SOX, respectively. Conversion surgery (odds ratio (OR), 0.17; 95% confidence interval (CI), 0.04-0.64; p=0.01) was the only significant independent predictor of longer survival in multivariate Cox regression analysis. Patients (median age, 74 years) receiving SOX were significantly older than those receiving CS (median age=67 years) (p<0.01), although the rates of response, severe toxicity or conversion surgery did not differ significantly between the two treatment groups.. Conversion surgery after a response to CS or SOX chemotherapy may have survival benefit in selected unresectable gastric cancer patients, for both non-elderly and elderly patients responding to SOX.

Topics: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Databases, Factual; Disease Progression; Drug Combinations; Female; Humans; Male; Middle Aged; Neoplasm Staging; Odds Ratio; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Proportional Hazards Models; Retrospective Studies; Stomach Neoplasms; Tegafur; Treatment Outcome

A triplet regimen of docetaxel, cisplatin, and S-1(DCS) is highly effective against metastatic gastric cancer. We performed this study to clarify the safety and efficacy of surgical resection in patients with initially unresectable gastric cancer, after down-staging or disease control was achieved by DCS chemotherapy.. The subjects of this retrospective study were 31 consecutive patients with initially unresectable gastric cancer, who underwent surgical resection between October, 2006 and December, 2012, after down-staging or disease control was achieved by DCS chemotherapy. We evaluated the clinicopathological factors and clinical outcomes and assessed radiographic response based on the RECIST criteria, not by central review.. Before DCS chemotherapy, 18 patients had extra-regional lymph node metastasis, 5 had liver metastasis, 8 had macroscopic peritoneal metastasis, and 8 had pancreatic head invasion. Twenty-three (74.2%) of the 31 patients underwent R0 resection. Postoperative morbidity and mortality rates were 16.1 and 0%. During chemotherapy, grade 3/4 toxicities included neutropenia (54.8%), leukopenia (32.3%), and anemia (16.1%). Median progression-free survival and median overall survival (OS) were 42.1 and 56.1 months, respectively. These results were similar for all patients, except those with locally advanced disease alone. In the multivariate analysis for OS, ypN remained an independent negative prognostic factor (p = 0.018).. Surgical resection after DCS chemotherapy for initially unresectable gastric cancer was safe and provided a reasonable R0 resection rate and good mid-term survival.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Cohort Studies; Combined Modality Therapy; Docetaxel; Drug Combinations; Female; Follow-Up Studies; Gastrectomy; Humans; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Pancreaticoduodenectomy; Stomach Neoplasms; Survival Rate; Taxoids; Tegafur; Treatment Outcome

The theory of extravasated platelet aggregation in cancer lesions was recently introduced. We investigated the association of platelet aggregation in gastric cancer stroma with clinicopathological features, chemotherapeutic response, pathological response, and survival.. The study comprised 78 patients with advanced gastric cancer who had undergone gastrectomy with or without combination of docetaxel, cisplatin and S-1 (DCS) as preoperative chemotherapy between 2005 and 2014. The patients were divided into two groups: patients who had received preoperative DCS therapy forming the p-DCS group and patients who had not received preoperative DCS therapy forming the control group. The 39 patients in the control group had received gastrectomy and postoperative chemotherapy of S-1 alone. Platelet aggregation in biopsy specimens before preoperative DCS therapy in the p-DCS group and at the time of diagnosis in the control group were evaluated using CD42b immunohistochemical staining.. Twenty-four patients in the p-DCS group and 19 in the control group were found to have platelet aggregation in their cancer stroma. Patients with histologically confirmed platelet aggregation had significantly higher rates of chemoresistance (58.3%) than those without platelet aggregation (20.0%) (P = 0.019). According to multivariate analysis, CD42b expression (odds ratio: 5.102, 95% confidence interval: 1.039-25.00, P = 0.045) was correlated with chemoresistance. CD42b expression and histological non-responder status were both significantly correlated with poor overall survival (OS) (P = 0.012, P = 0.016); however, RECIST was not correlated with OS. In the control group, CD42b expression was also significantly correlated with poor overall survival (OS) (P = 0.033). In the p-DCS group, according to multivariate analysis, male sex (hazard ratio: 0.281, 95% confidence interval: 0.093-0.846, P = 0.024) was correlated with good prognosis and CD42b expression (hazard ratio: 4.406, 95% confidence interval: 1.325-14.65, P = 0.016) with poor prognosis.. This study suggests that platelets in gastric cancer stroma may create a favorable microenvironment for chemoresistance. CD42b immunohistochemical staining of biopsy specimens is a promising candidate for being a prognostic marker in patients with gastric cancer.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Biomarkers; Cisplatin; Docetaxel; Drug Combinations; Female; Follow-Up Studies; Humans; Liver Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Grading; Oxonic Acid; Platelet Aggregation; Preoperative Care; Prognosis; Retrospective Studies; Stomach Neoplasms; Survival Rate; Taxoids; Tegafur

We retrospectively investigated the efficacy and safety of S-1 and oxaliplatin(SOX)as the first-line chemotherapy in patients with metastatic/recurrent gastric cancer. A total of 27 patients who received SOX as the first-line chemotherapy in our hospital were considered for the study. The SOX chemotherapy schedule consisted of 1 course every 3 weeks. S-1 was administered orally, at 80-120mg-body, every day for 14 days. Oxaliplatin was infused at 100mg/m2 on day 1 of each course. The median number of treatment courses was 7. The response rate and disease control rate were 47.6% and 76.2%, respectively. The observed adverse events of Grade 3 or more included neutropenia(33.3%); peripheral neuropathy and anorexia(11.1%); thrombocytopenia(7.4%); and anemia, diarrhea, fatigue, and hypercalcemia(3.7%). The median overall survival was not achieved, and the 1-year survival rate was 63.2%. Therefore, SOX is an effective and feasible first-line chemotherapy that is easily available for ambulatory treatment of patients with metastatic/recurrent gastric cancer.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Female; Humans; Male; Middle Aged; Neoplasm Metastasis; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Recurrence; Retrospective Studies; Stomach Neoplasms; Tegafur; Treatment Outcome

Curative gastrectomy followed by adjuvant S-1 chemotherapy for 12 months is one of the standard treatments for patients with pathological stage (p-stage) II or III gastric cancer. Although some patients have difficulty maintaining compliance with adjuvant S-1, the risk factors for poor compliance are unknown.. We retrospectively analyzed the data of patients at 21 institutions who underwent curative gastrectomy followed by adjuvant S-1 for p-stage II or III gastric cancer. Patients who had a recurrence within 12 months after surgery were excluded from the analysis. Associations between clinicopathological factors and both 12-month compliance and the cumulative continuation rate of S-1 were analyzed.. Of 359 patients, 252 (70.2%) continued adjuvant S-1 until 12 months after surgery. Older age (>65 years) and postoperative infectious complications (Clavien-Dindo grade III or higher) were significantly correlated with low compliance with S-1 for 12 months (p = 0.008 and p = 0.042). These two factors also showed significant associations with low cumulative continuation rate (log-rank p < 0.001 and p = 0.018). Continuation rates at 12 months after surgery in patients aged ≤60 years, 61-65, 66-70, 71-75, and 76-80 years were 81.5, 75.9, 65.4, 58.7, and 62.9%, respectively. Type of gastrectomy or body weight loss at 1 month after surgery did not affect either 12-month compliance or the cumulative continuation rate of S-1.. Older age, especially over 65 years, and postoperative infectious complications were independent risk factors for poor compliance with adjuvant S-1 chemotherapy for gastric cancer.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Drug Combinations; Female; Gastrectomy; Humans; Infections; Male; Medication Adherence; Middle Aged; Neoplasm Staging; Oxonic Acid; Postoperative Complications; Retrospective Studies; Risk Factors; Stomach Neoplasms; Tegafur; Young Adult

Topics: Administration, Oral; Aged; Breast Neoplasms; Capecitabine; Cardiotoxicity; Colorectal Neoplasms; Coronary Vasospasm; Drug Combinations; Drug Substitution; Female; Humans; Male; Middle Aged; Oxonic Acid; Stomach Neoplasms; Tegafur

A 77-year-old man was diagnosed with gastric cancer with synchronous single liver metastasis and portal vein thrombus. His HER2 immunohistochemistry tumor score was 3+; therefore, we administered trastuzumab plus capecitabine plus cisplatin. After 2 courses of chemotherapy, we observed disappearance of the portal vein thrombus and tumor reduction as a partial response, according to the RECIST guidelines. We performed distal gastrectomy and right lobectomy; the therapeutic grades of the primary and metastatic tumors were 1a and 2, respectively. We administered postoperative chemotherapy, and no recurrent lesions have appeared 2 years after surgery. Multidisciplinary treatment for gastric cancer with liver metastasis might be a feasible and useful strategy.

Topics: Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Cisplatin; Combined Modality Therapy; Drug Combinations; Gastrectomy; Humans; Liver Neoplasms; Male; Oxonic Acid; Portal Vein; Stomach Neoplasms; Tegafur; Time Factors; Trastuzumab; Venous Thrombosis

The outcome of gastric cancer patients with peritoneal metastasis remains poor. We treated these patients with intraperitoneal and intravenous paclitaxel plus oral S-1 (tegafur/gimeracil/oteracil), followed by gastrectomy in responders. We evaluated the clinical significance of peritoneal lavage carcinoembryonic antigen (CEA) messenger RNA (mRNA) levels as a biomarker for indication of conversion gastrectomy.. The peritoneal lavage of 68 patients who received the above regimen as induction chemotherapy was repeatedly collected via intraperitoneal access ports. Gastrectomy was considered when improvement of peritoneal metastasis was confirmed by a second laparoscopic examination with negative peritoneal cytology. CEA and porphobilinogen deaminase mRNAs were chronologically quantified using the transcription reverse-transcription concerted reaction method. The CEA mRNA index (CmRI) was calculated as CEA mRNA/porphobilinogen deaminase mRNA × 10,000.. Thirty-nine patients underwent gastrectomy and 29 patients did not (median survival time, 27.8 vs. 10.7 months, respectively; P < 0.001). In gastrectomy-positive patients, the outcome largely differed according to CmRI values immediately prior to surgery. Patients with a preoperative CmRI value <100 (n = 20) were associated with a significantly longer survival than those with a preoperative CmRI value >100 (n = 19) (41.8 vs. 20.1 months, respectively; P < 0.001). A preoperative CmRI value <100 was confirmed as an independent predictor of survival for gastrectomy-positive patients in the multivariate analysis.. The CmRI reflects the response of peritoneal metastases to induction intraperitoneal chemotherapy. It may be a useful biomarker for indicating gastrectomy in gastric cancer patients with peritoneal metastasis.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoembryonic Antigen; Combined Modality Therapy; Drug Combinations; Female; Follow-Up Studies; Gastrectomy; Humans; Induction Chemotherapy; Injections, Intraperitoneal; Laparoscopy; Male; Middle Aged; Oxonic Acid; Paclitaxel; Peritoneal Lavage; Peritoneal Neoplasms; Prognosis; Retrospective Studies; RNA, Messenger; Stomach Neoplasms; Survival Rate; Tegafur

Taxane monotherapy is widely used for advanced gastric cancer (AGC) after failure of standard first-line chemotherapy with fluoropyrimidine and cisplatin. Triplet chemotherapy with docetaxel, cisplatin, and S-1 (DCS) is a promising regimen for first-line chemotherapy of AGC. The aim of this study was to evaluate the efficacy of taxane monotherapy in patients refractory to DCS.. We retrospectively evaluated the efficacy and safety of taxane monotherapy in patients with AGC refractory to first-line therapy with DCS between January 2010 and April 2015. Selection criteria were as follows: ECOG PS of 0-2, treatment with taxane monotherapy in second-line or third-line therapy after failure of second-line irinotecan, absence of massive ascites, and adequate organ function.. A total of 30 patients were included in this study. Of these, 15 patients received paclitaxel while another 15 received nanoparticle albumin-bound paclitaxel in either second- or third-line treatment. Median age for the second/third-line group was 64.0/62.0 (range 27-75/42-75); 14/13 (93.3/86.7%) had ECOG PS of 0 or 1. No patients achieved complete or partial response and stable disease was observed in 37.5/35.7% of the patients in the second/third line. Median progression-free survival and overall survival were 3.4 and 5.8 months in the second-line group, and 2.0 and 4.5 months in the third-line group, respectively. The incidences of any grade ≥3 adverse events in the second-line group and the third-line group were 60.0 and 33.3%, respectively. There was no treatment-related death.. Taxane monotherapy after DCS failure had acceptable toxicities but was ineffective in AGC patients.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bridged-Ring Compounds; Cisplatin; Docetaxel; Drug Combinations; Female; Humans; Male; Middle Aged; Oxonic Acid; Retrospective Studies; Stomach Neoplasms; Taxoids; Tegafur

Gastric carcinoma is a heterogeneous malignant disease involving genetic factors. To identify predictive markers for gastric cancer treatment in Chinese patients, we evaluated the association between polymorphisms of the gene encoding cytochrome P450 2A6 (CYP2A6) and outcomes of S-1 plus oxaliplatin (SOX) chemotherapy treatment. Clinical data on 60 consecutive gastric cancer patients receiving SOX regimen were collected prospectively. We sequenced all exons of CYP2A6 and a total of 22 different polymorphisms were detected in the present study. Comprehensive analyses of these genetic polymorphisms were performed to determine their association with both safety and efficacy of SOX regimen. Our results showed that polymorphisms of CYP2A6 were associated with the safety and efficacy of SOX treatment. Among them, missense mutations CYP2A6 rs60823196 and rs138978736 could be possible risk factors (P<0.05) for severe diarrhea induced by SOX, whereas CYP2A6 rs138978736 could be a conceivable predictor for overall survival of patients treated with SOX adjuvant chemotherapy. Further large-scale randomized prospective studies are warranted to confirm these findings.

Topics: Adult; Aged; Asian People; China; Cytochrome P-450 CYP2A6; Diarrhea; Drug Combinations; Drug Therapy, Combination; Female; Genotype; Haplotypes; Humans; Kaplan-Meier Estimate; Linkage Disequilibrium; Male; Middle Aged; Odds Ratio; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Polymorphism, Genetic; Prospective Studies; Severity of Illness Index; Stomach Neoplasms; Tegafur; Treatment Outcome

To compare capecitabine and oxaliplatin (XELOX) with S-1 as adjuvant chemotherapy in stage III gastric cancer after D2 gastrectomy.. Clinical data from 206 patients who received XELOX or S-1 regimens as adjuvant chemotherapy in stage III gastric cancer were collected. Patients were divided into 2 groups according to regimen; the groups were XELOX (n = 114) and S-1 monotherapy (n = 92).. 3-year disease-free survival (DFS) was higher in the S-1 group than in the XELOX group (66.6% vs 59.1%; p = 0.636). 3-year overall survival (OS) was 75.6% in the S-1 group and 69.6% in the XELOX group (p = 0.495). But, the difference was not statistically significant. Especially, for patients with stage IIIC disease, 3-year overall survival was 55.2% in the XELOX group and 39.0% in the S-1 group (hazard ratio, HR 0.50, 95% confidence interval, CI 0.23-1.10; p = 0.075). In multivariate analysis, N stage (HR, 5.639; 95% CI, 1.297-24.522; p = 0.021) and cycle completion as planned (HR, 5.734; 95% CI, 3.007-10.936; p<0.001) were independent predictors of overall survival.. Adjuvant XELOX and S-1 regimen did not prove anything superior for stage III gastric cancer in this study. But, XELOX had a tendency to be superior to S-1 in stage IIIC gastric cancer after D2 gastrectomy although the difference was not statistically significant. N stage and cycle completion as planned were prognostic factors.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Chemotherapy, Adjuvant; Disease-Free Survival; Drug Combinations; Drug-Related Side Effects and Adverse Reactions; Female; Gastrectomy; Humans; Male; Middle Aged; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Stomach Neoplasms; Tegafur; Treatment Outcome

A 55-year-woman presented with abdominal fullness. An abdominal MRI disclosed ovarian and uterine tumors. Under the pathological diagnosis of Kruckenberg tumor, total hysterectomy and bilateral adenexectomy were performed. Gastrointestinal endoscopy disclosed type 3 on the greater curvature and anterior wall of the middle gastric body. The gastric cancer had a similar histology, which suggested the tumor origin and led to the diagnosis of c-stage IV. She received 6 courses of SOX chemotherapy. Staging laparoscopy revealed no peritoneal metastasis and negative cytodiagnosis of ascites. She underwent total gastrectomy with D2 lymphadenectomy. In May 2017, after S-1 chemotherapy, no metastasis to other organs was observed.

Topics: Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Female; Humans; Hysterectomy; Krukenberg Tumor; Middle Aged; Organoplatinum Compounds; Ovarian Neoplasms; Oxaliplatin; Oxonic Acid; Stomach Neoplasms; Tegafur; Time Factors

Topics: Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Female; Fluorouracil; Humans; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Paclitaxel; Remission Induction; Stomach Neoplasms; Tegafur

A 67-year-old man was admitted to our hospital because of anemia and weight loss, and diagnosed with a type 3 tumor in the upper gastric body. Pathological examination suggested moderately differentiated adenocarcinoma with immunohistochemically negative staining for HER2. Abdominal CT revealed thickening of the gastric wall and multiple liver metastases. The clinical findings suggested Stage IV disease(T4aN0M1). Chemotherapy was administered with a combination of S-1 plus CDDP(SP). However, the level of CEA(ng/mL)increased from 49.2 to 634.6, and the treatment schedule was changed to a combination of S-1 plus oxaliplatin(SOX). After 3 courses of the SOX regimen, abdominal CT showed a reduction of liver metastases and the level of CEA decreased to 8.4 ng/mL. We performed total gastrectomy with D1 lymph node dissection in September 2016. Post-operative pathological findings were ypStage IV (T3N0M1)and chemotherapeutic effect was grade 2. CT scan revealed regrowth of the tumor in S2 3 months after the operation. The patient underwent transcatheter arterial chemoembolization(TACE)followed by a regimen of paclitaxel plus ramucirumab(PTX/RAM). At present, he is being treated with the PTX/RAM regimen in the outpatient department with no signs of tumor growth. Although the prognosis of gastric cancer with synchronous liver metastases is very poor, it is possible for survival to be prolonged with multimodality therapy.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Drug Combinations; Gastrectomy; Humans; Liver Neoplasms; Male; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Stomach Neoplasms; Tegafur; Treatment Outcome

A 78-year-old man underwent an upper gastrointestinal endoscopy for evaluation of epigastralgia. Endoscopy revealed a bulky type 3 tumor in the lesser curvature of the upper body. A biopsy showed a poorly differentiated adenocarcinoma with signet ring cell carcinoma. Additionally, abdominal computed tomography(CT)showed bulky lymph node metastases leading to a diagnosis of cT3N2M0, Stage III A carcinoma. Following administration of 2 courses of neoadjuvant chemotherapy (NAC)using S-1/cisplatin(CDDP), CT revealed significant regression of the primary lesion and lymph nodes. Eventually, laparoscopic total gastrectomy was performed. Histopathologically, almost all viable cancer cells had been cleared from the primary lesion, and no cancer cells were found in the lymph nodes, which indicated a pathological partial response(Grade 2). NAC could be a valid option for the treatment of advanced gastric cancer.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Signet Ring Cell; Cisplatin; Drug Combinations; Humans; Male; Neoadjuvant Therapy; Oxonic Acid; Prognosis; Stomach Neoplasms; Tegafur

We evaluate the feasibility and efficacy of combination chemotherapy including single intraperitoneal( IP)administration of paclitaxel(PTX), followed by triplet chemotherapy(PTX, cisplatin[CDDP]and S-1: PCS)for CY1P0 gastric cancer.. First of all, we performed staging laparoscopy and confirmed CY1P0, and secondary, administrated PTX intraperitoneally. Thirdly, patients received PCS chemotherapy for 2 courses. After antitumor effect had been confirmed, we performed second look laparoscopy. In the case of CY0P0, we performed gastrectomy with D2 lymph nodes dissection.. Total 4 patients were enrolled. Grade 3 leukopenia and neutropenia were observed in one patient while intraperitoneal and systemic-chemotherapy. One patients showed PR and 3 patients showed SD. All patients underwent second look laparoscopy. CY0P0 was observed in all patients and gastrectomy with D2 dissection was performed for all patients. Postoperative complications were observed in 2 patients. Two patients were still alive without recurrence, while the remaining 2 had died of liver metastasis and #16 LN metastasis.. Combination chemotherapy including single IP PTX followed by PCS systemic-chemotherapy for CY1P0 gastric cancer is feasible and efficient.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Female; Humans; Infusions, Parenteral; Lymphatic Metastasis; Male; Middle Aged; Oxonic Acid; Paclitaxel; Stomach Neoplasms; Tegafur

A 76-year-old man was referred to our hospital with gastric cancer.Esophagogastroduodenoscopy (EGD)revealed an irregular, nodulated lesion with ulcers in the lower part of the stomach, for which biopsy specimens indicated poorly differentiated adenocarcinoma.Abdominal computed tomography(CT)showed a well-defined mass lesion measuring 5.3 cm in the posterior segment of the liver.Under the clinical diagnosis of advanced gastric cancer with liver metastasis, the patient received chemotherapy using S-1 and oxaliplatin.After 8 courses of chemotherapy, abdominal CT and EGD revealed that the size of liver metastasis was reduced to 2.3 cm. He underwent distal gastrectomy with D2 lymphadenectomy and resection of the liver metastases because there was no evidence of further metastatic lesions in any other organs after 10 courses of chemotherapy.The gross appearance of the surgically resected specimen showed a shrunk gastric tumor measuring 3.5×3.0 cm and a well-circumscribed, solid liver mass.Pathological examination confirmed the diagnosis of solid-type, poorly differentiated adenocarcinoma in the stomach that had invaded the submucosal layer with no lymph node metastasis, and necrotic change of the liver mass.The postoperative course was uneventful, and the patient has been well, receiving maintenance chemotherapy using S-1, without evidence of recurrence for 9 months following the operation.Conversion surgery following chemotherapy might be a proposed treatment for patients with advanced gastric cancer; however, further studies and assessments are needed to establish this treatment strategy.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Gastrectomy; Hepatectomy; Humans; Liver Neoplasms; Male; Neoadjuvant Therapy; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Stomach Neoplasms; Tegafur

In recent years, the development of chemotherapy has been remarkable. Some cases of conversion surgery for unresectable gastric cancer have been reported.. The clinical outcome of 11 patients with far advanced gastric cancer who underwent conversion surgery in our hospital from January 2013 to May 2017 were analyzed retrospectively.. The median survival time was 592 days(355-1,460). Four patients died of recurrent gastric cancer. Patients with undifferentiated carcinoma dominant had significantly poor survival rather than with differentiated carcinoma dominant(p= 0.039). Meanwhile, the pathological responders for chemotherapy did not have significantly better survival rather than nonresponders.. Although the short term outcome of conversion surgery was acceptable, recurrent rate was still high. To improve the prognosis, clarifying the optimal timing of operation and more effective adjuvant chemotherapy are mandatory.

Topics: Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Female; Gastrectomy; Humans; Male; Middle Aged; Oxonic Acid; Retrospective Studies; Stomach Neoplasms; Tegafur

A woman approximately 70-years-old with duodenal invasive advanced gastric cancer was referred to our hospital. Meta- stasis to lymph node(LN)No.13 was suspected based on FDG/PET-CT. For better curability, we selected neoadjuvant chemotherapy( NAC)with S-1 plus oxaliplatin(SOX therapy). After 3 courses of SOX, distal gastrectomy with D2(+No.13) lymphadenectomy was performed. Upon pathological evaluation, no viable cancer cells were found in the primary tumor, but viable cancer cells were identified in LN No.6 and 13. LN No.13 was defined as M1 according to the current Japanese classification of gastric carcinoma. On the other hand, the 2014 Japanese gastric cancer treatment guidelines(ver. 4)mentioned that D2(+No.13)lymphadenectomy may be an option in potentially curative gastrectomy for tumors invading the duodenum. This case suggests that No.13 lymphadenectomy is necessary as a curative operation for duodenal invasive advanced gastric cancer, even if the primary tumor has achieved pCR after NAC.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Duodenum; Female; Gastrectomy; Humans; Lymphatic Metastasis; Neoadjuvant Therapy; Neoplasm Invasiveness; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Stomach Neoplasms; Tegafur

A 73-year-old man presented to a clinic complaining of upper abdominal pain with nausea and diarrhea. The patient was subsequently diagnosed with progressive gastric cancer: cT4a(SE), N3M1(H1P1), Stage IV . For first-line therapy, SP: S-1(120 mg, 3 weeks)and CDDP(90 mg, 8 days iv) were selected. Though the patient had Grade 3 thrombocytopenia and renal dysfunction, 13 courses were performed over 1 year 6 months. The primary lesion in the stomach showed complete response, while the metastatic foci in the liver reduced in size. Because of renal dysfunction and thrombocytopenia, 19 courses of SOX: S-1(80 mg, 2 weeks)and oxaliplatin(100 mg, 3 weeks)were administered for 1 year. Thereafter, S-1(80 mg, 4 weeks) was continued for 6 months. Appropriate administration of chemotherapy led to complete radiographic resolution of the gastric tumor, with survival currently approaching 3 years 6 months.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Humans; Liver Neoplasms; Male; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Peritoneal Neoplasms; Stomach Neoplasms; Tegafur

A 71-year-old man was diagnosed with locally advanced gastric cancer(cT4b[Panc], N2, M0, cStage III C). He was treated with a triplet neoadjuvant chemotherapy regimen including docetaxel, oxaliplatin and S-1, followed by laparoscopic total gastrectomy with pancreatosplenectomy which achieved R0 resection. He had no pancreatic fistula, leakage and abscess and was transferred to other hospital on POD18 for rehabilitation. Adjuvant chemotherapy wish S-1was started on 7 weeks after surgery. Although multidisciplinary treatment such as perioperative chemotherapy and radical surgery is necessary, careful and precise interpretation of diagnostic image is mandatory for undergoing curative surgery with composite resection laparoscopically. In this report, we demonstrated that totally laparoscopic radical surgery safely and allowed the patient to initiate adjuvant chemotherapy in the early postoperative period.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Docetaxel; Drug Combinations; Gastrectomy; Humans; Laparoscopy; Male; Neoadjuvant Therapy; Neoplasm Invasiveness; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Pancreatectomy; Splenectomy; Stomach Neoplasms; Taxoids; Tegafur

A 83-year-old female, with oppression in her chest, was subjected to type 2 advanced gasteric cancer in esophagogastric junction. Examinations revealed Stage III c of cT4, cN2, cM0. For adopting neoadjuvant chemotherapy, S-1 plus CDDP was not on the list, but S-1 plus oxaliplatin (SOX) was, because massive load of infusion along with the chemotherapy was not appropriate for the patient with low cardiac function. After 2 courses of SOX, the primary tumor as well as metastatic lymph nodes were shown with marked reduction in size by CT scan, which enabled total gastrectomy with D2 lymphadenectomy to be performed as a curative resection, leading to patient living with no recurrence more than 3 years. SOX was considered as one of safe neoadjuvant agent for gastric cancer combined with low cardiac function.

Topics: Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Female; Gastrectomy; Humans; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Neoadjuvant Therapy; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Stomach Neoplasms; Tegafur

The case was a 70s-year-old man. In July 2016, he was admitted to our hospital with a complaint of epigastralgia. Upper gastrointestinal endoscopy revealed type 3 advanced gastric cancer in the vestibule, directly infiltrating the pancreas and the left lobe of the liver to form an abscess, and swelling of the aortic lymph node and multiple liver metastases were observed. The cancer was diagnosed as cT4b(liver/pancreas), N2M1(H1P0CYX), cStage IV and diagnosed it as a chemotherapy policy. We initiated SOX plus trastuzumab therapy from August 2016. After 4 courses, the primary tumor shrunk significantly and invasion to the pancreas/liver had disappeared. Furthermore, the periarterial lymph node and multiple liver metastases were obscured(chemotherapy effect judgment: PR). With a diagnosis of ycT4aN1MX(HXP0CYX), in December 2016, we performed a pyloric side gastrectomy D2(+No.16)dissection and partial resection of the liver(S3, S4, S6), liver RFA(S4, S6, S7). Due to recent progress in chemotherapy and multidisciplinary therapy, there is a possibility that radical resection may be carried out for advanced gastric cancer, which was previously unresectable, by performing a treatment with surgery in mind.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Gastrectomy; Humans; Male; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Receptor, ErbB-2; Stomach Neoplasms; Tegafur; Trastuzumab

Oral fluoropyrimidine S-1 contains tegafur, which is metabolized to 5-fluorouracil by cytochrome P450 2A6 (CYP2A6). We here examined associations between CYP2A6 polymorphisms and treatment outcomes of adjuvant S-1 in gastric cancer patients.. Patients received adjuvant S-1 (40 mg/m. Patients (n = 200) were enrolled between November 2007 and July 2013 with the following clinical characteristics: median age, 57 years (range, 32-83 years); 128 men, 72 women. With a median follow-up of 46.4 months, the 3-year relapse-free survival (RFS) and overall survival (OS) rates were 83.1 % (95 % CI, 77.7-88.5 %) and 94.8 % (95 % CI, 91.6-98.0 %), respectively. Genotype distributions were as follows: W/W (n = 49, 24.5 %), W/V (n = 94, 47.0 %), and V/V (n = 57, 28.5 %). Overall toxicity did not differ according to genotype for any grade (p = 0.612) or grade ≥3 (p = 0.143). However, RFS differed significantly according to CYP2A6 genotype. The 3-year RFS rates were 95.9 % for W/W, 83.1 % for W/V, and 72.5 % for V/V (p = 0.032). Carriers of W/V and V/V genotypes had a poorer RFS with a hazard ratio of 3.41 (95 % CI, 1.01-11.52; p = 0.049) and 4.03 (95 % CI, 1.16-13.93; p = 0.028), respectively, compared with the W/W genotype.. CYP2A6 polymorphisms are not associated with toxicity of S-1 chemotherapy, but correlate with the efficacy of S-1 in the adjuvant setting for gastric cancer.

Topics: Adenocarcinoma, Mucinous; Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Biomarkers, Tumor; Carcinoma, Signet Ring Cell; Chemotherapy, Adjuvant; Cytochrome P-450 CYP2A6; Drug Combinations; Female; Follow-Up Studies; Gastrectomy; Genotype; Humans; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Polymorphism, Genetic; Prognosis; Real-Time Polymerase Chain Reaction; Retrospective Studies; Stomach Neoplasms; Survival Rate; Tegafur

Exploratory biomarker analysis was conducted to identify factors related to the outcomes of patients with stage II/III gastric cancer using data from the Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer, which was a randomized controlled study comparing the administration of an orally active combination of tegafur, gimeracil, and oteracil with surgery alone.. Formalin-fixed paraffin-embedded surgical specimens from 829 patients were retrospectively examined, and 63 genes were analyzed by quantitative real-time RT-PCR after TaqMan assay-based pre-amplification. Gene expression was normalized to the geometric mean of GAPDH, ACTB, and RPLP0 as reference genes, and categorized into low and high values based on the median. The impact of gene expression on survival was analyzed using 5-year survival data. The Benjamini and Hochberg procedure was used to control the false discovery rate.. IGF1R and AREG were most strongly correlated with overall survival, which was significantly worse in high IGF1R patients than low IGF1R patients, but better in high AREG patients than low AREG patients. The hazard ratio for death in the analysis of overall survival (S-1 vs. surgery alone) was reduced in the high IGF1R group compared with the low IGF1R group and in the low AREG group compared with the high AREG group. There were no significant interaction effects.. IGF1R gene expression was associated with poor outcomes after curative resection of stage II/III gastric cancer, whereas AREG gene expression was associated with good outcomes. No significant interaction effect on survival was evident between S-1 treatment and gene expression.

Topics: Adult; Aged; Aged, 80 and over; Amphiregulin; Antimetabolites, Antineoplastic; Biomarkers, Tumor; Chemotherapy, Adjuvant; Drug Combinations; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Prognosis; Real-Time Polymerase Chain Reaction; Receptor, IGF Type 1; Receptors, Somatomedin; Retrospective Studies; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Stomach Neoplasms; Survival Rate; Tegafur

Introduction Radiotherapy is not commonly used for the treatment of gastric cancer in Japan, where surgery is the standard local treatment. We report the results of chemoradiotherapy in patients with advanced or recurrent gastric cancer which was deemed difficult to treat surgically. Methods Twenty-one patients with gastric cancer (including sixteen with advanced/recurrent gastric cancer and five with poor general condition) underwent chemo-radiotherapy, for whom the therapeutic efficacy, toxicity and survival period were analysed. Results The tumour response to chemoradiotherapy was categorised as complete, partial, stable or progressive in 5, 9, 3, and 4 patients, respectively, with an overall response rate of 67%. No serious complications such as gastrointestinal perforation or bleeding occurred, and no cardiac, hepatic or renal dysfunction developed during the follow-up period. The mean survival time was 19.8 months (range, 3-51 months). One patient died of another disease, 18 died of primary cancer and the cause of death was unknown in 2 patients. Conclusions Chemoradiotherapy appears to be an effective treatment for localised gastric cancer without distant metastases, but further studies are needed to determine the indications for chemoradiotherapy and late adverse effects, as well as the chemotherapy regimens to be used.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Cisplatin; Drug Combinations; Female; Fluorouracil; Humans; Japan; Male; Neoplasm Recurrence, Local; Oxonic Acid; Radiotherapy, Conformal; Retrospective Studies; Stomach Neoplasms; Survival Rate; Tegafur

Because standard chemotherapy for advanced gastric cancer consists of oral fluoropyrimidines plus platinum as first-line therapy, with paclitaxel plus ramucirumab as the second line, irinotecan is usually positioned as third-line chemotherapy in clinical practice in Japan.. A retrospective evaluation was conducted to determine the efficacy and safety of irinotecan as third-line chemotherapy for advanced gastric cancer in patients refractory or intolerant to fluoropyrimidines, platinum, and taxanes.. Between February 2008 and December 2013, 52 patients received third-line irinotecan monotherapy. Among the 32 patients with measurable lesions, 1 patient achieved a confirmed partial response and 6 patients had stable disease. The overall response rate was 3% and the disease control rate was 22%. Median progression-free survival was 2.3 months [95% confidence interval (CI), 1.8-2.8] and median overall survival was 4.0 months (95% CI, 2.6-5.3). The most common adverse events of grade 3 severity or higher were neutropenia (27%), febrile neutropenia (12%), anorexia (12%), and diarrhea (6%). Although no treatment-related deaths occurred, 2 patients (4%) died of disease progression within 30 days after the last administration of irinotecan.. Irinotecan monotherapy appears to be tolerated but was shown to have modest activity as third-line chemotherapy for advanced gastric cancer.

Topics: Adult; Aged; Antineoplastic Agents; Camptothecin; Capecitabine; Disease-Free Survival; Drug Combinations; Drug Resistance, Neoplasm; Female; Humans; Irinotecan; Kaplan-Meier Estimate; Male; Middle Aged; Oxonic Acid; Platinum Compounds; Proportional Hazards Models; Retrospective Studies; Salvage Therapy; Stomach Neoplasms; Taxoids; Tegafur; Treatment Outcome

This study was designed to compare the efficacy and safety of paclitaxel/oxaliplatin/fluorouracil (TOF) regimen and S-1/oxaliplatin (SOX) regimen for metastatic gastric cancer (GC) patients.. Sixty patients were divided into TOF group and SOX groups randomly. Patients in the TOF group received paclitaxel (135 mg/m2 iv) on day 1, oxaliplatin (100 mg/m2 iv) on day 1, fluorouracil (500 mg/m2 continuous iv) on day 1-5. The patients in the SOX group received oxaliplatin (130 mg/m2 iv) on day 1 and S-1 (40 mg~60mg orally twice/day based on body surface area) on days 1-14. All the treatments were repeated every 21d for 4-6 cycles.. The ORR and DCR of TOF group was 43.3% and 60.0%, respectively while that of SOX group was 36.7% and 56.7%. There were no statistical differences between the ORRs (χ2 = 0.278) and the DCRs (χ2 = 0.069) of the 2 groups. The majority of adverse events of two groups were hematological and digestive ones. Most of them were grade I and II. The adverse event rate of TOF group was higher than SOX group. The PFS times of TOF and SOX groups were 6.5 and 5.8 months, respectively. There was no statistical difference between the PFSs of the 2 groups (P = 0.451).. The efficacies of TOF and SOX regimens are similar but the safety of SOX regimen better than TOF regimen.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Drug Combinations; Female; Fluorouracil; Humans; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Paclitaxel; Stomach Neoplasms; Survival Analysis; Tegafur; Tomography, X-Ray Computed; Treatment Outcome; Young Adult

The use of adjuvant chemotherapy with S-1 (tegafur, gimeracil, and oteracil potassium) has been shown to improve the outcome of patients with gastric cancer. There are limited data on the tolerability of S-1 in Chinese patients. In this multicentre retrospective study, we assessed the toxicity profile in local patients.. Patients with stage II-IIIC gastric adenocarcinoma who had undergone curative resection and who had received S-1 adjuvant chemotherapy were included in the study. Patient demographics, tumour characteristics, chemotherapy records, as well as biochemical, haematological, and other toxicity profiles were extracted from medical charts. Potential factors associated with grade 2-4 toxicities were identified.. Adjuvant S-1 was administered to 30 patients. Overall, 19 (63%) patients completed eight cycles. The most common grade 3-4 adverse events included neutropaenia (10%), anaemia (6.7%), septic episode (16.7%), diarrhoea (6.7%), hyperbilirubinaemia (6.7%), and syncope (6.7%). Dose reductions were made in 22 (73.3%) patients and 12 (40.0%) patients had dose delays. Univariate analyses showed that patients who underwent total gastrectomy were more likely to experience adverse haematological events (P=0.034). Patients with nodal involvement were more likely to report adverse non-haematological events (P=0.031). Patients with a history of regular alcohol intake were more likely to have earlier treatment withdrawal (P=0.044). Lower body weight (P=0.007) and lower body surface area (P=0.017) were associated with dose interruptions.. The tolerability of adjuvant S-1 in our patient population was similar to that in other Asian patient populations. The awareness of S-1-related toxicities and increasing knowledge of potential associated factors may enable optimisation of S-1 therapy.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Anemia; Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Drug Combinations; Female; Follow-Up Studies; Gastrectomy; Hong Kong; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Neutropenia; Oxonic Acid; Retrospective Studies; Risk Factors; Stomach Neoplasms; Survival Analysis; Tegafur; Treatment Outcome

Disseminated intravascular coagulation (DIC) is a rare complication of advanced gastric cancer (AGC). Despite reports of the efficacy of chemotherapy for AGC with DIC, little is known of platinum-based doublet therapy.. We conducted a single-institute, retrospective chart review of 500 consecutive chemotherapy-naïve patients with advanced gastric adenocarcinoma (recurrent or metastatic) from November 2010 to November 2015.. Six patients were diagnosed with AGC with DIC (1.2%); five (1.0%; 3 men, 2 women) received platinum-based doublet chemotherapy. All patients exhibited improved DIC and thrombocytopenia and survived for >100 days (range=114-313) with no therapy-related mortality. Grade ≥3 adverse effects included neutropenia, anemia, hyponatremia, catheter-related infection and diarrhea (maximum: 2 patients each).. Fluoropyrimidine plus platinum combination therapy was effective against DIC and yielded acceptable survival outcomes. Combination chemotherapy should be considered as a primary therapy for AGC with DIC.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Disseminated Intravascular Coagulation; Drug Combinations; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Oxonic Acid; Paclitaxel; Stomach Neoplasms; Tegafur; Treatment Outcome

Despite recent progress in systemic chemotherapy, the prognosis of gastric cancer patients with peritoneal metastasis (P1) or positive peritoneal cytology findings (CY1) is still poor. We developed a regimen combining intraperitoneal (IP) paclitaxel (PTX) with S-1 and PTX, which can produce notable efficacy with regard to peritoneal lesions. Surgery after response to combination chemotherapy is a promising option for P1 or CY1 gastric cancer. A retrospective study was performed to evaluate the safety and efficacy.. This study enrolled 100 primary P1 or CY1 gastric cancer patients treated with IP PTX plus S-1 and PTX at the University of Tokyo Hospital between 2005 and 2011. Radical gastrectomy was performed when peritoneal cytology findings became negative, and the disappearance or obvious shrinkage of peritoneal metastasis was confirmed by laparoscopy. The same chemotherapy regimen was restarted after surgery and repeated with appropriate dose reduction.. Gastrectomy was performed in 64 (P1 56, P0CY1 8) of 100 (P1 90, P0CY1 10) patients. R0 resection was achieved in 44 patients (69%). The median survival time was 30.5 months [95% confidence interval (CI) 23.6-37.7 months] from the initiation of intraperitoneal chemotherapy and 34.6 months (95% CI 26.8-39.4 months) from the diagnosis of gastric cancer. Postoperative complications included anastomotic leakage and pancreatic fistula, each in two patients, which were cured conservatively. There were no treatment-related deaths. The median survival time of the 36 patients who did not undergo surgery was 14.3 months (95% CI 10.0-17.8 months).. Surgery after response to intraperitoneal and systemic chemotherapy is safe and may prolong the survival of P1 and CY1 gastric cancer patients.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Drug Combinations; Female; Follow-Up Studies; Gastrectomy; Humans; Injections, Intraperitoneal; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Paclitaxel; Peritoneal Lavage; Peritoneal Neoplasms; Prognosis; Retrospective Studies; Stomach Neoplasms; Survival Rate; Tegafur

A network meta-analysis was performed to compare the short-term efficacy of different chemotherapy regimens in the treatment of advanced gastric cancer.. Randomized controlled trials of different chemotherapy regimens for advanced gastric cancer were included in this study. Network meta-analysis combined direct evidence and indirect evidence to evaluate the odds ratio and draw surface under the cumulative ranking curves of different chemotherapy regimens in advanced gastric cancer.. The results of surface under the cumulative ranking curves showed that S-1 and capecitabine regimens were better than fluorouracil. As for multi-drug combination regimens, the disease control rate of cisplatin + capecitabine, docetaxel + cisplatin + fluorouracil and etoposide + cisplatin + capecitabine regimens were relatively better, while fluorouracil + adriamycin + mitomycin regimen was relatively poorer when compared with cisplatin + fluorouracil regimen. Additionally, the overall response ratio of cisplatin + capecitabine, paclitaxel + fluorouracil, docetaxel + cisplatin + fluorouracil and etoposide + cisplatin + fluorouracil regimens were relatively better, while the disease control rate of fluorouracil + adriamycin + mitomycin regimen was relatively poorer when compared with cisplatin + fluorouracil regimen. Furthermore, the results of cluster analysis demonstrated that cisplatin + capecitabine, etoposide + cisplatin + capecitabine, S-1 + paclitaxel and S-1 + irinotecan chemotherapy regimens had better disease control rate and overall response ratio for advanced gastric cancer patients.. This network meta-analysis clearly showed that multi-drug combination chemotherapy regimens based on capecitabine and S-1 might be the best chemotherapy regimen for advanced gastric cancer.

Topics: Capecitabine; Drug Combinations; Fluorouracil; Humans; Network Meta-Analysis; Oxonic Acid; Stomach Neoplasms; Tegafur

A 55-year-old man experienced weight loss, as noted by a physician who was examining him for hypertension. Upper gastrointestinal endoscopy revealed a tumor lesion with an ulcer on the posterior wall of the greater curvature. A biopsy confirmed the presence of an adenocarcinoma(HER2 negative), and demonstrated enlarged para-aortic lymph nodes. Thus, stage IV type 3 ulcer infiltration-type gastric cancer was diagnosed. Computed tomography was included in the examination, and demonstrated nodular shadows in the right lower lobe and enlarged mediastinal nodes, as well as bilateral multiple granular shadows. Hence, bronchoscopy was performed, and another adenocarcinoma(EGFR mutation negative/EML4-ALK gene fusion negative)was diagnosed. Immunostaining showed that the pulmonary and gastric adenocarcinoma tissues were different, and synchronous double cancer was diagnosed. Four courses of CDDP/S-1were administered, and both the lesions showed a partial response.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasms, Multiple Primary; Oxonic Acid; Stomach Neoplasms; Tegafur; Treatment Outcome

The reported patient was a 90-year-old woman with anorexia. She was diagnosed with advanced gallbladder cancer that occurred concurrently with stomach cancer. Subsequent to intestinal bypass surgery, S-1(80mg/day)was administered for 14 days, followed by 7 days of rest for one course. Tumor marker levels returned to normal after 4 months. Computed tomography results indicated that, in regard to the gallbladder cancer, the patient had stable disease after 8 months. In addition, gastroscopy revealed a complete response of the gastric cancer after a year. The patient was able to continue treatment as an outpatient until she experienced aspiration pneumonia. The administration of S-1 was terminated after 4 years and 4 months. Treatment with S-1 monotherapy is considered safe for elderly patients, and has the additional benefit that it is deliverable as an outpatient treatment.

Topics: Aged, 80 and over; Antimetabolites, Antineoplastic; Drug Combinations; Fatal Outcome; Female; Gallbladder Neoplasms; Humans; Neoplasms, Multiple Primary; Oxonic Acid; Stomach Neoplasms; Tegafur; Time Factors

We previously demonstrated that body weight loss (BWL) at one month after gastrectomy, a common finding after surgery for gastric cancer, was an independent risk factor for the continuation of adjuvant chemotherapy with S-1. However, it is unclear whether BWL after gastrectomy leads to poor survival through poor compliance to adjuvant chemotherapy with S-1.. We conducted this follow-up study in the same cohort as our previous study. Overall survival (OS) and recurrence-free survival (RFS) were examined in 103 patients who underwent curative D2 surgery and were pathologically diagnosed with stage II or III gastric cancer, and who received postoperative adjuvant chemotherapy with S-1 between June 2002 and December 2011.. The median follow-up period was 64.3 months. The 5-year OS rate in the patients with a BWL of <15% was 59.9%, while that in the patients with a BWL of ≥15% was 36.4% (p = 0.004). Univariate and multivariate analyses for OS demonstrated that pathological T factor and BWL were significant risk factors. On the other hand, the 5-year RFS rate was 56.4% in the BWL <15% group and 36.4% in the BWL ≥15% group (p = 0.016), while univariate and multivariate analyses for RFS demonstrated that BWL was a marginally significant risk factor.. Severe postoperative BWL, which is closely related with poor S-1 compliance, is an important risk factor for survival. It merits testing if preventing BWL improves survival of gastric cancer patients who receive S-1 adjuvant chemotherapy.

Topics: Aged; Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Drug Combinations; Female; Follow-Up Studies; Gastrectomy; Humans; Male; Middle Aged; Multivariate Analysis; Oxonic Acid; Postoperative Period; Risk Factors; Stomach Neoplasms; Survival Rate; Tegafur; Treatment Outcome; Weight Loss

Laparoscopic gastrectomy (LG) is reported to be associated with faster recovery than open gastrectomy (OG); however, the influence of the surgical approach on initiation timing of adjuvant chemotherapy (AC) remains unclear.. This was a single-institutional retrospective observational study. Patients with pathological stage II/III gastric cancer undergoing LG with D2 lymphadenectomy (LG group: n = 74) were matched 1:1 with patients selected from 214 similar patients undergoing OG (OG group: n = 74), identically matching gender, age, pathological stage, and type of gastrectomy, and comparing AC initiation timing between the two groups. Factors associated with delayed initiation of AC were investigated in a multivariable analysis.. AC was performed in 86.5% (LG) and 83.8% (OG) of patients (p = 0.64). The median time interval before AC was significantly shorter in the LG vs. OG group (5.7 vs. 6.6 weeks, respectively, p < 0.001), and significantly more patients received AC within 6 weeks (60.8% vs. 27.0%, p < 0.001). Independent factors associated with delayed initiation of AC (>6 weeks) were: morbidity (≥grade 3a; odds ratio (OR): 16.1, 95% confidence interval (CI): 1.86-143), open surgery (OR: 5.17, 95% CI: 2.50-13.1), and postoperative weight loss ≥ 8% (OR: 2.47, 95% CI: 1.07-5.71).. LG may be associated with shorter intervals before AC. Postoperative morbidity should be reduced as much as possible.

Topics: Abdominal Abscess; Adult; Aged; Aged, 80 and over; Anastomotic Leak; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Case-Control Studies; Chemotherapy, Adjuvant; Cisplatin; Deoxycytidine; Drug Combinations; Female; Fluorouracil; Gastrectomy; Humans; Laparoscopy; Laparotomy; Lymph Node Excision; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Oxaloacetates; Oxonic Acid; Pancreatic Fistula; Postoperative Complications; Retrospective Studies; Stomach Neoplasms; Tegafur; Time Factors; Time-to-Treatment

This study was conducted to investigate whether human epidermal growth factor receptor 2 (HER2) status, epidermal growth factor receptor (EGFR) status, and c-MET status are independent prognostic factors for advanced gastric cancer patients who received standard chemotherapy.. Unresectable or recurrent gastric or gastroesophageal junction cancer patients with histologically confirmed adenocarcinoma treated with S-1 plus cisplatin as first-line chemotherapy were eligible. Formalin-fixed paraffin-embedded tumor samples were examined for HER2, EGFR, and c-MET status using immunohistochemistry (IHC). Additionally, gene amplification was examined using fluorescent in situ hybridization (FISH) for HER2. Positivity was defined as an IHC score of 3+ or an IHC score of 2+/FISH positive for HER2, and an IHC score of 2+ or 3+ for both EGFR and c-MET.. Of the 293 patients from nine institutions, 43 (15%) were HER2 positive, 79 (27%) were EGFR positive, and 120 (41%) were c-MET positive. Ten patients (3%) showed positive co-expression of HER2, EGFR, and c-MET. After a median follow-up time of 58.4 months with 280 deaths, there was no significant difference in overall survival (OS) in terms of HER2 and EGFR status. However, there was a significant difference in OS between c-MET-positive and c-MET-negative patients [median, 11.9 months vs 14.2 months; hazard ratio, 1.31 (95% confidence interval, 1.03-1.67); log-rank P = 0.024]. Multivariate analysis also showed that c-MET positivity was still a prognostic factor for OS [hazard ratio, 1.30 (95% confidence interval, 1.02-1.67); P = 0.037].. The study suggested that c-MET-positive status had poor prognostic value. These data could be used as the basis for future clinical trials for targeting agents for advanced gastric cancer patients.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Cisplatin; Drug Combinations; ErbB Receptors; Esophageal Neoplasms; Esophagogastric Junction; Female; Gene Expression Regulation, Neoplastic; Humans; Male; Middle Aged; Oxonic Acid; Prognosis; Proto-Oncogene Proteins c-met; Receptor, ErbB-2; Retrospective Studies; Stomach Neoplasms; Tegafur

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Epstein-Barr Virus Infections; Female; Fluorouracil; Follow-Up Studies; Herpesvirus 4, Human; Humans; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Paclitaxel; Prognosis; Stomach Neoplasms; Survival Rate; Tegafur; Time Factors

The prognosis for locally advanced gastric cancer (AGC) remains unsatisfactory, even with S-1 adjuvant chemotherapy. We investigated the efficacy of neoadjuvant chemotherapy consisting of docetaxel, cisplatin and S-1 (DCS).. We retrospectively reviewed 59 patients who underwent neoadjuvant DCS therapy for clinical stage III tumors or serosa-positive tumors between January 2009 and December 2013 at Niigata Cancer Center Hospital. The patients received S-1 (40 mg/m(2) bid) on days 1-14, and docetaxel (35 mg/m(2)) and cisplatin (35 mg/m(2)) on days 1 and 15 every 4 weeks.. Forty-three patients (72.9 %) received two courses of DCS therapy, while 16 patients (27.1 %) received one course of treatment. The clinical response rate of the primary tumor was 74.6 %, and the disease control rate was 100 %. A pathological response, defined as one-third or more of the affected tumor, was observed in 71.2 % of patients. The common grade 3/4 adverse events from chemotherapy were leucopenia (16.9 %), neutropenia (44.1 %), febrile neutropenia (8.5 %), anemia (10.2 %), anorexia (8.5 %) and nausea (6.8 %). Postoperative complications occurred in 11 patients (18.6 %). There was no treatment-related mortality or reoperation. The 3- and 5-year overall survival rates were 88 and 68.6 %, respectively. Clinical responders had a significantly higher survival rate than non-responders. Multivariate analysis identified clinical response as the only independent prognostic factor.. Neoadjuvant DCS therapy demonstrated a very high clinical and pathological response rate with acceptable toxicities. Therefore, this therapy may improve the prognosis of locally AGC.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cisplatin; Docetaxel; Drug Combinations; Febrile Neutropenia; Female; Gastrectomy; Humans; Male; Middle Aged; Nausea; Neoadjuvant Therapy; Neoplasm Staging; Oxonic Acid; Prognosis; Retrospective Studies; Stomach Neoplasms; Survival Rate; Taxoids; Tegafur

S-1 is an oral anticancer drug, containing tegafur (a prodrug of 5-fluorouracil, 5-FU), 5-chloro-2,4-dihydroxypyridine, and potassium oxonate. As renal dysfunction is known to increase exposure of 5-FU following S-1 administration, the incidence of severe adverse reactions is increased in patients with impaired renal function. However, no reliable information on its dose modification for patients with renal dysfunction has been provided.. We conducted a prospective pharmacokinetic study to develop an S-1 dosage formula based on renal function. Sixteen cancer patients with various degrees of renal function received a single dose of S-1 at 40 mg/m(2). A series of blood samples were collected at predefined times within 24 h to assess the plasma concentration profiles of 5-FU, 5-chloro-2,4-dihydroxypyridine, and tegafur. A mathematical model for the relationship between renal function and exposure of 5-FU was constructed by a population pharmacokinetic analysis.. The clearance of 5-FU following S-1 administration was related to body surface area and creatinine clearance in the range 15.9-108.8 mL/min as estimated by the Cockcroft-Gault equation. The S-1 dosage formula was derived as follows:[Formula: see text]where AUC is the area under the concentration-time curve, CLcr is creatinine clearance, and BSA is body surface area. The recommended daily doses of S-1 in Asia and Europe were also proposed as nomograms according to exposure matching to the previously reported area under the concentration-time curve of 5-FU, which confirmed the efficacy and toxicity in pivotal registration studies.. We have developed a novel formula for determining the S-1 dosage on the basis of renal function. Further validation is needed to confirm the formula for practical application.

Topics: Aged; Antimetabolites, Antineoplastic; Drug Combinations; Female; Fluorouracil; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Prognosis; Prospective Studies; Renal Insufficiency; Stomach Neoplasms; Tegafur; Tissue Distribution

Curative resection and adjuvant chemotherapy is the standard treatment for Stage II/III gastric cancer, and S-1 is widely used for adjuvant chemotherapy. The type 1 insulin-like growth factor receptor (IGF1R) is involved in cell proliferation and prevention of apoptosis in many tumors. We evaluated the relative expression of the IGF1R gene to determine whether such expression correlates with outcomes in patients with Stage II/III gastric cancer.. We measured the expression levels of the IGF1R gene in specimens of cancer and adjacent normal mucosa obtained from 134 patients with Stage II/III gastric cancer who received curative resection and adjuvant chemotherapy with S-1. We then evaluated whether the IGF1R gene expression levels correlate with clinicopathological characteristics and outcomes.. IGF1R mRNA expression levels tended to be higher in cancer tissue than in the normal adjacent mucosa (P = 0.078). Multivariate analysis showed that high IGF1R gene expression was a significant independent predictor of poor survival in Stage II/III gastric cancer after curative resection and adjuvant chemotherapy with S-1 (HR 3.681, P = 0.007). The overall survival rate was significantly lower in patients with high IGF1R gene expression than in those with low expression (P = 0.012).. IGF1R overexpression is considered a useful independent predictor of outcomes in Stage II/III gastric cancer after curative resection and adjuvant chemotherapy with S-1.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Drug Combinations; Female; Gastric Mucosa; Gene Expression; Humans; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Prognosis; Receptor, IGF Type 1; Receptors, Somatomedin; RNA, Messenger; Stomach Neoplasms; Survival Rate; Tegafur

For patients with liver metastases from gastric cancer (LMGC), combination chemotherapy with fluoropyrimidines and platinum agents has been recognized as standard treatment. However, the prognosis of hepatic progression after first-line treatment failure remains poor. When hepatic progression occurs, hepatic arterial infusion (HAI) chemotherapy may be helpful for preventing disease progression.. To retrospectively assess the feasibility and efficacy of HAI chemotherapy using 5-fluorouracil, epirubicin, and mitomycin C (FEM) for patients with LMGC after failure of systemic S-1 plus cisplatin.. We reviewed the records of patients who received HAI chemotherapy using FEM for LMGC that progressed during systemic S-1 plus cisplatin treatment while extrahepatic disease was decreased or did not appear. HAI chemotherapy was given as second-line therapy using 5-fluorouracil (330 mg/m(2) weekly), epirubicin (30 or 40 mg/m(2) every 4 weeks), and mitomycin C (2.7 mg/m(2) biweekly).. Fourteen patients were analyzed. Toxicity of HAI chemotherapy was generally mild. The objective response rate was 42.9%, including a complete response rate of 14.3%. Median times to hepatic and extrahepatic progression were 9.2 and 7.4 months, respectively. Of 12 patients with documented progression after HAI chemotherapy, 10 patients (83.3%) received additional treatment, including irinotecan or taxanes. Overall, median survival was 12.7 months.. Our findings suggest that HAI chemotherapy using FEM is a feasible and effective treatment for patients with LMGC after failure of systemic S-1 plus cisplatin. HAI chemotherapy employed in the second-line setting is useful for achieving long-term disease control of LMGC.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Catheters, Indwelling; Cisplatin; Disease Progression; Drug Combinations; Epirubicin; Female; Fluorouracil; Hepatic Artery; Humans; Infusions, Intra-Arterial; Liver Neoplasms; Male; Middle Aged; Mitomycin; Oxonic Acid; Stomach Neoplasms; Survival Rate; Tegafur; Tomography, X-Ray Computed; Treatment Failure; Treatment Outcome

Watering eyes is a common late adverse event associated with S-1 chemotherapy; however, the frequency and predictive factors are not known.. This study included 304 consecutive gastric cancer patients treated with adjuvant S-1 monotherapy for 1 year at Shizuoka Cancer Center. We retrospectively evaluated the frequency of watering eyes, and explored other nonhematological adverse events during the first course of S-1 monotherapy which could become predictive factors for watering eyes.. The severest grade of watering eyes during S-1 monotherapy was grade 2 in 41 patients (13.5 %) and grade 3 in 36 patients (11.8 %). The median time to onset of grade 2 and grade 3 watering eyes was 82 days (range 6-344 days) and 249 days (range 84-653 days), respectively, and the median cumulative S-1 dose at the onset of grade 2 and grade 3 watering eyes was 4174 mg/m(2) (range 491-16,095 mg/m(2)) and 10,243 mg/m(2) (range 4943-16,341 mg/m(2)), respectively. Multivariate analysis showed that anorexia (odds ratio 2.37, P = 0.008), oral mucositis (odds ratio 3.86, P = 0.0003), skin hyperpigmentation (odds ratio 3.84, P = 0.0001), and rash (odds ratio 3.76, P = 0.01) observed during the first course were significantly associated with watering eyes.. The risk of watering eyes was higher in patients who also had anorexia, oral mucositis, skin hyperpigmentation, or rash during first course of S-1 monotherapy than in those without them.

Topics: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Drug Combinations; Female; Follow-Up Studies; Humans; Incidence; Japan; Lacrimal Apparatus Diseases; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Prognosis; Retrospective Studies; Stomach Neoplasms; Tears; Tegafur

S-1 adjuvant chemotherapy is commonly administered postoperatively for stage II and III advanced gastric cancer.. This study included 113 patients treated with S-1 adjuvant chemotherapy after surgery for stage II and III advanced gastric cancer. These patients were divided into 4 groups: group A (n = 63), who had a longer duration (≥6 months) and earlier S-1 administration (≤6 weeks) after surgery; group B (n = 16), who had a longer and later S-1 administration (>6 weeks) after surgery; group C (n = 27), who had a shorter duration (<6 months) and earlier S-1 administration after surgery; and group D (n = 7), who had a shorter and later S-1 administration after surgery.. The recurrence rates in groups A, B, C, and D were 15.7, 43.8, 44.4, and 57.1 %, respectively (A vs. B, p < 0.05, A vs. C and D, p < 0.01). The survival time of group A was significantly longer than that of other groups (p < 0.005). In addition, the survival time of patients with severe complications was significantly shorter than that of patients with non-severe complications (p < 0.05). An earlier S-1 administration after surgery was the only independent prognostic factor in the multivariate analysis.. The prognosis of advanced gastric cancer was significantly related to the start of S-1 adjuvant treatment within 6 weeks after surgery.

Topics: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Combined Modality Therapy; Drug Combinations; Female; Follow-Up Studies; Gastrectomy; Humans; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Neoplasm Staging; Oxonic Acid; Prognosis; Retrospective Studies; Stomach Neoplasms; Survival Rate; Tegafur; Young Adult

The purpose of our study was to evaluate the efficacy of a new combination antiemetic therapy consisting of palonosetron, aprepitant, and dexamethasone in gastric cancer patients undergoing chemotherapy with S-1 plus cisplatin.. This prospective, multi-institutional observational study assessed patient-reported nausea, vomiting, use of rescue therapy, change of dietary intake, and Functional Living Index-Emesis (FLIE) questionnaire results. The percentages of patients showing complete response (CR; no emesis and non-use of any rescue antiemetics) and complete protection (CP; no significant nausea and non-use of any rescue antiemetics), change of dietary intake, and impact of chemotherapy-induced nausea and vomiting on daily life during the overall (0-120 h after cisplatin administration), acute (0-24 h), and delayed (24-120 h) phases were examined. These findings were compared with our previous study, which used granisetron, aprepitant, and dexamethasone, to assess the relative effectiveness of palonosetron versus granisetron in combination antiemetic therapy.. Of the 72 included patients, 66 (91.6 %), 70 (97.2 %), and 50 (69.1 %) achieved CR, and 48 (66.7 %), 61 (84.7 %) and 49 (68.1 %) achieved CP during in the overall, acute, and delayed phases of cisplatin administration, respectively. Approximately half of the patients had some degree of anorexia. FLIE results indicated that 78.6 % of patients maintained their quality of life. Palonosetron was not superior to granisetron in combination antiemetic therapy.. Three-drug combination antiemetic therapy with palonosetron, aprepitant, and dexamethasone was tolerable in gastric cancer patients undergoing treatment with S-1 plus cisplatin. The predominance of palonosetron to granisetron was not demonstrated in this study.

Topics: Aged; Aged, 80 and over; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Cisplatin; Dexamethasone; Drug Combinations; Drug Therapy, Combination; Female; Granisetron; Humans; Isoquinolines; Male; Middle Aged; Morpholines; Nausea; Oxonic Acid; Palonosetron; Prospective Studies; Quality of Life; Quinuclidines; Stomach Neoplasms; Surveys and Questionnaires; Tegafur; Vomiting

In Japan, the administration of S-1 following D2 gastrectomy is a standard treatment for stage II/III gastric cancer (GC). However, the survival of stage IIIB/IIIC GC remains unsatisfactory. To improve this, we conducted a multicenter phase II study to evaluate the safety and efficacy of a neoadjuvant S-1 and oxaliplatin regimen (SOX) followed by surgery targeted at stage III GC.. Oxaliplatin was administered intravenously (130 mg/m(2)) on day 1, and S-1 was administered orally (40 mg/m(2), twice a day) for 14 days followed by a seven-day rest period. After three cycles of therapy, D2 gastrectomy was performed.. A total of 14 patients were enrolled and completed the protocol treatment. Grade 3/4 toxicities included thrombocytopenia (21.4 %), anorexia (14.3 %), and diarrhea (7.1 %). Seven patients (50 %) underwent total gastrectomy, and seven patients underwent distal gastrectomy. Grade 3/4 surgical complications included pancreatic fistula (21.4 %) and lung infection (7.1 %). The pathological response rate was 85.7 %.. Although our data are limited and preliminary, neoadjuvant SOX followed by surgery can be performed safely with a high pathological response rate in patients with resectable advanced GC. Further investigation of this neoadjuvant approach is warranted.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Drug Combinations; Feasibility Studies; Female; Gastrectomy; Humans; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Stomach Neoplasms; Tegafur; Treatment Outcome; Young Adult

Topics: Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Clinical Trials, Phase III as Topic; Drug Combinations; Humans; Leucovorin; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Stomach Neoplasms; Tegafur

This study was conducted to propose the optimal duration of fluoropyrimidine-based adjuvant chemotherapy consisting of fluoropyrimidine derivatives alone or combined with intravenous platinum for stage II or III gastric cancer (GC).. We analyzed retrospectively the data from 2219 patients with histologically confirmed adenocarcinoma in the stomach, who underwent a curative gastrectomy with lymphadenectomy from 2005 to 2012. Five-year overall survival (OS) and 3-year relapse-free survival (RFS) were analyzed according to the duration of fluoropyrimidine-based adjuvant chemotherapy.. Data from 617 patients with stage II or III GC were analyzable; 187 patients (30.3%) were treated with surgery alone, while 430 patients (69.7%) were treated with postoperative adjuvant chemotherapy. The duration of adjuvant chemotherapy was less than 6 months [group 1] in 147 patients (34.2%), 6 months to less than 12 months [group 2] in 94 patients (21.9%), 1 year to less than 2 years [group 3] in 139 patients (32.3%), and over 2 years [group 4] in 50 patients (11.6%). The 5-year OS in groups 1, 2, 3, and 4 was 75.7, 87, 90.3, and 93.4%, respectively, while 3-year RFS was 52.5, 58.8, 81.4, and 94.0%, respectively.. In this retrospective study, we did not demonstrate any significant improvement in OS and RFS by longer periods of fluoropyrimidine-based adjuvant chemotherapy in stage II or III GCs. Further prospective randomized studies are needed.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Chemotherapy, Adjuvant; Cisplatin; Drug Combinations; Female; Floxuridine; Follow-Up Studies; Humans; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Prognosis; Retrospective Studies; Stomach Neoplasms; Survival Rate; Tegafur; Time Factors; Uracil

A 76-year-old man complained of hematemesis and melena, and consulted the doctor. An endoscopic examination revealed type 3 advanced gastric cancer and a gastric ulcer with a visible vessel. We performed total gastrectomy with peritoneal metastasis dissection. After surgery, he received sequential chemotherapy with S-1 followed by paclitaxel. He continued the adjuvant chemotherapy without severe adverse events. He was treated successfully in spite of risk factors such as old age and postoperative body weight loss. We report herein a rare case of gastric cancer with peritoneal dissemination who achieved 5- year survival after surgery along with the literature review.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Drug Combinations; Fatal Outcome; Humans; Male; Oxonic Acid; Paclitaxel; Peritoneal Neoplasms; Stomach Neoplasms; Tegafur

We performed this prospective study to identify both the incidence of adrenal insufficiency (AI) and health-related quality of life (HRQOL) in advanced gastric cancer (AGC) patients who were treated with the S-1 plus cisplatin (SP) regimen as a first-line palliative chemotherapy.. We assessed adverse events (AEs) observed in 52 patients who received the SP regimen for AGC between January 2009 and June 2010 using the Common Toxicity Criteria Adverse Events (CTCAE) version 3.0. Adrenal function was assessed at baseline and 12 weeks after chemotherapy using the low-dose adrenocorticotropic hormone stimulation test. HRQOL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire version 3.0 (EORTC-QLQ C30).. The incidence of AI was 30.8% (n = 16) and of AE observed 55% (n = 29) among 52 patients after 12 weeks of chemotherapy. Of 29 patients with AE, 34.4% (n = 10) were diagnosed with AI, and of 23 patients without AE, 26.1% (n = 6) were diagnosed with AI.. The incidence of secondary AI in AGC patients was not rare and was not correlated with the presence of nonspecific AEs. Although patients diagnosed with AI did not show any related symptoms, they are at risk of potentially life-threatening consequences. Thus, the evaluation of AI could be suggested for patients who received chemotherapy.

Topics: Adrenal Glands; Adrenal Insufficiency; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Biomarkers; Chemotherapy, Adjuvant; Cisplatin; Disease-Free Survival; Drug Combinations; Female; Gastrectomy; Health Status; Humans; Hydrocortisone; Incidence; Kaplan-Meier Estimate; Male; Middle Aged; Oxonic Acid; Pilot Projects; Prospective Studies; Quality of Life; Stomach Neoplasms; Tegafur; Treatment Outcome

A 51-year-old man who had undergone distal gastrectomy for gastric cancer was admitted in Kagoshima University Hospital under the diagnosis of anastomotic recurrence of gastric cancer. From abdominal CT results, the recurred tumor was suspected to invade into the pancreas with regional node metastases. Because of the intense radicality of surgical intervention, we planned 3 courses of docetaxel, cisplatin, and S-1 triplet therapy(DCS therapy). After the chemotherapy, the recurred tumor and lymph node metastases shrunk drastically. Segmental gastrectomy with lymph node dissection was performed with curative intent. Final pathology revealed complete regression of both the recurred tumor and lymph node metastases. The patient's postoperative course was uneventful without tumor relapse. DCS therapy seems to be suitable to obtain drastic tumor regression before surgical intervention as a neoadjuvant chemotherapy for locally advanced gastric cancer.

Topics: Anastomosis, Surgical; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Docetaxel; Drug Combinations; Humans; Male; Middle Aged; Neoadjuvant Therapy; Oxonic Acid; Recurrence; Stomach Neoplasms; Taxoids; Tegafur; Treatment Outcome

We report the case of a 67-year-old male with Virchow's lymph node recurrence of gastric cancer, who underwent distal gastrectomy for type 2 forecourt part of pylorus gastric cancer, showing complete response(CR)in response to S-1 monotherapy. The tumor was pathologically diagnosed as Stage IIIb(well to poorly differentiated adenocarcinoma, T3[SE], N2 [20/51], M0). Virchow's lymph node metastasis was confirmed 2 months after surgery. One week after S-1 administration, a reduction in lymph node size was observed. After 5 courses of S-1 monotherapy, he achieved CR. The patient maintained CR for 2 years, before we switched to uracil and tegafur(UFT)monotherapy. The patient maintained CR for 2 years, after which UFT was discontinued. No relapse was observed 22 months after discontinuation.

Topics: Aged; Antimetabolites, Antineoplastic; Drug Combinations; Gastrectomy; Humans; Lymphatic Metastasis; Male; Oxonic Acid; Recurrence; Stomach Neoplasms; Tegafur; Treatment Outcome

A 60-year-old man was diagnosed with adenocarcinoma of the esophagogastric junction with lymph node metastasis along the left gastric artery. The clinical stage was determined to be T4b, N1, M0, Stage IIIB, and a neoadjuvant chemotherapy (NAC)regimen of capecitabine/CDDP plus trastuzumab was selected for treatment. Before 3 courses of chemotherapy, the patient developed perforated gastric cancer. With conservative therapy, we were able to obtain closure of the perforation without affecting the curability of the cancer. We changed the chemotherapy regimen to S-1/CDDP plus trastuzumab, and the patient underwent curative resection.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Esophagogastric Junction; Humans; Male; Neoadjuvant Therapy; Oxonic Acid; Receptor, ErbB-2; Stomach Diseases; Stomach Neoplasms; Tegafur; Trastuzumab; Treatment Outcome

A 70-year-old woman was diagnosed with cStage IV gastric cancer with diffuse intra-tumoral calcifications. She underwent systemic chemotherapy with an S-1/cisplatin regimen. However, as the disease progressed after 5 courses of the regimen, a secondary S-1/docetaxel regimen was administered. The target lesions showed complete response after 6 courses of this regimen, and surgery with curative intent was planned. The patient underwent total gastrectomy because no factors that would compromise the curative intent were observed during laparotomy. Postoperatively, the disease showed pathological complete response to chemotherapy.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Calcinosis; Docetaxel; Drug Combinations; Female; Gastrectomy; Humans; Neoplasm Staging; Oxonic Acid; Remission Induction; Stomach Neoplasms; Taxoids; Tegafur

Gastric cancer patients with main portal vein tumor thrombus usually have a short survival time, owing to its aggressive behavior. Herein, we report a long-surviving case of gastric cancer with main portal vein tumor thrombus. A 78-year-old man presenting with anorexia and body weight loss was diagnosed with gastric cancer. The patient was referred to our hospital for further examination and treatment. Endoscopy revealed a type 3 tumor (8.0 cm in length) in the body of the stomach. Biopsy led to the diagnosis of moderately differentiated adenocarcinoma. Enhanced computed tomography revealed a large tumor thrombus extending from the gastric coronary vein to the portal trunk. A total gastrectomy with lymphadenectomy, splenectomy, and thrombectomy was performed. Postoperative chemotherapy with S-1 was administered for 18 months. The patient died a natural death without recurrence at 49 postoperative months. To the best of our knowledge, the patient was the oldest to be diagnosed with gastric cancer with main portal vein tumor thrombus at diagnosis, who survived >36 months. Although gastric cancer with main portal vein tumor thrombus is a rare occurrence, its prognosis is extremely poor. Intensive surgery and long-term chemotherapy may be effective at improving survival time in these patients.

Topics: Adenocarcinoma; Aged; Chemotherapy, Adjuvant; Drug Combinations; Follow-Up Studies; Gastrectomy; Humans; Male; Neoplastic Cells, Circulating; Oxonic Acid; Portal Vein; Positron Emission Tomography Computed Tomography; Stomach Neoplasms; Survivors; Tegafur; Thrombosis

A 70-year-old man with left abdominal pain was referred to our hospital, and was diagnosed with type 1 advanced gastric cancer with lymph node metastasis. Neoadjuvant chemotherapy(NAC)with docetaxel and S-1 combination was administered. After 2 courses of chemotherapy, total gastrectomy with D2 lymph node dissection, splenectomy, and cholecystectomy were performed. Pathologically, viable cancer cells were not evident in the primary lesion and lymph nodes. The pathological response of NAC was judged to be Grade 3. On immunohistochemical analysis of the biopsy specimens obtained before treatment, the cancer cells were positive for class III b-tubulin and negative for TS, DPD, and ERCC1. The anti-tumor effect of S-1 may have led to the pCR.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Biopsy; Docetaxel; Drug Combinations; Humans; Male; Neoadjuvant Therapy; Oxonic Acid; Stomach Neoplasms; Taxoids; Tegafur

The patient was a 58-year-old man with advanced gastric cancer with multiple liver metastases. He received TXL/TS-1 therapy during February 2009, but treatment was stopped immediately when he developed anorexia, diarrhea, and numbness in his fingers. Therefore, only TS-1 was administered. Following treatment initiation, tumor marker levels promptly dropped. The gastric lesion disappeared and, to date, only a slight scar remains since April 2010. Similarly, liver metastases have not been detected since August 2011. There has been no lesion progression for 6 years since the start of the chemotherapy.

Topics: Antimetabolites, Antineoplastic; Drug Combinations; Humans; Liver Neoplasms; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Stomach Neoplasms; Tegafur; Time Factors; Treatment Outcome

To evaluate the efficacy of protein-bound polysaccharide K (PSK) added to S-1 adjuvant chemotherapy for treatment of advanced gastric cancer.. We retrospectively examined clinicopathological and recurrence-free survival (RFS) data for 136 patients with stage II or III advanced gastric cancer who underwent S-1 adjuvant chemotherapy with or without PSK.. Among 13 clinicopathological factors, non-T4 stage (odds ratio (OR)=0.61; 95% confidence interval (CI)=0.41-0.89; p<0.01), N0-1 (OR=0.65; 95% CI=0.43-0.95; p=0.03) and number of treatment cycles ≥7 (OR=0.37; 95% CI=0.20-0.67; p<0.01) were significant independent factors for better RFS. The number of treatment cycles of S-1 plus PSK was significantly higher than that of S-1 alone (p<0.01).. S-1 adjuvant chemotherapy combined with PSK may reduce recurrence by prolonging the treatment cycles in patients with advanced non-T4 or N0-1 gastric cancer.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Disease-Free Survival; Drug Combinations; Female; Fungal Proteins; Humans; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Polysaccharides; Postoperative Period; Stomach Neoplasms; Tegafur

A 64-year-old man with advanced gastric cancer presented with chief complaints of chest pain. His preoperative blood examination revealed positive results for serum HIV-antibody. His HIV-RNA level was 1.0×10 / 5 copies/mL, and his CD4lymphocyte count was 491 cell/mL; the patient was diagnosed with advanced gastric cancer and HIV infection. Distal gastrectomy with D2 lymphadenectomy and Roux-en-Y reconstruction were performed for treatment of the gastric cancer. Pathological examination revealed T3(SS)N3aM0, Stage III C cancer. After surgery, the patient was administered S-1 monotherapy as adjuvant treatment with antiretroviral therapy including tenofovir/emtricitabine and raltegravir. He completed 8 courses of S- 1 chemotherapy with no adverse events, such as a decrease in the CD4lymphocyte count or an increase in the HIV-RNA level. This patient with gastric cancer and HIV infection was safely treated using both antiretroviral therapy and chemotherapy owing to treatment intervention by chemotherapy and infectious diseases specialists.

Topics: Anti-Retroviral Agents; Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Drug Combinations; HIV Infections; Humans; Male; Middle Aged; Oxonic Acid; Stomach Neoplasms; Tegafur; Treatment Outcome

Objectives To evaluate the effects of the timing of warfarin (WF) administration in patients with gastric cancer who received S-1 oral chemotherapy. Methods This retrospective chart review collected patient data including the prothrombin time international normalized ratio (PT-INR). Patients were categorized into three groups based on the timing of WF administration in relation to S-1 oral chemotherapy: group A patients received WF before S-1 chemotherapy; group B patients started WF during S-1 chemotherapy; and group C patients started WF after completing S-1 chemotherapy. Results A total of 21 patients with gastric cancer were included in the study; group A ( n = 8), group B ( n = 10) and group C ( n = 3). Seven patients (88%) in group A, seven (70%) in group B and all of the patients (100%) in group C had >2.5 PT-INR. There was no significant difference in the time-to-exceed 2.5 PT-INR between groups A and B. Conclusions These findings suggest that the timing of WF use in relation to S-1 chemotherapy might not be an important factor for PT-INR, although the low patient numbers included in the study should be taken into consideration.

Topics: Adult; Aged; Aged, 80 and over; Anticoagulants; Antimetabolites, Antineoplastic; Drug Combinations; Drug Interactions; Female; Humans; International Normalized Ratio; Male; Middle Aged; Oxonic Acid; Prothrombin Time; Retrospective Studies; Stomach Neoplasms; Tegafur; Warfarin

The aim of this study was to clarify the clinical outcomes of staging laparoscopy(SL)for patients with positive peritonealwashing cytology(CY1P0)after S-1 administration.. Since 2007, eight CY1P0 patients who underwent SL after S-1 administration were enrolled. S-1 was administered according to the ACTS-GC and SL was performed after 8 courses of S-1 treatment.. SL was ended with adequate observation of intra-abdominalcavity in allthe patients with a median time of 68 minutes(range: 52-76 minutes). The timing of SL was after 8 courses of S-1 administration in 6 patients, after 11 courses in 1, and 12 courses in 1. Based on the SL results, CY0P0 was attained in 6 patients; CY1P0, in 1 and CY1P1, in 1. For the 6 patients who attained CY0P0, S-1 administration was completed. For the 2 patients who attained CY1P0 and CY1P1, chemotherapy was continued. Only 1 of the patients who attained CY0P0 had peritoneal recurrence 3 months after completion of S-1 administration.. When CY0P0 is detected by using SL, S-1 administration may be completed. More cases need to be studied to determine the suitable courses or timing of S-1 administration for CY0P0 patients.

Topics: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Drug Combinations; Female; Gastrectomy; Humans; Laparoscopy; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Peritoneal Neoplasms; Stomach Neoplasms; Tegafur; Treatment Outcome

To observe the short-term efficacy and safety of S-1 combined with cisplatin (DDP) chemotherapy for advanced gastric cancer (AGC).. Sixty-six patients were diagnosed with AGC and were admitted to our department from February 2012 to January 2015 and retrospectively analyzed. Of these patients, 31 (experimental group) underwent S-1 combined with DDP chemotherapy and 35 received oxaliplatin combined with tegafur and calcium folinate chemotherapy regimen (control group). The chemotherapy regimen for the experimental group included S-1, 60 mg bid on d1-d14 and 60 mg/m 2 DDP by intravenous dripping on d1-d3, with 4 weeks in a cycle. The chemotherapy regimen for the control group consisted of 130 mg/m 2 oxaliplatin by intravenous dripping, d1; 600 mg/m 2 tegafur by intravenous dripping on d1-d5; and 120 mg/m 2 calcium folinate by intravenous dripping on d1-d5, with 3 weeks in a cycle. The efficacies and adverse effects of the two regimens were assessed after three cycles.. After three cycles, the objective response rates of the experimental and control groups were 41.94% and 42.86%, without significantly difference (P > 0.05), respectively. However, the incidence rate of adverse drug reactions in Grades 3-4 in the experimental group was significantly lower than that of control group (P < 0.05).. The short-term efficacy of primary S-1 with DDP chemotherapy for AGC is relatively satisfactory with less adverse effects.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Female; Humans; Male; Middle Aged; Neoplasm Grading; Neoplasm Metastasis; Neoplasm Staging; Odds Ratio; Oxonic Acid; Stomach Neoplasms; Tegafur; Treatment Outcome

A 63-year-old man was admitted to our hospital owing to weight loss and vertigo. Endoscopic examination revealed advanced gastric cancer type 2. Abdominal CT showed a 62mm liver tumor in segment 4 and a 26mm tumor in segment 8. Distal gastrectomy and D2 lymph node dissection were performed. After surgery, he was administered chemotherapy with S- 1. After 2 courses of treatment, the tumors' in segments 4 and 8 were reduced to 52mm and 16mm, respectively. No other metastases were detected. Left lobectomy and partial resection of segment 8 were performed. The pathological therapeutic effects were rated as Grade 1b for the tumor in segment 4 and Grade 3 for the tumor in segment 8. After hepatectomy, he was administered adjuvant chemotherapy with S-1 for 1 year. No recurrence has been detected for 4 years and 6months after hepatectomy.

Topics: Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Drug Combinations; Gastrectomy; Hepatectomy; Humans; Liver Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Oxonic Acid; Stomach Neoplasms; Tegafur; Treatment Outcome

We report a case of advanced esophageal and gastric cancer that was successfully treated via multimodal therapy. A 65- year-old man with hoarseness was referred to our hospital. He was diagnosed with clinical T4aN2M0, Stage IV esophageal squamous cell carcinoma and clinical T3N1M0, Stage II B gastric adenocarcinoma. He was treated with 3 courses of chemotherapy, administered over 4weeks, with S-1(80mg/m / / 2: day 1-14), cisplatin(60mg/m2: day 1), and docetaxel(40mg/m2: day 1). Computed tomography(CT)revealed shrinkage of the primary esophageal tumor, gastric tumor, and lymph node metastases. Next, we selected definitive radiation chemotherapy(CRT), because lymph node metastases remained around the bilateral recurrent laryngeal nerves. After CRT with a total 60 Gy plus administration of 5-fluorouracil and cisplatin, CT showed that the primary esophageal tumor and lymph node metastases had disappeared. Then, distal gastrectomy was performed for the remaining gastric cancer, as part of the multimodal therapy. After gastrectomy, no systemic chemotherapy was performed. At a follow-up examination 5 years and 6 months after the start of chemotherapy, the patient is alive without recurrence.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Chemoradiotherapy; Cisplatin; Docetaxel; Drug Combinations; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Gastrectomy; Humans; Male; Neoplasms, Multiple Primary; Oxonic Acid; Stomach Neoplasms; Taxoids; Tegafur

The MRN complex of meiotic recombination 11 (MRE11), DNA repair protein Rad50 (RAD50) and Nijmegen breakage syndrome 1 (NBS1) proteins coordinate the detection and repair of DNA double-strand breaks (DSBs). DNA DSB repair-dependent chemoresistance likely has an effect on the treatment of human cancer.. We investigated the expression of MRN complex in human gastric cancer (GC) tissues using immunohistochemistry and analyzed its clinical significance and prognostic relevance.. The expression of MRN complex was significantly associated with clinical factors including poorer prognosis and negatively associated with the expression of DNA damage marker phosphorylated H2A histone family, member X (γH2AX) in the nucleus. In the biopsy specimens, low expression of MRE11 correlated with good response to chemotherapy and surgical resection after down-staging by chemotherapy. Furthermore, the expression levels of MRE11 and RAD50 were independent predictors of surgical resection after chemotherapy.. The high expression of MRN complex constituents could be a predictor for poor prognosis and chemoresistance in GC.

Topics: Acid Anhydride Hydrolases; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Cell Cycle Proteins; Cisplatin; DNA Repair Enzymes; DNA-Binding Proteins; Drug Combinations; Drug Resistance, Neoplasm; Humans; MRE11 Homologue Protein; Nuclear Proteins; Oxonic Acid; Paclitaxel; Prognosis; Stomach Neoplasms; Tegafur

The prognosis after neoadjuvant chemotherapy(NAC)is expected to improve in patients with resectable advanced gastric cancer who are at high risk of recurrence or those with unfavorable prognostic factors.. This retrospective study examined treatment outcomes and survival of 25 patients with advanced gastric cancer who received NAC with S-1 and cisplatin(CDDP)between October 2008 and December 2015.. Among patients with clinical Stage II (4 patients)and III (21 patients)tumors, 13 had partial response(PR)and 12 had stable disease(SD). Neither complete response(CR)nor progressive disease(PD)was noted. CR of lymph node metastases was observed in 6 patients, PR in 9 patients, and SD in 7 patients. R0 resection was performed in 16 patients, R1 in 3 patients, and R2 in 6 patients. Histologic grades of primary tumors were Grade 0(1 patient), Grade 1a(16 patients), Grade 1b(5 patients), Grade 2(3 patients), and Grade 3(none). The 3-year survival rate after R0 resection was 46%, 3-year progression-free survival rate was 68%, and 3-year recurrence-free survival rate was 69%. Significant differences were observed for pathologic stages ypN0/1, 2, and 3(p=0.04), tumor down-stage(p=0.02), and overall tumor fStage I , II / III , and IV (p<0.01).. It is conceivable that R0 resection and downstaging after NAC will improve prognosis.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Female; Humans; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Oxonic Acid; Retrospective Studies; Stomach Neoplasms; Tegafur; Treatment Outcome

It has been suggested that port site recurrence is a potential complication after laparoscopic distal gastrectomy for gastric cancer, especially considering the increased number of laparoscopic surgeries being performed. We encountered a case of an 84-year-old man who was diagnosed with 2 port site recurrences at the navel and right hypochondrium after laparoscopic distal gastrectomy(D2). Pathological diagnosis for the original tumor was tub2, pT4a, pN1(1/38), M0, pStage III A, and HER2(0). As first-line chemotherapy with S-1 plus CDDP for the port site recurrence failed, second-line chemotherapy with ramucirumab plus paclitaxel(RAM plus PTX)was administered. Although RAM plus PTX therapy induced shrinkage of the port site recurrence, liver metastasis was detected as a new lesion. RAM mono-therapy maintained good QOL for 18 months after surgery.

Topics: Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Gastrectomy; Humans; Laparoscopy; Male; Oxonic Acid; Recurrence; Skin Neoplasms; Stomach Neoplasms; Tegafur

A 37-year-old woman was diagnosed with advanced gastric cancer. Pancreatic invasion of the tumor and positive cytology from peritoneal washing was found on staging laparoscopy. The patient received chemotherapy consisting of S-1 and CDDP, but the tumor size increased after 5 courses. The patient then received 2 courses of second line chemotherapy consisting of biweekly CPT-11; however, the tumor progressed and caused stenosis of the stomach. After gastrojejunostomy for the stenosis, negative cytology of intraperitoneal lavage was found. The patient underwent pancreatoduodenectomy with right hemicolectomy and wedge resection of the portal vein as curative resection. The patient was alive without recurrence 10 months after the surgery.

Topics: Adult; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cisplatin; Disease Progression; Drug Combinations; Female; Humans; Irinotecan; Neoplasm Invasiveness; Oxonic Acid; Pancreas; Pancreaticoduodenectomy; Stomach Neoplasms; Tegafur; Treatment Outcome

We report a case of a 23-year-old womanwho developed pulmonary embolism(PE)during chemotherapy for advanced gastric cancer following total gastrectomy(R1). She presented with type 4 gastric cancer with peritoneal dissemination and positive washing cytology. Palliative total gastrectomy was performed(R1)and first-line chemotherapy with S-1(80mg/m2, days 1 to 21) plus CDDP(60mg/m2, day 8)(SP; every 35 days)was administered. PE occurred on day 15 of the 3rd courses of SP. Computed tomography(CT)revealed massive PE in both the pulmonary arteries, and ultrasonography indicated an increase in right-sided pressure. Thrombolysis using urokinase and heparin was performed immediately, and she recovered after 10 days in intensive care. Dehydration caused by the adverse event, as well as nausea and the anticancer drug itself, are risk factors for DVT and PE. Risk stratification, prevention, and early treatment are very important for PE.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Female; Gastrectomy; Humans; Oxonic Acid; Pulmonary Embolism; Stomach Neoplasms; Tegafur; Young Adult

The following is a case report of moderately differentiated tubular adenocarcinoma of the stomach with widespread thrombosis of the portal vein, for which chemotherapy proved effective. A 75-year-old man presented to the clinic with a new onset ofmalaise. The patient had anemia, elevation ofliver and biliary enzymes, and significantly elevated CA19-9 levels at 43,581 U/mL and CEA levels at 2,560 ng/mL. An upper endoscopy revealed a mass lesion extending from the fundus to the pylorus as well as to the duodenum along the smaller curvature of the stomach. A biopsy revealed moderately differentiated tubular adenocarcinoma. Abdominal CT showed a mass lesion extending from the body of the stomach and penetrating through the gastric wall, and extensive lymphadenopathy in the surrounding areas. In addition, multiple thromboses were identified in the portal vein and its tributaries, including the inferior mesenteric vein, splenic vein, and intrahepatic capillaries. The patient subsequently received a single round ofS -1 and CDDP. The tumor demonstrated a marked response; the tumor size and lymphadenopathy showed a significant improvement and the CA19-9 level decreased. Because the patient's condition deteriorated, this chemotherapy regimen was discontinued. The patient was switched to S-1 monotherapy and is still alive today, 2 years 10 months after the initial diagnosis.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Humans; Male; Oxonic Acid; Portal Vein; Stomach Neoplasms; Tegafur; Venous Thrombosis

A 75-year-old man admitted for left lateral abdominal pain was found to have advanced poorly differentiated gastric adenocarcinoma with abdominal para-aortic and Virchow's lymph node metastases, which was diagnosed to be clinical Stage IV (T3N3H0M1[LYM]). As curative surgery was not deemed possible, we started chemotherapy administration using S-1 (120mg/day)administered orally for 3 weeks and cisplatin(CDDP 100mg/body)administered intravenously on day 8. After 6 courses of chemotherapy, a CT scan showed that all lymph nodes metastases had disappeared, resulting in downstaging to clinical Stage II (T3[SE]N0H0P0M0). Thus, we performed total gastrectomy, lymph node dissection(D2), and splenectomy. Histological findings showed no residual tumor cells in any of the lymph nodes. However, cancer cells remained in the primary gastric lesion. The pathological response to chemotherapy was judged to be Grade 2. The patient has been recurrence-free for 5 years after surgery.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Humans; Male; Neoadjuvant Therapy; Oxonic Acid; Salvage Therapy; Stomach Neoplasms; Tegafur

A 57-year-old man with advanced gastric cancer and multiple liver metastases was referred to our hospital. He underwent a palliative gastrectomy to treat hemorrhage, and S-1 and cisplatin therapy was administered. After 7 courses of chemotherapy, a new liver metastatic lesion and a tumor thrombus in the right portal vein appeared. Moreover, the serum level of ammonia was elevated(296 mg/dL)following a consciousness disorder. Enhanced CT revealed an inferior mesenteric vein to left renal vein shunt, which led to the diagnosis of portal systemic encephalopathy due to portosystemic shunt. Percutaneous transvenous coil embolization was performed. The serum ammonia level decreased, and the encephalopathy disappeared. As a result, he was able to continue chemotherapy.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Embolization, Therapeutic; Gastrectomy; Humans; Male; Middle Aged; Oxonic Acid; Recurrence; Stomach Neoplasms; Tegafur

We studied the clinical efficacy of pre-operative combination chemotherapy using S-1 plus oxaliplatin for advanced gastric cancer. Four patients hadclinical Stage IV disease, 1 patient had clinical Stage III C disease, 2 patients had clinical Stage III B disease, and 1 patient had clinical Stage III A disease. The patients received 2-8 courses of oxaliplatin(130mg/m2)on day 1, andS -1 on days 1-14 every 3 weeks. The response rate was 56%(5 PR, 1 PD, and2 SD), andthe disease control rate was 88%. Toxicities were Grade 2 anemia, Grade 1 peripheral neuropathy, Grade 1 fatigue, and anorexia. Five of the 8 patients underwent R0 surgery after SOX chemotherapy, and no severe complications occurred. Histological responses were Grade 3 for 2 cases, Grade 2 for 2 cases, andGrad e 1a for 1 case. The SOX regimen showeda high objective tumor response, andis one of the promising regimens in the neoadjuvant setting for well-advanced gastric cancer.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Female; Humans; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Stomach Neoplasms; Tegafur; Treatment Outcome

A 68-year-old woman was diagnosed with advanced gastric cancer with a type 3 deep ulcer of the middle stomach by endoscopy. An abdominal computed tomography scan revealed multiple lymph node metastases and peritoneal disseminations. The clinical stage was determined to be T4a(SE), N2P1M1(PER), H0 and stage IV . A gastrectomy was scheduled after 2 courses of S-1 plus oxaliplatin(SOX)with curative intent. On day 3 after initiatingSOX therapy, the patient complained of severe abdominal pain. Because the abdominal CT scan showed intra-abdominal free air and a defect in the gastric wall, we performed an emergency total gastrectomy. The defect in the gastric wall was about 1 cm in diameter and was located in the anterior wall of the lower body, consistent with the center of the tumor. The operative findings suggested that the perforation was caused by chemotherapy-induced necrosis of gastric cancer cells. The patient was discharged 16 days after surgery and received post-operative chemotherapy. Our findings suggest that the risk of gastric perforation should be considered when administeringchemotherapy to patients with advanced gastric cancer and a deep ulcer.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Female; Humans; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Peritonitis; Stomach Diseases; Stomach Neoplasms; Tegafur; Time Factors; Treatment Outcome

Gastric cancer with portal tumor embolus is rare and there is no definite strategy for its surgical resection. We report 2 cases ofgastric cancer with portal vein tumor embolus treated using gastrectomy and thrombectomy. Case 1: The patient was a 56- year-old man. We performed total gastrectomy, distal pancreatectomy, splenectomy, and thrombectomy. The patient was treated with 4 courses ofS -1 plus CDDP chemotherapy followed by S-1 administration. Eight months after surgery, CT revealed metastasis in the left adrenal gland and he died 2 years after surgery. Case 2: The patient was a 57-year-old man. We performed total gastrectomy, distal pancreatectomy, splenectomy, partial resection of the transverse colon, and thrombectomy. The patient was treated using adjuvant S-1 chemotherapy followed by UFT administration for 3 years. The patient has been alive with no tumor recurrence for the past 10 years. If there is no other therapeutic option for portal vein embolus, gastrectomy with thrombectomy could increase the possibility oflong -term survival.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Gastrectomy; Humans; Male; Middle Aged; Oxonic Acid; Portal Vein; Stomach Neoplasms; Tegafur; Thrombectomy; Thromboembolism

Eye disorders are one of the characteristic adverse events associated with S-1 chemotherapy. In this retrospective study, we investigated the frequency and outcome of eye disorders associated with S-1 chemotherapy in gastric cancer patients. This retrospective study included 75 advanced gastric cancer patients who received S-1 monotherapy between January 2014 and December 2015. We retrospectively evaluated the frequency, Grade, and treatment of eye disorders. Eye disorders were observed in 16 patients(21%). The median time of onset was 3(range, 1-8)months. Grade 2 watering eyes, eye discharge, and conjunctivitis were reported in 14, 8, and 4 patients, respectively. Artificial tears, fluorometholone eye-drops, and both of these treatments were used in 7, 1, and 8 patients, respectively. Ophthalmologic examination was performed for 3 patients. No delay or reduction of S-1 therapy was required for the eye disorders. Eye disorders associated with S-1 therapy in gastric cancer patients did not affect treatment if managed properly using eye drops.

Topics: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Drug Combinations; Eye Diseases; Female; Gastrectomy; Humans; Male; Middle Aged; Oxonic Acid; Retrospective Studies; Stomach Neoplasms; Tegafur

The patient was a 49-year-old woman with advanced gastric cancer.CT and PET-CT revealed para-aortic lymph node metastases.She was diagnosed with Stage IV T4aN3M1(LYM)and underwent neoadjuvant chemotherapy with S-1 plus CDDP.After 3 courses, both the tumor and para-aortic lymph node metastases decreased in size.Because radical resection was considered possible, she underwent distal gastrectomy with D3(D2+No.1 6a2-b1)dissection and Roux-en-Y reconstruction. Histopathological findings revealed the cancer was Stage I B(yp T1b N1)with the disappearance of cancer cells in the para-aortic lymph nodes.She was discharged on POD 32.She underwent adjuvant chemotherapy with S-1 and was followed up for 3 years with no recurrence.Para -aortic lymph node metastases are factors predicting a poor outcome; however, when neoadjuvant chemotherapy is effective, long-term survival can be expected from gastrectomy with curative PAND.

Topics: Antineoplastic Combined Chemotherapy Protocols; Aorta; Cisplatin; Drug Combinations; Female; Humans; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Middle Aged; Neoadjuvant Therapy; Oxonic Acid; Stomach Neoplasms; Tegafur

This report describes a patient with unresectable advanced gastric cancer who was successfully treated with potentially curative conversion surgery after chemotherapy with S-1 plus oxaliplatin(SOX). An 82-year-old man was diagnosed with type 5 gastric cancer(por1, HER2-negative)with multiple granular mucosal necroses that had metastasized throughout his body. Computed tomography revealed multiple lymph node metastases, tumor thrombosis in the splenic and portal veins, and peritoneal dissemination. After 9 courses of first-line chemotherapy with SOX, there was no tumor thrombosis in the splenic and portal veins or peritoneal dissemination, and the primary tumor and lymph node metastases were markedly reduced in size, indicative of a partial response(PR). The patient subsequently underwent total gastrectomy as curative conversion surgery. The histological diagnosis was ypT2N0M0, ypStage I B, and the primary lesion was categorized as Grade 2 gastric cancer. At present, 1 year after surgery, the patient remains alive without tumor recurrence.

Topics: Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Humans; Male; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Peritoneal Neoplasms; Stomach Neoplasms; Tegafur; Thrombosis

We describe a 67-year-old man with long-term CR by S-1 chemotherapy for gastric cancer with para-aortic lymph node metastases after reduction surgery. The patient presented at our hospital with epigastric pain. He was diagnosed with gastric cancer with para-aortic lymph node metastases. We performed gastrectomy and D1 lymphadenectomy without any resection of the para-aortic lymph node metastases. We treated the patient with oral S-1 chemotherapy. The initial treatment schedule was 100mg/body/day, twice daily for 4weeks with 2weeks of rest. Grade 1 neutropenia developed at the end of the second course of treatment. The regimen was changed to 2 weeks of administration, with 1 week of rest. The para-aortic lymph node metastases immediately responded to the chemotherapy. Abdominal CT showed almost complete regression of the lymph node metastases 10 months postoperatively. The patient has received S-1 chemotherapy and remained in remission for more than 5 years 6 months.

Topics: Aged; Antimetabolites, Antineoplastic; Aorta; Drug Combinations; Gastrectomy; Humans; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Male; Oxonic Acid; Stomach Neoplasms; Tegafur

A 63-year-old man was seen by his family doctor for epigastric distress, and he was referred to our hospital with a diagnosis of gastric cancer. Upper gastrointestinal endoscopy revealed type 3 gastric cancer(por1>tub2>tub1)at the lesser curvature of the stomach. Computed tomography suggested thickening of the wall of the stomach at the lesser curvature and bulky lymph node swelling. After a diagnosis of cT4a cN2M0, cStage III B advanced gastric cancer, we treated him with neoadjuvant chemotherapy consisting of 3 courses of SOX(oxaliplatin 100mg/m / 2 on day 1, S-1 120mg/day on day 1-14, followed by 7 days of rest). After the chemotherapy, because the primary tumor and lymph nodes were reduced, we performed distal gastrectomy with D2 lymph node dissection. Histopathological examination revealed no residual cancer cells, indicating a pathological complete response(Grade 3). We report a case of advanced gastric cancer with a pathological complete response after neoadjuvant chemotherapy.

Topics: Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Gastrectomy; Humans; Lymphatic Metastasis; Male; Middle Aged; Neoadjuvant Therapy; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Stomach Neoplasms; Tegafur; Treatment Outcome

The patient was a 78-year-old woman. She was referred to our hospital and diagnosed with advanced gastric cancer with para-aortic lymph node(#16)metastasis. She received the SOX regimen(L-OHP 100mg/m2)chemotherapy and developed fatigue, anorexia, and neutropenia. After 4 courses of the SOX regimen, the #16 metastasis was reduced remarkably. A curative operation was performed and histological evaluation of the primary and lymphatic lesion after chemotherapy showed Grade 3 findings. The SOX regimen is tolerable in the outpatient clinic and is useful as part of multidisciplinary treatment for advanced gastric cancer.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Female; Gastrectomy; Humans; Lymphatic Metastasis; Neoadjuvant Therapy; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Stomach Neoplasms; Tegafur; Treatment Outcome

The patient was an 80-year-old man. He had a chief complaint of epigastric pain. The upper gastrointestinal endoscopy showed a type 4 tumor of the stomach, and the CT scan showed multiple para-aortic lymph node metastases. The patient was diagnosed with cStage IV gastric cancer. At first, he could take only small amounts of liquid. After starting S-1 and oxaliplatin (SOX), he was able to resume a full diet and his general condition was improved. A CT scan after 4 courses of chemotherapy showed a significant reduction in the wall thickness of the stomach and the size of the lymph nodes. SOX chemotherapy could be a promising treatment option for elderly patients with advanced gastric cancer.

Topics: Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Humans; Male; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Stomach Neoplasms; Tegafur; Treatment Outcome

We report a case of rectal metastasis of gastric cancer associated with dermatomyositis showing paraneoplastic syndrome. The patient was a 70-year-old man who had undergone curative total gastrectomy for Stage III Agastric cancer in March 2005. He was diagnosed with dermatomyositis and treated with prednisolone after gastrectomy. In April 2006, erythema of his face relapsed, and his serum CPK level was abnormally elevated. He experienced muscle weakness and dysphagia, and was treated with increased doses of prednisolone and gamma-globulin. At this time, endoscopic examination and computed tomography(CT)revealed a rectal tumor with hepatic metastasis. We performed Hartmann's operation in July 2006. The rectal tumor was predominantly submucosal, was 7 cm in diameter, involved #251 lymph node, and had positive peritoneal lavage cytology. The histopathological findings of the rectal tumor were comparable with those of gastric cancer, and we therefore diagnosed metastatic adenocarcinoma of gastric cancer. After surgery, we could control the patient's dermatomyositis with prednisolone at a reduced dose. However, chemotherapy with S-1 was ineffective and the patient died 8 months postoperatively.

Topics: Adenocarcinoma; Aged; Antimetabolites, Antineoplastic; Dermatomyositis; Drug Combinations; Fatal Outcome; Humans; Male; Oxonic Acid; Rectal Neoplasms; Stomach Neoplasms; Tegafur

The standard of care for stage II/III gastric cancer in Japan is D2 dissection followed by adjuvant S-1 monotherapy. Outcome of patients with stage III disease remains unsatisfactory, calling for a more intensive adjuvant chemotherapy regimen, for which evidence in advanced/metastatic cancer research suggests S-1/cisplatin (CDDP) as a candidate. Although S-1/CDDP was poorly tolerated postoperatively in the previous trial, compliance was dramatically improved by insertion of one cycle of S-1 monotherapy, which delayed administration of CDDP by 6 weeks.. A feasibility study of post-gastrectomy S-1/CDDP was performed. Patients with stage III/IV gastric cancer were eligible. The first cycle of chemotherapy consisted of S-1 monotherapy, and intensive antiemetic drugs were prescribed when patients were administered CDDP. The primary endpoint was the completion rate of four cycles of S-1/CDDP. The secondary endpoints were the relative dose intensity, safety, progression-free survival time and overall survival time. Several criteria to skip, postpone or reduce the dose had been predetermined.. Between 2010 and 2011, 33 patients were enrolled. Four patients had stage IIIA disease, 7 patients had stage IIIB disease, 11 patients had stage IIIC disease, and 11 patients had stage IV disease. The completion rate of the protocol treatment was 60.6%. The relative dose intensity of S-1 was 77.3% and that of CDDP was 72.3%.. The protocol-specified delay in the administration of CDDP dramatically improved the relative drug intensity in the postoperative adjuvant setting, although the completion rate did not reach the expected level.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cisplatin; Drug Combinations; Feasibility Studies; Female; Follow-Up Studies; Humans; Japan; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Postoperative Care; Prognosis; Stomach Neoplasms; Tegafur; Young Adult

Microenvironments control cancer growth and progression. We explored the prognostic impact of stromal reaction and cancer stromal cells on relapse risk and survival after curative gastrectomy in gastric cancer patients.. Tissue samples were obtained from 107 patients with gastric adenocarcinoma who underwent curative (R0) gastrectomy. Primary stromal cells isolated from gastric cancer tissue (GCSC) and normal gastric tissue (Gastric stromal cell: GSC) in each patient were cultured and subjected to comprehensive proteome (LC-MS/MS) and real-time RT-PCR analysis. Expression of Ephrin A2 receptors (EphA2) in cancers and GCSC was evaluated immunohistochemically. Intermingling of EphA2-positive cancer cells and GCSC (IC/A2+) and overexpression of EphA2 in cancer cells (Ca/A2+) in invasive parts of tumors were assessed, as were relationships of IC/A2+, Ca/A2+, and clinicopathological factors with relapse-free survival and overall survival.. Proteome analysis showed that EphA2 expression was significantly higher in GCSC than GSC. Real-time RT-PCR analysis showed that levels of EphA1/A2/A3/A5 and EphB2/B4 were ≥2.0-fold higher in GCSC than GSC. Ca/A2 and IC/A2 were positive in 65 (60.7 %) and 26 (24.3 %) patients, respectively. Relapse was significantly more frequent in IC/A2-positive than in IC/A2-negative (HR, 2.12; 95 % CI, 1.16-5.41; p = 0.0207) patients. Among the 54 patients who received S-1 adjuvant chemotherapy, relapse-free survival (RFS) was significantly shorter in those who were IC/A2-positive than in those who were IC/A2-negative and Ca/A2-negative (HR, 2.83; 95 % CI, 1.12-12.12; p = 0.0339). Multivariable analysis indicated that pathological stage (p = 0.010) and IC/A2+ (p = 0.008) were independent risk factors for recurrence.. IC/A2+ was predictive of relapse after curative (R0) gastrectomy.

Topics: Adenocarcinoma; Chemotherapy, Adjuvant; Disease-Free Survival; Drug Combinations; Humans; Immunohistochemistry; Oxonic Acid; Prognosis; Receptor Protein-Tyrosine Kinases; Receptor, EphA2; Receptor, EphA3; Receptor, EphA5; Receptor, EphB2; Retrospective Studies; Stomach Neoplasms; Stromal Cells; Tegafur; Tumor Microenvironment

Palliative chemotherapy is used to prolong survival among elderly patients with inoperable gastric cancer (GC). We analyzed differences between single and combination first-line palliative chemotherapy among these patients.. Included patients were >70 years old and were treated for GC at four clinical centers of the Catholic University of Korea. Baseline characteristics, the first-line chemotherapy regimen, treatment responses, toxicities, progression-free survival (PFS), and overall survival (OS) were evaluated.. Between 2005 and 2012, 178 > 70-year-old patients with GC received palliative chemotherapy using single or combination regimens. Median ages were 77 years (range 71-89) in the single regimen group (SG, 70 patients) and 73 years (range 71-81) in the combination group (CG, 108 patients). Patients in the SG received S-1 or capecitabine. The most common regimen in the CG was platinum combined with fluorouracil. The most common response in both groups was stable disease (SG, 45.7 %; CG, 48.1 %). In the SG and CG, median PFS times were 4.4 months (95 % confidence interval [CI] 2.85-5.95) and 4.1 months (95 % CI 2.62-5.57; P = 0.295), respectively; median OS times were 6.6 months (95 % CI 4.17-9.08) and 7.6 months (95 % CI 5.50-9.69; P = 0.782), respectively. Hematologic (P < 0.001) and non-hematologic toxicities (P < 0.001) were more frequent in the CG. The most common causes of chemotherapy cessation were disease progression in the SG and decreased performance status in the CG.. Single-agent treatment should be considered a first-line palliative chemotherapy option for elderly patients with GC.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Drug Combinations; Female; Fluorouracil; Humans; Kaplan-Meier Estimate; Leucovorin; Male; Organoplatinum Compounds; Oxonic Acid; Palliative Care; Prognosis; Retrospective Studies; Stomach Neoplasms; Tegafur; Treatment Outcome

A positive cytology of peritoneal lavage fluid (CY1) is a poor prognostic factor in patients with gastric cancer (GC). We have recently reported that CY1 often changes to negative (CY0) following combination chemotherapy including intraperitoneal (IP) paclitaxel (PTX), which results in marked prolongation of survival in GC patients with peritoneal dissemination (P1).. A total of 95 P1 GC patients who received combination chemotherapy with S-1 and intravenous and IP PTX were enrolled. Peritoneal lavage fluid was periodically examined cytologically at the start of every cycle of chemotherapy, and the impact of CY status on patient outcome was retrospectively evaluated.. Seventy-three (76.8%) of 95 patients were diagnosed as CY1 before initial treatment. Median survival time (MST) of the CY1 group was significantly shorter than that of the CY0 group (19.1 vs. 32.5 months, P = 0.033). Cytological status changed from CY1 to CY0 in 68 (93.2%) of 73 CY1 patients during the whole treatment period and MST of patients who showed a negative change was significantly longer than that of the unchanged group (20.0 vs. 13.0 months, P = 0.0017). In 64 patients who achieved CY0 by IP PTX regimen, the median time to achieve CY0 was 1.4 months, and patients who achieved a negative change within 1 month showed a particularly good outcome (MST = 26.1 months).. Periodic cytological examination of peritoneal lavage fluid is clinically useful to evaluate the efficacy of treatment as well as to predict the outcome of patients with P1 GC.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Cytodiagnosis; Drug Combinations; Female; Follow-Up Studies; Gastrectomy; Humans; Injections, Intraperitoneal; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Oxonic Acid; Paclitaxel; Peritoneal Lavage; Peritoneal Neoplasms; Prognosis; Retrospective Studies; Stomach Neoplasms; Survival Rate; Tegafur

Compliance with S-1 adjuvant chemotherapy is not satisfactory, and the aim of the present study was to clarify risk factors for the continuation of S-1 after gastrectomy.. This retrospective study selected patients who underwent curative D2 surgery for gastric cancer, were diagnosed with stage II/III disease, had a creatinine clearance >60 ml/min, and received adjuvant S-1 at our institution between June 2010 and March 2014. The time to S-1 treatment failure (TTF) was calculated.. Fifty-eight patients were selected for the present study. When the TTF curves stratified by each clinical factor were compared using the log-rank test, lean body-mass loss (LBL) of 5 % was regarded as a critical cutoff point. Univariate Cox's proportional hazard analyses demonstrated that LBL was a significant independent risk factor for continuation. The 6-month continuation rate was 91.7 % in patients with an LBL < 5 %, and 66.3 % for patients with an LBL > 5 % (p = 0.031).. The present study demonstrated that LBL might be an important risk factor for a decrease in compliance to adjuvant chemotherapy with S-1 in patients with stage II/III gastric cancer who underwent D2 gastrectomy. A multicenter, double-blinded, prospective cohort study is necessary to confirm whether LBL would affect adjuvant S-1 continuation.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Body Composition; Body Weight; Drug Combinations; Electric Impedance; Female; Gastrectomy; Humans; Male; Medication Adherence; Middle Aged; Oxonic Acid; Proportional Hazards Models; Retrospective Studies; Risk Factors; Stomach Neoplasms; Tegafur

Patient with α-Fetoprotein (AFP)-producing gastric cancer usually has a short survival time due to frequent hepatic and lymph node metastases. Gastric cancer with portal vein tumor thrombus (PVTT) is rare and has an extremely poor prognosis.. A 63-year-old man was found to have a huge Type 3 gastric cancer with a PVTT and a highly elevated serum AFP level. Chemotherapy with S-1 plus cisplatin was given to this patient with unresectable gastric cancer for 4 months. The serum AFP level decreased from 6,160 ng/mL to 60.7 ng/mL with chemotherapy. Since the PVTT disappeared after the chemotherapy, the patient underwent total gastrectomy. Histological findings of the primary tumor after chemotherapy showed poorly differentiated adenocarcinoma without hepatoid cells and viable tumor cells remaining in less than 1/3 of the neoplastic area of mucosa and one lymph node. The cancerous cells were immunohistochemically stained by anti-AFP antibody. The patient has survived for 48 month without recurrence.. AFP-producing gastric cancer with a PVTT has an extremely poor prognosis, but long-term survival was achieved for this dismal condition by salvage surgery after chemotherapy.

Topics: Adenocarcinoma; alpha-Fetoproteins; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Chemotherapy, Adjuvant; Cisplatin; Drug Combinations; Gastrectomy; Humans; Male; Middle Aged; Neoadjuvant Therapy; Oxonic Acid; Portal Vein; Salvage Therapy; Stomach Neoplasms; Tegafur; Thrombosis

This retrospective study aimed to address the therapeutic outcome for scirrhous gastric cancer patients by evaluating the effect of neoadjuvant chemotherapy prior to gastrectomy.. Two cycles of a 3-week regimen of fluoropyrimidine S-1 (40 mg/m(2), orally, twice daily), together with cisplatin (60 mg/m(2), intravenously, day 8), were administered to patients, separated by a 2-week rest period. Surgery was performed 3 weeks later in the neoadjuvant group (n = 27). We retrospectively evaluated overall survival and prognostic factors in these patients.. Univariate analysis showed that positive lavage cytology indicated significantly worse prognoses. In the 15 patients who also underwent curative gastrectomies after S-1 plus cisplatin chemotherapy, the pathological response grade was a significant prognostic factor for 5-year survival. Additionally, lymph node metastasis tended to be an adverse prognostic factor.. After S-1 plus cisplatin neoadjuvant chemotherapy, a grade 2-3 pathological response may predict favorable outcomes in scirrhous gastric cancer patients receiving curative gastrectomy, but further studies are needed to confirm these results.

Topics: Adenocarcinoma, Scirrhous; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cisplatin; Drug Administration Schedule; Drug Combinations; Female; Gastrectomy; Humans; Kaplan-Meier Estimate; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Invasiveness; Neoplasm Staging; Oxonic Acid; Prognosis; Retrospective Studies; Sample Size; Stomach Neoplasms; Tegafur; Treatment Outcome

This report describes a case of recurrent gastric cancer successfully treated with S-1 oral administration. A 77-year old female patient underwent distal gastrectomy for gastric cancer, followed by adjuvant chemotherapy with tegafur-uracil (UFT). However, 1 year after surgical resection, recurrence in the lymph node of the hepatic hilum was diagnosed by abdominal computed tomography. The patient was treated with S-1 alone after refusing in travenous infusion chemotherapy. Three months after treatment, the size of the target lesion decreased significantly, and a complete response was seen on imaging examination during the 2 years of chemotherapy treatment. One year and 5 months after the discontinuation of chemotherapy, recurrence was noted again. Although supportive care was eventually provided to the patient, S-1 oral administration was resumed that resulted in tumor growth control for>6 months. In this patient, S-1 treatment was effective in tumor growth suppression without deteriorating the patient's quality of life (QOL). Further studies are needed to identify patients for whom S-1 therapy is optimal treatment.

Topics: Administration, Oral; Aged; Antimetabolites, Antineoplastic; Drug Combinations; Fatal Outcome; Female; Humans; Lymphatic Metastasis; Oxonic Acid; Quality of Life; Recurrence; Stomach Neoplasms; Tegafur

We wished to evaluate the impact of S-1 combined with oxaliplatin (SOX regimen) as neoadjuvant chemotherapy on surgical outcomes after gastrectomy with D2 lymphadenectomy.. From February 2012 to September 2013, 170 patients with American Joint Committee on Cancer (AJCC) stage II-III gastric cancer were assessed retrospectively. Eighty patients underwent neoadjuvant chemotherapy before radical gastrectomy, and 90 patients received surgical treatment with adjuvant chemotherapy. Patients received S-1 (80 mg/m(2)/day; days 1-14) and oxaliplatin (130 mg/m(2); day 1) as neoadjuvant or adjuvant chemotherapy, and this schedule was repeated every 3 weeks. Gastrectomy with D2 lymphadenectomy was standard therapy for each patient. Surgical outcomes between the two groups were analyzed statistically.. There was no significant difference in the total prevalence of complications between neoadjuvant and adjuvant groups (18.8% vs. 22.2%, P = 0.704). The most common postoperative complications were surgical site infection (6.5%) and gastrointestinal motility disorders (3.5%). The clinical response rate was 68.8%, and ten patients (12.5%) had a pathological complete response after neoadjuvant chemotherapy. The SOX regimen as neoadjuvant chemotherapy for AJCC stage II/III gastric cancer can be effective without increasing the risk of postoperative complications.. The SOX regimen could be a neoadjuvant chemotherapy for advanced gastric cancer worldwide in the future.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Combined Modality Therapy; Drug Combinations; Female; Fluorouracil; Follow-Up Studies; Gastrectomy; Humans; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Postoperative Complications; Prognosis; Prospective Studies; Remission Induction; Retrospective Studies; Stomach Neoplasms; Survival Rate; Tegafur; Young Adult

This study is a retrospective analysis evaluating the efficacy and toxicity of combination chemotherapy with S-1 and oxaliplatin (SOX) as first-line treatment in elderly patients with advanced gastric cancer. One hundred and twenty-nine patients with recurrent or metastatic gastric adenocarcinoma were treated with SOX; S-1 (40-60 mg depending on patient's body surface area) was given orally, twice daily on days 1 to 14 followed by a 7-day rest period, 130 mg/m(2) oxaliplatin was given as an intravenous infusion over 2-hours on day one. The cycle was repeated every three weeks. All of the patients were older than 65 years. Among 129 patients enrolled, nine patients could not be evaluated for responses because of the absence of any measurable lesions or early discontinuation of therapy. Assessment of the response of 120 patients was made. The overall objective response rate was 54.2 % (95 %CI, 45.3-63.1 %), with three complete responses and 62 partial responses. The disease control rate was 80.8 % (95 %CI, 73.8-87.8 %). The median follow-up period was 23 months (range, 5-42 months). The median time to progression was 6.9 months (95 %CI, 5.5-8.3 months) and the median overall survival was 12.8 months (95 %CI, 11.4-14.2 months). The one-year survival rate was 57.5 % (95 %CI, 48.7-66.3 %). In 129 patients assessed safety, grade 3 and 4 toxicities included leucopenia (20.9 %), neutropenia (24.0 %), anemia (10.9 %), thrombocytopenia (10.1 %), anorexia (3.1 %), peripheral neurotoxicity (15.5 %), and fatigue (12.4 %). No treatment-related deaths occurred. Combination chemotherapy with SOX offers an effective, safe and well-tolerated regimen for elderly patients with advanced gastric cancer.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Female; Follow-Up Studies; Humans; Male; Neoplasm Metastasis; Neoplasm Recurrence, Local; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Prognosis; Retrospective Studies; Stomach Neoplasms; Survival Rate; Tegafur

The prognosis of unresectable gastric cancer is poor. Chemotherapy occasionally converts an initially unresectable gastric cancer to a resectable cancer.. The responses of noncurative factors to initial chemotherapy and the outcomes of additional (conversion) surgery were retrospectively evaluated in 151 patients with unresectable gastric cancer receiving combination chemotherapy with S-1 plus cisplatin or paclitaxel from February 2003 to December 2013.. Forty (26 %) of 151 patients underwent conversion surgery. After chemotherapy, R0 resection was accomplished in 32 patients (80 %). The 5-year overall survival (OS) rate among the 40 patients who underwent conversion surgery was 43 % (median survival time, 53 months). The 5-year OS rate in the 111 patients treated with chemotherapy alone was 1 % (median survival time, 14 months). Patients who underwent conversion surgery had significantly longer OS times than patients who underwent chemotherapy alone (P < 0.01). The 5-year OS rate among patients who underwent R0 resection was 49 % (median survival time, 62 months). Patients who underwent R0 resection had significantly longer OS times than those who underwent R1 and R2 resection (P = 0.03). Among patients who underwent conversion surgery, multivariate Cox regression analysis showed that one noncurative factor (odds ratio 0.49; 95 % confidence interval 0.28-0.88; P = 0.02) and R0 resection (odds ratio 0.52; 95 % confidence interval 0.28-0.95; P = 0.03) were significant independent predictors for favorable OS.. Patients with unresectable gastric cancer initially exhibiting one noncurative factor may obtain a survival benefit from chemotherapy and subsequent curative surgery.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cisplatin; Disease-Free Survival; Drug Combinations; Female; Gastrectomy; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Grading; Neoplasm Staging; Neoplasm, Residual; Oxonic Acid; Paclitaxel; Proportional Hazards Models; Retrospective Studies; Stomach Neoplasms; Survival Rate; Tegafur

An oral antineoplastic drug, S-1, is known to be more effective with less toxicity and fewer gastrointestinal side effects than the conventional intravenous 5-fluorouracil. We report a case of limbal stem cell deficiency that occurred in a patient receiving chemotherapy using S-1 alone for gastric cancer.. A 65-year-old woman with symptoms of grittiness and epiphora in both eyes for several months was referred to the ophthalmology clinic. She had been receiving S-1 orally after total gastrectomy for advanced gastric cancer. Slit lamp examination revealed an irregular hazy corneal epithelium in both eyes that extended to the center of the cornea overlying the pupil and showed late staining with fluorescein dye. Palisades of Vogt at the superior limbus were absent in both eyes. Best-corrected distance vision was 20/50 in both eyes with all other structures of the anterior and posterior segment unremarkable including a patent lacrimal drainage system. There was no change in the corneal lesions of either eye despite 3 months of topical therapy. The lesions did resolve in 4 months after discontinuation of S-1 therapy owing to acute renal failure.. Early detection of this adverse reaction before significant visual loss through regular follow-up appears to be important in patients receiving S-1 therapy.

Topics: Aged; Antimetabolites, Antineoplastic; Corneal Diseases; Drug Combinations; Epithelium, Corneal; Female; Gastrectomy; Humans; Limbus Corneae; Oxonic Acid; Stem Cells; Stomach Neoplasms; Tegafur; Visual Acuity

We analyzed the expression levels of fluoropyrimidine-metabolizing enzymes (thymidylate synthase [TS], dihydropyrimidine dehydrogenase [DPD], thymidine phosphorylase [TP] and orotate phosphoribosyltransferase [OPRT]) to identify potential biomarkers related to treatment outcomes in gastric cancer (GC) patients receiving adjuvant S-1 chemotherapy. In this study, 184 patients who received curative gastrectomy (D2 lymph node dissection) and adjuvant S-1 were included. Immunohistochemistry and quantitative reverse transcription polymerase chain reaction were performed to measure the protein and mRNA levels of TS, DPD, TP, and OPRT in tumor tissue. In univariate analysis, low intratumoral DPD protein expression was related to poorer 5-year disease-free survival (DFS; 78% vs. 88%; P = 0.068). Low intratumoral DPD mRNA expression (1st [lowest] quartile) was also related to poorer DFS (69% vs. 90%; P < 0.001) compared to high intratumoral DPD expression (2nd to 4th quartiles). In multivariate analyses, low intratumoral DPD protein or mRNA expression was related to worse DFS (P < 0.05), irrespective of other clinical variables. TS, TP, and OPRT expression levels were not related to treatment outcomes. Severe non-hematologic toxicities (grade ≥ 3) had a trend towards more frequent development in patients with low intratumoral DPD mRNA expression (29% vs. 16%; P = 0.068). In conclusion, GC patients with high intratumoral DPD expression did not have inferior outcome following adjuvant S-1 therapy compared with those with low DPD expression. Instead, low intratumoral DPD expression was related to poor DFS.

Topics: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Drug Combinations; Female; Gene Expression Regulation, Enzymologic; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Oxonic Acid; Prognosis; Stomach Neoplasms; Tegafur; Treatment Outcome

Fifteen years after receiving a distal gastrectomy for advanced gastric cancer, a 70-year-old woman was admitted to our hospital because of abdominal fullness due to ascites. Although cytological examination showed adenocarcinoma cells in the fluid, no examination revealed the primary lesion. Peritoneal metastasis was detected via immunohistochemistry using the cell block technique. After chemotherapy failure (S-1 plus CDDP, weekly PTX, and S-1 plus DOC), the patient received S-1 and weekly intravenous and intraperitoneal injections of PTX. The ascites decreased, and she has been doing well. Our experience with this case suggests that S-1 and weekly intravenous and intraperitoneal injections of PTX is a promising means of treating gastric cancer with peritoneal metastasis.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Ascites; Drug Combinations; Female; Gastrectomy; Humans; Infusions, Intravenous; Injections, Intraperitoneal; Oxonic Acid; Paclitaxel; Peritoneal Neoplasms; Recurrence; Stomach Neoplasms; Tegafur; Time Factors

Topics: Antineoplastic Agents; Cisplatin; Clinical Trials as Topic; Drug Combinations; Humans; Oxonic Acid; Stomach Neoplasms; Tegafur

S-1, cisplatin, and docetaxel (DCS) constitute an effective regimen for gastric cancer. We conducted a retrospective cohort study of systemic DCS and a prospective phase I trial of intraperitoneal DCS in the preoperative setting for marginally resectable gastric cancer.. Under the systemic regimen, patients received cisplatin (60 mg/m(2)) plus docetaxel (40 mg/m(2)) intravenously on day 1 and S-1 (80 mg/m(2)) on days 1-14, of a 28-day cycle. With the intraperitoneal regimen, the schedule for S-1 and cisplatin was the same. Dose escalation for docetaxel started at 30 mg/m(2) (level 1).. Between August 2010 and July 2013, 26 consecutive patients were treated with the systemic regimen. Grade 3-4 neutropenia occurred in 81% but the toxicity profile was very tolerable. The response rate based on the Response Evaluation Criteria in Solid Tumors (RECIST) was 89%. Between April 2012 and April 2014, 5 patients with linitis plastica, large ulcero-invasive type tumors, positive washing cytology or peritoneal metastasis were enrolled in the phase I trial of the intraperitoneal regimen. Grade 3-4 elevations in aspartate/ alanine aminotransferase (AST/ALT) occurred in the first 2 patients. The next 3 patients, who received docetaxel (20 mg/m(2)) on days 1 and 15 (level 0), had no dose-limiting toxicity. Four patients, including 3 with peritoneal metastasis and/or positive cytology before treatment, underwent R0 resection after intraperitoneal chemotherapy.. Our studies revealed the efficacy of the systemic regimen and the safety of the intraperitoneal regimen. Further investigation of these two types of preoperative DCS chemotherapy is warranted.

Topics: Adult; Aged; Cisplatin; Docetaxel; Drug Combinations; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Male; Middle Aged; Oxonic Acid; Peritoneal Neoplasms; Retrospective Studies; Stomach Neoplasms; Taxoids; Tegafur

The aim of the present study was to evaluate the clinical significance of protein-bound polysaccharide K (PSK) in patients with primary gastric cancer who were being treated with an oral fluoropyrimidine (S-1).. Clinical reports of 190 gastric cancer patients treated with S-1 chemotherapy, with or without PSK, at Kochi Medical School between 2007 and 2012 were investigated retrospectively to analyze survival. The neutrophil:lymphocyte ratio (NLR) was also evaluated as indicator of the immunoenhancing effect of PSK.. Overall survival was significantly longer in patients treated with S-1 + PSK than in those given S-1 alone (hazard ratio for death, 0.608; 95% confidence interval 0.375-0.985; P = 0.041). Furthermore, there was a tendency for changes in the NLR during chemotherapy to be lower in the S-1 + PSK group than in the S-1 group, but the difference did not reach statistical significance (P = 0.054). When patients were divided into groups based on preoperative NLR (i.e. <2.5 and ≥2.5), the mean (±SEM) NLR 1 month after the beginning of chemotherapy in the NLR ≥2.5 subgroup was significantly lower in patients treated with S-1 + PSK rather than S-1 alone (1.7 ± 0.7 vs. 3.3 ± 4.1, respectively; P = 0.043).. Immunochemotherapy using PSK improves the survival of patients with advanced gastric cancer. The NLR may be a useful biomarker for evaluating prognosis in these patients.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Female; Fungal Proteins; Humans; Immunotherapy; Kaplan-Meier Estimate; Lymphocyte Count; Lymphocytes; Male; Middle Aged; Neutrophils; Oxonic Acid; Polysaccharides; Retrospective Studies; Stomach Neoplasms; Survival Rate; Tegafur

Objective evaluation of intestinal mucosal damage due to anticancer drugs is generally difficult. Serum diamine oxidase (DAO) activity is reported to reflect the integrity and maturity of the small intestinal mucosa. Therefore, we investigated whether serum DAO activity is an indicator of gastrointestinal toxicity or nutritional status in patients receiving chemotherapy.. We prospectively enrolled 20 patients with unresectable metastatic gastric cancer who received oral S-1 (80 mg/m(2) ) on days 1-14, and intravenous cisplatin (60 mg/m(2) ) and docetaxel (50 mg/m(2) ) on day 8 every 3 weeks. Serum DAO activity was measured by colorimetry. Gastrointestinal toxicity was evaluated by Common Toxicity Criteria for Adverse Events version 4.0. Endoscopic examination and biopsy of duodenal mucosa assessed mucosal damage. Malnutrition was evaluated by measuring serum total protein and albumin levels.. Serum DAO activity decreased step-by-step significantly during anticancer drug treatment and recovered after drug holidays. In all 14 patients who experienced diarrhea, serum DAO activity significantly decreased prior to diarrhea onset. Percent decrease in DAO activity was significantly correlated with severity of diarrhea. Significant correlation was observed between percent decrease in DAO activity and percent decrease in duodenal villus height or surface area from baseline. There were also significant correlations between percent decrease in serum DAO activity at day 14 and percent decrease in serum total protein or albumin levels at day 21 from baseline.. Serum DAO activity sensitively indicates gastrointestinal damage prior to symptom onset and can be a useful predictor of intestinal mucosal damage and nutritional status in patients receiving chemotherapy.

Topics: Adult; Aged; Amine Oxidase (Copper-Containing); Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Biomarkers; Cisplatin; Docetaxel; Drug Combinations; Duodenum; Female; Gastrointestinal Diseases; Humans; Intestinal Mucosa; Male; Malnutrition; Middle Aged; Oxonic Acid; Prospective Studies; Sensitivity and Specificity; Stomach Neoplasms; Taxoids; Tegafur

In our hospital, a clinical trial on the effects of preoperative 2-week S-1 administration for advanced gastric cancer is being conducted. A7 5-year-old man presented to our hospital with a type 2 tumor(poorly differentiated adenocarcinoma)in the pyloric antrum. Subpyloric lymph node enlargement and a c-T2(MP), N1, M0, Stage II A tumor (according to the gastric cancer handling agreement, 14th edition)were diagnosed, and S-1(100mg/day)was subsequently administered for 14 days. On day 15, we performed laparoscopy-assisted distal gastrectomy, with D2 dissection. Analysis of the resected specimen, ie the primary tumor and metastatic lymph nodes, confirmed the effect of the treatment as Grade 2, and revealed a type 2 gastric cancer of 30×20mm in size; this tumor was downstaged to yp-T1b(SM), N1, Stage I B. No adverse events associated with perioperative S-1 were observed, and the postoperative course was good. At the latest follow-up(6 years after treatment), no recurrence was observed.

Topics: Adenocarcinoma; Aged; Antimetabolites, Antineoplastic; Drug Combinations; Gastrectomy; Humans; Lymph Node Excision; Male; Neoadjuvant Therapy; Neoplasm Staging; Oxonic Acid; Stomach Neoplasms; Tegafur

Massive malignant ascites originating from peritoneal metastasis of gastric cancer is difficult to control and resistant to chemotherapy. Cell-free and Concentrated Ascites Reinfusion Therapy (CART) is one of the types of apheresis therapy, by which filtered and concentrated ascites containing albumin and globulin is reinfused intravenously to patients. We retrospectively studied the feasibility of intraperitoneal (IP) chemotherapy combined with CART in gastric cancer patients with massive malignant ascites.. Paclitaxel (PTX) was administered via an IP access port implanted in the subcutaneous space. If patient had massive ascites at the start of treatment, paracentesis was performed through a percutaneous IP catheter and then CART was performed. PTX was administered through the catheter until the ascites diminished.. A total of 127 CART procedures in 30 patients were analyzed. The average volume of processed ascites was 3.1 L, which was concentrated to 0.33 L containing 85.5 g protein on average. Significant increases in urine volume, serum total protein and albumin level were found after the CART. Increase in body temperature (0.3°C), decrease in platelet count (3.8 × 10(4)/μl), and changes in blood pressure (2 mm Hg) were found after the CART procedure, but no clinically significant adverse event was experienced. The median survival time and 1-year survival of 30 patients who received IP chemotherapy combined with the CART procedure was 10.2 months and 43.3% respectively.. IP chemotherapy combined with CART might be a promising strategy for patients with massive malignant ascites originating from peritoneal metastasis of gastric cancer.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Ascites; Ascitic Fluid; Blood Proteins; Body Temperature; Cell-Free System; Drug Combinations; Female; Follow-Up Studies; Humans; Infusions, Intravenous; Infusions, Parenteral; Kaplan-Meier Estimate; Laparoscopy; Male; Middle Aged; Oxonic Acid; Paclitaxel; Peritoneal Neoplasms; Platelet Count; Retrospective Studies; Second-Look Surgery; Serum Albumin; Stomach Neoplasms; Tegafur; Tomography, X-Ray Computed; Treatment Outcome

Recent advances in gastric cancer chemotherapy have made macroscopic complete resection possible in some patients with stage IV disease.. We retrospectively investigated the efficacy of multimodal therapy with combined docetaxel, cisplatin, and S-1 (DCS) and conversion gastrectomy in 57 patients with stage IV gastric cancer.. Of the 57 patients, 15 patients were categorized into potentially resectable case, which is defined as patients with single incurable factor including the upper abdominal para-aortic lymph node metastasis (16a2b1 PAN metastasis) or fewer than three peripheral liver metastases. The other 42 were categorized as initially unresectable. All of patients underwent DCS therapy, and then 34 patients underwent conversion gastrectomy. The 3-year overall survival (OS) rate among the patients who underwent conversion gastrectomy was 50.1% with MST of 29.9 months. They had significantly longer OS than patients who underwent DCS therapy alone (p < 0.01). Univariate analysis among the patents with conversion gastrectomy identified 16a2b1PAN metastasis, peritoneal metastasis, potential resectable case, R0 resection as significant prognostic factors. A 3-year OS in potential resectable cases was 92.9%. Multivariate analysis identified potential resectability as the only independent prognostic factor contributing to OS (HR 0.133, 95%CI 0.024-0. 744, p = 0.021). In contrast, clinical response was selected as the only independent prognostic factor in the subgroup of initially unresectable cases (HR 0.354, 95%CI 0.151-0.783, p = 0.021).. Patients with potentially resectable disease had a remarkably good prognosis among stage IV gastric cancer patients, and might be ideal candidates for conversion gastrectomy following DCS therapy.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Aorta; Cisplatin; Cohort Studies; Docetaxel; Drug Combinations; Female; Gastrectomy; Humans; Liver Neoplasms; Lymph Nodes; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Oxonic Acid; Retrospective Studies; Stomach Neoplasms; Taxoids; Tegafur; Treatment Outcome

A phase 3 evidence indicates that S-1 adjuvant is beneficial among East Asian patients with stage II/III gastric cancer (GC). However, little is known about the changes in prognostic factors and recurrence patterns after it has become widespread as a standard of care. The present study compared prognostic factors of patients with stage II/III GC treated with or without S-1 adjuvant with formulate appropriate risk stratification strategies.. We enrolled 171 patients with stage II/III GC, 92 patients who underwent gastrectomy alone, and 79 patients treated with S-1 adjuvant. To balance more strictly the essential variables including stage of progression, we conducted propensity score analysis and 70 pairs of patients were generated from each group. Prognostic factors were compared between the groups and initial recurrence patterns were investigated to explore reasons for the change.. In concordance with the previous phase 3 trial, overall and recurrence-free survival were better for the S-1 adjuvant group. In the surgery alone group, carcinoembryonic antigen ≥ 5 ng/mL, total gastrectomy, vessel invasion, pT4, and stage 3 were identified as significant prognostic factors. In striking contrast, macroscopic tumor size ≥ 50 mm was the only significant prognostic factor for the S-1 adjuvant group. The lower overall recurrence rate of the S-1 adjuvant group was attributable mainly to a significant decrease of peritoneal recurrence.. Prognostic factors changed substantially after implementation of S-1 adjuvant treatment. Macroscopic tumor size should be considered for patient stratification and selection of treatment options for patients with stage II/III GC.

Topics: Aged; Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Combined Modality Therapy; Drug Combinations; Female; Gastrectomy; Humans; Male; Matched-Pair Analysis; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Oxonic Acid; Postoperative Care; Prognosis; Propensity Score; Retrospective Studies; Risk Factors; Stomach Neoplasms; Survival Rate; Tegafur; Treatment Outcome

We report a case of Stage IV breast cancer in a 62-year-old woman who responded well to alternate-day S-1/letrozole combination therapy. She was admitted to our hospital because of appetite loss and vomiting, and was diagnosed with invasive lobular carcinoma (ER+/HER2-) with gastric metastasis. After gastrointestinal stenting was performed, we initiated oral administration of S-1 (100 mg/body) and letrozole (2.5 mg) as systemic therapy. To reduce adverse effects, we administered S-1 on alternate days. Computed tomography and endoscopic examination revealed that the patient has been showing partial response since 1 year after initiating treatment. Therefore, we conclude that alternate-day S-1/letrozole combination therapy could be an effective and sustainable treatment for advanced ER-positive, HER2-negative breast cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Carcinoma, Lobular; Drug Combinations; Female; Humans; Letrozole; Middle Aged; Nitriles; Oxonic Acid; Stomach Neoplasms; Tegafur; Treatment Outcome; Triazoles

A 77-year-old man presented with epigastralgia. Gastrointestinal endoscopic examination showed advanced gastric cancer, type 3, in the distal antrum. The patient refused surgery and preferred chemotherapy. The regimen consisted of 80 mg/body/day of S-1, continuously administered from day 1-14, followed by discontinuation for 2 weeks. After 2 courses, the patient experienced fatigue and recurrent vomiting. Laboratory studies revealed severe anemia; the hemoglobin level was 5.5 g/dL. An upper gastrointestinal endoscopy revealed pyloric stenosis and significant tumor reduction. Therefore, distal gastrectomy was performed. Histological examination did not reveal any viable cancer cells in the stomach and lymph nodes. Thus, a Grade 3 postchemotherapeutic effect was revealed.

Topics: Aged; Antimetabolites, Antineoplastic; Drug Combinations; Gastrectomy; Humans; Lymphatic Metastasis; Male; Neoadjuvant Therapy; Oxonic Acid; Stomach Neoplasms; Tegafur

Endoscopic ultrasonography-guided fine needle aspiration (EUS-FNA) is a useful and relatively safe tool for the diagnosis and staging of pancreatic cancer. However, there have recently been several reports of tumor seeding after EUS-FNA of adenocarcinomas. A 78-year-old man was admitted to our hospital due to upper gastric pain. Examinations revealed a 20 mm mass in the pancreatic body, for which EUS-FNA was performed. The cytology of the lesion was adenocarcinoma, and the stage of the cancer was T3N0M0. The patient underwent surgery with curative intent, followed by adjuvant chemotherapy with S-1. An enlarging gastric submucosal tumor was found on gastroscopy at 28 mo after surgery accompanied by a rising level of CA19-9. Biopsy result was adenocarcinoma, consistent with a pancreatic primary tumor. Tumor seeding after EUS-FNA was strongly suspected. The patient underwent surgical resection of the gastric tumor with curative intent. The pathological result of the resected gastric specimen was adenocarcinoma with a perfectly matched mucin special stain result with the previously resected pancreatic cancer. This is the first case report of tumor seeding after EUS-FNA which was surgically resected and inspected pathologically.

Topics: Adenocarcinoma; Aged; Antimetabolites, Antineoplastic; Biopsy; Chemotherapy, Adjuvant; Drug Combinations; Endoscopic Ultrasound-Guided Fine Needle Aspiration; Gastrectomy; Humans; Male; Neoplasm Seeding; Neoplasm Staging; Oxonic Acid; Pancreatectomy; Pancreatic Neoplasms; Stomach Neoplasms; Tegafur; Time Factors; Tomography, X-Ray Computed; Treatment Outcome

Peritoneal lavage cytology cancer-positive (CY1) is a critical prognostic factor and is taken as representing stage IV in gastric cancer. There is no consensus treatment strategy for CY1-gastric cancer, and the detailed clinicopathological features remain obscure.. Among 790 gastric cancer patients between 2005 and 2009, 52 cases of CY1 were identified (6.6%). A multivariate prognostic model was applied to the univariate prognostic factors to identify independent prognostic factors and factors associated with long-term survival in CY1-gastric cancer.. (1) Five-year overall survival (OS) was 17.6% in CY1-gastric cancer as compared with 93.9% in CYX and 77.7% in CY0 (77.7%), where tumors with pT2 or beyond were included in 11% of CYX, 73% of CY0, and 98% of CY1 cases. (2) On univariate analysis, factors associated with a negative prognosis were the presence of peritoneal dissemination (p = 0.029) and high preoperative serum albumin (p = 0.011) in CY1-gastric cancer. The multivariate Cox proportional hazards and logistic regression model using propensity score identified preoperative albumin as a critical independent prognostic indicator. (3) Long-term survivors were identified and, were often characterized by long-term postoperative adjuvant treatment.. Reduced preoperative serum albumin and absence of peritoneal dissemination may be predictive factors for long-term survival in patients with advanced gastric cancer with positive cytology test. Long-term postoperative adjuvant therapy might improve survival of patients with CY1.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cisplatin; Disease-Free Survival; Docetaxel; Drug Combinations; Female; Gastrectomy; Humans; Hypoalbuminemia; Logistic Models; Male; Middle Aged; Multivariate Analysis; Oxonic Acid; Peritoneal Lavage; Peritoneal Neoplasms; Preoperative Period; Prognosis; Proportional Hazards Models; Retrospective Studies; Serum Albumin; Stomach Neoplasms; Taxoids; Tegafur

To examine the effect of S-1 adjuvant chemotherapy on muscle volume after curative gastrectomy in gastric cancer patients.. Forty-eight gastric cancer patients (31 men and 17 women) who underwent curative gastrectomy (distal gastrectomy: n=37, and total gastrectomy: n=11) between April 2010 and July 2011 were enrolled in this study. Sixteen patients underwent S-1 adjuvant chemotherapy (S-1 group) for 1 year after the operation, and 32 patients did not (NT group).. The psoas muscle areas were measured at the fourth lumbar vertebrae on CT images obtained before the operation, and at 6, 12, and 24 months after the operation. Muscle areas was statistically examined by comparing the preoperative and postoperative ratios.. The muscle areas 12 months after the operation decreased to 0.86 ± 0.11 in the S-1 group and to 0.96 ± 0.08 in the NT group (p<0.05), and the significant difference disappeared at 24 months (0.93 ± 0.10 vs. 0.93 ± 0.11, NS). In the patients who underwent distal gastrectomy, the muscle areas decreased to 0.90 ± 0.05 in the S-1 group and to 0.96 ± 0.09 in the NT group at 12 months (p<0.05). Meanwhile, in those who underwent total gastrectomy, the muscle areas decreased to 0.80 ± 0.15 and 0.93 ± 0.03, respectively (NS).. S-1 adjuvant chemotherapy affected muscle volume loss after gastrectomy in the gastric cancer patients, but the patients recovered from the adverse effect by 12 months after chemotherapy.

Topics: Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Drug Combinations; Female; Gastrectomy; Humans; Male; Muscle, Skeletal; Neoplasm Staging; Oxonic Acid; Stomach Neoplasms; Tegafur; Treatment Outcome

A 67-year-old man underwent distal gastrectomy via the Billroth Ⅱ method (B-Ⅱ) for a duodenal ulcer. He presented with appetite loss and nausea in May 2014. Gastrointestinal endoscopy revealed wall thickness around gastrojejunostomy and the gastric mucosal fold. Biopsy and re-biopsy revealed a group 2 tumor. Laparotomy for diagnosis was performed because of stenosis and tumor progression. Intraoperative frozen section examination revealed adenocarcinoma in the lymph nodes of the jejunum. Residual gastrectomy with reconstruction using the Roux-en-Y method was performed for residual gastric cancer. Histopathological findings revealed pT4a, pN0, pM1 for the tumor in the lymph nodes of the jejunum, pStage Ⅳ. A distorted gastrojejunostomy site and the presence of anastomotic strictures are important for the rapid diagnosis of residual gastric cancer.

Topics: Aged; Antimetabolites, Antineoplastic; Biopsy; Chemotherapy, Adjuvant; Drug Combinations; Duodenal Ulcer; Fatal Outcome; Gastric Bypass; Humans; Male; Oxonic Acid; Stomach Neoplasms; Tegafur; Time Factors; Tomography, X-Ray Computed

We studied the effects of preoperative chemotherapy with S-1 plus cisplatin for advanced gastric cancer. There were 16 patients who underwent radical surgery with neoadjuvant chemotherapy between 2000 and 2015. The indications for this were advanced gastric cancer with bulky N2 or N3 lymph nodes, or stage above T4a. Seven patients (43%) showed adverse events, all of which were tumors above Grade 3. Response evaluation showed PR in 13 cases (81%). The histopathological evaluation was Grade 0 in 8 patients (50%) and Grade 1a or above in 8 (50%). Death from recurrence within a year occurred in 4 cases, and 7 patients survived with no recurrence for over 5 years. All cases of survivors with no recurrence had a histopathological evaluation of Grade 1 or above. Three cases (75%) with recurrence and death within a year all had with Grade 0 tumors. We concluded that neoadjuvant chemotherapy with S-1 plus cisplatin was effective for advanced gastric cancer and that histopathological evaluation was invaluable for accurate prognosis.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Female; Gastrectomy; Humans; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Prognosis; Stomach Neoplasms; Tegafur

Peritoneal dissemination (PD) is the most common type of metastasis in advanced gastric cancer. The standard treatment of gastric cancer patients with PD is combination therapy with S-1 and cisplatin (SP therapy). Here, we describe the results of SP therapy for gastric cancer with PD. Sixteen gastric cancer patients with PD were treated with SP therapy as first-line chemotherapy. Second-look staging laparoscopy was performed for 10 patients who showed a good response to SP therapy. Gastrectomy was performed for 5 patients with P0CY0 and 1 case with P0CY1. The median survival time of all 16 patients was 571 days (19 months). The patients, who had surgery, had a significantly better survival time than the others (25 months vs 12.7 months). In conclusion, SP therapy is effective for gastric cancer with PD, and surgery for cases showing a good response to chemotherapy might improve the prognosis of patients with PD.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Drug Combinations; Female; Gastrectomy; Humans; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Peritoneal Neoplasms; Prognosis; Stomach Neoplasms; Tegafur

A woman in her 50s underwent distal gastrectomy and D1+b dissection in December 2005 for early gastric cancer that was diagnosed as a signet-ring-cell carcinoma, fStage Ⅱ (T1a, N2, H0, P0, CY0, M0) with 12 lymph node metastases in the second field. Multiple bone metastases were diagnosed on the basis of CT and bone scintigraphy findings and serum ALP elevation (2,743 IU/L) I n December 2010. Fourteen courses of S-1 plus CDDP and 4 mg of zoledronate were administered from January to September in 2011. Pancytopenia, D-dimmer elevation, myelocytes, and metamyelocytes were observed in October 2012, indicating she had bone marrow metastasis. She was treated with a transfusion, anti-DIC therapy, and paclitaxel. She died from gastric cancer in December 2012. We report a rare case of recurrence with bone metastasis from early gastric cancer. S-1 plus CDDP chemotherapy and zoledronate therapy is an effective treatments for multiple bone metastases from gastric cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Cisplatin; Drug Combinations; Female; Gastrectomy; Humans; Lymphatic Metastasis; Middle Aged; Oxonic Acid; Recurrence; Stomach Neoplasms; Tegafur; Time Factors

We report a rare case of surgical resection for pulmonary metastasis from gastric cancer. A 71-year-old man underwent total gastrectomy for gastric cancer in October 2012. After the operation, he received S-1 chemotherapy for 1 year. In January 2014, computed tomography of the chest showed a nodule shadow with a cavity at S3 in the right lung. Because it showed a tendency to gradually enlarge, we performed an operation in September 2014. The nodule was diagnosed as metastatic adenocarcinoma from gastric cancer on pathology. The patient is being treated with S-1 chemotherapy during follow-up. The pulmonary metastases of gastric cancer often develop along with carcinomatous lymphangiosis or carcinomatous pleurisy, and isolated pulmonary metastasis is rare. A consensus has not been reached about the usefulness of surgical resection, and the accumulation of further cases is required.

Topics: Adenocarcinoma; Aged; Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Drug Combinations; Gastrectomy; Humans; Lung Neoplasms; Male; Oxonic Acid; Pneumonectomy; Stomach Neoplasms; Tegafur; Tomography, X-Ray Computed

We present a successful case of treatment of colonic metastasis and peritoneal recurrence of type 4 gastric cancer by using colectomy and chemotherapy. A 70-year-old woman with a diagnosis of type 4 advanced gastric cancer underwent distal gastrectomy. The final pathological diagnosis was LM, circ, type 4, sig, pT4a (SE), ly1, v1, pN1, M0, P0, CY0, pStage Ⅲa. Adjuvant chemotherapy was conducted with oral administration of S-1, though regrettably the chemotherapy was interrupted because of diarrhea, an adverse effect of S-1. Metastatic recurrence occurred on the transverse colon, for which she underwent transverse colectomy 2.9 years after the initial surgery. Another colonic metastasis in the ascending colon along with peritoneal recurrence was diagnosed 3.11 years after the initial surgery, and the patient underwent a palliative colostomy and received chemotherapy with S-1 plus docetaxel. She was successfully treated up to a clinical CR with chemotherapy, and she died 5.10 years after the initial surgery. In this case, a good prognosis was obtained through the combination of resection of the recurrence sites, palliative surgery for avoiding obstruction, and chemotherapy using S-1 plus docetaxel for metachronous multiple metastases.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Colectomy; Colonic Neoplasms; Docetaxel; Drug Combinations; Fatal Outcome; Female; Humans; Oxonic Acid; Recurrence; Stomach Neoplasms; Taxoids; Tegafur

A 60-year-old male patient underwent curative surgical resection for gastric cancer. After the surgery, the patient was diagnosed with T4b, N3b, ly3, v2, CY0, fStageⅢc gastric cancer, and adjuvant systemic chemotherapy using S-1 and CDDP was administered. However, follow-up computed tomography (CT) scan examination taken 2 months after surgery revealed a pancreatic fistula and retroperitoneal abscess, and percutaneous drainage was performed. After 1 month, the enhanced CT scan detected liver metastasis measuring 25 mm in diameter at segment 7. The CT-guided percutaneous radiofrequency ablation (RFA) combined with transcatheter arterial chemoembolization (TACE) procedure was performed on the liver metastasis using degradable starch microspheres (DSM). Two months after the RFA, a follow-up CT scan revealed local recurrence of the lesion in the medial side of the ablated area in segment 7. A second CT-guided RFA, which was combined with DSM-TACE, was performed on the recurrent lesion. The patient has since survived more than 2 years after the second treatment without any further recurrences. This case report suggests that RFA treatment combined with DSM-TACE might be a safe and feasible treatment for liver metastasis from gastric cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; Catheter Ablation; Chemoembolization, Therapeutic; Cisplatin; Combined Modality Therapy; Drug Combinations; Humans; Liver Neoplasms; Male; Oxonic Acid; Starch; Stomach Neoplasms; Tegafur

A 62-year-old man was diagnosed with gastric cancer and underwent distal gastrectomy, and D1+b lymph node dissection. He was diagnosed postoperatively with T1b (sm2) N0M0, StageⅠA gastric adenocarcinoma and did not receive any adjuvant chemotherapy after surgery. One year and 6 months after gastrectomy, blood analysis indicated high levels of carcinoembryonic antigen (CEA 262.1 ng/mL) while abdominal computed tomography (CT) revealed multiple liver tumors (S7: 15 mm, S7/8: 20 mm). The patient was diagnosed with metachronous multiple liver metastases from gastric cancer. Chemotherapy, combined with molecular targeted therapy (S-1 plus cisplatin [CDDP] plus trastuzumab), was administered because of overexpression of the human epidermal growth factor receptor 2 (HER2) protein in the primary tumor as assessed by immunohistochemistry, the CEA levels decreased immediately after 2 cycles of the chemotherapy, and the liver metastases shrank markedly with no evidence of new lesions on abdominal CT. However, after treatment, Grade 3 neutropenia and diarrhea were observed. Chemotherapy was suspended and hepatic resection was performed. After hepatic resection, the liver tumors were histologically evaluated as Grade 2 metastatic gastric adenocarcinoma, and the HER2 expression of remnant carcinoma cells was established. The patient has been in good health and remained free of recurrences in the 2 years and 3 months after the liver resection. Surgery with preoperative chemotherapy (S-1 plus CDDP plus trastuzumab) can be an effective treatment for liver metastasis from HER2-positive gastric cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Gastrectomy; Hepatectomy; Humans; Liver Neoplasms; Lymph Node Excision; Lymphatic Metastasis; Male; Middle Aged; Molecular Targeted Therapy; Oxonic Acid; Recurrence; Stomach Neoplasms; Tegafur; Trastuzumab; Treatment Outcome

A man in his 70s underwent distal gastrectomy and D1 dissection with Roux-en-Y reconstruction in March 2009 for advanced gastric cancer with peritoneal metastasis. He was diagnosed with signet-ring cell carcinoma, Stage Ⅳ(T4a, N3a, H0, P1, CY1, M1) and R2. Seventeen cycles of S-1 plus CDDP were administered from April 2009 to December 2010 and 19 cycles of S-1 monotherapy were administered from January 2011 to March 2014. He developed peritoneal recurrence with serum tumor marker elevation in May 2014. Stenosis of the common bile duct, hydronephrosis, and rectal stenosis in Ra-Rs was observed in June 2014. A bile duct stent and a double J catheter was inserted. A colonic stent (NitiTM, 22 mm×6 cm) was also inserted. He could eat after the surgery and was discharged from the hospital. We suggest that a colonic stent is an effective treatment for colon stenosis due to peritoneal metastasis from gastric cancer.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Fatal Outcome; Gastrectomy; Humans; Intestinal Obstruction; Male; Oxonic Acid; Recurrence; Stents; Stomach Neoplasms; Tegafur

It is sometimes difficult to differentiate between metastatic and primary liver tumors, when the liver tumor occurs simultaneously with a gastric cancer. We encountered a case of resected gastric cancer, which occurred concomitantly with intrahepatic cholangiocarcinoma after S-1 plus cisplatin chemotherapy, in a patient who was previously diagnosed with metastatic liver tumor before treatment. An 80-year-old man was admitted to our hospital because of epigastralgia. Endoscopic study of the upper gastrointestinal tract showed a type 3 tumor at the upper body of the stomach. A plain CT scan showed an irregular, low-density area, which was enhanced by contrast medium in the lateral segment of the liver. We performed an ultrasound- guided needle biopsy, because it was impossible to make a definitive diagnosis by dynamic CT, contrast-enhanced ultrasonography, and MRI. Immunohistochemical analysis for cytokeratin 7/20 resulted in 7 (+)/20 (-) for both the gastric cancer and the liver tumor. Therefore, we diagnosed the patient with gastric cancer, which occurred concomitantly with the metastatic liver tumor, and administered chemotherapy with S-1 plus cisplatin. After 3 courses of the regimen, a reduction in the size of mass was observed in the stomach and the liver. We subsequently performed left hepatectomy and total gastrectomy with lymph node dissection. Microscopic examination revealed the gastric cancer, which occurred simultaneously with the intrahepatic cholangiocarcinoma. The postoperative course was uneventful, and the patient remains well without recurrences.

Topics: Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bile Duct Neoplasms; Cholangiocarcinoma; Cisplatin; Drug Combinations; Humans; Male; Neoplasms, Multiple Primary; Oxonic Acid; Stomach Neoplasms; Tegafur; Treatment Outcome

The patient, a 76-year-old man, presented to his local doctor's clinic with complaints of fatigue and lightheadedness. Because blood test results indicated anemia, he was referred to our hospital. Upper gastrointestinal endoscopy indicated a type 2 tumor of approximately 5 cm at the top of the gastric corpus. Biopsy results indicated that the lesion was a poorly differentiated adenocarcinoma. Computed tomography showed multiple liver metastases and the patient was diagnosed with stage Ⅳ gastric cancer. After a blood transfusion, chemotherapy with S-1 was started. However, as the patient experienced continued hemorrhage from the primary lesion, treatment was changed to total gastrectomy in order to control the bleeding. The pathologic examination of the resected specimen indicated that the tumor was located in the muscle and subserosal layers. The tumor cells were spindle-shaped, c-kit positive, cytokeratin-negative, and Dog-1 positive. Therefore, a diagnosis of gastrointestinal stromal tumor (GIST) was made. Postoperatively, chemotherapy with imatinib was administered and the patient was alive with no progression of disease 1 year following surgery. Intraductal growth pattern GISTs of the stomach that protrude into the epithelium and exhibit ulceration can be difficult to distinguish from gastric carcinomas. We experienced a case of gastric GIST that was difficult to diagnose preoperatively.

Topics: Aged; Antineoplastic Agents; Biopsy; Drug Combinations; Gastrectomy; Gastrointestinal Stromal Tumors; Humans; Imatinib Mesylate; Liver Neoplasms; Male; Oxonic Acid; Stomach Neoplasms; Tegafur

A 56-year-old man who underwent a radical operation and adjuvant chemotherapy for recurrent rectal cancer had been followed-up and had no recurrence for one and a half years. Thereafter, CT and upper endoscopy showed a submucosal tumor with a central recess developing in the stomach wall. It was suspected that the gastric tumor was either a metastasis of rectal cancer or a submucosal tumor-like gastric cancer. We performed a radical operation to remove the lesion. In the resected specimen, immunohistopathological findings including HER2 status suggested that the gastric tumor was a primary gastric cancer resembling a submucosal tumor.

Topics: Antimetabolites, Antineoplastic; Drug Combinations; Gastric Mucosa; Humans; Male; Middle Aged; Neoplasms, Second Primary; Oxonic Acid; Rectal Neoplasms; Stomach Neoplasms; Tegafur

A 71-year-old man was admitted to our hospital because of abdominal pain. An upper gastrointestinal endoscopy revealed a type 3 tumor in the lesser curvature of the gastric body. A computed tomography (CT) scan showed synchronous liver metastasis in liver S6 and S8, and a large 8a lymph node that could be encased within the common hepatic artery. The patient was diagnosed with gastric cancer with liver metastasis, Stage Ⅳ, and treated with chemotherapy (S-1 plus CDDP). After 3 courses, a CT scan showed that the liver metastasis in S8 was reduced in size.The one in S6 completely disappeared. The 8a lymph node was also reduced in size and revealed to be separated from the common hepatic artery. Total gastrectomy (D2) and radiofrequency ablation (RFA) for the S8 lesion were performed. The postoperative course was favorable and the patient was treated with postoperative adjuvant chemotherapy consisting of S-1. No recurrence has been observed for 17 months after diagnosis. After chemotherapy, if R0 resection is performed, surgical resection and RFA for liver metastasis may be a useful option for gastric cancer with liver metastasis.

Topics: Aged; Antimetabolites, Antineoplastic; Catheter Ablation; Combined Modality Therapy; Drug Combinations; Gastrectomy; Humans; Liver Neoplasms; Lymph Node Excision; Lymphatic Metastasis; Male; Oxonic Acid; Stomach Neoplasms; Tegafur

A 77-year-old man was found to have advanced gastric cancer and underwent total gastrectomy (pT4aN2H0P0M0, Stage ⅢB). Two years after gastrectomy, we found an elevated tumor marker level, and a liver metastasis appeared in segment 5 (20 mm in diameter). He was treated with S-1/CDDP combination chemotherapy. After 2 courses of chemotherapy, the tumor marker level kept rising and a CT scan detected a progressive tumor. S-1/irinotecan combination chemotherapy was administered as second-line chemotherapy. After 6 courses of chemotherapy, the size of the liver metastasis was reduced and the tumor marker level normalized. Because lymph node metastasis or peritoneal recurrence was observed, a partial resection of the liver (S5) was performed. After the operation, he was treated with S-1 chemotherapy again for 1 year and has had no recurrence.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cisplatin; Drug Combinations; Gastrectomy; Hepatectomy; Humans; Irinotecan; Liver Neoplasms; Male; Oxonic Acid; Stomach Neoplasms; Tegafur; Treatment Outcome

We report a long surviving case of gastric cancer with a synchronous adrenal metastasis in a patient who underwent curative resection. The patient was a 74-year-old man. Endoscopic examination revealed a type 3 gastric cancer in the proximal stomach. Abdominal computed tomography (CT) revealed a soft tissue density mass in the right adrenal gland and a high-density mass suspected as hemangioma in the left adrenal gland. The CT scan indicated no other distant metastasis. The patient had no endocrine abnormalities according to blood test results. Total gastrectomy with D2 lymphadenectomy and right adrenalectomy were performed in August 2003. On histopathological examination, the gastric tumor was diagnosed as a poorly differentiated adenocarcinoma. The histopathological findings of the right adrenal tumor were compatible with those of gastric cancer. The final diagnosis was por1, 105×65 mm, pT2 (SS), pN1 (#1: 2/8, #3: 1/11), P0, H0, CY0, pM1 (ADR), pStage Ⅳ. Two months after the surgery, the patient was treated with adjuvant TS-1 monotherapy (80 mg/m2 day 1-28/q6w) for 1 year 9 months. The patient had been in good health without a recurrence for more than 9 years 3 months after the operation.

Topics: Adenocarcinoma; Adrenal Gland Neoplasms; Adrenalectomy; Aged; Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Drug Combinations; Gastrectomy; Humans; Male; Oxonic Acid; Prognosis; Stomach Neoplasms; Tegafur

The patient was a 75-year-old man with a history of gastrectomy with combined resection of the transverse colon ligament for gastric cancer in July 2011. He was diagnosed with adenocarcinoma (tub2, tub1), L, Ant-Gre, type 2, pT4b (SI: transverse colon ligament) and pN3b, H0, M0, P0, CY0, Stage ⅢC. On abdominal computed tomography 7 months after surgery a peritoneal metastasis was seen near the transverse colon. The patient was treated with resection for peritoneal dissemination with part of the transverse colon. Three years after the last surgery, the patient is still alive without relapse.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Gastrectomy; Humans; Male; Oxonic Acid; Paclitaxel; Peritoneal Neoplasms; Stomach Neoplasms; Tegafur; Time Factors

The patient was a 59-year-old woman with advanced double cancers of the stomach and endometrium with peritoneal metastasis. Abdominal computed tomography revealed that the endometrial cancer was more advanced than the gastric cancer; therefore, the peritoneal metastasis was diagnosed as arising from the endometrial cancer. Treatment of the endometrial cancer with cytoreductive surgery followed by adjuvant chemotherapy was performed first. She underwent total hysterectomy, bilateral salpingo-oophorectomy, and omentectomy. Disseminated nodules were found throughout her abdomen. The histopathological findings indicated carcinosarcoma of the uterus, pT3bNXM1, Stage Ⅳb. One month after surgery, she received 6 courses of adjuvant chemotherapy with paclitaxel plus carboplatin. After the adjuvant chemotherapy, abdominal computed tomography revealed that both the ascites and the disseminated nodules had disappeared. Therefore, a second-look surgery for the endometrial cancer and definitive surgery for the gastric cancer were planned. At the laparotomy, no disseminated nodules were found, so distal gastrectomy and D2 lymphadenectomy were performed. The histopathological findings were pT4aN1M0P0Cy0, Stage ⅢA. She received adjuvant chemotherapy with S-1 for 1 year, and has been alive with no evidence of recurrence for 2 years and 7 months after the initial surgery.

Topics: Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Drug Combinations; Endometrial Neoplasms; Female; Gastrectomy; Humans; Hysterectomy; Middle Aged; Oxonic Acid; Paclitaxel; Peritoneal Neoplasms; Prognosis; Stomach Neoplasms; Tegafur

The patient was a 57-year-old woman. In October 2011, she underwent distal gastrectomy, D2 lymphadenectomy, and Roux-en-Y reconstruction for gastric cancer (pT4a, pN3b, Stage ⅢC [JCGC 14th Edition]). She then received S-1 plus CDDP combination therapy and S-1 monotherapy as postoperative adjuvant chemotherapies for 1 year, and was followed up as an outpatient. In April 2013, a significant increase in the CA19-9 level was noted, and CT indicated a right ovarian tumor. Ovarian metastasis from the gastric cancer was diagnosed, and the response to 3 courses of weekly PTX was stable disease. No findings indicated metastasis to other organs. In July 2013, a salpingo-oophorectomy was performed, after which her CA19-9 level returned to the normal range. Follow-up was adopted as the postoperative strategy in part due to the desires of the patient. Presently, 3 years and 6 months after the initial surgery and 1 year and 9 months after the last surgery, no recurrence has been detected. Generally, ovarian metastasis from gastric cancer is considered to be associated with a poor prognosis. However, our patient showed long-term survival after surgeries for gastric cancer and asynchronous ovarian metastasis. Here, we report the details of our case and review the relevant literature.

Topics: Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Female; Gastrectomy; Humans; Middle Aged; Ovarian Neoplasms; Ovariectomy; Oxonic Acid; Paclitaxel; Stomach Neoplasms; Tegafur; Time Factors

A 68-year-old man was admitted to our hospital. He was diagnosed with advanced gastric cancer with multiple liver metastases. The primary tumor was treated with distal gastrectomy with D2 dissection and anti-cancer agents, and then he was scheduled for a 2-stage hepatic resection. After surgery, the liver metastases disappeared, and he was diagnosed with a CR. However he complained of dizziness and was diagnosed with metachronous brain matastasis. Multidisciplinary treatment including resection and radiotherapy was administerd and he survived for 5 years after diagnosis.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Cisplatin; Combined Modality Therapy; Drug Combinations; Gastrectomy; Humans; Liver Neoplasms; Lymphatic Metastasis; Male; Oxonic Acid; Prognosis; Radiosurgery; Stomach Neoplasms; Tegafur

A 79-year-old woman with symptomatic pyloric stenosis was diagnosed with advanced gastric cancer. CT revealed that the tumor had invaded into the pancreatic head.Since no contraindications were found at laparotomy, we performed pancreatoduodenectomy. The histopathologic diagnosis was pT4b (panc), pN3a (11/35), P0, CY0, H0, M0, pStage ⅢC, R0. The patient received adjuvant chemotherapy with S-1 for 1 year. The patient has survived without recurrence for more than 2 years. The efficacy of pancreatoduodenectomy for advanced gastric cancer is still controversial. Pancreatoduodenetomy may be indicated for selected cases of advanced gastric cancer, if an R0 resection can be achieved.

Topics: Aged; Antimetabolites, Antineoplastic; Drug Combinations; Female; Gastrectomy; Humans; Neoplasm Invasiveness; Oxonic Acid; Pancreas; Pancreaticoduodenectomy; Stomach Neoplasms; Tegafur; Time Factors

A 60s male was admitted to our hospital because of appetite loss and nausea. After examination, he was diagnosed with type 3 advanced gastric cancer in the antrum. Abdominal computed tomography showed gastric cancer invasion to the left liver lobe. We initiated neoadjuvant chemotherapy using S-1 plus CDDP after laparoscopic gastrojejunostomy. S-1 was orally administered for 3 weeks followed by a 2-week drug-free period. CDDP was administered intravenously on day 8 of each course. After 5 courses of chemotherapy, the gastric cancer was reduced in size. We therefore performed total gastrectomy with D2-affiliated left liver resection. S-1 plus CDDP is expected to improve outcomes in unresectable or locally advanced gastric cancer.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Humans; Liver Neoplasms; Lymphatic Metastasis; Male; Neoadjuvant Therapy; Oxonic Acid; Recurrence; Stomach Neoplasms; Tegafur

A 71-year-old man was diagnosed with gastric cancer (LM, Less, type 2, T4aN2M0, cStageⅢb). A diagnostic laparoscopic surgery revealed serosal invasion without peritoneal dissemination. Two courses of neoadjuvant chemotherapy (NAC) for locally advanced gastric cancer using DCS (DTX: 20 mg/m2 on day 1, CDDP: 50 mg/m2 on day 1, S-1: 120 mg/day, twice a day on days 1-14) was performed, which resulted in a clinical partial response. Consequently, distal gastrectomy with D2 lymph node dissection, and BillrothⅠreconstruction were carried out. Histopathological examination revealed no residual cancer cells both in the primary lesion and in the lymph nodes, indicating a pathological complete response (grade 3). Six courses of S-1 (120 mg/day on days 1-28, followed by 2 weeks of rest) were administered as adjuvant chemotherapy. At the 2 years 10 months follow-up after adjuvant therapy, the patient has had no recurrence. Combination chemotherapy with NAC-DCS can be a safe and effective regimen for locally advanced gastric cancer.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Docetaxel; Drug Combinations; Humans; Lymph Node Excision; Lymphatic Metastasis; Male; Neoadjuvant Therapy; Oxonic Acid; Prognosis; Stomach Neoplasms; Taxoids; Tegafur

A 59-year-old man presented with epigastralgia. A diagnosis of advanced gastric cancer MLU, Circ, Type 3, 160 mm, tub2, cT4b (SI: panc), cN1, cM0, cH0, cP0, cCY0, cStage ⅢB was made. Because of difficulty with oral intake due to malignant outlet obstruction and tumor bleeding, endoscopic self-expanding metallic stent placement was performed. We administered chemotherapy involving docetaxel, cisplatin, and S-1(DCS). After 2 courses of chemotherapy, the primary lesion and regional lymph nodes had reduced in size. His response was judged as SD according to the RECIST criteria. The patient elected to undergo explorative laparotomy for assessment of the gastric cancer. The intraoperative findings showed that there was no pancreatic invasion, peritoneal dissemination, or distal metastasis, so a total gastrectomy and D2 lymph node dissection was performed. The pathological findings showed that there were very few cancer cells in the primary lesion, and a lymph node metastasis was found. The final stage was gastric cancer MLU, Circ, Type 3, 100 mm, muc, ypT4a(SE), ypN3a (13/51), ypM0, ypH0, ypP0, ypCY0, ypStage ⅢC. The therapy evaluation was Grade 1b. In summary, we encountered a patient with gastric cancer in whom curative surgery was made possible by undergoing chemotherapy and metallic stent placement.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Docetaxel; Drug Combinations; Gastrectomy; Humans; Lymph Node Excision; Lymphatic Metastasis; Male; Metals; Middle Aged; Neoadjuvant Therapy; Oxonic Acid; Stents; Stomach Neoplasms; Taxoids; Tegafur

A 72-year-old man underwent surgery for advanced gastric cancer. Systemic chemotherapy was started, using a regimen of S-1/CDDP for 4 courses, followed by 8 courses of S-1. Three years and 8 months after the surgery, abdominal CT demonstrated ascites, and the serum CA19-9 level was abnormally high (1,165.1 U/mL). Adenocarcinoma cells were found in the ascites. Treatment with S-1/docetaxel (DOC) was started. After 10 courses, the ascites disappeared and the serum CA19-9 value returned to normal. Four years and 7 months after the operation, the patient has been in good health, with no signs of recurrence.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Docetaxel; Drug Combinations; Gastrectomy; Humans; Male; Oxonic Acid; Peritoneal Neoplasms; Stomach Neoplasms; Taxoids; Tegafur; Treatment Outcome

Here, we report 2 patients with gastric cancer and peritoneal dissemination who were successfully treated with chemotherapy after undergoing treatment for an oncologic emergency caused by peritoneal dissemination. Case 1 involved obstruction of the sigmoid colon caused by peritoneal dissemination. After urgent colostomy, S-1/IP IV paclitaxel chemotherapy was introduced. The patient continued the therapy for 2 years and 2 months. Case 2 involved acute renal failure due to bilateral ureter obstruction and obstructive jaundice caused by peritoneal dissemination. This patient underwent emergency treatment consisting of Double-J ureteral stent insertion and endoscopic nasobiliary drainage. He was successfully started on chemotherapy with S-1/oxaliplatin/IP paclitaxel. He continued the therapy for 8 months without symptoms. Aggressive treatment might be effective for advanced gastric cancer showing oncologic emergency.

Topics: Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Female; Humans; Ileus; Jaundice, Obstructive; Male; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Paclitaxel; Peritoneal Neoplasms; Stomach Neoplasms; Tegafur

Here, we report a 54-year-old man diagnosed with type 3 advanced gastric cancer who underwent a total gastrectomy and splenectomy plus D2 lymphadenectomy. The pathologic diagnosis was Stage Ⅳ (T3N0H0P0CY1M1). Sixteen courses of combined S-1/CPT-11 chemotherapy were completed, at which time the CPT-11 was discontinued because of malaise, and S-1 alone was continued for a year. The patient is well and has been recurrence-free for 7 years. Thus, he is considered a long- term survivor who was treated with combination S-1/CPT-11 chemotherapy.

Topics: Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Drug Combinations; Humans; Irinotecan; Lymph Node Excision; Lymphatic Metastasis; Male; Middle Aged; Oxonic Acid; Prognosis; Splenectomy; Stomach Neoplasms; Tegafur; Time Factors

Here, we report a case of advanced gastric cancer that demonstrated CR after treatment with S-1 and paclitaxel. The patient was an 80-year-old woman with gastric cancer in whom upper gastrointestinal endoscopy (GIF) revealed a type 3 tumor in the cardia of the stomach that was pathologically diagnosed as a well-differentiated adenocarcinoma. Computed tomography showed no lymph node involvement or metastasis. Considering her advanced age and cardinal functional disorder, she was administered chemotherapy consisting of S-1 and paclitaxel. Depending on a state, a side effect, I changed a dose and inter-dose interval from head to foot and I treated it by foreign going to hospital and continued it. Gradual tumor reduction was observed on GIF (2011/1/25). CR was diagnosed without tumor disappearance, with accepted malignant findings on biopsy. The patient has now survived for 7 years 9 months after diagnosis. The present case demonstrates that combination therapy of S-1 and paclitaxel is safe and useful for patients with risk factors such as advanced age and underlying disease.

Topics: Adenocarcinoma; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Female; Humans; Oxonic Acid; Paclitaxel; Prognosis; Remission Induction; Stomach Neoplasms; Tegafur

This study aimed to evaluate the efficacy of protein-bound polysaccharide K (PSK)-containing chemotherapy in patients with unresectable advanced or recurrent gastric cancer (AGC). We retrospectively analyzed 190 patients with AGC who received systemic chemotherapy including 69 patients who were treated with a PSK-containing regimen. Using propensity score matching, we obtained 62 matched patients in the S-1 and S-1 plus PSK groups for outcomes analysis. There was a tendency for overall survival to be higher in the S-1 plus PSK group than in the S-1 alone group. In particular, there was a tendency for overall survival in the S-1 plus PSK group to be higher in patients with a neutrophil/lymphocyte ratio (NLR)<2.2 than in patients with a NLR<2.2. There was a tendency for fewer changes in the NLR after the beginning of treatment in the S-1 plus PSK group than in the S-1 alone group. PSK-containing chemotherapy may contribute to improved treatment outcomes of AGC patients. In particular, it may be effective in patients with a high NLR. Further investigations, including a prospective randomized controlled trial, are expected to verify the mechanisms of interaction between cancer cells and the immunoreaction.

Topics: Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Humans; Leukocyte Count; Lymphocytes; Neutrophils; Oxonic Acid; Polysaccharides; Retrospective Studies; Stomach Neoplasms; Tegafur; Treatment Outcome

A 69-year-old man was diagnosed with advanced gastric cancer and underwent total gastrectomy (tubular adenocarcinoma, tub2, pT3N0M0, stageⅡA). Eight months after the surgery, recurrence on the anastomosis was observed. Tumor invasion of the aortic artery was suspected, and the patient was considered inoperable. He was treated with S-1/CDDP plus trastuzumab therapy as a neoadjuvant chemotherapy regimen. After 4 courses of the chemotherapy, significant tumor reduction was observed, and the patient underwent anastomosis resection. Chemotherapy with trastuzumab appears to be an effective NAC treatment for HER2-positive, advanced gastric cancer.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Gastrectomy; Humans; Male; Neoplasm Recurrence, Local; Oxonic Acid; Stomach Neoplasms; Tegafur; Trastuzumab

Trastuzumab, a humanized monoclonal antibody against human epidermal growth factor receptor 2 (HER2), has been proven to result in a survival benefit for the treatment of patients with HER2-positive advanced gastric cancer (AGC). However, data are lacking for the treatment of those with disseminated intravascular coagulation (DIC) and diffuse bone marrow carcinomatosis. A 77-year-old woman presented with back pain and fatigue since 2 months. Esophagogastroduodenoscopy showed a scirrhous lesion in the gastric corpus, which was biopsied and identified as signet-ring cell carcinoma with HER2 overexpression on immunohistochemistry. Laboratory testing, bone scintigraphy, and bone marrow biopsy were conducted, and she was diagnosed with HER2-positive AGC with DIC and diffuse bone marrow carcinomatosis. She underwent chemotherapy with the following regimen: oral administration of 80 mg/m2 S-1 for 2 weeks and 6 mg/kg trastuzumab infusion on day 6 every 3 weeks, which significantly improved the DIC. She was discharged from the hospital 73 days after admission and survived for 438 days after diagnosis. To the best of our knowledge, this is the first case report in which HER2-positive AGC complicated by DIC with diffuse bone marrow carcinomatosis was successfully treated with combined chemotherapy consisting of S-1 plus trastuzumab.

Topics: Aged; Anticoagulants; Antineoplastic Combined Chemotherapy Protocols; Biopsy; Bone Marrow Neoplasms; Bone Neoplasms; Carcinoma, Signet Ring Cell; Disseminated Intravascular Coagulation; Drug Combinations; Fatal Outcome; Female; Humans; Oxonic Acid; Receptor, ErbB-2; Stomach Neoplasms; Tegafur; Trastuzumab

A 58-year-old woman with advanced gastric cancer underwent total gastrectomy in May 2012. The histological diagnosis was poorly differentiated adenocarcinoma, cT4a (SE), pN1, cM0; fStage IIIA. Chemotherapy by S-1 was started after surgery. Six months after the operation, two metastatic nodules were noticed on the liver. Therefore, the chemotherapy was switched to S-1 plus cisplatin (CDDP) in November 2012. TS-1 (80 mg/body) was administrated from day 1 to 21 followed by 14 days rest as one course. CDDP (70 mg/body) was infused on day 1. After 3 courses of this combination chemotherapy, remarkable diminution of the metastatic lesions on CT images was observed. Because of the adverse event of Grade 2 nausea, the patient was forced to discontinue chemotherapy. The patient underwent partial resection of the liver (Hr-0: S8, S7) at 1 year after the first operation. The resected specimens showed no sign of malignancy, although uneven fatty deposition was observed more frequently than in the surroundings, and designated as histologically complete response (CR). The patient has been alive 30 months after the second operation without any recurrent sites. Thus, combined use of peroral S-1 and CDDP should be recommended for multiple liver metastases after gastrectomy.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Biopsy; Chemotherapy, Adjuvant; Cisplatin; Drug Combinations; Female; Gastrectomy; Gastroscopy; Hepatectomy; Humans; Liver Neoplasms; Middle Aged; Neoplasm Staging; Oxonic Acid; Remission Induction; Stomach Neoplasms; Tegafur; Time Factors; Tomography, X-Ray Computed; Treatment Outcome

We previously reported that S-1 plus cisplatin was feasible as adjuvant chemotherapy for stage III gastric cancer after D2 gastrectomy. Herein we evaluate the recurrence-free survival and overall survival rates as secondary endpoints based on updated follow-up data.. Patients with stage III gastric cancer who underwent D2 gastrectomy were enrolled. Treatment consisted of 3 cycles of S-1 (40 mg/m(2) PO) twice daily on days 1-21 and cisplatin (60 mg/m(2) IV) on day 8, and S-1 was given on days 1-28 every 6 weeks until 1 year after surgery.. From August 2007 to September 2009, 63 patients were accrued. Overall, 34 and 25 patients had stage IIIA and IIIB disease, respectively. After a median follow-up of 3.9 years, 16 patients experienced recurrence and 11 patients died. The 3-year recurrence-free survival rate was 74.1 % (95 % CI: 60.8-83.5 %, IIIA 81.8 %, IIIB 64.0 %). The 3-year overall survival rate was 84.5 % (95 % CI: 72.3-91.6 %, IIIA 87.9 %, IIIB 80.0 %). Recurrence sites included the peritoneum (n = 8), hematogenous sites (n = 6), and lymph nodes (n = 4).. The present results indicate that adjuvant therapy with S-1 plus 3 cycles of cisplatin may provide a survival benefit to patients with stage III gastric cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cisplatin; Drug Combinations; Follow-Up Studies; Humans; Lymphatic Metastasis; Neoplasm Recurrence, Local; Neoplasm Staging; Oxonic Acid; Peritoneal Neoplasms; Prognosis; Stomach Neoplasms; Survival Rate; Tegafur

Peritoneal metastasis of gastric cancer has extremely poor clinical outcomes. Recently, we developed a combination chemotherapy that used intraperitoneal (IP) paclitaxel (PTX) and produced excellent antitumor effects against peritoneal lesions. However, no information is available about the benefit of gastrectomy in cases with malignant ascites.. A total of 64 patients with severe peritoneal metastasis and ascites received IP PTX at 20 mg/m(2) via implanted subcutaneous peritoneal access ports as well as intravenous (IV) PTX at 50 mg/m(2) on days 1 and 8. S-1 was administered at 80 mg/m(2) day for 14 consecutive days, followed by 7 days of rest. In all patients, investigative laparoscopy was performed around the combination chemotherapy, and gastrectomy was performed on patients who showed apparent shrinkage of their peritoneal nodules as well as negative peritoneal cytology at the second laparoscopy.. Gastrectomy was performed in 34 patients. The median course of chemotherapy before surgery was 5 courses (range 2-16). R0 operation was achieved in 22 patients (65%), and grade 2 and 3 histological responses were obtained in 7 (21%) and 1 (3%) patient(s), respectively. The median survival time and 1-year overall survival of the gastrectomized patients were 26.4 months and 82%, and those of the 30 patients who did not receive gastrectomy were 12.1 months and 26%, respectively. Morbidity was minimal, and there was no mortality.. Salvage gastrectomy after chemotherapy of S-1 with IV and IP PTX is promising, even for patients with highly advanced gastric cancer and severe peritoneal metastasis and malignant ascites.

Topics: Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Ascites; Combined Modality Therapy; Drug Combinations; Female; Follow-Up Studies; Humans; Injections, Intraperitoneal; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Ovarian Neoplasms; Oxonic Acid; Paclitaxel; Peritoneal Neoplasms; Prognosis; Salvage Therapy; Stomach Neoplasms; Survival Rate; Tegafur

The long-term outcomes of advanced gastric cancer (AGC) patients treated with S-1 plus cisplatin (SP) combination chemotherapy remain unclear. Therefore, we sought to evaluate these outcomes to identify the prognostic factors affecting patient survival.. We retrospectively analyzed 153 AGC patients treated with SP at a single institution between January 2005 and July 2011.. Median overall survival (OS) was 15.0 months [95 % confidence interval (CI), 12.5-17.9 months]. Three independent prognostic factors affecting poor survival were identified: performance status (PS) ≥ 1 [hazard ratio (HR) = 2.39, 95 % CI, 1.58-3.62); >1 metastatic site (HR = 1.57, 95 % CI, 1.10-2.26], and elevated alkaline phosphatase levels (HR = 1.70, 95 % CI, 1.16-2.49). A simple prognostic index was generated using three risk groups: good (no risk factor), moderate (one or two risk factors), and poor (three risk factors). The median OS for good-, moderate-, and poor-risk groups was 28.6, 14.8, and 7.3 months, respectively (log-rank test; P < 0.0001). Among the twelve 3-year survivors, 9 (75 %) had a PS of 0 and 8 (67 %) had only one metastatic site.. Three prognostic factors were identified in AGC patients treated with SP. Using a simple prognostic index, the patients were divided into three risk groups, in which the survival differences were markedly significant, suggesting that patients with good PS and only one metastatic site may have a higher chance of long-term survival than those with poor PS and multiple metastatic sites.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Disease-Free Survival; Drug Combinations; Female; Fluorouracil; Humans; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Prognosis; Stomach Neoplasms; Tegafur; Treatment Outcome

Combination chemotherapy with trastuzumab and cisplatin plus capecitabine or 5-fluorouracil has been used as a standard regimen for HER2-positive gastric cancer (GC) since the Trastuzumab for Gastric Cancer (ToGA) trial. Before the ToGA trial, HER2-positive GC in Japan was treated with S-1 plus cisplatin (SP). The primary objective of this retrospective study was to explore the efficacy of SP in HER2-positive GC.. We reviewed patients who had received SP as first-line chemotherapy at our institute between April 2007 and March 2011 and from whom we had enough samples to examine HER2 status. Seventy-seven patients fulfilled the selection criteria and were tested for HER2 status with immunohistochemical staining (IHC) and fluorescence in situ hybridization. The patients' backgrounds were investigated to evaluate the clinicopathologic features of their HER2-positive GC, including survival.. Seven (9.1 %) of 77 patients were judged to be IHC3+, and all of these had predominantly differentiated histology. HER2 positivity was associated with differentiated histology (P = 0.016) and liver metastasis (P = 0.025). Median overall survival was 23.6 months [95 % confidence interval (CI) 0.8-44.7] in HER2-positive GC and 12.9 months (95 % CI 8.3-17.5) in HER2-negative disease, but the difference was not statistically significant (P = 0.615). In multivariate analysis, HER2 status was not associated with survival outcomes.. Because of the retrospective nature of this study, we cannot conclude whether HER2 status influences the survival of patients who receive SP as first-line chemotherapy. Our study provides important historical data for prospective phase II studies of SP plus trastuzumab.

Topics: Adult; Aged; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Female; Humans; In Situ Hybridization, Fluorescence; Japan; Male; Middle Aged; Oxonic Acid; Receptor, ErbB-2; Retrospective Studies; Stomach Neoplasms; Tegafur; Trastuzumab

S-1 has been recommended as adjuvant chemotherapy in patients after curative surgery for gastric cancer. However, some patients suffer recurrence even after S-1 adjuvant chemotherapy. The present study was conducted to find a predictive marker of the efficacy of S-1 adjuvant chemotherapy. We examined the microRNA (miRNA) expression of 35 patients who underwent S-1 adjuvant chemotherapy after curative surgery (R0) for pathological stage II or III gastric cancer. miRNAs were extracted from formalin-fixed, paraffin-embedded specimens for analysis and miRNA expression was examined using miRNA oligo chips. Fifteen patients relapsed and 20 did not over 5 years. Five miRNAs (miR-92b, 422a, 4732-5p, 4758-3p and 221) were highly expressed according to the tumor/normal (T/N) ratio in the patients who relapsed but not in those who did not relapse (P-value <0.05) by microarray analysis. If tumors showed high expression of 4 miRNAs (miR-92b, 422a, 4732-5p and 4758-3p) their positive predictive value of relapse was 93.8% and negative predictive value was 92.3%. In this case, their disease-free survival rate and overall survival rate were very poor. Our findings indicate that miR-92b, miR‑422a, miR-4732-5p and miR-4758-3p are closely associated with relapse following S-1 adjuvant chemotherapy in gastric cancer.

Topics: Aged; Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Disease-Free Survival; Drug Combinations; Female; Gene Expression Regulation, Neoplastic; Humans; Male; MicroRNAs; Middle Aged; Neoplasm Recurrence, Local; Oxonic Acid; Stomach Neoplasms; Survival; Tegafur

Management of peritoneal disseminated gastric cancer (GC) remains a challenging problem. The purpose of our study was to evaluate the outcome of bidirectional induction chemotherapy [bidirectional intraperitoneal and systemic induction chemotherapy (BIPSC)] in patients with peritoneal carcinomatosis (PC) arising from GC who underwent cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC).. Overall, 194 patients with PC arising from GC were treated with BIPSC comprising intraperitoneal docetaxel at a dose of 20 mg/m(2) and cisplatin at a dose of 30 mg/m(2) followed by four cycles of oral S-1 at a dose of 60 mg/m(2). CRS and HIPEC were performed in responders to BIPSC.. Of these 194 patients, 152 (78.3 %) underwent CRS and HIPEC between January 2005 and December 2012. Treatment-related mortality was 3.9 %, and major complications occurred in 23.6 % of patients. The median survival rate was 15.8 months, with 1-, 2-, and 5-year survival rates of 66, 32 and 10.7 %, respectively, in the patients treated with combined treatment. Multivariate analysis identified pathologic response to BIPSC (p = 0.001), low tumor burden [peritoneal cancer index (PCI) ≤ 6] (p = 0.001), and completeness of CRS (CC-0, CC-1) (p = 0.001) as independent predictors for a better prognosis.. As a viable option, BIPSC with CRS and HIPEC for patients with PC arising from GC may be performed safely, with acceptable morbidity and mortality, in a specialized unit. Response to BIPSC, optimal CRS and limited peritoneal dissemination seem to be essential to achieve the best outcomes in these patients.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Cancer, Regional Perfusion; Cisplatin; Combined Modality Therapy; Docetaxel; Drug Combinations; Female; Follow-Up Studies; Gastrectomy; Humans; Hyperthermia, Induced; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Oxonic Acid; Peritoneal Neoplasms; Prognosis; Prospective Studies; Stomach Neoplasms; Survival Rate; Taxoids; Tegafur

This study is aimed to assess the efficacy and toxicity of weekly liposome-paclitaxel and S-1 combination therapy as first-line treatment for advanced gastric cancer.. The chemotherapy regime was 80 mg/m(2) liposome-paclitaxel given on days 1, 8, 15 and 22, combined with S-1 60 mg (body surface area > 1.5) or 50 mg (1.25 < body surface area < 1.5) twice a day on days 1-28, 6 weeks as one cycle. The patients continued to be treated until they received four cycles or until they developed either progressive disease or untolerated toxicity. The response rate, progression-free survival, overall survival and toxicity were evaluated.. A total of 56 patients were enrolled, and the median age was 60 years (range = 38-70 years; 39 males and 17 females). The response rate and disease control rate were 25% (14/56) and 87.5% (49/56), respectively. The median progression-free survival was 6.1 months (95% confidence interval: 5.0-7.2), and the median overall survival was 10.6 months (95% confidence interval: 7.2-14.0). The most frequent hematological toxicities were neutropenia and anemia, which occurred in 22 (48.9%) and 11 (19.6%) patients, respectively.. The weekly administration of a combined regimen of liposome-paclitaxel plus S-1 is effective and has a favorable toxicity profile for advanced gastric cancer.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Diarrhea; Disease-Free Survival; Drug Administration Schedule; Drug Combinations; Female; Humans; Kaplan-Meier Estimate; Liposomes; Male; Middle Aged; Neutropenia; Oxonic Acid; Paclitaxel; Stomach Neoplasms; Tegafur; Treatment Outcome

The optimal radiotherapy technique and combination with systemic therapy in locally advanced gastric cancer patients are far from being resolved despite the fact that radiochemotherapy is becoming more attractive in contemporary clinical practice.. 40 patients with locally advanced gastric cancer received intensity-modulated radiotherapy (IMRT) at a dosage of 45-50.4 Gy concurrent with chemotherapy using S-1 solely or with a combination of oxaliplatin. Surgery was recommended for those who were evaluated as resectable. Sequential chemotherapy with various regimens was adopted based on the efficacy and tolerance of radiochemotherapy.. The overall response rate was 75% according to Response Evaluation Criteria in Solid Tumors and Japanese Gastric Cancer Association criteria. 24 finally underwent surgery, with 22 (91.7%) receiving an R0 resection (resection for cure or complete remission). The overall pathological response rate was 37.5% (9/24). Patients receiving an R0 resection had a higher 2-year overall survival rate (64.7 vs. 16.2%, p = 0.001) and local relapse-free survival rate (90.2 vs. 29.3%, p = 0.000), while there was no difference in distant metastasis-free survival rate (66.1 and 48.1% p = 0.231). Hematological and gastrointestinal toxicities of grade 1 or grade 2 were relatively common.. The high rate of R0 resections and low rate of locoregional recurrence suggest that IMRT combined with S-1-based chemotherapy is an effective treatment for locally advanced gastric cancer patients.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Chemoradiotherapy; Disease-Free Survival; Drug Combinations; Female; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Oxonic Acid; Radiotherapy, Conformal; Retrospective Studies; Stomach Neoplasms; Survival Rate; Tegafur; Treatment Outcome

Both docetexal plus S-1 (DS) and oxaliplatin plus S-1 (SOX) are active regimens currently used in patients with advanced gastric cancer. In this retrospective study, efficacy and safety of these 2 combination regimens were evaluated.. Patients received docetaxel infusion 75 mg/m(2) in the DS group or oxaliplatin infusion 130 mg/m(2) in the SOX group at day 1 of each 3-week cycle. S-1 40 mg/m(2) was administered orally twice daily on days 1-14 in the 3-week cycle in both groups. Progression-free survival (PFS), overall survival (OS) and safety perimeters were evaluated.. 84 patients were retrospectively evaluated in the study: 36 patients in the DS group and 48 patients in the SOX group. The median PFS was 6.55 months in the DS group and 5.73months in the SOX group. The median OS was 13.97 in the DS group and 13.13 months in the SOX group. The overall response rates were 41.7% and 43.8% and the disease control rates were 77.8% and 87.5% for DS and SOX, respectively. The most frequent grade 3 and 4 toxicities were thrombocytopenia for DS (19.4%) and anemia for SOX (12.5%).. Both regimens were active and well tolerated in advanced gastric cancer patients. © 2014 S. Karger GmbH, Freiburg.

Topics: Adult; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Female; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Retrospective Studies; Stomach Neoplasms; Tegafur; Thrombocytopenia; Treatment Outcome

A 78-year-old woman was admitted to our hospital complaining of anorexia and purpura of the extremities. She presented with prominent peripheral eosinophilia and disseminated intravascular coagulation (DIC). Despite receiving intensive therapy for DIC, her illness worsened. Esophagogastroduodenoscopy revealed advanced gastric cancer (AGC), and a bone marrow biopsy led to a diagnosis of disseminated carcinomatosis of the bone marrow caused by AGC. We initiated combination chemotherapy with S-1 and cisplatin, which lead to a significant improvement of the DIC and eosinophilia, and the patient was finally discharged. The primary symptoms of DIC and eosinophilia were both considered to be caused by AGC, and we successfully treated the patient's critical condition.

Topics: Aged; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Biopsy; Bone Marrow; Bone Marrow Neoplasms; Cisplatin; Disseminated Intravascular Coagulation; Drug Combinations; Eosinophilia; Female; Humans; Oxonic Acid; Purpura; Stomach Neoplasms; Tegafur; Treatment Outcome

Here we report a case of unresected gastric cancer that maintained long tumor dormancy by use of paclitaxel+S-1 combination therapy. A 58-year-old woman was admitted to the hospital for peritoneal dissemination of unresectable gastric cancer. The patient further showed ileus with peritoneal dissemination in computed tomography(CT), and we performed resection of the intestine to release the stenosis. In addition, combination chemotherapy using paclitaxel(60mg/m2, weekly) and S-1(80mg/m2, every 2 weeks)was started after the operation. The patient was discharged from the hospital 7 3 days after the operation, and we continued combination chemotherapy as an outpatient over the following 3 years without serious side effects. Furthermore, tumor makers for gastric cancer were stable, although we could not examine tumor size since the patient rejected examinations such as CT. After 3 years, the patient was admitted to the hospital with cholecystitis, and we were able to evaluate the benefit of the chemotherapy against gastric cancer. The tumor size clearly remained unchanged compared to previous measurements, suggesting that the tumor maintained dormancy in this case.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Female; Humans; Middle Aged; Oxonic Acid; Paclitaxel; Peritoneal Neoplasms; Stomach Neoplasms; Tegafur; Treatment Outcome

We report a case of a patient with unresectable gastric cancer who showed complete response(CR)to S-1 and paclitaxel (PTX)combination therapy. The patient(a 67-year-old woman)was diagnosed with unresectable advanced gastric cancer with metastases in the Virchow's lymph nodes and para-aortic lymph nodes. Systemic chemotherapy with 70mg/m2 S-1 (days 1-14)and 70mg/m2 PTX(day 1)was administered every 3 weeks. At the end of 7 courses of chemotherapy, the primary lesion and swollen lymph nodes became markedly smaller. After 7 courses, an additional 39 courses were administered over 2.5 years. No notable adverse events were seen, and the patient's performance status(PS)was 0. CR was monitored by imaging studies. No cancer cells were detected on cytological examination of the primary lesion. Monotherapy with 70mg/m2 S-1(days 1-28, 2-week drug holiday)has been administered for the past 3 years. The patient is currently treated as an outpatient and maintains CR and a PS of 0.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Female; Humans; Lymphatic Metastasis; Neoplasm Staging; Oxonic Acid; Paclitaxel; Remission Induction; Stomach Neoplasms; Tegafur

A 67-year-old woman with epigastralgia was admitted to our hospital and was diagnosed with type 3 advanced gastric cancer with lymph node metastases.The clinical diagnosis was Stage III A(cT3, N2, M0).Since curative surgery was not feasible, we administered preoperative combination chemotherapy with docetaxel, cisplatin(CDDP), and S-1.After 3 courses of chemotherapy, the lymph nodes became undetectable on computed tomography(CT).Distal gastrectomy was performed with curative intent, and the final diagnosis was Stage IIA(ypT3, N0, M0).There has been no recurrence for 1 year and 4 months after the operation.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Docetaxel; Drug Combinations; Female; Gastrectomy; Humans; Lymphatic Metastasis; Neoadjuvant Therapy; Neoplasm Staging; Oxonic Acid; Stomach Neoplasms; Taxoids; Tegafur

A 73-year-old man was referred to our hospital because of appetite loss and weight loss in January 2009. Endoscopy showed an advanced type II gastric tumor at the middle of the gastric wall, and computed tomography showed multiple liver metastases. Immunohistological examination confirmed a diagnosis of large cell neuroendocrine carcinoma which was chromogranin A(+), CD56(+), and synaptophysin(+). Oral administration of S-1(100mg/body)was given 5 days on and 2 days off, while cisplatin(CDDP 40 mg/body)was administered intravenously once every 2 weeks. The patient achieved a partial response(PR), and no serious adverse effects were observed. This case suggests that S-1/CDDP chemotherapy may be an effective treatment in patients with large cell neuroendocrine carcinoma of the stomach.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Large Cell; Carcinoma, Neuroendocrine; Cisplatin; Drug Combinations; Fatal Outcome; Humans; Liver Neoplasms; Male; Oxonic Acid; Stomach Neoplasms; Tegafur

The prognosis of patients with advanced gastric cancer is poor. The goal of this study was to evaluate the efficacy and safety of combination therapy of cetuximab and S-1 combined with oxaliplatin (SOX) in Chinese patients with advanced gastric cancer.. For patients in the experimental group (cetuximab in combination with SOX (Ce-SOX), 30 patients), once-weekly cetuximab (400 mg/m2 at the first infusion then 250 mg/m2 every week) was administered. For patients in both the control (SOX alone, 26 patients) and experimental groups, oxaliplatin (100 mg/m2) was administered intravenously on day 1, while S-1 (80 mg/m2/day) was given orally twice daily for 14 days. The endpoints of this study included progression-free survival, response rate, and disease-control rate.. There was no statistically significant difference in response rate between the Ce-SOX and SOX groups (54.8% versus 44%, P=0.225). The difference in disease-control rate was also statistically insignificant between the two groups (87.1% versus 76%, P=0.162). Median progression-free survival in the Ce-SOX group was significantly higher than that in the SOX group (12.8 versus 10.1 months, P=0.007). The median overall survival of the Ce-SOX group and SOX group was 14.0 and 12.2 months, respectively (P=0.043). The one-year survival rate for the Ce-SOX group was 57% compared to 40% in the SOX group. There was no statistical difference in the grade 3 or 4 adverse effects between the two groups.. These findings suggest that the cetuximab combined with SOX regimen is feasible and shows promising efficacy with tolerable adverse effects in Chinese patients with advanced gastric cancer.

Topics: Adult; Aged; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Cetuximab; Drug Combinations; Female; Follow-Up Studies; Humans; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Peritoneal Neoplasms; Prognosis; Safety; Stomach Neoplasms; Survival Rate; Tegafur

A 66-year-old man complaining of epigastralgia was referred to our hospital. We examined the patient and diagnosed advanced gastric cancer (ML, type 3, por, cT3, cN3, cH0, cP0, cM1[LYM], cStage IV). A poor outcome was predicted, so we attempted induction chemotherapy and expected tumor downstaging. We chose S-1/CDDP therapy. S-1 was administered orally for 21 days, followed by CDDP div on day 8. Total gastrectomy and lymph node dissection (D2+No. 12a, No. 13,16) was performed using Roux-en-Y reconstruction. Histological examination of the resected stomach and lymph nodes revealed no residual cancer cells, suggesting complete histological remission (grade 3) according to the Japanese classification of gastric carcinoma. The patient has been in good health without recurrence for 12 months after surgery.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Aorta; Cisplatin; Combined Modality Therapy; Drug Combinations; Humans; Lymphatic Metastasis; Male; Neoplasm Staging; Oxonic Acid; Stomach Neoplasms; Tegafur

We present a case of recurrent gastric cancer in which stable disease status was achieved for four months due to treatment with capecitabine/cisplatin (CDDP)after the failure of multiple anticancer drugs including S-1/CDDP. A 67-year-old man was diagnosed with multiple liver metastases one year after distal gastrectomy+D2 dissection for gastric cancer. S-1/CDDP was given as the first-line treatment, followed by paclitaxel (PTX), irinotecan (CPT-11), and docetaxel (DOC). The tumor in the anterior segment of the liver was resistant to all of these chemotherapies except for PTX, which is why the regimens were changed. However, this tumor shrank and achieved stable disease status for four months after capecitabine/CDDP therapy given as fifth-line treatment. Our case suggests that S-1 and capecitabine do not always exhibit cross-resistance. Therefore, capecitabine may be effective in S-1-pretreated patients, and vice versa.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Cisplatin; Combined Modality Therapy; Deoxycytidine; Drug Combinations; Drug Resistance, Neoplasm; Fluorouracil; Humans; Liver Neoplasms; Male; Neoplasm Staging; Oxonic Acid; Stomach Neoplasms; Tegafur

Prognosis of patients with metastatic gastric cancer is abysmal, usually just a few months. S-1 is a peroral fluoropyrimidine antitumor drug. It is a fixed combination of three effective drugs - tegafur, gimeracil and oteracil potassium.. This is a case report of a 71-year-old man treated for local advanced and metastatic gastric carcinoma treated with combination of S-1 and cisplatin as a first line of therapy. Treatment response reached partial remission and lasted for six months. Treatment was very well tolerated, with no grade 3 and 4 toxicity. After progression, the patient was treated with further lines of therapy.. In the Czech Republic, experience with S-1 drug is very limited. Our case report showed a good treatment response and minimal toxicity of this treatment, in concordance with results of the study FLAGS.

Topics: Aged; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Cisplatin; Czech Republic; Drug Combinations; Humans; Male; Oxonic Acid; Pyridines; Stomach Neoplasms; Tegafur; Treatment Outcome

The purpose of this study was to retrospectively examine the effect of concomitant administration of gastric secretion inhibitors or gastrectomy on the frequency of gastrointestinal toxicity caused by 5-fluorouracil (5-FU) in gastric cancer patients receiving chemotherapy with S-1. In 62 gastric cancer patients treated with S-1 alone, data relating to the occurrence of gastrointestinal toxicity (diarrhea, vomiting, and nausea) and possible contributing factors were retrospectively collected, and logistic regression analysis was performed. Time-to-event data relating to the occurrence of gastrointestinal toxicity were also collected, and the effect of gastric secretion inhibitors on the time-to-event profiles was examined using a log-rank test. Logistic regression analysis suggested that the frequency of gastrointestinal toxicity was significantly reduced by the administration of gastric secretion inhibitors (p=0.01; odds ratio, 0.197; 95% confidence interval (CI), 0.056-0.694) and that gastrointestinal toxicity correlated with the estimated glomerular filtration rate (p=0.04; odds ratio, 0.956; 95% CI, 0.916-0.997). The median time-to-event of gastrointestinal toxicity was 85 d for patients that received gastric secretion inhibitors, which was significantly different from the 42 d for patients that did not receive the inhibitors (p=0.02, log-rank test). No clear effect of gastrectomy was found in the present study. The prophylactic use of gastric secretion inhibitors in gastric cancer patients treated with S-1 may decrease and delay the occurrence of gastrointestinal toxicity.

Topics: Aged; Diarrhea; Dose-Response Relationship, Drug; Drug Combinations; Female; Gastric Mucosa; Histamine H2 Antagonists; Humans; Kaplan-Meier Estimate; Logistic Models; Male; Middle Aged; Nausea; Oxonic Acid; Proton Pump Inhibitors; Retrospective Studies; Stomach Neoplasms; Tegafur; Vomiting

Breast, gastric and lung cancers are the most common cancers that cause pulmonary lymphangitis carcinomatosa. However, little is known about the clinical features of pulmonary lymphangitis carcinomatosa in advanced gastric cancer.. We retrospectively reviewed the data throughout the clinical courses of 33 patients with gastric cancer who developed pulmonary lymphangitis carcinomatosa. Pulmonary lymphangitis carcinomatosa was confirmed by both a pulmonologist and a diagnostic radiologist on the basis of computed tomography findings of interstitial patterns such as thickening or irregularity of interlobular septa and bronchovascular bundles.. The median age of the 33 patients was 55 years old (range, 25-73 years). The percentages of female patients, those with performance status 3 or 4, and those with respiratory symptoms at diagnosis were 70, 36 and 76%, respectively. The histologically diffuse type of gastric cancer accounted for 85% of cases. Mediastinal lymph node, peritoneal and bone metastases were found in 64, 61 and 39% of patients, respectively. Disseminated intravascular coagulation was noted in 21% of patients. The median survival time of the 18 chemotherapy-naïve patients treated with chemotherapy was 5.7 months (range, 0.4-37.0 months). Two patients obtained symptomatic relief, and one patient treated with S-1 + cisplatin + sunitinib survived >3 years.. Pulmonary lymphangitis carcinomatosa caused by gastric cancer has some specific clinicopathological features. While the prognosis of gastric cancer patients with pulmonary lymphangitis carcinomatosa is extremely poor, some patients may have survival benefit from chemotherapy.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Female; Humans; Indoles; Kaplan-Meier Estimate; Lung Diseases; Lymphangitis; Lymphatic Metastasis; Male; Middle Aged; Oxonic Acid; Pyrroles; Retrospective Studies; Stomach Neoplasms; Sunitinib; Tegafur; Tomography, X-Ray Computed; Treatment Outcome

A 50-year-old female patient underwent distal gastrectomy and intraperitoneal CDDP administration for advanced gastric cancer accompanied by severe peritoneal dissemination. She valued her quality of life and chose an oral anticancer drug, S-1, as a postoperative chemotherapy agent. S-1 was administered at a dose of 100mg/body/day for 4 weeks, followed by a 2- week rest. There were no adverse events due to S-1 and no exacerbation of peritoneal dissemination in the 5 years following surgery. The S-1 administration schedule was then changed to alternate-day administration. Eight years after the surgery, the patient discontinued S-1 treatment and has since survived for 11 years with no obvious cancer recurrence.

Topics: Antimetabolites, Antineoplastic; Combined Modality Therapy; Drug Combinations; Female; Gastrectomy; Humans; Lymph Node Excision; Lymphatic Metastasis; Middle Aged; Neoplasm Invasiveness; Oxonic Acid; Peritoneal Neoplasms; Stomach Neoplasms; Tegafur; Treatment Outcome

Gastric adenosquamous carcinoma is a rare malignancy with a poor prognosis. We recently performed palliative gastrectomy for a gastric adenosquamous carcinoma with peritoneal dissemination and provided a course of systemic chemotherapy with S-1 plus paclitaxel(PTX)after the surgery. No serious adverse events were observed, and treatment with S-1 plus PTX was continued for 1 year before being switched to adjuvant chemotherapy with S-1 alone for another year. The tumor maker levels normalized within 2 months of the initial treatment, and the peritoneal dissemination could no longer be detected by abdominal computed tomography(CT). The patient remained in clinical remission and maintained long-term survival of over 8 years.

Topics: Antineoplastic Combined Chemotherapy Protocols; Biopsy; Carcinoma, Adenosquamous; Chemotherapy, Adjuvant; Drug Combinations; Gastrectomy; Humans; Male; Oxonic Acid; Paclitaxel; Peritoneal Neoplasms; Stomach Neoplasms; Tegafur; Time Factors

The results of the Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer(ACTS-GC)demonstrated that postoperative chemotherapy using S-1 is a standard treatment in Japan for patients with p-Stage II and p-Stage III gastric cancer. We retrospectively reviewed the effect of adjuvant chemotherapy received by 47 patients with p-Stage II and p-Stage III gastric cancer between January 2007 and June 2012. Our hospital is a local university hospital with a high intensive care unit. S-1 monotherapy was administered to 32 patients(adjuvant S-1 group, 68.1%); 22 patients(68.8%)among them completed one year of therapy without any modification to the administration schedule. A total of 8 patients(25.0%)experienced grade 3 adverse events, and 9 patients required a dose reduction, a modification of the administration schedule, or termination of the therapy. S-1 was not administrated to 15 patients(no adjuvant S-1 group, 31.9%); among these patients, 12(80.0%) were not administered S-1 because of their advanced age and comorbidity. The 3-year overall survival rate was 89.3% in the adjuvant S-1 group and 77.1% in the no adjuvant S-1 group. The completion rate of S-1 and survival rate were high for patients in the adjuvant S-1 group, which was similar to the results of the ACTS-GC. However, 25 of 47 patients(53.2%) with p-Stage II and p-Stage III gastric cancer did not improve after sufficient adjuvant therapy; therefore, it is important to develop new treatment strategies for these patients.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Drug Combinations; Female; Humans; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Retrospective Studies; Stomach Neoplasms; Tegafur

A 74-year-old man was diagnosed with advanced gastric cancer(cStage III B). Laparotomy showed N2 lymph node metastasis and pancreatic invasion. Radical resection appeared impossible and was thus not performed. Chemotherapy consisting of a combination of S-1(80mg/m 2, 2-week administration and 1-week rest), and docetaxel(40mg/m2day 1)was administered with the expectation of tumor downstaging. A partial response(PR)was obtained after five courses of this regimen in which the primary lesion and lymph node swelling remarkably improved. Total gastrectomy, splenectomy, partial colectomy, and D2 lymph node dissection were then performed. Pathological analysis revealed very few cancer cells in the primary lesion and that the lymph nodes had become scarred and fibrotic. The histological appearance was judged to be grade 2 and the final diagnosis was T1N0H0P0CY0M0, fStage I A, curability A. Currently, more than 6 years and 4 months after the operation, the patient is alive without any evidence of recurrence. Thus, docetaxel/S-1 combination therapy was an effective neoadjuvant chemotherapy for this case of advanced gastric cancer.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Docetaxel; Drug Combinations; Humans; Lymphatic Metastasis; Male; Neoadjuvant Therapy; Neoplasm Grading; Neoplasm Invasiveness; Neoplasm Staging; Oxonic Acid; Pancreas; Stomach Neoplasms; Taxoids; Tegafur; Treatment Outcome

An 82-year-old man died because of squamous cell carcinoma of the right lung with metastasis to the left femoral bone. At the age of 75 years, he was admitted to our hospital because of hematemesis. Widespread type 3 gastric cancer was detected in the lesser curvature. Computed tomography(CT)showed multiple liver metastases. Preoperative chemotherapy with TS-1/cisplatin(CDDP)was administered. TS-1 was orally administered at 80mg/body/day and CDDP was administered by intravenous infusion at 20mg/body/day every week for 3 weeks and this was followed by a drug-free 2-week period as the first course. After the fourth course, gastrectomy was performed for the primary lesion and radiofrequency ablation(RFA)was performed for the liver metastases. The patient survived for more than 7 years with a complete response (CR)and died thereafter because of squamous cell carcinoma of the lung.

Topics: Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Autopsy; Cisplatin; Drug Combinations; Humans; Liver Neoplasms; Male; Neoplasms, Squamous Cell; Oxonic Acid; Stomach Neoplasms; Tegafur; Time Factors; Treatment Outcome

A 79-year-old man was diagnosed with advanced gastric cancer (cT3, N1, M0, cStage II B) showing regional bulky lymph node metastasis. Invasion of the pancreas and common hepatic artery was suspected. He was treated with S-1/CDDP plus trastuzumab therapy as a neoadjuvant chemotherapy (NAC) regimen. After two courses, significant tumor reduction was observed, and the patient underwent distal gastrectomy with D2 dissection. S-1/CDDP plus trastuzumab therapy as NAC for HER2-positive, advanced gastric cancer appears to be an effective treatment.

Topics: Aged; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Gastrectomy; Humans; Male; Neoadjuvant Therapy; Neoplasm Staging; Oxonic Acid; Stomach Neoplasms; Tegafur; Trastuzumab

We report a case of gastric cancer with peritoneal dissemination that was successfully treated with low-dose S-1 or capecitabine chemotherapy over a 5-year period. In September 2007, distal gastrectomy was performed for treating gastric cancer with synchronous peritoneal dissemination in a 78-year-old man. Combination chemotherapy of S-1 and CDDP was administered after the surgical procedure. Following the completion of 9 courses, this regimen was discontinued owing to adverse events; therefore, S-1 (40-50mg/body/day) or capecitabine (1,800 mg/body/day) chemotherapy was initiated. S-1 or capecitabine were orally administered for 2 weeks, followed by a 2-week or 1-week interval, respectively; this regimen was continued for over 5 years. The patient died in June 2013.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Deoxycytidine; Drug Combinations; Fatal Outcome; Fluorouracil; Humans; Male; Oxonic Acid; Peritoneal Neoplasms; Stomach Neoplasms; Tegafur; Time Factors

The patient was a 58-year-old man diagnosed with type 2 advanced gastric cancer located at the fundus with multiple liver, lung, and lymph node metastases(Stage IV). Examination of an endoscopically obtained biopsy specimen revealed poorly differentiated adenocarcinoma (por), which stained positive for human epidermal growth factor receptor 2 (HER2) on immunohistochemistry. We started chemotherapy with S-1 plus cisplatin (CDDP) plus trastuzumab. The treatment was effective, as the tumor had reduced in size by 22.5% and 36.2%(partial response[PR])after 3 and 6 courses, respectively. Adverse events related to the treatment were limited to grade 1 fever, nausea, vomiting, and diarrhea. The patient's chief complaints of right upper abdominal pain and abdominal fullness remarkably improved after treatment initiation. Although the therapy was effective against the multiple liver metastases and could be continued for 11 courses, the lymph nodes metastases did not respond to therapy (progressive disease [PD]), and the patient died 9 months after the start of treatment. Chemotherapy with S-1 pus CDDP plus trastuzumab may be effective for HER2-positive advanced gastric cancer with liver metastasis.

Topics: Adenocarcinoma; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Fatal Outcome; Humans; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Oxonic Acid; Stomach Neoplasms; Tegafur; Trastuzumab

This retrospective study evaluated immunity in elderly patients with unresectable gastric cancer receiving S-1/ Lentinan combination chemotherapy.. This study included 10 patients aged≥70 years with unresectable gastric cancer who received S-1/Lentinan combination chemotherapy between October 2008 and December 2012. All patients gave written informed consent. Immune parameters for regulatory T cell(Treg)ratio, prostaglandin E2(PGE2), C3, CH50, and granulocyte/lymphocyte ratio were measured before chemotherapy initiation and at 7 weeks after it. Clinicopathological or immune parameters affecting overall survival(OS)were consequently evaluated.. A high Treg ratio(p=0.02) and low PGE2(p=0.05)levels at 7 weeks after chemotherapy and a decrease in the Treg ratio(p=0.02)were found to be significant favorable factors affecting OS.. The outcome of elderly patients with unresectable gastric cancer receiving S-1/Lentinan combination chemotherapy seemed to be correlated with the change in immunity.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Complement C3; Dinoprostone; Drug Combinations; Female; Humans; Lentinan; Male; Oxonic Acid; Prognosis; Stomach Neoplasms; T-Lymphocytes, Regulatory; Tegafur

We retrospectively analyzed the feasibility and adverse events for two regimens, postoperative chemoradiation (CRT) with 5-fluorouracil/leucovorin (5-FU/LV) compared to S-1 in D2-resected gastric cancer patients.. The study included 405 gastric cancer patients who underwent curative gastrectomy with D2 lymph node dissection and received adjuvant therapy between January 2008 and July 2009. Feasibility and adverse events for the CRT and S-1 regimens were analyzed.. Out of the 405 patients, 244 (60.2%) had CRT and 161 (39.8%) had S-1 treatment. The regimen was selected based on the preferences of the physician and the patient. S-1 was more frequently administered to patients with older age (age≥70) and those with early-stage disease (stage II). The stage was significantly more advanced in the CRT group compared to the S-1 group (S-1 vs. CRT: stage II, 59.6% vs. 36.1%; stage III/IV, 28.0% vs. 48.3%, respectively; p<0.001). The completion rate of the planned therapy was significantly higher in the CRT group than in the S-1 group (95.1% vs. 72.8%, respectively; p<0.001). Regarding severe adverse events (grade 3-4), neutropenia (CRT vs. S-1; 40.2% vs. 8.7%, respectively, p<0.001), nausea (CRT vs. S-1; 5.7% vs. 0%, respectively; p=0.002) and stomatitis (CRT vs. S-1; 7.4% vs. 2.5%, respectively; p=0.034) were significantly more frequent in the CRT cohort compared to the S-1 group.. Both adjuvant CRT with 5-FU/LV and adjuvant S-1 are safe and feasible in D2-resected gastric cancer patients. Patients with old age or early stage disease tend to prefer S-1 therapy to chemoradiation.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Signet Ring Cell; Chemoradiotherapy, Adjuvant; Combined Modality Therapy; Drug Combinations; Feasibility Studies; Female; Fluorouracil; Follow-Up Studies; Gastrectomy; Humans; Leucovorin; Lymph Node Excision; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Oxonic Acid; Prognosis; Retrospective Studies; Stomach Neoplasms; Survival Rate; Tegafur

The patient was a 77-year-old woman who underwent gastrectomy for gastric cancer. Since the patient had positive peritoneal washing cytology and positive peritoneal dissemination, she was started on oral S-1 therapy post-surgery for 4 weeks, followed by a 2-week rest period. During the first course of therapy, her white blood cell count decreased; therefore, the regimen was changed to a 1-week administration, followed by a 1-week rest period. No subsequent adverse events were noted. The patient has experienced no relapse in the four years she has been followed up after surgery in our outpatient clinic. We report our experience with an elderly patient for whom S-1 monotherapy was effective in the treatment of gastric cancer with peritoneal dissemination.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Disease-Free Survival; Drug Combinations; Female; Gastrectomy; Humans; Oxonic Acid; Peritoneal Neoplasms; Stomach Neoplasms; Tegafur; Time Factors

To analyze and compare the economic outcomes of adjuvant chemotherapy with capecitabine plus oxaliplatin (referred to as the XELOX strategy) and of S-1 (the S-1 strategy) for gastric cancer patients after D2 gastrectomy.. A Markov model was developed to simulate the lifetime disease course associated with stage II or III gastric cancer after D2 gastrectomy. The lifetime quality-adjusted life years (QALYs), associated costs, and incremental cost-effectiveness ratios (ICERs) were estimated. The clinical data were derived from the results of pilot studies. Direct costs were estimated from the perspective of the Chinese healthcare system, and the utility data were measured from end-point observations of Chinese patients. Sensitivity analyses were used to explore the impact of uncertainty on the model's outcomes.. The combined adjuvant chemotherapy strategy with XELOX yielded the greatest increase in QALYs over the course of the disease (8.1 QALYs compared with 7.8 QALYs for the S-1 strategy and 6.2 for surgery alone). The incremental cost per QALY gained using the XELOX strategy was significantly lower than that for the S-1 strategy ($3,502 vs. $6,837, respectively). The results were sensitive to the costs of oxaliplatin and the hazard ratio of relapse-free survival.. The observations reported herein suggest that adjuvant therapy with capecitabine plus oxaliplatin is a highly cost-effective strategy and more favorable treatment option than the S-1 strategy in patients with stage II or III gastric cancer who have undergone D2 gastrectomy.

Topics: Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Chemotherapy, Adjuvant; China; Clinical Trials as Topic; Cost-Benefit Analysis; Deoxycytidine; Disease-Free Survival; Drug Combinations; Fluorouracil; Gastrectomy; Humans; Markov Chains; Models, Economic; Oxaloacetates; Oxonic Acid; Quality-Adjusted Life Years; Stomach Neoplasms; Survival Rate; Tegafur

The standard treatment for stage IV gastric cancer is chemotherapy, but outcomes remain poor. The effectiveness of induction chemotherapy followed by surgery in selected patients who had a good response to chemotherapy is unclear.. A total of 59 patients with stage IV gastric cancer received induction chemotherapy with S-1 and cisplatin. In each cycle, oral S-1 (80 mg/m2) was administered for 3 weeks, followed by a 2-week drug holiday. Intravenous cisplatin (60 mg/m2) was administered on day 8 after adequate premedication and hydration. If unresectable features resolved after chemotherapy, patients underwent curative (R0) resection. The safety and outcomes of this treatment combination were evaluated, and predictive factors for survival were determined.. Thirteen of 59 patients (22%) were eligible for R0 resection after induction chemotherapy. Kaplan-Meier analysis showed an overall median survival time of 13 months and a 3-year survival rate of 18.2%. Among patients who underwent R0 resection, the median survival time was 53 months and the 3-year survival rate was 53.8%. Multivariate analyses showed that negative para-aortic lymph nodes and undergoing R0 resection were independent predictors of survival.. Treatment of stage IV gastric cancer with S-1 and cisplatin induction chemotherapy followed by R0 resection is safe and may improve survival compared with chemotherapy alone. Further study of this dual-modality therapy is warranted.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Drug Combinations; Female; Follow-Up Studies; Humans; Induction Chemotherapy; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Neoplasm Staging; Oxonic Acid; Prognosis; Retrospective Studies; Stomach Neoplasms; Survival Rate; Tegafur

We here describe a case of Stage IV breast and gastric cancer in which S-1/paclitaxel therapy was effective in maintaining the patient's QOL. A 50-year-old woman visited our hospital with complaints of her right breast tumor and right brachialgia. She was diagnosed with breast cancer with multiple bone metastases including cervical vertebrae. Accordingly, local radiation therapy and tamoxifen(TAM)administration was started immediately. Gastrointestinal endoscopy revealed gastric cancer, but laparotomy disclosed the gastric cancer was unresectable. At that time, the complaints of pain, nausea, and fatigue had increased and S-1/paclitaxel therapy was started immediately. The treatment reduced the size of the lesions in the breast and stomach and improved the QOL without serious adverse events. We have been maintaining partial response(PR)in this patient for 28 months.

Topics: Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Combined Modality Therapy; Drug Combinations; Female; Humans; Middle Aged; Neoplasm Staging; Neoplasms, Multiple Primary; Oxonic Acid; Paclitaxel; Stomach Neoplasms; Tegafur

We report here an experience treating a patient who developed gastric cancer at the same time as a multifocal intrahepatic recurrence of hepatocellular carcinoma (HCC). The patient was a 76-year-old woman who underwent partial liver resection after diagnosis of HCC in August 2008. Histopathological examination revealed moderately differentiated hepatocellular carcinoma and stage III pathology. Six months following surgery, an upper gastrointestinal endoscopy revealed a typeIIa+IIc gastric tumor in the angle of the stomach, which was pathologically diagnosed as adenocarcinoma(por2/sig) in the biopsy. Simultaneously, abdominal CT scan revealed multifocal intrahepatic recurrence of HCC, so Lip-TACE as performed. Eight days after TACE, S-1 (80 mg/body) was initiated. About one month after TACE, abdominal CT scan revealed multiple new hepat- ic lesions. The patient was repeatedly treated with a combination of Lip-TACE on day 1 and S-1 80 mg/body/day, administered on days 8 to 35 for 28 days, followed by a 7 day interval as 1 course. After 5 courses of medication of S-1, liver function had deteriorated and thrombocytopenia occurred. Although there was no progression of gastric cancer, medication of S-1 was discontinued. Lip-TACE was performed nine times. About one year after the initial TACE, the patient was admitted to our hospital in order to control ascites, 3 days after admission, she suffered a cerebral infarction and died 3 days later.

Topics: Aged; Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Combined Modality Therapy; Drug Combinations; Fatal Outcome; Female; Hepatectomy; Humans; Liver Neoplasms; Oxonic Acid; Recurrence; Stomach Neoplasms; Tegafur

Recent advances in anti-cancer drug treatments enable us to improve prognosis in Stage IV gastric cancer. In particular, in recent reports patients with only cytology positive (CY1) non-curative factors have comparatively better prognosis than others. This study was designed to evaluate our outcomes, to allow identification of CY1 gastric cancer patients and to investigate new treatment strategies.. Between 2000 and 2008, 336 patients underwent peritoneal washing cytology for gastric cancer intra-operatively. Of these, 35 patients (10.4%) were diagnosed with CY1 gastric cancer.. 1 ) In all CY1 gastric cancers, 1-year, 3-year, and 5-year survival rates were 49%, 11%, and 5.7%, respectively. Clinical factors such as number of non-curative factors (p=0.008) and gastrectomy (p=0.001)were significantly related to poor prognosis. 2 ) The number of CY1 patients with only CY1 non-curative factors (Group C) and multiple non-curative factors (Group CM)were 14 and 21, respectively. The number of CY1 patients with gastrectomy and without gastrectomy were 30 (MST 366 days, Group C: 14 Group CM: 16) and 5 (MST: 88 days, Group CM: 5), respectively. 3 ) In CY1 patients with gastrectomy, patients treated with S-1 based chemotherapy had better prognosis in both Group C and Group CM. 4 ) 8 CY1 patients with neoadjuvant chemotherapy (NAC) followed by gastrectomy (MST 501 days, 1-year survival rate 62.5%) tended to have better prognosis than those without NAC (MST 132 days, 1-year survival rate 25.0% (p= 0.055).. Gastrectomy, number of non-curative factor, S-1 based chemotherapy and NAC were keys to improving prognosis by subgroup analyses in CY1 gastric cancer.

Topics: Adult; Aged; Aged, 80 and over; Drug Combinations; Female; Gastrectomy; Humans; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Oxonic Acid; Prognosis; Retrospective Studies; Stomach Neoplasms; Tegafur

Since 2011, we have performed routine staging laparoscopy on 7 patients presenting with type 4 gastric cancer at our department. After staging laparoscopy, the patients received neoadjuvant chemotherapy with docetaxel, cisplatin, and S-1 (DCS). After the completion of 2 courses of chemotherapy, radical gastrectomy with D2 gastrectomy or greater was performed, followed by postoperative adjuvant chemotherapy with S-1 for 1 year. In the present study, we evaluate the outcomes of the treatment strategies for the type 4 gastric cancer patients treated at our institution. Staging laparoscopy and peritoneal lavage cytology revealed that none of the patients had peritoneal metastasis, while peritoneal cytology detected carcinoma cells in 3 patients. Grade 3 or greater neutropenia developed in 3 patients, and Grade 3 or greater nonhematological toxicity developed in 3 patients after neoadjuvant chemotherapy. The disease control rate was 100% and all patients underwent radical gastrectomy. Of the 3 patients who had positive peritoneal cytology on staging laparoscopy, 2 patients had no peritoneal cancer cells at the time of gastrectomy. Six patients underwent R0 surgery after DCS chemotherapy, and the response rate was 57.1%. The median survival time was 540 days. Four patients experienced peritoneal recurrence, and 1 developed lymph node recurrence. Our therapeutic strategy for type 4 gastric cancer contributed to prolonged survival; however, it is necessary to develop better strategies that can prevent or control the peritoneal recurrence.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cisplatin; Docetaxel; Drug Combinations; Female; Gastrectomy; Humans; Male; Middle Aged; Neoadjuvant Therapy; Oxonic Acid; Stomach Neoplasms; Taxoids; Tegafur; Treatment Outcome

The ACTS-GC trial showed the efficacy of S-1 adjuvant chemotherapy in patients with pathological Stage II/III gastric cancer who had undergone D2 gastrectomy; however, T1 patients were excluded from this trial.In this study, we compared the prognosis of T1N2/3 gastric cancer with the outcomes of ACTS-GC.From 2000 to 2009, out of 480 patients with resected T1 gastric cancer, 27 patients(5.6%) were pN2/3.Six patients received S-1 adjuvant chemotherapy (group S), whereas 21 patients did not(group N).The 3-year overall survival rates of T1N0/1 and T1N2/3 were 91.7% and 71.3%, respectively. Among T1N2/3 gastric cancer patients, the 3-year survival rate and relapse-free survival rate were 100%/100% in group S and 72.7%/71.1% in group N, respectively. The prognosis of group N was poorer than that of the surgery-alone group in Stage II of ACTS-GC.Furthermore, 5 patients (23.8%) of group N had recurrences; the primary sites of recurrences were lymph nodes in 4 cases, and lymph nodes and liver in 1 case.The prognosis of T1N2/3 gastric cancer is poor; we should, therefore, consider evaluating the efficacy of adjuvant chemotherapy in T1N2/3 gastric cancer patients.

Topics: Aged; Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Drug Combinations; Female; Gastrectomy; Humans; Male; Neoplasm Staging; Oxonic Acid; Prognosis; Stomach Neoplasms; Tegafur

We report 2 cases of resectable advanced gastric cancer who achieved pathological complete response by preoperative chemotherapy with S-1 plus weekly low-dose cisplatin (CDDP). S-1 (80 mg/m²)was administered consecutively for 21 days followed by 14 days' rest, with CDDP (25mg/m²) injected on days 1, 8, and 21. Case 1: A man in his 70s diagnosed with cStage III gastric cancer with lymph node metastases received 2 courses of preoperative chemotherapy with S-1 plus weekly low-dose CDDP followed by total gastrectomy with D2 lymph node dissection. Case 2: A man in his 60s diagnosed with cStage III gastric cancer with lymph node metastases received 4 courses of preoperative chemotherapy with S-1 plus weekly low-dose CDDP followed by total gastrectomy with D2 lymph-node dissection. In both cases, postoperative pathological examination revealed no cancer cells in the resected stomach and lymph nodes. The therapeutic effect of preoperative chemotherapy was assessed as Grade 3. With this regimen, we accomplished preoperative chemotherapy successfully without inpatient care. This regimen can be a promising option as preoperative chemotherapy for advanced gastric cancer.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Gastrectomy; Humans; Lymphatic Metastasis; Male; Neoadjuvant Therapy; Neoplasm Invasiveness; Oxonic Acid; Remission Induction; Stomach Neoplasms; Tegafur

The patient was a 74-year-old woman with advanced gastric cancer in the greater curvature of the antrum and lesser curvature of the angle.Abdominal computed tomography revealed bulky lymph node metastases of No. 3, 8a, and 11p.She was diagnosed with clinical Stage IIIA gastric cancer (cT3N2M0) and underwent surgery.Laparotomy findings revealed invasion of bulky lymph nodes to the common hepatic artery and pancreas.Since radical resection was not feasible, exploratory laparotomy was performed.After the surgery, she received 1 course of S-1 monotherapy and 3 courses of S-1/cisplatin (CDDP) therapy.The therapeutic response, as assessed by imaging studies, was partial for the primary lesions and complete for the enlarged lymph nodes.Distal gastrectomy and D2 lymph node dissection were performed.Histopathological findings showed no evidence of lymph node involvement, allowing the patient to undergo radical surgery.The patient received postoperative adjuvant chemotherapy with S-1.She is alive 11 months after the surgery, with no evidence of recurrence.Induction chemotherapy appears to be a promising option for advanced gastric cancer with significant lymph node involvement.

Topics: Aged; Antimetabolites, Antineoplastic; Drug Combinations; Female; Gastrectomy; Humans; Induction Chemotherapy; Lymphatic Metastasis; Neoplasm Invasiveness; Oxonic Acid; Stomach Neoplasms; Tegafur

A 6 2-year-old man with advanced gastric cancer was referred to our hospital. A gastroscopy revealed a type 3 tumor invading the esophagus in the lesser curvature of the stomach cardia. We diagnosed the tumor as cStageIIIB(T4bN1M0) gastric cancer. For the best chance of a pathological complete response, we selected neoadjuvant chemotherapy (NAC) with S-1+CDDP (SP therapy). A total gastrectomy with lymph node dissection was performed after 2 courses of SP therapy. Pathological evaluation of the resected stomach and lymph nodes indicated an absence of cancerous cells, confirming a pathological complete response (pCR). The patient has been followed up for 4 months without evidence of recurrence.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Gastrectomy; Humans; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Invasiveness; Oxonic Acid; Stomach Neoplasms; Tegafur

We report a case of advanced gastric cancer that was successfully treated with second-line chemotherapy followed by curative conversion gastrectomy. The patient was a 71-year-old man. Endoscopic examination revealed a type 3 gastric cancer in the lower third of the stomach. Abdominal computed tomography (CT) revealed multiple lymph node metastases and metastasis to the peritoneal cavity. The clinical diagnosis was cT4N3aP1H0M1(LYM), cStage IV. The patient was treated with S-1 (80 mg/m² on days 1-28, every 6 weeks [q6w]) in November 2009. Temporarily, both the size of the primary lesion and the swelling of the lymph nodes were markedly reduced. However, after 10 courses of chemotherapy, the primary lesion was found to be enlarged again. The patient was then treated with S-1(80 mg/m², on days 1-14, every 6 weeks [q3w]) plus CPT- 11 (150 mg/m² on day 1, q3w) as the second-line chemotherapy. After 8 courses, an abdominal CT showed no peritoneal or lymph node metastases, but gastric endoscopy revealed the presence of a residual primary lesion. After staging laparoscopy, distal gastrectomy with D2 lymphadenectomy was performed. The histological diagnosis was ypT3 (SS) N1M0, Stage IIB. Analysis of the histological features of the primary tumor and peritoneal metastases resulted in their classifications as Grade 1a and Grade 3, respectively. After surgery, there were no serious adverse events. The patient has been in good health without recurrence for over 3 years after surgery.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Combined Modality Therapy; Drug Combinations; Gastrectomy; Humans; Irinotecan; Lymph Node Excision; Lymphatic Metastasis; Male; Oxonic Acid; Peritoneal Neoplasms; Remission Induction; Stomach Neoplasms; Tegafur

In June 2010, a 67-year-old man presented with advanced gastric cancer. He underwent 2 courses of combination chemo- therapy with S-1/CDDP. After chemotherapy, total gastrectomy was performed (pT4aN3aM0, Stage IIIC). Although he underwent S-1 chemotherapy, colon tumors recurred 22 months after the operation. Colonoscopy revealed the presence of type 2 advanced cancer in the ascending colon, and type IIa early cancer in the transverse colon, which were diagnosed as either primary colon cancers or recurrent gastric cancers upon pathological examination. In October 2012, resection of the right side of the colon was performed in order to prevent malignant bowel obstruction. Pathological examination of the resected specimen identified recurrent gastric cancers. After the surgery, he is currently undergoing S-1 chemotherapy and has no sign of recurrent tumors.

Topics: Aged; Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Colonic Neoplasms; Drug Combinations; Gastrectomy; Humans; Intestinal Obstruction; Male; Oxonic Acid; Recurrence; Stomach Neoplasms; Tegafur

We report here the effectiveness of chemoradiotherapy for a patient with local recurrence followed by curable gastrectomy. A 57-year-old man presented with a history of total gastrectomy with distal pancreatectomy and splenectomy, D2 lymphadenectomy, and Roux-en-Y reconstruction for advanced gastric cancer arising from the cardia. Esophageal intramural metastasis and lymph node metastasis around the right recurrent nerve were detected by chest-abdominal computed tomography and gastrointestinal endoscopy 27 months after the initial gastrectomy. Stable disease was achieved following 7 courses of chemotherapy using S-1 plus CDDP. Concurrent chemoradiotherapy including administration of S-1 and radiation of total 50 Gy (2 Gy/25 Fr) was selected for local tumor control. The patient was not able to eat solid food because of esophageal stenosis from regrowth of intramural metastasis of the esophagus 60 months after the chemotherapy. A WallFlex™ Duodenal Stent was placed to improve the dysphagia 67 months after chemotherapy. The patient died from recurrence of gastric cancer 69 months after completion of the initial chemotherapy and 2 months after the stent insertion.

Topics: Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Cisplatin; Drug Combinations; Esophageal Neoplasms; Gastrectomy; Humans; Male; Middle Aged; Oxonic Acid; Recurrence; Stomach Neoplasms; Tegafur

Stage IV gastric cancer has poor prognosis, and median survival time (MST) is reported to range from 6 to 13 months. We report a case of long-term survival in a Stage IV gastric cancer patient who was successfully treated with multi combination chemotherapy with S-1. A 73-year-old woman presenting with gastric cancer with pyloric stenosis and peritoneal dissemination at the sigmoid colon underwent distal gastrectomy with D2 lymphadenectomy and sigmoidectomy. She received adjuvant chemotherapy with S-1 and CDDP after surgery. During the twelfth administration of S-1 and CDDP, she developed an anaphylactic reaction against CDDP; therefore, only S-1 was administered for the next 6 courses. Thirty one months postgastrectomy, a left ovarian metastasis (about 4 cm) was detected by computed tomography. Two courses of S-1 and CPT-11 were administered; however, the ovarian metastasis grew to twice its initial size. She underwent hysterectomy and bilateral ovariectomy. The pathological diagnosis was metastatic tumors in the uterus and ovary(Krukenberg tumor). After the second surgery, S-1 and docetaxel therapy was initiated. A metastasis (S2, 5mm diameter) appeared in the right lung around 65 months after the gastrectomy. The patient received a total of 28 courses, up until 69 months post-gastrectomy. At present, she hopes to finish the chemotherapy and is consulting a palliative care facility. At 80 months post-gastrectomy, she has no symptoms because the lung metastasis exhibits slow growth (15 mm diameter), and is maintaining her quality of life (QOL).

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Female; Gastrectomy; Humans; Lung Neoplasms; Neoplasm Staging; Ovarian Neoplasms; Oxonic Acid; Stomach Neoplasms; Tegafur

A 61-year-old man was referred to our hospital because of gastric pain and weight loss.Upper gastrointestinal endoscopy revealed a superficial depressed (Type 3) tumor with pyloric stenosis.The tumor was diagnosed as tubular adenocarcinoma by pathological examination.Abdominal computed tomography showed enlarged paraaortic and No. 8a lymph nodes.The patient underwent distal gastrectomy (D0)and Roux-en-Y reconstruction.After surgery, chemotherapy combined with molecular targeted therapy (S-1+cisplatin[CDDP]+trastuzumab), based on overexpression of the HER2 protein in the primary tumor as assessed by immunostaining, was administered.After the molecular targeted chemotherapy, the carcinoembryonic antigen (CEA )levels decreased to the normal range and the enlarged lymph nodes were remarkably decreased in size. The patient is currently alive without progressive disease.

Topics: Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Gastrectomy; Humans; Male; Middle Aged; Molecular Targeted Therapy; Oxonic Acid; Pyloric Stenosis; Receptor, ErbB-2; Stomach Neoplasms; Tegafur; Trastuzumab

A 62-year-old man was diagnosed with esophagogastric junction cancer following esophagogastroduodenoscopy in response to hematemesis. Although liver metastasis was detected during surgery, a total gastrectomy and lower esophagus resection for local control was performed. Alpha-fetoprotein(AFP)-producing tumor with hepatoid adenocarcinoma was diagnosed on the basis of the pathological examination. Serum AFP levels remained high postoperatively and multiple liver metastases were detected on computed tomography imaging. After 6 courses of chemotherapy with S-1 and cisplatin (CDDP), a significant reduction in the size of the liver metastases and a decrease of serum AFP levels were achieved. Postoperative 2-year tumor control using S-1 single agent chemotherapy was obtained. AFP-producing esophagogastric junction cancer has a poor prognosis. This case raises the possibility that long-term survival can be obtained by combining surgery for local control with systemic chemotherapy.

Topics: alpha-Fetoproteins; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Esophageal Neoplasms; Esophagogastric Junction; Humans; Liver Neoplasms; Male; Middle Aged; Oxonic Acid; Stomach Neoplasms; Tegafur

A 66-year-old man underwent a curative operation for advanced gastric cancer (T4aN0M0, Stage IIB). A gastric cancer recurrence with paraaortic lymph node (PALN) metastasis was diagnosed fifteen months after the operation. Systemic chemotherapy was initiated, using a regimen of S-1/CDDP. After 7 courses, abdominal computed tomography (CT) examination indicated the regression of PALN swelling. However, peritoneal dissemination was detected in the neighborhood of the right kidney. S-1/docetaxel (S-1/DOC) was selected as the second-line chemotherapy. After 3 courses, the peritoneal dissemination could not be detected. Five years since the curative operation, the patient has been doing well, with no signs of recurrence. In summary, we successfully treated a case of peritoneal dissemination from gastric cancer with S-1/DOC chemo- therapy.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Docetaxel; Drug Combinations; Gastrectomy; Humans; Lymphatic Metastasis; Male; Oxonic Acid; Peritoneal Neoplasms; Recurrence; Stomach Neoplasms; Taxoids; Tegafur

We report on a patient who underwent total gastrectomy with D2 lymph node dissection for metastatic gastric cancer. We administered S-1 at 60 mg/m² as postoperative adjuvant chemotherapy. Six months after surgery, recurrence was detected in the para-aortic lymph node. As a first-line treatment for the recurrent cancer, the patient underwent capecitabine/CDDP therapy(capecitabine 1,800 mg/m², CDDP 60 mg/m²). A significant reduction in the recurrent lymph nodes was observed by CT after 6 months of administration, resulting in 24 months of progression-free survival. S-1/CDDP therapy is recommended as a first-line chemotherapy for recurrent gastric carcinoma in the Japanese gastric cancer treatment guidelines. Likewise, single agent S-1 administration is recommended as postoperative adjuvant chemotherapy for advanced gastric cancer patients. However, in cases of recurrence after S-1 therapy, there is insufficient evidence on the efficacy of S-1/CDDP; thus, the type of administration and time to recurrence could be considered for optimization. We identified a case of gastric cancer showing response to first-line capecitabine/CDDP therapy after lymph node recurrence following the administration of S-1 as postoperative adjuvant chemotherapy. Since capecitabine and S-1 differ in their mechanisms of action and as predictive factors for therapeutic effect, capecitabine may be an efficient option in cases of S-1 failure. The present case suggests that capecitabine/CDDP therapy may be an effective treatment for S-1 pretreated patients with advanced or metastatic gastric cancer.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Chemotherapy, Adjuvant; Cisplatin; Deoxycytidine; Drug Combinations; Female; Fluorouracil; Humans; Lymphatic Metastasis; Oxonic Acid; Recurrence; Salvage Therapy; Stomach Neoplasms; Tegafur

We report a case of a patient with resection margin involvement gastric carcinoma that recurred 5.5 years after additional resection. A 64-year-old man underwent distal gastrectomy for advanced gastric carcinoma (sig+por2, pSE, pN0, pStage IIB) in January 2008. A total gastrectomy was performed 2 months after the initial gastrectomy because of proximal resection line involvement, and curative resection was obtained. Adjuvant chemotherapy with S-1 was completed, and follow-up surveillance was finished 5 years after the additional surgery. In November 2013, the patient experienced bouts of vomiting, and a computed tomography (CT) scan showed an abdominal abscess that had spread to the liver and communicated with the intestine. Despite abscess drainage and antibiotic therapy, infection control was difficult and the patient died 20 days after hospitalization. An autopsy showed the recurrence lesions had diffusely spread to the peritoneum and was also disseminated around the Roux-Y jejunum. These findings suggest that peritoneal recurrence might lead to penetration of the intestine and abscess formation.

Topics: Abdominal Abscess; Anti-Bacterial Agents; Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Drainage; Drug Combinations; Fatal Outcome; Gastrectomy; Humans; Male; Middle Aged; Oxonic Acid; Recurrence; Stomach Neoplasms; Tegafur

A man in his 60s received SP (S-1+CDDP) therapy for gastric cancer with multiple liver metastases. After completion of 3 courses, liver metastases had reduced significantly, and the paraaortic lymph nodes, which had swelled previously, had reduced in size. Furthermore, the serum carcinoembryonic antigen (CEA) level had also improved to the standard value from 814.3 ng/mL. The patient was able to discontinue the opioid he had needed for pain control. The chemotherapy was continued for 18 courses, with the dose reduced at the time of the adverse events along the way. By completion of the 18 courses, we recognized regrowth of the primary lesion and a rise in the serum CEA over the standard value. There was no sign of the regrowth of liver metastases and distant lymph nodes according to examinations for enhanced computed tomography (CT) and ¹⁸F-fluorodeoxyglucose positron-emission tomography (FDG-PET) CT.The patient received distal gastrectomy. The CEA level decreased in standard value or less after surgery and we believed the cancer was limited to the primary stomach lesion.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoembryonic Antigen; Cisplatin; Combined Modality Therapy; Drug Combinations; Gastrectomy; Humans; Liver Neoplasms; Male; Oxonic Acid; Stomach Neoplasms; Tegafur

A 55-year-old man suffering from gastric cancer associated with metastases to the lymph node, gallbladder, and liver was administered chemotherapy with S-1 and cisplatin. Before initiation of therapy, the primary tumor, lymph node metastases, and liver metastases showed fluorodeoxyglucose (FDG) accumulation by positron emission tomography (PET). After 1 course of chemotherapy, the patient received curative surgical treatment including distal gastrectomy, partial hepatectomy, cholecystectomy, and lymph node dissection. The final pathological finding was moderately differentiated adenocarcinoma, T4b(SI), N3a(10/20), P0, CY0, pH1, pM1, Stage IV. Five months after surgery, the serum carcinoembryonic antigen (CEA) level was found to be increasing and PET examination identified an FDG-accumulating nodule in the ascending colon. Colonoscopy identified a submucosal tumor diagnosed as a metastasis from the gastric cancer. Right colectomy was performed 7 months after the first surgery resulting in a curative resection. In each surgery, PET examination indicated that no other distant metastases existed, and curative resection would be possible. Furthermore, although solitary metastatic colorectal lesions are rare, PET examination revealed them accurately. Thus, FDG-PET is very useful for identifying metastases in patients with gastric cancer.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Colonic Neoplasms; Combined Modality Therapy; Drug Combinations; Gallbladder Neoplasms; Humans; Liver Neoplasms; Male; Middle Aged; Oxonic Acid; Recurrence; Stomach Neoplasms; Tegafur

A 74-year-old woman underwent distal gastrectomy and D1+ α dissection for the treatment of gastric cancer (pT2a, pN2, H0, P0, M0, Stage IIIA) in February 2008. She was treated with adjuvant postoperative chemotherapy consisting of TS-1. However, 32 months after the operation, paraaortic lymph node recurrence was confirmed by computed tomography (CT). She was treated with combined TS-1 and cisplatin chemotherapy. After 14 courses, CT revealed that the paraaortic lymph node metastasis had disappeared, and a complete response was attained. The patient is currently disease-free, 6 years after the operation.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Female; Gastrectomy; Humans; Lymphatic Metastasis; Oxonic Acid; Recurrence; Remission Induction; Silicates; Stomach Neoplasms; Tegafur; Titanium

A 46-year-old female underwent total gastrectomy with a combined resection of the pancreatic tail, spleen, and lateral segment of the liver surgery after conservative medical management for a perforated advanced gastric cancer. The histological findings showed poorly differentiated adenocarcinoma, and the tumor was Stage IIIC. S-1 and "Kampo-Juzen-taiho-to" were administered as postoperative adjuvant chemo-immunotherapy. A Krukenberg tumor was identified 4 years later. The histological findings strongly suggested the presence of peritoneal dissemination, and S-1-based combined chemotherapies using key drugs such as CDDP, CPT-11, and taxane with the biochemical response modifier "Lentinan" was administered. However, the Krukenberg tumor rapidly increased in size after 4 years and she complained of abdominal distension. Therefore, it was removed with neither difficulties nor apparent recurrent disease, which was thought to be due to the S-1-based combined chemotherapy and the immunological agents are likely to have contributed to her long survival and good quality of life.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Combined Modality Therapy; Drug Combinations; Drugs, Chinese Herbal; Female; Gastrectomy; Humans; Immunotherapy; Krukenberg Tumor; Middle Aged; Ovarian Neoplasms; Ovariectomy; Oxonic Acid; Phytotherapy; Postoperative Care; Stomach Neoplasms; Tegafur; Treatment Outcome

We report two cases of unresectable advanced gastric cancer treated with S-1, CDDP and trastuzumab. A significant reduction of tumors was observed in these cases. A 77-year-old man was diagnosed as unresectable gastric cancer. The pathological diagnosis was tub2 and human epidermal growth factor receptor 2(HER2)positive(3+IHC method). We started chemotherapy(S-1+CDDP+trastuzumab). After 2 courses of S-1+CDDP, the findings of upper gastrointestinal endoscopy and CT were much improved to PR. But after 6 courses of S-1+CDDP, they worsened to PD. The regimen of chemotherapy was changed to weekly paclitaxel. The other patient, a 68-year-old woman, was diagnosed as far advanced gastric cancer. The pathological diagnosis was tub2=por2 and HER2 positive(3+IHC method). We started chemotherapy(S- 1+CDDP+trastuzumab). After 3 courses of S-1+CDDP, the tumor reduced significantly to PR. We continued this regimen. From the result of the ToGA trial, addition of trastuzumab to chemotherapy(capecitabine+CDDP or fluorouracil+CDDP) has been recommended as a new standard first-line regimen for HER2-positive advanced gastric cancer. But there is no evidence that trastuzumab added to the other regimen improved survival in patients with advanced gastric cancer. It is necessary to conduct a clinical trial to evaluate the treatment effect of this chemotherapy.

Topics: Aged; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Female; Humans; Male; Oxonic Acid; Stomach Neoplasms; Tegafur; Trastuzumab

A 63-year-old- female was admitted to our hospital complaining of cough. Based on CT, bone centigram and peripheral blood findings, a diagnosis of gastric carcinoma accompanied by bone marrow metastasis was made. As DIC developed following hospital admission, S-1 and docetaxel(DOC)therapy was initiated(daily oral administration of 80 mg/m(2) S-1 for 14 days and DOC at 40 mg/m(2) on day 1, q3w). Recovery from DIC was achieved. S-1 and DOC therapy is considered to be effective for DIC due to bone marrow metastasis of gastric carcinoma. S-1/DOC is thought to be an effective chemotherapy against progressive gastric carcinoma accompanied by disseminated carcinomatosis bone marrow with DIC.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Neoplasms; Bone Neoplasms; Disease Progression; Disseminated Intravascular Coagulation; Docetaxel; Drug Combinations; Female; Humans; Middle Aged; Oxonic Acid; Stomach Neoplasms; Taxoids; Tegafur

The aim of this study was to investigate the impact of the prognostic nutritional index (PNI) on the long-term outcomes in gastric cancer patients.. This study reviewed the medical records of 548 patients with gastric cancer who underwent gastrectomy. The PNI was calculated as 10 × serum albumin (g/dl) + 0.005 × total lymphocyte count (per mm(3)). The receiver operating characteristic (ROC) curve analysis was performed to determine the cutoff value of the PNI. The multivariate analysis was performed to identify the prognostic factors.. The mean PNI was significantly lower in patients with T3-T4 tumors (P < 0.001) and lymph node metastasis (P < 0.001) than in those without such factors. Patients who had a postoperative complication had a lower mean PNI than those without (P = 0.023). When the ROC curve analysis was performed, the optimal cutoff value of the PNI for predicting the 5-year survival was 48. In the multivariate analysis, a low PNI was an independent predictor for poor overall survival (P < 0.001). In the subgroup analysis, the overall and relapse-free survival rates were significantly lower in the PNI-low group than in the PNI-high group among patients with stage I and stage III disease.. The PNI is a simple and useful marker for predicting the long-term outcomes of gastric cancer patients independent of the tumor stage. Based on our results, we suggest that the PNI should be included in the routine assessment of gastric cancer patients.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoembryonic Antigen; Chemotherapy, Adjuvant; Cisplatin; Deoxycytidine; Disease-Free Survival; Drug Combinations; Female; Fluorouracil; Gastrectomy; Humans; Lymphatic Metastasis; Lymphocyte Count; Male; Middle Aged; Nutritional Status; Oxonic Acid; Predictive Value of Tests; Retrospective Studies; Serum Albumin; Stomach Neoplasms; Tegafur; Time Factors; Uracil; Young Adult

Our aim was to evaluate postoperative adjuvant chemotherapy using S-1 plus cisplatin(S-1/CDDP)for type 4 gastric cancer.. We investigated 18 patients who had undergone curative operations for type 4 gastric cancer. They were classified into two groups of patients, one using S-1/CDDP(group A: 9)and one using S-1 alone(group B: 9), after surgery between 2000 and 2010. Median survival time(MST)and survival rates were reported retrospectively. Patients as- signed to group A were treated with the following regimen: S-1, 80-120mg/day(body surface area 1. 25m2>: 80mg/day, 1. 25-1. 5m2: 100mg/day, 1. 5m2<: 120mg), was administered for 21 consecutive days followed by a 14-day rest period, and CDDP, 60mg/m2, was administered on day 8 for 5 courses. After this course, S-1 80mg/m2 was given for 18 months. S- 1(80-120mg/day, body surface area 1. 25m2>: 80mg/day, 1. 25-1. 5m2: 100mg/day, 1. 5m2<: 120mg)was administered for 28 days followed by 14-day rest as one course.. MST differed significantly between group A and group B (MST; group A: 1, 603 vs group B: 955 days). The overall survival rate at 5 years was 64. 8% in group A and 13% in group B, and the overall survival rate in group A was statistically better than that in group B(p=0. 02).. Postoperative adjuvant chemotherapy using S-1/CDDP for resected type 4 gastric cancer contributes to prolonged life, compared with using S-1 in overall survival.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cisplatin; Drug Combinations; Female; Humans; Male; Middle Aged; Oxonic Acid; Retrospective Studies; Stomach Neoplasms; Tegafur

We report a case of a 32-year-old woman with a septic pulmonary embolism-related implanted central venous port. She was treated with S-1/cisplatin(CDDP)chemotherapy for recurrent gastric cancer. Her disease was progressive after five courses of S-1/CDDP combination therapy. Because of peritonitis carcinomatosa, her oral intake was poor, so we placed an implanted central venous port in her right subclavian vein. We administered 5-FU/Leucovorin/paclitaxel combination therapy and total parenteral nutrition from the port. Chemotherapy was effective, so we stopped total parenteral nutrition after one month. Two months later, multiple nodular shadows appeared in her left lung fields without apparent symptoms. Because we suspected septic pulmonary embolism related to the venous port, we removed the venous port promptly and administered antibiotics with a broad spectrum. Pulmonary shadows disappeared immediately, and no recurrence was observed afterward.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Catheterization, Central Venous; Catheters, Indwelling; Cisplatin; Drug Combinations; Female; Humans; Neoplasm Recurrence, Local; Oxonic Acid; Pulmonary Embolism; Sepsis; Stomach Neoplasms; Tegafur

The trastuzumab for Gastric Cancer study newly defined tumors that were positive for human epidermal receptor-2 (Her-2) and created a Her-2-oriented treatment strategy that is also applicable in the adjuvant setting for stage 2/3 cancers. However, there is currently no information available on the rate of Her-2 positivity and the relapse-free survival (RFS) stratified by Her-2 status in stage 2/3 patients.. The Her-2 status, defined by the current standard method, was examined in 100 gastric cancer patients who underwent curative D2 surgery, who were pathologically diagnosed with stage 2/3 cancer, and received adjuvant S-1 chemotherapy between June 2002 and December 2011.. Ten of the 100 patients were Her-2 positive. Her-2-positive status was more frequently seen in tumors with a differentiated histology. The 5-year RFS rate was 56.3 % in Her-2-positive cases, and 48.8 % in Her-2 negative cases, which was not significantly different (P = 0.786).. The Her-2-positive rate for stage 2/3 gastric cancer patients was low, at only 10 %. Although the RFS was not significantly different based on the Her-2 status, the low positive rate made interpretation difficult. A multi-center study with a large sample size is necessary to clarify the prognostic impact of Her-2 in stage 2/3 gastric cancer patients.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Disease-Free Survival; Drug Combinations; Gastrectomy; Humans; Neoplasm Staging; Oxonic Acid; Prognosis; Receptor, ErbB-2; Stomach Neoplasms; Tegafur

Choroidal or cutaneous metastasis of gastric cancer is rare. Gastrointestinal cancer was found in only 4% in patients with uveal metastasis. Choroidal metastasis from gastric cancer was reported in two cases in earlier literature. The frequency of gastric cancer as a primary lesion was 6% in cutaneous metastasis of men, and cutaneous metastasis occurs in 0.8% of all gastric cancers. We report a patient with gastric adenocarcinoma who presented with visual disorder in his left eye and skin pain on his head as his initial symptoms. These symptoms were diagnosed to be caused by choroidal and cutaneous metastasis of gastric adenocarcinoma. Two cycles of chemotherapy consisted of oral S-1 and intravenous cisplatin (SPIRITS regimen); this was markedly effective to reduce the primary gastric lesion and almost all the metastatic lesions.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Biopsy; Choroid Neoplasms; Cisplatin; Drug Combinations; Endoscopy, Gastrointestinal; Head and Neck Neoplasms; Humans; Magnetic Resonance Imaging; Male; Multimodal Imaging; Oxonic Acid; Positron-Emission Tomography; Predictive Value of Tests; Scalp; Skin Neoplasms; Stomach Neoplasms; Tegafur; Tomography, Emission-Computed, Single-Photon; Tomography, Optical Coherence; Treatment Outcome

The Adjuvant Chemotherapy Trial of TS-1 for Gastric Cancer (ACTS-GC) demonstrated that S-1(TS-1, an oral fluoropyrimidine) was effective as adjuvant chemotherapy for patients with pathological stage II or III gastric cancer who underwent curative gastrectomy. The objective of this study was to clarify the risk factors for recurrence in patients who received S-1 adjuvant chemotherapy.. We retrospectively analyzed the factors predicting recurrence in 77 patients with stage II or III gastric cancer who received S-1 chemotherapy following R0 gastrectomy between April 2003 and October 2008.. The tumor diameter, macroscopic appearance, and presence of lymph node metastasis were significant factors predictive of recurrence identified by the univariate analysis. Moreover, the tumor diameter was an independent risk factor identified by the multivariate analysis.. It is necessary to establish a chemotherapeutic regimen for patients with stage II/III gastric cancers with large tumor diameter.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Drug Combinations; Female; Follow-Up Studies; Humans; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Oxonic Acid; Prognosis; Retrospective Studies; Risk Factors; Stomach Neoplasms; Survival Rate; Tegafur

To investigate the effect of surgery and chemotherapy for gastric cancer with multiple synchronous liver metastases (GCLM).. A total of 114 patients were entered in this study, and 20 patients with multiple synchronous liver metastases were eligible. After screening with preoperative chemotherapy, 20 patients underwent curative gastrectomy and hepatectomy for GCLM; 14 underwent major hepatectomy, and the remaining six underwent minor hepatectomy. There were 94 patients without aggressive treatment, and they were in the non-operative group. Two regimens of perioperative chemotherapy were used: S-1 and cisplatin (SP) in 12 patients, and docetaxel, cisplatin and 5-fluorouracil (DCF) in eight patients. These GCLM patients were given preoperative chemotherapy consisting of two courses chemotherapy of SP or DCF regimens. After chemotherapy, gastrectomy and hepatectomy were preformed. Evaluation of patient survival was by follow-up contact using telephone and outpatient records. All patients were assessed every 3 mo during the first year and every 6 mo thereafter.. Twenty patients underwent gastrectomy and hepatectomy and completed their perioperative chemotherapy and hepatic arterial infusion before and after surgery. Ninety-four patients had no aggressive treatment of liver metastases because of technical difficulties with resection and severe cardiopulmonary dysfunction. In the surgery group, there was no toxicity greater than grade 3 during the course of chemotherapy. The response rate was 100% according to the response evaluation criteria in solid tumors criteria. For all 114 patients, the overall survival rate was 8.0%, 4.0%, 4.0% and 4.0% at 1, 2, 3 and 4 years, respectively, with a median survival time (MST) of 8.5 mo (range: 0.5-48 mo). For the 20 patients in the surgery group, MST was 22.3 mo (range: 4-48 mo). In the 94 patients without aggressive treatment, MST was 5.5 mo (range: 0.5-21 mo). There was a significant difference between the surgery and unresectable patients (P = 0.000). Three patients in surgery group were still alive at the end of the cut-off date.. Perioperative weekly DCF and SP achieved a good response, and combined with surgery, they could improve prognosis of GCLM.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Docetaxel; Drug Combinations; Female; Fluorouracil; Glycosylation; Humans; Liver Neoplasms; Male; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Pilot Projects; Stomach Neoplasms; Taxoids; Tegafur; Treatment Outcome

The development of aortic thrombosis without the presence of atheroscrelosis, dissection, or aneurysms is rare. A cancer-related hypercoagulable state is a well-known risk factor for venous thrombosis, however, atrial thrombosis has rarely been reported in cancer patients. Cisplatin-based chemotherapy is known to cause various side-effects. Detecting aortic thrombosis is important because it is a fatal condition. We herein present the first reported case of endo-aortic thrombosis occurring during cisplatin-based chemotherapy for gastric cancer.

Topics: Acute Disease; Anticoagulants; Antineoplastic Combined Chemotherapy Protocols; Aortic Diseases; Aortography; Arterial Occlusive Diseases; Carcinoma, Signet Ring Cell; Cisplatin; Dexamethasone; Drug Combinations; Heparin; Humans; Oxonic Acid; Stomach Neoplasms; Tegafur; Thrombosis; Tomography, X-Ray Computed; Warfarin

A 35-year-old female with scirrhous stomach cancer (stage IV) was treated with a combination of 5-aminolevulinic acid (ALA), sodium dichloroacetate (DCA), hyperthermotherapy, and immunotherapy as terminal care. The patient survived for one year and seven months, during which her quality of life was markedly improved and she returned to work. The patient was diagnosed with poorly-differentiated adenocarcinoma and progressive signet-ring cell carcinoma, accompanied by left ovarian metastasis, peritoneal dissemination, and right hydronephrosis stage IV, and treated with combination chemotherapy with tegafur-gimeracil-oteracil potassium (TS-1) and docetaxel. Oral ALA and DCA were concomitantly administered at 50 mg each three times a day (150 mg/day, respectively). In addition, hyperthermotherapy using thermotron was concomitantly performed at 2- to 3-week intervals. Cellular immunotherapy with αβ T- and immature dendritic cells was also performed. The disease did not progress for 11 months, her quality of life was markedly improved, and she was able to return to work. However, the signs of enlargement of the ovarian metastatic lesion were noted later, for which chemotherapy with four cycles of second-line paclitaxel and a half dose of irinotecan and cisplatin as third-line treatment were performed. Combination of ALA/DCA, hyperthermotherapy, and cellular immunotherapy may be a low-invasive palliative therapy superior in maintaining quality of life of tumor-bearing terminally ill individuals.

Topics: Adenocarcinoma, Scirrhous; Adult; Aminolevulinic Acid; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Carcinoma, Signet Ring Cell; Cisplatin; Combined Modality Therapy; Dichloroacetic Acid; Docetaxel; Drug Combinations; Drug Therapy, Combination; Female; Humans; Hyperthermia, Induced; Irinotecan; Ovarian Neoplasms; Oxonic Acid; Paclitaxel; Peritoneal Neoplasms; Photosensitizing Agents; Prognosis; Silicates; Stomach Neoplasms; Taxoids; Tegafur; Titanium

We retrospectively examined the feasibility and outcome of S-1 adjuvant chemotherapy for 18 patients with gastric cancer treated based on the liaison-clinical pathway (liaison group), and compared them with those of 26 patients treated before the induction of the liaison-clinical pathway (non-liaison group). The persistent rate of S-1 adjuvant chemotherapy for one year except for recurrence, the relative performance (RP) value of cases who had received S-1 for one year, and Grade 3/4 adverse events in non-liaison group/liaison group, were 88.5/87.5% (p = 0.93), 87.0/92.9% (p = 0.56), and 26.9/5.6% (p = 0.07), respectively. This did not show a significant difference. The rate of patients administered medication for coexistent diseases in our hospital in the non-liaison group/liaison group was 53.8/0% (p = 0.0002), which reflected the accomplishment of the transfer of medical care for coexistent disease from a hospital to a clinic on the liaison-clinical pathway. Furthermore, a neighboring clinic could be arranged to accommodate 9 (64.3%) of 14 patients living quite far from the hospital in the liaison group. In conclusion, S-1 adjuvant chemotherapy for patients with gastric cancer treated based on the liaison-clinical pathway was feasible, led to the effective practice of sharing between hospital and clinic, and the shorter trip for treatment at a neighboring clinic by patients living far from a hospital.

Topics: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Critical Pathways; Drug Combinations; Feasibility Studies; Female; Humans; Male; Middle Aged; Oxonic Acid; Stomach Neoplasms; Tegafur; Treatment Outcome

An 84-year-old man had the wall thickness of his stomach accidentally detected by CT scan, and was diagnosed as type 2 advanced gastric cancer with liver and lung metastasis. Chemotherapy with docetaxel, cisplatin and S-1 combination therapy was adopted. Grade 4 neutropenia was revealed, but the treatment could be continued by G-CSF or by down dosing the anticancer agents. By maintaining CR of the primary lesion and PR of the liver and lung metastases, he has been kept at a PS 0 state and has been receiving regular outpatient treatment for 28 months now since the beginning of treatment.

Topics: Aged, 80 and over; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Docetaxel; Drug Combinations; Humans; Male; Oxonic Acid; Stomach Neoplasms; Taxoids; Tegafur

A 71-year-old man, diagnosed with advanced gastric cancer and severe pyloric stenosis, was introducted to our hospital. Para-aortic lymph nodes metastasis and pancreas invasion were seen with enhanced CT scan. Serum AFP showed a high price (1,465.3 ng/mL). Because significant peritoneal metastases were seen in the abdominal cavity, gastrojejunostomy was performed. Overexpression of the HER2 gene was seen by immunostaining for peritoneal dissemination of the omentum. After starting S-1 + CDDP + trastuzumab, the AFP was normalized immediately (7. 6 ng/mL). We then performed colostomy for a sigmoid colon stenosis. S-1 + DOC + trastuzumab was administered afterward, and we performed closure of the colostomy because the stenosis was improved. Macroscopic peritoneal dissemination in the abdomen disappeared. AFP-producing gastric cancer with peritoneal metastasis has a poor prognosis, but chemotherapy, mainly with S-1 and trastuzumab, was effective for it.

Topics: Aged; alpha-Fetoproteins; Antibodies, Monoclonal, Humanized; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Humans; Male; Oxonic Acid; Peritoneal Neoplasms; Stomach Neoplasms; Tegafur; Trastuzumab

S-1 adjuvant chemotherapy following radical surgery has been the standard therapy for the pStage II/III gastric cancer in Japan. However, there are few reports regarding treatment for gastric cancer recurrence during S-1 therapy. Here, we present a case of recurrent gastric cancer during S-1 adjuvant therapy that showed partial response to CDDP + capecitabine therapy. A 72-year-old man was diagnosed as having gastric cancer. We performed a distal gastrectomy+D2 dissection, with Roux-en Y reconstruction. The patient was treated with S-1 for adjuvant chemotherapy. Six months after operation, multiple mediastinal lymph node recurrence developed. CDDP + CPT-11 was applied for two courses as first-line treatment for the recurrence. However, the disease progressed with worsening mediastinal lymph node metastases (progressive disease). After two courses of CDDP + capecitabine as second-line chemotherapy, the recurrence site became smaller. After five courses, partial response (PR) had been achieved. Two years and five months after gastrectomy, capecitabine monotherapy was applied as third-line chemotherapy.

Topics: Aged; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Chemotherapy, Adjuvant; Cisplatin; Deoxycytidine; Drug Combinations; Fluorouracil; Humans; Lymphatic Metastasis; Male; Oxonic Acid; Stomach Neoplasms; Tegafur

A 47-year-old woman was diagnosed as advanced gastric cancer of cardia(poorly-differentiated adenocarcionoma), with multiple para-aortic lymph node and liver metastasis, in March, 2005. We attempted neo-adjuvant chemotherapy with docetaxel(DOC), cisplatin(CDDP), and S-1(DCS). After 3 courses of DCS, we confirmed that the para-aortic lymph nodes and liver metastasis became small. Then, we were able to perform total gastrectomy, splenectomy, and D2 lymph node dissection. Additionally, we performed an intraoperative radiofrequency ablation to the scar of the liver metastasis. Histopathologically, we identified lymph node metastases in #1 and #16b1 pre. S-1 and DOC were administered as adjuvant chemotherapy. At seven years since the operation, the patient has shown no signs of recurrence. Combined modality therapy for advanced gastric cancer diagnosed with stage IV can be an effective treatment, so we hope that it will be established as a standard therapy.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Docetaxel; Drug Combinations; Female; Gastrectomy; Humans; Middle Aged; Neoplasm Staging; Oxonic Acid; Stomach Neoplasms; Taxoids; Tegafur; Time Factors

Carcinomatous peritonitis may develop after operation for gastric cancer. As ascites are difficult to control, especially for gastric cancer postoperative carcinomatous peritonitis, many cases are difficult to treat. The present case was a female patient with carcinomatous peritonitis that occurred 2 years post-surgery. Administration of docetaxel (DOC)and S-1 combination therapy achieved a complete response. However, she had a relapse of carcinomatous peritonitis 3 years post-surgery. She underwent bypass operation, followed by DOC and S-1 combination therapy again. She achieved a good quality of life for more than two years. As side effects in patients worsen with the repeated exposure to chemotherapy, continuing the same treatment is difficult. Therefore, we changed the therapy method to irinotecan(CPT-11)/cisplatin(CDDP)therapy, weekly paclitaxel(PTX)and methotrexate(MTX)/5-fluorouracil(5-FU)therapy, and bypass operation when necessary. Rapid progression of her condition was sequentially suppressed, allowing her to continue her everyday life. Overall, this treatment method provided survival benefits of approximately four years following the recurrence of carcinomatous peritonitis.

Topics: Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cisplatin; Combined Modality Therapy; Drug Combinations; Fatal Outcome; Female; Fluorouracil; Gastrectomy; Humans; Irinotecan; Methotrexate; Middle Aged; Oxonic Acid; Paclitaxel; Peritoneal Neoplasms; Peritonitis; Stomach Neoplasms; Tegafur; Time Factors

A 71-year-old man was diagnosed with gastric cancer[cT4, cN0, cH1(S6), cP0, cM0, cStage IV]and underwent distal gastrectomy with cholecystectomy, partial colectomy for the invasion to the mesentery of transverse colon, and partial hepatectomy for metastatic liver tumor(segment 6). Although chemotherapy with S-1+CDDP was administered after the operation, a recurrent lesion appeared in the remnant of liver(segment 6). The chemotherapy regimen was changed to S-1+CPT-11. Since the only recurrent tumor was found in the remnant liver, it was resected. After S-1 chemotherapy, no recurrence has been detected since the first operation. A good outcome was obtained for this patient with synchronous liver metastasis and the recurrence remnant liver originating from gastric cancer, possibly as a result of the combination of chemotherapy and surgical resection for the primary lesion and liver metastasis.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cisplatin; Combined Modality Therapy; Drug Combinations; Gastrectomy; Hepatectomy; Humans; Irinotecan; Liver Neoplasms; Male; Oxonic Acid; Stomach Neoplasms; Tegafur; Tomography, X-Ray Computed

A 53-year-old man was diagnosed with advanced gastric cancer(cT4aN2M0, StageIII B), with regional bulky lymph node metastases invading the splenic artery. S-1 plus cisplatin treatment(S-1/CDDP)was administered as neoadjuvant chemo- therapy(NAC). S-1(80mg/m2)was administered orally for 21 days, followed by 14 drug-free days as a course. CDDP(60 mg/m2)was administered by intravenous drip on day 8. After two courses, significant tumor reduction was obtained, and the patient then had total gastrectomy and splenectomy performed with a D2 dissection. Distal pancreatectomy was avoided. Macroscopically, the stomach seemed to be penetrated by the tumor into the serosa, yet the histological diagnosis revealed complete disappearance of cancer cells in all of the lymph nodes, and very few residual tumor cells were noted, only on the gastric mucosa(pT1aN0M0, Stage I A). Therefore, downstaging was confirmed. S-1/CDDP as a NAC regimen for advanced gastric cancer appears to be an effective treatment.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Gastrectomy; Humans; Lymphatic Metastasis; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Oxonic Acid; Remission Induction; Splenectomy; Stomach Neoplasms; Tegafur

A 75-year-old man was found, by endoscopic examination, to have type 2 advanced gastric adenocarcinoma with esophageal invasion in the cardia. Endoscopy and other modalities revealed observable esophageal invasion. To minimize surgical intervention, we treated him with S-1 and cisplatin as neoadjuvant therapy. Treatment was as follows: S-1(80mg/m2)was administered orally for 3 weeks followed by 2 weeks of rest, and cisplatin(60mg/m2)was administered by intravenous drip on day 8. Two courses of treatment resulted in marked shrinkage of the primary lesion and improvement of the esophageal invasion. Total gastrectomy with splenectomy, and D2 lymph node dissection were performed with an adequately long proximal margin, without thoracotomy. Pathological efficacy was Grade 2. At present, 1 year after the operation, the patient presents no evidence of a recurrence. We concluded that through neoadjuvant chemotherapy for advanced gastric cancer with esophageal invasion, thoracotomy could be avoided, thereby reducing risks associated with surgery.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Esophagus; Gastrectomy; Humans; Male; Neoadjuvant Therapy; Neoplasm Invasiveness; Oxonic Acid; Splenectomy; Stomach Neoplasms; Tegafur

Polysaccharide K (PSK) is widely used in Japan as a biological response modifier for cancer patients. We investigated the effects of PSK with S-1 based chemotherapy for advanced gastric cancer patients in immune response.. Nine advanced gastric cancer patients who underwent chemotherapy at the University of Tokushima were included in this study. In all patients, 3g PSK was received orally and S-1 based chemotherapy for 2 weeks alternately for 8 weeks. Serial changes in immunological parameters (Foxp3, Natural killer (NK), CD4/CD8) were monitored.. The levels of Foxp3 at 8 weeks was significantly decreased compared with 2 weeks (4.26% vs. 3.11%). In NK activity at 8 weeks was significantly increased compared with 2 weeks (27% vs. 47%).. These results of this study suggested that chemotherapy with PSK improved the immune response in advanced gastric cancer patients. Especially Foxp3 was concerned in this mechanism.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Female; Forkhead Transcription Factors; Humans; Killer Cells, Natural; Male; Middle Aged; Oxonic Acid; Proteoglycans; Stomach Neoplasms; Tegafur

Tetraspanin CD151 is known to be involved in cancer invasion and metastasis, and its overexpression appears to be associated with a poor prognosis for various types of cancer. However, the expression status of CD151 and its prognostic impact in advanced gastric cancer (AGC) has not yet been clarified.. Immunohistochemistry was used to investigate the expression of CD151, c-erbB2, and c-Met in 159 cases of AGC. The clinicopathological and prognostic significance of these biomarkers were then evaluated.. The overexpression of CD151 was observed in a subset of advanced gastric adenocarcinomas (25.8 %), and c-erbB2 and c-Met were overexpressed in 15.1 and 35.2 % of the cohort, respectively. CD151 overexpression was more frequently observed in tumors from younger patients (P = 0.028). There were close associations between CD151 and c-erbB2 overexpression (P = 0.033) and between c-erbB2 and c-Met overexpression (P = 0.001). CD151 overexpression was closely correlated with patient' overall survival (OS; P < 0.001) and disease-free survival (DFS; P < 0.001). Furthermore, the expression rate of CD151 seemed to increase gradually according to the depth of invasion (T stage) (χ(2) test for trend; P = 0.101), N stage (P = 0.238), and pathologic stage (P = 0.153), although trends were not statistically significant. In a multivariate analysis, CD151 overexpression was an independent prognostic factor predicting worse OS (P = 0.002) and DFS (P = 0.005), along with the T and N stage.. CD151 was found to be an independent prognostic marker for patients with AGC.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Cisplatin; Cohort Studies; Digestive System Surgical Procedures; Drug Combinations; Female; Humans; Immunohistochemistry; Lymph Node Excision; Male; Middle Aged; Oxonic Acid; Pilot Projects; Prognosis; Receptor Protein-Tyrosine Kinases; Receptor, ErbB-2; Stomach Neoplasms; Tegafur; Tetraspanin 24; Young Adult

Pancreatic cancer is frequently complicated by malignancies in other organs. However, synchronous triple cancers including pancreatic cancer have been seldom reported in the English language literature.. We describe the rare case of a 77-year-old man with triple cancers of the pancreas, stomach, and cecum. Biopsies revealed that all three tumors were adenocarcinomas. The pancreatic and gastric tumors were positive for cytokeratin 7 and negative for cytokeratin 20, whereas the cecal tumor was negative for cytokeratin 7 and positive for cytokeratin 20. K-ras mutations were present at codon 12 in the pancreatic tumor and at codon 13 in the cecal tumor, but were absent from the gastric tumor. Since the three tumors had different characteristics, the patient was diagnosed with synchronous triple cancers. Because invasive surgery was required to remove all three tumors and the patient had risk factors for surgery, we elected to treat him with chemotherapy. All three cancers were markedly reduced in size by treatment with cycles of 100 mg/day S-1 for 2 weeks, followed by a 1-week rest. The patient later developed hypoproteinemia and anasarca, which was diagnosed as pancreatic exocrine insufficiency due to pancreatic head cancer. Treatment with pancrelipase resulted in dramatic improvements in hypoproteinemia and anasarca.. This is the first case report in which S-1 was effective in triple cancers of the pancreas, stomach, and cecum. Patients with pancreatic head cancer should be monitored for pancreatic exocrine insufficiency.

Topics: Adenocarcinoma; Aged; Antineoplastic Agents; Cecal Neoplasms; Drug Combinations; Edema; Humans; Hypoproteinemia; Keratin-20; Keratin-7; Male; Mutation; Neoplasms, Multiple Primary; Oxonic Acid; Pancreatic Neoplasms; Pancrelipase; Proto-Oncogene Proteins; Proto-Oncogene Proteins p21(ras); ras Proteins; Stomach Neoplasms; Tegafur; Treatment Outcome

A 66-year-old man was admitted to our hospital with a diagnosis of advanced gastric cancer, with a tumor embolus in the portal vein and lymph node metastases. Since curative surgery was deemed impossible, we started neoadjuvant chemotherapy using S-1 plus CDDP. After 1 course of chemotherapy, the embolus in the portal vein disappeared. After additional chemotherapy, the primary tumor and lymph nodes were reduced in size, and a total gastrectomy with splenectomy and lymph node dissection was performed. Although he received S-1 medication as adjuvant chemotherapy, a tumor embolus in the portal vein appeared 8 months after the operation. Chemoradiotherapy(S-1+total of 50.4 Gy)was performed and the tumor embolus disappeared.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Cisplatin; Drug Combinations; Embolism; Humans; Male; Neoadjuvant Therapy; Oxonic Acid; Portal Vein; Stomach Neoplasms; Tegafur

We retrospectively examined patients with advanced gastric cancer who underwent gastrectomy following neoadjuvant chemotherapy (NAC) with S-1 plus weekly low-dose cisplatin (CDDP). Between 2007 and 2009, 27 patients with advanced gastric cancer not amenable to curative surgery were enrolled. One course of NAC comprised S-1 (80 mg/m2/day) for 21 consecutive days and CDDP (20 mg/m2) on days 1, 8, and 15; this was followed by a 2-week rest after the end of S-1 administration. Grade 3 side effects were observed in 5 patients: 3 experienced neutropenia and 2 experienced digestive symptoms. The outpatient completion rate was 81.5% (22/27); there was no incidence of renal dysfunction. During pretherapy diagnosis, depth of invasion was classified as T4 in all cases. Postoperative pathologic results showed that the depth of invasion was T3 or lower in 4 patients. In addition, the number of patients with N0 and M0 classification increased and downstaging was observed in 12 patients (44.4%). A comprehensive assessment revealed that a partial response (PR) was observed in 13 patients and stable disease (SD) was observed in 12 patients, resulting in a response rate of 48.1%. The median survival time was 580 days, and the 1-year survival rate was 72%. NAC with S-1 plus weekly low-dose CDDP can also be administered on an outpatient basis, and it is a potential regimen for the treatment of advanced gastric cancer associated with a poor prognosis.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Administration Schedule; Drug Combinations; Female; Gastrectomy; Humans; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Oxonic Acid; Prognosis; Stomach Neoplasms; Tegafur

Ten patients aged 75 years or more with advanced or metastatic gastric cancer were prescribed S-1 plus docetaxel (DOC) combination therapy. None of the patients showed complete response, but 2 showed partial response and 4 showed stable disease. Grade 3 or 4 toxicities occurred in 3 patients. Three patients with performance status (PS) 1 achieved partial response or stable disease and were free of Grade 3 or 4 toxicities, whereas the response and occurrence of adverse events in 7 patients with PS 2 varied widely. In these patients, an investigation of the relationship between response to treatment and the Vulnerable Elders Survey (VES-13) score showed that VES-13 scores were higher in the non-response group than in the other patients and in patients who experienced adverse events than in those who did not. These findings suggest that VES-13 could be a useful screening tool for predicting response and the occurrence of adverse events in elderly patients undergoing combined S-1 plus DOC therapy for advanced or metastatic gastric cancer.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Data Collection; Docetaxel; Drug Combinations; Female; Humans; Male; Neoplasm Metastasis; Oxonic Acid; Stomach Neoplasms; Taxoids; Tegafur

We retrospectively examined the efficacy and safety of S-1 alone or S-1 plus cisplatin (SP) for elderly patients with advanced gastric cancer because the benefit of adding cisplatin in these patients still remains unclear.. Among 175 patients aged 70 years or older who received S-1 alone or SP as a first-line therapy between April 2000 and November 2010 at our institution, 104 patients who met eligibility criteria were examined. We investigated safety and efficacy of S-1 and SP.. Among these 104 patients, 73 patients received S-1 and 31 patients received SP. The median age was 75 years in the S-1 group and 74 years in the SP group. The response rate was 26.3 % in the S-1 group and 44.0 % in the SP group. Major grade 3 or higher adverse events were observed as follows (S-1 vs. SP): nausea (1.4 vs. 16.1 %), anorexia (16.4 vs. 41.9 %), neutropenia (4.1 vs. 35.5 %), and febrile neutropenia (0 vs. 9.7 %). The median overall survival (OS) was 10.4 months in the S-1 group and 17.8 months in the SP group. Treatment of SP and histology of intestinal type were detected as independent, good prognostic factors in multivariate analysis.. SP might improve OS with some added toxicity compared to S-1 alone in elderly patients with advanced gastric cancer.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Disease Progression; Drug Combinations; Female; Humans; Male; Neoadjuvant Therapy; Oxonic Acid; Retrospective Studies; Stomach Neoplasms; Tegafur; Treatment Outcome

We aimed to evaluate the safety and efficacy of TS-1 adjuvant chemotherapy in Taiwanese patients with gastric cancer.. We included in this study patients with locally advanced gastric cancer who received adjuvant TS-1 or 5-fluorouracil chemotherapy after curative surgery and extended lymph node dissection between 1 June 2008 and 31 December 2012 at Chang Gung Memorial Hospital. Patient characteristics, tumor features, safety profiles and compliance with TS-1 treatment were retrospectively analyzed from medical charts.. Forty patients received adjuvant chemotherapy with TS-1 and 193 with 5-fluorouracil within the study period. The 1- and 2-year overall survival rates were 90.6% and 87% in the TS-1 group and 95.4% and 86.8% in the 5-fluorouracil group (P = 0.34). The 1- and 2-year disease-free survival rates were 90.6% and 74.7% in the TS-1 group and 88% and 75.7% in the 5-fluorouracil group (P = 0.66). In the TS-1 group, tumor recurrence was more frequent in those with >15 metastatic lymph nodes than ≤15. Overall, 78.9%, 74.3%, 62.1% and 56% of patients underwent TS-1 treatment for at least 3, 6, 9 and 12 months, respectively. The most common adverse events of TS-1 were skin hyperpigmentation (55%), diarrhea (27.5%), dizziness (27.5%) and leucopenia (20%). Severe adverse events (SAEs; grade III or IV toxicity) were diarrhea (7.5%), stomatitis (7.5%), leukopenia (5%), vomiting (2.5%), anorexia (2.5%) and dizziness (2.5%). Patients who underwent total gastrectomy had a significantly greater risk of TS-1-related SAEs than patients who underwent subtotal gastrectomy (40% versus 8%, P = 0.014).. The incidence of SAEs during TS-1 therapy was more common in Taiwanese patients with gastric cancer who underwent total gastrectomy compared with those who underwent subtotal gastrectomy. Clinicians must be aware of and able to manage these SAEs to maximize patient compliance with adjuvant TS-1.

Topics: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Combined Modality Therapy; Drug Combinations; Drug-Related Side Effects and Adverse Reactions; Female; Follow-Up Studies; Gastrectomy; Humans; Incidence; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Prognosis; Retrospective Studies; Stomach Neoplasms; Survival Rate; Tegafur

The aim of this study was to assess the feasibility and safety of adjuvant chemotherapy with S-1 followed by docetaxel.. Twenty-eight patients with advanced gastric cancer underwent gastrectomy without preoperative chemotherapy. These patients were divided into 3 groups on the basis of cytologic results of peritoneal lavage (CY) and the presence of local peritoneal metastatic nodules (P): CY1-P0, CY0-P1, and CY1-P1. Oral S-1 (80 mg/m(2)/day) was administered for 3 consecutive weeks, followed by intravenous docetaxel (35 mg/m(2)) on days 29 and 43 (1 cycle). This cycle was repeated every 8 weeks. The primary endpoint was the ability to complete 6 cycles of S-1 followed by docetaxel. The secondary endpoints were safety, progression-free survival, mean survival time (MST), and overall survival (OS).. The subjects were 18 men and 10 women (39 to 78 years old, median age, 64 years). The extent of peritoneal metastasis was CY1-P0 in 8 patients, CY0-P1 in 14 patients, and CY1-P1 in 6 patients. Both hematologic and nonhematologic toxicities were generally mild. The completion rate of the planned 6 cycles of the protocol was 71.4% (20 of 28 patients). Median progression-free survival was 22.9 months, and the 2-year survival rate was 78.6%. The overall MST was 34.3 months, and the MST by group was 34.5 for CY1-P0, 34.3 for CY0-P1, and 19.3 months for CY1-P1. The OS in the CY1-P0 and CY0-P1 groups was significantly longer than that in the CY1-P1 group (P<0.05).. Adjuvant chemotherapy with S-1 followed by docetaxel is safe and well tolerated and has the potential to improve OS in patients with a status of CY1P0 following relatively curative resection.

Topics: Administration, Intravenous; Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Chemotherapy, Adjuvant; Disease Progression; Disease-Free Survival; Doxorubicin; Drug Administration Schedule; Drug Combinations; Feasibility Studies; Female; Gastrectomy; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Oxonic Acid; Peritoneal Neoplasms; Stomach Neoplasms; Survival Rate; Tegafur; Time Factors; Treatment Outcome

We encountered cases of unresectable gastric cancer in which patients had difficulty with ingestion because of pyloric stenosis and diffuse invasion. We examined the improvement in the quality of life(QOL)of patients and the effect and usefulness of S-1 treatment in such cases. The median survival time(MST; 310 days)of patients who received S-1 as primary treatment was significantly longer than that(105 days)of patients who did not receive S-1 treatment(p=0.0001). Of the 25 patients who underwent gastrojejunostomy, S-1 was administered to 10 patients(MST: 384 days). The MST of patients who received drugs other than S-1 was 121 days. Thus, the MST of patients who did receive S-1 was significantly longer than that of patients who did not receive S-1. In univariate analysis, oral ingestion, performance status(PS), best supportive care(BSC), and S-1 administration were prognostic factors. Of these factors, oral ingestion(p=0.0278, hazard ratio[HR]: 2.992)and S- 1 administration(p=0.0002, HR: 14.956)were prognostic factors in multivariate analysis. Gastrojejunostomy is desirable for the treatment of cases of unresectable gastric cancer with poor ingestion. In addition, the use of postoperative chemotherapy with S-1 alone or with S-1 as combination therapy may help improve prognosis.

Topics: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Drug Combinations; Female; Humans; Male; Middle Aged; Oxonic Acid; Patient Discharge; Quality of Life; Stomach Neoplasms; Tegafur

Here, we report the case of a patient with advanced gastric cancer complicated by pyloric stenosis and direct invasion into the pancreas who underwent curative resection after bi-weekly S-1/docetaxel(DS)therapy after gastrojejunostomy. A 73-year-old man consulted a general practitioner because of indigestibility, and upper gastrointestinal endoscopy indicated gastric cancer. He was referred to our hospital. Gastric cancer, whole stomach tumor(LMU), 150×80 mm, Type 3, T4a(SE), N2, M0, stage III B was diagnosed, and surgery was performed. The tumor was seen to directly invade the pancreas and the middle colic artery intraoperatively, so only a gastrojejunostomy was performed. After the operation, the patient was treated with DS therapy for 13 courses, and the response was defined as non-complete response(CR)and non-progressive disease (PD). During the second laparotomy, a curative operation was performed via distal gastrectomy because frozen-section diagnosis revealed that no cancer cells were present at the oral margin. Postoperatively, the tumor was diagnosed as LM, 10× 7 mm, 10×2.5 mm, pType 4, pT2(MP), pN0, pM0, CY0, stage I B. The patient is now receiving S-1 adjuvant chemotherapy and is still alive 2 years and 4 months after the first operation.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Docetaxel; Drug Combinations; Gastrectomy; Humans; Male; Oxonic Acid; Stomach Neoplasms; Taxoids; Tegafur

A 64-year-old man was diagnosed with advanced gastric cancer type 3 and regional celiac trunk lymph node metastases. We performed preoperative chemotherapy with docetaxel, cisplatin, and S-1(DCS therapy). Total gastrectomy with lymph node dissection was performed after 2 courses of DCS. Pathologically, no viable cells were found in the primary lesion or in the dissected lymph nodes. The pathological response to preoperative DCS therapy was classified as grade 3. The postoperative course was uneventful; the patient is currently healthy and receives periodic medical examinations.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Docetaxel; Drug Combinations; Humans; Lymphatic Metastasis; Male; Middle Aged; Oxonic Acid; Stomach Neoplasms; Taxoids; Tegafur

A questionnaire survey on postoperative adjuvant chemotherapy for gastric cancer was conducted for 76 hospitals affiliated with the Hiroshima Oncology Group of Gastric Cancer in Hiroshima prefecture in January 2011. Responses were obtained from 29 hospitals, including 12 core cancer treatment hospitals, and the following results were obtained. The percentage of patients completing 1 year of oral S-1 was >70%, affecting approximately 75% of the entire hospital cohort. Dose reduction was conducted in approximately 30% of patients because of age, poor PS, and renal insufficiency. The standard S-1 regimen (4 weeks of S-1 treatment followed by 2 weeks of rest)was adopted in almost half of the patients, whereas the rest of the patients received another treatment schedule such as 2 weeks of treatment followed by 1 week of rest. Dose reduction and withdrawal of S-1 due to adverse events were conducted more frequently in hospitals with low completion rates of 1-year S- 1 treatment than those with a high completion rate. S-1 was most commonly discontinued because of subjective adverse events and patient request, although the discontinuation rate according to objective adverse events such as bone marrow depression was not very high. The fact that some hospitals had high completion rates suggested the importance of supplementary tools for patient IC.

Topics: Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Drug Combinations; Humans; Japan; Neoplasm Staging; Oxonic Acid; Stomach Neoplasms; Surveys and Questionnaires; Tegafur

First-line postoperative adjuvant chemotherapies with S-1 and capecitabine and oxaliplatin (XELOX) were first recommended for resectable gastric cancer patients in the 2010 and 2011 Chinese NCCN Clinical Practice Guidelines in Oncology: Gastric Cancer; however, their economic impact in China is unknown.. The aim of this study was to compare the cost-effectiveness of adjuvant chemotherapy with XELOX, with S-1 and no treatment after a gastrectomy with extended (D2) lymph-node dissection among patients with stage II-IIIB gastric cancer.. A Markov model, based on data from two clinical phase III trials, was developed to analyse the cost-effectiveness of patients in the XELOX group, S-1 group and surgery only (SO) group. The costs were estimated from the perspective of Chinese healthcare system. The utilities were assumed on the basis of previously published reports. Costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICER) were calculated with a lifetime horizon. One-way and probabilistic sensitivity analyses were performed.. For the base case, XELOX had the lowest total cost ($44,568) and cost-effectiveness ratio ($7,360/QALY). The relative scenario analyses showed that SO was dominated by XELOX and the ICERs of S-1 was $58,843/QALY compared with XELOX. The one-way sensitivity analysis showed that the most influential parameter was the utility of disease-free survival. The probabilistic sensitivity analysis predicted a 75.8% likelihood that the ICER for XELOX would be less than $13,527 compared with S-1. When ICER was more than $38,000, the likelihood of cost-effectiveness achieved by S-1 group was greater than 50%.. Our results suggest that for patients in China with resectable disease, first-line adjuvant chemotherapy with XELOX after a D2 gastrectomy is a best option comparing with S-1 and SO in view of our current study. In addition, S-1 might be a better choice, especially with a higher value of willingness-to-pay threshold.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bayes Theorem; Capecitabine; Chemotherapy, Adjuvant; China; Clinical Trials, Phase III as Topic; Cost-Benefit Analysis; Deoxycytidine; Disease Progression; Disease-Free Survival; Drug Combinations; Fluorouracil; Gastrectomy; Humans; Markov Chains; Middle Aged; Models, Statistical; Oxaloacetates; Oxonic Acid; Probability; Quality-Adjusted Life Years; Stomach Neoplasms; Tegafur

In 2007, we began using neoadjuvant chemotherapy for the treatment of Stage IV gastric cancer and then performing R0/1 surgery in patients in whom chemotherapy was effective. Here, we evaluate the use of this therapeutic strategy combining chemotherapy and surgery for the treatment of Stage IV gastric cancer. The subjects of our investigation were 46 patients with Stage IV gastric cancer treated from 2007 through 2012. We divided these patients into the NAC group (19 patients), in whom we performed R0/1 surgery after chemotherapy, and the Cx group (27 patients), who continued chemotherapy. We also included 79 patients with Stage IV gastric cancer treated from 2001 to 2006, divided into the OPE group (36 patients), in whom we performed R0/1 surgery without neoadjuvant chemotherapy, and the NC group (43 patients), in whom we performed R2 surgery. We plotted the survival curves of these 4 groups. The chemotherapy protocols used were S-1+cisplatin( CDDP) and S-1+docetaxel( DOC). The disease control rate of these chemotherapies was 72%, and R0/1 surgery was performed in 53.8% of patients with liver metastasis, 62.5% of those with paraaortic lymph node (PALN) metastasis, 29.4% of those with peritoneal metastasis, 100% of patients with T4N2 disease, and 0% of patients with distant metastasis. The 2-year survival rates of the NAC, OPE, Cx, and NC groups were 69%, 55%, 0%, and 20%, respectively. The 5-year survival rates of the NAC, OPE, Cx, and NC groups were 35%, 30%, 0%, and 5%, respectively.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Docetaxel; Drug Combinations; Female; Gastrectomy; Humans; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Oxonic Acid; Stomach Neoplasms; Taxoids; Tegafur

The aim of this study was to clarify the human epidermal growth factor receptor 2( HER2) positivity, clinicopathological characteristics, and survival of patients with recurrent HER2-positive gastric cancer who received S-1 adjuvant chemotherapy.. Thirty-eight patients with recurrent gastric cancer who underwent curative D2 surgery and received S-1 adjuvant chemotherapy between June 2002 and December 2011 were examined. HER2 positivity was determined as defined in the ToGA study.. The positivity score was assessed by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) as follows: IHC 0 in 27 patients, IHC 1+in 4, IHC 2+/FISH-in 3, IHC 2+/FISH+in 1, and IHC 3+in 3. The HER2 positivity rate was 10.5% (4/38). HER2-positive recurrent gastric cancer was characterized by a differentiated histological feature and frequent blood vessel invasion. However, the recurrence and survival rates were not significantly different between the HER2-negative and HER2-positive tumors.. The HER2 positivity rate after S-1 adjuvant chemotherapy did not differ significantly between patients with recurrent gastric cancer and those with primary Stage II/III gastric cancer, suggesting that S-1 adjuvant chemotherapy was equally effective, regardless of HER2 status.

Topics: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Drug Combinations; Female; Humans; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Receptor, ErbB-2; Recurrence; Stomach Neoplasms; Tegafur

Herein, we report four cases of a single liver metastasis after gastric cancer resection. Initially, we chose to perform hepatic arterial infusion( HAI) with high-dose 5-fluorouracil( 5-FU)( 6,000 mg/week) or weekly 500-750 mg of 5-FU. Three patients showed a partial response (PR) and one patient showed no change (NC). Therefore, we performed hepatectomy or radiofrequency ablation( RFA) 300-350 days after HAI. All four patients received postoperative HAI. Two patients survived without recurrence for 12 and 21 months. One patient developed prostate cancer but survived for 22 months as an outpatient. Finally, one patient experienced recurrence in the residual liver, but at a site not supplied by the hepatic artery. This patient survived for 36 months as an outpatient. In conclusion, HAI, liver resection, and RFA are effective in the management of single liver metastasis from gastric cancer.

Topics: Aged; Antimetabolites, Antineoplastic; Catheter Ablation; Combined Modality Therapy; Drug Combinations; Humans; Infusions, Intra-Arterial; Liver Neoplasms; Male; Oxonic Acid; Recurrence; Stomach Neoplasms; Tegafur

The patient was a 71-year-old woman who was referred to our hospital with a diagnosis of gastric cancer. Computed tomography( CT) scans revealed a liver tumor, which we diagnosed as liver metastasis from the gastric cancer. A type 2 tumor was observed in the lesser curvature side of the gastric angle, and a huge tumor measuring 75 mm was seen in the lateral segment of the liver. A tumor thrombus from the metastatic lesion in the liver jutting out into the umbilical portion of the portal vein was observed. Measurement of tumor marker levels showed that the α-fetoprotein (AFP) level was slightly elevated at 20.7 ng/mL. Distal gastrectomy and resection of the left lobe of the liver were performed at surgery. The results of the pathological examination indicated a tub2, T3 (ss), N1, M1 (HEP), ly0, v2, stage IV gastric cancer with liver metastasis, and without AFP expression. The postoperative course was favorable, and the patient was treated in the outpatient clinic with postoperative adjuvant chemotherapy consisting of 80 mg of S-1. No adverse events were noted, and it was possible to complete 10 courses of chemotherapy. Because there was no evidence of recurrence, treatment was completed in 1 year and 2 months. No recurrence was observed until the third year after surgery. Consistent with a slight elevation in the tumor marker levels at 3 years and 6 months, recurrence was observed in the remnant liver. The patient died of her disease at 3 years and 10 months. Gastric cancers that give rise to portal vein tumor thrombosis are rare. Their outcome is generally poor, and early recurrence in the remnant liver is common. In the present case, R0 resection was possible because the liver metastasis was solitary and the tumor thrombosis was mild. To a certain extent, an improvement in the outcome was observed. However, the recurrence progressed rapidly, making it impossible to perform adequate treatment. More diligent examinations and continuation of long-term treatment might have been required to improve the patient's prognosis.

Topics: Aged; Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Drug Combinations; Fatal Outcome; Female; Gastrectomy; Hepatectomy; Humans; Liver Neoplasms; Oxonic Acid; Stomach Neoplasms; Tegafur; Thrombosis

A 69-year-old man with a history of distal gastrectomy for early gastric cancer consulted our department concerning a possible diagnosis of sigmoid colon cancer. After detailed examination, he was diagnosed with type 3 advanced sigmoid colon cancer with colonic stenosis and large type 3 gastric cancer in the residual stomach with gross infiltration of the adjacent organs. The patient first underwent sigmoidectomy and then received a regimen of neoadjuvant combination chemotherapy with S-1, cisplatin( CDDP), and Lentinan( LNT)( S-1 80 mg/m2, CDDP 60 mg/m2, and LNT 2 mg/body twice weekly for 2 weeks) for gastric cancer( cT4b[ SI, liver, pancreas], N2M0H0, Stage IIIC). After 2 courses of treatment, the gastric tumor had reduced in size but had penetrated the transverse colon. We performed total resection of the gastric remnant, D2 lymph node dissection, and en bloc resection of the transverse colon, partial liver, pancreas body and tail, partial diaphragm, and pericardium. S-1/CDDP (a total of 11 courses) followed by single-agent S-1 therapy was continued as adjuvant chemotherapy. With a follow-up time of 3 years and 10 months, no recurrence was noted following total resection of the gastric remnant.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Gastrectomy; Humans; Lentinan; Male; Neoplasm Invasiveness; Neoplasm Staging; Oxonic Acid; Stomach Neoplasms; Tegafur; Treatment Outcome

A 45-year-old man was transferred to our hospital because of advanced gastric cancer and peritoneal dissemination. After he received an S-1 plus cisplatin( CDDP) regimen for 6 courses, the primary lesion and ascites had disappeared. However, the primary lesion recurred, and he underwent treatment with 16 courses of an S-1 plus docetaxel regimen. He subsequently developed peripheral neuropathy, and was switched to the irinotecan (CPT-11) regimen. As he experienced appetite loss, it was impossible to continue the chemotherapy. Therefore, he underwent a salvage surgery and an R0 resection was performed. However, 9 months after the surgery, he experienced paraaortic lymph node recurrence and peritoneal dissemination. The patient died 13 months after the surgery.

Topics: Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Docetaxel; Drug Combinations; Fatal Outcome; Humans; Lymphatic Metastasis; Male; Middle Aged; Oxonic Acid; Peritoneal Neoplasms; Salvage Therapy; Stomach Neoplasms; Taxoids; Tegafur

We report a case of advanced gastric cancer successfully treated with preoperative S-1/Lentinan (LTN)chemotherapy followed by curative gastrectomy. The patient was a 75-year-old man with right hypochondralgia. Endoscopic examination revealed a huge type 2 gastric cancer in the middle body of the stomach. Abdominal computed tomography (CT) revealed multiple perigastric lymph node metastases and bulky para-aortic lymph node metastases. The clinical diagnosis was cT 4N3M1( LYM) with cStage IV. We thought a complete resection would be difficult, so he was treated with S-1( 80 mg/m2 day 1-28/q6w) and LTN (2 mg weekly) in May 2010. After 3 courses, the primary lesion was markedly reduced, and gastric endoscopic biopsy showed no malignant lesion. After 4 courses, abdominal CT showed no lymph node swelling at the perigastric and para-aortic areas. After 5 courses, distal gastrectomy with D2 lymphadenectomy was performed. The histological diagnosis was ypT2( MP) N0M0, Stage IB. Histological features of the primary tumor and lymph nodes were judged to be Grade 2 and Grade 3, respectively. After surgery, S-1/LTN treatment was continued for 1 year. During this period, there were no serious adverse events. The patient has been in good health without recurrence for 28 months after surgery.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Aorta; Biopsy; Drug Combinations; Gastrectomy; Humans; Lentinan; Lymphatic Metastasis; Male; Neoadjuvant Therapy; Oxonic Acid; Stomach Neoplasms; Tegafur

We report 2 cases of human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer successfully treated with a combination therapy of S-1, cisplatin( CDDP), and trastuzumab followed by curative resection. Case 1 involved a 62-year-old man with type 3 HER2-positive gastric cancer spanning the antrum of the stomach to the duodenal bulb and directly invading the pancreatic head( cT4b[ Panc] N3H0P0M0, Stage IIIC). We diagnosed it as an unresectable cancer, and selected S-1, CDDP, and trastuzumab for combination chemotherapy. S-1 (120 mg/body/day) was administered orally for 2 weeks, followed by 1 drug-free week as a course, and CDDP (60 mg/m2) and trastuzumab (8 mg/kg loading dose and 6 mg/kg maintenance) were administered by intravenous infusion on day 1. After the third course, significant tumor and lymph node reduction was observed; however, pyloric stenosis developed. Distal gastrectomy with D2 lymphadenectomy was performed. Case 2 involved a 62-year-old woman with type 4 HER2-positive gastric cancer from the angle of the stomach to the duodenal bulb and directly invading the pancreatic head (cT4b [Panc] N2H0P0M0, Stage IIIC). After the third course of combination therapy, significant tumor reduction and disappearance of lymph nodes metastasis was observed. We diagnosed the patient as having a resectable cancer, and performed distal gastrectomy with D2 lymphadenectomy.

Topics: Adenocarcinoma; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Female; Gastrectomy; Humans; Male; Middle Aged; Neoadjuvant Therapy; Oxonic Acid; Receptor, ErbB-2; Stomach Neoplasms; Tegafur; Trastuzumab

The patient was a 49-year-old man who was diagnosed as having gastric cancer and was suspected of having lymph node metastasis on computed tomography( CT) scans. He received neoadjuvant chemotherapy with S-1 and cisplatin (CDDP). He underwent total gastrectomy after 2 courses of neoadjuvant chemotherapy. The pathological effect was Grade 1b. The patient was treated with oral S-1 as postoperative adjuvant chemotherapy on an outpatient basis, and there are no signs of recurrence as of 3 years and 10 months after surgery.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Gastrectomy; Humans; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Grading; Oxonic Acid; Stomach Neoplasms; Tegafur

Here, I examined the efficacy of neoadjuvant chemotherapy( NAC) with S-1/CDDP( SP) in my hospital. The subjects were 8 patients with advanced gastric cancer who had undergone NAC since 2007 (7 men and 1 woman; median age, 70 years). The staging before the treatment was Stage II A: 1 patient, II B: 2 patients, III B: 3 patients, III C: 1 patient, and IV: 1 patient. The macroscopic type of 3 and 5 patients was large type 3 and type 4, respectively. Gastrectomy was performed following the NAC with SP. The NAC response rate was 62.5%. In the histological response criteria, 1 patient was grade 0, 2 patients were grade 1a, 2 patients were grade 1b, and 3 patients were grade 2. Adverse events following the NAC were in the acceptable range. We noted that the presence of Stage IV or grade 0 histological response criteria to NAC indicated poor prognosis. Thus, I believe that preoperative surgery after NAC in Stage III gastric cancer should be considered to be curative.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Female; Gastrectomy; Humans; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Oxonic Acid; Prognosis; Stomach Neoplasms; Tegafur

A 60-year-old man was diagnosed as having type 3 advanced gastric cancer in the gastric antrum and multiple liver metastases( S2, S3, S4, and S7)( cT3[ SS] N0M0H1, Stage IV). The patient received combined neoadjuvant chemotherapy with S-1 and cisplatin( CDDP). S-1( 80 mg/body/day) was administered orally for 3 weeks followed by 2 drug-free weeks as a course, and CDDP (60 mg/m2) was administered by intravenous infusion on day 8. The gastric tumor reduced in size and the liver metastases improved after 5 courses of treatment. Distal gastrectomy, D2 lymph node dissection, and partial liver resection( 4 sites) were performed. S-1 alone was continued as adjuvant chemotherapy; no recurrence was detected in 2 years and 2 months after surgery. Although there is insufficient evidence to support the benefit of surgical resection in patients with advanced gastric cancer with liver metastases, chemotherapy combined with surgical resection would improve the survival time without deterioration of quality of life of these patients. This case suggests that neoadjuvant chemotherapy is effective against advanced gastric cancer even with multiple liver metastases.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Gastrectomy; Hepatectomy; Humans; Liver Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm, Residual; Oxonic Acid; Stomach Neoplasms; Tegafur

In the present study, we evaluated the outcome of preoperative treatment with S-1 and CDDP for the treatment of advanced gastric cancer. Fifty-five cases of advanced gastric cancer received pre-operative treatment with S-1 and CDDP. The tumor control rate( PR and CR according to RECIST criteria) was 55%. The clinical response and histological response to the treatment and curative resection were closely related to favorable postoperative survival. We noted that patients who demonstrated CR or PR received S-1 as postoperative treatment, whereas those with SD or PD were more likely to receive paclitaxel as postoperative treatment. Preoperative treatment with S-1 and CDDP was not only an effective initial treatment, but also demonstrated favorable results in a S-1 in vivo sensitivity test.

Topics: Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cisplatin; Drug Combinations; Humans; Neoadjuvant Therapy; Neoplasm Metastasis; Oxonic Acid; Paclitaxel; Prognosis; Stomach Neoplasms; Tegafur

A 55-year-old man with melena was referred to our hospital with suspicion of pancreatic cancer. Upper gastrointestinal endoscopy revealed a type 3 tumor in the greater curvature of the pylorus invading the duodenum. Examination of biopsy specimens showed poorly differentiated adenocarcinoma. Abdominal computed tomography (CT) and positron emission tomography (PET)-CT revealed a gastric tumor in the antrum and regional lymph node metastases invading the pancreas, indicating clinical stage IIIB (cT3, N2, H0, P0, M0) disease. Following 2 courses of neoadjuvant chemotherapy with S-1 plus cisplatin( CDDP), distal gastrectomy with D2 lymphadenectomy was performed. Histological examination revealed no residual cancer cells in the surgically obtained stomach and lymph node specimens, suggesting a complete pathological response( Grade 3). The patient was treated with S-1 for 1 year after surgery. Currently, at 54 months after surgery, the patient is in good health without recurrence.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Gastrectomy; Humans; Lymphatic Metastasis; Male; Middle Aged; Neoadjuvant Therapy; Oxonic Acid; Stomach Neoplasms; Tegafur

We report a case of a 64-year-old man with multiple lung metastases after gastric cancer surgery. This patient was initially treated with S-1. However, he experienced adverse effects, and subsequently, he was effectively treated with cisplatin (CDDP) and irinotecan (CPT-11). In July 2010, the patient experienced a decrease in appetite and underwent a detailed examination. He also underwent distal gastrectomy in the same month. The postoperative diagnosis was T4a( SE), N2, M0, Stage IIIB. In November 2010, adjuvant chemotherapy with S-1 was initiated. In February 2011, the patient developed a skin disorder( grade 3) and generalized edema along with walking difficulty, which were identified as adverse effects of S-1. Evidently, S-1 was contraindicated for this patient, and adjuvant therapy was discontinued. In September 2011, contrast -enhanced thoracoabdominal computed tomography( CT) was performed and para-aortic lymph node metastasis and multiple lung metastases were detected. CDDP+CPT-11 therapy was initiated. By June 2012, 8 courses had been administered, and the patient had a good partial response. With regard to chemotherapy for advanced or recurrent gastric cancer, there is no consensus on a treatment policy for cases in which S-1 cannot be used owing to adverse effects. CDDP+CPT-11 therapy is considered a safe and effective choice.

Topics: Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cisplatin; Contraindications; Drug Combinations; Humans; Irinotecan; Lung Neoplasms; Male; Middle Aged; Neoadjuvant Therapy; Oxonic Acid; Recurrence; Stomach Neoplasms; Tegafur

The patient was a 50-year-old man diagnosed as having a large type 3 advanced gastric cancer with para-aortic lymph node metastasis and with positive peritoneal cytology. We administered a combined systemic and intraperitoneal chemotherapy involving docetaxel, cisplatin, and S-1 (DCS). After 2 courses of treatment, the primary tumor and lymph nodes were significantly reduced in size, suggesting that this therapy induced a partial response (PR). No cancer cells were observed in the peritoneal cytology, and therefore, we performed curative total gastrectomy with para-aortic lymph node dissection. Histological findings revealed that there were no cancer cells in either the primary tumor or the lymph nodes, and pathological grading indicated that the resected lesions were grade 3. Adjuvant chemotherapy with S-1 was administered after surgery. At 18 months after surgery, the patient is still alive and free of disease.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Docetaxel; Drug Combinations; Gastrectomy; Humans; Lymph Node Excision; Lymphatic Metastasis; Male; Middle Aged; Neoadjuvant Therapy; Oxonic Acid; Stomach Neoplasms; Taxoids; Tegafur

We report a case of gastric cancer accompanied by disseminated carcinomatosis of the bone marrow treated with S-1 and cisplatin( CDDP) combination chemotherapy. The patient was a 68-year-old woman who was detected as having disseminated intravascular coagulation( DIC) during an examination for gastric cancer and she was diagnosed as having disseminated carcinomatosis of the bone marrow by lumbar puncture. She was immediately treated with S-1 and CDDP combination chemotherapy( S-1, 80 mg/body orally administered[ po] on days 1-21 and CDDP, 60 mg/body intravenously [iv] administered on day 8) and her DIC improved on the fourth day. Subsequently, the patient was treated with 3 courses of combination chemotherapy and she survived for 184 days from the initiation of the treatment. Although disseminated carcinomatosis of the bone marrow is associated with a poor prognosis, we believe that the duration of survival of our patient was extended due to initiation of chemotherapy at an early stage.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Neoplasms; Carcinoma; Cisplatin; Disseminated Intravascular Coagulation; Drug Combinations; Fatal Outcome; Female; Humans; Oxonic Acid; Stomach Neoplasms; Tegafur

A 66-year-old man underwent distal gastrectomy with Roux-en-Y anastomosis and D2 dissection for the treatment of advanced gastric cancer (pT4a, N0, M0, stage IIB) in June 2009. He was treated with adjuvant postoperative chemotherapy consisting of S-1. However, in September 2010, computed tomography (CT) showed #16a2 lymph node recurrence, which was treated with combination chemotherapy of S-1 and cisplatin. After 7 courses of this combination chemotherapy, CT revealed a significant reduction in the size of the metastatic lesion as well as a new peritoneal dissemination recurrence around the right kidney. We therefore changed the regimen to combination chemotherapy of S-1 and docetaxel. After 3 courses of this treatment, the dissemination lesion was no longer evident by CT. After 6 more courses of treatment, the lymph node and peritoneal dissemination recurrence showed no regrowth. In response to the patient's wish, we changed the chemotherapy to S-1 alone beginning in June 2012. He survived without recurrence for approximately 2 years after gastrectomy. We suggest that the taxane drug was effective as second-line chemotherapy for the treatment of patients with peritoneal dissemination recurrence.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Docetaxel; Drug Combinations; Gastrectomy; Humans; Male; Oxonic Acid; Peritoneal Neoplasms; Recurrence; Stomach Neoplasms; Taxoids; Tegafur

A 63-year-old man visited our clinic with a chief complaint of a left axillary mass, and after a series of examinations, gastric cancer was diagnosed. Histopathological examination revealed a human epidermal growth factor receptor (HER)-2- positive( immunohistochemistry[ IHC], 2+; fluorescence in situ hybridization[ FISH], positive) poorly differentiated adenocarcinoma, and SPT therapy( S-1 at 120 mg/m2/day+cisplatin[ CDDP] at 60 mg/m2+trastuzumab at 8 mg/kg) was initiated. The primary lesion and swollen lymph nodes initially decreased markedly in size; however, the lymph node swelling worsened at 186 days( 6.2 months) after the initiation of treatment. Progressive disease( PD) was diagnosed, and SPT therapy was terminated. One cycle of S-1+docetaxel was administered as second-line therapy, but the regimen was changed to docetaxel monotherapy due to adverse effects. After 5 cycles of this treatment, the primary lesion had decreased in size and the lymphadenopathy disappeared. Positron emission tomography( PET)-computed tomography (CT) revealed fluorodeoxyglucose( F18)( FDG) accumulation only in the primary lesion, and therefore, with the patient's informed consent distal gastrectomy was performed approximately 14 months after the first treatment. The postoperative diagnosis was gastric cancer fStage IA (T1a, N0, and M0). Here, we discuss a case of HER2-positive gastric cancer with references. Among the advanced recurrent gastric cancers tested between April 2011 and February 2013, 16.4% (11/67) were HER2-positive.

Topics: Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Humans; Lymphatic Metastasis; Male; Middle Aged; Oxonic Acid; Receptor, ErbB-2; Stomach Neoplasms; Tegafur; Trastuzumab

We report the case of a patient with paclitaxel (PTX) -resistant recurrent gastric cancer who was effectively treated with S-1 plus docetaxel( DOC). A 62-year-old woman underwent total gastrectomy for Stage IV advanced gastric cancer (type 4, por 2>sig, pT4a (SE), pN3a, pP1, CY1) in 2009. Although S-1 was administered as first-line chemotherapy, recurrent peritoneal metastasis was diagnosed 22 months after surgery. S-1 plus irinotecan (CPT-11) was administered as second-line chemotherapy, and this was followed by weekly PTX (80 mg/m2) as third-line chemotherapy. However, computed tomography (CT) showed increased ascites and peritoneal wall thickening in the pelvis. As the tumor proved resistant to PTX, making the treatment ineffective, S-1( 80 mg/m2, day 1-14, q3w) plus DOC( 40 mg/m2, day 1, q3w) was initiated. Two months later, the ascites and peritoneal wall thickening in the pelvis disappeared. Twelve months after initiation of S-1 plus DOC chemotherapy, no sign of recurrence has been noted.

Topics: Antineoplastic Combined Chemotherapy Protocols; Docetaxel; Drug Combinations; Drug Resistance, Neoplasm; Female; Humans; Middle Aged; Oxonic Acid; Paclitaxel; Recurrence; Stomach Neoplasms; Taxoids; Tegafur

We encountered a case of delayed subcutaneous metastases of gastric carcinoma. The patient underwent distal gastrectomy for advanced gastric carcinoma 11 years ago. Postoperative pathological diagnosis indicated stage IIIB disease, poorly differentiated adenocarcinoma (scirrhous, T4a, ly2, v2, N2, H0, P0). Three courses of adjuvant chemotherapy with 5-fluorouracil (5-FU)+cisplatin (CDDP) were administered; however, the patient discontinued the treatment. No signs of recurrence were observed for 11 years after the treatment. However, subcutaneous metastases in the front portion of the head and the back and an ovarian tumor were detected after the remission period. The specimen from the resected subcutaneous tumor from the back indicated signet-ring cell carcinoma, and delayed subcutaneous and ovarian metastases of the gastric carcinoma was diagnosed. Therefore, 8 courses of the S-1+CDDP combination therapy were administered. The cutaneous metastases disappeared, but the ovarian tumor progressed and was therefore resected. Analysis of the resected ovarian tumor also indicated signet-ring cell carcinoma. We report a case of delayed recurrence of gastric carcinoma that was effectively treated with chemotherapy.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Signet Ring Cell; Cisplatin; Drug Combinations; Female; Humans; Lymphatic Metastasis; Middle Aged; Ovarian Neoplasms; Oxonic Acid; Skin Neoplasms; Stomach Neoplasms; Tegafur; Time Factors

An 82-year-old man underwent total gastrectomy(D2 lymph node dissection)in August 2006. The pathological findings indicated T4a, N3, M0, Stage IIIC gastric cancer, but adjuvant chemotherapy was not initiated. In October 2009, he presented to the hospital with dyschezia. During colonoscopy, the scope could not pass through the colon, thus indicating rectal stenosis. The biopsy findings indicated the presence of signet ring cell carcinoma, which was determined to be due to the peritoneal dissemination from the gastric cancer. To avoid the need for creating a stoma, radiation therapy(2 Gy×20; total dose, 40 Gy)and chemotherapy(weekly paclitaxel and S-1)were initiated. Rectal stenosis was improved and complete remission was maintained until May 2013.

Topics: Aged, 80 and over; Antimetabolites, Antineoplastic; Antineoplastic Agents, Phytogenic; Chemoradiotherapy; Constriction, Pathologic; Drug Combinations; Humans; Male; Oxonic Acid; Paclitaxel; Peritoneal Neoplasms; Rectal Diseases; Stomach Neoplasms; Tegafur

Eicosapentaenoic acid-enriched oral nutritional supplements (Prosure®; Abbott Japan, Tokyo, Japan) may attenuate surgical stress and catabolism after gastric cancer surgery. The present study aimed to evaluate the effects of Prosure® on body weight loss( BWL) and compliance with S-1 adjuvant chemotherapy after gastrectomy.. Patients who underwent curative total gastrectomy for gastric cancer were selected to undergo adjuvant S-1 chemotherapy at Kanagawa Cancer Center between December 2010 and October 2011. The patients received a normal postgastrectomy diet and two 240 mL packs of Prosure® for 21 postoperative days. BWL was defined as %BWL and calculated as %BWL=(preoperative body weight-1-month postoperative body weight)×100/preoperative body weight. Time to S-1 treatment failure was calculated.. Five patients were enrolled in this study. The median age was 62.0 years. One patient was male, and 4 were female. The 1-month postoperative BWL was 92.1%. Compared to our previous report, a 20% risk reduction was observed in this study (Prosure® group vs control group, 92.1% vs 89.7%). Moreover, all the patients continued with the S-1 adjuvant chemotherapy for longer than 6 months.. Prosure® may inhibit BWL at 1 month after gastrectomy. Moreover, Prosure® improved the patients' compliance with the adjuvant chemotherapy after gastrectomy.

Topics: Chemotherapy, Adjuvant; Drug Combinations; Eicosapentaenoic Acid; Enteral Nutrition; Female; Gastrectomy; Humans; Male; Middle Aged; Oxonic Acid; Stomach Neoplasms; Tegafur; Weight Loss

We present a case of a 63-year-old man who was admitted to another hospital because of abdominal distension and body weight loss. Gastric endoscopy revealed a type III tumor at the posterior wall of the upper gastric body. The tumor had invaded into the esophagogastric junction. On the basis of the pathology of the biopsy specimen, the tumor was diagnosed as neuroendocrine carcinoma of the esophagogastric junction. Computed tomography (CT) scans showed regional lymph node swelling. Cisplatin( CDDP) +irinotecan( CPT-11) therapy was selected and administered to the patient. After 2 courses, the patient received S-1+CDDP. He was considered to have stable disease. We performed partial resection of the lower esophagus, total gastrectomy, splenectomy, and cholecystectomy. On pathology, the tumor was immunohistochemically positive for chromogranin A, AE1/AE3, neural cell adhesion molecule (NCAM), neuron-specific enolase (NSE), and p53. The Ki-67 index was 80%. The tumor was diagnosed as a mixed adenoneuroendocrine carcinoma (MANEC) of the esophagogastric junction. The patient was treated with S-1 and CDDP. Neuroendocrine cell carcinoma of the esophagogastric junction is rare and usually has a very poor prognosis. We herein report a case of mixed adenoneuroendocrine carcinoma of the esophagogastric junction that was curatively resected and resulted in patient survival without recurrence.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Carcinoma, Neuroendocrine; Cisplatin; Drug Combinations; Esophagogastric Junction; Gastrectomy; Humans; Irinotecan; Male; Middle Aged; Neoadjuvant Therapy; Oxonic Acid; Stomach Neoplasms; Tegafur

A 77-year-old woman diagnosed as having advanced gastric cancer with para-aortic lymph node metastasis received neoadjuvant chemotherapy with docetaxel, cisplatin, and S-1. After 2 courses of chemotherapy, distal gastrectomy with D2 lymphadenectomy was performed. There were no viable cancer cells in the primary lesion and lymph nodes. Currently, the patient is visiting our hospital for treatment with S-1 as adjuvant chemotherapy, and shows no signs of recurrence.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cisplatin; Docetaxel; Drug Combinations; Female; Gastrectomy; Humans; Neoadjuvant Therapy; Oxonic Acid; Stomach Neoplasms; Taxoids; Tegafur

We report a case of lethal interstitial pneumonia that occurred after neoadjuvant chemotherapy for advanced gastric cancer. A 76-year-old man with no history of interstitial pneumonia received 2 courses of S-1 (100 mg/body) following 1 course of S-1 plus cisplatin( CDDP) from June 2012. He complained of dyspnea on exertion 6 days after completion of the treatment. Chest radiography and computed tomography (CT) revealed diffuse interstitial lesions in bilateral lung fields. Bronchoalveolar lavage( BAL) revealed an increased number of lymphocytes and leukocytes. Transbronchial lung biopsy (TBLB) revealed interstitial pneumonia with fibrous thickening in the alveolar septum. The drug lymphocyte stimulation test (DLST) was positive for S-1 and negative for CDDP. These results suggested that S-1 had induced interstitial pneumonia. Steroid therapy( 40 mg/day prednisolone following 500 mg methylprednisolone pulse therapy) and an antibiotic agent were administered but were ineffective. He rapidly developed respiratory failure and required tracheal intubation and mechanical ventilation on hospital day 24, and died on hospital day 38.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Fatal Outcome; Humans; Lung Diseases, Interstitial; Male; Neoadjuvant Therapy; Oxonic Acid; Stomach Neoplasms; Tegafur

Trousseau's syndrome involves unexplained thrombotic events along with malignancy. We report the cases of 3 patients undergoing chemotherapy for gastric cancer in whom Trousseau's syndrome occurred. Case 1 involved a 43-year-old woman undergoing S-1/cisplatin( CDDP) combination therapy as first-line chemotherapy for type 4 remnant gastric cancer( cT4bN2M1P1/stage IV) who experienced left hemiplegia. Cerebral hemorrhage of the right parietal lobe was diagnosed by computed tomography( CT), and thrombosis from the upper sagittal sinus to the right sinus sigmoideus was diagnosed by magnetic resonance venography( MRV). Case 2 involved a 59-year-old man undergoing S-1/irinotecan (CPT-11) combination therapy as second-line chemotherapy for type 3 gastric cancer( cT3N1M0H1/stage IV) who experienced ataxic, stuttering, and left membrum inferius paralysis. Multiple cerebral infarction of the right parietal lobe was diagnosed by magnetic resonance imaging (MRI). Case 3 involved a 67-year-old woman undergoing S-1/CDDP combination therapy as preoperative chemotherapy for type 3 gastric cancer( cT4aN1M0/stage IIIA) who experienced right cerebellum incontinentia, nystagmus, and right facioplegia. Multiple cerebral infarction of the right cerebellum and pedunculus cerebellaris medius was diagnosed by MRI. An anticoagulant was administered orally for stroke, and chemotherapy for gastric cancer was resumed after activities of daily living( ADL) improved in all 3 patients. Recurrent stroke was not diagnosed in any of the 3 patients. Patients with malignancy often exhibit hypercoagulability associated with cancer. Accordingly, periodic blood tests for coagulation should be performed and dehydration should be prevented to prevent strokes in cancer patients.

Topics: Adult; Aged; Anticoagulants; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cisplatin; Drug Combinations; Female; Humans; Irinotecan; Male; Middle Aged; Oxonic Acid; Stomach Neoplasms; Stroke; Tegafur

A 77-year-old woman with Stage IV gastric cancer was admitted to our hospital because of high fever, poor appetite, and abdominal pain during combined chemotherapy with S-1 and cisplatin( CDDP). Abdominal computed tomography (CT) revealed the presence of gas in the submucosal layer on the basis of which emphysematous cholecystitis (EC) was diagnosed. We performed cholecystectomy and were able to proceed with the chemotherapy 1 month after surgery. Destruction of the gallbladder mucosa by ischemia has been reported to be a possible cause of emphysematous cholecystitis. Moreover, underlying systemic diseases such as arterial sclerosis and diabetes mellitus could be risk factors for EC. Our case suggested that chemotherapeutic agents might trigger ischemic changes in the gallbladder and thus result in EC.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Emphysematous Cholecystitis; Female; Humans; Neoplasm Staging; Oxonic Acid; Stomach Neoplasms; Tegafur

A phase III clinical trial to evaluate the efficacy of combination chemotherapy with intraperitoneal administration of paclitaxel for gastric cancer with peritoneal metastasis has been ongoing in Japan. A male patient in his 50s who was diagnosed as having advanced gastric cancer with peritoneal metastasis was enrolled in this trial. The patient was assigned to receive a regimen of intravenous and intraperitoneal paclitaxel combined with S-1. Although an intraperitoneal access port had been implanted to provide access to the peritoneal cavity, tube obstruction occurred twice. Laparoscopic examination revealed that the tube in the abdominal cavity had been totally covered with the great omentum. Therefore, the intraperitoneal regimen was discontinued. Although intraperitoneal chemotherapy for the treatment of peritoneal dissemination in gastric cancer is promising, precaution should be taken to avoid tube obstruction, which is a complication of the intraperitoneal tube placement.

Topics: Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Humans; Male; Middle Aged; Oxonic Acid; Paclitaxel; Peritoneal Cavity; Peritoneal Neoplasms; Stomach Neoplasms; Tegafur; Vascular Access Devices

We treated a patient who had gastrointestinal perforation during chemotherapy with docetaxel and S-1 which was successfully treated with percutaneous drainage. A 66-year-old man was admitted to our hospital with complaints of abdominal pain. Gastric cancer (T3N1M0) had been diagnosed 3 years earlier, and distal gastrectomy had been performed. Two years later, intrapelvic recurrence of the cancer was diagnosed. We administered docetaxel and S-1. After 3 courses of chemotherapy, he complained of abdominal pain of sudden onset. Computed tomography showed free air and limited ascites, and gastrointestinal perforation was diagnosed. We performed percutaneous drainage. The abdominal pain improved 3 days later, and he was able to eat meals 15 days after the onset of abdominal pain. He was discharged 27 days after admission. Because the patient's general condition was poor, we started providing best supportive care only. He died 10 months after the perforation was found.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Docetaxel; Drug Combinations; Fatal Outcome; Humans; Intestinal Perforation; Male; Oxonic Acid; Radiography, Abdominal; Stomach Neoplasms; Taxoids; Tegafur; Tomography, X-Ray Computed

Although S-1 plus cisplatin (SP) therapy is recognized as the standard treatment for advanced gastric cancer (AGC) in Japan, its safety and efficacy in elderly patients have not been investigated sufficiently.. We retrospectively reviewed the data of 58 patients with AGC selected from 82 consecutive patients who were ≥70 years old and were treated with SP or S-1 monotherapy as the first-line therapy. In SP, S-1 (40 mg/m(2), bid) was administered for 3 weeks and cisplatin (60 mg/m(2)) on day 8, every 5 weeks. In S-1 monotherapy, S-1 (40 mg/m(2), bid) was administered for 4 weeks, every 6 weeks.. SP and S-1 was administered in 21 and 37 patients, respectively. There were some differences in patient characteristics between the treatment groups, such as histological type (P = 0.16); the presence of liver metastasis (P = 0.07); and the presence of peritoneal metastasis (P = 0.02). The incidences of grade 3/4 hematological toxicities were 57% (12/21) in the SP and 35% (13/37) in the S-1 group (P = 0.17). Those of non-hematological toxicities were 14% (3/21) and 14% (5/37) for anorexia, 10% (2/21) and 14% (5/37) for fatigue, and 5% (1/21) and 5% (2/37) for nausea in the SP and S-1 groups, respectively. Median progression-free survival and median overall survival in the SP and S-1 groups were 5.0 and 5.2 months, and 14.4 and 10.9 months, respectively.. SP and S-1 therapy were both feasible in elderly patients, though there is the risk of a high incidence of hematological toxicities.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Disease-Free Survival; Drug Combinations; Female; Humans; Liver Neoplasms; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Retrospective Studies; Stomach Neoplasms; Tegafur

There are few data on the efficacy of combination chemotherapy with a fluoropyrimidine plus cisplatin for patients with advanced or recurrent gastric cancer (AGC) complicated by peritoneal metastasis, especially massive ascites.. We retrospectively evaluated the efficacy and safety of a fluoropyrimidine (S-1 or capecitabine) plus cisplatin as first-line chemotherapy in 120 patients with AGC and peritoneal metastasis.. Ascites was detected in 50 patients, with 11 patients having massive ascites. Median progression-free survival (PFS) and overall survival (OS) of all patients was 6.1 and 15.9 months, respectively. The PFS and OS were shorter in patients with massive ascites (n = 11; 3.7 and 9.5 months) compared with patients with small or moderate ascites (n = 39; 5.8 and 13.5 months) or patients without ascites (n = 70; 6.9 and 18.1 months). The objective response in terms of ascites was similar whether ascites was massive (4 of 11 patients; 36.4%) or small or moderate (16 of 39 patients; 41%). The frequencies of grade 3 or higher toxicity or treatment discontinuation due to toxicity are relatively similar across ascites groups.. Fluoropyrimidine plus cisplatin appears to be tolerated in selected patients with peritoneal metastasis.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Ascites; Capecitabine; Cisplatin; Deoxycytidine; Disease-Free Survival; Drug Combinations; Female; Fluorouracil; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Oxonic Acid; Peritoneal Neoplasms; Retrospective Studies; Stomach Neoplasms; Survival Rate; Tegafur; Time Factors; Treatment Outcome

Based on the results of the SPIRITS trial, combination chemotherapy of S-1 plus cisplatin (SP) is now considered the standard treatment for patients with advanced gastric cancer (AGC) in Japan. On the other hand, several non-Japanese studies have shown the efficacy of capecitabine plus cisplatin (XP), which has been used as the reference arm in recent global studies of AGC.. We retrospectively compared the efficacy and safety of SP and XP in first-line treatment for patients with AGC.. From August 2006 to November 2008, 26 AGC patients received XP in the context of 2 global trials (AVAGAST and ToGA), and 50 patients received SP during the same period. The objective response rate was 43.2 % in the SP group and 50 % in the XP group, with no significant difference (p = 0.62). There were also no significant differences in progression-free survival (median 5.8 vs. 5.2 months; p = 0.91) and overall survival (median 13.8 vs. 13.5 months; p = 0.97) between the SP and XP groups. The frequencies of hematological toxicities of grade 3 or more and non-hematological toxicities were not significantly different between the 2 groups. Although grade 1 or 2 hand-foot syndrome was more common in the XP group, no patients experienced grade 3 or more.. Although the retrospective nature of this study and the small number of patients is a major limitation, SP and XP were associated with similar efficacy and safety in patients with AGC.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Cisplatin; Deoxycytidine; Disease-Free Survival; Drug Combinations; Female; Fluorouracil; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Oxonic Acid; Retrospective Studies; Stomach Neoplasms; Tegafur

The purpose of this study was to determine an effective treatment strategy for patients with Stage IV gastric cancer.. We analyzed the significant prognostic factors in 74 patients who underwent surgery between 1989 and 2005, and were finally determined to have Stage IV gastric cancer. These patients were classified as curability A (n = 0), B (n = 29) and C (n = 45) according to the criteria outlined by Japanese Gastric cancer society. Anti-tumor drugs were used after surgery in some cases. There were 32 patients who received either no treatment or an oral anti-tumor drug, and 42 patients who received new chemotherapeutic regimens.. According to a univariate analysis, the postoperative mean survival times were significantly different; tumor size ≤ 12 cm, a tumor without lymphatic involvement, more than D2 lymphadenectomy, and classification as curability B were favorable prognostic factors. The multivariate analysis revealed that tumor size, lymphadenectomy and curability were independent prognostic factors. In curability B patients, venous involvement was an independent prognostic factor. In curability C patients, both the tumor size and postoperative chemotherapy affected their prognosis.. In patients with curable Stage IV gastric cancer, at least a D2 gastrectomy to reduce the absolute volume of tumor cells, followed by adjuvant chemotherapy, may be essential to improve their prognosis. In incurable cases, aggressive new chemotherapeutic regimens should be the treatment of choice for the prolongation of survival.

Topics: Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Chemotherapy, Adjuvant; Cisplatin; Drug Combinations; Gastrectomy; Humans; Irinotecan; Kaplan-Meier Estimate; Multivariate Analysis; Neoplasm Staging; Oxonic Acid; Paclitaxel; Prognosis; Stomach Neoplasms; Survival Rate; Tegafur

The Response Evaluation Criteria in Solid Tumors (RECIST) was revised in 2009, based on a large dataset of 6512 patients from 16 trials. However, no gastric cancer patients were included in those data. The purpose of this study was to clarify the difference between RECIST version 1.0 and version 1.1 in advanced gastric cancer.. From 2004 to 2009, 129 consecutive patients with advanced gastric cancer received S-1 plus cisplatin as first-line treatment at the National Cancer Center Hospital East. Ninety-seven of these patients who had had baseline and post-treatment computed tomography scans performed were included in this study. Measurements of tumors were conducted retrospectively.. At the baseline of first-line chemotherapy, 172 lymph nodes in 54 patients were considered to be candidate target lesions by RECIST version 1.0. However, only 38% of the lymph nodes were classified as target lesions by RECIST version 1.1, with 47% classified as non-target lesions and 15% classified as non-pathological. By RECIST version 1.0, the proportion of patients with target lesions at the baseline of first-line chemotherapy was 67% (65/97), and this percentage was significantly reduced according to RECIST version 1.1 (53%; 51/97) (McNemar's exact test, P < 0.001). The findings at the baseline of second-line chemotherapy were similar (reduced from 62 to 49%; McNemar's exact test, P = 0.002). Overall response rates of first-line chemotherapy were 52% (34/65) according to RECIST version 1.0 and 55% (28/51) according to version 1.1.. The revision of RECIST significantly reduced the proportion of patients classified with target lesions at the baselines of first-line and second-line chemotherapies. No obvious difference in overall response rates was observed.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Female; Humans; Male; Middle Aged; Oxonic Acid; Retrospective Studies; Stomach Neoplasms; Tegafur; Tomography, X-Ray Computed; Treatment Outcome

This study was performed to investigate the compliance, safety, dosage modifications (dose reduction and/or schedule change [including permanent S-1 withdrawal]), and clinical parameters that predict S-1 dosage modification in gastric cancer patients receiving adjuvant S-1 chemotherapy. One hundred and forty-nine patients who underwent curative D2 surgery and received adjuvant S-1 chemotherapy were enrolled. S-1 was administered orally (40 mg/m(2) twice daily on days 1-28 every 6 weeks) for 1 year. For patients unable to tolerate S-1, the dosage was reduced or the schedule was changed to a 3-weekly schedule of 2 weeks on treatment followed by 1 week off treatment. The planned 1-year treatment was completed in 73.8% of patients; 69 patients required dosage modification because of toxicity. The most frequent cause of dosage modification was enterocolitis (37 patients; defined as ≥ grade 2 abdominal pain and/or ≥ grade 2 diarrhea). Most dosage modification occurred during the early cycles of treatment (within the first 3 months). Severe toxicities (≥ grade 3) included neutropenia (13.4%), abdominal pain (8.1%) and diarrhea (8.1%). In multivariate analyses, decreased relative dose intensity was related to poor disease-free survival independent of stage, and only low creatinine clearance predicted S-1 dosage modification. In conclusion, although adjuvant S-1 therapy has a high compliance rate, meticulous monitoring of adverse events is required in the early period of treatment. Decreased creatinine clearance was the only factor that predicted dosage modification. In patients with creatinine clearance <50 mL/min, dosage reduction should be considered from the initiation of S-1 treatment.

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Cohort Studies; Drug Combinations; Female; Humans; Male; Middle Aged; Oxonic Acid; Patient Compliance; Stomach Neoplasms; Survival Rate; Tegafur; Treatment Outcome

This retrospective study was carried out to compare computed tomographic (CT) gastrography and conventional optical gastroscopy (GS) in order to evaluate the effectiveness of chemotherapy in primary gastric lesions.. Patients with unresectable advanced and unresected early gastric cancer who had primary lesions and had received chemotherapy were enrolled. For primary lesions, CT gastrography and endoscopic assessment were done after chemotherapy, based on the Japanese Classification of Gastric Carcinoma (JCGC) criteria, 13th edition, and the Response Evaluation Criteria in Solid Tumors (RECIST). For metastatic solid lesions including lymph nodes, CT assessment was done based on the RECIST criteria.. Data from 23 patients were analyzed. With median follow-up of 9.4 months (range 2-23 months), 58 examinations were assessed by GS and CT gastrography. Setting optical endoscopic results as the gold standard, the accuracy of CT gastrography for primary gastric lesions was 77.6 % (45 of 58) (weighted κ = 0.72; P < 0.01) according to the JCGC 13th edition criteria and 90.0 % (52 of 58) (weighted κ = 0.75; P < 0.01) according to the RECIST. When all results were divided into two groups [the non-progressive disease (non-PD) group and PD group], accuracy was 93.1 % (52 of 58) (κ = 0.81; P < 0.01), sensitivity was 100 %, and specificity was 75.0 % (12 of 16). In addition, the predictability of PD was 100 % (12 of 12). The four cases of failure in specification were the following: a case of gastric remnant cancer, a case with insufficient distension of the stomach, a healed case with stenosis and scarring, and a case in which the wrong position had been selected for the examination. The average period until PD was 9.9 months (range 5-18 months), and the concordance period between GS and CT gastrography was 7.2 months in both non-PD and PD cases.. There was good concordance between the evaluations of GS and CT gastrography. CT gastrography exhibited favorable results in accuracy as well as 100 % PD predictability, which implied the possibility of using CT gastrography as a substitute for endoscopic assessments at post-chemotherapy assessments.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Docetaxel; Drug Combinations; Female; Follow-Up Studies; Gastroscopy; Humans; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Paclitaxel; Prognosis; Retrospective Studies; Stomach Neoplasms; Taxoids; Tegafur; Tomography, X-Ray Computed; Validation Studies as Topic

Compliance of S-1 adjuvant chemotherapy is not high. The aim of the present study is to clarify risk factors for continuation of S-1 after gastrectomy.. This retrospective study selected patients who underwent curative D2 surgery for gastric cancer, were diagnosed with stage 2/3 disease, creatinine clearance more than 60 ml/min, and received adjuvant S-1 at our institution between June of 2002 and December of 2011. Time to S-1 treatment failure (TTF) was calculated.. A total of 103 patients were selected for the present study. When TTF curve stratified by each clinical factor was compared by the log-rank test, body weight loss (BWL) of 15 % was regarded as a critical point. Both univariate and multivariate Cox proportional hazard analyses demonstrated that BWL was the significant independent risk factor. Moreover, BWL remained a significant factor in both the univariate and multivariate analyses in the subset excluding 8 patients who discontinued S-1 because of recurrence. The 6-month continuation rate was 66.4 % in the patients with BWL < 15 and 36.4 % in patients with BWL ≥ 15 % (P = .017).. BWL was the most important risk factor for the compliance of adjuvant chemotherapy with S-1 in the patients with stage 2/3 gastric cancer who underwent D2 gastrectomy. To improve drug compliance that leads to survival, it is a key to maintain body weight before starting S-1 adjuvant. Our study emphasizes the requirement for adequate studies of perioperative nutritional intervention in patients who receive gastrectomy for advanced gastric cancer.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Drug Combinations; Female; Follow-Up Studies; Gastrectomy; Humans; Kaplan-Meier Estimate; Male; Medication Adherence; Middle Aged; Multivariate Analysis; Oxonic Acid; Risk Factors; Stomach Neoplasms; Tegafur; Weight Loss

A 66-year-old man presented with anemia. Endoscopy revealed an elevated lesion with ulceration in the posterior wall of the lesser curvature of the lower gastric body. Endoscopic biopsy demonstrated pathological diagnosis, neuroendocrine carcinoma. A computed tomography scan showed liver metastasis and portal vein invasion. We started chemotherapy with S-1 and cisplatin. After six courses of treatment over seven months, partial response was assessed. We are continuing this chemotherapy now.

Topics: Antimetabolites, Antineoplastic; Antineoplastic Agents; Carcinoma, Neuroendocrine; Cisplatin; Drug Combinations; Humans; Liver Neoplasms; Male; Middle Aged; Neoplasm Invasiveness; Oxonic Acid; Portal Vein; Stomach Neoplasms; Tegafur

A 74-year-old woman was referred to our hospital for a close examination. A gastrointestinal endoscopic examination revealed an advanced gastroesophageal junction cancer type 3, which was diagnosed as well-differentiated adenocarcinoma. Computed tomography(CT)showed liver and para-aortic lymph node metastases.She was treated with oral S-1 at 100mg/ day for 28 days, followed by a 14-day rest. After 3 courses of treatment, the primary tumor was greatly reduced. After 18 months of treatment, CT showed a complete response of the liver and also the para-aortic lymph node metastases. She is alive without severe adverse effects and recurrence 2.5 years after the start of S-1 administration.

Topics: Aged; Antimetabolites, Antineoplastic; Biopsy; Drug Combinations; Esophagogastric Junction; Female; Humans; Oxonic Acid; Stomach Neoplasms; Tegafur

The patient was a 48-year-old woman, admitted for pleural effusion detected on chest X-ray in July 2005. Computer tomography(CT)scan showed massive pericardial and pleural effusion. We performed pericardial drainage, and the cytological diagnosis of the pericardial effusion was class V. Because endoscopic examination revealed advanced gastric cancer, we diagnosed it as gastric cancer complicated with carcinomatous pericarditis. The serum tissue polypeptide antigen(TPA) level was markedly elevated. In August 2005, we started combination chemotherapy using oral S-1(100mg/body/day; day 1- 21)and intravenous CDDP(100mg/body/day; day 8)for 5 weeks. After 2 courses, TPA was reduced and pericardial effusion disappeared. However, after 3 courses, pericardial effusion recurred. We changed treatment to weekly docetaxel. After 2 courses, we changed it to paclitaxel/CDDP. However, TPA was increased and pleural effusion and dyspnea occurred. There- fore, we changed to a course of combination chemotherapy using oral S-1(100mg/body/day; day 1-14)and intravenous CPT-11(100mg/body/day; day 1 and 8)for 4 weeks from March 2006. After 10 courses, we were unable to control pleural effusion, and dyspnea recurred. She died in December 2006. Gastric cancer complicated with carcinomatous pericarditis has a poor prognosis, but systemic chemotherapy mainly with S-1 was effective.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Fatal Outcome; Female; Humans; Middle Aged; Oxonic Acid; Pericarditis; Stomach Neoplasms; Tegafur

A 70-year-old female presented with epigastralgia. Gastrointestinal endoscopic examination showed advanced gastric cancer type 2. Computed tomography(CT)showed a liver tumor of 37mm in segment 6. She was treated with oral S-1, 80 mg/body for 14 days, followed by a 7-day rest, and CDDP 20mg/m2(day 1 and 8). After ten courses of treatment, CT showed reduction of the primary cancer, the liver tumor, and the affected lymph nodes. Then, distal gastrectomy, lymph node dissection, and partial liver resection were performed. The histological diagnosis was no viable cancer cells found in stomach, liver or lymph nodes. One year and 1 month postoperatively, the patient is alive without recurrence.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Drug Combinations; Female; Humans; Liver Neoplasms; Oxonic Acid; Remission Induction; Stomach Neoplasms; Tegafur

Although the standard treatment for liver metastasis from gastric cancer is chemotherapy, there are several reports demonstrating better survival after hepatectomy. However, repeat hepatectomy for liver metastasis is still rare. We present a case of long-term survival after repeat hepatectomy for liver metastasis from gastric cancer. A 68-year-old male underwent distal gastrectomy with D2 lymphadenectomy for a gastric cancer. The histopathological finding revealed that the tumor was a moderately-differentiated tubular adenocarcinoma 43mm in diameter, with invasion to subserosa(T3; SS). There was one metastasis to the regional lymph node(#11p). The tumor was classified as T3N1M0(stage II B)according to the 14th edition of the Japanese Classification of Gastric Carcinoma. Fourteen months after the operation, computed tomography revealed two metastases in the lateral segment of the liver. He underwent left lateral segmentectomy followed by adjuvant chemotherapy with S-1(100mg)for one year. Sixteen months after the hepatectomy, a solitary hepatic metastasis 30mm in size at segment 8 was found by follow-up CT scan. He underwent repeat hepatectomy. He is free of recurrence now without adjuvant chemotherapy four years after repeat hepatectomy.

Topics: Aged; Antimetabolites, Antineoplastic; Combined Modality Therapy; Drug Combinations; Hepatectomy; Humans; Liver Neoplasms; Male; Oxonic Acid; Recurrence; Stomach Neoplasms; Tegafur; Time Factors

The regenerating gene Iα (REG Iα) is involved in gastric carcinogenesis as an antiapoptotic factor. Therefore, we investigated whether REG Iα confers resistance to chemotherapeutic drugs in gastric cancer (GC) cells and whether REG Iα expression is useful for predicting the response to chemotherapy and outcome in patients with GC.. A total of 70 patients with unresectable stage IV GC received first-line chemotherapy with S-1 and cisplatin (S-1/CDDP). The expression of REG Iα was evaluated immunohistochemically using biopsy samples obtained before chemotherapy, and its relationship to clinicopathological parameters was analysed statistically. The effects of REG Iα gene induction on resistance to 5-FU or CDDP treatment were examined by cell survival assay and flow cytometry.. Of the 70 patients with unresectable stage IV GC, 19 (27%) were positive for REG Iα expression. The expression of REG Iα was independently predictive of poorer progression-free and overall survival in such patients (hazard ratio (HR) 2.46; P=0.002 and HR 1.89; P=0.037, respectively). The gene induction of REG Iα conferred resistance to cell death induced by 5-FU or CDDP in GC cells.. In patients with stage IV GC, REG Iα, which confers resistance to chemotherapeutic drugs in GC cells, is a potential biomarker for predicting resistance to S-1/CDDP treatment.

Topics: Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Cell Line, Tumor; Cell Survival; Cisplatin; Drug Combinations; Drug Resistance, Neoplasm; Female; Fluorouracil; Humans; Lithostathine; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Stomach Neoplasms; Tegafur; Treatment Outcome

We aimed to evaluate the efficacy of a new combination antiemetic therapy comprising aprepitant, granisetron, and dexamethasone in gastric cancer patients undergoing chemotherapy with cisplatin and S-1.. Gastric cancer patients scheduled to receive their first course of chemotherapy with cisplatin (60 mg/m(2)) and S-1 (80 mg/m(2)) were treated with a new combination antiemetic therapy aprepitant, granisetron, and dexamethasone on day 1; aprepitant and dexamethasone on days 2 and 3; and dexamethasone on day 4. The patients reported vomiting, nausea, use of rescue therapy, and change in the amount of diet intake, and completed the Functional Living Index-Emesis (FLIE) questionnaire. The primary endpoint was complete response (CR; no emesis and use of no rescue antiemetics) during the overall study phase (0-120 h after cisplatin administration). The secondary endpoints included complete protection (CP; CR plus no significant nausea); change in the amount of diet intake; and the impact of chemotherapy-induced nausea and vomiting (CINV) on daily life during the overall, acute (0-24 h), and delayed (24-120 h) phases.. Fifty-three patients were included. CR was achieved in 88.7, 98.1, and 88.7% of patients in the overall, acute, and delayed phases, respectively. The corresponding rates of CP were 67.9, 96.2, and 67.9%. Approximately half of the patients had some degree of anorexia. FLIE results indicated that 79.5% of patients reported "minimal or no impact of CINV on daily life".. Addition of aprepitant to standard antiemetic therapy was effective in gastric cancer patients undergoing treatment with cisplatin and S-1.

Topics: Aged; Aged, 80 and over; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Cisplatin; Dexamethasone; Drug Combinations; Drug Therapy, Combination; Female; Granisetron; Humans; Male; Middle Aged; Morpholines; Nausea; Neoplasm Staging; Oxonic Acid; Prospective Studies; Psychometrics; Quality of Life; Stomach Neoplasms; Tegafur; Treatment Outcome; Vomiting

We examined the adverse gastrointestinal events associated with tegafur/gimeracil/oteracil potassium (S-1) plus cisplatin therapy for unresectable recurrent gastric cancer and risk factors for discontinuing therapy due to adverse events. A total of 65 subjects who had received S-1 plus cisplatin therapy for gastric cancer at Ogaki Municipal Hospital were examined. We found that the risk factors for discontinuation of the therapy due to adverse events were serum albumin (Alb) level less than 3.5 g/dL (odds ratio [OR]: 321.14, P = .0015), creatinine clearance (CrCl) rate less than 78 mL/min (OR: 35.23, P = .0123), and performance status (PS) more than 1 (OR:12.62, P = .0243). Moreover, grade 3 or 4 nonhematological toxicities (including malaise and anorexia) were significantly higher in subjects with Alb less than 3.5 g/dL and CrCl less than 78 mL/min (P < .01). In conclusion, we should pay attention to the safety and continuity of S-1 plus cisplatin therapy in cases where the Alb level is <3.5 g/dL, CrCl level is <78 mL/min, and PS level is >1. Pharmacists should consider reducing the treatment dosage and providing nutritional support in such cases.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Creatinine; Drug Combinations; Female; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Oxonic Acid; Pharmacy Service, Hospital; Stomach Neoplasms; Tegafur

This report describes very rare intramucosal gastric cancer with metastasis to 15 lymph nodes. A 65-year-old Japanese man was admitted to our hospital with epigastralgia. Endoscopic examination revealed a 3.5 cm type IIc ulcerated lesion on the posterior wall near the lesser curvature of the angle of the stomach with mucosal tumor invasion. Neither enlarged lymph nodes nor distant metastasis was revealed by abdominal computer tomography. He was treated by pylorus-preserving gastrectomy with lymph node dissection. A histological examination of biopsy specimens revealed signet-ring cell carcinoma with ulcer scar that was limited to the mucosal layer. Although lymphatic vessel invasion was not evident, 15 of 23 retrieved nodes were actually involved. The final diagnosis was stage II gastric cancer, designated T1N2M0 according to the Japanese classification of gastric carcinoma. Twelve months after surgery, the patient remains alive without recurrence.

Topics: Aged; Antimetabolites, Antineoplastic; Biopsy; Carcinoma, Signet Ring Cell; Chemotherapy, Adjuvant; Drug Combinations; Gastrectomy; Gastric Mucosa; Gastroscopy; Humans; Immunohistochemistry; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Male; Neoplasm Staging; Oxonic Acid; Stomach Neoplasms; Tegafur; Tomography, X-Ray Computed; Treatment Outcome

The safety and feasibility of administering S-1 adjuvant chemotherapy for gastric cancer has not been fully evaluated in elderly patients.. This retrospective study selected patients who underwent curative D2 surgery for gastric cancer, were diagnosed with stage II or III disease, and received adjuvant S-1 at our institution. Patients were categorized into two groups; non-elderly patients (age <70 years: group A) and elderly patients (age ≥70 years: group B). The toxicity and S-1 continuation rates in the two groups were compared.. A total of 75 patients were evaluated in the study. There were no grade 4 toxicities. The incidences of grade 3 hematological and non-hematological toxicities were <5% in both groups, and the differences were not significant. The continuation rate at 6 months was 69% in group A and 70% in group B, and this difference was also not significant.. These results suggest that S-1 adjuvant chemotherapy for gastric cancer is safe and feasible, regardless of the age of the patient; especially for elderly patients who could be candidates for clinical trials.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Drug Combinations; Feasibility Studies; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Retrospective Studies; Stomach Neoplasms; Tegafur; Treatment Outcome

Our previous phase I study indicated that combination chemotherapy with intraperitoneal docetaxel and S-1 was well tolerated by gastric cancer patients with peritoneal carcinomatosis (PC). This study evaluated the benefits of this combination chemotherapy and subsequent surgery.. Neoadjuvant Intra-Peritoneal and Systemic chemotherapy (NIPS) was introduced to gastric cancer patients with positive cytology or with PC. Two cycles of intraperitoneal chemotherapy with docetaxel combined with S-1, were administrated and gastrectomy with lymph node dissection was performed in cases without macroscopic PC at post-NIPS staging laparoscopy.. Eighteen patients were enrolled in this study. Eight patients had measurable lymph node metastases by the RECIST criteria and computed tomography (CT) showed that five (62.5%) displayed a major response to the treatment. Out of 18 patients, 14 (78%) showed negative results on peritoneal cytology and no macroscopic PC, while the remaining four were cancer cell positive on peritoneal cytology or showed macroscopic PC even after NIPS. The median survival time of the entire group was 24.6 months. No treatment-related mortality was observed during NIPS and surgery.. This study indicated that the NIPS combined with surgery was highly active and well tolerated by advanced gastric cancer patients with PC.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Combined Modality Therapy; Docetaxel; Drug Combinations; Female; Follow-Up Studies; Humans; Injections, Intraperitoneal; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Peritoneal Neoplasms; Postoperative Complications; Prospective Studies; Stomach Neoplasms; Survival Rate; Taxoids; Tegafur; Treatment Outcome

The prognosis of gastric cancer with para-aortic lymph node (PAN) metastasis is poor. We applied triple combination chemotherapy with docetaxel, cisplatin, and S-1 (DCS therapy) as pre-operative chemotherapy and investigated the outcome of the combination of this therapy and gastrectomy with para-aortic lymph node dissection (PAND).. We retrospectively identified 44 patients with pathologically positive PAN who underwent curative surgery at Kanazawa University Hospital between 1990 and 2008. Among the 44 patients, 16 received pre-operative DCS therapy and subsequent surgical resection after two courses of the therapy.. Pre-operative DCS therapy showed high clinical response ratio (68.8%) and disease control ratio (100%). The pathological response ratio of resected specimen was 87.5%. At 2 years after surgery, the overall survival ratio was 93.8% and relapse-free survival was 75.0%. Pre-operative DCS therapy was only independent prognostic factor in multivariate analysis. Grade 3/4 toxicity was observed only in 25.0% of patients who underwent DCS therapy. Surgical complication was observed in 31.3% of patients, and this ratio was equal to that of patients who did not receive DCS therapy.. Multimodal therapy comprising combined pre-operative DCS therapy and gastrectomy with PAND was extremely effective and feasible for advanced gastric cancer with PAN metastasis.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cisplatin; Docetaxel; Drug Combinations; Female; Gastrectomy; Humans; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Multivariate Analysis; Neoadjuvant Therapy; Oxonic Acid; Postoperative Complications; Retrospective Studies; Stomach Neoplasms; Survival Analysis; Taxoids; Tegafur

Overexpression of human epidermal growth factor receptor (EGFR) has been detected in gastric cancer (GC) and is associated with poor outcomes. Combination treatment regimens with EGFR-targeting agents and cytotoxic agents are considered to be a potential therapeutic option for EGFR-overexpressing GC. Herein, we have investigated the effects of combination treatment with the oral fluoropyrimidine S-1 and the EGFR-targeting agent cetuximab in GC cells with or without EGFR overexpression. EGFR expression was determined by FACS and quantitative PCR in GC cells. Experimental 5-fluorouracil (5FU) was used instead of S-1 for in vitro experiments. The efficacy of 5FU or cetuximab monotherapy or combination 5FU/cetuximab therapy was examined in vitro and in vivo. Clinical specimens were examined for EGFR by immunohistochemistry (IHC). EGFR expression score was defined as strong membrane and cytoplasmic staining in at least 50-75% of cells. The combination of 5FU and cetuximab synergistically inhibited cell proliferation and exhibited an enhanced proapoptotic effect in GC cells with EGFR overexpression. Cetuximab also induced down-regulation of phosphorylation of EGFR and AKT, leading to diminished signaling. The antitumor effect of the combination of S-1 and cetuximab in vivo was also greater than that of either drug alone. Our preclinical findings thus indicate that the combination of S-1 and EGFR-targeting therapy is a promising treatment option for GC with EGFR overexpression.

Topics: Adult; Aged; Aged, 80 and over; Animals; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Cetuximab; Combined Modality Therapy; Drug Combinations; ErbB Receptors; Female; Fluorouracil; Gene Amplification; Humans; Male; Mice; Mice, Nude; Middle Aged; Oxonic Acid; Phosphorylation; Proto-Oncogene Proteins c-akt; Signal Transduction; Stomach Neoplasms; Tegafur; Xenograft Model Antitumor Assays

The peritoneum is still the most frequent site of recurrence in stage II/III gastric cancer patients, although the survival rate was improved by the introduction of S-1 adjuvant chemotherapy. The objective of this retrospective study was to clarify the risk factors for peritoneal recurrence in patients who received S-1 adjuvant chemotherapy.. Peritoneal recurrence-free survival was examined in 100 gastric cancer patients who underwent curative D2 surgery, which were diagnosed with stage II or III disease pathologically, and received adjuvant S-1 between June 2002 and March 2011. The univariate and multivariate analyses were performed to identify risk factors by a Cox proportional hazards analysis.. The P-RFS was 64.3% at 3 years and 58.8% at 5 years. A total of 18 patients were diagnosed with peritoneal recurrence. The macroscopic tumor diameter, depth of tumor invasion, and lymph node metastasis were the significant factors identified by the univariate analysis, while the tumor diameter and lymph node metastasis were the only significant independent risk factors identified by the multivariate analysis.. The macroscopic tumor diameter and presence of lymph node metastasis were the most important risk factors for peritoneal recurrence. When patients had these risk factors, S-1 was not sufficient to inhibit peritoneal recurrence. A novel adjuvant chemotherapeutic agent targeting peritoneal metastasis in these patients should be developed.

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Disease-Free Survival; Drug Combinations; Female; Follow-Up Studies; Gastrectomy; Humans; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Oxonic Acid; Peritoneal Neoplasms; Proportional Hazards Models; Retrospective Studies; Risk Factors; Stomach Neoplasms; Tegafur; Tomography, X-Ray Computed

The S-1(tegafur/gimeracil/oteracil potassium)granule was developed to meet the needs of patients with cancer. Although the choice of the patients was thought to spread by the addition of the new agent type, the recognition of the S-1 granule is still low and you should adapt yourself to what kind of patients or are unknown. Therefore, we conducted a questionnaire survey of patients with gastric cancer undergoing treatment with S-1 capsules to investigate the adaptation and taste of the patients. As a result, although it was the investigation by the patients during S-1 capsule remedy, it was replied when 21. 3%(13/61 case)'had good granule,'and all cases raised it by the reason of there'not being the sense of incongruity of the throat at taking.'Also, about the global assessment of granule, the proportion of patient who replied'very good'or'good'were 31. 1% and 47%, in all cases and in the cases that felt the sense of incongruity of the throat during S-1 capsule remedy, respectively. Therefore, in the patients treated with the S-1 capsule, there were thought to be the patients who expected treatment with a granule. By the results of this survey, it was found that it is necessary to perform a medical teaching including dosage form to contribute to the adherence improvement of the patients.

Topics: Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Capsules; Deglutition; Drug Combinations; Female; Humans; Male; Middle Aged; Oxonic Acid; Powders; Stomach Neoplasms; Surveys and Questionnaires; Tegafur

We describe a 46-year-old man who presented with the chief complaint of lower back pain. The patient was diagnosed with advanced gastric cancer accompanied by multiple bone metastases, with compression fractures in the thoracolumbar vertebrae as well as distant lymph node metastases. He was administered eight courses of S-1/CDDP combination chemotherapy. Treatment results were as follows: primary lesion, non-CR/non-PD; lymph node metastases, CR; and bone metastases, non-CR/non-PD. As only the primary lesion showed a tendency toward progression after completion of eight courses, distal gastrectomy with D1 dissection was performed. Histopathological test results were ypT1b(SM1)and ypN1(2/22). The histological grade following treatment was grade 2 for both the primary lesion and the lymph nodes Following subsequent treatment with S-1 monotherapy and zoledronic acid, the disease did not progress, and at one year and four months since diagnosis and six months since surgery, CR and non-CR/non-PD have been maintained for the lymph node metastases and bone metastases, respectively.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Cisplatin; Drug Combinations; Humans; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Stomach Neoplasms; Tegafur

A 76-year-old man was admitted to our hospital for the treatment of remnant gastric cancer. Laparotomy revealed massive lymph node metastasis, direct invasion of the transverse colon, and peritoneal dissemination. Partial resection of remnant stomach with transverse colon and intraperitoneal infuser port implantation were performed. After surgery, he underwent chemotherapy with docetaxel(DOC)administered intraperitoneally, and S-1. CT scan showed no tumors, and the patient was judged to be a complete response(CR)without serious adverse events. We switched DOC to intravenous injection because of port damage, and grade 3 adverse events appeared frequently until the chemotherapy was stopped. It has been 30 months since we stopped the chemotherapy, and the patient is still alive with no evidence of tumor recurrence 48 months after surgery.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Biopsy; Combined Modality Therapy; Docetaxel; Drug Combinations; Humans; Male; Oxonic Acid; Peritoneal Neoplasms; Remission Induction; Stomach Neoplasms; Taxoids; Tegafur; Tomography, X-Ray Computed

We conducted this retrospective study to evaluate the effectiveness of giving oral anti-cancer drugs for 2 years as postoperative adjuvant chemotherapy to gastric cancer patients.. The subjects were 76 patients with stage II and III gastric cancer, who underwent curative surgery between 1989 and 2008. We divided the 20 years chronologically into the UFT term (1989-2003) and the S-1 term (2004-2008). The patients from each term were then divided into three groups according to the length of drug administration; namely, the surgery alone group, the 1-year group, and the 2-year group.. The survival time of the 2-year group was better than that of the surgery alone group, not only in the UFT term, but also in the S-1 term (P = 0.0224). Longer relapse-free survival was evident in the S-1 term, especially for the 2-year group (P = 0.0110). A multivariate analysis showed both the stage of the cancer and 2 years of postoperative adjuvant chemotherapy to be independent factors predictive of prolonged survival (P = 0.0040 and P = 0.0022, respectively).. The 2-year administration of oral anti-cancer drugs as postoperative adjuvant chemotherapy might improve the outcome of stage II, III gastric cancer patients. Randomized control trials are warranted to prove the effectiveness of this 2-year regimen.

Topics: Administration, Oral; Adult; Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Drug Administration Schedule; Drug Combinations; Female; Follow-Up Studies; Gastrectomy; Humans; Male; Middle Aged; Multivariate Analysis; Neoplasm Staging; Oxonic Acid; Prognosis; Retrospective Studies; Stomach Neoplasms; Survival Analysis; Tegafur; Treatment Outcome; Uracil

Topics: Adenocarcinoma; Antimetabolites, Antineoplastic; Drug Combinations; Female; Gastrectomy; Humans; Male; Oxonic Acid; Stomach Neoplasms; Tegafur

C-reactive protein (CRP) has been associated with the development of many carcinomas, but the significance of CRP remains unclear for metastatic gastric cancer (MGC).. Sixty one patients who received S-1 plus cisplatin for MGC were retrospectively identified and categorized into two groups depending on the serum CRP level before chemotherapy.. Overall survival was significantly shorter in the CRP≥1.0 group than in the CRP<1.0 group (median, 292 days versus 451 days; p=0.0004). Moreover, progression-free survival was significantly shorter in the CRP≥1.0 group than in the CRP<1.0 group (median, 115 days versus 188 days; p=0.0010). In a multivariate analysis, serum CRP level before chemotherapy was an independent prognostic factor for MGC (hazard ratio 4.20 [95% CI, 1.66 to 10.64] p=0.002).. Serum CRP level before chemotherapy might be a potential prognostic factor for MGC.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; C-Reactive Protein; Cisplatin; Disease-Free Survival; Drug Combinations; Female; Humans; Male; Middle Aged; Multivariate Analysis; Oxonic Acid; Retrospective Studies; Stomach Neoplasms; Survival Rate; Tegafur

The patient was a 76-year-old man with no chief complaint. He presented to an internist of our hospital for an evaluation of anemia. An upper gastrointestinal endoscopy revealed a type 2 tumor at the lesser curvature of the gastric body. Although the blood analysis showed a high amount of AFP(2, 328 ng/mL), there was no abnormality found in the liver with a CT scan. The tumor was presumed to be an AFP-producing gastric cancer on the basis of the tumor biopsy. We performed total gastrectomy, splenectomy and cholecystectomy. The tumor cells were positive for AFP by immunohistochemistry. The final diagnosis was hepatoid adenocarcinoma, pT3(SS), INF b, ly1, v2, pN1(3/42), pStage II B. Tumor cells were negative for antihepatocyte antibody and anti-HER2 antibody. The amount of AFP normalized postoperatively. After discharge, he was treated with S-1(80mg/day)orally. He is relapse-free now, 14 months after the operation. Hepatoid adenocarcinoma is an extremely aggressive tumor with a poor prognosis, and effective chemotherapy has still not been established. A larger number of analyses, along with a molecular biological approach, is sure to be helpful for the establishment of an effective treatment for hepatoid adenocarcinoma.

Topics: Adenocarcinoma; Aged; alpha-Fetoproteins; Antimetabolites, Antineoplastic; Combined Modality Therapy; Drug Combinations; Humans; Male; Neoplasm Staging; Oxonic Acid; Stomach Neoplasms; Tegafur; Tomography, X-Ray Computed; Treatment Outcome

The patient was a 67-year-old male with type-3 gastric cancer from the upper body of the stomach to the cardia. An abdominal computed tomography scan revealed liver metastases(S8)(T2N0M0H1, Stage IV). The patient received neoadjuvant combined chemotherapy with S-1 and CDDP. S-1(120mg/body/day)was orally administered for 3 weeks followed by 2 drug-free weeks as a course, and CDDP(60mg/m2)was administered by intravenous infusion on day 8. After the second course, significant tumor reduction and disappearance of liver metastases resulted. Total gastrectomy, splenectomy, cholecystectomy, and D2 nodal dissection were performed. The histological diagnosis revealed no metastases in all lymph nodes: Stage I B. The combined neoadjuvant chemotherapy with S-1 and CDDP can be considered an effective treatment for advanced gastric cancer.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Biopsy; Cisplatin; Drug Combinations; Humans; Liver Neoplasms; Male; Neoadjuvant Therapy; Neoplasm Staging; Oxonic Acid; Stomach Neoplasms; Tegafur; Tomography, X-Ray Computed

A 65-year-old male with type 5 gastric cancer and two lesions of liver metastases was initially treated with S-1/CDDP. After completion of the second course, however, the progression of liver metastases and appearance of massive ascites were detected with CT scan, and dysphagia appeared. Total gastrectomy was performed to improve the symptoms. Later, chemotherapy with weekly PTX was performed, demonstrating the regression of liver metastases and disappearance of ascites after 2 courses. Thus, partial liver resection for liver metastases was performed. PTX has been readministered weekly, and the patient is currently attending the outpatient clinic without recurrence, although two years have passed since his first examination.

Topics: Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Biopsy; Cisplatin; Drug Combinations; Humans; Liver Neoplasms; Male; Neoplasm Staging; Oxonic Acid; Paclitaxel; Remission Induction; Salvage Therapy; Stomach Neoplasms; Tegafur; Tomography, X-Ray Computed

To report dacryoendoscopic observations and the incidence of lacrimal obstruction/stenosis associated with S-1, an oral anticancer drug.. Retrospective, nonrandomized clinical trial.. A total of 52 patients (41 men, 11 women; age 42-93 years) who were prescribed the anticancer drug S-1 were studied. Patients who suffered eye complaints following S-1 treatment underwent ophthalmic examination, probing and lacrimal irrigation. Patients whose tear meniscus was high or had abnormal lacrimal irrigation were evaluated by dacryoendoscopy.. Overall, 5 of 52 S-1-treated patients (9.6%) experienced lacrimal passage stenosis/obstruction. One patient had punctal stenosis, and four patients had canalicular obstruction/stenosis. The onset of epiphora ranged from 2 to 8 months (4.4 ± 2.2 months, mean ± SD) after the initiation of chemotherapy.. Patients receiving S-1 treatment should be evaluated for potential lacrimal disorders, particularly canalicular obstruction/stenosis. Dacryoendoscopic observation is effective for the diagnosis of this side effect.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Colonic Neoplasms; Drug Combinations; Endoscopy; Female; Humans; Incidence; Lacrimal Duct Obstruction; Lung Neoplasms; Male; Middle Aged; Nasolacrimal Duct; Oxonic Acid; Pancreatic Neoplasms; Retrospective Studies; Stomach Neoplasms; Tegafur

Postoperative adjuvant chemotherapy with S-1 is a standard treatment for several digestive cancers. We conducted alter- nate-day oral therapy as postoperative adjuvant chemotherapy with S-1, for 31 patients with pathological stage II / IIIgastric cancer for whom radical resection had been performed. We examined the effects, the rate of compliance with all of the dosing instructions, cancer recurrence, and the survival rate with S-1 by the administration method for 31 cases. Twenty-eight patients(90. 3%)could be administered S-1 for one year. Those with side effects were admitted in 4 cases(13%). Those with side effects of grade 3 or more were not admitted. The 3-year survival rate was obtained; stage II 91%, and stage III 67% in gastric cancer. Four patients had recurrences at; the rate of 13%. In conclusion, the number of side effects was decreased, and a high rate of compliance with all dosing instructions was achieved in alternate-day oral therapy with S-1, compared with the daily oral method. This method can be a safe and useful way to administer S-1 oral therapy.

Topics: Administration, Oral; Aged; Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Drug Combinations; Female; Humans; Male; Neoplasm Staging; Oxonic Acid; Stomach Neoplasms; Tegafur

Our patient was a 74-year-old man with abdominal pain. A gastrofiberscope revealed type 2 advanced gastric cancer. An abdominal computed tomography(CT)demonstrated liver and lymph node metastases. The No. 8a lymph node was 7 cm in diameter, and it invaded the head of the pancreas. Since a curative operation was deemed impossible, S-1 was administered orally for 28 consecutive days with a 14-day interval. After 2 courses of monotherapy, CT showed that metastatic lymph nodes were reduced and that liver metastases had mostly disappeared. After 8 courses, the primary lesion was scarred and the lymph node metastases were remarkably reduced. Therefore, we conducted distal gastrectomy and lymph node resection (D2). Histological findings revealed that there were no cancer cells in either the primary tumor or the lymph nodes, meaning that the resected lesions were Grade 3 in pathology. This rare case showed that S-1 monotherapy enabled curative surgery of unresectable gastric cancer with pathological CR.

Topics: Aged; Antimetabolites, Antineoplastic; Combined Modality Therapy; Drug Combinations; Humans; Male; Oxonic Acid; Remission Induction; Stomach Neoplasms; Tegafur; Tomography, X-Ray Computed

A 64-year-old man with advanced gastric cancer who underwent a curative total gastrectomy(LM, Less, Type 3, 70×55 mm, por1>tub2>sig, pT3(ss), med, INF b, ly3, v3, pN3b(41/61), pPM0, pDM0, pT3N3bM0, Stage III B)followed by adjuvant chemotherapy(paclitaxel+S-1)a year ago, revealed an increasing level of serum CEA and para-aortic lymphnode (#16b1)recurrence on abdominal CT. He was given chemotherapy with low-dose weekday CDDP+S-1 for the recurrence, after which he failed to respond. Thereafter, he received 2nd-line chemotherapy with bi-weekly CPT-11+CDDP as a S-1- refractory regimen. 3 courses of the regimen reduced the serum CEA level accompanied by grade 3 of anemia. After recovery from the adverse event, another 4 courses at a 20% lower dosage for safety were administered. Complete response to the lymphnode was ensured on the abdominal CT with a reduced serum CEA level into the normal range. The patient has no signs of recurrence and has survived in fair condition for more than 5 years after the surgery. The combination treatment of biweekly CPT-11+CDDP can be a worthwhile regimen for patient with S-1-refractory recurrence of the resected advanced gastric cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; Aorta, Abdominal; Camptothecin; Cisplatin; Drug Combinations; Drug Resistance, Neoplasm; Humans; Irinotecan; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Recurrence; Stomach Neoplasms; Tegafur

A 81-year-old man presented with anemia. He received a distal gastrectomy for gastric ulcer as a 40-year-old, and was also diagnosed with prostate cancer with bone metastasis as an 80-year-old. He has been undergoing treatment with anti-androgen therapy. Gastrointestinal endoscopic examination showed advanced gastric cancer, which was diagnosed as poorly differentiated adenocarcinoma. Computed tomography(CT)showed enlarged para-aortic lymph nodes. The clinical Stage was IV: cT3, N3, M1. He was treated with oral S-1 alternate-day administration of 100mg/day. The tumor in his remnant stomach shrunk in size by 3 months after beginning S-1 administration, and an endoscopic examination revealed a scar, but no cancer cells were found in a biopsy specimen of the scar tissue. Furthermore, CT scan showed that the swollen para-aortic lymph nodes were obviously reduced in size. As a result, we diagnosed this as a partial response to chemotherapy with S-1 alternate-day administration. No adverse events during the treatment were due to S-1 administration. His quality of life and poor food intake remarkably improved. S-1 alternate-day therapy demonstrated efficacy and tolerable toxicity even for a patient who was elderly and /or with poor performance status. S-1 can be managed safely on an outpatient basis without side effects for a long duration, and has been superior in terms of continuity of treatment.

Topics: Aged, 80 and over; Antimetabolites, Antineoplastic; Drug Combinations; Fatal Outcome; Gastric Stump; Gastroscopy; Humans; Male; Neoplasm Staging; Neoplasms, Second Primary; Oxonic Acid; Stomach Neoplasms; Tegafur; Tomography, X-Ray Computed

To improve the prognosis of locally advanced gastric cancer, clinical trials of neoadjuvant chemotherapy (NAC) are being performed. Although neoadjuvant chemoradiotherapy (NACRT) generally achieves superior local tumor control to NAC, its efficacy for locally advanced gastric cancers remains unclear. Therefore, a prospective trial was conducted to explore the feasibility and safety of NACRT with oral S-1 in a series of cases.. Patients who had Japanese Gastric Cancer Association (JGCA) cStage IIIB gastric cancer were enrolled onto this study and received oral S-1 (65 mg/m(2)/day) administration and 50-Gy radiotherapy followed by radical surgery. The primary end points were completion of therapy and safety.. Between October 2005 and September 2008, 12 eligible patients were enrolled. Two could not complete the chemotherapy because of grade 3 toxicity. R0 resections were performed in 11 patients (91.7 %) (95 % confidence interval 61.5-99.8). Although operative morbidity was observed in two cases, there were no postoperative deaths. A pathologic response was observed in 10 patients (83.3 %). In five (62.5 %) of eight gastric cancers with invasion to adjacent structures, microscopic tumor deposits were not found in the affected organs. The 3-year survival rate was 58.3 % during a median follow-up period of 36 months.. Although this study is preliminary, the present regimen seems to be feasible and safe as a treatment for locally advanced gastric cancers featuring adjacent tissue invasion or JGCA bulky N2 disease. This treatment approach should now be tested using the new tumor, node, metastasis staging system in a large clinical trial.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Anorexia; Antimetabolites, Antineoplastic; Chemoradiotherapy, Adjuvant; Dose Fractionation, Radiation; Drug Combinations; Female; Gastrectomy; Humans; Kaplan-Meier Estimate; Lymph Node Excision; Lymphatic Metastasis; Male; Middle Aged; Nausea; Neoadjuvant Therapy; Neoplasm Grading; Neoplasm Staging; Oxonic Acid; Pilot Projects; Stomach Neoplasms; Tegafur

A 66-year-old male with a chief complaint of dysphagia was admitted to our hospital. Upper gastrointestinal endoscopy revealed a type 3 tumor on the gastric upper body, and pathological examinations of the biopsy specimens revealed a poorly differentiated adenocarcinoma. Computed tomography (CT) of the abdomen showed significant wall thickness of the stomach, and regional and para-aortic lymph node metastases. The CA19-9 level was high: 978 U/mL on admission. He received neoadjuvant chemotherapy using S-1 (120 mg/body, days 1-21) and cisplatin (108 mg/body, days 8) for faradvanced gastric cancer. After neoadjuvant chemotherapy, upper gastrointestinal endoscopy revealed that the gastric carcinoma had significant reductions in the size of its tumors, and CT showed that the lymph node metastases had disappeared, leading to a partial response. He underwent total gastrectomy, distal pancreatectomy, splenectomy and Roux-en Y reconstruction. Pathological examination of the resected specimens showed a small number of cancer cells in the submucosal layer, suggesting a Grade 2 pathological response, and gave a positive reaction to CA19-9 staining. The postoperative CA19-9 level decreased to a normal level. This case is diagnosed as CA19-9-producing gastric cancer. He was treated on an outpatient basis with adjuvant therapy.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; CA-19-9 Antigen; Cisplatin; Drug Combinations; Humans; Male; Neoadjuvant Therapy; Oxonic Acid; Stomach Neoplasms; Tegafur; Tomography, X-Ray Computed

CASE 1: A 72-year-old man with epigastralgia was diagnosed with gastric cancer and referred to our hospital. An abdominal CT scan revealed liver metastasis and para-aortic lymph node metastasis. He was treated with S-1+CDDP. After 4 courses of this treatment, the liver metastasis and para-aortic lymph node metastasis disappeared, and adjuvant surgery was performed. There has been no recurrence for 16 months postoperatively. CASE 2: A 66-year-old man with anorexia was diagnosed with gastric cancer and referred to our hospital. An abdominal CT scan revealed para-aortic lymph node metastasis. He was treated with S-1+CDDP. After 9 courses of this treatment, para-aortic lymph node metastasis disappeared, and adjuvant surgery was performed. Eight months after the operation, lymph node metastases were confirmed by abdominal CT scan, and he was treated with chemotherapy as an outpatient as of 13 months after the operation. We experienced two cases of Stage IV gastric cancer undergoing adjuvant surgery after down staging by chemotherapy. It was suggested that adjuvant surgery to highly advanced gastric cancer could improve the prognosis of patients.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Humans; Liver Neoplasms; Lymphatic Metastasis; Male; Neoadjuvant Therapy; Neoplasm Invasiveness; Neoplasm Staging; Oxonic Acid; Stomach Neoplasms; Tegafur; Tomography, X-Ray Computed

A 46-year-old woman with lower abdominal distension was diagnosed as gastric cancer in our hospital. She had multiple metastases of lungs, lymph nodes, bilateral ovaries, and uterus. After she underwent sub-total gastrectomy, bilateral oophorectomy, and total hysterectomy, she received adjuvant chemotherapy followed by docetaxel and S-1. After 6 courses of chemotherapy, PET/CT revealed no recurrences (complete response), and she was therefore administered S-1 for only 6 months. She has remained without recurrence 15 months after the operation.

Topics: Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Docetaxel; Drug Combinations; Female; Humans; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Positron-Emission Tomography; Remission Induction; Stomach Neoplasms; Taxoids; Tegafur

We report two cases of advanced gastric cancer. The first was a 77-year-old man who had experienced distal gastrectomy about 35 years ago. He complained of abdominal bloating, and a gastrointestinal scope showed that he had advanced gastric cancer. CT scan revealed massive ascites. Dissemination of the peritoneum was suspected, and chemotherapy using S-1 (80mg/m², biweekly)plus paclitaxel (50mg/m², on days 1 and 8) was selected, He had no major side effects and the ascites disappeared. He was able to receive 18 courses on an outpatient basis. The second case was a 79-year-old man who had total gastrectomy performed 1 year ago. Invasion to the diaphragm and lymph node metastasis were detected. We selected S-1 (80 mg/m²)as adjuvant chemotherapy but that caused severe fatigue. Eventually he refused the drug. Six month later, he had abdominal bloating and CT scan revealed that he had massive ascites. UFT-E (1. 5 g/body) was administered and paclitaxe (l 50 mg/m²) was added. The ascites disappeared and he has had a stable life. DIF (S-1, UFT) plus paclitaxel is considered to be a useful chemotherapy combination against advanced gastric cancer that has peritoneal dissemination or ascites, even for older patients.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Ascites; Dihydrouracil Dehydrogenase (NADP); Drug Combinations; Humans; Male; Oxonic Acid; Paclitaxel; Peritoneal Neoplasms; Peritonitis; Quality of Life; Stomach Neoplasms; Tegafur; Tomography, X-Ray Computed

Patients with bone metastasis originating from gastric cancer experience complications from DIC. They are treated with anticoagulation therapy or platelet transfusion, but their prognosis is poor. Our case was a 50-year-old male who had undergone distal gastrectomy for early gastric cancer[pT1a(M)N0M0, pStage I a]ten years previously. He was admitted to our hospital complaining of backache. As a result of his examination, he was diagnosed with disseminated carcinosis of bone marrow with DIC as a postoperative recurrence of gastric cancer. The patient was treated with combination chemotherapy of S-1 and cisplatin(S-1 80 mg/body, po, day 1-21 and cisplatin 50mg/body, iv, day 8). After one course of treatment, DIC was resolved and his pain was relieved. He survived for about nine months. S-1 and cisplatin are considered to be effective for disseminated carcinosis of bone marrow.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Neoplasms; Carcinoma; Cisplatin; Disseminated Intravascular Coagulation; Drug Combinations; Fatal Outcome; Gastrectomy; Humans; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Stomach Neoplasms; Tegafur

A 47 -year-old male presented with gastric cancer, with right cervical and para-aortic lymph node metastases. The patient had not undergone a curative operation, but was treated with immunochemotherapy in combination with S-1 60 mg/m2(2 weeks administration and 2 weeks rest), paclitaxel 60 mg/m²(day 1, 8, 15), and Lentinan 2mg/body(day 1, 8, 15). After 3 courses of this treatment, no hot-spots were identified on cervical and para-aorta lymph nodes by PET-CT examination. We decided to perform total gastrectomy with D3 lymphadenectomy and Roux-en Y reconstruction. On histopathological examination, no malignancy was seen in the lymph nodes and the main tumor was judged to be grade 2. With this combined immunochemotherapy, the patient had a favorable outcome without side effects, which proved effective for far advanced gastric cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Drug Combinations; Gastrectomy; Humans; Lentinan; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Paclitaxel; Remission Induction; Stomach Neoplasms; Tegafur

The patient was a 72-year-old woman diagnosed with advanced gastric cancer, hepatic portal lymph node and para-aortic lymph node metastases. After five courses of S-1/CDDP combination therapy, both the primary tumor and lymph node metastases disappeared clinically. She wished to continue chemotherapy instead of having a resection. After three more courses of S-1/CDDP therapy, gastric cancer and lymph node metastases were still completely regressed, but complications of carcinoma of the gallbladder were suspected. Gastrectomy was performed with cholecystectomy, and a histopathological examination revealed cancer cells remaining in the gastric submucosa and xanthogranulomatous cholecystitis. We consider surgical therapy for clinically completely disappearing advanced gastric cancer by chemotherapy, in addition to case report.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Drug Combinations; Female; Gastrectomy; Humans; Neoplasm Staging; Oxonic Acid; Remission Induction; Stomach Neoplasms; Tegafur; Tomography, X-Ray Computed

This study was conducted to determine the incidence and clinical characteristics of lacrimal drainage obstruction (LDO) in patients receiving S-1 chemotherapy.. Consecutive 170 patients with gastric cancer who underwent curative surgery and received adjuvant S-1 chemotherapy were enrolled. S-1 was administered orally (40 mg/m2 b.i.d. on days 1-28 every 6 weeks) for 1 year. Ophthalmologic examinations were carried out on patients complaining of epiphora.. Thirty-one patients (18%) developed epiphora. Among 31 patients, 25 underwent ophthalmologic examinations and 22 (88%) were diagnosed with LDO. The median time to the onset of LDO was 2.9 months. The most common site of obstruction was the nasolacrimal duct [86% (19/22)]; punctal [23% (5/22)] and canalicular obstruction [14% (3/22)] were also noted. In multivariate analysis, total gastrectomy [versus partial gastrectomy: hazard ratio (HR), 2.9; P=0.014] and creatinine clearance<50 ml/min (versus ≥50 ml/min: HR, 2.9; P=0.038) were independent risk factors for the development of LDO.. Considering the high incidence of LDO in patients receiving S-1 chemotherapy, oncologists should be alert to epiphora and cooperate with ophthalmologists in the early stages to improve the quality of life of patients and avoid more complicated ophthalmologic procedures.

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Female; Humans; Lacrimal Duct Obstruction; Male; Middle Aged; Nasolacrimal Duct; Oxonic Acid; Stomach Neoplasms; Tegafur

S-1 plus cisplatin is the standard first-line chemotherapy for metastatic gastric cancer (MGC) in Japan, but the relationship between dose intensity and antitumor effects remains unclear.. We retrospectively studied 64 patients who received S-1 plus cisplatin for MGC from January 2006 to December 2010 in two Japanese hospitals.. The median relative dose intensity (RDI) of S-1 plus cisplatin was 87% (range, 59.5%-100%). The cut-off value of RDI of S-1 plus cisplatin was identified to be 80% by a receiver operating characteristic analysis of the tumor response. In the RDI<80% (n=19) and the RDI≥80% (n=45) groups, the response rates were 20.0% and 37.5% (p=0.182), the median survival times were 394 and 376 days (p=0.915), and the median progression-free survival (PFS) was 188 and 170 days (p=0.851), respectively.. An appropriate RDI reduction may be permitted for patients with MGC in palliative settings.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Disease-Free Survival; Drug Combinations; Female; Humans; Male; Middle Aged; Neoplasm Metastasis; Oxonic Acid; ROC Curve; Stomach Neoplasms; Tegafur

Developed as a biological response modifier (BRM), lentinan mitigates patients' symptoms by boosting the immune system. In combination with S-1 (tegafur, gimeracil, oteracil), lentinan is reported to mitigate adverse reactions to therapy for unresectable recurrent gastric cancer and prolong survival. However, there are few reports from actual clinical practice, and precise methods of using lentinan have not yet been established. This study retrospectively examined the usefulness of lentinan in patients.. The subjects of this study were 39 patients who were diagnosed with unresectable gastric cancer, based on preoperative examinations or findings at laparotomy in our Department. These patients underwent S-1/paclitaxel therapy. Nineteen of the patients received lentinan while 20 did not, and these two groups of patients were compared.. There were no significant differences in patients' characteristics such as the male:female ratio, age at the start of chemotherapy, and staging classification of the 19 patients receiving lentinan and the 20 patients not receiving lentinan. Comparison of the two groups revealed no significant differences in overall survival time, but comparison of the duration of therapy revealed that therapy tended to be longer for the group taking lentinan than the group not taking lentinan. Adverse events were noted in 61.5% (24 patients) of the total patients group; such events tended to occur less frequently in the group receiving lentinan.. Lentinan inclusion in therapy did not seem to prolong survival. Nevertheless, the duration of therapy tended to be longer for patients taking lentinan. This may be due to the fact that adverse events tended to occur less frequently in these patients during therapy. A decline in the incidence of adverse events increases the duration of therapy and improves the patients' quality of life (QOL); it may also prolong survival. Optimal methods of using lentinan need to be established.

Topics: Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Female; Humans; Kaplan-Meier Estimate; Lentinan; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Paclitaxel; Retrospective Studies; Stomach Neoplasms; Tegafur

We investigated the efficacy of gastrojejunostomy followed by S-1-based chemotherapy for unresectable gastric cancer with pyloric stenosis. We performed gastrojejunostomy and S-1-based chemotherapy in 14 unresectable gastric cancer patients with gastric outlet obstructions between April 2006 and June 2010. Although there were two complications after surgery, no treatment-related deaths were observed. The response rate of the S-1-based chemotherapy was 41.7%, and the median survival after surgery was 12.3 months. All patients were tolerating a regular diet and a significant improvement in oral intake lasted for at least 6 months. In conclusion, gastrojejunostomy followed by chemotherapy with S-1 appears to be an effective treatment modality for unresectable gastric cancer with pyloric stenosis. It enables us to practice S-1-based standard chemotherapy for advanced gastric cancer and improve the quality of life of patients.

Topics: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Combined Modality Therapy; Drug Combinations; Female; Gastric Bypass; Humans; Male; Middle Aged; Oxonic Acid; Pyloric Stenosis; Stomach Neoplasms; Tegafur

Reported here is the case of a 76-year-old male with gastric cancer. Distal gastrectomy was performed after his admission to our hospital. Histopathologically, the cancer was determined to be in the advanced stage. Combination chemotherapy with CDDP and S-1 was administered for 6 courses, after which S-1 was used alone. Chest X-ray and CT showed multiple dispersed lesions in the lung. Further examination by bronchoscope was performed. Histopathological examination of a biopsy specimen revealed the lesion to be organizing pneumonia. A drug-induced lymphocyte stimulation test (DLST) for S-1 proved to be positive. Discontinuation of S-1 administration led to natural improvement of the pneumonia. These results suggest that S-1 had induced the organizing pneumonia.

Topics: Aged; Antimetabolites, Antineoplastic; Biopsy; Drug Combinations; Humans; Lung Injury; Male; Oxonic Acid; Pneumonia; Stomach Neoplasms; Tegafur; Tomography, X-Ray Computed

The present patient was a 69-year-old male diagnosed as gastric cancer with peritoneal dissemination by staging laparoscopy. He was treated with chemotherapy using S-1 (120 mg/body/day) and docetaxel (70 mg/body/day 1) administered for 2 weeks, followed by one drug-free week in three-week courses. After 4 courses of treatment, the primary tumor regressed, but only slightly. Because of an adverse event, we continued with a lower dose. After 4 more courses of treatment, the primary tumor and dissemination were undetectable on abdominal CT scan but were endoscopically detected. The patient has been followed on an outpatient basis without surgical treatment for 2 years.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Docetaxel; Drug Combinations; Humans; Male; Neoplasm Staging; Oxonic Acid; Peritoneal Neoplasms; Stomach Neoplasms; Taxoids; Tegafur; Tomography, X-Ray Computed

A 74-year-old woman was referred to us for patterns of liver metastases found in abdominal ultrasonography. Upper gastrointestinal endoscopy revealed advanced gastric cancer, and the subsequent abdominal CT examination confirmed multiple liver metastases. After the first regimen, a combination of 5-FU and CDDP failed due to adverse events, so monotherapy of S-1 was introduced. An abdominal CT examination in the 21st month showed disappearance of liver metastases. She was judged to have a complete response and continued with this treatment. She survived five years and eight months on monotherapy of S-1 before she died of bronchiectasis.

Topics: Aged; Antimetabolites, Antineoplastic; Bronchiectasis; Drug Combinations; Fatal Outcome; Female; Humans; Liver Neoplasms; Oxonic Acid; Stomach Neoplasms; Tegafur; Tomography, X-Ray Computed

Complete remission from advanced-stage synchronous double primary (SDP) esophageal and gastric adenocarcinoma by chemotherapy alone is rare. We report a case of advanced-stage SDP esophageal and gastric adenocarcinoma in which a complete response to treatment was obtained with S-1 and cis-diamminedichloroplatinum (CDDP).. The patient was a 74-year-old man referred to our hospital complaining of dysphagia. Gastrointestinal endoscopy was performed and advanced-stage SDP esophageal and gastric adenocarcinoma diagnosed. Computed tomography revealed multiple regional lymph node metastases in the mediastinum. Neoadjuvant chemotherapy with S-1 and CDDP for advanced esophageal and gastric cancer was planned. An endoscopy following two courses of chemotherapy revealed that the esophageal cancer had been replaced with a normal mucosal lesion and the gastric tumor with a scar lesion; the results of biopsies of both were negative for cancer. Computed tomography revealed that the multiple lymph node metastases had disappeared. We diagnosed a complete response to S-1 and CDDP in advanced-stage SDP esophageal and gastric cancer. The patient is still alive with no signs of recurrence 22  months after the disappearance of the original tumor and metastatic lesions without surgical treatment.. These results suggest that complete remission from advanced-stage esophageal and gastric cancer can be obtained with chemotherapy with S-1 plus CDDP.

Topics: Adenocarcinoma; Aged; Antimetabolites, Antineoplastic; Cisplatin; Disease Progression; Drug Combinations; Drug Therapy, Combination; Esophageal Neoplasms; Humans; Male; Oxonic Acid; Stomach Neoplasms; Tegafur; Treatment Outcome

Recent advances in the treatment of metastatic unresectable gastric cancers (MGC) include the development of new antitumor drugs and new regimens for their use. However, the selection of individually designed regimens by gastric cancer (GC) subtype remains problematic. Here, we investigated the clinical usefulness of programmed chemotherapy.. MGC patients were classified into three groups by clinical condition. We implemented a chemotherapy program consisting of S-1 combination regimens. Median survival time (MST) of level 1 patients was 416 days (95% CI: 313-506 days), with an overall response rate of 47%. MSTs of level 2 and 3 patients were 208 (95% CI: 153-287 days) and 95 days (95% CI: 28-136 days), respectively. Grade 3-4 toxicities were neutropenia in 12% and anorexia in 6%. All treatment- related toxicities were resolved, and no treatment-related deaths occurred.. This program provided reasonable selection of case-matching regimens and may improve the survival of patients with MGC. Further, it may represent the first clinical tool to provide efficient chemotherapy course selection for MGC. Ongoing analysis of newly developed drugs and regimens will allow the efficacy of this chemotherapy program to be improved.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Clinical Trials, Phase II as Topic; Drug Combinations; Female; Humans; Liver Neoplasms; Male; Middle Aged; Oxonic Acid; Prognosis; Stomach Neoplasms; Survival Rate; Tegafur

The patient was a 66-year-old male, admitted and diagnosed as having advanced gastric cancer with peritoneal dissemination, leading to ascites and obstructive jaundice. After reducing the degree of obstructive jaundice, combination chemotherapy of S-1 80mg/m2/day(2 weeks administration and 1 week rest)and docetaxel(TXT)40mg/m2(day 1)was administered from February, 2008. After 3 courses of this regimen, CT revealed no evidence of ascites, and this chemotherapy was successively continued on an outpatient basis until June, 2009. After the relapse of ascites from July, 2009, combination chemotherapy of irinotecan(CPT-11)60mg/m2 and cisplatin(CDDP)30mg/m2 biweekly was performed as second-line chemotherapy, and the ascites disappeared again after around 2 courses of this regimen. This chemotherapy was continued on an outpatient basis until February, 2010. No major adverse reaction to either chemotherapy was observed. This case suggests that these chemotherapies, such as the combination chemotherapy of S-1 plus TXT as a first-line treatment and CPT-11 plus CDDP as the following second-line treatment, can be administered to an outpatient, can keep good patient's QOL and can be one of the effective chemotherapy options for advanced gastric cancer with peritoneal dissemination.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Ascites; Camptothecin; Cisplatin; Docetaxel; Drug Combinations; Fatal Outcome; Humans; Irinotecan; Male; Oxonic Acid; Peritoneal Neoplasms; Salvage Therapy; Stomach Neoplasms; Taxoids; Tegafur

A 59-year-old man with type 3 gastric cancer(signet-ring cell carcinoma)underwent simple laparotomy because of peritoneal dissemination.S -1/CDDP was started.Since the icterus of Grade 2 had appeared after 2 courses, S-1 and biweekly paclitaxel combination chemotherapy was started as second-line treatment.Throughout treatment, there was no adverse event, and this regimen was continued for 14 courses(25 months).He died 32 months after his first visit.S -1/PTX may play an important role as second-line chemotherapy for patients with unresectable advanced gastric carcinoma.

Topics: Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Fatal Outcome; Humans; Male; Middle Aged; Oxonic Acid; Paclitaxel; Peritoneal Neoplasms; Salvage Therapy; Stomach Neoplasms; Tegafur

A 54-year-old man underwent distal gastrectomy for early gastric cancer in September 2002. CT performed 6 months after the operation revealed liver metastases, and they were resected. Hepatic arterial infusion therapy of 5-FU was performed; however, multiple liver metastases appeared in October 2003. We added arterial infusion of CDDP to 5-FU, but liver metastases increased. We then applied a combination chemotherapy of S-1 and paclitaxel from February 2004. Subsequently, stable disease continued, and after 67 courses of S-1 plus paclitaxel, we changed the administration to S-1 alone from August 2009. After that, liver metastases did not increase, so we discontinued chemotherapy on August 2010, followed by observation. Progression of liver metastases has not been to date.

Topics: Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Drug Combinations; Humans; Liver Neoplasms; Male; Middle Aged; Oxonic Acid; Paclitaxel; Stomach Neoplasms; Tegafur; Tomography, X-Ray Computed

Leiomyosarcoma (LMS) of the gastrointestinal tract is an extremely rare high-grade neoplasm with poor prognosis. For advanced LMS with distant metastasis, the decision as to the choice of the most appropriate therapeutic strategy, including chemotherapy and surgery, is difficult. Here, we present an unusual case of LMS of the sigmoid colon with liver metastases and gastric cancer. The survival of this patient was prolonged by a combined modality therapy involving chemotherapy and surgery.. A 66-year-old woman who had been diagnosed with advanced gastric cancer and multiple liver metastases was referred to our hospital. The initial treatment with docetaxel and S-1 considerably reduced both the gastric cancer and liver tumors; consequently we performed surgical resection. Pathological examination revealed that no viable tumor cells remained in the stomach and chemotherapy resulted in complete remission of the gastric cancer. The liver tumors were immunohistochemically diagnosed as LMS. A tumor of the sigmoid colon was subsequently discovered and the liver tumors were found to have recurred. The surgically resected sigmoid colon and liver tumors were all immunohistochemically diagnosed as LMS. These findings indicated that the multiple liver metastases arose from the LMS in the sigmoid colon, and that they were accompanied by advanced gastric cancer. We performed another surgical resection and administered chemotherapy to treat the recurring liver metastases. The patient survived for 4 years and 10 months after initial presentation at our hospital.. Colonic LMS is rare and its joint occurrence with gastric cancer is extremely unusual. Although LMS is a high-grade neoplasm, a multimodal therapeutic approach can increase patient survival time even when multiple liver metastases are present.

Topics: Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Docetaxel; Drug Combinations; Fatal Outcome; Female; Humans; Immunohistochemistry; Leiomyosarcoma; Liver Neoplasms; Neoplasm Recurrence, Local; Oxonic Acid; Sigmoid Neoplasms; Stomach Neoplasms; Taxoids; Tegafur

Gastrointestinal (GI) luminal obstruction or malignant biliary obstruction (MBO) is not a rare condition in gastric cancer patients with peritoneal metastasis. The role of endoscopic or percutaneous interventions is not fully elucidated in this setting.. A total of 123 patients with unresectable or recurrent gastric adenocarcinoma with peritoneal metastasis receiving intravenous and intraperitoneal paclitaxel combined with S-1 were retrospectively studied. Safety and efficacy of interventions for GI luminal obstruction and MBO were evaluated.. A total of 27 patients (22%) underwent GI luminal and/or biliary interventions; GI luminal alone in 10, biliary alone in 10 and both in seven, with a technical success rate of 100%. Clinical success rate was 65% in self-expandable metallic stents (SEMS) placement for GI luminal obstruction. Eastern Cooperative Oncology Group (ECOG) performance status (PS) was prognostic of clinical success in GI luminal stenting (100% in PS of 1 vs 14% in PS of 2-3, P < 0.001). Biliary drainage (endoscopic SEMS placement in four and percutaneous transhepatic biliary drainage in 12) relieved obstructive jaundice in 94%. Six complications were observed: four after GI luminal stenting (two occlusion and one aspiration pneumonia) and two after biliary stenting (one cholangitis and one cholecystitis). Median survival after the initial intervention was 5.7 months. PS at interventions was prognostic of survival after interventions (12.3 months in PS of 1 vs 2.2 months in PS of 2 or 3, P < 0.001).. Endoscopic or percutaneous interventions for GI luminal obstruction or MBO were feasible and effective in gastric cancer patients with peritoneal dissemination receiving combination chemotherapy.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cholestasis; Drainage; Drug Combinations; Endoscopy, Digestive System; Female; Humans; Intestinal Obstruction; Male; Middle Aged; Oxonic Acid; Paclitaxel; Peritoneal Neoplasms; Prognosis; Retrospective Studies; Stents; Stomach Neoplasms; Tegafur

Adjuvant chemotherapy with S-1 was proven to be effective in Japanese patients with advanced gastric cancer curatively resected with D2 lymph node dissection.. We retrospectively evaluated the medical records of 305 patients with stage II, III or IV (M0) gastric cancer who had received adjuvant S-1 chemotherapy following curative gastrectomy with D2 lymph node dissection between October 2007 and December 2009. Adjuvant S-1 was administered at a dose of 40 mg/m(2) twice daily for 4 weeks followed by 2 weeks of rest, every 6 weeks for eight cycles.. Of the 305 patients, 248 (81.3 %) and 198 (64.9 %) completed four and eight cycles of adjuvant chemotherapy, respectively. The most common reasons for discontinuing treatment prior to the planned eight cycles were adverse events (n = 47, 15.4 %) and tumor recurrence (n = 28, 9.2 %). Sixty-five (21.3 %) patients required dose reduction due to adverse events. The most common grade 3/4 toxicities were neutropenia (n = 39, 12.8 %), diarrhea (n = 15, 4.9 %). Multivariate analysis showed that total gastrectomy [odds ratio (OR) 2.44; 95 % confidence interval (CI) 1.29-4.62, p = 0.006] was an independent risk factor for grade 3/4 hematologic toxicities, and age > 65 years (OR 2.60; 95 % CI 1.34-5.07, p = 0.005) was an independent risk factor for grade 3 non-hematologic toxicities.. Adjuvant chemotherapy with S-1 for 1 year is safe and feasible in Korean patients. Age > 65 years and total gastrectomy are independent risk factors for severe adverse events caused by adjuvant S-1 chemotherapy.

Topics: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Drug Combinations; Female; Gastrectomy; Humans; Logistic Models; Male; Middle Aged; Oxonic Acid; Retrospective Studies; Stomach Neoplasms; Tegafur

This study was conducted to determine the prognostic value of the Glasgow Prognostic Score (GPS), an inflammation-based prognostic score composed of C-reactive protein and albumin, for patients with advanced cancer.. A total of 83 advanced gastric cancer patients receiving biweekly docetaxel/S-1 treatment (DS) were included in the study. To identify the value of GPS as prognostic factor for disease-specific survival (DSS) and progression-free survival (PFS), univariate and multivariate analyses were performed.. Unresectable tumors were observed in 78 patients and recurrent tumors were detected in 5 patients. Of these, 12 patients underwent gastrectomy. There were significant correlations between the GPS and the neutrophil/lymphocyte ratio. Univariate analysis revealed that the GPS, Eastern Cooperative Oncology Group performance status and gastrectomy after DS treatment significantly affected prognosis. Multivariate analysis showed that the GPS, age and gastrectomy independently influenced DSS, and that the GPS and gastrectomy also influenced PFS. Multivariate analysis restricted to patients without gastrectomy showed that the GPS and age independently affected DSS, and that the GPS influenced PFS.. In the low GPS group, it may be possible to obtain favorable outcomes by chemotherapy in advanced gastric cancer patients. However, a well-designed prospective trial in a large patient cohort is required to corroborate the prognostic value of the GPS.

Topics: Adult; Aged; Aged, 80 and over; Albumins; Antineoplastic Combined Chemotherapy Protocols; C-Reactive Protein; Clinical Trials, Phase II as Topic; Docetaxel; Drug Combinations; Female; Follow-Up Studies; Humans; Inflammation; Male; Middle Aged; Oxonic Acid; Prognosis; Retrospective Studies; Stomach Neoplasms; Survival Rate; Taxoids; Tegafur

After Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer(ACTS-GC), adjuvant chemotherapy with S-1 is a standard treatment for stage II or III gastric cancer patients. In this study, we retrospectively examined factors that influence the continuity of S-1 adjuvant chemotherapy. We analyzed the clinical documentation of 27 gastric cancer patients being treated with S-1 adjuvant chemotherapy. Patients who completed the treatment without reduction dose were classified into a complete group(n=14), and those for whom S-1 was discontinued or reduced due to adverse reactions were classified into a reduced/discontinuation group(n=13). First, we examined the background factors at baseline between these two groups. Univariate logistic regression analysis revealed that the operative procedure, leukocyte count, and serum creatinine level at baseline were identified as factors that influence the continuity of S-1 chemotherapy. Next, we investigated the hematological and nutritional conditions of these patients during the treatment period. The loss of body mass index(BMI)during the treatment period was remarkable in the reduced/discontinuation group regardless of the operative procedure. This result suggests that an early nutritional intervention might be important for gastric cancer patients undergoing S-1 adjuvant chemotherapy.

Topics: Adult; Aged; Aged, 80 and over; Body Mass Index; Chemotherapy, Adjuvant; Drug Combinations; Female; Humans; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Retrospective Studies; Stomach Neoplasms; Tegafur

This retrospective study examined the extent to which S-1 plus cisplatin is applicable to the elderly as a primary therapy for advanced or recurrent gastric cancer. Subjects under age 70 were categorized as the L group(n=42), and those age 70 and over were categorized as the O group(n=18). The 2 groups were compared in terms of their creatinine clearance(Ccr), performance status(PS), dose intensity(DI), reasons for regimen modification or discontinuation, and adverse reactions. The DI of S-1 was 100(50-100)% in the L group and 83(67-100)% in the H group(p<0. 0001), and the DI of cisplatin was 100(70-100)% in the L group and 87(75-100)% in the H group(p<0. 0001). The incidence of adverse reactions was similar for both groups. However, the S-1 plus cisplatin regimen was discontinued either at the patient's request, or based on the physician's determination that there were adverse reactions such as fatigue or anorexia. There were significantly more of these reactions in the H group(72. 2%)in comparison to the L group(42. 9%)(p=0. 0369). The elderly often had complications, and a decrease in PS as a result of repeatedly undergoing chemotherapy was noted(p=0. 0185). In conclusion, the elderly may have a low tolerance to S-1 plus cisplatin. When administering cancer chemotherapy to the elderly aged 70 and older, the patient's renal function, PS and Ccr, should be studied, and a regimen and dosage should be carefully selected.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Creatine; Drug Combinations; Drug Tolerance; Female; Humans; Kidney Function Tests; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Recurrence; Retrospective Studies; Stomach Neoplasms; Tegafur

A screening CT of a 78-year-old man suffering from a laryngeal foreign body revealed multiple lymph nodes swelling at the left subclavicular, mediastinal, perigastric, and paraaortic space. He was diagnosed as advanced gastric cancer. After five courses of S-1/docetaxel therapy, the primary tumor became flat and lymph nodes became undetectable. After seven courses, he received operation(total gastrectomy and D2 lymph nodes dissection)because of tumor bleeding and severe adverse effects. The pathological chemotherapeutic effect was Grade 1b for the primary tumor and Grade 3 for lymph nodes. He received S-1 maintenance therapy for three years afterward, and is now still in good condition without recurrence 53 months after the first administration. S-1/docetaxel therapy was thought to be a useful optional regimen for highly advanced gastric cancer.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Docetaxel; Drug Combinations; Humans; Lymphatic Metastasis; Male; Oxonic Acid; Remission Induction; Stomach Neoplasms; Taxoids; Tegafur; Time Factors; Tomography, X-Ray Computed

A 49-year-old woman who complained of abdominal bloating and numbness in the bilateral lower limbs was diagnosed as advanced scirrhous gastric cancer with massive ascites. The biopsy specimen showed a poorly-differentiated adenocarcinoma. She was therefore treated with combined chemotherapy of tri-weekly docetaxel(40mg/m2, day 1, 22)and S-1(60mg/m2, day 1-14 with 1-week rest)for unresectable gastric cancer. After 5 courses, computed tomography showed no ascites. Furthermore, after 31 courses, the loss of ascites continued, and the thickening of the stomach walls was reduced. These findings suggested that a complete response in terms of Evaluation Criteria in Solid Tumors(RECIST)was obtained. The side effects throughout chemotherapy were Grade I anemia and Grade I alopecia. Docetaxel and S-1 chemotherapy may well be one of the effective treatments for advanced scirrhous gastric cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; Ascites; Biopsy; Docetaxel; Drug Combinations; Female; Humans; Middle Aged; Oxonic Acid; Peritoneal Neoplasms; Stomach Neoplasms; Taxoids; Tegafur; Tomography, X-Ray Computed

We report a gastric cancer patient with positive peritoneal lavage cytology (CY1) who achieved 20-month progression free survival by S-1 monotherapy. An 82-year-old male patient who underwent distal gastrectomy with residual disease for type 4 scirrhous gastric cancer manifesting pyloric stenosis, direct invasion to the pancreas, and CY1. He received S-1 monotherapy postoperatively. His ECOG performance status (PS) was 0. The initial treatment schedule was 100mg/day, twice daily for 4 weeks with a 2-week rest, repeated every 6 weeks. Grade 2 thrombocytopenia at the end of the 5th course of treatment required discontinuation of one course of treatment, and subsequent treatment was continued with a dose reduction to 80mg/day. Afterwards, although treatment was temporarily postponed for 2 weeks, the dose modification enabled him to receive S-1 for 20 months, leading to a relative dose intensity of 81%. There was no evidence of disease progression. The most severe adverse events were transient grade 3 neutropenia as well as leukocytopenia, anemia, and thrombocytopenia, grade 2 each, without gastrointestinal toxicities. His PS was not deteriorated. Although survivalrates of CY1 gastric cancer patients are still poor, our case suggests that S-1 monotherapy is effective against CY1, even for patients aged over 80, if the relative dose intensity is maintained by comprehensive patient management and appropriate dose modification.

Topics: Aged, 80 and over; Antimetabolites, Antineoplastic; Combined Modality Therapy; Drug Combinations; Gastrectomy; Humans; Male; Neoplasm Staging; Oxonic Acid; Peritoneal Lavage; Peritoneal Neoplasms; Stomach Neoplasms; Tegafur; Time Factors; Tomography, X-Ray Computed

A57 years old man with gastric cancer underwent distal gastrectomy (pT3N1M0, pStage II B). Three months after gastric resection, he was admitted to our hospital because of acute right dorsal pain. Abdominal computed tomography showed multiple liver tumors with subcapsular hemorrhage. He was diagnosed as multiple liver metastases from gastric cancer. We judged liver tumors to be unresectable and decided to start systemic chemotherapy with S-1 and cisplatin (CDDP) because he was hemodynamically stable. After 8 courses of chemotherapy, the liver tumors were markedly reduced and judged as clinical partial response. Left hepatectomy and S5, S6, S7 partial hepatectomy for liver metastasis was performed. Histopathological examination of the resected specimen revealed no cancer cell in the liver, suggesting a pathologically complete response. We consider that systemic chemotherapy is one of the effective treatments for unresectable liver metastasis with subcapsular hemorrhage from gastric metastasis.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Drug Combinations; Fatal Outcome; Gastrectomy; Hemorrhage; Hepatectomy; Humans; Liver Neoplasms; Male; Middle Aged; Oxonic Acid; Salvage Therapy; Stomach Neoplasms; Tegafur; Tomography, X-Ray Computed

S-1 and capecitabine are orally administered fluoropyridines reported to be effective in the treatment of advanced gastric cancer(AGC). In fact, both S-1/CDDP and capecitabine/CDDP are considered to be the standard first-line treatments for AGC.However, no information concerning on the activity of capecitabine in S-1-pretreated patients with AGC has been reported. Here, we present a case of recurrent gastric cancer that showed a partial response resulting in 6 months of progres-sion-free survival, thanks to capecitabine/CDDP after the failure of multiple anticancer drugs such as S-1/CDDP. S -1 and capecitabine may exhibit cross-resistance because they both have the same final active metabolite: 5-fluorouracil(5-FU). Dihydropyrimidine dehydrogenase(DPD)is the rate-limiting enzyme in the degradation of 5-FU, and S-1 contains the inhibitor of DPD. Thus, S-1, but not capecitabine, is active against tumors with high DPD expression. On the other hand, capecitabine is activated to 5-FU by thymidine phosphorylase(TP)within the tumor tissue and is more effective against tumors with high TP expression. The present case suggests that S-1 and capecitabine do not always exhibit cross-resistance, and that capecitabine may be effective in S-1-pretreated patients with AGC.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Cisplatin; Deoxycytidine; Drug Combinations; Fluorouracil; Humans; Male; Oxonic Acid; Recurrence; Salvage Therapy; Stomach Neoplasms; Tegafur

Advanced gastric cancer (AGC) accompanied by disseminated intravascular coagulation(DIC)has a poor prognosis, and has no established therapy. Here, we report a case of a 69-year-old woman referred to our hospital due to severe anemia and thrombocytopenia. Esophagogastroduodenoscopy demonstrated an AGC in the cardiac part of the stomach, which was histologically diagnosed as poorly-differentiated adenocarcinoma. Bone scintigraphy showed multiple metastases to the bone marrow. Her diagnosis was DIC resulting from AGC, with multiple bone metastases. She underwent chemotherapy with the following regimen: 60mg/m2 docetaxel(DOC)infusion on day 1 and daily oral administration of 100 mg/m2 S-1 for two weeks every three weeks. DIC subsided rapidly after initiation of the therapy and resolved in 12 days. She was discharged from the hospital 56 days after admission and survived 303 days. To our knowledge, this is the first case of AGC reported in the Japanese and English literature to obtain long-term survival in this setting. Combined chemotherapy of S-1 plus DOC may play an important role in the treatment of AGC developing DIC.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Disseminated Intravascular Coagulation; Docetaxel; Drug Combinations; Fatal Outcome; Female; Humans; Oxonic Acid; Stomach Neoplasms; Taxoids; Tegafur

The case of a patient with gastric adenosquamous carcinoma with positive cancer cells on intraperitoneal washing cytology (CY1) who achieved a long recurrence-free survival is herein reported. A 74-year-old man was found to have adenosquamous carcinoma of the stomach. Partial gastrectomy was performed, and a pathological examination confirmed a diagnosis of adenosquamous carcinoma with invasion into the serosa and lymph node metastasis. S-1 monotherapy was administered because a cytologic examination revealed that the patient's peritoneal washings were positive for cancer cells. The patient remains alive with no recurrence two years and 10 months after undergoing surgery. Postoperative chemotherapy with S-1 monotherapy is effective for treating adenosquamous carcinoma of the stomach with CY1 and might contribute to long-term survival.

Topics: Aged; Antineoplastic Agents; Ascitic Fluid; Carcinoma, Adenosquamous; Combined Modality Therapy; Drug Combinations; Gastrectomy; Humans; Male; Oxonic Acid; Stomach Neoplasms; Tegafur

Conventional gas chromatography-mass spectrometry (GC-MS) was compared with a new immunoassay method for measuring plasma (5-FU) concentrations in adjuvant chemotherapy with TS-1 for patients with gastric cancer. TS-1 was administered orally to patients after gastrectomy. Blood samples for pharmacokinetic analysis were collected on the seventh day of treatment. The mean area under the time concentration curve (AUC)(0-8), half-life (t(1/2)), and maximum drug concentration (C(max)) obtained by the two methods were as follows: GC-MS, 847.9 μg/ml/hr, 2.76 h, and 186.6 ng/ml; and immunoassay, 1311.2 μg/ml/hr, 3.5 h, and 259.8 ng/ml. Significant correlations were observed for AUC(0-8) (p=0.0001), C(max) (p=0.0007), and changes in the 5-FU concentration in blood over time (p=0.018) for the two methods. Compared with the conventional GC-MS method, the new immunoassay method provides similar results, but is simpler and results can be obtained earlier. This method will be useful for monitoring the 5-FU concentration in serum from patients with gastric cancer receiving TS-1.

Topics: Aged; Antineoplastic Agents; Area Under Curve; Chemotherapy, Adjuvant; Drug Combinations; Female; Fluorouracil; Gas Chromatography-Mass Spectrometry; Humans; Immunoassay; Male; Oxonic Acid; Stomach Neoplasms; Tegafur

Chemotherapy for gastric cancer is improving continuously through conducting randomized clinical trials and developing new anti-cancer drugs. Patient survivals are prolonged and their QOL are maintained for longer periods. S-1 and CDDP chemotherapy is recommended for unresectable advanced disease, and adjuvant chemotherapy with S-1 is also recommended for stage II/III disease. Recently, combination chemotherapy with trastuzumab has been shown to be effective for HER2 positive gastric cancer. Conversely, new chemotherapeutic agents are needed for peritoneal metastasis patients, elderly patients, and patients with a poor organ function. Neo-adjuvant chemotherapy is expected to improve the overall survival for initially unresectable gastric cancer patients. Collaboration between Japan and Korea is expected to accelerate clinical trials to resolve these unmet needs.

Topics: Aged; Antibodies, Monoclonal, Humanized; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cisplatin; Drug Combinations; Humans; Oxonic Acid; Peptide Fragments; Receptor, ErbB-2; Stomach Neoplasms; Tegafur; Trastuzumab

The objective of this study was to investigate the influence of digestive gastrointestinal absorption function on the pharmacokinetics of the orally-administered anticancer drug, Tegafur-gimestat-otastat potassium (TS-1), by measuring the plasma 5-fluorouracil (5-FU) concentration using stable isotope breath tests.. Twenty-nine patients with progressive/recurrent digestive organ cancer were enrolled for this pharmacokinetic study, and blood samples were obtained from each patient. The area under-the-time-concentration curve between 0 and 480 min (AUC0-480 min), time-of-drug concentration peak (T(max)), maximum drug concentration (C(max)) and the half-life period (t(1/2)) of 5-FU were investigated. Simultaneously, a continuous (13)C-acetate breath test was performed for each patient. The parameters measured with the breath test were the area under the (13)CO(2) excretion rate curve between 0-4 h (AUC(0-4h)), peak (13)CO(2) value and elimination rate constant (K(el)) value.. The AUC(0-8h) and C(max) of 5-FU were significantly correlated with K(el) (p=0.012 and p=0.024, respectively), and the 5-FU C(max) value was significantly correlated with the peak value of (13)CO(2) (p=0.037). Multivariate regression analysis also found the C(max) of 5-FU to be associated with K(el) (p=0.0118). The C(max) and AUC(0-8h) of 5-FU were also significantly correlated (p<0.0001).. The results of this study suggest that gastrointestinal absorption is closely-related to plasma 5-FU concentration after oral administration of TS-1.

Topics: Acetates; Administration, Oral; Aged; Antimetabolites, Antineoplastic; Breath Tests; Carbon Isotopes; Drug Combinations; Esophageal Neoplasms; Female; Fluorouracil; Humans; Intestinal Absorption; Male; Oxonic Acid; Stomach Neoplasms; Tegafur

Although neoadjuvant chemotherapy(NAC)has been recognized as an important option for improving the clinical outcome of patients with advanced gastric carcinoma, convincing evidence that it prolongs life and brings about a good prognosis are both lacking. We retrospectively evaluated the efficacy and safety of NAC in ten patients with advanced gastric cancer.. A total of ten patients with advanced gastric cancer, who received NAC with the combination of S-1 and cisplatin in our hospital from April 2008 to March 2010, were retrospectively investigated.. A total of 5 patients responded to neoadjuvant chemotherapy, and 2 patients showed a complete regression of the primary gastric carcinoma. Four of the 5 patients who responded had solid-type poorly-differentiated adenocarcinoma.. NAC with the combination of S-1 and cisplatin was suggested to be effective for advanced gastric carcinoma, especially for solid-type poorly differentiated adenocarcinomas(por1).

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Female; Humans; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Oxonic Acid; Stomach Neoplasms; Tegafur

A 74-year-old man was referred to our hospital because of abdominal distension. Upper gastrointestinal endoscopy revealed advanced gastric cancer and early gastric cancer. HER2-positive and AFP-producing gastric cancer with peritonitis carcinomatosa showing no indication for operation was diagnosed by histopathological and radiological examinations. He was treated with trastuzumab, docetaxel, and S-1 combination chemotherapy. At the end of the second course of therapy, the primary lesion was remarkably decreased in size and was associated with a significant decrease in serum AFP level. No serious adverse events occurred except for grade 3-4 leukopenia and neutropenia. We carried out eight courses of chemotherapy. Trastuzumab, docetaxel, and S-1 combination chemotherapy promise to be one of the effective treatments for HER2-positive and AFP-producing gastric cancer that have no indication for radical cure excision.

Topics: Aged; alpha-Fetoproteins; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Docetaxel; Drug Combinations; Humans; Male; Oxonic Acid; Receptor, ErbB-2; Stomach Neoplasms; Taxoids; Tegafur; Trastuzumab

We report a case of advanced gastric cancer with pyloric stenosis, in which a curative resection was performed following gastrojejunostomy and S-1 based chemotherapy. A 46-year-old female presenting with vomiting was diagnosed with unresectable gastric cancer with pyloric stenosis after a detailed examination. She underwent laparotomy, which revealed a T4 tumor invading the pancreas head and involving the gallbladder. A gastrojejunostomy was performed. After the operation, chemotherapy of S-1(100mg/body, days 1-21)plus cisplatin(85mg/body, day 8)was administered. After 4 courses, the tumor size was markedly reduced upon imaging examinations. Six months after gastrojejunostomy, distal gastrectomy was curatively performed. The pathological findings were type 3, por1, pT4a(SE), pN1, M0, pStage III A. After 5 courses of S-1(100mg/day, days 1-28)as adjuvant chemotherapy, she had a recurrence at a lymph node behind the pancreas head. Despite irinotecan+cisplatin following docetaxel therapy, she had no effective benefits and died from the cancer 17 months after the first operation. The prognosis of unresectable gastric cancer with pyloric stenosis is not promising; however, gastrojejunostomy following S-1-based chemotherapy could lead such patients to curative resection and a longer survival time.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Drug Combinations; Fatal Outcome; Female; Gastrectomy; Gastric Bypass; Humans; Middle Aged; Oxonic Acid; Pyloric Stenosis; Stomach Neoplasms; Tegafur

A 87-year-old woman was diagnosed with pancreatic body cancer(Stage II ). Because of her age and history of open distal partial gastrectomy, it seemed that having her undergo an invasive surgery would be difficult. Therefore, S-1 was administered orally at a dose of 50mg/day for 28 consecutive days followed by a 14-day rest course(low-dose S-1 monotherapy). After 2 courses, the tumor marker(CA19-9)dramatically decreased to within the normal range. After 5 courses, the tumor could not be identified on the abdominal CT image, and it was judged to be a complete response. Low-dose S-1 monotherapy may be useful for improving the prognosis of pancreatic cancer without causing intolerable toxicity, especially for elderly patients.

Topics: Aged, 80 and over; Antimetabolites, Antineoplastic; Biomarkers, Tumor; Drug Combinations; Female; Humans; Oxonic Acid; Pancreatic Neoplasms; Stomach Neoplasms; Tegafur

A 57-year-old woman suffering from lower abdominal malaise was diagnosed with cStage IV advanced gastric cancer because of simultaneous liver metastasis and peritoneal dissemination. Because she was regarded as inoperable, she was administered combined immunochemotherapy comprising S-1/paclitaxel(PTX) and Krestin(PSK). One course of therapy lasted for 3 weeks as follows: 80 mg/m2 of S-1 on days 1-14 orally, 50 mg/m2 of PTX on days 1 and 8 intravenously, and 3g/day of PSK on days 1-21 orally. After 20 courses of this treatment, the metastatic liver tumor and peritoneal dissemination had disappeared on the abdominal computed tomography scan. At that time, curative resection was considered possible and she underwent total gastrectomy (Roux-en Y) with D2 lymphadenectomy. Histopathological examination revealed pStage IB [pT2 (mp), pN0] and the histological effects of the main tumor were diagnosed as grade 2. She is alive and free from recurrent disease for more than 6 years, and remains in a good condition. This combination of immunochemotherapy using S-1/PTX/PSK can be safe and effective, and is an initial treatment option for unresectable advanced gastric cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Female; Humans; Immunotherapy; Liver Neoplasms; Middle Aged; Oxonic Acid; Paclitaxel; Peritoneal Neoplasms; Proteoglycans; Stomach Neoplasms; Tegafur

Body weight loss is a common outcome in patients with gastric cancer who have undergone gastrectomy. However, the rate of body weight loss after surgery is unknown.. In this retrospective study, we selected patients who underwent radical gastrectomy for gastric cancer and were diagnosed with Stage II or III disease. Further, we compared the body weight loss after surgery between patients in the surgery alone group and the S-1 adjuvant chemotherapy group.. We evaluated 163 patients, of which 81 underwent only surgery, and 82 underwent surgery followed up with S-1 adjuvant chemotherapy. The body weight loss rate at 1, 3, and 6 months in the surgery alone group were 93.1%, 92.9%, and 94.9%, while those in the S-1 adjuvant group were 92.9%, 90.4%,and 91.9%, which was a significant difference.. Body weight loss after gastrectomy was higher in the S-1 adjuvant group than in the surgery alone group. Further, nutritional support is required for these patients to maintain body weight after surgery.

Topics: Aged; Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Drug Combinations; Gastrectomy; Humans; Middle Aged; Oxonic Acid; Stomach Neoplasms; Tegafur; Weight Loss

The patient was a 31-year-old man with advanced gastric cancer, clinically diagnosed as ML, Less, Type 3, sig, cT3, cN0, cH0, cP0, cM0, cCY0, cStage IIA. He underwent D2 distal gastrectomy. On microscopic examination, tumor cells were detected in the distal margin of the resected stomach. After surgery, he received 1 course of S-1 followed by chemoradiation therapy(1.8 Gy×25, a total of 45 Gy) with 90 mg/m2 of paclitaxel and 40 mg/m2 of CDDP on days 1, 15, and 29 over 5 weeks. Subsequently, he received 5 cycles of S-1 chemotherapy. To date, no recurrence has been observed 5 years after surgery. This sequential therapy is an option to consider for enabling local and systemic control after gastric cancer surgery.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Cisplatin; Drug Combinations; Humans; Male; Neoplasm Staging; Oxonic Acid; Paclitaxel; Stomach Neoplasms; Tegafur

We report a rare case of a patient with multiple liver metastases of gastric and rectal cancers after laparoscopic sigmoidectomy, who responded completely to S-1 therapy followed by open gastrectomy. A 72-year-old man with a chief complaint of occult blood in the feces was referred to our hospital and was diagnosed with rectal cancer by colonoscopy. In addition, we found concomitant gastric cancer by gastrointestinal fiberscopy. Abdominal plain computed tomography showed no liver metastasis. In August 2010, we performed laparoscopic resection of the rectal cancer. However, at the time of discharge, abdominal enhanced computed tomography showed multiple liver metastases. Then, we administered 4 courses of S-1 therapy. In December 2010, abdominal enhanced computed tomography showed no liver metastasis. In March 2011, because no other lesion without residual gastric cancer was detected, the patient underwent gastrectomy followed by S-1 therapy. As of January 2012, the patient is alive and disease free. S-1 therapy with laparoscopic resection for rectal cancer and gastrectomy may help prolong the survival of patients with multiple liver metastases of gastric and rectal cancers.

Topics: Aged; Antimetabolites, Antineoplastic; Colectomy; Combined Modality Therapy; Drug Combinations; Gastrectomy; Humans; Laparoscopy; Liver Neoplasms; Male; Neoplasms, Multiple Primary; Oxonic Acid; Rectal Neoplasms; Stomach Neoplasms; Tegafur

S-1/cisplatin(CDDP) combination therapy(SP therapy)(S-1: 80 mg/m2/day, day 1-21, CDDP: 60 mg/m2, day 8, q35 days) is a standard regimen for advanced gastric cancer in Japan. Hydration under hospitalization is necessary for CDDP administration to prevent renal toxicity; nevertheless, ambulatory chemotherapy has recently become commonly used. Therefore CDDP administration using a short hydration regimen for gastric cancer outpatients undergoing SP therapy has been performed in our institute. Between August 2009 and November 2011, 23 patients who were treated with SP therapy as a first line therapy and began CDDP treatment in the outpatient setting were examined, and monitored for adverse events, response rate[best objective response rate(ORR)], time to treatment failure(TTF) and overall survival. A short hydration regimen means 2,550 mL of fluid in 4 h and 55 min, and the necessity of an oral intake of more than 1,000 mL liquid per day on day 7 to 9 was explained to the patients. Grade 1/2 serum creatinine elevation occurred in 5 patients (22%), but there were no incidences of grade 3/4 serum creatinine elevation or heart failure. The best ORR was 69%, median time to treatment failure(mTTF) was 11.5 months, the 1-year survival rate was 77.8%, and the 2-year survival rate was 44.7%.. CDDP administration using a short hydration regimen for gastric cancer outpatients undergoing SP therapy was considered to be feasible.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Feasibility Studies; Female; Humans; Male; Middle Aged; Outpatients; Oxonic Acid; Stomach Neoplasms; Tegafur

Clinical efficacy and safety were analyzed in patients with unresectable gastric cancer receiving S-1 plus CDDP(CS) therapy or S-1 plus weekly CDDP (w-CS) therapy as first-line treatment between April 2007 and December 2010. Fifteen patients received CS therapy and 17 received w-CS therapy. CS therapy was used according to the SPIRITS regimen, and w-CS therapy of S-1 80 mg/(m2·day) was administered for 2 weeks followed by a 1-week rest, with CDDP 20 mg/m2 being injected intravenously on days 1 and 8. In the CS therapy group and w-CS therapy group, the overall response rates were 33.3% and 70.1%, the median overall survival periods were 135 and 174 days (p=0.113), and the median follow- up times were 196 and 352 days (p=0.196), respectively. The w-CS therapy group showed less adverse events than did the CS therapy group. This study suggested that the w-CS regimen is a useful treatment modality showing clinical efficacy and safety for unresectable gastric cancer.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Female; Follow-Up Studies; Humans; Male; Middle Aged; Oxonic Acid; Stomach Neoplasms; Tegafur

Adjuvant chemotherapy with S-1 monotherapy might be insufficient for Stage IIIB highly advanced gastric cancer patients. Our retrospective study was to evaluate the feasibility and safety of adjuvant chemotherapy with S-1 plus docetaxel.. S-1 (80 mg/m2) was administered orally for 2 weeks then followed by a 1-week rest period. Docetaxel (40 mg/m2) was simultaneously administered on day 1. The treatment was administered for 1 year and began 6 weeks after D2 curative surgery.. Five patients tolerated adjuvant chemotherapy with S-1 plus docetaxel for 1 year (17 courses of treatment). Grade 3/4 hematological toxicities were observed in 10% patients (n=1). Grade 3/4 non-hematological toxicities were observed in 20% patients (n=2).. We concluded that S-1 plus docetaxel as adjuvant chemotherapy is a promising strategy for patients with highly advanced gastric cancer.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Docetaxel; Drug Combinations; Female; Humans; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Retrospective Studies; Stomach Neoplasms; Taxoids; Tegafur

S-1+cisplatin (CDDP) combination therapy is a standard regimen for advanced gastric cancer and is usually administered within the hospital environment. Recently, ambulatory chemotherapy has been applied to treat various cancers. For the realization of outpatient treatment, it is necessary to strengthen supportive therapy. We developed a comprehensive and supportive care clinical pathway. The use of this pathway in combination with the expertise of pharmacists has resulted in enhanced supportive therapy, reduced side effects, and increased treatment intensity.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Critical Pathways; Drug Combinations; Female; Humans; Male; Middle Aged; Outpatients; Oxonic Acid; Stomach Neoplasms; Tegafur

We report a case of recurrent gastric cancer with paraaortic lymph nodes (No.16LNs) that was effectively controlled with chemoradiation therapy. A 63-year-old man underwent distal gastrectomy, cholecystectomy, and D2 dissection in July 2004 for advanced gastric cancer in the lower third area that was diagnosed as moderately differentiated stage II adenocarcinoma [T1(SM), N2, H0, P0, CY0, M0]. He suffered from No.16LNs metastasis with serum CEA elevation in October 2007, and therefore, 4 courses of S-1, followed by 3 courses of CPT-11 as second-line treatment, 14 courses of docetaxel as third-line treatment, and 15 courses of paclitaxel+cisplatin as fourth-line chemotherapy, were administrated. Enlargement of No.16LNs with serum CEA elevation was observed in October 2010. Other metastases were not observed, and hence, chemoradiotherapy (CRT; S-1: 80 mg/body+total of 65 Gy per 26 Fr) for No.16LNs was performed. A partial response and reduction of serum CEA level were noted, and the patient is alive with no sign of progression 18 months after CRT. Grade 1 adverse events including anemia, fatigue, and anorexia were recognized. It is thought that chemoradiation therapy is an effective treatment for localized LN metastasis originating from gastric cancer resistant to chemotherapy.

Topics: Antimetabolites, Antineoplastic; Aorta; Chemoradiotherapy; Drug Combinations; Humans; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Salvage Therapy; Stomach Neoplasms; Tegafur

A 61-year-old man exhibiting epigastric malaise on hunger was diagnosed with early gastric cancer by upper gastrointestinal endoscopy. Since no obvious metastasis was recognized by abdominal computed tomography(CT), he underwent distal gastrectomy with D1+ lymphadenectomy. Histopathological examination revealed a pStage IA lesion[pT1a (m), pN0]. He received no adjuvant chemotherapy, and he remained alive and in good health without recurrence for more than 5 years. At 5 years and 7 months after gastrectomy, he noticed cervical lymph node swelling and underwent further examination. He was diagnosed with recurrent gastric cancer in cervical lymph nodes, and treatment with S-1 (120 mg/ day) was initiated. He remained alive and free of progression for approximately 1 year on S-1 therapy, but he suddenly died from disseminated intravascular coagulation without an obvious cause. We report a rare case of late recurrence after curative resection in a patient treated for early gastric cancer.

Topics: Biopsy; Combined Modality Therapy; Disseminated Intravascular Coagulation; Drug Combinations; Fatal Outcome; Gastrectomy; Humans; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Oxonic Acid; Recurrence; Stomach Neoplasms; Tegafur; Time Factors

A 72-year-old man was admitted to our hospital complaining of upper abdominal pain and back pain. Advanced gastric cancer was found at the fundus of the stomach, and severe dysplasia was found at the lower esophagus. We proceeded with neoadjuvant chemotherapy (S-1+CDDP) because the lymph nodes in the lesser curvature of the stomach were metastasized and invasion of the pancreas and some vessels was suspected by computed tomography. The tumor size was reduced remarkably, the esophageal dysplasia disappeared after preoperative chemotherapy, and we were able to perform total gastrectomy.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Esophageal Neoplasms; Gastrectomy; Humans; Male; Neoadjuvant Therapy; Neoplasm Invasiveness; Neoplasms, Multiple Primary; Oxonic Acid; Stomach Neoplasms; Tegafur

A man is his 50s experienced epigastric discomfort and body weight loss from 60 to 56 kg over 3 months. A lesion was diagnosed as type 3 advanced gastric cancer (group 5, tub2) with para-aortic lymph node and multiple liver metastases. Pretreatment hemoglobin(Hb), albumin(Alb), and C-reactive protein(CRP) levels were 11.0 mg/dL, 3.0 g/dL, and 2.40 mg/dL, respectively. S-1+cisplatin (CDDP) combined chemotherapy (S-1 120 mg/day, day 1-21, CDDP 60 mg/ m2, day 8, q35 days) with nutritional supportive care using enteral nutrition (EN) agent (Prosure) enriched with eicosapentaenoic acid (EPA) was initiated. After 6 weeks, body weight, Hb, Alb, and CRP improved to 60 kg, 13.6 mg/dL, 4.6 g /dL, and 0.14 mg/dL, respectively. Moreover, a marked reduction in para-aortic lymph node and multiple liver metastases was seen on computed tomography (CT) scans 12 weeks after treatment initiation. Accordingly, nutritional supportive care using EN agent enriched with EPA during chemotherapy might be an effective treatment for patients with gastric cancer who show increased CRP and decreased albumin levels.

Topics: Antineoplastic Combined Chemotherapy Protocols; C-Reactive Protein; Cisplatin; Drug Combinations; Eicosapentaenoic Acid; Enteral Nutrition; Humans; Liver Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Oxonic Acid; Serum Albumin; Stomach Neoplasms; Tegafur

A 52-year-old man who was diagnosed with esophagogastric junction cancer underwent left thoracolaparotomy and total gastrectomy. At 3 years and 11 months after the surgery, his carcinoembryonic antigen value was elevated, and cervical and right paraesophageal lymph node enlargement was detected by chest computed tomography(CT). Although lymph node dissection was performed, the presence of microscopic cancer-positive surgical stumps was confirmed. Since then, combination chemoradiotherapy using S-1 and radiation(60 Gy) has been applied. Currently, the patient is alive with no signs of lesion recurrence according to CT findings 8 years and 11 months after the initial surgery.

Topics: Adenocarcinoma; Antimetabolites, Antineoplastic; Chemoradiotherapy; Drug Combinations; Esophagogastric Junction; Humans; Lymph Node Excision; Lymphatic Metastasis; Male; Middle Aged; Oxonic Acid; Recurrence; Stomach Neoplasms; Tegafur

Gastrointestinal tract endoscopy revealed the presence of a 5-cm-diameter type 3 tumor in the cardiac portion of the stomach. The tumor was chromogranin positive, and stomach small cell cancer was diagnosed by immunostaining and biopsy pathology. S-1+CDDP therapy was administered as the first-line treatment. A switch to S-1 monotherapy was made after the patient experienced grade 4 hyponatremia. However, following 7 courses of therapy the disease had progressed. Second-line chemotherapy of CPT-11+CDDP was initiated and after 2 courses the disease stabilized.

Topics: Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Carcinoma, Small Cell; Cisplatin; Drug Combinations; Female; Humans; Irinotecan; Neoplasm Staging; Oxonic Acid; Stomach Neoplasms; Tegafur

The study is to investigate the pharmacokinetics of S-1 capsule (tegafur, gimeracil and potassium oxonate capsule) in patients with advanced gastric cancer after single and multiple oral administration. Twelve patients with advanced gastric cancer were recruited to the study. The dose of S-1 for each patient was determined according to his/her body surface area (BSA). The dose for single administration was 60 mg every subject. The dose for multiple administration for one subject was as follows: 100 mg x d(-1) or 120 mg x d(-1), 28-days consecutive oral administration. The pharmacokinetic parameters of tegafur, 5-fluorouracil, gimeracil, potassium oxonate and uracil after single oral administration were as follows: (2,207 +/- 545), (220.0 +/- 68.2), (374.9 +/- 103.0), (110.5 +/- 100.8) and (831.1 +/- 199.9) ng x mL(-1) for Cmax; (11.8 +/- 3.8), (4.4 +/- 3.3), (7.8 +/- 5.1), (3.1 +/- 0.9) and (8.8 +/- 4.1) h for t1/2, respectively. After six days oral administration, the average steady state plasma concentrations (Cav) of tegafur, 5-fluorouracil, gimeracil, potassium oxonate and uracil were (2,425 +/- 1,172), (73.88 +/- 18.88), (162.6 +/- 70.8), (36.89 +/- 29.35) and (435.3 +/- 141.0) ng x mL(-1), respectively, and the degree of fluctuation (DF) were (1.0 +/- 0.2), (2.5 +/- 0.4), (3.1 +/- 0.8), (2.4 +/- 0.8) and (1.5 +/- 0.3), respectively. The cumulative urine excretion percentage of tegafur, 5-fluorouracil, gimeracil and potassium oxonate in urine within 48 h were (4.2 +/- 2.8) %, (4.7 +/- 1.6) %, (18.5 +/- 6.0) % and (1.7 +/- 1.2) %, repectively, after single oral administration of S-1. The results exhibited that tegafur had some drug accumulation observed, and gimeracil, potassium oxonate, 5-fluorouracil and uracil had no drug accumulation observed.

Topics: Administration, Oral; Adult; Aged; Antimetabolites, Antineoplastic; Capsules; Drug Combinations; Female; Fluorouracil; Humans; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Pyridines; Stomach Neoplasms; Tegafur; Uracil

The combination of oxaliplatin and S-1 is effective in patients with advanced gastric cancer. The purpose of this study was to analyze the safety and compliance of this combination regimen as adjuvant chemotherapy in patients with gastric cancer.. Clinical data of 71 patients with gastric cancer treated with oxaliplatin plus S-1 as adjuvant chemotherapy in the Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) from Jan 1(st), 2010 to Jan 1(st), 2012 were retrospectively reviewed. The types and incidence rate of adverse events related to chemotherapy and the results of follow up of the patients were analyzed.. Among the 71 cases, 17 were treated with oxaliplatin biweekly, while 54 with oxaliplatin triweekly. The most common adverse events were neutropenia (n = 49, 69.0%), nausea/vomiting (n = 51, 71.8%), and anorexia (n = 49, 69.0%). The most frequent grade 3-4 toxicities were neutropenia (n = 13, 18.3%), thrombocytopenia (n = 10, 14.1%), anorexia (n = 5, 7.0%) and nausea/vomiting (n = 4, 5.6%). Seven (87.5%) of the 8 patients previously treated with neoadjuvant chemotherapy experienced thrombocytopenia in the postoperative adjuvant chemotherapy, and four (50%) of the 8 patients experienced grade 3-4 thrombocytopenia. The rates of grade 3-4 adverse events in patients aged 65-years or older were similar to that in younger patients.. The combination of oxaliplatin and S-1 used as adjuvant chemotherapy is well tolerated by patients with gastric cancer. Neutropenia, thrombocytopenia, nausea/vomiting and anorexia are the major treatment-related adverse events. Patients who received neoadjuvant chemotherapy do not well tolerate this regimen as postoperative adjuvant chemotherapy. This combination regimen has a manageable tolerability profile in adjuvant setting in patients ≥ 65 years old.

Topics: Adenocarcinoma; Adult; Aged; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Drug Combinations; Female; Follow-Up Studies; Humans; Male; Middle Aged; Nausea; Neoadjuvant Therapy; Neoplasm Staging; Neutropenia; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Retrospective Studies; Stomach Neoplasms; Survival Rate; Tegafur; Thrombocytopenia

This study was performed to analyze the impact of protein expression related to fluoropyrimidine and cisplatin metabolism (thymidylate synthase, dihydropyrimidine dehydrogenase, thymidine phosphorylase, orotate phosphoribosyltransferase [OPRT], excision repair cross-complementation 1, Fanconi anemia complementation group D2, glutathione S-transferase P1, and X-ray repair cross-complementing group 1) on treatment outcomes in patients with metastatic or relapsed gastric cancer (MRGC) receiving S-1/cisplatin chemotherapy. Protein expression was measured by immunohistochemistry (IHC). Of the 43 patients who had received S-1 (80 mg/m2/day; days 1-14) and cisplatin (60 mg/m2; day 1) every 3 weeks and had available tissue blocks, IHC was successfully performed in 41 patients. Patients with high OPRT levels in tumor tissues (IHC score≥6) had superior progression-free survival (PFS) (23.3 vs. 14.1 weeks [median]) and overall survival (OS) (72.4 vs. 55.4 weeks [median]) to those with low OPRT levels (IHC score≤5; P-values<.05). Expression levels of other proteins were not predictive of treatment outcomes. In multivariate analysis, both a good performance status and a high OPRT level were independently associated with prolonged PFS and OS. The OPRT expression level may be a good predictive marker in S-1/cisplatin-treated patients with MRGC.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Cisplatin; Disease-Free Survival; Drug Combinations; Female; Humans; Immunohistochemistry; Kaplan-Meier Estimate; Male; Middle Aged; Orotate Phosphoribosyltransferase; Oxonic Acid; Stomach Neoplasms; Tegafur; Treatment Outcome

Total gastrectomy and chemotherapy with S-1 after surgery were performed in a 50-year-old woman with gastric cancer associated with acquired immunodeficiency syndrome (AIDS). She was given a diagnosis of gastric cancer at the lesser curvature of the body of the stomach, and distal gastrectomy was performed in December 2004. The postoperative course was eventful, with persistent high fever of unknown origin after surgery and infiltrative shadows in the bilateral lung fields showing on CT scan. Polymerase chain reaction (PCR) for pneumocystis carinii on bronchoscopy was positive, serum HIV antibody was positive, HIV-RNA was 2.2 × 10(5) copies/ml, and the serum CD4 lymphocyte level was 25/mm(3) on postoperative day 28. She was given a diagnosis of pneumocystis carinii with AIDS. Pneumocystis carinii and fever improved immediately when ST mixture and highly active antiretroviral therapy (HAART) were performed. After 3 months, the serum CD4 lymphocyte level was elevated to 125/mm(3), and she underwent total gastrectomy because cancer cells at the cut end of the resected stomach were positive microscopically. The postoperative course was uneventful, and she underwent adjuvant chemotherapy with S-1 because the serum CD4 lymphocyte level was 568/mm(3). S-1 therapy was continued for 2 years (each course consisting of 2 weeks of administration followed by 2 weeks off) while performing HAART and monitoring CD4 lymphocyte levels. No side effects such as decreases in white blood cell counts or CD4 lymphocyte levels were seen during S-1 therapy. She is alive and well without recurrence of gastric cancer 5 years after initial gastrectomy.

Topics: Acquired Immunodeficiency Syndrome; Antimetabolites, Antineoplastic; Antiretroviral Therapy, Highly Active; CD4 Lymphocyte Count; Combined Modality Therapy; Drug Combinations; Female; Gastrectomy; Humans; Middle Aged; Oxonic Acid; Pneumocystis carinii; Pneumocystis Infections; Stomach Neoplasms; Tegafur; Treatment Outcome

Topics: Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Combined Modality Therapy; Drug Combinations; Humans; Oxonic Acid; Peritoneal Lavage; Stomach Neoplasms; Tegafur

We report a case of sclerosing cholangitis caused by oral chemotherapy with S-1. A 79-year-old woman with a history of hypertension presented with epigastric discomfort. Upper gastrointestinal endoscopy revealed advanced gastric cancer in the gastric antrum and abdominal computed tomography showed multiple lymph node metastasis. The patient underwent chemotherapy with S-1. Since 2 months later, blood chemistry analysis showed liver dysfunction and hyperbilirubinemia, and chemotherapy was discontinued. Endoscopic retrograde cholangiopancreatography revealed stenosis of the bile duct at the hepatic hilum. There was no evidence of tumor in the liver. We diagnosed chemotherapy-induced sclerosing cholangitis (CISC) caused by S-1. Although treatment with ursodeoxycholic acid and corticosteroids was temporarily effective, she eventually died of CISC and gastric cancer. To the best of our knowledge, this is the first case report of CISC caused by S-1. We present this rare condition with a review of the literature.

Topics: Administration, Oral; Aged; Antimetabolites, Antineoplastic; Cholangitis, Sclerosing; Drug Combinations; Female; Humans; Oxonic Acid; Stomach Neoplasms; Tegafur

The aim of this study was to determine the optimal management of adjuvant S-1 therapy for stage II or III gastric cancer, encompassing the details of dose reduction and treatment schedule modification.. We retrospectively examined 97 patients with stage II or III gastric cancer who received S-1 chemotherapy following gastrectomy between January 2003 and December 2007. S-1 (80 mg/m² per day) was orally administered twice daily for 4 weeks, followed by a 2-week rest. As a rule, treatment was continued for 1 year after gastrectomy. Dose reduction or treatment schedule modification was performed according to toxicity profiles.. Among the 97 patients, 57 (59%) underwent dose reduction at least once and 39 (40%) received treatment schedule modification. Of the 57 patients who required dose reduction, 45 (79%) underwent reduction within 3 months of the beginning of treatment. The most common reasons for dose reduction were anorexia (47%), followed by diarrhea (32%), leukopenia (24%), and rash (16%), with the reasons overlapping. Although the difference in the requirement for dose reduction was not significant, patients with a low creatinine clearance level or those who underwent total gastrectomy had a greater tendency to require dose reduction. The duration of the S-1 treatment period was at least 3 months in 88% of the patients, at least 6 months in 82%, and the planned 1-year period in 73% of the patients.. In most patients, the planned 1-year adjuvant S-1 therapy for stage II or III gastric cancer could be completed by modifying the dose reduction and treatment schedule.

Topics: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Female; Follow-Up Studies; Gastrectomy; Humans; Male; Middle Aged; Oxonic Acid; Retrospective Studies; Stomach Neoplasms; Tegafur

Some patients experience a recurrence of cancer even after curative D2 gastrectomy followed by adjuvant S-1 chemotherapy. The objective of this retrospective study was to clarify the survival and prognosticators in these patients.. The study selected patients who underwent curative D2 surgery, were diagnosed with stage II, IIIA, or IIIB cancer, received adjuvant S-1 for more than 4 weeks, and experienced recurrence confirmed by an imaging study.. A total of 34 patients were evaluated. The median overall survival (OS) was significantly longer in the 26 patients who received palliative chemotherapy than that in the 8 who did not (8.5 vs. 2.5 months, P = 0.002). Only 1 patient received S-1, 21 received taxane-containing regimens, and 4 received irinotecan plus cisplatin as the first-line chemotherapy. Univariate and multivariate analyses showed that the histological type was only independent significant prognosticator.. These results suggested that the survival did not reach the level expected for first-line chemotherapy. The histological type was a significant prognosticator in patients who experienced recurrence after adjuvant S-1 therapy and thereafter received palliative chemotherapy.

Topics: Adenocarcinoma; Aged; Antineoplastic Agents; Camptothecin; Chemotherapy, Adjuvant; Cisplatin; Drug Combinations; Gastrectomy; Humans; Irinotecan; Kaplan-Meier Estimate; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Oxonic Acid; Palliative Care; Proportional Hazards Models; Stomach Neoplasms; Taxoids; Tegafur

Choriocarcinoma- and yolk sac tumor-like differentiation have rarely been reported in gastric cancers. We report a case of gastric adenocarcinoma, concurrently possessing choriocarcinoma and yolk sac tumor components, of a 74-year-old man. A hemorrhagic, 11 × 8 × 3 cm, tumor with ulceration was located in the body and pre-pylorus of the stomach. Histological examination of the resected specimens demonstrated intermingled proliferation of three different components, namely, adenocarcinoma, choriocarcinoma and yolk sac tumor, which were immunoreactive for carcinoembryonic antigen (CEA), beta-subunit of human chorionic gonadotropin (HCG) and alpha-fetoprotein (AFP), respectively. Gastric cancers with germ cell tumor components are uncommon and this is the second reported case of gastric cancer with choriocarcinoma and yolk sac tumor components.

Topics: Adenocarcinoma; Aged; alpha-Fetoproteins; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Carcinoembryonic Antigen; Choriocarcinoma; Chorionic Gonadotropin, beta Subunit, Human; Cisplatin; Disease-Free Survival; Drug Combinations; Endodermal Sinus Tumor; Humans; Male; Neoplasms, Multiple Primary; Oxonic Acid; Radiotherapy, Adjuvant; Stomach Neoplasms; Tegafur

We evaluated the association between polymorphisms of cytochrome P450 2A6 (CYP2A6)/excision repair cross-complementation group 1 (ERCC1)/X-ray repair cross-complementing group 1(XRCC1) and treatment outcomes of metastatic gastric cancer (MGC) patients treated with S-1/cisplatin.. Among MGC patients (n=108), who received S-1 (40 mg m(-2) b.i.d., days 1-14) and cisplatin (60 mg m(-2), day 1) every 3 weeks, we analysed the wild-type allele (W) and variants (V) of CYP2A6 (*4, *7, *9, *10), and the polymorphisms of ERCC1 (rs11615, rs3212986) and XRCC1 (rs25487).. Patients having fewer CYP2A6 variants had better response rates (W/W vs W/V other than *1/*4 vs V/V or *1/*4=66.7 vs 58.3 vs 32.3%; P=0.008), time to progression (TTP) (7.2 vs 6.1 vs 3.5 months, P=0.021), and overall survival (23.2 vs 15.4 vs 12.0 months, P=0.004). ERCC1 19442C>A (rs3212986) was also associated with response rate (C/C, 46.7% vs C/A, 55.3% vs A/A, 87.5%) (P=0.048) and TTP (4.4 vs 7.6 vs 7.9 months) (P=0.012). Patients carrying both risk genotypes of CYP2A6 (V/V or 1/*4) and ERCC1 19442C>A (C/C) vs those carrying none showed an adjusted odds ratio of 0.113 (P=0.004) for response, and adjusted hazard ratios of 3.748 (P=0.0001) for TTP and 2.961 (P=0.006) for death.. Polymorphisms of CYP2A6 and ERCC1 19442C>A correlated with the efficacy of S-1/cisplatin.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Aryl Hydrocarbon Hydroxylases; Cisplatin; Cytochrome P-450 CYP2A6; DNA-Binding Proteins; Drug Combinations; Endonucleases; Female; Genotype; Humans; Male; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Polymorphism, Genetic; Stomach Neoplasms; Tegafur; X-ray Repair Cross Complementing Protein 1

A 63-year-old woman with advanced gastric cancer was referred to our hospital.Upper gastrointestinal endoscopy revealed a type 2 tumor in the lesser curvature of the angle of stomach. Moderately-differentiated adenocarcinoma was found in the biopsy specimens. Lymph node metastases of No.3 and No.7 were suspected by abdominal CT. We diagnosed the tumor as cStage III A (cT2N2H0P0M0) gastric cancer.For better curability, we selected neoadjuvant chemotherapy with TS-1/ CDDP. Two courses were completed without serious side effects. Upper gastrointestinal endoscopy and abdominal CT revealed that the primary tumor and metastatic lymph nodes had become smaller, suggesting that a partial response had been achieved. The patient underwent curative surgery, including distal gastrectomy and D2 lymph node dissection.No cancer cells were found by pathological evaluation of the resected stomach and all the regional lymph nodes, confirming a pathological complete response. It is suggested that the neoadjuvant chemotherapy is a useful therapeutic strategy for advanced gastric cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; Biopsy; Cisplatin; Combined Modality Therapy; Drug Combinations; Female; Humans; Middle Aged; Neoplasm Staging; Oxonic Acid; Stomach Neoplasms; Tegafur; Tomography, X-Ray Computed

A 75-year-old man was found to have a type 2 gastric cancer on the pyloric side. In February 2006, he underwent gastrectomy, followed by oral medication with 300 mg/day of UFT on an ambulatory basis. In June 2006, the lymph nodes in the hepatoduodenal ligament became swollen. The patient was started on S-1 monotherapy(S-1 was given orally 80 mg/body/ day for the first 4 weeks of a 6 week cycle). S-1 was given for 6 courses over 9 months. In March 2007, further swelling of the lymph nodes in the hepatoduodenal ligament(PD)and a CEA level increase were noted, and therapy of S-1 combined with CDDP(divided into small dosages)was started in April 2007. Since then until July 2009, 16 courses of S-1 combined with CDDP therapy were completed. During this period(for 2 years and 3 months), the lymph nodes in the hepatoduodenal ligament remained generally unchanged(SD)in imaging observations. However, no new lesions were discovered, The CEA level was reduced and the patient remained free of clinical symptoms. While there are no adverse effects and he could receive continued care on an ambulatory basis. In September 2009, obstructive jaundice was found, and it was treated by biliary stenting. He suffered repeated bouts of cholangitis, which contributed to the exacerbation of his systemic condition. The patient succumbed in January 2010. S-1 monotherapy was found to be ineffective but a combination therapy of S-1 plus CDDP(divided into small dosages)was effective in dealing with a recurrence of the gastric cancer. A case was presented in which such treatment allowed a patient with recurrent gastric cancer to survive for 3 years and 11 months following surgery.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoembryonic Antigen; Cisplatin; Drug Combinations; Fatal Outcome; Humans; Male; Oxonic Acid; Recurrence; Stomach Neoplasms; Tegafur

Eight patients with inoperable advanced gastric cancer were treated with combination chemotherapy of S-1, low-dose cisplatin(CDDP)and Lentinan. S-1 80 mg/ m² was orally administered for 2 weeks followed by 1-week rest, CDDP 15 mg/ m² and Lentinan 2 mg/body were given intravenously on day 1 and 8. One complete response and four partial responses were observed for an overall response rate of 63%(5 of 8 patients). Only one patient developed over grade 3 toxicity leukocytopenia. Many patients could be maintained by long-term continuous treatment. Since combination chemotherapy of S-1/low-dose CDDP/Lentinan for advanced gastric cancer was very tolerable, it could be used for a long time.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Female; Humans; Lentinan; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Stomach Neoplasms; Tegafur; Tomography, X-Ray Computed

A 62-year-old woman visited our hospital with diarrhea, bloating, vomiting, and black stool. Borrmann-type 3 gastric cancer with hemorrhaging was revealed by stomach endoscopy. The biopsy showed a poorly-differentiated adenocarcinoma. Moreover, peritoneal dissemination was found by computed tomography and we combined S-1 80 mg/m²(4 weeks administration and week rest)with paclitaxel(PTX)50 mg/ m² (day 1, 8, 15, 3 weeks rest). After 2 courses, endoscopy showed tumor shrinkage. Therefore, we conducted total gastrectomy with resection of gall bladder and spleen. The final findings were Stage II .We conducted S-1/PTX combination chemotherapy(4 courses)followed by monotherapy as adjuvant chemotherapy. Recently, the woman had been living without relapse four years after operation.

Topics: Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Female; Gastroscopy; Humans; Middle Aged; Oxonic Acid; Paclitaxel; Peritoneal Neoplasms; Remission Induction; Stomach Neoplasms; Tegafur; Time Factors; Tomography, X-Ray Computed

A 64-year-old female who has undergone D2 total gastrectomy was started on adjuvant treatment with TS-1. Four weeks after initiation of TS-1, the patient developed a rare complication of life-threatening toxic epidermal necrolysis. TS-1 was discontinued and the patient received treatment with intravenous immunoglobulin and supportive care with resolution of toxic epidermal necrolysis. TS-1 has been used for the treatment of gastric cancer, both in the adjuvant and metastatic setting, and is increasingly being used in other malignancies such as colon, pancreatic and non-small cell lung cancer. TS-1 is generally well tolerated. To our knowledge, this is the first reported case of toxic epidermal necrolysis associated with the usage of TS-1.

Topics: Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Diagnosis, Differential; Drug Combinations; Female; Gastrectomy; Humans; Immunoglobulins, Intravenous; Middle Aged; Oxonic Acid; Palliative Care; Stevens-Johnson Syndrome; Stomach Neoplasms; Stomatitis; Tegafur

In patients with stage II/III gastric cancer, tumors often recur even after curative D2 gastrectomy followed by adjuvant S-1 chemotherapy. The objective of this retrospective study was to clarify the prognostic factors in these patients that might be useful for future patients.. Overall survival (OS) was examined in 82 gastric cancer patients who underwent curative D2 surgery; were diagnosed with stage IIA, IIB, IIIA, IIIB, or IIIC pathologically; and received adjuvant S-1 after surgery between June 2002 and March 2010.. When length of OS was evaluated by the log-rank test, significant differences were observed with regard to macroscopic tumor diameter and the depth of tumor invasion. A macroscopic tumor diameter >70 mm was regarded as a critical point of classification considering survival. Univariate and multivariate Cox's proportional hazard analyses demonstrated that macroscopic tumor diameter was the only significant independent prognosticator. The 5-year survival was 64.9% in patients with a macroscopic tumor diameter <70 mm, and 33.1% in patients with a macroscopic tumor diameter ≥70 mm (P = 0.022).. The macroscopic tumor diameter was the most important prognostic factor for survival in patients with stage II/III gastric cancer who underwent D2 gastrectomy followed by adjuvant S-1 chemotherapy. Prognostic factors can be affected by adjuvant chemotherapy.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Combined Modality Therapy; Drug Combinations; Female; Follow-Up Studies; Gastrectomy; Humans; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Neoplasm Staging; Oxonic Acid; Prognosis; Prospective Studies; Stomach Neoplasms; Survival Rate; Tegafur

A 38-year-old man with complaints of nausea, epigastralgia, cough, and decrease body weight was given a diagnosis of advanced gastric cancer (type 4) with carcinomatous lymphangitis of the lung (UM-circ cT3, N3, H0, P0, M1, stage IV, por2). He was treated with combination of docetaxel (DOC) 40 mg/m(2)/day (days 1, 15) and S-1 orally 80 mg/m(2)/day (days 1-7, 15-21), 1 week administered 1 week rest. After 2 courses of treatment, the patient achieved a partial response in the carcinomatous lymphangitis of the lung. Tumor markers decreased and symptoms improved. He experienced grade 2 peripheral neuropathy but with no grade 3 adverse events. Although the prognosis of gastric cancer with carcinomatous lymphangitis is poor. These results indicate that bi-weekly DOC and S-1 combination chemotherapy might be effective for gastric cancer with carcinomatous lymphangitis of the lung.

Topics: Adenocarcinoma; Adult; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Docetaxel; Drug Combinations; Humans; Lung Neoplasms; Lymphangitis; Male; Oxonic Acid; Stomach Neoplasms; Taxoids; Tegafur

The purpose of this study was to clarify the efficacy and safety of docetaxel and cisplatin as second-line treatment for patients with S-1 refractory advanced gastric cancer. Between 1999 and 2006, 32 patients received docetaxel (60 mg/m²) and cisplatin (60 mg/m²) (Dp regimen) on day 1 every 3 weeks. This regimen was repeated at least three times at 3-week intervals until disease progression or unacceptable toxicity was detected. The overall response rate was 21.9%. Seven patients showed partial response, 17 showed stable disease and 8 showed disease progression. The median survival time was 12.3 months after the start of the first-line treatment. The median survival time and time to progression following the DP regimen was 7.8 months and 4.0 months, respectively. The major adverse effects were leukopenia and neutropnea. Non-hematological toxicities were generally mild to moderate and controllable. this study showed satisfactory therapeutic outcomes for patients with gastric cancer refractory to S- 1 chemotherapy.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Disease Progression; Docetaxel; Drug Combinations; Drug Resistance, Neoplasm; Female; Humans; Leukopenia; Male; Middle Aged; Oxonic Acid; Prognosis; Retrospective Studies; Stomach Neoplasms; Survival Rate; Taxoids; Tegafur; Watchful Waiting

We report a case of early-stage mucosal esophageal cancer, showing a complete response to S-1 and cis-diamminedichloplatinum (CDDP). The patient was a 67-year-old man with synchronous double primary early-stage mucosal esophageal and advanced gastric cancer. We planned neoadjuvant chemotherapy with S-1 and CDDP for the advanced gastric cancer and endoscopic mucosal resection for the early-stage esophageal cancer. After the first course of chemotherapy, the endoscopy revealed that the esophageal cancer had become a normal mucosal lesion, and the biopsy was negative for cancer. We diagnosed a complete response to S-1 and CDDP in early-stage esophageal cancer. After two courses of chemotherapy, distal gastrectomy was performed. The patient is still alive with no sign of recurrence at 16 months after the disappearance of the original tumor. These results suggest that chemotherapy with S-1 plus CDDP may be effective in early-stage esophageal cancer.

Topics: Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Endoscopy, Gastrointestinal; Esophageal Neoplasms; Humans; Male; Mucous Membrane; Neoplasm Staging; Oxonic Acid; Stomach Neoplasms; Tegafur; Tomography, X-Ray Computed; Treatment Outcome

In our hospital, the starting dose of S-1 for patients over 75 years of age with advanced gastric cancer was determined by body surface of area, creatinine clearance, performance status(PS)and the presence of complications. The objective of this retrospective study was to investigate the proper administration of S-1 in elderly patients by comparing patients given a standard dose of S-1 to those given a reduced dose.. Twenty patients participated. Six patients were administered S-1 at a standard dose(standard group)and fourteen patients with at a reduced dose(reduced group). Safety, feasibility and anti-tumor effects were assessed.. Three cases of grade 3 adverse events were found in the standard group, and one case was found in the reduced group. Time to treatment failure was 4. 4 months for the standard group and 8. 2 months for the reduced group. The overall response rate was 25% in the standard group and 30% in the reduced group.. It is important to reduce S-1 administration to patients over 75 years of age with caution, and take into account the patient's renal function, PS and Ccr complications.

Topics: Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Drug Combinations; Female; Humans; Male; Oxonic Acid; Stomach Neoplasms; Tegafur

The aim of this study was to investigate the efficacy and safety of an alternating regimen of S-1 plus low-dose cisplatin and S-1 alone as adjuvant therapy in patients with advanced gastric cancer.. The study group comprised 100 patients with stage IIIA, stage IIIB, or stage IV. Patients postoperatively received three 5-week cycles of chemotherapy. In the first cycle, S-1 (80 mg/m(2)) was given daily for 3 weeks, followed by 2 weeks of rest, and low-dose cisplatin (10 mg) was given on days 1 to 5 and 8 to 12. In the second and third 5-week cycles, S-1 alone was given. The primary endpoints were median survival time, and survival at 1 and 3 years. Secondary endpoints were safety and overall response rates.. Median survival time was 18 months in stage IV and 32 months in stage IIIB. The rates of survival at 1 and 3 years were 68.7% and 30.6% in stage IV, 100% and 68.4% in stage IIIA, and 100% and 46.6% in stage IIIB, respectively. Adverse events of grade 3 or 4 occurred in 14% of the patients. The overall response rate of target lesions was 54%.. Our regimen is effective and safe for adjuvant therapy in patients with curatively resected stage III gastric cancer.

Topics: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Cisplatin; Dose-Response Relationship, Drug; Drug Combinations; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Incidence; Japan; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Retrospective Studies; Stomach Neoplasms; Survival Rate; Tegafur; Time Factors; Young Adult

A 64-year-old woman presented with advanced gastric cancer (signet ring cell carcinoma) and underwent total gastrectomy in 1996. Postoperative recovery was good, and she was monitored regularly on an outpatient basis. Abdominal computed tomography in 1999 revealed a soft tissue shadow ventral to the origin of the celiac artery. Careful monitoring was continued on an outpatient basis. The patient began to experience gluteal swelling and pain in April 2008. Symptoms rapidly exacerbated and the patient was hospitalized for further examination. Gluteal muscle biopsy revealed signet ring cell carcinoma and bilateral hydronephrosis. Gluteal recurrence of the original gastric cancer was suggested, and systemic chemotherapy consisting of S-1 at 100 mg/day (3 weeks on, 1 week off) and CDDP (day 8) was started. Following the 6th cycle of chemotherapy, gluteal symptoms disappeared and the patient was judged to have achieved clinical complete response (CR). No adverse events or image findings suggesting new recurrence have since been identified. The patient received a total CDDP dose of 585 mg and clinical CR has been maintained as of 14 years after total gastrectomy and 18 months after recurrence.

Topics: Antineoplastic Combined Chemotherapy Protocols; Buttocks; Carcinoma, Signet Ring Cell; Cisplatin; Drug Combinations; Female; Humans; Middle Aged; Muscle Neoplasms; Neoplasm Recurrence, Local; Oxonic Acid; Peritoneal Neoplasms; Remission Induction; Retroperitoneal Neoplasms; Stomach Neoplasms; Tegafur; Time Factors; Tomography, X-Ray Computed

Next to ACTS-GC (Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer), adjuvant chemotherapy with S-1 is the standard treatment for stage II or III gastric cancer patients.In this study, we retrospectively examined the continuity and adverse reaction of S-1 adjuvant chemotherapy in 30 gastric cancer patients who visited our hospital from 2007 to 2008, and compared them with those of patients treated with ACTS-GC. Whereas the persistent rate of S-1 adjuvant chemotherapy for one year in ACTS-GC was 65.8%, it was 86.7% in our hospital.The RP (Relative performance) value in cases who completed S-1 adjuvant therapy for one year in ACTS-GC and for one year in our hospital was 81.2% and 88.5%, respectively. Grade 3/4 adverse events in our hospital were leukopenia (3.3%), neutropenia (16.7%), and anorexia(6.7%). In conclusion, our hospital has shown a far greater continuity with S- 1 adjuvant chemotherapy than with ACTS-GC, a result suggesting that S-1 adjuvant chemotherapy is feasible in clinical practice.

Topics: Adult; Aged; Aged, 80 and over; Chemotherapy, Adjuvant; Drug Combinations; Female; Gastrectomy; Humans; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Patient Care Team; Stomach Neoplasms; Tegafur

A 75-year-old man was admitted for anemia, and a tar stool found by endoscopic examination revealed a type 3 advanced gastric cancer in the lower stomach. Multiple liver metastases 4 cm in diameter were shown on CT. Because we thought that the case was unresectable, S-1/CPT-11 chemotherapy was performed. S-1 (80mg/body/day) was orally administered for 2 weeks followed by a drug-free 1 week, and CPT-11 (100mg/body/day) was given intravenously on days 1 and 8. After 3 courses of chemotherapy, the primary lesion, the regional lymph nodes, and the metastatic lesion of the liver were slightly reduced in size. He was judged as clinical PR, and distal gastrectomy and lymph node dissection were performed. One month after surgery the tumor marker values became normal, and CT could hardly detect metastatic liver tumors. Now, after 3 years, the PR stage has been maintained. Combined use of peroral S-1 and CPT-11 by intravenous infusion is effective for multiple liver metastasis after gastrectomy in gastric cancer.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Biopsy; Camptothecin; Combined Modality Therapy; Drug Combinations; Humans; Irinotecan; Liver Neoplasms; Lymph Node Excision; Male; Oxonic Acid; Remission Induction; Stomach Neoplasms; Tegafur; Tomography, X-Ray Computed