s-1-(combination) and Adenocarcinoma

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

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

About one-third of the lung tumors are staged as locally advanced at the time of initial diagnosis; however, the optimal induction treatment before curative resection has not been elucidated. To date, the evidence regarding the preoperative apatinib plus S-1 for locally advanced pulmonary adenocarcinoma is scarce.. A 29-year-old female was admitted because of persistent cough, sputum, and chest distress for 2 months.. Primary pulmonary adenocarcinoma (cT3N2M0, IIIB) with unknown driver gene mutation status.. The patient had received 4 months of neoadjuvant therapy using oral apatinib (425 mg daily) plus S-1 (60 mg, twice daily for 4 weeks with a 2-week drug-free interval), followed by anatomical lobectomy with curative intent. Adjuvant apatinib (425 mg daily for a month, and 250 mg daily for another month) plus S-1 at the same dosage were administered for 2 months. Thereafter, maintenance of low-dose S-1 monotherapy (40 mg, twice daily for 4 weeks with a 2-week drug-free interval) was continued for 6 months.. The adverse events were tolerable and well-controlled. A postoperative recurrence-free survival for 2 years and a half up to now was indicated.. Preoperative apatinib plus S-1 showed efficacy in locally advanced pulmonary adenocarcinoma. However, high-quality trials are warranted before the recommendation of this therapeutic regimen.

Topics: Adenocarcinoma; Adult; Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Female; Humans; Lung Neoplasms; Neoadjuvant Therapy; Oxonic Acid; Pneumonectomy; Pyridines; 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

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

A 62-year-old male was diagnosed with large cell lung cancer(c-Stage IV)based on pathological examination of an anterior chest tumor. He received chemotherapy with cisplatin, pemetrexed, and bevacizumab. He suffered from persistent hiccups from day 2 of the first course of chemotherapy. He was unsuccessfully treated with chlorpromazine, shakuyakukanzoto, and gabapentin. Therefore, we administered pregabalin to him, and his hiccups subsided immediately. To prevent hiccups, he subsequently took pregabalin along with his chemotherapy regimen, and was able to receive 4 courses of chemotherapy without persistent hiccups. Pregabalin is a possible therapeutic option for treating persistent chemotherapy-induced hiccups.

Topics: Adenocarcinoma; Adenocarcinoma of Lung; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Hiccup; Humans; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Pregabalin; 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 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

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

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

There is no clear consensus on what type of adjuvant therapy should be used for patients with pancreatic cancer. Chemoradiation is the favored treatment modality by many in the United States while gemcitabine based chemotherapy is favored in Europe. Both of these approaches have been shown by large prospective, randomized trials to improve disease free intervals and in some studies overall survival. This year at the American Society of Clinical Oncology (ASCO) Gastrointestinal Cancer Symposium, the randomized phase III study presented by Uesaka et al. from Japan (Abstract #145) represents a newer paradigm of oral adjuvant S-1 chemotherapy in place of the traditional standard of care intravenous gemcitabine in terms of prolonging patients' survival. Another study by Fan et al. (Abstract #269) examined the value of targeted therapy using erlotinib with adjuvant chemoradiation and chemotherapy. We present the summary of these two studies and discuss the potential impact on our clinical practice on this highly lethal cancer.

Topics: Adenocarcinoma; Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Drug Combinations; Humans; Models, Biological; Oxonic Acid; Pancreatic Neoplasms; Radiotherapy, Adjuvant; Randomized Controlled Trials as Topic; Tegafur

At the time of diagnosis most of patients present with advanced or metastatic pancreatic cancer, thereby precluding surgical resection. While the standard of care in the first line setting is established, there are limited data to support a standard second-line chemotherapy regimen. The authors summarize two interesting studies (Abstract #263 and Abstract #287) presented at the 2013 ASCO Gastrointestinal Cancers Symposium. These studies concern two phase II trials about second-line chemotherapy in pancreatic cancer. The first one evaluated the role of fluoropyrimidine as monotherapy versus fluoropyrimidine in combination with irinotecan (Abstract #263) and the second one compared the fluoropyrimidine treatment with the continuation of gemcitabine as monotherapy (Abstract #287).

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Chemotherapy, Adjuvant; Clinical Trials, Phase II as Topic; Drug Combinations; Fluorouracil; Humans; Irinotecan; Oxonic Acid; Pancreatic Neoplasms; Randomized Controlled Trials as Topic; Tegafur

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

A 5 3-year-old woman was admitted to our hospital because of vomiting. CT scan and gastroduodenoscopy showed severe stenosis of the duodenal 3rd portion. There was no evidence of malignancy. We diagnosed a stricture due to a duodenal ulcer and laparotomy was performed. By means of biopsy of No.14d lymph node in the operation, adenocarcinoma of the duodenum was pointed out and we performed a pancreatoduodenectomy. Although adjuvant chemotherapy with S-1/paclitaxel (S-1 80 mg/body, po, day 1-14 and paclitaxel 120 mg/body iv day 1, 8)was administered after operation, the patient's serum CEA was elevated and metastic lymph nodes around the supra mesenteric artery were pointed out. The patient was started on combined chemotherapy with S-1/CPT-11(S-1 80 mg/body, po, day 1-14 and CPT-11 120 mg/body iv day 1), serum CEA levels returned to normal range, and marked reduction of lymph node size was observed on CT. The patient is still alive and free of disease three years after the operation. S-1/CPT-11 could therefore be a treatment option for patients with duodenal carcinoma.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Combined Modality Therapy; Drug Combinations; Duodenal Neoplasms; Female; Humans; Irinotecan; Middle Aged; Oxonic Acid; Remission Induction; Tegafur

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

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

The primary small intestinal cancer is rare in gastrointestinal cancer, and there are much advanced/recurrent cases. However, there were a few case reports about chemotherapy for advanced or recurrent small intestinal cancer, and a treatment resume was inconsistent. We reported that S-1 and UFT/LV therapy was effective with the two cases as an oral chemotherapy for the primary small intestinal cancer.

Topics: Adenocarcinoma; Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Humans; Jejunal Neoplasms; Leucovorin; Male; Middle Aged; Oxonic Acid; Tegafur; Uracil

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

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

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

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

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

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

To investigate the efficacy and safety of nab-paclitaxel plus S-1 (nab-P/S) versus nab-paclitaxel plus gemcitabine (nab-P/G) as first-line chemotherapy in patients with advanced pancreatic ductal adenocarcinoma (PDAC).. Treatment-naïve patients with advanced PDAC were equally randomized to receive nab-P/S or nab-P/G. The primary endpoint was the objective response rate (ORR). The secondary endpoints were ORR of the primary lesion, disease control rate, progression-free survival (PFS), overall survival (OS) and safety. The trial was registered at https://clinicaltrials.gov as NCT03636308.. A total of 110 patients were planned for enrollment, but the trial was prematurely closed because no better ORR was observed with nab-P/S among the first 40 patients assigned between 08/2018 and 06/2019. The ORR was numerically higher with nab-P/S versus nab-P/G (35.0% vs 25.0%, P = 0.49). The ORRs of the primary lesion for both arms were similar (30.0% and 25.0%, P = 0.72). Disease control rate was 70.0% in each arm. There was no significant difference in PFS and OS between the two arms (median PFS, 6.3 vs 5.7 months, P = 0.34; median OS, 10.2 vs 10.2 months, P = 0.92). Risks of hematological toxicity, liver injury and rash were significantly decreased in the nab-P/S arm.. A biweekly combination of nab-P/S yielded comparable efficacy with nab-P/G but improved safety profile. It may be a promising and convenient alternative as first-line and neoadjuvant settings for advanced PDAC.

Topics: Adenocarcinoma; Adult; Aged; Albumins; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Pancreatic Ductal; Deoxycytidine; Drug Combinations; Female; Gemcitabine; Humans; Male; Middle Aged; Neoadjuvant Therapy; Oxonic Acid; Paclitaxel; Pancreatic Neoplasms; Progression-Free Survival; Tegafur

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

Preoperative chemoradiotherapy (CRT), the current standard of care for locally advanced rectal cancer (LARC), is associated with many radiotherapy (RT)-related side effects. We aimed to evaluate whether S-1 and oxaliplatin (SOX) or folinic acid, 5-FU, and oxaliplatin (mFOLFOX6) can be as effective as neoadjuvant chemotherapy (NAC) regimens for LARC without RT.. Patients with untreated resectable LARC were randomly assigned to receive SOX or mFOLFOX6. The NAC protocol period was 3 months. The primary endpoint was 3-year disease-free survival (DFS), and the secondary endpoints included pathological effects, surgical completion rate, 3-year survival, and safety.. From September 2013 to October 2015, 56 and 54 patients were enrolled in the SOX and mFOLFOX6 arms, respectively. The 3-year DFS rates were 69.4% (95% confidence interval [CI] 54.9-83.6) and 73.4% (95% CI 58.7-83.6) in the SOX and mFOLFOX6 arms, respectively; no significant differences were found between the arms (log-rank test; P = 0.5315, hazard ratio: 0.808, 95% CI 0.414-1.578). The 3-year survival rates were 92.3 and 91.8% in the SOX and mFOLFOX6 arms, respectively. The surgical completion rate was 98.1% overall, 100% in the SOX arm, and 96.0% in the mFOLFOX6 arm. The incidences of pathological response rates ≥grade 1b were 41.5 and 43.8% in the SOX and mFOLFOX6 arms, respectively. Both treatments were manageable and tolerable.. We demonstrated the effectiveness and safety of SOX and mFOLFOX6, both of which may be new neoadjuvant treatment candidates in previously untreated LARC cases.. Date of enrolment of the first participant to the trial: 3rd Oct 2013; This study was registered in the UMIN clinical trials registry on 14th Aug, 2013. (Prospectively registered, UMIN-CTR number UMIN000011486). https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&recptno=R000013441&language=J.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Drug Combinations; Female; Fluorouracil; Follow-Up Studies; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Oxaliplatin; Oxonic Acid; Prognosis; Rectal Neoplasms; Survival Rate; Tegafur

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

Neoadjuvant chemotherapy (NAC) represents a promising alternative to pancreatic ductal adenocarcinoma (PDAC) planned resection, but the survival impact remains undefined. To assess the feasibility and survival outcomes of NAC with gemcitabine and S1 (GS) for PDAC planned resection by prospective study.. Patients with resectable or borderline resectable PDAC received 2 cycles of NAC-GS and were offered curative resection followed by gemcitabine adjuvant. The primary endpoint was 2-year overall survival (OS). Adverse events during NAC, radiological and tumor marker responses, resection rate, and surgical safety were evaluated as secondary endpoints (UMIN000004148).. We enrolled 104 patients between 2010 and 2012, with 101 patients treated using NAC-GS as the full analysis set (FAS). Of the 101 patients, 88% received the planned 2 cycles of NAC. Grade 3 neutropenia was common (35%). Radiological partial response and decreased carbohydrate antigen 19-9 concentration (> 50% decrease) were noted in 13% and 41%, respectively. R0/1 resections with M0 were performed in 65 patients without surgical mortality. Of the 65 patients, 44 received planned gemcitabine adjuvant for 6 months as the on-protocol cohort. The primary endpoint for the 2-year OS rate was 55.9% in the FAS (n = 101) and 74.6% in the on-protocol cohort (n = 44).. NAC-GS was feasible and actively prolonged survival following PDAC planned resection. Randomized control trials are needed to further clarify the survival benefit of NAC-GS in addition to surgery followed by adjuvant therapy.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; CA-19-9 Antigen; Chemotherapy, Adjuvant; Deoxycytidine; Disease-Free Survival; Drug Combinations; Female; Gemcitabine; Humans; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm, Residual; Neutropenia; Oxonic Acid; Pancreatectomy; Pancreatic Neoplasms; Prospective Studies; Survival Rate; Tegafur

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

In our previous randomised phase 2 study for patients with gemcitabine-refractory advanced pancreatic cancer, S-1 plus leucovorin improved progression-free survival compared with S-1 alone. Here, we evaluated the efficacy of TAS-118 (S-1 plus leucovorin) versus S-1 in overall survival (OS).. This randomised, open-label, phase 3 study was conducted at 58 centres in Japan and Korea. Patients with metastatic pancreatic cancer that progressed during first-line gemcitabine-based chemotherapy or recurred during or after post-operative gemcitabine-based adjuvant treatment were randomly assigned (1:1) to receive either S-1 (40-60 mg, twice daily for 4 weeks in a 6-week cycle) or TAS-118 (S-1 40-60 mg plus leucovorin 25 mg, twice daily for 1 week in a 2-week cycle). The primary end-point was OS.. A total of 603 patients were randomised, and 300 and 301 patients received TAS-118 and S-1, respectively. There was no difference in OS between groups (median OS for TAS-118 versus S-1, 7.6 months versus 7.9 months; hazard ratio [HR], 0.98 [95% confidence interval (CI), 0.82-1.16]; P = 0.756). Progression-free survival was significantly longer with TAS-118 than S-1 (median, 3.9 months versus 2.8 months; HR, 0.80 [95% CI, 0.67-0.95]; P = 0.009). There were interactions between Japan and Korea (P = 0.004) and between unresectable and recurrent disease (P = 0.025) in OS. Incidence, profile and severity of adverse events were similar between groups.. TAS-118 did not improve OS in patients with gemcitabine-refractory advanced pancreatic cancer compared to S-1. Further studies are needed to find patients who have benefit from adding leucovorin to S-1.

Topics: Adenocarcinoma; Adult; Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Adenosquamous; Deoxycytidine; Disease Progression; Drug Combinations; Drug Resistance, Neoplasm; Female; Gemcitabine; Humans; Japan; Leucovorin; Male; Middle Aged; Oxonic Acid; Pancreatic Neoplasms; Progression-Free Survival; Republic of Korea; Tegafur; Time Factors

Several recent studies have shown that salvage chemotherapy following PD-1 blockade produces high antitumor activity in some patients with non-small lung cancer (NSCLC). However, the underlying synergistic mechanisms remain uncertain. The blood neutrophil-to-lymphocyte ratio (NLR) and absolute neutrophil count (ANC) can reflect the number of circulating myeloid-derived suppressor cells and tumor-associated neutrophils. The immunosuppressive status of the tumor microenvironment could be monitored by the time-series patterns of NLR and ANC. The dynamics of NLR and ANC during nivolumab treatment were retrospectively explored in 15 patients: 8 patients receiving subsequent salvage chemotherapy (2 groups: 3 non-responders and 5 responders), and 7 responders to nivolumab alone (2 groups: 4 partial response and 3 complete response). The dynamics of NLR and ANC during nivolumab differed among these four groups (NLR P = 0.045, ANC P = 0.067). NLR and ANC during nivolumab treatment increased over time in non-responders to salvage chemotherapy, with an inverse relationship between drug response and NLR or ANC at four to six weeks among the four groups. We hypothesize that the early dynamics of NLR and ANC during nivolumab may be associated with the late efficacy of subsequent salvage chemotherapy. Further studies involving a large cohort are needed to confirm these findings, which could provide insight into the role of myeloid immunosuppressor cells in combination PD-1 blockade and chemotherapy.

Topics: Adenocarcinoma; Aged; Albumins; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Carboplatin; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Case-Control Studies; Docetaxel; Drug Combinations; Female; Follow-Up Studies; Humans; Lung Neoplasms; Lymphocytes; Male; Middle Aged; Neutrophils; Nivolumab; Oxonic Acid; Paclitaxel; Prognosis; Ramucirumab; Retrospective Studies; Salvage Therapy; 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

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

Alternate-day administration of S-1 is thought to reduce toxicities. This phase II study evaluated S-1 on alternate days combined with bevacizumab as first-line treatment for elderly patients with metastatic colorectal cancer.. Of 54 enrolled patients, 50 patients were evaluated for efficacy and 53 for safety. The median age was 79 years (range 75-88 years). The median progression-free survival was 8.1 months (95% confidence interval (CI) 6.7-9.5 months). The median overall survival was 23.1 months (95% CI 17.4-28.8 months). The response rate was 44% (95% CI 30.2-57.8%), and the disease control rate was 88% (95% CI 79.0-97.0%). Grade 3 or higher hematologic, non-hematologic, and bevacizumab-related adverse events occurred in 9%, 11%, and 25% of patients, respectively. The most common grade 3 and 4 treatment-related adverse events were hypertension (11%), nausea (6%), fatigue (6%), anemia (6%), and proteinuria (6%). Only 6 patients discontinued treatment due to adverse events.. S-1 on alternate days combined with bevacizumab showed better tolerability and comparable survival compared with the results of similar studies.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Colorectal Neoplasms; Drug Administration Schedule; Drug Combinations; Female; Humans; Male; Neoplasm Metastasis; Oxonic Acid; Prognosis; Prospective Studies; Survival Rate; Tegafur

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

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

Combination therapy with oral fluoropyrimidine and irinotecan has not yet been established as first-line treatment of metastatic colorectal cancer (mCRC). We carried out a randomized, open-label, phase III trial to determine whether S-1 and irinotecan plus bevacizumab is noninferior to mFOLFOX6 or CapeOX plus bevacizumab in terms of progression-free survival (PFS).. Patients from 53 institutions who had previously untreated mCRC were randomly assigned (1 : 1) to receive either mFOLFOX6 or CapeOX plus bevacizumab (control group) or S-1 and irinotecan plus bevacizumab (experimental group; a 3-week regimen: intravenous infusions of irinotecan 150 mg/m2 and bevacizumab 7.5 mg/kg on day 1, oral S-1 80 mg/m2 twice daily for 2 weeks, followed by a 1-week rest; or a 4-week regimen: irinotecan 100 mg/m2 and bevacizumab 5 mg/kg on days 1 and 15, S-1 80 mg/m2 twice daily for 2 weeks, followed by a 2-week rest). The primary end point was PFS. The noninferiority margin was 1.25; noninferiority would be established if the upper limit of the 95% confidence interval (CI) for the hazard ratio (HR) of the control group versus the experimental group was less than this margin.. Between June 2012 and September 2014, 487 patients underwent randomization. Two hundred and forty-three patients assigned to the control group and 241 assigned to the experimental group were included in the primary analysis. Median PFS was 10.8 months (95% CI 9.6-11.6) in the control group and 14.0 months (95% CI 12.4-15.5) in the experimental group (HR 0.84, 95% CI 0.70-1.02; P < 0.0001 for noninferiority, P = 0.0815 for superiority). One hundred and fifty-seven patients (64.9%) in the control group and 140 (58.6%) in the experimental group had adverse events of grade 3 or higher.. S-1 and irinotecan plus bevacizumab is noninferior to mFOLFOX6 or CapeOX plus bevacizumab with respect to PFS as first-line treatment of mCRC and could be a new standard treatment.. UMIN000007834.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Capecitabine; Colorectal Neoplasms; Disease-Free Survival; Drug Combinations; Female; Fluorouracil; Humans; Irinotecan; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Progression-Free Survival; Tegafur; Young Adult

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

Chemotherapy remains a viable option for the management of advanced non-small-cell lung cancer (NSCLC) despite recent advances in molecular targeted therapy and immunotherapy. We evaluated the efficacy of oral 5-fluorouracil-based S-1 as second- or third-line therapy compared with standard docetaxel therapy in patients with advanced NSCLC.. Patients with advanced NSCLC previously treated with ≥1 platinum-based therapy were randomized 1 : 1 to docetaxel (60 mg/m2 in Japan, 75 mg/m2 at all other study sites; day 1 in a 3-week cycle) or S-1 (80-120 mg/day, depending on body surface area; days 1-28 in a 6-week cycle). The primary endpoint was overall survival. The non-inferiority margin was a hazard ratio (HR) of 1.2.. A total of 1154 patients (577 in each arm) were enrolled, with balanced patient characteristics between the two arms. Median overall survival was 12.75 and 12.52 months in the S-1 and docetaxel arms, respectively [HR 0.945; 95% confidence interval (CI) 0.833-1.073; P = 0.3818]. The upper limit of 95% CI of HR fell below 1.2, confirming non-inferiority of S-1 to docetaxel. Difference in progression-free survival between treatments was not significant (HR 1.033; 95% CI 0.913-1.168; P = 0.6080). Response rate was 8.3% and 9.9% in the S-1 and docetaxel arms, respectively. Significant improvement was observed in the EORTC QLQ-C30 global health status over time points in the S-1 arm. The most common adverse drug reactions were decreased appetite (50.4%), nausea (36.4%), and diarrhea (35.9%) in the S-1 arm, and neutropenia (54.8%), leukocytopenia (43.9%), and alopecia (46.6%) in the docetaxel arm.. S-1 is equally as efficacious as docetaxel and offers a treatment option for patients with previously treated advanced NSCLC.. Japan Pharmaceutical Information Center, JapicCTI-101155.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Large Cell; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Docetaxel; Drug Combinations; Drug Resistance, Neoplasm; Female; Follow-Up Studies; Humans; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Prognosis; Salvage Therapy; Survival Rate; Taxoids; Tegafur; Young Adult

Gemcitabine and S-1 are drugs commonly used for treating locally advanced pancreatic cancer (LAPC). However, the safety and efficacy of combination of these agents for induction chemotherapy (IC) followed by chemoradiotherapy are not well-defined.. Fifteen patients with LAPC (IC-CRT group) were treated with gemcitabine and S-1 IC, followed by S-1 chemoradiotherapy. The clinical outcomes were compared to a cohort of 38 patients who received chemoradiotherapy alone (CRT group).. Disease control rates in the CRT and IC-CRT groups were 84% and 93%, respectively (p=0.024). The median time of disease progression was 10.8 and 15.4 months in the CRT and IC-CRT group, respectively (p=0.043). The median overall survival time was longer in the IC-CRT group compared to CRT (23.4 vs. 17.3 months), but this increase was not statistically significant.. Gemcitabine and S-1 combination chemotherapy, followed by CRT, is a promising IC regimen for treating LAPC.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Deoxycytidine; Drug Combinations; Female; Gemcitabine; Humans; Induction Chemotherapy; Kaplan-Meier Estimate; Male; Middle Aged; Oxonic Acid; Pancreatic Neoplasms; Tegafur; Treatment Outcome

We aimed to compare the efficacy and safety of irinotecan/S-1 (IRIS) therapy with S-1 monotherapy in patients with gemcitabine-refractory pancreatic cancer.. Patients were treated with oral S-1 (80-120 mg for 14 days every 4 weeks) plus intravenous irinotecan (100 mg m. Of 137 patients enrolled, 127 were eligible for efficacy. The median PFS in the IRIS group and S-1 monotherapy group were 3.5 and 1.9 months, respectively (hazard ratio (HR)=0.77; 95% confidence interval (CI), 0.53-1.11; P=0.18), while the median overall survival (OS) were 6.8 and 5.8 months, respectively (HR=0.75; 95% CI, 0.51-1.09; P=0.13). Response rate was significantly higher in the IRIS group than in the S-1 monotherapy group (18.3% vs 6.0%, P=0.03). Grade 3 or higher neutropenia and anorexia occurred more frequently in the IRIS group.. There was a trend for better PFS and OS in the IRIS group that could be a treatment arm in the clinical trials for gemcitabine-refractory pancreatic cancer.

Topics: Adenocarcinoma; Administration, Intravenous; Administration, Oral; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Carcinoma, Adenosquamous; Deoxycytidine; Disease-Free Survival; Drug Combinations; Drug Resistance, Neoplasm; Female; Gemcitabine; Humans; Irinotecan; Male; Middle Aged; Oxonic Acid; Pancreatic Neoplasms; Tegafur; Treatment Outcome

The GEST study showed non-inferiority of S-1 but not superiority of gemcitabine plus S-1 (GS) to gemcitabine alone for overall survival with the data by the cut-off date of 31st July in 2010 for chemo-naïve patients with advanced pancreatic cancer. We considered it important to determine whether S-1 maintains non-inferiority after a long-term follow-up in the GEST study and to obtain a firm positive conclusion. In addition, it may be an interesting challenge to explore the efficacious profile of GS in the long-term follow-up study. Using the data from the follow-up period, background and efficacy in patients from Taiwan and Japan, as well as the rates of tumor shrinkage in locally advanced and metastatic patients (Waterfall plot) were also analyzed.. The results of the primary analysis were reconfirmed, and subset analysis of overall survival and progression-free survival was performed based on the overall survival data updated by the cut-off date of 31st July in 2011.. The median follow-up period was 29.8 months, and 795 deaths occurred (95.6%). The median overall survival was 8.8 months for gemcitabine, 9.7 months for S-1 (hazard ratio [HR], 0.96; 97.5% confidence interval [CI], 0.79-1.17), and 9.9 months for GS (HR 0.91; 97.5% CI 0.75-1.11). In patients with performance status (PS) 0, the median overall survival was 9.8 months for gemcitabine, 10.9 months for S-1, and 10.5 months for GS. In patients with PS 1, the median overall survival was 6.2 months for gemcitabine, 6.3 months for S-1, and 9.6 months for GS.. Our survey reconfirmed the non-inferiority of S-1 to gemcitabine and showed S-1 can be used as one of the standard treatment options for advanced pancreatic cancer.. ClinicalTrials.gov: NCT00498225.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Deoxycytidine; Disease Progression; Drug Combinations; Female; Follow-Up Studies; Gemcitabine; Humans; Male; Middle Aged; Neoadjuvant Therapy; Oxonic Acid; Pancreatic Neoplasms; Tegafur

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 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

The objective of this study was to determine the recommended dose (RD) of a biweekly S-1, oxaliplatin, and irinotecan (SOXIRI) regimen in patients with unresectable pancreatic ductal adenocarcinoma.. This phase I study used a traditional "3+3" dose-escalation design, with four dose levels. A dose-escalation schedule consisted of two doses of S-1 (60 and 80 mg/m(2) twice daily) for 2 weeks in alternate-day administration, three doses of irinotecan (125, 150, and 180 mg/m(2)) on day 1, and a single dose of oxaliplatin (85 mg/m(2)) on day 1 of a 2-week cycle. Dose-limiting toxicities (DLTs) were assessed in the first four cycles to determine the maximum tolerated dose. This clinical study was registered at UMIN000014339.. Fifteen patients received this regimen (median, eight cycles; range 4-12). At dose level 3 (S-1, 80 mg/m(2); irinotecan, 150 mg/m(2)), 2/6 patients experienced DLTs of grade 3 fatigue and grade 4 neutropenia. At dose level 4, all three patients experienced DLTs: grade 3 fatigue (n = 1) and grade 4 neutropenia (n = 2). The RD was 80, 85, and 150 mg/m(2) of S-1, oxaliplatin, and irinotecan, respectively. We found the following: response rate, 47 %; disease control rate, 80%; median progression-free survival, 6.7 months; overall survival, 13.4 months.. The SOXIRI regimen's RD is 80, 85, and 150 mg/m(2) of S-1, oxaliplatin, and irinotecan, respectively.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Carcinoma, Pancreatic Ductal; Disease-Free Survival; Dose-Response Relationship, Drug; Drug Combinations; Feasibility Studies; Female; Humans; Irinotecan; Male; Maximum Tolerated Dose; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Pancreatic Neoplasms; Survival Rate; Tegafur; Treatment Outcome

This study aimed to determine the maximum tolerated dose and the recommended dose of combining S-1 with gemcitabine and cisplatin for advanced biliary tract adenocarcinoma first-line therapy.. Chemotherapy-naive patients with histologically or cytologically proven unresectable or metastatic biliary tract adenocarcinoma were enrolled. Patients with advanced biliary tract adenocarcinoma received gemcitabine and cisplatin intravenously on Days 1 and 8 and S-1 orally twice daily from Days 1 to 14. Cycles were repeated every 21 days until disease progression. Patients were scheduled to receive gemcitabine (mg/m(2)/week), cisplatin (mg/m(2)/week) and S-1 (mg/m(2)/day) at four dose levels: 800/25/40 (level 0), 1000/25/40 (level 1), 1000/25/60 (level 2) and 1000/25/80 (level 3). Level 1 was chosen as the starting dose. For cases where recommended dose could not be determined within the triweekly schedule, we prepared a biweekly schedule to find recommended dose.. Seventeen patients with advanced biliary tract adenocarcinoma were treated across three dose levels. Maximum tolerated dose and recommended dose were defined as level 0. Dose-limiting toxicities included a Grade 3 maculopapular rash, Grade 4 thrombocytopenia and consecutive administration skips of gemcitabine and cisplatin on Day 8. Five partial responses were observed.. This triweekly triplet regimen was well tolerated and showed promising antitumor activity in patients with advanced biliary tract adenocarcinoma. We recommend level 0, gemcitabine at 800 mg/m(2)/week, cisplatin at 25 mg/m(2)/week and S-1 at 40 mg/m(2)/day during a 21-day cycle, in further studies with this schedule.

Topics: Adenocarcinoma; Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Biliary Tract Neoplasms; Cisplatin; Deoxycytidine; Disease Progression; Drug Administration Schedule; Drug Combinations; Female; Gemcitabine; Humans; Infusions, Intravenous; Kaplan-Meier Estimate; Male; Maximum Tolerated Dose; Middle Aged; Oxonic Acid; 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

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

In this subanalysis of a phase III trial using three categorized doses of S-1, the influence of the actual doses on safety and efficacy was evaluated.. We compared the efficacy and safety of the S-1 or gemcitabine plus S-1 combination (GS) arm between the top 10% group and the bottom 10% group according to the initial doses of S-1: ≥77.6 versus ≤65.9 mg/m2/day (n = 28 vs. 28) in the S-1 arm, and ≥65.1 versus ≤53.8 mg/m2/day (n = 27 vs. 28) in the GS arm.. Overall and progression-free survival were not significantly different between these two groups: hazard ratios of 0.818 and 0.761 with p values of 0.498 and 0.330 in the S-1 arm, and hazard ratios of 0.836 and 0.759 with p values of 0.557 and 0.323 in the GS arm, respectively. Incidences of grade 3-4 hematological toxicities were significantly higher in the top 10% group than in the bottom 10% group: 42.9 versus 14.3 and 85.2 versus 57.1%, with p values of 0.037 and 0.037 in the S-1 and the GS combination arm, respectively.. Higher actual doses of S-1 were associated with a higher incidence of hematological toxicity even in the same dose setting.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Adenosquamous; Deoxycytidine; Disease-Free Survival; Drug Combinations; Female; Gemcitabine; Hematologic Diseases; Humans; Male; Middle Aged; Oxonic Acid; Pancreatic Neoplasms; Retrospective Studies; Survival Rate; Tegafur

Objectives The aim of this study was to evaluate the safety and efficacy of intravenous and intraperitoneal paclitaxel (PTX) combined with S-1 for treatment of gemcitabine-refractory pancreatic cancer with malignant ascites. Methods After the feasibility of this regimen was first confirmed in an interim analysis in 10 patients, a total of 35 patients were enrolled between April 2011 and December 2014. PTX was administered intravenously (50 mg/m(2)) and intraperitoneally (20 mg/m(2)) on days 1 and 8, and 80 mg/m(2) S-1 was administered on days 1-14 every 3 weeks. The primary endpoint was overall survival (OS). The secondary endpoints were progression-free survival (PFS), the objective tumor response, efficacy against malignant ascites, and safety. Result In all 35 patients, the median OS and PFS were 4.8 (95 % confidence interval [CI], 2.1-5.3) months and 2.8 (95 % CI, 0.9-4.1) months, respectively. The 26 patients who were evaluable for efficacy achieved a response rate of 8 % and a disease control rate of 69 %. Malignant ascites had disappeared or decreased in 18 (69 %) patients, including complete resolution in 4 (15 %), and a negative change in cytological status was achieved in 8 (31 %) patients. The major grade 3/4 adverse events included neutropenia (34 %), anemia (31 %), nausea (9 %), and catheter-related infections (6 %). Conclusion Combination chemotherapy consisting of intravenous and intraperitoneal PTX with S-1 showed acceptable toxicity and favorable efficacy in pancreatic cancer patients with malignant ascites. (. UMIN000005306).

Topics: Adenocarcinoma; Administration, Intravenous; Adult; Aged; Antimetabolites, Antineoplastic; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Ascites; Deoxycytidine; Disease-Free Survival; Drug Combinations; Drug Resistance, Neoplasm; Female; Gemcitabine; Humans; Infusions, Parenteral; Kaplan-Meier Estimate; Male; Middle Aged; Oxonic Acid; Paclitaxel; Pancreatic Neoplasms; Tegafur; Treatment Outcome

The purpose of this phase I study of the dose escalation of oxaliplatin in combination with oral S-1 and pelvic radiation preoperatively for poor-risk lower rectal cancer was to determine the dose-limiting toxicity (DLT) and recommended dose of oxaliplatin.. Patients with cT4 and lateral pelvic lymph node metastasis, and without distant metastasis (cM0), were treated with weekly oxaliplatin, oral S-1 40 mg/m(2) twice daily for 5 days a week, and radiation. A total of 5 weekly doses of oxaliplatin were planned. RT was administered to a total dose of 50.4 Gy in 28 fractions.. We enrolled 11 patients between December 2009 and January 2012. DLTs were observed at dose level 1 (50 mg/m(2)) in two patients, one of whom experienced grade 3 aspartate aminotransferase elevation and a grade 3 alanine aminotransferase increase, and the other developed grade 4 hypokalemia and a grade 3 alanine aminotransferase increase. Five patients at dose level 2 (60 mg/m(2)) showed no DLTs. The hematological toxicities in all patients were mild and reversible. One patient showed distant metastasis after chemoradiation. Ten of the 11 patients achieved R0 resection by mesorectal resection and lateral lymph node dissection; three of the 10 underwent combined resection of the other organs.. This phase I trial of preoperative S-1 in combination with oxaliplatin and radiation for lower rectal cancer with T4 and lateral pelvic lymph node metastasis revealed that the recommended dose of oxaliplatin was 60 mg/m(2) weekly.

Topics: Adenocarcinoma; Adult; Aged; Alanine Transaminase; Antineoplastic Combined Chemotherapy Protocols; Aspartate Aminotransferases; Chemoradiotherapy, Adjuvant; Diarrhea; Dose Fractionation, Radiation; Drug Combinations; Female; Humans; Lymph Node Excision; Lymphatic Metastasis; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Neutropenia; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Pelvis; Preoperative Care; Rectal Neoplasms; Tegafur; Vomiting

This phase I study was performed to determine the maximum tolerated dose (MTD), recommended dose (RD), and dose-limiting toxicities (DLTs) of oxaliplatin combined with preoperative chemoradiotherapy with S-1, oxaliplatin, and bevacizumab in locally advanced rectal cancer.. Eligible patients had a newly diagnosed clinical stage T1-4 N0-3 M0 rectal adenocarcinoma within 12 cm of the anal verge suitable for curative resection. Conformal radiation therapy was given (4 fields, 2 Gy daily fractions, 5 days/week, total dose 40 Gy) with concurrent S-1 (80 mg/m(2)/day orally, days 1-5, 8-12, 15-19, and 22-26), bevacizumab (90 min continuous intravenous infusion at 5 mg/kg, days 1 and 15), and oxaliplatin (120 min continuous intravenous infusion, days 1, 8, 15, and 22). The initial oxaliplatin dose (40 mg/m(2)/day) was gradually increased to determine the MTD and RD. Surgery was performed 6 weeks after completion of preoperative chemoradiotherapy.. 11 patients were enrolled. The MTD of oxaliplatin was considered to be 60 mg/m(2), because three of five patients developed DLTs such as diarrhea and hives. The recommended dose of oxaliplatin was set at 50 mg/m(2). Of the patients who received oxaliplatin at ≤ RD, 5 (83.3%) had a clinical response [four pathological responses and one pathological complete response (Grade 3)].. With this new regimen, the MTD of oxaliplatin was 60 mg/m(2), and the RD for phase II studies was 50 mg/m(2). This new regimen appears to provide worthwhile outcomes for locally advanced rectal cancer and merits a phase II study.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Chemoradiotherapy; Dose-Response Relationship, Drug; Drug Combinations; Female; Humans; Male; Maximum Tolerated Dose; Middle Aged; Neoadjuvant Therapy; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Radiotherapy, Conformal; Rectal Neoplasms; Rectum; Tegafur

The FIRIS study previously demonstrated non-inferiority of IRIS (irinotecan plus S-1) to FOLFIRI (5-fluorouracil/leucovorin with irinotecan) for progression-free survival as the second-line chemotherapy for metastatic colorectal cancer (mCRC) as the primary endpoint. The overall survival (OS) data were immature at the time of the primary analysis.. Between 30 January 2006 and 29 January 2008, 426 patients with mCRC who failed in first-line chemotherapy were randomly assigned to receive either FOLFIRI or IRIS. After the primary analysis, the follow-up survey was cut off on 29 July 2010, and the final OS data were analysed.. With a median follow-up of 39.2 months, the median OS was 17.4 months in the FOLFIRI group and 17.8 months in the IRIS group [hazard ratio (HR) 0.900; 95% confidence interval (CI) 0.728-1.112]. In the pre-planned subgroup of patients who received prior chemotherapy containing oxaliplatin, the median OS was 12.7 months in the FOLFIRI group and 15.3 months in the IRIS group (HR 0.755; 95% CI 0.580-0.983).. IRIS is non-inferior to FOLFIRI for OS as second-line chemotherapy for mCRC. IRIS can be an option for second-line chemotherapy of mCRC. (ClinicalTrials.gov Number: NCT00284258).

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colorectal Neoplasms; Drug Combinations; Female; Fluorouracil; Follow-Up Studies; Humans; Irinotecan; Leucovorin; Male; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Prognosis; Survival Rate; Tegafur

A single-arm phase II clinical trial was conducted to evaluate the safety and efficacy of preoperative chemoradiotherapy (CRT) with concurrent S-1, bevacizumab, and radiation in patients with locally advanced rectal cancer (LARC).. Fifty-two patients with LARC were enrolled. A total dose of 45 Gy was delivered in 25 fractions over 5 weeks, S-1 was administered orally twice a day on days 1-14 and 22-35, and bevacizumab was administered on days 1, 15, and 29. Surgical resection was scheduled 8 weeks (6-10 weeks) after completing the CRT.. All 52 patients underwent R0 radical surgery. Sphincter preservation was possible in 38 (73.1%) patients. A pathologic complete response was obtained in 10 (19.2%) patients, a pathologic downstaging was achieved in 37 (71.2%) patients, and the tumor shrinkage rate was 77.1%. The only grade 3 adverse events were leukopenia and rash in 1 (1.9%) patient. The rate of postoperative complications was 28.8%. Anastomotic leakage occurred in 9 (23.7%) of the 38 patients who underwent sphincter-preserving surgery. Perineal wound dehiscence developed in 2 (14.3%) of the 14 patients who received an abdominoperineal resection.. Adding bevacizumab to S-1 clearly increased the incidence of wound-related complications, with no distinct enhancement of tumor response.

Topics: Adenocarcinoma; Adult; Aged; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Chemoradiotherapy; Drug Combinations; Female; Humans; Male; Middle Aged; Oxonic Acid; Postoperative Complications; Rectal Neoplasms; Tegafur

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

We investigated the efficacy and safety of S-1 and cisplatin with concurrent thoracic radiation (SCCR) over cisplatin alone plus concurrent thoracic radiation (CCR) for unresectable stage III non-small-cell lung cancer (NSCLC).. Between January 2009 and November 2011, 40 eligible patients with NSCLC were included and divided randomly into two groups. Twenty patients received SCCR with S-1 (orally at 40 mg/m(2) per dose, b.i.d.) on days 1 through 14, cisplatin (60 mg/m(2) on day 1) every 4 weeks for two cycles, and radiotherapy (60 Gy/30 fractions over 6 weeks) beginning on day 1. Twenty subjects received CCR (cisplatin and radiotherapy, the same as for SCCR).. The 3-year overall response rate was 59.3% and 52.4% for the SCCR and CCR groups, respectively, and the difference was statistically significant, while the median overall survival was 33 months (range, 4-41 months) and 24 months (range, 2-37 months), respectively (P = 0.048). The median progression-free survival was 31 months for SCCR (range, 5-39 months), whereas it was 20 months (range, 2-37 months) for CCR (P = 0.037). The toxicity profile was similar in both groups.. In summary, we demonstrated that S-1 and cisplatin with concurrent thoracic radiation was more effective than cisplatin plus radiotherapy in NSCLC patients with acceptable toxicity.. Chinese Clinical Trials Register: ChiCTR-TRC-13003997 .

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Large Cell; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Chemoradiotherapy; Cisplatin; Drug Combinations; Female; Follow-Up Studies; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Pilot Projects; Prognosis; Radiotherapy Dosage; Survival Rate; Tegafur; Young Adult

Although cytotoxic chemotherapy is essential in epidermal growth factor receptor (EGFR)‑mutated non‑small cell lung cancer (NSCLC), it is unclear which regimen is most effective. We retrospectively compared the efficacy of standard platinum‑based chemotherapy with that of combination chemotherapy using vinorelbine (VNR) plus dihydropyrimidine dehydrogenase‑inhibitory fluoropyrimidine (DIF) in EGFR‑mutated lung adenocarcinomas, and we investigated a potential mechanism by which the combination chemotherapy of VNR + DIF was favorable in the treatment of EGFR‑mutated lung adenocarcinoma in vitro. In our retrospective analysis, the response rate and disease control rate afforded by the VNR + DIF treatment tended to be better than those by platinum‑based chemotherapy, and the progression‑free survival of the 24 VNR + DIF‑treated patients was significantly longer than that of the 15 platinum‑based chemotherapy patients. In EGFR‑mutated PC9 cells, VNR induced EGFR dephosphorylation at a clinically achievable concentration. 1BR3‑LR cells, a line of fibroblast cells transfected with a mutant EGFR construct, were completely resistant to gefitinib in the medium containing 10% fetal bovine serum (FBS), whereas the sensitivity of these cells to gefitinib was increased in 0.5% FBS‑containing medium. Similarly, the sensitivity of 1BR3‑LR cells to VNR was increased when they were cultured in low‑serum condition. In addition, sodium orthovanadate (Na3VO4) inhibited the EGFR dephosphorylation induced by VNR or gefitinib and suppressed the cell growth inhibition by these agents in PC9 cells. VNR and gefitinib showed synergistic cell growth inhibition in combination with 5‑fluorouracil (5‑FU) in PC9 cells. We propose that the EGFR dephosphorylation induced by VNR is related to cell growth inhibitory activity of VNR, and that this is one of the mechanisms of the synergistic effect of VNR + 5‑FU in EGFR‑mutated lung cancer cells. In conclusion, the combination chemotherapy of VNR + DIF may be a promising treatment for NSCLC patients with EGFR mutations.

Topics: Adenocarcinoma; Adenocarcinoma of Lung; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Dihydrouracil Dehydrogenase (NADP); Drug Combinations; ErbB Receptors; Female; Fluorouracil; Gefitinib; Humans; Kaplan-Meier Estimate; Lung Neoplasms; Male; Middle Aged; Mutation; Oxonic Acid; Quinazolines; Retrospective Studies; Tegafur; Treatment Outcome; Vinblastine; Vinorelbine

The objective of this phase I study was to determine the maximum tolerated dose (MTD) and recommended dose (RD) of preoperative chemoradiotherapy (CRT) with S-1 plus oxaliplatin in patients with locally advanced rectal cancer.. Patients received radiotherapy in a total dose of 50.4 Gy in 28 fractions. Concurrent chemotherapy consisted of a fixed oral dose of S-1 (80 mg/m(2)/day) on days 1-5, 8-12, 22-27, and 29-33, plus escalated doses of oxaliplatin as an intravenous infusion on days 1, 8, 22, and 29. Oxaliplatin was initially given in a dose of 40 mg/m(2)/week to three patients. The dose was then increased in a stepwise fashion to 50 mg/m(2)/week and the highest dose level of 60 mg/m(2)/week until the MTD was attained.. Thirteen patients were enrolled, and 12 received CRT. Dose-limiting toxicity (DLT) occurred in two of six patients (persistent grade 2 neutropenia, delaying oxaliplatin treatment by more than 3 days) at dose level 3; there were no grade 3 or 4 adverse events defined as DLT. The RD was 60 mg/m(2)/week of oxaliplatin on days 1, 8, 22, and 29. Twelve patients underwent histologically confirmed R0 resections, and two out of six patients (33%) given dose level 3 had pathological complete responses.. The RD for further studies is 80 mg/m(2) of S-1 5 days per week plus 60 mg/m(2) of oxaliplatin on days 1, 8, 22, and 29 and concurrent radiotherapy. Although our results are preliminary, this new regimen for neoadjuvant chemoradiotherapy is considered safe and active.. This trial was registered with Clinicaltrials.gov (identifier: NCT01227239 ).

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Drug Combinations; Female; Follow-Up Studies; Humans; Male; Maximum Tolerated Dose; Middle Aged; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Pelvis; Prognosis; Rectal Neoplasms; Remission Induction; Tegafur; Young Adult

A phase II study was conducted to evaluate the efficacy and safety of gemcitabine and S-1 combination chemotherapy in patients with metastatic biliary tract cancer (BTC).. Patients with pathologically confirmed, unresectable, recurrent, or metastatic adenocarcinoma that originated from the intrahepatic or extrahepatic biliary ducts or gallbladder were assessed for eligibility. The primary end point was the overall response rate (ORR). The treatment consisted of 1,000 mg/m(2) intravenous gemcitabine administered over 30 min on days 1 and 8, and 80 mg/m(2) oral S-1 on days 1-14 of each cycle. The treatment was repeated every 3 weeks.. Thirty-eight patients were enrolled between November 2005 and 2010. All patients had metastatic disease, and the primary sites of cancer were as follows: gallbladder in 12 (31.6%), intrahepatic and extrahepatic bile ducts in 23 (60.5%), and the ampulla of Vater in 3 (7.9%) patients. One patient achieved a complete response, and six experienced a partial response. The ORR was 20.6% (95% CI 8.5-36.7] in the per-protocol (PP) population, and 18.4% (95%CI 6.1-30.7) in the intention-to-treat (ITT) population; the median response duration was 10.8 months. Nineteen patients had stable disease, and the disease control rate was 76.5% (95%CI 60.6-87.6) in the PP population. The median progression-free survival was 4.4 months (95%CI 1.8-6.9), and the median overall survival was 9.0 months (95%CI 4.0-13.9) with a 1-year survival rate of 44.7% (95%CI 29.0-61.5) in the ITT population. Grade 3/4 hematologic toxicities, neutropenia, anemia, and thrombocytopenia were observed in 13 (37.1%), 9 (25.7%), 2 (5.7%), and 2 (5.7%) patients, respectively. One patient experienced a grade 3 febrile neutropenia without any documented infection. The grade 3/4 non-hematologic toxicities were hepatic toxicity (11.4%), anorexia (2.9%), and renal toxicity (2.9%).. Gemcitabine and S-1 combination chemotherapy showed acceptable efficacy and favorable toxicity profiles. Therefore, it might offer an alternative therapeutic strategy in patients with BTC.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Biliary Tract Neoplasms; Deoxycytidine; Disease-Free Survival; Drug Administration Schedule; Drug Combinations; Female; Gemcitabine; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Multivariate Analysis; Neoplasm Metastasis; Neoplasm Recurrence, Local; Oxonic Acid; Tegafur

To assess, in a randomized, phase 2 trial, the efficacy and safety of chemoradiotherapy with or without induction chemotherapy (ICT) of S1 and oxaliplatin for esophageal cancer.. Patients with stage II, III, or IVA esophageal cancer were randomly allocated to either 2 cycles of ICT (oxaliplatin 130 mg/m(2) on day 1 and S1 at 40 mg/m(2) twice daily on days 1-14, every 3 weeks) followed by concurrent chemoradiotherapy (CCRT) (46 Gy, 2 Gy/d with oxaliplatin 130 mg/m(2) on days 1 and 21 and S1 30 mg/m(2) twice daily, 5 days per week during radiation therapy) and esophagectomy (arm A), or the same CCRT followed by esophagectomy without ICT (arm B). The primary endpoint was the pathologic complete response (pCR) rate.. A total of 97 patients were randomized (arm A/B, 47/50), 70 of whom underwent esophagectomy (arm A/B, 34/36). The intention-to-treat pCR rate was 23.4% (95% confidence interval [CI] 11.2-35.6%) in arm A and 38% (95% CI 24.5% to 51.5%) in arm B. With a median follow-up duration of 30.3 months, the 2-year progression-free survival rate was 58.4% in arm A and 58.6% in arm B, whereas the 2-year overall survival rate was 60.7% and 63.7%, respectively. Grade 3 or 4 thrombocytopenia during CCRT was more common in arm A than in arm B (35.4% vs 4.1%). The relative dose intensity of S1 (89.5% ± 20.6% vs 98.3% ± 5.2%, P=.005) and oxaliplatin (91.4% ± 16.8% vs 99.0% ± 4.2%, P=.007) during CCRT was lower in arm A compared with arm B. Three patients in arm A, compared with none in arm B, died within 90 days after surgery.. Combination chemotherapy of S1 and oxaliplatin is an effective chemoradiotherapy regimen to treat esophageal cancer. However, we failed to show that the addition of ICT to the regimen can improve the pCR rate.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Chemoradiotherapy; Confidence Intervals; Drug Administration Schedule; Drug Combinations; Esophageal Neoplasms; Esophagectomy; Humans; Induction Chemotherapy; Intention to Treat Analysis; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Prospective Studies; Tegafur

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

This randomised, open-label, multicenter phase II study compared progression-free survival (PFS) of S-1 plus oxaliplatin (SOX) with that of S-1 alone in patients with gemcitabine-refractory pancreatic cancer.. Patients with confirmed progressive disease following the first-line treatment with a gemcitabine-based regimen were randomised to receive either S-1 (80/100/120 mg day(-1) based on body surface area (BSA), orally, days 1-28, every 6 weeks) or SOX (S-1 80/100/120 mg day(-1) based on BSA, orally, days 1-14, plus oxaliplatin 100 mg m(-2), intravenously, day 1, every 3 weeks). The primary end point was PFS.. Between January 2009 and July 2010, 271 patients were randomly allocated to either S-1 (n=135) or SOX (n=136). Median PFS for S-1 and SOX were 2.8 and 3.0 months, respectively (hazard ratio (HR)=0.84; 95% confidence interval (CI), 0.65-1.08; stratified log-rank test P=0.18). Median overall survival (OS) was 6.9 vs 7.4 months (HR=1.03; 95% CI, 0.79-1.34; stratified log-rank test P=0.82). The response rate (RR) was 11.5% vs 20.9% (P=0.04). The major grade 3/4 toxicities (S-1 and SOX) were neutropenia (11.4% and 8.1%), thrombocytopenia (4.5% and 10.3%) and anorexia (12.9% and 14.7%).. Although SOX showed an advantage in RR, it provided no significant improvement in PFS or OS compared with S-1 alone.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Adenosquamous; Deoxycytidine; Drug Combinations; Drug Resistance, Neoplasm; Female; Follow-Up Studies; Gemcitabine; Humans; Male; Middle Aged; Neoplasm Grading; Neoplasm Metastasis; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Pancreatic Neoplasms; Prognosis; Survival Rate; Tegafur

Platinum-based two-drug combination chemotherapy has been standard of care for patients with advanced nonsmall-cell lung cancer (NSCLC). The primary aim was to compare overall survival (OS) of patients with advanced NSCLC between the two chemotherapy regimens. Secondary end points included progression-free survival (PFS), response, safety, and quality of life (QoL).. Patients with previously untreated stage IIIB or IV NSCLC, an Eastern Cooperative Oncology Group performance status of 0-1 and adequate organ function were randomized to receive either oral S-1 80 mg/m(2)/day on days 1-21 plus cisplatin 60 mg/m(2) on day 8 every 4-5 weeks, or docetaxel 60 mg/m(2) on day 1 plus cisplatin 80 mg/m(2) on day 1 every 3-4 weeks, both up to six cycles.. A total of 608 patients from 66 sites in Japan were randomized to S-1 plus cisplatin (n = 303) or docetaxel plus cisplatin (n = 305). OS for oral S-1 plus cisplatin was noninferior to docetaxel plus cisplatin [median survival, 16.1 versus 17.1 months, respectively; hazard ratio = 1.013; 96.4% confidence interval (CI) 0.837-1.227]. Significantly higher febrile neutropenia (7.4% versus 1.0%), grade 3/4 neutropenia (73.4% versus 22.9%), grade 3/4 infection (14.5% versus 5.3%), and grade 1/2 alopecia (59.3% versus 12.3%) were observed in the docetaxel plus cisplatin than in the S-1 plus cisplatin. There were no differences found in PFS or response between the two arms. QoL data investigated by EORTC QLQ-C30 and LC-13 favored the S-1 plus cisplatin.. Oral S-1 plus cisplatin is not inferior to docetaxel plus cisplatin and is better tolerated in Japanese patients with advanced NSCLC.. UMIN000000608.

Topics: Adenocarcinoma; Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Large Cell; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Cisplatin; Docetaxel; Drug Combinations; Female; Follow-Up Studies; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Prognosis; Quality of Life; Survival Rate; Taxoids; Tegafur

Postoperative adjuvant chemotherapy for patients with stage III Colorectal cancer (CRC) is now internationally accepted as standard care for improving patient outcomes. The Adjuvant Chemotherapy Trial of S-1 for Colorectal Cancer (ACTS-CC) confirmed the non-inferiority of S-1 to tegafur/urcail/leucovorin in terms of overall survival and disease-free survival in patients with stage III CRC after curative surgery. However, the 6-month completion rate of S-1 treatment was 76.5% in the ACTS-CC. Therefore, treatment completion remains an unresolved problem.. A randomized phase II trial was designed to evaluate the efficacy and safety of oral daily administration and alternate-day administration of S-1 as adjuvant chemotherapy in curatively resected stage III CRC. Enrolled patients were assigned to either S-1 daily administration (Arm A) or alternate-day S-1 administration (Arm B). Assigned treatment will start within 8 weeks after surgery. In both arms, S-1 dosing (oral) will be based on body surface area (80 mg/day for body surface area<1.25 m2, 100 mg/day for 1.25-1.5 m2, or 60 mg/day for >1.5 m2). In Arm A, S-1 will be administered orally for 28 days, followed by a 14-day rest. Administration will be conducted for 24 weeks from the date of therapy start. In Arm B, S-1 will be administered orally on alternate days for 28 weeks from the date of the start of therapy. After treatment, all patients will be observed without additional therapy unless recurrent lesions or other cancer lesions occur. The primary endpoint is treatment completion rate. Secondary endpoints include 3-year disease-free survival, compliance, and adverse events.. Previously, S-1 alternate-day intake maintained the efficacy of chemotherapy while reducing adverse effects for patients with R0-resected stage II/III gastric cancer. Improvement of chemotherapy completion rate for patients with colorectal cancer will lead to an improved patient prognosis. Therefore, a randomized phase II trial has been designed to examine the efficacy of alternate-day versus current standard daily S-1 administration as adjuvant chemotherapy for R0-resected stage III colorectal cancer.. This study was registered on 18 February 2014 with University Hospital Medical Information Network Clinical Trials Registry: UMIN000013185.

Topics: Adenocarcinoma; Administration, Oral; Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Body Surface Area; Chemotherapy, Adjuvant; Colonic Neoplasms; Disease-Free Survival; Drug Administration Schedule; Drug Combinations; Drug Dosage Calculations; Humans; Medication Adherence; Middle Aged; Oxonic Acid; Rectal Neoplasms; Research Design; Tegafur; Young Adult

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

Metastatic colorectal cancer carries a poor prognosis and cannot be cured by currently available therapy. Chemotherapy designed to prolong survival and improve the quality of life (QOL) of patients is the mainstay of treatment. Standard regimens of FOLFOX/bevacizumab and CapeOX/bevacizumab can cause neurotoxicity, potentially disrupting treatment. The results of 3 phase II studies of combination therapy with S-1, irinotecan, and bevacizumab showed comparable efficacy to mFOLFOX6/bevacizumab and CapeOX/bevacizumab, without severe neurotoxicity. Therefore, the establishment and evaluation of S-1-containing irinotecan-based regimens for first-line treatment are expected to become more important.. The TRICOLORE trial is a multicenter, randomized, open-label, controlled phase III study which aims to evaluate the non-inferiority of combination therapy with S-1/irinotecan/bevacizumab (a 3-week regimen [SIRB] or 4-week regimen [IRIS/bevacizumab]) to oxaliplatin-based standard treatment (mFOLFOX6/bevacizumab or CapeOX/bevacizumab) in patients with metastatic colorectal cancer who had not previously received chemotherapy. Patients will be randomly assigned to either the control group (mFOLFOX6/bevacizumab or CapeOX/bevacizumab) or study group (SIRB or IRIS/bevacizumab). The target sample size is 450 patients. The primary endpoint is progression-free survival (PFS), and the secondary endpoints are overall survival (OS), response rate (RR), time to treatment failure (TTF), relative dose intensity (RDI), the incidence and severity of adverse events, quality of life (QOL), quality-adjusted life years (QALY), health care costs, and relations between biomarkers and treatment response (translational research, TR).. The results of this study will provide important information that will help to improve the therapeutic strategy for metastatic colorectal cancer, and we believe that this study is very meaningful from the perspective of comparative effectiveness research.. UMIN000007834.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Clinical Trials, Phase III as Topic; Colorectal Neoplasms; Cost-Benefit Analysis; Disease-Free Survival; Drug Combinations; Female; Fluorouracil; Health Care Costs; Humans; Irinotecan; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Quality of Life; Tegafur; Young Adult

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

The purpose of this study was to evaluate the rate of pathologic complete response (pCR) in patients with locally advanced rectal cancer (LARC) treated with neoadjuvant chemoradiation therapy (CRT) with leucovorin (FL) versus irinotecan/S-1 (IS).. Patients with resectable LARC (clinical stage T3/4, lymph node positive, or both) were randomly assigned to receive preoperative radiation (45-50.4 Gy in 25 to 28 daily fractions) and concomitant chemotherapy either with a bolus injection of FL (400 mg/m(2)/day 5-fluorouracil and 20 mg/m(2)/day leucovorin) for 3 consecutive days every 4 weeks for 2 cycles (FL group) or with 40 mg/m(2) irinotecan on days 1, 8, 15, 22, and 29, and 35 mg/m(2) S-1 twice on the day of irradiation (IS group). Curative surgery was performed approximately 4 to 8 weeks after the completion of CRT. The postoperative chemotherapy regimen was FL with a primary endpoint of a pCR rate evaluation.. One hundred forty-two eligible patients were randomly assigned, and the median follow-up duration was 43.8 months (95% confidence interval, 40.8-46.8 months). One hundred thirty-three patients (93.7%) of 142 underwent total mesorectal excision; pCR was achieved in 11 (16.7%) of 66 patients in the FL group and 17 (25.8%) of 67 patients in the IS group (P=.246). When good responders were defined as patients with Mandard grades 1 and 2, the rate of good responders was significantly higher in the IS group than in the FL group (54.6% vs 36.4%, respectively, P=.036). The preoperative rates of grade 3 and 4 toxicities were higher in the IS group (7.0%) than in the FL group (1.4%, P=.095). The 3-year disease-free survival was not significantly different between the 2 groups (79.7% vs 76.6%, respectively, P=.896).. IS-based preoperative CRT did not increase pCR rate, but it did increase acute toxicities compared with standard 5-FU treatment. Therefore, further investigation is needed.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Chemoradiotherapy, Adjuvant; Chi-Square Distribution; Confidence Intervals; Disease-Free Survival; Drug Administration Schedule; Drug Combinations; Female; Fluorouracil; Humans; Induction Chemotherapy; Irinotecan; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Oxonic Acid; Rectal Neoplasms; Tegafur

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

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

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 is a novel oral anticancer agent containing a combination of two modulators and tegafur. We conducted a phase I study of concurrent chemoradiotherapy with S-1 for head and neck cancer.. S-1 was administered once daily, and radiotherapy was performed by 2 Gy/day, five days/week, for a total of 30 fractions. S-1 dosage was started at level 1 (55.3 mg/m(2)/day), and was increased to level 2 (66.7 mg/m(2)/day).. A total of 12 patients were registered. Concerning hematological toxicities, no grade ≥3 or more hematological toxicity was confirmed at any level. With regard to non-hematological toxicities, at level 2, three cases of grade 3 mucositis and two cases of grade 3 dermatitis were confirmed.. The results showed that the maximum tolerated dose was level 2 and that dose-limiting toxicity was mucositis. Having determined that the recommended dose is level 1, we have begun the phase II clinical study.

Topics: Adenocarcinoma; Administration, Oral; Adult; Aged; Carcinoma, Squamous Cell; Chemoradiotherapy; Dose Fractionation, Radiation; Dose-Response Relationship, Drug; Drug Combinations; Female; Follow-Up Studies; Head and Neck Neoplasms; Humans; Male; Maximum Tolerated Dose; Middle Aged; Neoplasm Staging; Oxonic Acid; Prognosis; Tegafur; Young Adult

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

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

Here, we reported an interim analysis of feasibility and safety in the first 10 cases of 30 cases in a phase II trial of intravenous and intraperitoneal paclitaxel combined with S-1 for gemcitabine-refractory pancreatic cancer with malignant ascites.. Paclitaxel was administered intravenously at 50 mg/m2 and intraperitoneally at 20 mg/m2 on days 1 and 8 every 3 weeks, and S-1 was administered at 80 mg/m2/day for 14 consecutive days, followed by 7-day rest.. Between April 2011 and February 2012, ten patients were enrolled. A partial response was achieved in two patients (20%) and a disease control rate of 50%. The median time to progression and overall survival were 2.1 and 3.4 months, respectively. Malignant ascites was completely resolved in two patients (20%). Major grade 3/4 adverse events were myelosuppression including neutropenia (50%) and catheter-related infection (10%).. This novel combination chemotherapy was feasible and showed promising results in pancreatic cancer patients with malignant ascites (clinical trial registration number: UMIN000005306).

Topics: Adenocarcinoma; Aged; Alopecia; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Ascites; Catheter-Related Infections; Deoxycytidine; Drug Administration Schedule; Drug Combinations; Drug Resistance, Neoplasm; Fatigue; Feasibility Studies; Female; Gastrointestinal Diseases; Gemcitabine; Hematologic Diseases; Humans; Infusions, Intravenous; Infusions, Parenteral; Male; Middle Aged; Oxonic Acid; Paclitaxel; Pancreatic Neoplasms; Prospective Studies; Salvage Therapy; 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

For patients with advanced non-small cell lung adenocarcinoma that fail to respond to first-line chemotherapy and that do not involve epidermal growth factor receptor (EGFR) mutations, previous empirical analysis showed that a single second-line chemotherapy agent may be inadequate for the control of further tumor development. This study examines the combination of S-1 drugs and nedaplatin that has no cross-resistance to first-line treatments; 179 cases of IIIb-IV stage non-small-cell lung adenocarcinoma that failed to respond to first-line chemotherapy were included, and these subjects did not have mutated EGFRs. In the present study, S-1 plus nedaplatin chemotherapy was better than standard second-line chemotherapy options in the treatment of advanced lung adenocarcinoma that did not involve EGFR mutations and that failed to respond to first-line chemotherapy. Additionally, the combination of S-1 and nedaplatin seemed to be well tolerated, making this chemotherapy technique a potentially strong candidate for the treatment of advanced non-small-cell lung adenocarcinoma.

Topics: Adenocarcinoma; Adult; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Disease-Free Survival; Drug Combinations; Drug Therapy; ErbB Receptors; Female; Humans; Logistic Models; Lung Neoplasms; Male; Middle Aged; Multivariate Analysis; Mutation; Nausea; Neoplasm Staging; Organoplatinum Compounds; Oxonic Acid; Tegafur; Treatment Failure; Treatment Outcome; Vomiting

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 (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

S-1 combination with oxaliplatin and oral leucovorin (SOL regimen) demonstrated well tolerability and efficacy in Japanese patients with metastatic colorectal cancer. The present study was conducted to confirm the safety and efficacy of SOL regimen in Chinese patients with untreated metastatic colorectal cancer.. We planned to enroll 20 untreated, unresectable or recurrent advanced colorectal adenocarcinoma patients. The treatment schedule comprised S-1 40-60 mg bid and leucovorin (LV) 25 mg bid for one week and 2 hour drip infusion of oxaliplatin (L-OHP) 85 mg/m2 on day 1, 1 week off, repeated every 2 weeks. The primary study endpoints were safety. Secondary endpoints were overall response rate (ORR), progression free survival (PFS) and time to treatment failure (TTF).. A total of 21 patients (median age: 65; range: 30-79) were enrolled between August 2009 and December 2009. There were 15 patients with colon cancer and 6 with rectal cancer. Data cut-off date was April, 2011. In total, 168 cycles were administered (median 7 per patient; range 1-19). The common toxicities were neutropenia, thrombocytopenia, fatigue, diarrhea, nausea/vomiting, peripheral neurotoxicity and anemia. The common grade 3/4 adverse events were diarrhea (19.1%), thrombocytopenia (9.5%) and nausea/vomiting (9.5%). Dose-adjusted was executed in 11 patients owing to AEs, including S-1 in 9 cases and L-OHP in 9 cases. Death due to adverse event was not observed. Responses were evaluated in 20 patients with measurable disease, the overall response rate was 45% (1 CR and 8 PR: 95% CI, 23-68%) and the disease control rate was 70% (95% CI, 46%-88%). Pathologic complete response was observed in 1 patient after 5 cycles of treatment. Median PFS was 9.0 (95% CI, 3.7- 14.4) months. Median TTF was 4.2 (95% Cl, 3.5-5.6) months.. This result indicates that the SOL regimen is well tolerated and effective in Chinese patients with metastatic colorectal cancer.

Topics: Adenocarcinoma; Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; China; Colorectal Neoplasms; Disease Progression; Disease-Free Survival; Drug Administration Schedule; Drug Combinations; Feasibility Studies; Female; Humans; Infusions, Intravenous; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Tegafur; Time Factors; Treatment Outcome

To determine the recommended dose (RD) in concurrent conformal radiotherapy with S-1 and cisplatin chemotherapy for inoperable stage III non-small-cell lung cancer.. Eligible patients with inoperable stage III non-small-cell lung cancer, age ≥ 20 years, performance status 0-1 received 4 cycles of intravenous cisplatin (60 mg/m(2), day 1) and oral S-1 (80, 100, or 120 mg based on body surface area, days 1-14) repeated every 4 weeks. Radiation doses were 66, 70, and 74 Gy for arms 1, 2, and 3, respectively.. A total of 24 patients were enrolled in our study, including 6 in arm 1, 6 in arm 2, and 12 in arm 3. The patients consisted of 14 men and 10 women, with a median age of 63 years (range, 44-73 years). The median follow-up was 27.3 months (range, 8.5-42.6 months) for all patients and 33.9 months (range, 15.2-42.6 months) for those still alive. Grade 3 febrile neutropenia, lung toxicities, and heart toxicities occurred in 2, 2, and 2 patients, respectively. Dose-limiting toxicity occurred in 2, none, and 1 patient in arms 1, 2, and 3, respectively. The median survival was not reached, and the 2-year survival rate was 70% (95% CI, 51%-89%). Two-year local relapse-free survival and distant metastasis-free survival were 74% (95% CI, 56%-92%) and 45% (95% CI, 25%-65%), respectively.. High-dose radiotherapy with S-1 and cisplatin is feasible, and 74 Gy was determined as the recommended dose.

Topics: Adenocarcinoma; Adenocarcinoma, Bronchiolo-Alveolar; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Large Cell; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Chemoradiotherapy; Cisplatin; Dose Fractionation, Radiation; Drug Combinations; Female; Follow-Up Studies; Humans; Imaging, Three-Dimensional; Lung Neoplasms; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Oxonic Acid; Prognosis; Radiotherapy, Conformal; Survival Rate; Tegafur

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

To evaluate the efficacy and safety of combined gemcitabine and S-1 as first-line chemotherapy for patients with locally advanced or metastatic pancreatic cancer.. This study included patients who had been diagnosed with unresectable, locally advanced or metastatic adenocarcinoma arising from the pancreas, which was histologically or cytologically confirmed and involved at least 1 unidimensionally measurable lesion. The regimen consisted of intravenous 1,000 mg/m(2) gemcitabine on day 1 and 8 combined with oral S-1 on days 1-14 every 21 days. The dosage of S-1 was based on the body surface area (BSA) as follows: 40 mg bid (total 80 mg/day) for a BSA of <1.25, 50 mg bid (total 100 mg/day) for a BSA of ≥1.25 but <1.5, and 60 mg bid (total 120 mg/day) for a BSA of ≥1.5. Treatment consisted of at least 2 courses unless rapid disease progression was noted. The primary end points were the response and disease control rates, and the secondary end points were toxicity and survival.. Thirty-seven patients were enrolled between August 2005 and December 2010. The median number of chemotherapy cycles was 4 (range 1-28 cycles). Response to treatment could be evaluated in 31 patients. None of the patients showed complete response, but 5 achieved partial response. The response rate was thus 13.5 % [95 % confidence interval (CI) 2.7-24.3 %] in the intent-to-treat population. Sixteen patients (43.2 %; 95 % CI 27-59.5 %) showed stable disease, and the overall disease control rate was 56.8 % (95 % CI 40.6-72.9 %). For all 37 patients, the median progression-free survival was 4.6 months (95 % CI 1.8-7.6 month), and the median overall survival was 9.4 month (95 % CI 5.8-12.6 month). Chemotherapy-related grade 3/4 hematological toxicities were neutropenia (36.1 %), leucopenia (22.2 %), and anemia (13.9 %). The non-hematological toxicities were generally mild.. Combination chemotherapy with gemcitabine and S-1 was effective, convenient, and safe in patients with advanced pancreatic cancer.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Deoxycytidine; Disease-Free Survival; Drug Combinations; Female; Gemcitabine; Humans; Male; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Pancreatic Neoplasms; Prospective Studies; Survival Rate; 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 trial was to evaluate the efficacy and toxicity of S-1 and concurrent radiation therapy for locally advanced pancreatic cancer (PC).. Locally advanced PC patients with histologically or cytologically confirmed adenocarcinoma or adenosquamous carcinoma, who had no previous therapy were enrolled. Radiation therapy was delivered through 3 or more fields at a total dose of 50.4 Gy in 28 fractions over 5.5 weeks. S-1 was administered orally at a dose of 80 mg/m2 twice daily on the day of irradiation during radiation therapy. After a 2- to 8-week break, patients received a maintenance dose of S-1 (80 mg/m2/day for 28 consecutive days, followed by a 14-day rest period) was then administered until the appearance of disease progression or unacceptable toxicity. The primary efficacy endpoint was survival, and the secondary efficacy endpoints were progression-free survival, response rate, and serum carbohydrate antigen 19-9 (CA19-9) response; the safety endpoint was toxicity.. Of the 60 evaluable patients, 16 patients achieved a partial response (27%; 95% confidence interval [CI], 16%-40%). The median progression-free survival period, overall survival period, and 1-year survival rate of the evaluable patients were 9.7 months (95% CI, 6.9-11.6 months), 16.2 months (95% CI, 13.5-21.3 months), and 72% (95%CI, 59%-82%), respectively. Of the 42 patients with a pretreatment serum CA19-9 level of ≥100 U/ml, 34 (81%) patients showed a decrease of greater than 50%. Leukopenia (6 patients, 10%) and anorexia (4 patients, 7%) were the major grade 3-4 toxicities with chemoradiation therapy.. The effect of S-1 with concurrent radiation therapy in patients with locally advanced PC was found to be very favorable, with only mild toxicity.

Topics: Adenocarcinoma; Administration, Oral; Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; CA-19-9 Antigen; Carcinoma, Adenosquamous; Chemoradiotherapy; Disease-Free Survival; Dose Fractionation, Radiation; Drug Administration Schedule; Drug Combinations; Female; Humans; Japan; Maintenance Chemotherapy; Male; Middle Aged; Oxonic Acid; Pancreatic 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

A phase I dose-escalation study was performed to investigate the safety and pharmacokinetics of the combination of S-1 and gefitinib in patients with pulmonary adenocarcinoma who had failed previous chemotherapy.. Patients received gefitinib at a fixed daily oral dose of 250 mg, and S-1 was administered on days 1-14 every 21 days at doses starting at 60 mg/m(2) (level 1) and escalating to 80 mg/m(2) (level 2). The primary end point of the study was determination of the recommended dose for S-1 given in combination with a fixed dose of gefitinib.. Twenty patients were enrolled in the study. Two of the first six patients at dose level 2 experienced a dose-limiting toxicity (elevation of alkaline phosphatase of grade 3 in one patient; elevations of aspartate and alanine aminotransferases of grade 3 in the other). The recommended dose was thus determined as level 2, and an additional 11 patients were assigned to this level. All observed adverse events were well managed. The response rate was 50 % (10 of 20 patients), and the median progression-free survival (PFS) and overall survival times were 10.5 and 21.2 months, respectively. In EGFR mutation-positive patients (n = 9), seven patients achieved an objective response and the median PFS was 12.4 months, whereas none with wild-type EGFR (n = 6) responded. No pharmacokinetic interaction between S-1 and gefitinib was detected.. The combination of S-1 and gefitinib is well tolerated and appears to possess activity against EGFR mutation-positive NSCLC.

Topics: Adenocarcinoma; Adenocarcinoma of Lung; Aged; Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Female; Gefitinib; Humans; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Quinazolines; 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

S-1 is a new oral fluoropyrimidine anticancer agent shown to be effective for pancreatic cancer. In a previous phase I trial, we evaluated the safety of S-1 combined with radiotherapy to determine the maximum tolerated dose and dose-limiting toxicity in patients with unresectable pancreatic cancer. The recommended dose of S-1 for phase II trials of chemoradiotherapy was determined as 80 mg/m(2)/day given on days 1-21 of a 28-day cycle. This phase II study was conducted to further evaluate the efficacy and toxicity of radiotherapy combined with S-1 (UMIN000004794).. Eligible patients had locally advanced and unresectable pancreatic cancer without distant metastases, an Eastern Cooperative Oncology Group performance status of 0-1, adequate organ and marrow functions, and no prior anticancer therapy. Patients initially received 4 weeks of chemoradiotherapy. S-1 was given orally at a dose of 80 mg/m(2)/day twice daily on days 1-21. Radiotherapy was delivered in fractions of 1.25 Gy twice daily, 5 days per week for 4 weeks (total dose: 50 Gy in 40 fractions). One month after the completion of chemoradiotherapy, S-1 was administered for 14 days followed by a 14-day rest period. This cycle was repeated as maintenance therapy until disease progression or unacceptable toxicity.. Fifty patients were enrolled in this phase II study. Median follow-up was 14.6 months (range 5.4-58.9 months). Forty-three patients (86%) completed the scheduled course of chemoradiotherapy. There was no treatment-related death or grade 4 toxicity. The major toxic effects were leukopenia and nausea. The objective tumor response according to the Response Evaluation Criteria in Solid Tumours criteria was partial response in 15 patients (30%) (95% confidence interval (CI), 18-45%), stable disease in 23 (46%), and progressive disease in 12 (24%). Median progression-free survival and median overall survival were 6.7 months (95% CI, 4.7-11.2 months) and 14.3 months (95% CI, 10.8-20.8 months), respectively. Survival rates at 1 and 2 years were 62 and 27%, respectively.. Combination therapy with S-1 and radiation in patients with locally advanced and unresectable pancreatic cancer is considered a promising, well-tolerated regimen that can be recommended as an effective treatment for locally advanced pancreatic cancer.

Topics: Adenocarcinoma; Administration, Oral; Aged; Antimetabolites, Antineoplastic; Dose-Response Relationship, Drug; Drug Combinations; Female; Follow-Up Studies; Humans; Japan; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Pancreatic Neoplasms; Radiotherapy, Conformal; Retrospective Studies; Survival Rate; Tegafur

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 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

To evaluate the efficacy and safety of the combination of gemcitabine (GEM) and S-1 (GS) in comparison to GEM alone (G) for unresectable pancreatic cancer.. In this multicenter randomized phase II study, we randomly assigned unresectable pancreatic cancer patients to either the GS group or the G group. The GS group regimen consists of intravenous 1,000 mg/m(2) GEM during 30 min on days 1 and 8, combined with 80 mg/m(2) oral S-1 twice daily on days 1-14, repeated every 3 weeks. On the other hand, the G group regimen consists of intravenous 1,000 mg/m(2) GEM on days 1, 8, and 15, repeated every 4 weeks. The primary endpoint was objective response rate (ORR). Secondary end points included treatment toxicity, clinical response benefit, progression-free survival (PFS), and overall survival.. We registered 117 patients from 16 institutions between June 2007 and August, 2010. The ORR of the GS group was 28.3%, whereas that of the G group was 6.8%. This difference was statistically significant (P = 0.005). The disease control rate was 64.2% in the GS group and 44.1% in the G group. Median PFS was 6.15 months in the GS group and 3.78 month in the G group. This was also statistically significant (P = 0.0007). Moreover, the median overall survival (OS) of the GS group was significantly longer than that of the G group (13.7 months vs. 8.0 months; P = 0.035). The major grade 3-4 adverse events were neutropenia (54.7% in the GS group and 22.0% in the G group), thrombocytopenia (15.1% in the GS group and 5.1% in the G group), and skin rash (9.4% in the GS group).. The GS group showed stronger anticancer activity than the G group, suggesting the need for a large randomized phase III study to confirm GS advantages in a specific subset.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Deoxycytidine; Disease-Free Survival; Drug Combinations; Female; Gemcitabine; Humans; Male; Middle Aged; Oxonic Acid; Pancreatic Neoplasms; Survival Rate; Tegafur; Time Factors; 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 study evaluated long-term outcomes for patients who received adjuvant gemcitabine plus S-1 chemotherapy after resection for pancreatic carcinoma.. Seventy patients who underwent surgical resection of pancreatic carcinoma were enrolled prospectively into this study. All patients received adjuvant chemotherapy with 10 cycles of gemcitabine plus S-1 every 2 weeks. Each cycle consisted of intravenous gemcitabine 700 mg/m(2) on day 1 and oral S-1 50 mg/m(2) for seven consecutive days, followed by a 1-week pause of chemotherapy. Long-term survival results of adjuvant gemcitabine plus S-1 chemotherapy were analyzed for this cohort.. Median follow-up time was 51.2 months. Sixty percent of patients had node-positive disease and 79% of patients underwent R0 resection. Fifty-six patients (80%) completed adjuvant chemotherapy. Median overall and disease-free survival times were 35.4 and 23.8 months, respectively. Actuarial overall and disease-free survival rates were 89% and 64% at 1 year, 64% and 50% at 2 years, and 33% and 33% at 5 years, respectively. Only negative lymph node metastasis (P = 0.010) independently correlated with long-term survival by multivariate analysis.. Long-term results of adjuvant gemcitabine plus S-1 chemotherapy suggest this regimen may be safe and promising as treatment for this patient population.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Analysis of Variance; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Cohort Studies; Deoxycytidine; Disease-Free Survival; Drug Combinations; Female; Gemcitabine; Humans; Japan; Kaplan-Meier Estimate; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Pancreatic Neoplasms; Prospective Studies; Tegafur; Time Factors; Treatment Outcome

In Japan, a study comparing the effectiveness and safety of irinotecan plus S-1 (IRIS) with those of a combination of 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) as second-line treatment in patients with advanced or recurrent colorectal cancer demonstrated that IRIS was non-inferior to FOLFIRI. We previously reported that IRIS is also effective as first-line treatment.. Eligibility criteria included inoperable recurrent colorectal cancer with a confirmed diagnosis of adenocarcinoma, age ≥20 years, and no history of prior chemotherapy. S-1 (40-60 mg twice daily) was given orally on Days 1 to 14, and irinotecan (100 mg/m(2)) and bevacizumab (5 mg/kg) were given intravenously on Days 1 and 15 of a 28-day cycle. The primary endpoint was safety. The secondary endpoints included overall response (OR), progression-free survival (PFS), and overall survival (OS).. A total of 52 eligible patients were enrolled from October 2007 through March 2009. In safety analysis, the incidences of grade 3 or 4 adverse reactions were as follows: neutropenia, 27%; hypertension, 21%; and diarrhea, 17%. The overall response rate was 57.7%. Median progression-free survival was 16.7 months.. IRIS plus bevacizumab is a well-tolerated, highly effective chemotherapeutic regimen that is easy to administer.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Colorectal Neoplasms; Diarrhea; Drug Administration Schedule; Drug Combinations; Female; Humans; Hypertension; Irinotecan; Japan; Kaplan-Meier Estimate; Male; Middle Aged; Neoplasm Staging; Neutropenia; Oxonic Acid; Severity of Illness Index; Tegafur; Treatment Outcome

We evaluated the efficacy and safety of a combination of S-1 and cisplatin (SP) versus gemcitabine and cisplatin (GP) as first-line therapy for advanced biliary tract adenocarcinoma (ABTA).. Patients were randomized to receive cisplatin (60 mg/m(2) intravenously [IV] on Day 1) plus S-1 (40 mg/m(2) bid orally on Days 1-14) or gemcitabine (1000 mg/m(2) IV at 10 mg/m(2)/min on Days 1 and 8) every three weeks. The primary end point was six-month progression-free survival (PFS).. Of 96 eligible patients, 49 were randomized to GP and 47 to SP. At a median follow-up time of 14.2 months, the six-month PFS rates were 43.8% and 34.7%, respectively [unadjusted HR (GP/SP) =0.85, 95% CI 0.52-1.36]. The median OS values in the GP and SP groups were 10.1 months and 9.9 months, respectively [unadjusted HR (GP/SP) =0.72, 95% CI 0.45-1.17]. Grade 3-4 toxicities in the GP and SP groups included neutropenia (49.0% vs. 31.8%), anemia (22.4% vs. 2.3%), thrombocytopenia (22.4% vs. 4.5%), and asthenia (4.1% vs. 2.1%).. Both GP and SP has comparable efficacy with favorable safety profile as first-line treatment for ABTA. (ClinicalTrials.gov number NCT 01375972).

Topics: Adenocarcinoma; Adult; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Asthenia; Biliary Tract Neoplasms; Cisplatin; Deoxycytidine; Disease-Free Survival; Drug Administration Schedule; Drug Combinations; Female; Follow-Up Studies; Gemcitabine; Humans; Infusions, Intravenous; Kaplan-Meier Estimate; Male; Middle Aged; Neutropenia; Oxonic Acid; Severity of Illness Index; Tegafur; Thrombocytopenia; Treatment Outcome

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

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

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

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

To perform a Phase I study of preoperative chemoradiation (CRT) with S-1, a novel oral fluoropyrimidine, plus oxaliplatin in patients with locally advanced rectal cancer, to determine the maximum tolerated dose and the recommended dose.. Radiotherapy was delivered to a total of 45 Gy in 25 fractions and followed by a coned-down boost of 5.4 Gy in 3 fractions. Concurrent chemotherapy consisted of a fixed dose of oxaliplatin (50 mg/m2/week) on Days 1, 8, 22, and 29 and escalated doses of S-1 on Days 1-14 and 22-35. The initial dose of S-1 was 50 mg/m2/day, gradually increasing to 60, 70, and 80 mg/m2/day. Surgery was performed within 6±2 weeks.. Twelve patients were enrolled and tolerated up to Dose Level 4 (3 patients at each dose level) without dose-limiting toxicity. An additional 3 patients were enrolled at Dose Level 4, with 1 experiencing a dose-limiting toxicity of Grade 3 diarrhea. Although maximum tolerated dose was not attained, Dose Level 4 (S-1 80 mg/m2/day) was chosen as the recommended dose for further Phase II studies. No Grade 4 toxicity was observed, and Grade 3 toxicities of leukopenia and diarrhea occurred in the same patient (1 of 15, 6.7%). Pathologic complete responses were observed in 2 of 15 patients (13.3%).. The recommended dose of S-1 was determined to be 80 mg/m2/day when combined with oxaliplatin in preoperative CRT, and a Phase II trial is now ongoing.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Diarrhea; Drug Administration Schedule; Drug Combinations; Female; Humans; Male; Maximum Tolerated Dose; Middle Aged; Nausea; Neutropenia; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Preoperative Care; Radiotherapy Dosage; Rectal Neoplasms; Tegafur; Thrombocytopenia; Vomiting

Curcumin, a plant-derived natural polyphenol, could be a promising anti-cancer drug and shows synergic effects with cytotoxic agents. We evaluated the safety and feasibility of combination therapy using curcumin with gemcitabine-based chemotherapy.. Gemcitabine-resistant patients with pancreatic cancer received 8 g oral curcumin daily in combination with gemcitabine-based chemotherapy. The primary endpoint was safety for phase I and feasibility of oral curcumin for phase II study.. Twenty-one patients were enrolled. No dose-limiting toxicities were observed in the phase I study and oral curcumin 8 g/day was selected as the recommended dose for the phase II study. No patients were withdrawn from this study because of the intolerability of curcumin, which met the primary endpoint of the phase II study, and the median compliance rate of oral curcumin was 100% (Range 79-100%). Median survival time after initiation of curcumin was 161 days (95% confidence interval 109-223 days) and 1-year survival rate was 19% (4.4-41.4%). Plasma curcumin levels ranged from 29 to 412 ng/ml in five patients tested.. Combination therapy using 8 g oral curcumin daily with gemcitabine-based chemotherapy was safe and feasible in patients with pancreatic cancer and warrants further investigation into its efficacy.

Topics: Adenocarcinoma; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Curcumin; Deoxycytidine; Drug Combinations; Drug Resistance, Neoplasm; Drug Synergism; Female; Gemcitabine; Humans; Male; Medication Adherence; Middle Aged; Oxonic Acid; Pancreatic Neoplasms; Survival Rate; Tegafur

Standard second-line chemotherapies for non-small cell lung cancer (NSCLC) have been established but have limited clinical relevance. S-1 is a recently developed agent with potential activity against NSCLC.. Patients with confirmed NSCLC recurrence after previous single- or two-regimen chemotherapy with platinum, performance status of 0 to 1, adequate organ functions, and measurable lesions were treated with S-1 (60 mg/m/d, twice a day) on days 1 to 14 and gemcitabine (1000 mg/m) on days 8 and 15, which were repeated every 3 weeks until tumor progression.. Treatment was administered for a median of 4 courses (range, 1-13) over a median of 125-day period in 34 patients. The overall response rate was 23.5% (no complete response and eight partial response; 95% confidence interval: 9.1-38.0%). The median progression-free and overall survival times were 6.6 and 19.9 months, respectively. The 1- and 2-year survival rates were 58.8 and 30.9%, respectively. Toxicity was mild during the entire treatment period, except for three grade 3 interstitial pneumonia.. The primary end point was met with the relatively high overall response rate. Randomized phase III studies for elucidating survival outcome of the regimen are warranted.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Large Cell; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Deoxycytidine; Drug Combinations; Drug Resistance, Neoplasm; Female; Gemcitabine; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Oxonic Acid; Platinum; Salvage Therapy; Survival Rate; Tegafur; Time Factors; 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

Currently available agents for the treatment of advanced stage non-small cell lung cancer (NSCLC) have limited efficacy. S-1 is a novel formulation of oral fluoropyrimidine shown to be tolerable and active in patients with NSCLC in Japan. We conducted a multicenter phase II study in previously treated patients with NSCLC to evaluate the efficacy of single-agent S-1 in a predominantly non-Asian population.. Patients with advanced NSCLC and previously treated with only one line of chemotherapy received oral S-1 at 30 mg/m every 12 hours for 14 consecutive days followed by a 7-day rest until meeting discontinuation criteria. The primary end point was to evaluate the overall response rate.. Fifty-seven patients were accrued from 21 centers across the United States. Overall response rates and stable disease according to independent review were 7.1% and 48.2%, respectively, with a disease control rate of 55.3%. Progression-free survival was 2.9 months, median overall survival 7.3 months, and 1-year survival 31.6%. There were no significant differences in survival according to histologic subtype. The treatment was well tolerated, with the most common treatment-related side effects being nausea (54%) and diarrhea (49%).. Single-agent S-1 is well tolerated and has activity comparable with the other agents approved for use in recurrent/relapsed NSCLC.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Carcinoma, Large Cell; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Drug Combinations; Female; Follow-Up Studies; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Prognosis; Salvage Therapy; Survival Rate; Tegafur

Advanced biliary cancer is often treated with fluoropyrimidine-based chemotherapy. In this study, we evaluated the efficacy and tolerability of a combination of S-1, an oral fluoropyrimidine prodrug, and oxaliplatin in patients with metastatic biliary cancer.. Patients with histologically confirmed metastatic biliary cancer and no history of radiotherapy or chemotherapy were enrolled. Oxaliplatin was administered intravenously (130 mg m(-2)), followed by 14-day administration of oral S-1 (40 mg m(-2) twice daily) with a subsequent 7-day rest period every 21 days. Pharmacokinetic analysis of S-1 was performed at cycle 1. Patients were genotyped for CYP2A6 polymorphisms ((*)1, (*)4, (*)7, (*)9 or (*)10), and pharmacokinetic and clinical parameters compared according to the CYP2A6 genotype.. In total, 49 patients were evaluated, who received a median of four cycles. The overall response rate was 24.5%. Median progression-free and overall survival was 3.7 and 8.7 months, respectively. The most common haematological grade 3 out of 4 toxicity was neutropenia (14%), while non-hematological grade 3 out of 4 toxicities included anorexia (14%), nausea (12%), asthenia (10%), vomiting (10%), and diarrhoea (4%). Biotransformation of S-1 (AUC(0-24 h) of 5-fluorouracil/AUC(0-24 h) of tegafur) was 1.85-fold higher for the *1/*1 group than for the other groups (90% confidence interval 1.37-2.49). Diarrhoea (P=0.0740), neutropenia (P=0.396), and clinical efficacy (response rate, P=0.583; PFS, P=0.916) were not significantly associated with CYP2A6 genotype, despite differences in 5-FU exposure.. The combination of S-1 and oxaliplatin appears to be active and well tolerated in patients with metastatic biliary cancer, and thus is feasible as a therapeutic modality. CYP2A6 genotypes are associated with differences in the biotransformation of S-1. However, the impact of the CYP2A6 polymorphism on variations in clinical efficacy or toxicity requires further evaluation.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Aryl Hydrocarbon Hydroxylases; Biliary Tract Neoplasms; Biomarkers, Pharmacological; Biomarkers, Tumor; Cytochrome P-450 CYP2A6; Drug Combinations; Female; Humans; Inactivation, Metabolic; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Polymorphism, Single Nucleotide; 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 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

This phase II study was designed to evaluate the efficacy and safety of oral fluoropyrimidine S-1 plus irinotecan (IRIS regimen) in patients with previously untreated metastatic colorectal cancer.. The response rate was the primary endpoint. Safety, progression-free survival time, and median survival time were secondary endpoints. The subjects were untreated patients with inoperable advanced colorectal cancer. Irinotecan was administered at a dose of 100 mg/m² (on days 1 and 15). S-1 (40 mg/m²) was administered for 2 weeks (on days 1 to 14) and followed by a 2-week rest.. Forty patients were enrolled. Four patients had grade 4 neutropenia, and six patients had grade 3 diarrhea. No other serious hematologic or nonhematologic adverse reactions occurred, and all patients received IRIS safely on an outpatient basis. The response rate was 52.5% (95% confidence interval [CI], 36.1-68.5%). Median progression-free survival was 8.6 months (95% CI, 5.3-11.9), and median survival time was 23.4 months (95% CI, 15.9-30.8).. IRIS produced a high response rate and could be given safely. IRIS may become a first-line treatment for inoperable or recurrent advanced colorectal cancer.

Topics: Adenocarcinoma; Adult; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colorectal Neoplasms; Drug Combinations; Female; Humans; Irinotecan; Leukopenia; Male; Middle Aged; Neoplasm Recurrence, Local; Neutropenia; Oxonic Acid; Tegafur; Treatment Outcome

S-1 is a rationally designed oral agent that combines the 5-fluorouracil prodrug tegafur with gimeracil and oteracil, which inhibit 5-fluorouracil degradation by dihydropyrimidine dehydronase and phosphorylation within the gastrointestinal tract, respectively, to increase antineoplastic activity while reducing gastrointestinal toxicity. We investigated the activity and toxicity of S-1 in combination with cisplatin in patients with unresectable non-small cell lung cancer (NSCLC).. Cisplatin, 75 mg/m, was administered intravenously on day 1, with S-1, 25 mg/m PO two times a day, days 1 to 14, every 21 days for a maximum of six cycles. Primary end point was overall response.. A total of 58 patients received at least one cycle of protocol-specified therapy. The best overall response rate was 23.2% (95% confidence interval: 13.0-36.4), and the disease control rate was 67.9%. The median progression-free survival was 4.0 months (95% confidence interval: 3.3-5.5). There did not appear to be any relationship between response to therapy and tumor histology. The most frequently reported adverse events of G3 or more (≥10%) were neutropenia (28%), hyponatremia (19%), diarrhea (17%), hypokalemia (12%), fatigue (10%), dehydration (10%), and deep vein thrombosis (10%).. Although the S-1 + cisplatin regimen used in this study appeared to have a similar level of antitumor activity and toxicity to that of established cisplatin-based doublets in NSCLC, the protocol-specified criteria of sufficient efficacy to warrant further study with an objective response rate ≥30% was not achieved. Therefore, while S-1 appears to be a promising agent in NSCLC, further evaluation should be conducted to determine the optimal S-1-based regimen to take forward for additional study.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Large Cell; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Cisplatin; Drug Combinations; Female; Follow-Up Studies; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Oxonic Acid; Survival Rate; Tegafur; Treatment Outcome

The aim of this multicenter Phase II study was to assess the efficacy and toxicity of gemcitabine and S-1 combination therapy for metastatic pancreatic cancer.. Chemotherapy-naïve patients with histologically or cytologically proven metastatic pancreatic adenocarcinoma were eligible for this study. Gemcitabine was administered at a dose of 1000 mg/m(2) over 30 min on days 1 and 8, and oral S-1 at a dose of 40 mg/m(2) twice daily from days 1 to 14, repeated every 3 weeks.. A total of 55 patients were included and the efficacy and toxicity were analyzed in 54 patients who received at least one dose of gemcitabine and S-1 combination therapy. Although no complete response was seen, a partial response was achieved in 24 patients, resulting in an overall response rate of 44.4% (95% confidence interval: 30.9-58.6%). The median progression-free survival was 5.9 months (95% confidence interval: 4.1-6.9 months) and the median overall survival was 10.1 months (95% confidence interval: 8.5-10.8 months) with a 1-year survival rate of 33.0%. The major Grade 3-4 toxicities were neutropenia (80%), leucopenia (59%), thrombocytopenia (22%), anorexia (17%) and rash (7%). Hematological toxicity was mostly transient and there was only one episode of febrile neutropenia ≥Grade 3.. Gemcitabine and S-1 combination therapy produced a high response rate with good survival in patients with metastatic pancreatic cancer. A randomized Phase III study to confirm the efficacy of gemcitabine and S-1 combination therapy is ongoing.

Topics: Adenocarcinoma; Adult; Aged; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Adenosquamous; Deoxycytidine; Disease-Free Survival; Drug Combinations; Drug Eruptions; Female; Gemcitabine; Humans; Kaplan-Meier Estimate; Leukopenia; Male; Middle Aged; Neoplasm Metastasis; Neutropenia; Oxonic Acid; Pancreatic Neoplasms; Tegafur; Thrombocytopenia; Treatment Outcome

To assess the maximum tolerability of a combination of S-1 and preoperative radiotherapy and to evaluate the feasibility and activity in patients with locally advanced rectal cancer.. Patients (n = 30) with adenocarcinoma of the middle or lower rectum were enrolled in a phase I (n = 9) and/or phase II (n = 21) trial. A total dose of 45 Gy was delivered in 25 fractions over 5 weeks, and S-1 was orally administered twice a day on days 1-14 and 22-35. Surgical resection was scheduled 4-8 weeks after the completion of chemoradiation.. In phase I, the recommended dose (RD) of S-1 was 80 mg/m(2)/day, and the maximum-tolerated dose was never reached. A total of 27 cases, including the 6 RD cases in phase I, were enrolled in phase II. In phase II, a pathological complete response (pCR) was observed in 6/27 patients (22%), pathological downstaging was observed in 21/27 patients (78%), and a tumor volume reduction of 69 ± 22% was obtained. These results were similar to the previously reported pCR rates of 16-18%, pathological downstaging rates of 49-59%, and tumor volume reduction of 68% after chemoradiotherapy with capecitabine. Grade 3 adverse events consisted of one case of leukopenia (4%), 2 cases of anemia (7%) and 3 cases of diarrhea (11%). Overall, the adverse events were very mild. Hand-foot syndrome was not observed.. The efficacy of chemoradiotherapy with S-1 seems to be equivalent to the efficacy reported for chemoradiotherapy with capecitabine, but the adverse events were much milder, although further study is warranted.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Chemoradiotherapy; Combined Modality Therapy; Drug Combinations; Female; Humans; Male; Maximum Tolerated Dose; Middle Aged; Neoadjuvant Therapy; Oxonic Acid; Postoperative Complications; Radiotherapy Dosage; Rectal Neoplasms; Tegafur; Tumor Burden

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

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

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

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

This study was conducted to evaluate the efficacy and safety and to compare dosing schedules of gemcitabine combined with S-1 in chemo-naïve non-small cell lung cancer patients.. Patients with chemo-naïve stage IIIB/IV non-small cell lung cancer were randomized into two treatment arms. Patients were given oral S-1 (60 mg/m/d, twice a day) from days 1 to 14 with gemcitabine (1000 mg/m/d) on days 1 and 8 (arm A) or on days 8 and 15 (arm B). This cycle was repeated every 21 days.. A total of 80 patients were entered in this trial. The primary end point of this study was response rate. The response rates of arm A and arm B were 22.0 and 28.9%, respectively (p = 0.606). Median time to treatment failure in arm A was 3.6 months and 4.8 months in arm B. Median time to progression in arm A was 4.1 months and 5.5 months in arm B. Median survival time in arm A and arm B was 15.5 months and 18.8 months, respectively. The toxicity profile was relatively mild and did not differ very much between two arms.. The combination of gemcitabine and S-1 was determined to be feasible and effective for advanced non-small cell lung cancer. We selected arm B for further studies because of its higher response rate and survival data.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Deoxycytidine; Drug Combinations; Female; Gemcitabine; Humans; Lung Neoplasms; Male; Neoplasm Staging; Oxonic Acid; Safety; Survival Rate; Tegafur; Treatment Outcome

To determine the dose-limiting toxicity and recommended dose (RD) of cisplatin (CDDP) combined with S-1 (tegafur, 5-chloro-2, 4-dihydroxypyridine, and potassium oxonate) for patients with non-small cell lung cancer and to evaluate efficacy and toxicity of this regimen at RD.. Patients with stages III and IV non-small cell lung cancer received 3-week cycles of treatment, each consisting of oral administration of S-1 at 80 mg/m in 2 divided doses per day for 14 consecutive days, intravenous administration of CDDP (60 mg/m, 70 mg/m, or 80 mg/m) on the first day, and no medication during the subsequent 7 days. The primary objective of phase I study was to estimate the maximum tolerable dose and the RD, and the primary end point of phase II study was response.. RD of CDDP in the analysis of 18 eligible patients was 60 mg/m. Evaluation of efficacy and toxicity at RD in 55 eligible patients showed that partial response was observed in 18 patients (32.7%, 95% confidence interval: 20.7-46.7%). The median survival time was 18.1 months, and the time to disease progression was 3.8 months. Grade 3 or severer adverse events were observed in 27 patients (49.1%).. CDDP combined with S-1 showed a satisfactory overall survival time and acceptable toxicity profile. However, the response as the primary end point did not reach the predetermined threshold level.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Cisplatin; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Maximum Tolerated Dose; Middle Aged; Neoplasm Staging; Oxonic Acid; Safety; Survival Rate; 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

We carried out this study to examine the health-related quality of life (HRQOL) of patients with advanced colorectal cancer treated with the oral fluoropyrimidine S-1 plus irinotecan (CPT-11).. HRQOL was assessed at baseline (pretreatment) and at 5-week intervals during treatment, using the European Organization for Research and Treatment of Cancer QLQ-C30 and QLQ-CR38 questionnaires. The HRQOL data for 12 preselected scales and 21 courses of treatment were then analyzed longitudinally.. Thirty-seven patients completed the baseline and post-treatment HRQOL assessments. Statistically significant differences between the baseline and post-treatment HRQOL scores were observed for the global QOL, social function, and pain scales (all QLQ-C30), as well as the body image, future perspective, gastrointestinal tract symptoms, weight loss, and chemotherapy side effects scales (all QLQ-CR38); favorable post-treatment results were observed for all the scales except for body image and chemotherapy side effects, for which post-treatment deteriorations were observed. The changes in body image, future perspective, weight loss, and chemotherapy side effects were each greater than ten points and seemed clinically significant.. Combined treatment with S-1 plus CPT-11 resulted in an acceptable deterioration in HRQOL functioning and symptoms, compared with baseline levels.

Topics: Adenocarcinoma; Adult; Aged; Antimetabolites, Antineoplastic; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colorectal Neoplasms; Drug Combinations; Female; Humans; Irinotecan; Longitudinal Studies; Male; Middle Aged; Oxonic Acid; Quality of Life; Surveys and Questionnaires; Tegafur; Time Factors; Treatment Outcome

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

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

The survival impact of single-agent treatment with docetaxel, the standard regimen for relapsed patients with non-small cell lung cancer (NSCLC), remains modest. We conducted a randomized phase II study to evaluate the efficacy and safety of the combination of docetaxel and S-1 in the second-line setting.. Patients with relapse of NSCLC after first-line platinum-based chemotherapy were randomly assigned to docetaxel alone (60 mg/m, day 1, q3 weeks; arm A) or a combination of docetaxel (40 mg/m, day 1, q3 weeks) and S-1 (80 mg/m, days 1-15; arm B). The primary end point was response rate, whereas secondary endpoints included overall survival, progression-free survival, and toxicity.. Between 2005 and 2008, a total of 60 patients were enrolled in the study. The objective response rates were 20.7% and 16.1% in arms A and B, respectively (p = 0.81). Progression-free survival was comparable in the two arms (median: 3.7 versus 3.4 months, p = 0.27), whereas overall survival time was longer in arm A (22.9 versus 8.7 months, p = 0.02). The major toxicity was myelosuppression with grade > or =3 neutropenia in 89.7% of patients versus 64.5% in arms A and B, respectively.. This study suggests that docetaxel monotherapy should continue to be considered the standard for second-line chemotherapy against NSCLC.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Cisplatin; Docetaxel; Drug Combinations; Female; Humans; Irinotecan; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Salvage Therapy; Survival Rate; Taxoids; Tegafur; Treatment Outcome

Fluorouracil and folinic acid with either oxaliplatin (FOLFOX) or irinotecan (FOLFIRI) are widely used as first-line or second-line chemotherapy for metastatic colorectal cancer. However, infusional fluorouracil-based regimens, requiring continuous infusion and implantation of an intravenous port system, are inconvenient. We therefore planned an open-label randomised controlled trial to verify the non-inferiority of irinotecan plus oral S-1 (a combination of tegafur, 5-chloro-2,4-dihydroxypyridine, and potassium oxonate; IRIS) to FOLFIRI as second-line chemotherapy for metastatic colorectal cancer.. Between Jan 30, 2006, and Jan 29, 2008, 426 patients with metastatic colorectal cancer needing second-line chemotherapy from 40 institutions in Japan were randomly assigned by a computer-based minimisation method to receive either FOLFIRI (n=213) or IRIS (n=213). In the FOLFIRI group, patients received folinic acid (200 mg/m(2)) and irinotecan (150 mg/m(2)) and then a bolus injection of fluorouracil (400 mg/m(2)) on day 1 and a continuous infusion of fluorouracil (2400 mg/m(2)) over 46 h, repeated every 2 weeks. In the IRIS group, patients received irinotecan (125 mg/m(2)) on days 1 and 15 and S-1 (40-60 mg according to body surface area) twice daily for 2 weeks, repeated every 4 weeks. The primary endpoint was progression-free survival, with a non-inferiority margin of 1.333. Statistical analysis was on the basis of initially randomised participants. This study is registered with ClinicalTrials.gov, number NCT00284258.. All randomised patients were included in the primary analysis. After a median follow-up of 12.9 months (IQR 11.5-18.2), median progression-free survival was 5.1 months in the FOLFIRI group and 5.8 months in the IRIS group (hazard ratio 1.077, 95% CI 0.879-1.319, non-inferiority test p=0.039). The most common grade three or four adverse drug reactions were neutropenia (110 [52.1%] of 211 patients in the FOLFIRI group and 76 [36.2%] of 210 patients in the IRIS group; p=0.0012), leucopenia (33 [15.6%] in the FOLFIRI group and 38 [18.1%] in the IRIS group; p=0.5178), and diarrhoea (ten [4.7%] in the FOLFIRI group and 43 [20.5%] in the IRIS group; p<0.0001). One treatment-related death from hypotension due to shock was reported in the FOLFIRI group within 28 days after the end of treatment; no treatment-related deaths were reported in the IRIS group.. Progression-free survival with IRIS is not inferior to that with FOLFIRI in patients receiving second-line chemotherapy for metastatic colorectal cancer. Treatment with IRIS could be an additional therapeutic option for second-line chemotherapy in metastatic colorectal cancer.. Taiho Pharmaceutical Co Ltd and Daiichi Sankyo Co Ltd.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colorectal Neoplasms; Disease-Free Survival; Drug Combinations; Female; Fluorouracil; Humans; Irinotecan; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Prodrugs; 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

The combination of an oral fluoropyrimidine derivative, S-1, and irinotecan is expected to be a promising regimen for advanced colorectal cancer. This study was performed to determine the maximum tolerated dose (MTD) and recommended dose (RD) of irinotecan combined with S-1 in a 3-week cycle regimen and to observe the safety and efficacy for patients with previously untreated advanced colorectal cancer. Eighty milligrams per m(2) of S-1 was given orally for 14 consecutive days and escalated doses of irinotecan were administered on days 1 and 8 every 3 weeks in the phase I trial. Forty patients were treated at the RD during the phase II trial. Forty-three patients were enrolled between February 2005 and March 2007. The dose-limiting toxicity was diarrhea and abdominal pain. The MTD of irinotecan was 100 mg/m(2) and the RD was determined to be 80 mg/m(2) of irinotecan combined with 80 mg/m(2) of S-1. The phase II trial showed that 22 of 40 patients achieved a complete or partial response and eight had stable disease. The overall response rate was 55.0%. The median progression-free survival time and median survival time were 6.7 and 21 months, respectively. There were no treatment-related deaths. The main toxicities were leukopenia, neutropenia, anorexia and diarrhea. This study suggests the combination of irinotecan and S-1 repeated every 3 weeks is tolerable and effective for patients with previously untreated advanced colorectal cancer.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colorectal Neoplasms; Disease-Free Survival; Dose-Response Relationship, Drug; Drug Combinations; Female; Humans; Irinotecan; Kaplan-Meier Estimate; Male; Maximum Tolerated Dose; Middle Aged; Neoplasm Staging; Oxonic Acid; Tegafur

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

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 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

This is a feasibility trial of oral uracil/tegafur (UFT)/oral leucovorin (LV) and irinotecan (TEGAFIRI) with maximum dose confirmed in Japan. To document the toxicity and define the objective response rate (RR); and determine progression-free and overall survival.. Patients with advanced or metastatic colorectal cancer (CRC) received: UFT 300 mg/m(2), LV 75 mg/body and CPT-11 150 mg/m(2) (UFT and LV given on days 1-14, and CPT-11 on day 1, every 3 weeks). Eligibility: ECOG performance status (PS) 0-1, adequate bone marrow/liver function and serum creatinine level less than institutional normal value.. Eighteen patients enrolled, 17 evaluable for toxicity and response and 1 patients recalled chemotherapy upon registration. Characteristics: 61% male, median age 63.5 years (51-71). Seventy-two per cent PS 0, 50% first line. One hundred and eighty-six cycles have been delivered. The common Grade 3-4 toxicities were neutropenia (35.3%), leukopenia (29.4%), diarrhea (5.9%), anorexia (5.9%), vomiting (5.9%) and dizziness (5.9%). There was no episode of febrile neutropenia. No death occurred on treatment: Overall RR was 41.2% [7/17: 1 complete response (CR) + 6 partial response (PR)]. Progression-free survival (PFS) is 6.9 months, median survival time (MST) is 25.1 months and 1-year survival rate is 70.6%, whereas PFS 15.0 months, MST 43.6+ months and 1-year survival rate 100% in cases with CR or PR.. Approved dose of CPT-11 is 150 mg/m(2) in Japan. As is lower dose with CPT-11, TEGAFIRI for patients with advanced or metastatic CRC in Japan seems to have the similar effect with that reported abroad and indicates prolonged PFS and MST in cases with CR or PR.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colorectal Neoplasms; Drug Combinations; Feasibility Studies; Female; Humans; Immunoenzyme Techniques; Irinotecan; Leucovorin; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Prognosis; Survival Rate; Tegafur; Uracil

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

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

Gemcitabine monotherapy or gemcitabine-containing combination chemotherapy is the standard first-line therapy for advanced pancreatic cancer. After disease progression, there is no standard regimen available. In a previous phase II trial, S-1 has been reported to show considerable efficacy, achieving a response rate of 37.5% in chemo-naïve patients with pancreatic cancer. This study evaluated the efficacy and toxicity of S-1 in patients with gemcitabine-refractory metastatic pancreatic cancer.. Eligibility criteria were histologically proven pancreatic adenocarcinoma with confirmation of progressive disease while receiving gemcitabine-based first-line chemotherapy, 20-74 years of age, Karnofsky performance status of 80-100 points, with measurable metastatic lesions, adequate hematological, renal and liver functions, and written informed consent. S-1 was administered orally at 40 mg/m(2) twice daily for 28 days with a rest period of 14 days as one course. Administration was repeated until the appearance of disease progression or unacceptable toxicity. The primary endpoint of this study was an objective response, and secondary endpoints included toxicity, progression-free survival (PFS) and overall survival, as well as clinical benefit response in symptomatic patients.. Forty patients from two institutions were enrolled between September 2004 and November 2005. The most common adverse reactions were fatigue and anorexia, although most of those adverse reactions were tolerable and reversible. One patient developed grade 3 pneumonitis without neutropenia and recovered with appropriate antibiotic treatment. Although no complete response was seen, partial response was obtained in six patients (15, 95% confidence interval, 3.9-26%). Stable disease was noted in 17 patients (43%), and progressive disease in 15 patients (38%). Out of 19 evaluable patients, a clinical benefit response was observed in four patients (21%). The median PFS was 2.0 months, and the median survival time was 4.5 months with a 1-year survival rate of 14.1%.. S-1 as monotherapy had marginal anti-tumor activity with tolerable toxicity in patients with gemcitabine refractory metastatic pancreatic cancer.

Topics: Adenocarcinoma; Adult; Aged; Deoxycytidine; Disease-Free Survival; Drug Combinations; Drug Resistance, Neoplasm; Female; Gemcitabine; Humans; Male; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Pancreatic Neoplasms; 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

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

This study evaluated the antitumor effect and safety of S-1, an oral fluoropyrimidine derivative, in patients with metastatic pancreatic cancer. Chemo-naive patients with pancreatic adenocarcinoma, and measurable metastatic lesions were enrolled. S-1 was administered orally twice daily after meals at a dose of 80, 100, or 120 mg/day for body surface areas (BSAs) of less than 1.25 m(2), between 1.25 m(2) and less than 1.5, or 1.5 m(2) or greater, respectively, for 28 consecutive days, followed by a 14-day rest. Fifteen (37.5%) of 40 patients responded to treatment, including 1 complete response and 14 partial responses. The median time to progression and the overall survival time were 3.7 months (95% confidence interval, 2.2-5.6 months) and 9.2 months (95% confidence interval, 7.5-10.8 months), respectively. The major adverse events were anorexia, fatigue, hemoglobin reduction, nausea and pigmentation change, although most were tolerable and reversible. Although disseminated intravascular coagulation occurred in two patients, the condition resolved with anticoagulant therapy. S-1 is an effective and well-tolerated drug. The effectiveness of this drug should be confirmed in a phase III study.

Topics: Adenocarcinoma; Adult; Aged; Antimetabolites, Antineoplastic; Drug Combinations; Female; Humans; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Oxonic Acid; Pancreatic Neoplasms; Survival Analysis; Tegafur

Optimal chemotherapy for advanced biliary tract cancer (BTC) is yet to be defined. We carried out this study to evaluate the efficacy and toxicity of combination chemotherapy with S-1 and cisplatin in metastatic or relapsed BTC.. Patients with pathologically proven BTC were eligible. The chemotherapy regimen consisted of S-1 (40 mg/m(2) p.o. b.i.d. from D1-14) and cisplatin (60 mg/m(2) on D1), repeated every 3 weeks.. Fifty-one BTC patients (metastatic:relapsed = 37:14, Gall-bladder:intrahepatic bile ducts:extrahepatic bile ducts = 16:25:10) were enrolled from January 2005 to December 2006. Median age was 57 years (range, 31-71) and most patients had a good performance status. The overall response rate was 30% [95% confidence interval (CI), 17.3-42.7] and complete response was observed in two patients (4%), partial response in 13 (26%), stable disease in 21 (42%), and progressive disease in 9 (18%). With a median follow-up of 12.4 months, the median time to progression was 4.8 months (95% CI, 3.3-6.3) and median overall survival was 8.7 months (95% CI, 6.0-11.4). Major toxic effects were grade 3/4 neutropenia (8.9% of all cycles) and febrile neutropenia was observed in six cycles (2.7% of all cycles).. Combination chemotherapy with S-1 and cisplatin was a moderately effective outpatient-based regimen in BTC patients. Toxic effects were moderate but manageable.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Biliary Tract Neoplasms; Cisplatin; Disease Progression; Disease-Free Survival; Drug Combinations; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Neutropenia; Oxonic Acid; Pyridines; Salvage Therapy; Survival Analysis; Tegafur; Thrombocytopenia

A pilot phase II study showed S-1 monotherapy to be safe and active against biliary tract cancer (BTC). We, therefore, conducted a multicenter phase II study to evaluate the antitumor effect and safety of S-1 in previously untreated patients with advanced BTC. Eligible patients had pathologically proven, unresectable adenocarcinoma with no prior chemotherapy or radiotherapy. Patients received S-1 orally at 80 mg/m2 total daily dose divided b.i.d. for 28 days followed by 14 days of rest. Of the 41 enrolled patients, 40 were assessable. The primary tumor sites were as follows: gallbladder (n = 20), extrahepatic bile duct (n = 15), and the ampulla of Vater (n = 5). One patient (2.5%) achieved a complete response, 13 patients (32.5%) had partial responses, 17 patients (42.5%) had no change, 7 patients (17.5%) had progressive disease, and 2 patients (5.0%) were not evaluable. The overall objective response rate was 35.0%. The median overall survival (median OS) was 9.4 months, and the median time to progression was 3.7 months. Grade 3 or 4 toxicities included fatigue (7.5%), anorexia (7.5%) and T-Bil elevation (7.5%). Significant antitumor activity combined with a mild toxicity profile was observed. This monotherapy warrants further evaluation in a randomized study.

Topics: Adenocarcinoma; Adult; Aged; Antimetabolites, Antineoplastic; Biliary Tract Neoplasms; Drug Combinations; Female; Humans; Karnofsky Performance Status; Male; Middle Aged; Oxonic Acid; 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

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

S-1 is a novel, oral fluoropyrimidine and a known radiosensitizer. We conducted a phase I trial to establish a schedule of S-1/irinotecan with standard pelvic radiotherapy as a preoperative treatment of locally advanced rectal cancer. Our findings suggest that this new combination is feasible and well tolerable.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Combined Modality Therapy; Drug Combinations; Female; Humans; Irinotecan; Male; Maximum Tolerated Dose; Middle Aged; Neoadjuvant Therapy; Oxonic Acid; Radiation-Sensitizing Agents; Radiotherapy Dosage; Radiotherapy, High-Energy; Rectal 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

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

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 combination of irinotecan with continuous intravenous infusions of 5-fluorouracil (5-FU) and leucovorin (LV) is often used to treat advanced colorectal cancer. However, recent concerns about safety and convenience have prompted the development of new oral fluoropyrimidine derivatives and improved regimens. This phase II study evaluated the efficacy and safety of the oral fluoropyrimidine S-1 plus irinotecan in patients with previously untreated advanced or recurrent colorectal cancer.. Forty eligible patients with histologically confirmed colorectal adenocarcinoma received this treatment. S-1 was administered orally on days 1 to 14 of a 21-day cycle. Patients were assigned on the basis of body surface area (BSA) to receive one of the following oral doses twice daily: 40 mg (BSA < 1.25 m(2)), 50 mg (BSA > or = 1.25 to < 1.50 m(2)), or 60 mg (BSA > or = 1.50 m(2)). Irinotecan (150 mg/m(2)) was administered by intravenous infusion on day 1.. A total of 327 courses of treatment were administered to 40 patients. Five patients had complete responses, and 20 had partial responses. The overall response rate was 62.5% (95% confidential interval, 47.5%-77.5%). Median progression-free survival was 8.0 months (95% confidential interval, 5.2-11.4 months). The rates of grade 3 or 4 toxicity were as follows: neutropenia, 15%; anemia, 7.5%; anorexia, 12.5%; and diarrhea, 7.5%.. Combined treatment with S-1 and irinotecan is an effective, well tolerated, and convenient regimen in patients with advanced colorectal cancer. Our findings suggest that combined treatment with S-1 and irinotecan is a promising regimen, offering benefits in terms of safety and survival as compared with conventional regimens in patients with advanced colorectal cancer.

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

A 67-year-old man was admitted to our hospital, complaining of productive cough and chest pain. Chest radiograph and computed tomography revealed a huge mass invading the mediastinum, enlargement of right hilar and cardiophrenic lymph nodes and nodules in right lower lobe and left upper lobe. Multiple space occupying regions in the liver were also observed. Cytology for exfoliated sputum revealed adenocarcinoma, so he was diagnosed with advanced lung cancer (clinical stage T 4 N 2 M 1, stage IV). He was enrolled in a clinical phase II study, and received combination chemotherapy with TS-1 and cisplatin. TS-1 was administered on days 1-21. Cisplatin was administered on day 8. Every cycle was repeated every 5 weeks. The patient then received 6 cycles of chemotherapy,and yielded a partial response (87% decrease in size determined by RECIST criteria version 2. 0). Grade 2 leukopenia and neutropenia were observed, and non-hematologic toxicities were also mild. The disease progressed after the end of chemotherapy, and he was given 5 regimens of chemotherapy, including gefitinib. He died of brain metastases. Time to progression of his disease for combination chemotherapy using TS-1 and cisplatin chemotherapy was 240 days. Survival time was 709 days. This combination chemotherapy was effective in the present case, and might prolong survival. We think it is valuable to confirm the efficacy of TS-1 and cisplatin combination chemotherapy.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Cisplatin; Drug Administration Schedule; Drug Combinations; Humans; Leukopenia; Lung Neoplasms; Male; Neutropenia; Oxonic Acid; Pyridines; Tegafur

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

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

The incidence and mortality of pancreatic cancer has increased very rapidly in Japan. The five-year survival rate is still poor at less than 10%, because it is commonly considered to be linked to a high incidence of distant metastasis even at the initial diagnosis as well as to the tumor's resistance to anticancer agents. Although gemcitabine has been the most widely used chemotherapeutic agent in patients with advanced pancreatic cancer (APC), gemcitabine monotherapy has obvious limitations. Therefore, various combinations with other agents have been investigated to improving the survival of patients with APC. Under these circumstances, we conducted a phase I /II trial of gemcitabine with S-1, an oral fluorouracil derivative, to determine the maximum tolerated dose and to evaluate the activity and toxicity of such a combination in patients with APC. S-1 was administered orally twice daily each day for 14 days and gemcitabine on days 8 and 15 of each cycle, and this cycle was repeated every 21 days. As a result, S-1 30 mg/m2 orally twice daily and gemcitabine 1,000 mg/m2 were selected as the recommended dose. The toxicities observed were mainly hematological ones with mild non-hematological toxicities. An encouragingly high response rate was observed. This result is very promising, but the survival benefit in comparison with gemcitabine monotherapy needs to be confirmed in a future randomized clinical trial.

Topics: Adenocarcinoma; Administration, Oral; Adult; Aged; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Deoxycytidine; Drug Administration Schedule; Drug Combinations; Gemcitabine; Humans; Maximum Tolerated Dose; Middle Aged; Nausea; Oxonic Acid; Pancreatic Neoplasms; Survival Rate; Tegafur; Thrombocytopenia

We have previously reported on phase I/II studies of irinotecan plus S-1 therapy for advanced gastric cancer. Based on the safety and efficacy data that were obtained, this phase II study was planned to assess the efficacy of irinotecan plus S-1 for patients with advanced colorectral cancer. A total of 40 patients are enrolled at 13 medical institutions. The objective of this study was to establish a useful chemotherapy regimen for an out-patient setting.

Topics: Adenocarcinoma; Administration, Oral; Adolescent; Adult; Aged; Ambulatory Care; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colorectal Neoplasms; Drug Administration Schedule; Drug Combinations; Humans; Irinotecan; Middle Aged; Oxonic Acid; Pyridines; Tegafur

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

The goal of the current study was to evaluate the objective response rate and toxicity associated with the oral fluoropyrimidine S-1 (a combination of tegafur, 5-chloro-2,4-dihydroxypyridine, and potassium oxonate) in patients with previously untreated metastatic colorectal carcinoma.. Thirty-eight patients were enrolled in the study. S-1 was administered orally at a dose of 40 mg/m2 twice daily for 28 days, followed by a 14-day rest period. Treatment was repeated every 6 weeks unless disease progression was observed.. A combined total of 173 courses of S-1 were administered to the 38 enrolled patients. The median number of courses administered to a given patient was 3.5 (range, 1-18). Although no patient exhibited a complete response to treatment, 15 had partial responses (response rate, 39.5%; 95% confidence interval, 24.0-56.6%). In addition, 5 patients had minor responses, and 14 had stable disease. Four patients were found to have progressive disease after two courses of treatment. The median survival time was 358 days (95% confidence interval, 305-490 days), and the 1-year survival rate was 47.4%. The most common adverse reactions included myelosuppression and gastrointestinal toxicity; most cases involved Grade 1 or 2 toxicity, but Grade 3 toxicities (anemia [7.9% of patients], neutropenia [5.3% of patients], diarrhea [2.6% of patients], and abnormal bilirubin levels [7.9% of patients]) also were noted. Neither Grade 4 toxicity nor treatment-related death was observed during the study.. Orally administered S-1 is active against metastatic colorectal carcinoma and has an acceptable toxicity profile. This promising agent has the potential to become a valuable chemotherapeutic option.

Topics: Adenocarcinoma; Administration, Oral; Adult; Aged; Antimetabolites, Antineoplastic; Colorectal Neoplasms; Drug Combinations; Female; Humans; Male; Middle Aged; Oxonic Acid; Pyridines; Survival Rate; Tegafur; Treatment Outcome

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

To evaluate the efficacy and toxicity of a novel combination chemotherapeutic regimen including cisplatin with an oral anticancer agent, S-1 that consisted of tegafur, 5-chloro-2, 4-dihydroxypyridine, and potassium oxonate, for non-small-cell lung cancer (NSCLC) patients.. In this phase II trial, patients with locally advanced and metastatic NSCLC were treated with the oral administration of S-1 at 40 mg/m(2) twice a day for 21 consecutive days while cisplatin (60 mg/m(2)) was administered intravenously on day 8. This schedule was repeated every 5 weeks.. Of 56 patients enrolled in the study, 55 patients were eligible and analyzed. The median number of cycles administered was 3 (range, 1-12 cycles). Among these 55 patients, one complete response and 25 partial responses were observed with an overall response rate of 47% (95% confidence interval, 34-61%). The median survival time was 11 months and the 1-year survival rate was 45%. Hematologic toxicities of grades 3 and 4 included neutropenia (29%) and anemia (22%). No grade 4 nonhematologic toxicity was observed. Grade 3 toxicity included anorexia (13%), vomiting (7%), or diarrhea (7%).. S-1 plus cisplatin combination chemotherapy showed a promising effectiveness with acceptable toxicity rates in patients with advanced NSCLC. These results warrant further investigations of this regimen including a randomized controlled trial for its use as a first line treatment for NSCLC.

Topics: Adenocarcinoma; Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Cisplatin; Drug Administration Schedule; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Pyridines; Survival Rate; 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

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

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

Topics: Adenocarcinoma; Drug Combinations; Female; Humans; Hypertriglyceridemia; Middle Aged; Oxonic Acid; Pancreatic Neoplasms; Tegafur

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

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

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

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

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

Gemcitabine has been standard of care in advanced pancreatic adenocarcinomas (PC) for almost two decades. Randomized, primarily Japanese, studies have shown promising efficacy when combined with S-1 (GemS-1); however, no data are published in Caucasian patients. We report the first study with a combination of GemS-1 in an unselected cohort of Caucasian PC patients.. In this observational cohort study, we analyzed efficacy and toxicity prospectively.. From July 2012 to July 2014, 64 patients received at least one cycle of GemS-1. 16 patients started therapy with gemcitabine and capecitabine (GemCap) but switched to GemS-1 after median 3 cycles of GemCap due to toxicity (hand-foot syndrome). 48 patients received GemS-1 as initial therapy. For the complete cohort, median age was 68 years (range 44-80); 22 patients (34%) had locally advanced PC; 42 patients (66%) had metastatic disease. Five patients had received prior adjuvant therapy with gemcitabine and 9 pts had received prior first-line therapy. The most common adverse event was fatigue (86%), however, only grade 3 in 3%. Five patients (8%) developed febrile neutropenia. Median PFS was 8.1 (95% CI 6.9-9.0) months and median OS was 11.7 (95% CI 10.7-13.1) months in the whole GemS-1 population. In the 48 patients starting with GemS-1, median PFS was 7.7 (95% CI 6.7-8.9) months and median OS was 11.5 (95% CI 9.7-12.3) months.. The combination of gemcitabine and S-1 is safe and associated with promising efficacy in a Caucasian population; however, this needs to be confirmed in prospective clinical trials.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cohort Studies; Deoxycytidine; Diarrhea; Drug Combinations; Fatigue; Female; Gemcitabine; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Neutropenia; Oxonic Acid; Pancreatic Neoplasms; Tegafur; Treatment Outcome; White People

Background: Copper transporter 1 (CTR1) is a critical determinant of the uptake and cytotoxic effect of the platinum\ drugs carboplatin and cisplatin. Thymidylate synthase (TS) is an enzyme involved in DNA synthesis and is associated\ with resistance of tumor cells to 5-fluorouracil. We investigated the correlation between CTR1 and TS expression levels\ and treatment outcomes in patients with advanced non-small-cell lung cancer (NSCLC) treated with S-1/carboplatin\ doublet chemotherapy. Methods: Twenty-nine patients were enrolled in this study. Tumor expression of CTR1 and\ TS was measured immunohistochemically and analyzed for correlation with tumor response, progression-free survival\ (PFS), and overall survival (OS). Results: Tumor response was significantly better in patients with CTR1High tumors\ than in patients with CTR1Low tumors (64% vs. 18%, P = 0.02). Patients with TSLow tumors had a significantly longer OS\ (median 21.2 vs. 8.5 months, P = 0.02), but not PFS, than patients with TSHigh tumors. When CTR1 and TS co-expression\ was analyzed, patients with either CTR1High or TSLow tumors showed a significantly better tumor response (50% vs. 0%,\ P = 0.01), longer PFS (median 4.2 vs. 2.1 months, P = 0.03), and longer OS (median 21.2 vs. 8.5 months, P = 0.01) than\ patients with both CTR1Low and TSHigh tumors. Conclusions: Our study suggests that combined CTR1/TS expression\ status has the potential to be an important predictor of good treatment outcomes in patients with advanced NSCLC\ treated with S-1/carboplatin doublet chemotherapy.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Carboplatin; Carcinoma, Non-Small-Cell Lung; Cation Transport Proteins; Copper Transporter 1; Drug Combinations; Female; Follow-Up Studies; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Survival Rate; Tegafur; Thymidylate Synthase; Treatment Outcome

A 56-year-old man was diagnosed with advanced adenocarcinoma of the esophagogastric junction. He received 1 course of neoadjuvant chemotherapy with S-1. After neoadjuvant chemotherapy, the primary tumor showed a remarkable decrease in size. Subtotalesophagectomy, D2 lymph node dissection, and reconstruction with a gastric tube through the posterior mediastinal route were performed. Pathological examination showed that most of the cancer cells had been destroyed, with a part where adenocarcinoma mucosa was seen. We successfully treated a case of advanced adenocarcinoma of the esophagogastric junction, with neoadjuvant S-1 chemotherapy and surgicalresection.

Topics: Adenocarcinoma; Antimetabolites, Antineoplastic; Drug Combinations; Esophageal Neoplasms; Esophagogastric Junction; Humans; Male; Middle Aged; Neoadjuvant Therapy; Oxonic Acid; Tegafur; Treatment Outcome

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

The patient was a woman in her 60's with an 11-month history ofpersistent epigastralgia and abdominal distension, without abnormal findings on upper endoscopy, abdominal ultrasonography, and abdominal computed tomography in other hospitals. She presented to our hospital with a complaint off requent vomiting; abdominal CT indicated intussusception in the jejunum due to a small intestinal tumor, and laparoscopic exploration and partial jejunectomy were performed. The histopathological diagnosis was tub1>tub2>pap, pT4(SE), pN1, pPM0, pDM0, pStage III A. She was treated with oral chemotherapy( S-1)and developed no recurrence 7 months after surgery. Laparoscopic exploration was useful to detect intussusception in the jejunum due to small intestinal adenocarcinoma.

Topics: Adenocarcinoma; Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Drug Combinations; Female; Humans; Intussusception; Jejunal Neoplasms; Oxonic Acid; Tegafur

A 47-year-old woman presented with a hard umbilical nodule that appeared red and was painful. A biopsy of the umbilical nodule revealed adenocarcinoma. As a result of general examinations, the patient was diagnosed with umbilical, hepatic, and ovarian metastases from transverse colon cancer. She was treated with S-1 and oxaliplatin(SOX)plus bevacizumab chemotherapy. After 4 courses of chemotherapy, CT revealed that the primary lesion and umbilical and hepatic metastases had reduced in size. We considered this to be a partial response and thus administered 4 additional courses of SOX plus bevacizumab chemotherapy. Finally, she remained well for 22 months and achieved relatively good prognosis. An umbilical metastasis from an internal malignancy is known as a Sister Mary Joseph's nodule, and it has very poor prognosis. Most studies show that the survival period from the time of diagnosis is within 1 year. However, our case suggests that novel anti-cancer drugs or molecular-targeted agents may improve survival.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Colon, Transverse; Colonic Neoplasms; Drug Combinations; Female; Humans; Middle Aged; Oxaliplatin; Oxonic Acid; Sister Mary Joseph's Nodule; 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

A 62-year-old Japanese female with primary lung adenocarcinoma received seven cycles of nivolumab as an eighth line of chemotherapy until she presented with hemoptysis. After transcatheter arterial embolization therapy, she received subsequent chemotherapy with paclitaxel and S-1. Four weeks later, a chest computed tomography examination revealed infiltrative shadows mainly in the right lung field, in addition to enlargement of the lung metastasis in the right middle lung lobe. Bronchofiberscopic examination revealed infiltration of lymphocytes without any malignant cells in the right segment 1 of the lung, which suggested interstitial lung disease. Corticosteroid therapy not only improved the infiltrative shadows but also reduced the lung metastasis. Even after the infiltrative shadows improved, the lung metastasis reduced further. This phenomenon resembles manifestation of pseudoprogression during treatments with immune checkpoint inhibitors, such as nivolumab.

Topics: Adenocarcinoma; Adenocarcinoma of Lung; Antibodies, Monoclonal; Drug Combinations; Female; Humans; Lung; Lung Neoplasms; Middle Aged; Neoplasm Metastasis; Nivolumab; Oxonic Acid; Paclitaxel; Tegafur; Tomography, X-Ray Computed

Preoperative chemoradiotherapy (CRT) using 5-fluorouracil (5-FU)-based chemotherapy is the standard of care for rectal cancer. The effect of additional chemotherapy during the period between the completion of radiotherapy and surgery remains unclear. Predictive factors for CRT may differ between combination chemotherapy with S-1 and with tegafur-uracil/leucovorin (UFT/LV).. The subjects were 54 patients with locally advanced rectal cancer who received preoperative CRT with S-1 or UFT/LV. The pathological tumor response was assessed according to the tumor regression grade (TRG). The expression levels of 18 CRT-related genes were determined using RT-PCR assay.. A pathological response (TRG 1-2) was observed in 23 patients (42.6%). In a multivariate logistic regression analysis for pathological response, the overall expression levels of four genes, HIF1A, MTHFD1, GGH and TYMS, were significant, and the accuracy rate of the predictive model was 83.3%. The effects of the gene expression levels of GGH on the response differed significantly according to the treatment regimen. The total pathological response rate of both high-GGH patients in the S-1 group and low-GGH patients in the UFT/LV group was 58.3%.. Additional treatment with 5-FU-based chemotherapy during the interval between radiotherapy and surgery is not beneficial in patients who have received 5-FU-based CRT. The expression levels of four genes, HIF1A, MTHFD1, GGH and TYMS, in tumor tissues can predict the response to preoperative CRT including either S-1 or UFT/LV. In particular, the gene expression level of GGH in tumor tissues may be a useful biomarker for the appropriate use of S-1 and UFT/LV in CRT.

Topics: Adenocarcinoma; Adult; Aged; Antidotes; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Chemoradiotherapy; Combined Modality Therapy; Drug Combinations; Female; Fluorouracil; gamma-Glutamyl Hydrolase; Gene Expression Regulation, Neoplastic; Humans; Leucovorin; Male; Middle Aged; Oxonic Acid; Rectal Neoplasms; Reproducibility of Results; Tegafur; Treatment Outcome

Standard therapy for advanced small bowel adenocarcinoma (SBA) has not yet been established. The present study assessed the efficacy and safety of chemotherapy (CT) in association with molecular targeting approaches for SBA.. The histories of 33 advanced SBA patients from six different institutions in Japan, who received CT from 2008 to 2016, were retrospectively examined for background, clinical course and outcome.. Median patient age was 65 years (range 39-83). Primary tumor was located in the duodenum in 21 patients (67%), the ampulla of Vater in three patients (9%), the jejunum in seven patients (21%) and the ileum in one patient (3%). Histologically, well-to-moderately and poorly differentiated adenocarcinoma were identified in 20 (61%) and nine (27%) patients, respectively. Thirteen patients received a single CT regimen, seven patients received two types of CT regimen, and 13 patients received three or more CT regimens. As first-line CT, modified FOLFOX6, capecitabine plus oxaliplatin, and S-1 plus cisplatin were employed in 13, 1, and 4 patients, respectively. The response rate (RR) and median progression-free survival (PFS) were 25% and 6.0 months, respectively. Median overall survival (OS) was 13.0 months. Nine out of the 33 patients received bevacizumab-containing CT and three received cetuximab-containing CT. Median OS of bevacizumab-containing CT patients was 21.9 months. No unexpected serious adverse events were observed.. The analysis indicates that combination CT for advanced SBA is associated with modest efficacy and safety, and bevacizumab-containing CT may contribute to favorable outcome in these patients.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Capecitabine; Cisplatin; Disease-Free Survival; Drug Combinations; Female; Fluorouracil; Humans; Intestinal Neoplasms; Intestine, Small; Japan; Leucovorin; Male; Middle Aged; Neoplasm Recurrence, Local; Organoplatinum Compounds; Oxonic Acid; Retrospective Studies; Survival Rate; Tegafur

Objective To explore the efficacy and toxicities of gemcitabine combined with S-1 in treating locally advanced and metastatic pancreatic ductal adenocarcinoma and prognostic factors. Methods We retrospectively analyzed the clinical data of patients with locally advanced and metastatic pancreatic cancer receiving gemcitabine and S-1 as first-line therapy in the Department of Medical Oncology,Peking Union Medical College Hospital from January 2014 to January 2017.Gemcitabine was administered at a dose of 1000 mg/m

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Deoxycytidine; Disease-Free Survival; Drug Combinations; Gemcitabine; Humans; Oxonic Acid; Pancreatic Neoplasms; Retrospective Studies; Tegafur; Treatment Outcome

Pancreatic cancer is common in people older than 40 years, and the incidence peaks at the age of 70 years and older. Chemoradiotherapy has been generally considered a high-risk procedure in elderly patients with local recurrent pancreatic cancer. Gamma knife stereotactic radiosurgery has the advantage in protecting the surrounding tissues, and providing short-term effects. It has been successfully used in patients with brain metastases.The efficacy of GKSRS in other malignancies has barely been studied.S-1 is one of the key drug against metastatic and local advanced pancreatic cancer. The combination of GKSRS and S-1 in local recurrent pancreatic cancer has hardly been reported.. We present a rare case of a 76-year-old man with pancreatic cancer. He complained of recurrent abdominal pain and chronic pain in the right shoulder for more than 3 years.. After several examinations, the diagnosis was carcinoma of the pancreas.. A resection of the pancreatic neoplasm was performed on June 21, 2011; he did not receive adjuvant chemotherapy. In April 2014, postoperative recurrence was confirmed in the head of the pancreas. The patient received gamma knife stereotactic radiosurgery (GKSRS) combined with S-1 treatment.. The patient showed complete response after 2 months. He has achieved an overall survival of 76 months with a very good performance status.. GKSRS applied to other malignancies has rarely been reported. S-1 is the key drug for adjuvant chemotherapy in resected pancreatic cancer. There are a few studies on this combination in local recurrent pancreatic cancer. GKSRS combined with S-1 seems to be a good option in improving efficacy and prolonging life in elderly patients with locally recurrent pancreatic cancer.

Topics: Adenocarcinoma; Aged; Chemotherapy, Adjuvant; Drug Combinations; Follow-Up Studies; Humans; Male; Neoplasm Recurrence, Local; Oxonic Acid; Pancreatic Neoplasms; Radiosurgery; Risk Assessment; Tegafur; Time Factors; Tomography, X-Ray Computed; Treatment Outcome

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

Recent studies indicated that isolated pulmonary metastases could define a favorable subgroup in metastatic pancreatic cancer. We report a case of isolated pulmonary metastases after curative resection of pancreas head cancer treated with chemotherapy and pulmonary metastasectomy survived for 79 months after recurrence. A 72-year-old male underwent pancreatoduodenectomy for pancreas head cancer. Adjuvant chemotherapy was done with gemcitabine hydrochloride (GEM)for 6 months and then S-1 for 2 months. Twenty-seven months after surgery, 2 small metastatic nodules in the left lung was detected. Chemotherapy with GEM was performed but the lesions grew larger very slowly. A new metastatic nodule was detected in the right lung 40 months after surgery and pleural effusion was detected 52 months after surgery. Then combination chemotherapy with GEM and S-1 was performed for 3 months followed chemotherapy with S-1 alone. Seventytwo months after surgery, chemotherapy with GEM was performed again because of patient's intolerance to S-1. Ninety months after initial surgery, pulmonary metastasectomy of the right lung was performed because of its resistance to chemotherapy. Chemotherapy with GEM was started again 4 months after pulmonary metastasectomy but serum levels of tumor markers remained increase. Combination chemotherapy with GEM and nab-paclitaxel was started 8 months after pulmonary metastasectomy but the patient died 16 months after pulmonary metastasectomy.

Topics: Adenocarcinoma; Aged; Albumins; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Deoxycytidine; Drug Combinations; Fatal Outcome; Gemcitabine; Humans; Lung Neoplasms; Male; Oxonic Acid; Paclitaxel; Pancreaticoduodenectomy; Pneumonectomy; Recurrence; Tegafur; Time Factors

Preoperative chemoradiotherapy (CRT) is a novel, emerging treatment strategy for pancreatic ductal adenocarcinoma (PDAC), but it remains unclear whether post-surgery adjuvant chemotherapy is feasible following preoperative CRT. This retrospective study evaluates the feasibility of adjuvant therapy after preoperative CRT.. The subjects of this study were 99 consecutive patients who underwent pancreatectomy for PDAC between January, 2007 and February, 2013 in our hospital. Sixty patients received preoperative CRT: as gemcitabine (GEM) and 40 Gy radiation in 28 (G-CRT group), and as GEM, S-1, and 50.4 Gy radiation in 32 (GS-CRT group). We also evaluated 39 patients who underwent surgery alone (SA group). We investigated adjuvant chemotherapy induction and completion rates and the frequency of adverse events rated ≥grade 3, based on Common Terminology Criteria for Adverse Events (version 4.0) in all three groups.. In the G-CRT, GS-CRT, and SA groups, the induction rates were 78 % (22/28), 78 % (25/32), and 72 % (28/39), respectively; completion rates were 86 % (19/22), 88 % (22/25), and 82 % (23/28), respectively; and adverse event frequencies were 36 % (8/22), 28 % (7/25), and 43 % (12/28), respectively. No significant difference was found among the three groups.. Preoperative CRT was demonstrated to be safe and did not compromise the feasibility of adjuvant chemotherapy.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Pancreatic Ductal; Chemoradiotherapy, Adjuvant; Chemotherapy, Adjuvant; Combined Modality Therapy; Deoxycytidine; Drug Combinations; Feasibility Studies; Female; Gemcitabine; Humans; Male; Middle Aged; Oxonic Acid; Pancreatectomy; Pancreatic Neoplasms; Preoperative Period; Radiotherapy Dosage; Retrospective Studies; 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

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

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

A 61-year-old woman with an abnormal radiograph shadow in her anterior mediastinum was admitted to our hospital and underwent an extended thymectomy. The pathological diagnosis of the tumor was a non-papillary adenocarcinoma of the thymus in pathological stage IV b using the Masaoka classification owing to mediastinal lymph node metastasis. We found parasternal lymph node metastases 5 months after her first operation, and subsequently, she underwent surgery and adjuvant radiotherapy. We found systemic lymph node metastases and metastatic lesions in distant organs, including her lungs, brain, and kidney 27 months after her first operation. Systemic chemotherapy, such as carboplatin plus paclitaxel and an ADOC regimen were not very effective, so we performed immunohistochemical staining of the primary thymic adenocarcinoma. The levels of both thymidylate synthase and dihydropyrimidine dehydrogenase were low; therefore, we started S-1 100mg/body (2 weeks of administration, 1 week of withdrawal)31 months after her first operation. She entered complete remission 6 months after the initiation of S-1. We surgically resected her solitary lung metastasis 13 months after initiation of S-1, and then continued the S-1 treatment. There was no recurrence for more than 2 years after the lung surgery. We believe that when the expression levels of thymidylate synthase or dihydropyrimidine dehydrogenase are low in cases of recurrent thymic adenocarcinoma, S-1 may be able to induce an effective response.

Topics: Adenocarcinoma; Antimetabolites, Antineoplastic; Drug Combinations; Female; Humans; Middle Aged; Ovarian Neoplasms; Oxonic Acid; Recurrence; Tegafur; Thymus Neoplasms; Time Factors

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

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

To elucidate the evolution of a lung-sparing strategy with sleeve lobectomy (SL) and induction therapy for non-small cell lung cancer (NSCLC).. We retrospectively reviewed 205 patients with NSCLC who underwent pneumonectomy (PN, n = 54) or SL (n = 151) from 1994 to 2013. The study period was divided into four 5-year periods, and surgical trends were analyzed, focusing on the PN:SL ratio.. PN was associated with a significantly advanced pathological stage, a larger tumor size and less pulmonary function compared with SL. The PN group had higher 30-day (3.7 vs. 0 %, p = 0.018) and 90-day (13.0 vs. 1.3 %, p = 0.0003) mortality than the SL group. The overall 5-year survival rate was significantly higher with SL (71.5 %) versus PN (42.8 %, p = 0.011) for patients with pN0-1. The ratio of PN among total surgeries decreased significantly over the four periods (1994-1998, 1999-2003, 2004-2008, and 2009-2013) from 5.63 % to 3.17, 1.40, and 1.38 %, respectively (p < 0.0001); in contrast, the PN:SL ratio increased significantly from 1.64 to 2.50, 3.71, and 5.44, respectively (p = 0.041). During the last period, when we introduced induction therapy, 38 of 651 who received surgery underwent induction therapy. The PN:SL ratios of those who did and did not undergo induction therapy were 15 (PN: 1, SL: 15) and 4.25 (PN: 8, SL: 34), respectively.. A lung-sparing strategy with SL for NSCLC can decrease the PN rate to less than 2 % with less mortality. Induction therapy may facilitate SL and increase the PN:SL ratio.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Carcinoma, Large Cell; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Chemoradiotherapy; Deoxycytidine; Drug Combinations; Female; Gemcitabine; Humans; Induction Chemotherapy; Lung; Lung Neoplasms; Lymph Nodes; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Organ Sparing Treatments; Oxonic Acid; Paclitaxel; Platinum Compounds; Pneumonectomy; Remission Induction; Retrospective Studies; Survival Rate; Tegafur; Tumor Burden

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

For the establishment of personalized therapy, we investigated biomarkers that can contribute to the selection of adjuvant therapy for pancreatic ductal adenocarcinoma (PDAC).. Between 2005 and 2014, of 141 consecutive patients with PDAC who underwent R0 or R1 resection, 61 patients given gemcitabine and 31 patients given S-1 as adjuvant therapy were enrolled. We evaluated the correlation between treatment outcomes and the expressions of intratumoral human antigen R (HuR), human equilibrative nucleoside transporter 1 (hENT1), thymidylate synthetase (TS) and dihydropyrimidine dehydrogenase (DPD).. There were no significant differences in clinicopathological features between the gemcitabine and S-1 groups. Among those with high HuR expression and high hENT1 expression, the disease-free survival (DFS) was significantly higher with gemcitabine than with S-1 (MST: 26.2 vs. 11.8 months, P = 0.024; 20.2 vs. 10.2 months, P = 0.029, respectively). Moreover, high HuR/hENT1 (high HuR or high hENT1) was significantly associated with better outcome for gemcitabine (HR for DFS: 0.43, P = 0.027) and low HuR/hENT1 was significantly associated with worse outcome for gemcitabine (HR for DFS: 2.24, P = 0.021). TS and DPD expression levels were not informative in this examination.. HuR and hENT1 were good candidates as selective biomarkers and this study's concept could contribute to personalized therapy for PDAC patients.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Biomarkers, Tumor; Biopsy, Needle; Carcinoma, Pancreatic Ductal; Chemotherapy, Adjuvant; Cohort Studies; Deoxycytidine; Disease-Free Survival; Drug Combinations; Female; Gemcitabine; Hospitals, University; Humans; Immunohistochemistry; Japan; Kaplan-Meier Estimate; Lymph Nodes; Male; Middle Aged; Oxonic Acid; Pancreatectomy; Pancreatic Neoplasms; Patient Selection; Precision Medicine; Prognosis; Proportional Hazards Models; Retrospective Studies; Risk Assessment; Statistics, Nonparametric; Survival Rate; Tegafur

Advanced sigmoid colon cancer with stenosis was discovered in a man in his 50's who presented with constipation. A radiological examination revealed peritoneal dissemination. Transverse colostomy was scheduled for the treatment of bowel obstruction. Multiple disseminated nodules were confirmed, and adenocarcinoma was detected from a nodule in the omentum. Eight courses of SOX plus bevacizumab caused the primary tumor to shrink and disseminated nodules to become radiologically undetectable. The patient underwent sigmoid colectomy 8 weeks after the last bevacizumab administration, and no disseminated nodules were found during the procedure. Histological assessment revealed no evidence of cancer cells in the colon and lymph nodes, and the histological effect was judged as Grade 3.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Constipation; Drug Combinations; Humans; Ileus; Male; Middle Aged; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Peritoneal Neoplasms; Sigmoid Neoplasms; 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

The anti-p53 autoantibody is an emerging tumor marker that is commonly produced in response to p53 mutations. The usefulness of this antibody has been suggested in screening for and the monitoring of recurrence in colorectal cancer; however, its significance as a marker during chemotherapy remains largely unknown.. We measured serum anti-p53 antibody levels in patients with unresectable colorectal cancer who underwent first-line systemic chemotherapy. Tumor responses were evaluated by computed tomography. We determined whether temporal changes in this antibody during therapy are associated with radiological responses.. Of the 83 patients in our study, 29 (35%) had elevated serum anti-p53 antibody levels before chemotherapy. Among these, antibody levels decreased in all 14 responders. In contrast, among those patients with elevated pretherapeutic serum anti-p53 antibody levels, 89% showed a paradoxical decrease in antibody levels and exhibited disease progression after chemotherapy. Moreover, serum anti-p53 antibody levels before and after chemotherapy were not associated with survival.. These results suggest that serum anti-p53 antibody levels are of limited value in the evaluation of responses to palliative chemotherapy in patients with colorectal cancer.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Autoantibodies; Bevacizumab; Camptothecin; Capecitabine; Carcinoembryonic Antigen; Cetuximab; Colorectal Neoplasms; Disease Progression; Drug Combinations; Female; Fluorouracil; Humans; Leucovorin; Middle Aged; Organoplatinum Compounds; Oxonic Acid; Palliative Care; Pregnancy; Survival Rate; Tegafur; Tumor Suppressor Protein p53

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

A 74-year-old man with IgG4-related cholangitis had been treated with steroids for 1 year. In the outpatient clinic, elevated levels of the tumor marker CA19-9 and serum IgG4 were observed. Abdominal enhanced CT showed a 20mm hypovascular tumor in the pancreatic head. ERCP showed narrowingof the main pancreatic duct in the pancreatic head with slight caudal dilation and stricture of the lower common bile duct. We made a diagnosis of pancreatic cancer, and the patient underwent pancreaticoduodenectomy. Pathological examination of the resected tissue revealed a well-differentiated adenocarcinoma surrounded by autoimmune pancreatitis, characteristic of lymphoplasmacytic sclerosingpancreatitis. He is receiving adjuvant chemotherapy with S-1 in the outpatient clinic.

Topics: Adenocarcinoma; Aged; Antimetabolites, Antineoplastic; Autoimmune Diseases; CA-19-9 Antigen; Chemotherapy, Adjuvant; Drug Combinations; Humans; Immunoglobulin G; Male; Oxonic Acid; Pancreatic Neoplasms; Pancreaticoduodenectomy; Pancreatitis; Tegafur; Treatment Outcome

A 60-year-old man visited a hospital with concerns about his physical health, including weight loss, thirst, and polyuria. He was diagnosed with acute onset of diabetes, and a pancreatic head tumor was observed on imaging studies. Computed tomography(CT)indicated that the tumor infiltrated the surrounding major vessels, portal vein(PV, 360 degrees), and superior mesenteric artery(SMA, <180 degrees). Endoscopic ultrasound-guided fine needle aspiration(EUS-FNA)was performed, and he was diagnosed with a borderline resectable(BR)clinical Stage IV a pancreatic ductal adenocarcinoma (PDAC). Chemoradiation therapy(CRT, S-1 plus gemcitabine [GEM] concurrent with 50.4 Gy radiation)followed by chemotherapy( GEM)was performed until a tumor response indicating sufficient reduction of SMA infiltration was observed on imaging studies. Twelve months after initiation of treatment, a pancreaticoduodenectomy and PV resection/reconstruction were performed. The pathological stage was ypT3N0M0(ypStage III ), and SMA infiltration was not detected in the resected specimen. He was discharged after an uneventful course following surgery, and adjuvant S-1 chemotherapy was continued from post-operative day 67 for 4 months. Now at post-operative 57 month, he has survived without recurrence. There have been some reports detailing long-term survival of patients with BR tumors who underwent multidisciplinary therapy as curative resection following preoperative CRT and postoperative adjuvant chemotherapy. During preoperative treatment, it is important to monitor the effects and determine the suitable timing to perform surgery to achieve long-term survival.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Deoxycytidine; Drug Combinations; Endoscopic Ultrasound-Guided Fine Needle Aspiration; Gemcitabine; Humans; Male; Oxonic Acid; Pancreaticoduodenectomy; Tegafur; Time Factors; Tomography, X-Ray Computed; Treatment Outcome

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 64-year-old man reporting dysphagia was examined. Upper gastrointestinal endoscopy showed a type 3 cancer at the esophagogastric junction. Enhanced CT scan showed several swollen mediastinal and abdominal lymph nodes. We diagnosed the patient with advanced adenocarcinoma of the esophagogastric junction with multiple lymph node metastases(Siewert type II , cT3N2M1[LYM], Stage IV ). After 5 courses of chemotherapy(S-1 plus cisplatin), a significant reduction was observed in the size of the tumor and lymph nodes. Therefore, we performed conversion surgery. The patient underwent esophagectomy and mediastinal lymph node dissection using a right thoracotomy approach. He has survived without recurrence in the 10 months since this radical surgery.

Topics: Adenocarcinoma; Antimetabolites, Antineoplastic; Combined Modality Therapy; Drug Combinations; Esophageal Neoplasms; Esophagectomy; Esophagogastric Junction; Humans; Lymphatic Metastasis; Male; Middle Aged; Oxonic Acid; Tegafur

A 76-year-old woman was referred to our hospital because of an abdominal tumor in September 2009. An irregularly shaped large tumor was detected in the right subcostal abdominal cavity on computed tomography, and was diagnosed as advanced gallbladder cancer without distant metastasis following further examination. We then performed a laparotomy. The tumor had invaded directly into the descending portion of the duodenum and transverse colon. We performed a curative resection of the tumor macroscopically. Pathological findings were moderately differentiated tubular adenocarcinoma derived from gallbladder cancer(T3N0M0, Stage III ). Postoperative antineoplasticc hemotherapy was not administered. At least 4 metastaticregions in the liver(segments 1, 5, 7, and 8)were detected using computed tomography 3 months after the operation, and we then initiated oral administration of S-1. After beginning treatment, we observed partial remission at 3 months and continued treatment. We changed the regimen of chemotherapy to gemcitabine 11 months later because of a drug-induced corneal disorder. One after treatment change also continues advertising, and treatment has ended 5 years after the operation. The patient has not received any treatment for the last 6 years and 7 months, and is now in the follow up period.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Deoxycytidine; Drug Combinations; Female; Gallbladder Neoplasms; Gemcitabine; Humans; Liver Neoplasms; Oxonic Acid; 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

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

We describe a case of liver metastasis of colorectal cancer that became resectable after bevacizumab (Bmab), CPT-11, and S-1 ie Bmab+IRIS combination chemotherapy. A 65-year-old man experienced repeated constipation and diarrhea in August of 2013. Colonoscopy was conducted by a local doctor, and a tumor(diagnosed as adenocarcinoma tub1 by biopsy)was found in the upper rectum. Computed tomography performed at our institution detected synchronous liver metastasis. On September 9, laparoscopic rectal anterior resection was performed to prevent metastasis to the ileus, and on October 9, the patient began receiving Bmab+IRIS combination chemotherapy. Before chemotherapy, 3 metastases with a maximum diameter of 7 cm diameter)were observed in the right lobe of the liver. After 4 courses of chemotherapy, their maximum diameter was 3 cm, which allowed resection. Ultimately, the metastases were completely resected. Conversion of non optimal resection cases of liver metastases to optimal cases by using Bmab+IRIS chemotherapy is extremely rare. We suggest that Bmab+IRIS chemotherapy could be an option for conversion of non optimal liver resection cases to optimal cases. We report this rare case and discuss the implications of adjuvant chemotherapy for this patient.

Topics: Adenocarcinoma; Aged; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Combined Modality Therapy; Drug Combinations; Humans; Irinotecan; Liver Neoplasms; Male; Oxonic Acid; Sigmoid Neoplasms; Tegafur

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

5-Fluorouracil-based chemotherapy is considered to be a radiosensitizer; however, conventional short-course radiotherapy combined with chemotherapy is generally thought to not be feasible because of the prevalence of side effects.. The aim of this study was to evaluate the feasibility of modified short-course radiotherapy combined with a chemoradiosensitizer for T3 rectal cancer.. This study was retrospective in nature and used a prospectively collected database.. Patients with T3 rectal cancer located below the peritoneum reflection were selected.. A total dose of 25 Gy of radiotherapy was administered in 10 fractions of 2.5 Gy each for 5 days. Radiotherapy was performed with S-1 as a radiosensitizer from day 1 to day 10. Surgery was targeted to be performed 4 weeks after radiotherapy.. The morbidity, sphincter-preserving rate, anal function, and long-term outcomes were assessed.. All patients (n = 170) completed the radiotherapy regimen and 166 (97.6%) completed the combination regimen with chemotherapy. A total of 149 patients (87.6%) had sphincter-preserving surgery (double stapling technique (DST), 58 patients; intersphincteric resection (ISR), 91 patients), and postoperative complications were relatively mild (anastomotic leakage, 15.4%; intra-abdominal infection, 8.2%). Among those undergoing sphincter preserving surgery, the 5-year local relapse-free survival rate was 94.3% in the DST group, and 89.8% in the ISR group. With respect to the anal function, the Wexner score the first year after stoma closure for the double-stapling technique group was 6 and that for intersphincteric resection was 15; however, the score for the intersphincteric resection group was improved to 8 at 4 years after stoma closure.. This study had limitations because it was an uncontrolled, 1-arm, retrospective review with a small sample size.. Modified short-course radiotherapy combined with chemoradiosensitizer is a feasible approach for treating T3 rectal cancer. With the use of the short-course approach, efforts to reduce the incidence of side effects by appropriately prolonging the waiting period enable the administration of combination treatment with short-course radiotherapy and chemotherapy.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Anal Canal; Antimetabolites, Antineoplastic; Chemoradiotherapy; Databases, Factual; Dose Fractionation, Radiation; Drug Combinations; Feasibility Studies; Fecal Incontinence; Female; Humans; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Organ Sparing Treatments; Oxonic Acid; Postoperative Complications; Radiation-Sensitizing Agents; Rectal Neoplasms; Rectum; Retrospective Studies; Tegafur; Treatment Outcome

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

Pancreatic cancer (PC) with arterial invasion is currently a contraindication to resection and has a miserable prognosis.. Seventeen patients with locally advanced PC involving the celiac axis and/or common hepatic artery (CHA) who received chemoradiotherapy (CRT) composed of gemcitabine, S-1, and external beam irradiation over the last 2 years were investigated. Thirteen patients underwent pancreatectomy with major arterial resection: 6 distal pancreatectomies with resection of the celiac axis, 4 total pancreatectomies with resection of both the celiac axis and the CHA, and 3 pancreatoduodenectomies with resection of the CHA. Preoperative arterial embolization and/or arterial reconstruction to prevent ischemic gastropathy and hepatopathy was performed in 7 of the 13 patients.. Distant metastases were found in 3 patients after CRT. One patient did not consent to operation after CRT. The morbidity rate of the 13 patients who underwent surgery was 62% (8/13), but no deaths occurred. Although there were no responders on CT, >90% of tumor cells were necrotic on histopathology in 5 of 13 tumors after CRT. Invasion of the celiac axis remained in 5 tumors, and extrapancreatic plexus invasion remained in 8 tumors, but an R0 resection was achieved in 12 of 13 tumors. Lymph node metastases were found in 3 of 13 cases. The overall 1-year survival rate from commencement of CRT and resection was 12 of 13 patients.. Neoadjuvant CRT containing gemcitabine and S-1 and subsequent pancreatectomy with major arterial resection for patients with locally advanced PC with arterial invasion were carried out safely with an acceptable R0 resection acceptable morbidity and mortality, and encouraging survival (12 of 13) at 1 year postoperatively.

Topics: Adenocarcinoma; Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Pancreatic Ductal; Celiac Artery; Chemoradiotherapy, Adjuvant; Deoxycytidine; Drug Combinations; Female; Gemcitabine; Hepatic Artery; Humans; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Invasiveness; Oxonic Acid; Pancreatectomy; Pancreatic Neoplasms; Prognosis; Tegafur; Vascular Neoplasms

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

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

Chemotherapy with S-1 and oxaliplatin is a new treatment for metastatic colorectal cancer. We present the first case of S-1, oxaliplatin, and bevacizumab therapy in our hospital. The patient was a 69-year-old woman with ascending colon cancer and multiple lung and liver metastases. She tended to suffer from constipation; stenoses at the cecum and colon cancer were detected by colon fiberscopy. Following surgical resection of the primary tumor, the patient received systemic chemotherapy with S-1, oxaliplatin, and bevacizumab. Following chemotherapy, CT showed no cancer in the lung and cancer reduction in the liver or dissemination. The patient had diarrhea and no appetite at first, so we reduced the oxaliplatin dose by 80%. After reduction of the oxaliplatin dose, we could treat the patient with S-1 and oxaliplatin continuously with no toxicity. S-1 and oxaliplatin chemotherapy is cost-effective, and has less toxicity than other chemotherapies, if proper measures are taken. It seemed to have a non-inferior response rate and disease control compared to other chemotherapies, such as FOLFOX. Thus, this chemotherapy is a valid choice for metastatic colorectal cancer.

Topics: Adenocarcinoma; Aged; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Colorectal Neoplasms; Drug Combinations; Fatal Outcome; Female; Humans; Neoplasm Metastasis; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; 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

A 64-year-old man was diagnosed with pancreatic cancer by abdominal computed tomography (CT). The examination showed a pancreatic tail cancer and a distal pancreatectomy was performed in 2010. Histopathologically, this tumor was a moderately-differentiated tubular adenocarcinoma. He received gemcitabine adjuvant chemotherapy for a year. In 2012, a chest CT scan revealed 4 nodules in the lower left lobe. We diagnosed gemcitabine-refractory lung metastases after distal pancreatectomy for pancreatic cancer. S-1 chemotherapy was administered as a second line chemotherapy for metastatic pancreatic cancer. After 2 courses of this regimen, the lung metastases were reduced. After 6 courses, a clinical complete response was obtained. Four years and 6 months after the operation, the patient is well without any signs of recurrence, and S-1 chemotherapy is still ongoing.

Topics: Adenocarcinoma; Antimetabolites, Antineoplastic; Deoxycytidine; Drug Combinations; Gemcitabine; Humans; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Pancreatectomy; Pancreatic Neoplasms; Recurrence; Tegafur

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 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

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 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 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

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

We performed laparoscopic liver resection in a patient with synchronous liver metastasis from advanced sigmoid colon cancer after induction with S-1 plus oxaliplatin (SOX) plus bevacizumab (BV) chemotherapy. A 61-year-old woman underwent laparoscopy-assisted sigmoidectomy for locally advanced sigmoid colon cancer with synchronous liver metastasis. SOX plus BV chemotherapy was initiated. After 3 courses, the liver tumor was downsized, and metastasectomy was performed laparoscopically with R0 resection. The postoperative course was uneventful and the patient was discharged on the 11th postoperative day. She has been free from recurrence. Induction with SOX plus BV chemotherapy is considered to be not only effective, but also beneficial for maintaining the quality of life (QOL) in patients with advanced colorectal cancer.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Drug Combinations; Female; Hepatectomy; Humans; Laparoscopy; Leucovorin; Liver Neoplasms; Middle Aged; Oxonic Acid; Sigmoid Neoplasms; Tegafur

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

The efficacy and safety of S-1/oxaliplatin (SOX) therapy in patients with recurrent adenocarcinoma of the uterine cervix were examined in a pilot study.. S-1 was orally administered for 14 days at a dose of 80-120 mg/body/day to 7 patients with recurrent adenocarcinoma of the uterine cervix, with oxaliplatin being administered intravenously at a dose of 100 mg/m(2) on day 1. Each therapy cycle was 21 days, and the patients received 6 cycles at most. The antitumor effect, adverse events, progression-free survival (PFS), and overall survival (OS) were investigated.. The median age of the patients was 49 years. The antitumor effect was rated as a complete response in 2 patients, partial response in 2, and stable disease in 3. The overall response rate was 57.1 %, and the disease control rate was 100 %. Regarding hematological toxicities of grade 3 or more, leukopenia, neutropenia and thrombocytopenia occurred in 42.9, 28.6 and 14.3 %, respectively; regarding non-hematological toxicities, grade 3 rectovaginal fistula occurred in 14.3 %, as well as grade 2 fatigue in 14.3 % of the patients. The median PFS and OS were 5 months (range 3-9 months) and 7 months (range 4-43 months), respectively.. These results suggest that SOX therapy is useful for the treatment of recurrent adenocarcinoma of the uterine cervix, having a promising antitumor effect and minimal adverse effects. It was also suggested that SOX therapy may contribute to improving the prognosis for patients with adenocarcinoma of the uterine cervix.

Topics: Adenocarcinoma; Administration, Oral; Adult; Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Female; Humans; Middle Aged; Neoplasm Recurrence, Local; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Pilot Projects; Quality of Life; Tegafur; Uterine Cervical Neoplasms

Little is known about the immunological effect of neoadjuvant chemoradiotherapy (NACRT) in the tumor microenvironment of pancreatic ductal adenocarcinoma. The objective of this study was to examine the immunological modifications induced by NACRT in patients with pancreatic cancer.. Fifty-two patients with pancreatic cancer who underwent surgical resection were enrolled in this study. NACRT was administered to 22 patients, whereas the other 30 patients underwent surgical resection without NACRT. The resected tumor specimens were analyzed for the presence of tumor-infiltrating lymphocytes by using immunohistochemical staining for CD4, CD8, CD68, CD163, Foxp3, and major histocompatibility complex class I (MHC class I) antigen.. The number of CD4+ and CD8+ lymphocytes was significantly higher in patients who received NACRT than in those who did not receive NACRT. No significant difference in MHC class I expression was observed between the groups. In the NACRT group, patients with a high accumulation of CD8+ cells experienced longer overall survival than those with a low number of CD8+ cells.. NACRT may induce the accumulation of CD4+ and CD8+ cells in the tumor microenvironment and a high accumulation of CD8+ cells might be a good prognostic marker for pancreatic cancer treated with NACRT.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Pancreatic Ductal; CD8-Positive T-Lymphocytes; Chemoradiotherapy; Combined Modality Therapy; Deoxycytidine; Drug Combinations; Female; Follow-Up Studies; Gemcitabine; Humans; Lymphocytes, Tumor-Infiltrating; Male; Neoadjuvant Therapy; Neoplasm Staging; Oxonic Acid; Pancreatectomy; Pancreatic Neoplasms; Prognosis; Survival Rate; Tegafur; Tumor Microenvironment

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

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

A 67-year-old woman presented with macroscopic hematuria and lower abdominal pain. Cystoscopy revealed a broad-stalk non-papillary tumor at the bladder dome. Computed tomography (CT) showed a tumor extending from the umbilicus to the bladder dome, together with multiple lung metastases. Serum carcinoembryonic antigen and cancer antigen (CA19-9) levels were elevated at 7.0 ng/ml and 180 U/ml, respectively. Transurethral resection of the tumor was performed and histopathology revealed adenocarcinoma. Therefore, the tumor was diagnosed as a stage IVB (Sheldon's category) urachal carcinoma. En bloc segmental resection of the urachal carcinoma with the bladder dome was performed, followed by chemotherapy with tegafur, gimestat, and otastat potassium (TS-1) and cisplatin. The disease remained stable for 8 months. However, a follow up CT scan after 11 chemotherapy cycles showed progression of the lung metastases. In spite of the change to a second-line gemcitabine and cisplatin chemotherapy regimen, the disease continued to progress after 4 cycles.

Topics: Adenocarcinoma; Aged; Antigens, Tumor-Associated, Carbohydrate; Antineoplastic Combined Chemotherapy Protocols; Carcinoembryonic Antigen; Drug Combinations; Female; Humans; Lung Neoplasms; Oxonic Acid; Tegafur; Urinary Bladder Neoplasms

The purpose of this study was to analyze the influence of variations in clinical practice regarding the timing of surgery with short-course chemoradiotherapy with delayed surgery (SCRT-delay) for lower rectal cancer.. A total of 171 patients with T3 N0-2 lower rectal cancer treated with SCRT-delay (25 Gy/10 fractions/5 days (S-1); days 1-10) were retrospectively evaluated. The median waiting period of 30 days was used as a discriminator (group A: waiting period, ≤30 days; group B: waiting period, ≥31 days). Preoperative treatment responses and oncological outcomes were analyzed.. The mean waiting periods for groups A and B were 24.4 ± 5.3 and 41.4 ± 12.3 days, respectively. There were no statistically significant differences between the two groups in any of the clinical variables. The clinicopathological outcomes were as follows: T downstaging (43.5 vs 37.2 %; p = 0.400), negative yp N (67.1 vs 75.6 %; p = 0.218), pCR (7.1 vs 1.2 %; p = 0.119). The 5-year local recurrence-free survival (89.3 vs 87.6 %; p = 0.956), the recurrence-free survival (82.2 vs 78.8 %; p = 0.662), and the overall survival (88.5 vs 84.4 %; p = 0.741), all of which were similar between the two groups.. The longer waiting period did not increase the tumor downstaging and not improve the oncological outcomes for T3 lower rectal cancer treated with SCRT-delay. In addition, considering that the impaired leukocyte response occurred during the sub-acute period, any time after the sub-acute period (day 12) up to 30 days after radiotherapy would be a suitable waiting period.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Chemoradiotherapy; Disease-Free Survival; Drug Combinations; Female; Humans; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Postoperative Complications; Rectal Neoplasms; Retrospective Studies; 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

A 62-year-old woman diagnosed with gallbladder cancer exhibiting broad liver invasion and metastasis to Couinaud's hepatic segments 4 and 8 (S4 and S8) consulted her regular doctor. Owing to the presence of liver metastases, she received treatment with gemcitabine plus S-1. After four cycles of chemotherapy, the size of the main lesion dramatically decreased and the two liver metastases disappeared. After six cycles of chemotherapy, the patient was referred to our hospital for surgical treatment. Upon admission, there was no evidence of any distant metastasis, based on a detailed radiological examination. Therefore, we performed cholecystectomy and central bisegmentectomy of the liver after obtaining the patient's informed consent. Pathological examination demonstrated viable cancer cells with granuloma formation and calcification in the gallbladder, as well as regenerative changes without viable cancer cells in S4 and S8 of the liver. Gemcitabine plus S-1 was again administered as postoperative adjuvant chemotherapy. One and a half years after the surgery, there were no signs of recurrence. In patients selected according to their response to chemotherapy, surgical treatment might therefore be effective against gallbladder cancer with metastasis.

Topics: Adenocarcinoma; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cholecystectomy; Deoxycytidine; Drug Combinations; Female; Gallbladder Neoplasms; Gemcitabine; Hepatectomy; Humans; Liver Neoplasms; Middle Aged; Neoadjuvant Therapy; Neoplasm Invasiveness; Oxonic Acid; 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

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Colon, Sigmoid; Diagnostic Imaging; Drug Combinations; Humans; Laparoscopy; Lymphatic Metastasis; Male; Mesentery; Oxonic Acid; Pancreatectomy; Pancreatic Neoplasms; Tegafur; Treatment Outcome

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

A 54-year-old man presented with an enlarged left (lt) lateral lymph node (LLN), which was detected by magnetic resonance imaging (MRI) and positron emission tomography/computed tomography (PET-CT). Endoscopic examination of the colon revealed the presence of a type 1 tumor, 20mm in diameter, in the lower rectum; the tumor was diagnosed as a well-differentiated adenocarcinoma (tub1). The patient received combined neoadjuvant chemoradiotherapy (nCRT)with S- 1 for treatment of the rectal cancer and LLN metastasis (MP, T2N3M0, Stage IIIb). S-1 was administered orally at a dose of 120 mg/day on days 1-14, and 22-35; a total dose of 45 Gy was delivered (1.8 Gy/day, for 25 days). Upon nCRT, there was a remarkable reduction in the tumor size, the primary tumor receded, and the LLN decreased from 16 mm to 8 mm in diameter. The maximum standardized uptake value (SUVmax) also decreased from 3.8 to 1.9 on PET-CT. Six weeks after nCRT, ultralow anterior resection and bilateral lymph node dissections were performed. Histopathological examination showed a partial presence of cancer cells in the scarred primary tumor; however, no viable cancer cells were observed in the lt. LLN.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Drug Combinations; Humans; Lymphatic Metastasis; Male; Middle Aged; Neoadjuvant Therapy; Oxonic Acid; Rectal Neoplasms; Tegafur

An 82-year-old man who complained of constipation, anal pain, and bleeding was diagnosed with internal hemorrhoid in another hospital 6 months previously. At the time of our consultation, a tumor was observed in the anal canal. Computed tomography (CT) imaging revealed that the tumor extended to the front of the coccyx with abscess formation. Histological examination of biopsy specimens confirmed a diagnosis of adenocarcinoma. Since the patient refused to undergo surgery, we recommended chemoradiotherapy for relieving pain. A total of 60 Gy of irradiation was administered to the lesser pelvis, and chemotherapy was initiated with S-1 at a dose of 8 0mg/day for 14 consecutive days followed by 7 days of rest. Subsequently, tumor reduction was seen and the pain was controlled. The patient showed improvement in activities of daily living (ADL). Currently, the patient continues to receive S-1 therapy. We conclude that chemoradiotherapy is useful as a palliative therapy in anal mucinous carcinoma.

Topics: Adenocarcinoma; Aged, 80 and over; Antimetabolites, Antineoplastic; Anus Neoplasms; Chemoradiotherapy; Drug Combinations; Humans; Male; Oxonic Acid; Palliative Care; Tegafur

A 6 1-year-old man who was admitted to our hospital because of obstructive jaundice. He was diagnosed with locally advanced cancer of the pancreatic head on computed tomography. Gemcitabine (1,000 mg/m² on days 8 and 15, every 21 days) + S-1 (6 0 mg/m² on day 1-15, every 21 days) chemotherapy was administered because the tumor had invaded the common hepatic artery and portal vein. The tumor was reduced following 9 months of chemotherapy. Thus, subtotal stomach- preserving pancreaticoduodenectomy (SSPPD)was performed. The histopathological findings indicated no invasion of the cancer into the surrounding tissues. No recurrence has occurred 7 months after surgery. Neoadjuvant chemotherapy is important for effective treatment of locally advanced pancreatic cancer.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Deoxycytidine; Drug Combinations; Gemcitabine; Humans; Male; Middle Aged; Neoadjuvant Therapy; Oxonic Acid; Pancreatic Neoplasms; Pancreaticoduodenectomy; Tegafur; Treatment Outcome

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

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

The purpose of the present study was to evaluate the efficacy and the tolerability of modified FOLFIRINOX (mFOLFIRINOX), administered as a second-line or beyond second-line chemotherapy drug in patients with locally advanced or metastatic pancreatic cancer (PC) after the failure of both gemcitabine (GEM) and S-1.. Treatment of mFOLFIRINOX consisted of oxaliplatin, leucovorin, irinotecan and fluorouracil; all the anticancer drugs were reduced to an 80% dose of the original regimen of FOLFIRINOX, repeated every three weeks. The primary end point was response rate (RR) and disease control rate (DCR). The secondary end points were overall survival (OS), progression-free survival (PFS), total survival time (TST), safety, and tolerability.. Between November 2011 and November 2013, 13 enrolled patients were treated with mFOLFIRINOX, with a median of 5 courses (range 1-33). The RR and DCR were 30.8% and 69.2%, respectively. The median OS, PFS, and TST were 176, 137, and 779 days, respectively. The 6-month and the 1-year OS was 46.1% and 23.1%, respectively. Major grade 3 or grade 4 adverse events included neutropenia (38.5%), and anorexia (25.0%).. mFOLFIRINOX was moderately effective in locally advanced or metastatic PC patients after the failure of both GEM and S-1.

Topics: Adenocarcinoma; Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Deoxycytidine; Disease Progression; Disease-Free Survival; Drug Combinations; Drug Resistance, Neoplasm; Female; Fluorouracil; Gemcitabine; Humans; Irinotecan; Japan; Kaplan-Meier Estimate; Leucovorin; Male; Middle Aged; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Pancreatic Neoplasms; Tegafur; Time Factors; Treatment Outcome

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

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

Pemetrexed(PEM)and S-1 are both cytotoxic anti-tumor drugs that target thymidylate synthase(TS). Here, we report a case of lung cancer resistant to PEM, but responsive to S-1 monotherapy. A 50-year-old male with lung cancer(adenocarcinoma, EGFR mutation negative)at Stage III B(T4N2M0)received PEM as third-line chemotherapy. However, metastatic mediastinal lymph nodes were increased in size. A switch to gemcitabine(GEM)resulted in further enlargement of the nodes and elevation of the serum CEA level. Introduction of S-1 monotherapy(120mg/body/day divided into two doses, 4-week administration every 6 weeks, 6 courses)reduced the size of the nodes and serum CEA was normalized. Although S-1 as well as PEM, target TS, the mechanisms in these two drugs that lead to resistance are not the same. Furthermore, S-1 induces dysfunction of RNA through the generation of fluoro-uridine monophosphate(FUMP). We conclude that S-1 can be a drug of choice, even in cases that show resistance to PEM.

Topics: Adenocarcinoma; Antimetabolites, Antineoplastic; Drug Combinations; Drug Resistance, Neoplasm; Glutamates; Guanine; Humans; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Pemetrexed; Tegafur; Tomography, X-Ray Computed

The aim of this study was to evaluate S-1 and oxaliplatin combination chemotherapy (SOX) in patients with refractory pancreatic cancer (PC).. Consecutive patients with advanced PC refractory to gemcitabine who were treated with oral S-1 (80 mg/m²) on days 1-14 and intravenous oxaliplatin (100 mg/m²) on day 1 every 3 weeks were studied retrospectively. The primary end point was the objective response rate (ORR). The secondary end points were progression-free survival (PFS), overall survival (OS), the disease control rate (DCR), and safety.. Between March 2009 and October 2011, 30 patients were treated with SOX, with a median of two courses (range 1-8). The ORR and DCR were 10.0 and 50.0 %, respectively. Median PFS and OS were 3.4 months (95 % confidence interval [CI] 1.3-5.3) and 5.0 months (95 % CI 3.4-7.4), respectively. The median PFS and OS were 5.6 and 9.1 months in patients receiving S-1 and oxaliplatin as a second-line treatment. Major grade 3 or 4 adverse events included neutropenia (10.0 %), anemia (3.3 %), and diarrhea (6.7 %).. SOX was well tolerated and moderately effective in patients with refractory PC.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Female; Follow-Up Studies; Humans; Incidence; Liver Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Neutropenia; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Pancreatic Neoplasms; Retrospective Studies; Salvage Therapy; Survival Analysis; Tegafur; Tokyo

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

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

A man in 30s was admitted to our hospital with a complaint of abdominal and back pain. Abdominal CT scan showed a large mass and double balloon endoscopy detected a tumor of the jejunum. The pathological diagnosis of biopsy samples was poorly differentiated adenocarcinoma. After radical resection, adjuvant chemotherapy with mFOLFOX6 was administered, however, a recurrent lesion developed. Although the lesion was successfully removed again, it did not react to the combination therapy with irinotecan and cisplatin. Because the tumor showed a high percentage of epidermal growth factor receptor (EGFR) expression and also had a wild-type KRAS status, a therapeutic strategy targeting EGFR was selected. The patient started on panitumumab associated with S-1 and obtained a complete response on CT 6 weeks later. Small bowel adenocarcinoma is an aggressive malignancy with a poor prognosis and little information about its definitive chemotherapy. Analysis of molecular characterization, an increase in reported experience, and prospective trials are needed to improve a prognosis.

Topics: Adenocarcinoma; Adult; Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Humans; Jejunal Neoplasms; Male; Oxonic Acid; Panitumumab; Recurrence; 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

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

We report a case of long-term survival after combination chemotherapy and surgical resection of a cancer of unknown primary site[ CUPs]. A septuagenarian female was identified as having high blood levels of carcinoembryonic antigen (CEA) during follow-up monitoring of asthma. Endoscopy and imaging studies including computed tomography (CT) and positron emission tomography (PET)-CT revealed a malignant lymph node adjacent to the abdominal aorta; however, no other lesion was detected. Therefore, we performed CT-guided biopsy and diagnosed the lesion to be a lymph node metastasis of poorly differentiated adenocarcinoma. As we considered this as a systemic disease, the patient received 2 courses of combination chemotherapy with 5-fluorouracil( 5-FU)/cisplatin( CDDP) and achieved a partial response (PR). Later, the patient received S-1 therapy as second-line chemotherapy and S-1/irinotecan( CPT-11) as third-line chemotherapy in an outpatient clinic. However, the tumor continued to grow, and therefore, we decided to perform surgical resection. Histopathological examination of the resected specimen yielded a diagnosis of metastatic adenocarcinoma of the lymph node. The patient has been well without any signs of recurrence for more than 9 years since surgery. As CUPs is generally associated with poor prognosis, this case raises the possibility that combination therapy might improve convalescence.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Drug Combinations; Female; Humans; Irinotecan; Lymph Node Excision; Lymphatic Metastasis; Neoplasms, Unknown Primary; Oxonic Acid; Tegafur; Time Factors

Preoperative chemoradiation therapy (CRT) significantly decreases local recurrence in locally advanced rectal cancer. Various biomarkers in biopsy specimens obtained before CRT have been proposed as predictors of response. However, reliable biomarkers remain to be established.. The study group comprised 101 consecutive patients with locally advanced rectal cancer who received preoperative CRT with oral uracil/tegafur (UFT) or S-1. We evaluated histologic findings on hematoxylin and eosin (H&E) staining and immunohistochemical expressions of Ki67, p53, p21, and apoptosis in biopsy specimens obtained before CRT and 7 days after starting CRT. These findings were contrasted with the histologic response and the degree of tumor shrinkage.. In biopsy specimens obtained before CRT, histologic marked regression according to the Japanese Classification of Colorectal Carcinoma (JCCC) criteria and the degree of tumor shrinkage on barium enema examination (BE) were significantly greater in patients with p21-positive tumors than in those with p21-negative tumors (P=.04 and P<.01, respectively). In biopsy specimens obtained 7 days after starting CRT, pathologic complete response, histologic marked regression according to both the tumor regression criteria and JCCC criteria, and T downstaging were significantly greater in patients with apoptosis-positive and p21-positive tumors than in those with apoptosis-negative (P<.01, P=.02, P=.01, and P<.01, respectively) or p21-negative tumors (P=.03, P<.01, P<.01, and P=.02, respectively). The degree of tumor shrinkage on both BE as well as MRI was significantly greater in patients with apoptosis-positive and with p21-positive tumors than in those with apoptosis-negative or p21-negative tumors, respectively. Histologic changes in H&E-stained biopsy specimens 7 days after starting CRT significantly correlated with pathologic complete response and marked regression on both JCCC and tumor regression criteria, as well as with tumor shrinkage on BE and MRI (P<.01, P<.01, P<.01, P<.01, and P=.03, respectively).. Immunohistochemical expressions of p21 and apoptosis together with histologic changes on H&E-stained biopsy specimens obtained 7 days after starting CRT are strong predictors of the response to CRT.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Apoptosis; Biomarkers, Tumor; Biopsy; Chemoradiotherapy; Cyclin-Dependent Kinase Inhibitor p21; Drug Combinations; Female; Humans; Ki-67 Antigen; Male; Middle Aged; Oxonic Acid; Rectal Neoplasms; Rectum; Tegafur; Time Factors; Treatment Outcome; Tumor Burden; Tumor Suppressor Protein p53

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

The efficacy of third-line and further-line chemotherapy for advanced non-small-cell lung cancer (NSCLC) remains unknown.. We evaluated the clinical outcome of third- and fourth-line chemotherapy for the treatment of advanced NSCLC in consecutive patients who received first-line chemotherapy at our institute between July 2002 and June 2006. From a hospital-based registry, the following data were extracted: (a) patient characteristics, (b) type of chemotherapeutic agents, and (c) objective response and survival data.. A total of 599 patients were included in this analysis. Overall, 69.3%, 38.4%, 17.7%, and 6.0% of the patients received second-, third-, fourth-, and fifth-line chemotherapy, respectively. Significant differences in age (P < .0001), performance status at the start of first-line chemotherapy (P < .0001), and histology (P = .0175) were observed between patients who received third-line chemotherapy and those who did not. Docetaxel, gefitinib, and S-1 were the most frequently used regimens for third- or fourth-line chemotherapy. Five percent of the patients had participated in phase I trials of investigational new drugs. The objective response rates and disease control rates of third- and fourth-line chemotherapy were 17.0% and 34.4% and 11.3% and 24.5%, respectively. The median survival times (95% confidence interval [CI]) from the start of first-, second-, third-, and fourth-line chemotherapy until death were 15.3 months (95% CI, 13.8-16.5 months), 12.8 months (95% CI, 10.7-14.5 months), 12.0 months (95% CI, 9.3-14.2 months), and 9.9 months (95% CI, 8.6-12.0 months), respectively.. As many as 38% of patients with advanced NSCLC who received first-line chemotherapy could receive third-line chemotherapy. This result emphasizes the need for randomized controlled trials of third-line treatment in patients with advanced NSCLC.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Large Cell; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Docetaxel; Drug Combinations; Female; Follow-Up Studies; Gefitinib; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Oxonic Acid; Quinazolines; Retrospective Studies; Taxoids; Tegafur; Treatment Outcome

Although postoperative adjuvant chemotherapy for pancreatic ductal adenocarcinoma (PDAC) improves survival in some patients, the effectiveness varies by individual, and the results remain unsatisfying. The aim of this study was to investigate whether intratumoral dihydropyrimidine dehydrogenase (DPD) and human equilibrative nucleoside transporter 1 (hENT1) expression can predict the survival of PDAC patients treated with adjuvant gemcitabine plus S-1 (GEM+S-1) chemotherapy.. Intratumoral DPD and hENT1 expression were examined by immunohistochemistry in 86 PDAC patients who received adjuvant GEM+S-1 chemotherapy after surgical resection (all R0 or R1). Relationships between clinicopathologic factors, including DPD and hENT1 expression, and disease-free or overall survival were evaluated by univariate and multivariate analyses.. DPD and hENT1 expression had no significant relationship with any other clinicopathologic factors. A multivariate disease-free survival analysis revealed that lymph node metastasis (hazard ratio [HR], 2.90: 95% confidence interval [CI], 1.51-5.90; P = 0.001), DPD expression (HR 2.47; 95% CI 1.37-4.44; P = 0.003), and hENT1 expression (HR 2.55; 95% CI 1.37-4.64; P = 0.004) as independent factors. Multivariate overall survival analysis also identified pT factor (HR 3.47; 95% CI 1.08-15.8; P = 0.03), lymph node metastasis (HR 2.08; 95% CI 1.01-4.57; P = 0.04), DPD expression (HR 1.98; 95% CI 1.06-3.71; P = 0.03), and hENT1 expression (HR 2.18; 95% CI 1.10-4.19; P = 0.02) as independent factors.. Combined analysis of DPD and hENT1 expression predicts the survival of PDAC patients treated with adjuvant GEM+S-1 chemotherapy.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Chemotherapy, Adjuvant; Deoxycytidine; Dihydrouracil Dehydrogenase (NADP); Disease-Free Survival; Drug Combinations; Equilibrative Nucleoside Transporter 1; Female; Gemcitabine; Humans; Immunohistochemistry; Kaplan-Meier Estimate; Lymphatic Metastasis; Male; Middle Aged; Multivariate Analysis; Oxonic Acid; Pancreatectomy; Pancreatic Neoplasms; Pancreaticoduodenectomy; Predictive Value of Tests; Proportional Hazards Models; Tegafur

The aim of this study was to compare short-term surgical results in pancreatic cancer patients who underwent surgical resection after neo-adjuvant chemoradiation therapy (NACRT) using S-1.. The study population comprised 77 patients with pancreatic cancer between 2006 and 2010. Out of 34 patients who underwent staging laparoscopy between 2008 and 2010, 31 patients without occult distant organ metastasis underwent chemoradiation and of whom 30 underwent pancreatectomy (NACRT group). Of the other 43 patients, 36 underwent surgical resection in 2006-2008, followed by adjuvant therapy (adjuvant group). The primary endpoint was frequency of pathological curative resection (R0).. The new regimen of NACRT was feasible and safe. Twenty-eight of 30 (93%) patients in the NACRT group had R0 resection, which was significantly higher than in the adjuvant group (21 of 36 patients, 58%, p = 0.005). The number and extent of metastatic lymph nodes in the NACRT group (1 (0-25), N0/1; 18 of 38) was significantly lower than in the adjuvant group (2 (0-19), N0/1; 23 of 30), p = 0.0363). The frequency of intractable ascites in the NACRT group (eight of 30) was significantly higher than in the adjuvant group (two of 36, p = 0.035).. Neo-adjuvant chemoradiation therapy using S-1 followed by pancreatectomy can improve the rate of pathologically curative resection and reduces the number and extent of lymph node metastasis.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Chemoradiotherapy; Chemotherapy, Adjuvant; Chi-Square Distribution; Deoxycytidine; Dose Fractionation, Radiation; Drug Combinations; Female; Gemcitabine; Humans; Lymphatic Metastasis; Male; Middle Aged; Neoadjuvant Therapy; Oxonic Acid; Pancreatectomy; Pancreatic Neoplasms; Statistics, Nonparametric; Tegafur

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

Topics: Adenocarcinoma; Adenocarcinoma of Lung; Adult; Anaplastic Lymphoma Kinase; Antimetabolites, Antineoplastic; Biomarkers, Tumor; Cell Cycle Proteins; Drug Combinations; Glutamates; Guanine; Humans; Lung Neoplasms; Male; Microtubule-Associated Proteins; Oxonic Acid; Pemetrexed; Positron-Emission Tomography; Receptor Protein-Tyrosine Kinases; Serine Endopeptidases; Tegafur; Treatment Outcome

The aim of this study is to determine the relationship between circulating tumor cells (CTCs) and response to chemotherapy in patients with unresectable metastatic colorectal cancer.. CTCs of twelve consecutive patients with K-ras wild type colorectal cancer with synchronous and/or metachronous unresectable metastatic lesions were measured by the cell search system between January 2009 and December 2010. CTCs were measured before and after chemotherapy. The regimen consisted of four courses (three months) of SOX (TS-1+L-OHP) + panitumumab.. Four patients (33%) had no detectable CTCs before chemotherapy. For these patients, no CTCs were detected after chemotherapy and their serum carcinoembryonic antigen (CEA) levels decreased after chemotherapy. Four of the other eight patients with positive CTCs had no detectable CTCs after chemotherapy and their serum CEA levels decreased after chemotherapy. The other four of eight patients with positive CTCs continued to have CTCs after chemotherapy and all four patients died of cancer within eight months after starting chemotherapy. On the other hand, all eight patients without CTCs after chemotherapy were alive over a year after starting chemotherapy.. CTCs may be able to predict the response to chemotherapy in patients with unresectable metastatic colorectal cancer.

Topics: Adenocarcinoma; Aged; Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Carcinoembryonic Antigen; Chi-Square Distribution; Colorectal Neoplasms; Disease Progression; Drug Combinations; Female; Humans; Male; Middle Aged; Neoplastic Cells, Circulating; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Panitumumab; Prospective Studies; Proto-Oncogene Proteins; Proto-Oncogene Proteins p21(ras); ras Proteins; Tegafur; Time Factors; Treatment Outcome

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

This study investigated the clinical efficacy and toxicity of the combination chemotherapy using S-1 plus irinotecan for esophageal adenocarcinoma.. This study included 10 patients with histologically confirmed adenocarcinoma of the esophagus or esophagogastric junction between April 2005 and August 2011. S-1 was administered orally at a dose of 80 mg/m²/day from day 1 to 14 and irinotecan was given intravenously on day 1 and 8 at a dose of 80 mg/m².. A total of 65 cycles were administered and the response rate was 62.5%. The 50% progression-free survival period and the 50% overall survival period for all of the patients was 8.4 months and 19.1 months, respectively and 5.9 months and 16.3 months for the 8 patients with unresectable or recurrent tumors, respectively. The 2 patients that received adjuvant chemotherapy demonstrated a prophylactic effect for the post-operative recurrence. On the other hand, this therapy showed no severe non-hematological toxicity and only 20% experienced grade 3 neutropenia. As a result, the treatment regimen could generally be performed in an outpatient basis.. The combination chemotherapy using S-1 and irinotecan showed tolerable clinical efficacy in terms of the response rate, survival and toxicity for esophageal adenocarcinoma.

Topics: Adenocarcinoma; Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Chemotherapy, Adjuvant; Disease-Free Survival; Drug Administration Schedule; Drug Combinations; Esophageal Neoplasms; Esophagectomy; Esophagogastric Junction; Female; Humans; Infusions, Intravenous; Irinotecan; Male; Middle Aged; Oxonic Acid; Pilot Projects; Survival Analysis; Tegafur; Time Factors; Treatment Outcome

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

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

Malignancy is not uncommon with immunosuppressive therapy, but pancreatic cancer is infrequently complicated in recipients of heart transplantation. Here we report a transplant case diagnosed with pancreatic cancer 4 years and 8 months after the heart transplantation. We changed the immunosuppressive regimen after the malignancy was detected, and administered everolimus along with chemotherapy using S-1, an oral fluoropyrimidine prodrug. The patient lived for 8 months after the diagnosis, and received metallic stenting for the biliary and duodenal obstruction. Also, to the best of our knowledge, this is the first report about chemotherapy and endoscopic intervention for pancreatic cancer in a heart transplantation patient.

Topics: Adenocarcinoma; Antimetabolites, Antineoplastic; Cholestasis, Extrahepatic; Combined Modality Therapy; Drug Combinations; Drug Therapy, Combination; Duodenal Obstruction; Everolimus; Follow-Up Studies; Graft Rejection; Heart Transplantation; Humans; Immunosuppressive Agents; Male; Middle Aged; Myocardial Ischemia; Neoplasm Staging; Oxonic Acid; Pancreatic Neoplasms; Postoperative Complications; Sirolimus; Stents; 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

There is no consensus on the indication for salvage chemoradiotherapy (CRT) after failure of primary chemotherapy for locally advanced pancreatic cancer (LAPC). Here we report on the retrospective analysis of patients who received salvage CRT after primary chemotherapy for LAPC. The primary objective of this study was to evaluate the efficacy and safety of salvage CRT after primary chemotherapy for LAPC.. Thirty patients who underwent salvage CRT, after the failure of primary chemotherapy for LAPC, were retrospectively enrolled from 2004 to 2011 at the authors' institution. All the patients had histologically confirmed pancreatic adenocarcinoma.. Primary chemotherapy was continued until progression or emergence of unacceptable toxicity. Eventually, 26 patients (87%) discontinued primary chemotherapy because of local tumor progression, whereas four patients (13%) discontinued chemotherapy because of interstitial pneumonitis caused by gemcitabine. After a median period of 7.9 months from starting chemotherapy, 30 patients underwent salvage CRT combined with either S-1 or 5-FU. Toxicities were generally mild and self-limiting. Median survival time (MST) from the start of salvage CRT was 8.8 months. The 6 month, 1-year and 2-year survival rates from the start of CRT were 77%, 33% and 26%, respectively. Multivariate analysis revealed that a lower pre-CRT serum CA 19-9 level (≤ 1000 U/ml; p = 0.009) and a single regimen of primary chemotherapy (p = 0.004) were independent prognostic factors for survival after salvage CRT. The MST for the entire patient population from the start of primary chemotherapy was 17.8 months, with 2- and 3-year overall survival rates of 39% and 22%, respectively.. CRT had moderate anti-tumor activity and an acceptable toxicity profile in patients with LAPC, even after failure of gemcitabine-based primary chemotherapy. If there are any signs of failure of primary chemotherapy without distant metastasis, salvage CRT could be a treatment of choice as a second-line therapy. Patients with relatively low serum CA19-9 levels after primary chemotherapy may achieve higher survival rates after salvage CRT. The strategy of using chemotherapy alone as a primary treatment for LAPC, followed-by CRT with salvage intent should be further investigated in prospective clinical trials.. 2011-136

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Chemoradiotherapy; Deoxycytidine; Drug Combinations; Female; Fluorouracil; Gemcitabine; Humans; Induction Chemotherapy; Kaplan-Meier Estimate; Male; Middle Aged; Oxonic Acid; Pancreatic Neoplasms; Prognosis; Proportional Hazards Models; Retrospective Studies; Salvage Therapy; Tegafur; Treatment Outcome

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

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

S-1 is one of the second-line candidate agents for gemcitabine-refractory unresectable pancreatic cancer. Two phase II studies have been reported for second-line chemotherapy with S-1, but these studies did not investigate introduction rate and suitable dose of second-line S-1. Therefore, we conducted a prospective multicenter study in which chemo-naïve patients were enrolled and had two levels of S-1 dose.. Chemo-naïve patients with unresectable pancreatic cancer were enrolled. This study started with 80 mg/m(2)/day dose of S-1 as second-line chemotherapy and tolerability was checked. When tolerability was not confirmed in initial patients, the dose of S-1 was shifted to 60 mg/m(2)/day. When tolerability was confirmed at 80 or 60 mg/m(2)/day, the study continued, and up to 20 patients were accumulated with the dose. In addition, the introduction rate of second-line S-1 was examined.. Six of the initial 7 patients with 80 mg/m(2)/day dose of S-1 completed one course of second-line chemotherapy. Twenty patients were accumulated with an 80 mg/m(2)/day dose of S-1. With the exception of one patient continued gemcitabine chemotherapy, two of the remaining 19 patients withdrew from this study because of toxicity during the period of gemcitabine chemotherapy. Fifteen of the remaining 17 gemcitabine-refractory patients could complete one course of S-1 as second-line chemotherapy with acceptable toxicity.. This prospective multicenter study showed that 15 (78.9%) out of 19 chemo-naïve unresectable pancreatic cancer patients could complete one course of 80 mg/m(2)/day dose of S-1 as second-line chemotherapy after first-line gemcitabine chemotherapy failure with tolerable toxicity.

Topics: Adenocarcinoma; Adult; Aged; Alanine Transaminase; Antimetabolites, Antineoplastic; Aspartate Aminotransferases; Bile; Deoxycytidine; Dose-Response Relationship, Drug; Drug Combinations; Drug Resistance, Neoplasm; Female; Follow-Up Studies; Gemcitabine; Humans; Injections, Intravenous; Male; Middle Aged; Oxonic Acid; Pancreas; Pancreatic Neoplasms; Prospective Studies; Survival Analysis; Tegafur; Treatment Failure

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

We describe the case of a 74-year-old male patient with synchronous double primary lung cancers: adenocarcinoma in the right lower lobe and squamous cell carcinoma in the left upper lobe (LUL). These tumors were difficult to differentiate radiographically from a single metastatic primary cancer, but their eventual diagnoses were triggered by their responses to chemotherapy, which included pemetrexed. After two courses of chemotherapy with pemetrexed and carboplatin, the right lower lobe mass had partially resolved; however, the LUL mass had increased. When S-1 was used as fourth-line chemotherapy, the size of the LUL mass decreased. Pemetrexed is a potentially useful drug for treating nonsquamous cell carcinoma, but may not be appropriate in cases with a coexisting squamous cell carcinoma. Our experience with this interesting case leads us to propose that S-1 monotherapy may provide a treatment option in pemetrexed-refractory cases.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Squamous Cell; Drug Combinations; Glutamates; Guanine; Humans; Lung Neoplasms; Male; Neoplasms, Multiple Primary; Oxonic Acid; Pemetrexed; 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

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 aim of this study is to investigate the prognostic value of intratumoral expression of thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), and orotate phosphoribosyltransferase (OPRT) in patients treated with S-1-based chemotherapy after surgical resection for pancreatic adenocarcinoma.. Intratumoral TS, DPD, and OPRT expression was investigated in 106 patients with resected pancreatic adenocarcinoma by immunohistochemistry. Associations between clinicopathological factors, including intratumoral TS, DPD, and OPRT expression, and survival were evaluated by univariate and multivariate analyses.. Of 106 patients, 72 had received S-1-based adjuvant chemotherapy (S-1(+) group), and 34 had not (S-1(-) group). High TS, DPD, and OPRT expression was observed in 64%, 37%, and 66% of patients, respectively. Among S-1(+) group patients, survival was significantly better for patients with low DPD expression than for patients with high DPD expression (P = 0.022). Intratumoral DPD expression was the only independent prognostic factor for patients treated with S-1-based adjuvant chemotherapy by multivariate analysis (P = 0.037). Intratumoral TS and OPRT expression did not appear to influence survival.. Intratumoral DPD expression may be a relevant predictive marker of survival benefit associated with S-1-based adjuvant chemotherapy for pancreatic adenocarcinoma.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Chemotherapy, Adjuvant; Dihydrouracil Dehydrogenase (NADP); Drug Combinations; Female; Humans; Male; Middle Aged; Orotate Phosphoribosyltransferase; Oxonic Acid; Pancreatectomy; Pancreatic Neoplasms; Prognosis; Tegafur; Thymidylate Synthase

We report a 75-year-old woman who suffered multiple metachronous osteosclerotic bone metastases 4 years after a distal gastrectomy for early gastric cancer (EGC). The primary tumor was a poorly differentiated adenocarcinoma, which had invaded the submucosal layer, and only one lymph node metastasis was noted. To the best of our knowledge, cases of EGC combined with metachronous osteosclerotic multiple bone and bone marrow metastases that respond to chemoradiotherapy are very rare. In this case, the multiple bone metastases were diagnosed 4 years after surgery. The patient's metastatic tumor was successfully treated using S-1, paclitaxel, and camptothecin, with subsequent irradiation. The patient survived for 24 months after the treatment, without having any major symptoms.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Neoplasms; Bone Neoplasms; Camptothecin; Chemoradiotherapy; Drug Combinations; Female; Humans; Lymphatic Metastasis; Oxonic Acid; Paclitaxel; Stomach Neoplasms; Tegafur; Treatment Outcome

A 62-year-old woman was admitted for epigastralgia, nausea and tarry stool.Abdominal CT showed a tumor to the jejunum from the duodenum, and peritoneal dissemination.Gastroduodenoscopy showed a type 2 tumor, and the histopathological examination revealed a well-to moderately-differentiated adenocarcinoma.Accordingly, she was diagnosed with primary adenocarcinoma of the small intestines and underwent surgery.The first-line chemotherapy with S-1/CPT-11 was started after surgery, and the tumor marker returned to normal.The treatment of 14 courses was continued until PD due to the enlargement of the peritoneal dissemination.Second - and third-line chemotherapy were performed; however, she died 20 months after the initial treatment.Although the incidence of primary adenocarinoma of the small intestines is relative- ly low, and there is no established chemotherapy at present, this case suggested that S-1/CPT-11may be an effective regimen for advanced primary adenocarcinoma of the small intestines.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Combined Modality Therapy; Drug Combinations; Duodenal Neoplasms; Fatal Outcome; Female; Humans; Irinotecan; Jejunal Neoplasms; Middle Aged; Oxonic Acid; Peritoneal Neoplasms; Tegafur; Tomography, X-Ray Computed

TS-1 is an oral anticancer agent containing two biochemical modulators for 5-fluorouracil (5-FU) and tegafur (FT), a metabolically activated prodrug of 5-FU. TS-1 has been recognized as an effective anticancer drug using standard therapies for patients with advanced pancreatic cancer along with gemcitabine. However, a high level of inherent and acquired tumor resistance to TS-1 induces difficulty in the treatment. To identify proteins linked to the TS-1-resistance of pancreatic cancer, we profiled protein expression levels in samples of TS-1-resistant and -sensitive pancreatic cancer cell lines by using two-dimensional gel electrophoresis (2-DE) and liquid chromatography-tandem mass spectrometry (LC-MS/MS). The cytotoxicity of a 5-FU/5-chloro-2,4-dihydroxypyridine (CDHP) combination towards pancreatic cancer cell lines was evaluated by MTS assay. Panc-1, BxPC-3, MiaPaCa-2 and PK59 showed high sensitivity to the 5-FU/CDHP combination (TS-1-sensitive), whereas PK45p and KLM-1 were much less sensitive (TS-1-resistant). Proteomic analysis showed that eleven spots, including T-complex protein 1 subunit beta, ribonuclease inhibitor, elongation factor 1-delta, peroxiredoxin-2 and superoxide dismutase (Cu-Zn), appeared to be down-regulated, and 29 spots, including hypoxia up-regulated protein 1, lamin-A/C, endoplasmin, fascin and annexin A1, appeared to be up-regulated in TS-1-resistant cells compared with -sensitive cells. These results suggest that the identified proteins showing different expression between TS-1-sensitive and -resistant pancreatic cancer cells possibly relate to TS-1-sensitivity. These findings could be useful to overcome the TS-1-resistance of pancreatic cancer cells.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Cell Line, Tumor; Drug Combinations; Drug Resistance, Neoplasm; Electrophoresis, Gel, Two-Dimensional; Fluorouracil; Humans; Mass Spectrometry; Neoplasm Proteins; Oxonic Acid; Pancreatic Neoplasms; Proteomics; Pyridines; Tegafur

The patient, a 58-year-old woman, underwent a partial excision of the right breast and an axillary lymph node dissection in October 2004. The histopathological findings were: solid tubular carcinoma with metastasis to 17 axillary lymph nodes; triple negative-type breast cancer. As adjuvant therapy, FEC60 was administered 6 times, followed by radiotherapy applied to the residual breast and the right supraclavicular fossa. In Novermber 2007, she noted a tumorous growth above the right clavicle. The pathological diagnosis via fine needle biopsy was adenocarcinoma. An oral antineoplastic agent was given for about 6 months, but did not alter the lymph nodes. No distant recurrence was noted during this time. In August 2008, the right supraclavicular lymph nodes were dissected. The patient has been under observation without treatment, but no signs of recurrence have been noted. It was thought that excision of the recurrent supra-clavicular lymph nodes should be considered after careful examination in some individual cases.

Topics: Adenocarcinoma; Antimetabolites, Antineoplastic; Biopsy, Needle; Breast Neoplasms; Clavicle; Combined Modality Therapy; Drug Combinations; Female; Humans; Lymph Node Excision; Lymphatic Metastasis; Middle Aged; Oxonic Acid; Recurrence; Remission Induction; Tegafur

The patient was a 66-year-old male with adenocarcinoma of the esophagogastric junction and severe esophageal invasion, which was diagnosed as cType 3, cT4a (SE) cN3cM1 (LYM), cStage IV(histopathology: por 1). We tried concurrent chemoradiotherapy consisting of PTX 60 mg/m(2) and CDDP 25 mg/m(2), respectively (once a week), and a total of 45 Gy of radiotherapy treatment. Then, for effective continuation, chemotherapy using S-1 was performed as second-line therapy. A complete response was achieved and continued for more than 2 years after initial chemoradiotherapy; his complaints abated and his quality of life improved. Although gastro-intestinal symptoms and bone marrow suppression were observed as adverse effects, they were within a tolerable range and did not interfere with the concurrent chemoradiotherapy. This regimen appears to be feasible and effective for advanced gastric carcinoma refractory to other regimens.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Drug Combinations; Esophageal Neoplasms; Esophagogastric Junction; Humans; Male; Neoplasm Invasiveness; Oxonic Acid; Paclitaxel; Stomach Neoplasms; Tegafur; Tomography, X-Ray Computed

The patient was an 80-year-old female with chief complaint of anemia. She was diagnosed as a type 3 gastric cancer (por/tub2) of the esophagogastric junction by gastrointestinal endoscopy in November 2010. CT scan revealed no distant metastasis and we diagnosed as c-stage II B (T4aN0M0). However, severe COPD was detected by the respiratory function test. Considering her age and respiratory function, we decided that total gastrectomy under general anesthesia was difficult. She was treated with radiation( 50.4 Gy/28 Fr) and the combination chemotherapy of S-1( 80 mg/m², day 1-21) plus low-dose CDDP (6 mg/m², day 1-5, 8-12, 15-19) during her hospitalization, and treated with S-1 mono-therapy as an outpatient. The tumor was reduced and the hemorrhage was not seen though the response was SD. Moreover, she did not experience any adverse event of grade 3 or more. The chemoradiation therapy appears to be effective for patients of adenocarcinoma of the esophagogastric junction.

Topics: Adenocarcinoma; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Chemoradiotherapy; Cisplatin; Drug Combinations; Esophageal Neoplasms; Esophagogastric Junction; Female; Humans; Neoplasm Staging; Oxonic Acid; Stomach Neoplasms; Tegafur

The aim of this study was to assess the feasibility of using S-1 as adjuvant chemotherapy after the resection of pancreatic cancer.. S-1 was initially administered or ally at a dose of 50 mg twice daily for 14 days, followed by a rest period of seven days to complete one course. Administration was repeated with dose escalation in each cycle until the recommended dose (RD; 80 mg/m2, maximum 120 mg/day), unless grade 3 adverse events were observed. Administration was planned to continue at least 6 months (eight courses).. Eighteen patients who had undergone resection of pancreatic adenocarcinoma were enrolled in this study. The RD could be administered to 12 patients(67%), and 80% of the RD was given to five patients(28%). Although grade 3 anemia occurred in one patient, grade 4 hematologic adverse events were not observed. Grade 3 cutaneous toxicity (hand-foot syndrome)was observed in two patients. The cumulative relative total administered dose rate of S-1 was 0. 86. The 3-year relapse-free survival rate was 31. 4%, and the median overall survival time was 25. 3 months.. Long-term postoperative administration of S-1 at the RD is safe and appears to be a promising method of adjuvant chemotherapy.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Disease-Free Survival; Drug Combinations; Feasibility Studies; Female; Humans; Male; Middle Aged; Oxonic Acid; Pancreatic Neoplasms; Pancytopenia; Survival Rate; Tegafur

This pilot study was carried out to evaluate the efficacy of chemotherapy for patients with peritoneal dissemination from gastric cancer or positive lavage cytology diagnosed by staging laparoscopy.. Sixteen patients were enrolled. Paclitaxel was administered at 120 mg/m(2) on day 1 and S-1 was administered orally at 80 mg/m(2) for 14 consecutive days, followed by a 1-week rest, as one course. After five courses of this therapy, the primary gastric tumors were evaluated and second-look laparoscopy was performed for patients showing partial response or stable disease with clinical benefit.. Partial response or stable disease with clinical benefit was confirmed in seven and five patients, respectively, and these patients underwent second-look laparoscopy. No viable cancer cells were detected on cytopathological investigation during second-look laparoscopy in 9 patients who underwent surgical treatment. The intent-to-treat response rate for gastric tumor was 44% and the rate of disappearance of peritoneal metastasis was 38% (6 cases) at surgery. The median survival time was 555 days. Leucopenia of grade 3 and neutropenia of grade 3 were recognized in two and three patients, respectively.. This chemotherapy regimen may be an acceptable option for patients with peritoneal dissemination. We plan to study this regimen further in gastric cancer patients with peritoneal dissemination.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Female; Humans; Laparoscopy; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Paclitaxel; Peritoneal Neoplasms; Pilot Projects; Prospective Studies; Stomach Neoplasms; Survival Rate; Tegafur

No established treatment exists for urachal carcinoma,except curative resection,and its prognosis is poor. More than 80% of urachal carcinomas are adenocarcinomas. We report a case of advanced urachal carcinoma treated with S-1 and cisplatin combination (S-1/CDDP) chemotherapy. The patient,a 61-year-old woman,presented with macroscopic hematuria. A tumor was detected on the bladder dome and transurethral resection was performed. Histopathological findings indicated poorly differentiated adenocarcinoma. Serum carcinoembryonic antigen and carbohydrate antigen 19-9 levels were 3.5 ng/ml and 140 U/ml respectively. Magnetic resonance images indicated an extension of this tumor to the retroperioneal space. Metastasis to her right ischium was suspected from bone scintigraphy results. The tumor was diagnosed as stage IVB (Sheldon's category) urachal carcinoma. After one cycle of S-1/CDDP chemotherapy,the size of the tumor on the bladder dome decreased,after which total cystectomy was performed. The surgical margin of the cystectomy specimen was negative for malignant cells,although poorly differentiated adenocarcinoma was still observed in this specimen. The findings of this study indicate that this therapy might be beneficial for treating advanced urachal carcinomas. This is the second report of successful treatment of advanced urachal carcinoma with S-1/CDDP chemotherapy.

Topics: Adenocarcinoma; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Cystectomy; Drug Combinations; Female; Humans; Middle Aged; Oxonic Acid; Tegafur; Urachus; Urinary Bladder Neoplasms

Although neoadjuvant chemotherapy has been recognized as an important option to improve the clinical outcome of patients with advanced gastric carcinoma, the precise histological effects of neoadjuvant chemotherapy on the primary and metastatic foci have not well been documented. The aim of the present study was thus to evaluate histological effects of S-1-based neoadjuvant chemotherapy on the resected specimens of gastric carcinoma and regional lymph nodes, and primarily to focus on the histology of the cases showing complete regression of the primary cancer cells. A total of 164 patients received neoadjuvant chemotherapy with the combination of S-1 (80 to 120 mg/body/day for 3 weeks) and cisplatin (35 to 60 mg/m2 on day 8). One course of the regimen was completed in 5 weeks and the next course was started after 2 weeks. A total of 9 patients who showed complete regression of the primary gastric cancer were subjects of the study. A total of 77 cases (46.9%) responded to the neoadjuvant chemotherapy and 9 cases (5.5%) showed a complete regression of the primary gastric carcinoma. Three out of 9 cases had remnant cancer cells in the metastatic foci; 1 in the liver and 2 in the regional lymph nodes. Five of 9 cases were solid-type poorly-differentiated adenocarcinoma (por1), and the incidence of responders was the highest in patients with por1. A total of 8 cases were alive and the mean postoperative survival was 612±192 days. One patient died 518 days after gastrectomy associated with hepatic resection. S-1-based neoadjuvant chemotherapy has significant histological effects on gastric carcinoma and metastatic foci, which may further improve long-term clinical outcome in patients with advanced gastric carcinoma.

Topics: Adenocarcinoma; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Female; Humans; Male; Middle Aged; Neoadjuvant Therapy; Oxonic Acid; Stomach Neoplasms; Tegafur; Treatment Outcome

A 29-year-old man with a type 4 tumor, in the lower third of the stomach, and carcinomatous ascites was diagnosed by aspiration cytology of the ascitic fluid. Curative resection was considered impossible, and S1 (120 mg/d) and cisplatin (90 mg/d) were given for 21 days in 1 course. The cancer lesion showed marked remission (partial response), and the ascites completely disappeared after the fourth course. Twenty-five days after completion of the S1 treatment, laparoscopy-assisted total gastrectomy was performed. Histopathological examination showed no remnant cancer cells in the resected specimen and no lymph node metastases. The tumor was replaced with fibrosis having a granulomatous change. The patient's postoperative course was uneventful. The patient was continued with S1 monotherapy after surgery, and no signs of recurrence or metastases have been seen on any examination 12 months after the surgery.

Topics: Adenocarcinoma; Adult; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Ascites; Cisplatin; Combined Modality Therapy; Drug Combinations; Endoscopy, Gastrointestinal; Gastrectomy; Humans; Laparoscopy; Lymph Node Excision; Male; Oxonic Acid; Stomach Neoplasms; Tegafur

The case was a 36-year-old male whose chief complaints were anorexia and weight loss. Upper gastrointestinal endoscopy revealed circumferential stenosis in the fourth portion of the duodenum, while CT revealed a tumor with a diameter of 60 mm continuing as a single mass from the pancreatic body and tail to the fourth portion of the duodenum, and this was accompanied by findings that raised suspicions of circumferential invasion of the superior mesentric artery (SMA). Based on these results and biopsy, the patient was diagnosed with pancreatic and SMA invasion of duodenal cancer that was considered to be unresectable. After performing gastrojejunostomy, we administered DOC (40 mg/m2, day 1), CDDP (60 mg/m2, day 1), and S-1( 80 mg/m2, day 1-14) for 3 courses. The tumor response was PR and the images indicated the SMA invasion was disappeared. We judged that the tumor could be gone by a resection while preserving the SMA. In the surgical findings, the tumor continued as a single mass from the pancreatic body and tail to the third portion of the duodenum, and the surrounding area exhibited marked fibrosis. We performed a pancreatic tail resection along with combined resection of third and fourth portions of the duodenum, transverse colon and splenic flexure, and left adrenal gland. The case was diagnosed to be well-differentiated invasive ductal pancreatic cancer with duodenal invasion. Cancer invasion was not observed in any of the stripped surfaces surrounding the pancreas. The T3, N1, M0, fStage III antitumor effects were mildly effective. In this case, the treatment was initially started by considering the case as one of duodenal cancer, but the final results of a pathological diagnosis revealed that it was pancreatic cancer. However, either way, even though the case was unresectable before the chemotherapy performed for duodenal cancer was significantly effective for the pancreatic cancer. Therefore, a resection became possible, and an R0 resection was also effective.

Topics: Adenocarcinoma; Adult; Antimetabolites, Antineoplastic; Antineoplastic Agents; Cisplatin; Combined Modality Therapy; Docetaxel; Drug Combinations; Duodenal Neoplasms; Humans; Male; Mesenteric Artery, Superior; Neoplasm Invasiveness; Oxonic Acid; Pancreatic Neoplasms; Taxoids; Tegafur

We report a successful case of chemotherapy with oral fluoropyrimidines. The patient was an 81-year-old woman who complained epigastric discomfort. Endoscopy revealed a type 3 advanced gastric cancer, and the biopsy specimen was defined histologically as poorly-differentiated adenocarcinoma. She didn't hope for an operation, but agreed to receive chemotherapy. S-1 (80 mg/day) was administered for 14 days, followed by 7 days rest. This schedule induced grade 1 thrombocytopenia and fatigue after two weeks administration. Therefore, we reduced the administration dosage to 60 mg/ day. Almost complete response (CR) was observed after 8 weeks of S-1 administration. But she was admitted urgently to other emergency hospital for stumbling due to dizziness accompanied with vomiting and anorexia. We considered it was difficult to continue S-1 administration. Therefore, we changed S-1 to UFT-E and started from 300 mg/day. One month later, as the adverse effects were not recognized, we increased a dosage of UFT-E to 400 mg/day for the purpose of more dose intensity. After 6 months, CR was confirmed continuously. We reduced UFT-E to 300 mg/day, and CR has been continued for 3 years until now without any adverse events. There was no evidence regarding the best timing to syop anticancer administration. As the adverse effect was very mild and her quality of life improved, we continued UFT-E administration for a long time.

Topics: Adenocarcinoma; Administration, Oral; Aged, 80 and over; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Female; Humans; Oxonic Acid; Remission Induction; Stomach Neoplasms; Tegafur; Uracil

The most common treatment for patients of peritoneal dissemination of gastric cancer is a systemic chemotherapy, but the prognosis of these patients is very poor. For these diseases, some have reported the usefulness of intraperitoneal chemotherapy with cisplatin (CDDP), because of the direct cytotoxicity. Here, we report an effective treatment by chemotherapy with S-1 plus CDDP, intraperitoneal administration for the patients of peritoneal dissemination of gastric cancer. The patient was a 41-year-old male with upper abdominal pain. Upper gastrointestinal endoscopy showed a large type 3 gastric cancer from the cardia to antrum. Intraoperative peritoneal lavage cytology and dissemination was positive, thus we performed the total gastrectomy and implanted the intraperitoneal (IP) port in the Douglas's pouch. S-1 was given orally twice daily for the first 3 weeks of a 5-week cycle. CDDP was given as an intraperitoneal infusion on day 8 of each cycle. After 10 courses, he was treated with S-1 alone because he had an allergic reaction of CDDP. In 35 courses, he had survived for 5 years as disease free. Intraperitoneal chemotherapy may be a promising treatment for the patients who have peritoneal dissemination from gastric cancer.

Topics: Adenocarcinoma; Administration, Oral; Adult; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Humans; Infusions, Parenteral; Male; Oxonic Acid; Peritoneal Neoplasms; Stomach Neoplasms; Tegafur

The prognosis of type 4 advanced gastric cancer is extremely poor, even the use of multidisciplinary treatment cannot provide satisfactory results. Presented here is a case of highly advanced gastric cancer in which preoperative chemotherapy was effective and resection possible.. A 64-year-old female complained of epigastric distress. Current medical history included: hypertension, hyperlipemia, diabetes, chronic heart disease and development of epigastric distress. Endoscopy was performed upon examination in the Gastroenterology Department. Visual inspection showed a lesion extending from the greater curvature of the fundus to the antrum. Type 4 advanced gastric cancer was strongly suspected. Biopsy samples taken from the antral lesser curvature and from the ulcer border on the upper anterior wall of the body were diagnosed as Group V, adenocarcinoma. Abdominal CT revealed no hepatic mass, but overall thickening of the gastric wall was noticeable and the lymph nodes in the area of the lesser curvature of the stomach and celiac artery were identified. Abdominal ultrasound showed an overall thickening of the gastric wall, and invasion into a portion of the left hepatic lobe and pancreas was suspected. Swelling of the lymph nodes surrounding the stomach was suspected.. Because of gastric cancer with suspected invasion of the left hepatic lobe and pancreas, it was decided to perform preoperative chemotherapy (S-1 + CDDP) and then perform a total gastrectomy. Four courses were performed.. Endoscopy revealed no change in the lesion within the stomach. Only scarring in the body and antrum was found, the enlargement was greatly reduced and visual inspection revealed no esophageal infiltration. Biopsy samples were taken from 2 sites, the body center on the lesser curvature side and the greater curvature of the antrum. Scar-like fibrosis was significant and it was not possible to distinguish an increase in poorly differentiated adenocarcinoma. Abdominal CT showed a reduction in gastric wall thickening. These findings showed preoperative chemotherapy to be effective. Following the chemotherapy, a total gastrectomy in addition to splenectomy and cholecystectomy were performed. Histopathological findings showed MLU, type 5, approx. 8.5 × 13 cm, poorly differentiated adenocarcinoma (por 2), INF γ, sci, pT2 (SS), ly2, v0, pN2 (#1: 2/8, #6: 1/6, #11p: 2/5), pPM (-), pDM (-), Stage IIIA. Along with the formation of fibrous scar tissue, an invasive growth of por 2 poorly differentiated adenocarcinoma was found from the submucosal layer to just beneath the serosal layer. Therapeutic effect of the chemotherapy was Grade 2. Post operative S-1 + CDDP was begun but nausea developed and S-1 was reduced. Because of a decrease of neutrophils and nausea, the therapy was changed to UFT. It is currently 6 months after surgery and there are no signs of recurrence.. Preoperative chemotherapy (S-1 + CDDP) is a therapy which shows promise in reducing tumor size even in highly advanced gastric cancer.

Topics: Adenocarcinoma; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Drug Combinations; Female; Gastrectomy; Humans; Middle Aged; Oxonic Acid; Preoperative Period; Stomach Neoplasms; Tegafur

A 68-year-old male who had undergone a distal gastrectomy for gastric cancer in 1996 visited our hospital. Gastroscopy revealed a type 2 tumor at upper corpus, and its biopsy showed poorly differentiated adenocarcinoma. Because enhanced CT showed lymph node swelling at para aorta, S-1 (100 mg/day) was administered for 14 days and CDDP (20 mg/day) was administered for 4 days as 1 course. After 2 courses, the main tumor and lymph node swelling reduced evidently. A total gastrectomy was performed and the pathology revealed no cancer cells in the stomach and dissected lymph nodes. Two months after the operation, speech disturbance and numbness of the left hand appeared. CT showed 3 metastatic brain tumors, and radiation therapy was administered. Four months after the operation, headache appeared and cerebrospinal fluid examination showed adenocarcinoma cells. Although MTX (10 mg) was administered intrathecally, he was died 5 months after the operation.

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

We report a patient with unresectable advanced gastric cancer who was successfully treated with chemotherapy after gastrojejunostomy. A 64-year-old man was admitted to our hospital complaining of appetite loss and body weight loss. Abdominal enhanced CT revealed a gastric wall thickening and swelling of lymph nodes in the lesser curvature. Upper gastrointestinal endoscopy showed a gastric cancer in the antrum of the stomach. He underwent laparotomy, which revealed a T4 tumor invading the pancreas. Gastrojejunostomy was performed. After the operation, intake therapy of 80-100 mg S-1 was started for four weeks followed by two weeks rest as one course. After 2 courses of the therapy, abdominal enhanced CT showed a partial response of the lymph nodes. He is alive for 19 months after the operation. Abdominal enhanced CT showed a stable disease. This case suggested that S-1 chemotherapy after gastrojejunostomy was effective for unresectable advanced gastric cancer because of the long-term survival and an improvement of the patient's quality of life.

Topics: Adenocarcinoma; Antimetabolites, Antineoplastic; Combined Modality Therapy; Drug Combinations; Gastric Bypass; Humans; Male; Middle Aged; Oxonic Acid; Stomach Neoplasms; Tegafur

Gastric endocrine cell carcinoma is rare and associated with a poor prognosis. The first case was a man in his sixties with gastric endocrine cell carcinoma, of which a clinical finding was T2N1M0H1 (Stage IV). S-1 + CDDP therapy was selected and failed. CDDP+CPT-11 therapy was started and CT showed a partial response in ten months. But the tumor was re-grown and the patient died twenty months after diagnosis. The second case was a man in his seventies with gastric endocrine cell carcinoma, of which a clinical finding was T3N1M0H0P0, Stage IIIa, underwent total gastrectomy. Abdominal contrast-enhanced CT scan performed a month after the operation disclosed hepatic metastasis. After two months of S-1 regimen, CDDP + CPT-11 therapy was started.

Topics: Adenocarcinoma; Aged; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cisplatin; Drug Combinations; Endocrine Gland Neoplasms; Humans; Irinotecan; Male; Middle Aged; Oxonic Acid; Stomach Neoplasms; Tegafur

A 77-year-old man had sigmoidectomy for sigmoid colon cancer. Two years later, a right hepatectomy for a liver metastasis was performed. Two years thereafter, abdominal computed tomography scanning and FDG-PET showed the right adrenal mass. Right adrenalectomy was performed with a diagnosis of solitary adrenal metastasis from sigmoid colon cancer. On pathology, adrenal metastasis was confirmed. The patient underwent adjuvant chemotherapy (IRIS). There have been no signs of recurrence for 6 months after the operation. We conclude that patients with solitary adrenal metastasis from colorectal cancer may benefit from surgical resection.

Topics: Adenocarcinoma; Adrenal Gland Neoplasms; Adrenalectomy; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Chemotherapy, Adjuvant; Drug Combinations; Humans; Irinotecan; Male; Oxonic Acid; Sigmoid Neoplasms; Tegafur

An 80-year-old female patient was undergone sigmoidectomy with D2 lymph node dissection for type 2 sigmoid colon cancer in February 2007. A post operative pathological finding of cancer was SS, N0, P0, H0, M0 (Stage II), curative A. Twelve months after the operation, elevated CEA level was observed. CT scan and MRI revealed a mass of 10 cm in diameter with multiple cysts in the pelvic cavity, which was diagnosed a malignant ovarian tumor. In May 2008, total hysterectomy, bilateral oophorectomy, and partial omentectomy were performed and its pathological finding was metastatic ovarian tumor originating from colon cancer. Adjuvant chemotherapy was administered, as cancer cells were detected in the ascites. The patient has been in good health without recurrence for 25 months after the second operation.

Topics: Adenocarcinoma; Aged, 80 and over; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Drug Combinations; Female; Humans; Hysterectomy; Krukenberg Tumor; Ovarian Neoplasms; Ovariectomy; Oxonic Acid; Sigmoid Neoplasms; Tegafur; Uracil

An 83-year-old man commuting to our hospital with postoperative ascending colon cancer was pointed out an increase of CA19-9. CT scan revealed an intrahepatic cholangiocarcinoma in the left lobe. In May 2007, an operation was performed. We recognized a lymph node swelling in the hepatoduodenal ligament. Pathologically, it was moderately differentiated adenocarcinoma. Therefore, the operation did only the cholecystectomy. Gemcitabine was administered once a week for 3 weeks followed by a week rest. It was administered for about 20 months and the evaluation during the period was PR or SD. Afterwards, the tumor had increased gradually. Gemcitabine was changed to S-1. Then, S-1 was changed to gemcitabine again because the enlargement of the tumor and the rise of tumor markers were observed. Consequently, tumor markers decreased. Now, the patient is under an outpatient care maintaining ADL.

Topics: Adenocarcinoma; Aged, 80 and over; Antimetabolites, Antineoplastic; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Cholangiocarcinoma; Deoxycytidine; Drug Combinations; Gemcitabine; Humans; Male; Oxonic Acid; Tegafur; Treatment Outcome

This is an account of a case of primary adenocarcinoma of the small intestine with peritoneal dissemination successfully treated with chemotherapy. A 64-year-old woman was admitted with a complaint of severe abdominal distension. Abdominal computerized tomography revealed a bowel obstruction with tumor and the remarkable small bowel dilation of oral side of tumor. The tumor was found at surgery to be at the ileum 15 cm proximal from the ileocecal region. Peritoneal dissemination was recognized around the ileocecal region, so ileum partial resection was performed for the primary cancer lesion and dissemination region. Pathological diagnosis of the resected specimen was adenocarcinoma with lymph nodes metastasis. The peritoneal dissemination consisted of metastatic adenocarcinoma from small intestine. After an operation, internal use of S-1 was performed as adjuvant chemotherapy. But a recurrent lesion at the ovarium was detected 6 months after surgery. The patient was subsequently treated with resection of the ovarium. For lung metastasis, the combination chemotherapy with mFOLFOX6 + bevacizumab was administered. Primary small intestinal adenocarcinoma is a rare disease, and it is often diagnosed as advanced cancer because of few characteristic symptoms. So carcinoma of the small intestine usually has a poor prognosis.

Topics: Adenocarcinoma; Angiogenesis Inhibitors; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Combined Modality Therapy; Drug Combinations; Female; Fluorouracil; Humans; Ileal Neoplasms; Intestinal Neoplasms; Leucovorin; Lymphatic Metastasis; Middle Aged; Organoplatinum Compounds; Ovarian Neoplasms; Oxonic Acid; Tegafur

A 66-year-old male was admitted to our hospital because of dyspnea in 2007. Cancerous pleural effusion and gastric cancer was diagnosed, and the chemotherapy consisted of S-1 + DOC was started for Stage IV gastric cancer. In 2009, lung cancer was found. The chemotherapy was changed to CDDP + CPT-11. This chemotherapy was effective for both lung and gastric cancers. Operation was performed for both tumors in 2010, and the pathological diagnosis revealed that gastric cancer was pStage I, Cur A, and the lung cancer was pStage IA, R0. Pathologic histology inspection of both tumors was judged to be effective for the chemotherapy prior to resection.

Topics: Adenocarcinoma; Aged; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cisplatin; Docetaxel; Drug Combinations; Humans; Irinotecan; Lung Neoplasms; Male; Neoadjuvant Therapy; Neoplasms, Multiple Primary; Oxonic Acid; Stomach Neoplasms; Taxoids; Tegafur

Few patients with pancreatic body or tail carcinoma are candidates for surgical resection, and the efficacy of postoperative adjuvant chemotherapy for patients with pancreatic body or tail carcinoma has not been elucidated. The aim of this study was to determine the effect of adjuvant gemcitabine and S-1 therapy for patients with adenocarcinoma of the body or tail of the pancreas who had undergone surgical resection by distal pancreatectomy.. Medical records of 34 patients with pancreatic body or tail carcinoma who underwent surgical resection were reviewed retrospectively. Eighteen patients received postoperative adjuvant gemcitabine and S-1 chemotherapy. Univariate and multivariate models were used to analyze the effect of various clinicopathological factors on long-term survival.. There were no deaths due to surgery. Overall, 1-, 2-, and 5-year survival rates were 69%, 40%, and 25%, respectively (median survival time, 14.4 months). Univariate analysis revealed that adjuvant gemcitabine plus S-1 chemotherapy, blood transfusion, splenic artery invasion, lymph node metastasis, surgical margin status, and International Union Against Cancer stage were associated significantly with long-term survival (P < 0.05). Furthermore, use of a Cox proportional hazards regression model indicated that adjuvant gemcitabine plus S-1 chemotherapy and absence of lymph node metastasis were significant independent predictors of a favorable prognosis (P < 0.05).. Postoperative adjuvant gemcitabine plus S-1 chemotherapy may improve survival after surgical resection for pancreatic body or tail carcinoma.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Deoxycytidine; Drug Combinations; Female; Follow-Up Studies; Gemcitabine; Humans; Male; Middle Aged; Oxonic Acid; Pancreatectomy; Pancreatic Neoplasms; Retrospective Studies; Ribonucleotide Reductases; Tegafur; Treatment Outcome

This study aimed to evaluate the safety and efficacy of oral fluoropyrimidines and cisplatin therapy in elderly patients with untreated advanced gastric cancer (AGC) retrospectively. In addition, we evaluated the relative activity and toxicity of these agents in this patient population.. Clinical data from 72 patients with previously untreated AGC, who were treated with capecitabine/cisplatin and S-1/cisplatin, were reviewed. Oral fluoropyrimidines were administered orally twice a day on Days 1-14. The dose of capecitabine was 1250 mg/m(2) and that of S-1 was 50 mg [body surface area (BSA) < 1.5 m(3)] or 60 mg (BSA > 1.5 m(3)) twice a day. Cisplatin was administered intravenously on Day 1 (before the first dose of capecitabine or S-1) at a dose of 70 mg/m(2) over a 2 h period. The chemotherapy cycle was of 3 weeks (with oral capecitabine or S-1).. Thirty-two and 40 patients received the S-1 and capecitabine regimens, respectively, and were included in the analysis. The S-1 protocol had a response rate of 40.6%, a median time-to-progression (TTP) of 5.4 months and a median survival of 9.6 months. The capecitabine had a response rate of 55%, a median TTP of 5.9 months and a median survival of 10.2 months. Each protocol had a similar incidence of Grade 3 or 4 adverse events. However, there was a higher rate of the hand-foot syndrome (6 versus 37%) and diarrhea (25 versus 32%) in the capecitabine group.. Oral fluoropyrimidines and cisplatin in elderly patients with untreated AGC showed encouraging results. The treatment was well tolerated with a manageable toxicity profile. The comparison of S-1 with capecitabine showed that capecitabine had a slightly higher response rate (statistically not significant) in addition to a higher rate of adverse events such as the hand-foot syndrome and diarrhea. These data should be warranted with further prospective studies.

Topics: Adenocarcinoma; Administration, Oral; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Cisplatin; Combined Modality Therapy; Deoxycytidine; Drug Combinations; Female; Fluorouracil; Follow-Up Studies; Humans; Male; Maximum Tolerated Dose; Neoplasm Recurrence, Local; Neoplasm Staging; Oxonic Acid; Prognosis; Retrospective Studies; Stomach Neoplasms; Tegafur

The standard beneficial chemotherapy proved for patients with pancreatic cancer is a regimen containing gemcitabine. Novel oral fluoropyrimidine, S-1, can be added to gemcitabine to improve the efficacy of chemotherapy and to provide better convenience for patients. We aimed to evaluate the efficacy and safety of S-1 plus gemcitabine combination chemotherapy as a first-line treatment in patients with locally advanced or metastatic pancreatic cancer.. Patients with histologically confirmed, bidimensionally measurable advanced/metastatic pancreatic cancer were eligible for the study. Chemotherapy consisted of S-1 (30 mg/m(2) p.o. bid from Day 1 to 14) and gemcitabine (1000 mg/m(2) on Days 8 and 15) every 3 weeks based on the results of a previously reported Phase I trial. Treatment was repeated until disease progression or unacceptable toxicity occurred.. From January 2005 to August 2007, 22 patients were enrolled. Median age was 62 years (range, 50-73). Nineteen patients (86.3%) had metastases and of these, 11 patients (57.9%) had multiple liver metastases. The overall response rate was 27.3% (95% CI, 8.7-45.9), with a partial response in six patients, stable disease in nine (40.9%) and progressive disease in seven (31.8%). With a median follow-up of 25.4 months, the median time to progression and overall survival were 4.6 (95% CI, 2-7.2 months) and 8.5 months (95% CI, 6.8-10.1 months), respectively, and 1-year survival rate was 27.3%. S-1 plus gemcitabine was well tolerated. Grade 3/4 hematological adverse events were neutropenia (9.1/9.1%) and anemia (4.5/0%). Non-hematological adverse events were mainly gastrointestinal events. Twenty patients (91%) received chemotherapy on an outpatient basis.. Combination chemotherapy of S-1 plus gemcitabine appears to be active and well tolerated as first-line treatment in patients with advanced/metastatic pancreatic cancer.

Topics: Adenocarcinoma; Administration, Oral; Aged; Ambulatory Care; Antineoplastic Combined Chemotherapy Protocols; Deoxycytidine; Drug Combinations; Female; Follow-Up Studies; Gemcitabine; Humans; Male; Maximum Tolerated Dose; Middle Aged; Neoplasm Staging; Oxonic Acid; Pancreatic Neoplasms; Prognosis; Retrospective Studies; Tegafur

We investigated the efficacy and safety of S-1 monotherapy for the treatment of advanced biliary tract adenocarcinoma (BTA) in a clinical practice setting.. We reviewed clinical data from 217 patients with advanced BTA who were treated with S-1 monotherapy between August 2004 and September 2007.. 162 eligible patients were identified. The primary tumors were intrahepatic (n = 57), in the gall bladder (n = 50), in extrahepatic bile ducts (n = 41) and in the ampulla of Vater (n = 14). Sixteen of 120 assessable patients achieved partial responses, with a response rate of 13.3% (95% CI 7.2-19.4%). Another 51 patients had stable disease, with an overall tumor control rate of 55.8% (95% CI 46.9-64.7%). The median time to progression was 2.7 months and the median overall survival time was 6.9 months. Response rates and survival differed significantly according to the primary site of the tumor (p = 0.002 and p < 0.001, respectively), with extrahepatic bile duct adenocarcinoma having the best prognosis. The treatment regimen produced only mild toxicity in most cases (grade 1 or 2), even for patients with hyperbilirubinemia.. S-1 has a favorable toxicity profile and can be safely administered to BTA patients with hyperbilirubinemia. The efficacy of S-1 against advanced BTA depends on the tumor site and is most effective in patients with extrahepatic BTA.

Topics: Adenocarcinoma; Administration, Oral; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Biliary Tract Neoplasms; Cohort Studies; Drug Combinations; Drug Delivery Systems; Female; Humans; Male; Middle Aged; Oxonic Acid; Retrospective Studies; Tegafur

A 59-year-old man diagnosed as gastric cancer with peritonitis carcinomatosa was treated with paclitaxel and TS-1; 60 mg/m(2)/day of paclitaxel was given on days 1 and 8, and 60-80 mg/m(2)/day of TS-1 was given for 2 weeks. Six courses of combination therapy were administered, and the ascites disappeared completely. Because multiple bone metastases occurred, we attempted combination therapy with cisplatin and irinotecan hydrochloride; 50 or 30 mg/m(2)/day of cisplatin was given on day 1 or day 15, and 70 mg/m(2)/day of irinotecam hydrochloride was given on days 1 and 15. The patient achieved a remarkable response, however, intrameningeal dissemination occurred and he died from rapidly progressive meningitis carcinomatosa.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Drug Combinations; Fatal Outcome; Humans; Male; Meningitis; Middle Aged; Oxonic Acid; Paclitaxel; Peritonitis; Stomach Neoplasms; Tegafur; Tomography, X-Ray Computed

Case one was a 76-year-old woman. She was diagnosed as having lung adenocarcinoma with multiple metastases (cT4N0M1, stage IV, mucinous BAC)in June, 2004. Starting in July, 2004, she received various modalities of chemotherapy( cisplatin+vinorelbine, gefitinib, pemetrexed, gemcitabine, docetaxel, paclitaxel). S-1 monotherapy given to her starting April, 2006 achieved a partial response(PR)as a seventh-line treatment. Case two was a 60-year-old woman. She was diagnosed as having lung adenocarcinoma with multiple metastases(cT4N3M1, stage IV)in October, 2004. That month, her chemotherapy began. After various treatments(cisplatin+vinorelbine, docetaxel, gefitinib), S-1 monotherapy was initiated in February, 2007 as the fourth-line treatment; as a result, PR was achieved. Even though chemotherapies were performed in succession, in the condition of good general status, salvage chemotherapy can be affected by the rotation of drugs. In such cases, S-1 monotherapy can be a reasonable choice from the standpoint of feasibility and effectiveness.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Drug Combinations; Fatal Outcome; Female; Humans; Lung Neoplasms; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Radiography; Recurrence; Salvage Therapy; Tegafur; Treatment Outcome

We report a case of advanced adenocarcinoma in the left ethmoid sinus invading the frontal sinus, the frontal skull base and the orbits(T4bN0M0 and Stage IVB). With the goal of functional preservation, we carried out radiation therapy with total 60 Gy irradiation and chemotherapy with S-1 80 mg/body/day before a radical operation. The tumor clinically disappeared without surgical treatment, and there was no sign of recurrence for 2.5 years. When we decide the treatment policy for advanced adenocarcinoma of the ethmoid sinus, chemoradiotherapy wit S-1 might be one of the effective treatments before radical operation to control the disease with preservation of functions.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Drug Combinations; Ethmoid Sinus; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Neoplasm Staging; Nose Neoplasms; Oxonic Acid; Remission Induction; Tegafur; Tomography, X-Ray Computed

Vascular endothelial growth factor (VEGF) and its receptors VEGF-R1, -R2 and -R3 play important roles in tumor angiogenesis and are associated with poor prognosis in several solid tumors. However, their functional significance remains unclarified. Here, we investigated the associations between the expression of these receptors and the clinical outcomes of colorectal cancer (CRC) patients.. An immunohistochemical approach was used to detect VEGF-R1, -R2 and -R3 expression in 91 CRC patients who underwent surgery and received chemotherapy at the National Cancer Center Hospital. Statistical analysis was performed to determine the prognostic significance of these biomarkers.. Immunoreactivity for VEGF-R2 and -R3 was localized in microvessels and that for VEGF-R1 in cancer cells and stromal microvessels. VEGF-R1 staining in cancer cells (>10% staining) was found in 84 patients (92%) and in stromal vessels in 75 patients (82%). VEGF-R2 staining in tumor vessels (>10% staining) was found in 84 patients (92%), whereas VEGF-R3 staining was found in 85 patients (93%). Strong positive staining (>60% staining) of VEGF-R1 in tumor cells, and VEGF-R1, -R2 and -R3 in vessels was identified in 58 (64%), 33 (36%), 52 (57%) and 60 (66%) patients, respectively. Univariate analysis revealed that VEGF-R1 strong positive staining correlated with shorter post-operative survival in patients with Stage II/III disease (P = 0.01), but neither VEGF-R2 nor R3 expression correlated with survival.. VEGF-R1, -R2 and -R3 were highly expressed in CRC cells and stromal vessels. VEGF-R1 strong positive staining correlated with shorter survival after CRC surgery.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Drug Combinations; Female; Fluorouracil; Humans; Immunoenzyme Techniques; Leucovorin; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Prognosis; Retrospective Studies; Survival Rate; Tegafur; Uracil; Vascular Endothelial Growth Factor Receptor-1; Vascular Endothelial Growth Factor Receptor-2; Vascular Endothelial Growth Factor Receptor-3

The aim of this study was to evaluate the efficacy and safety of single-agent S-1 in patients with advanced biliary tract cancer.. S-1 was administered orally at a dose of 80 mg/m2 for 28 days, followed by 14 days of rest (1 cycle); treatment was repeated until disease progression, unacceptable toxicity, or patient refusal.. Forty-five patients were enrolled between January 2005 and June 2008. Among these, 29 patients received S-1 as first-line chemotherapy and 16 patients received S-1 as second-line chemotherapy. The response rates for first- and second-line chemotherapy were 17.2 and 18.8%, respectively. The median times to progression for the first- and second-line chemotherapy groups were 4.2 and 5.5 months (p = 0.91), respectively. The median overall survival and 1-year survival rate for each group were 8.7 and 8.0 months and 42.2 and 38.2%, respectively (p = 0.62). Only the first-line chemotherapy group experienced grade 3/4 toxicities, including leukopenia (6.9%), neutropenia (10.3%), anemia (6.9%), thrombocytopenia (10.3%) and total bilirubin elevation (3.4%).. S-1 monotherapy is a feasible and moderately efficacious treatment for advanced biliary tract cancer, as a first- or second-line chemotherapy regimen.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Biliary Tract Neoplasms; Disease Progression; Drug Combinations; Feasibility Studies; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Oxonic Acid; Prognosis; Prospective Studies; Survival Rate; Tegafur; Treatment Outcome

We performed combination chemotherapy in the outpatient clinic on a 47-year-old man with nonresected gastric cancer accompanied by peritoneal dissemination. At first we administered S-1/DOC combination chemotherapy. Afterwards a rise of tumor marker (CEA) occurred accompanying taste disorder and edema of the lower limbs, so we changed to combination chemotherapy for PTX/CDDP. Since the only side effect was numbness, the patient was treated on an outpatient basis while working. The case achieved good QOL by these combination chemotherapy methods for 1 year 10 months post exploratory laparotomy.

Topics: Adenocarcinoma; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Docetaxel; Drug Combinations; Humans; Male; Middle Aged; Oxonic Acid; Paclitaxel; Peritoneum; Quality of Life; Stomach Neoplasms; Taxoids; Tegafur; Treatment Outcome

The prognosis for advanced pancreatic cancer with peritoneal dissemination is extremely poor, and no effective standard therapy has been established. We present a case of a very old patient whose QOL improved shortly after administration of only S-1 to treat advanced pancreatic cancer with peritoneal dissemination. A 85-year-old man presented to our hospital with anorexia and loss of weight. CT scanning showed severe ascites and a low-density area 2 cm wide at the tail of the pancreas. Ascitic cytology revealed adenocarcinoma and carcinomatous peritonitis due to pancreatic cancer. Considering his general condition due to old age, the regimen for oral S-1 (80 mg/body/day) was set at 4 consecutive weeks of administration followed by a 2-week rest period. His abdominal circumference decreased and his appetite improved by 14 days following commencement of the therapy. The blood examination one month following commencement showed a significant decrease in the tumor marker. There was no adverse drug reaction. Six months later CT scanning showed that the ascites had disappeared and that the low-density area at the tail of the pancreas had become less obvious. The tumor marker and biochemical parameters were within standard ranges. Twelve months since the therapy began: there still has been no adverse drug reaction and his QOL has been good. He is receiving the therapy as an outpatient. This case suggests that S-1 is a safe and effective drug for very elderly patients.

Topics: Adenocarcinoma; Administration, Oral; Aged, 80 and over; Antimetabolites, Antineoplastic; Drug Combinations; Humans; Male; Oxonic Acid; Pancreatic Neoplasms; Peritoneum; Peritonitis; Quality of Life; Tegafur

A 58-year-old woman was admitted to the hospital because of abdominal fullness and anorexia. Abdominal CT scan revealed pancreatic cancer with massive ascites showing peritoneal dissemination, combined with lymph node and liver metastases. Cytology of ascites showed malignancy. Abnormally high values of CA19-9 (1,908 U/mL) and CA125 (545 U/mL) were detected in serum. Histologically, metastatic adenocarcinoma was recognized by laparoscopic biopsy of peritoneal dissemination. We performed systemic chemotherapy of S-1, gemcitabine and peritoneal infusion of paclitaxel for nonresected pancreatic cancer. After 5 courses, ascites disappeared and the serum CA19-9 and CA125 levels regained their normal value. Peritoneal seeding was not found by second laparoscopic examination 20 months after beginning chemotherapy. Thus, we consider the patient had an effective response, and performed distal pancreatectomy and proximal resection of the stomach. Histological examination of the primary lesion revealed no cancer cells where fibrosis presented.

Topics: Adenocarcinoma; Antimetabolites, Antineoplastic; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; CA-125 Antigen; CA-19-9 Antigen; Deoxycytidine; Drug Combinations; Female; Gemcitabine; Humans; Liver Neoplasms; Middle Aged; Oxonic Acid; Paclitaxel; Pancreatic Neoplasms; Peritoneal Neoplasms; Tegafur

As there is no standard treatment for advanced gastric cancer refractory to first-line chemotherapy, the feasibility of S-1 plus weekly docetaxel combined with concurrent radiotherapy was evaluated.. Ten patients were enrolled in this study. Patients were given S-1 at a daily dose of 40 mg/m(2) and docetaxel at a weekly dose of 20 mg/m(2) for 5 consecutive weeks, with concurrent radiotherapy (RT) amounting to a total irradiation dose of 45 Gy or 50.4 Gy.. Hematological toxicities were grade 3 or less except for anemia. Non-hematological toxicities were all grade 2 or less, apart from one grade 3 asthenia. There was one treatment-related death, resulting from melena, in a patient with a mechanical device in the radiation field. Planned treatment was delivered with relative dose intensity for S-1, docetaxel and RT as 94%, 98% and 97%, respectively. Median survival time of 297 days was obtained, with an objective response seen in 2 patients and symptom relief achieved in all patients.. S-1 plus weekly docetaxel combined with concurrent RT exhibited a tolerable toxicity profile with sufficient symptom palliation and prolonged survival in patients with advanced gastric cancer refractory to first-line chemotherapy.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Docetaxel; Drug Combinations; Drug Resistance, Neoplasm; Feasibility Studies; Female; Humans; Intestinal Neoplasms; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Prognosis; Stomach Neoplasms; Survival Rate; Taxoids; Tegafur

A 68-year-old woman presented with severe bowel obstruction and was subsequently diagnosed with stage IV gastric cancer with peritoneal dissemination. She was immediately stabilized in the hospital with the placement of a nasointestinal tube. Abdominal computed tomography showed multiple intraperitoneal nodules consistent with peritoneal dissemination of the gastric cancer. The patient's inability to tolerate oral intake was a contraindication to using S-1 chemotherapy, currently one of the most effective medications used for gastric cancer in Japan. Therefore, she was initially treated with octreotide acetate (OA). Her bowel obstruction was sufficiently attenuated on the seventh day after the initiation of treatment with OA to permit the initiation of oral S-1, along with low-dose cisplatin (CDDP) and radiation. S-1 was orally administered at a dose of 100 mg/day per body (80 mg/m(2) per day) on days 1-28, and CDDP was infused at a dose of 7.8 mg/day per body (6 mg/m(2) per day) on days 1-5, 8-12, and 15-19. Radiation therapy (2 Gy/day for 5 days/week) was performed with the chemotherapy. Despite no change being shown on her imaging findings with the chemotherapy, the patient's bowel obstruction resolved and she was able to tolerate both liquids and solid food orally. She was discharged 2 months after admission. Seven months after beginning the chemotherapy, she was still doing well on outpatient chemotherapy with S-1 and CDDP, and had no decline in her quality of life or progression of her disease.

Topics: Adenocarcinoma; Administration, Oral; Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Signet Ring Cell; Chemotherapy, Adjuvant; Cisplatin; Drug Combinations; Female; Gastrointestinal Agents; Humans; Intestinal Obstruction; Neoplasm Staging; Octreotide; Oxonic Acid; Peritoneal Neoplasms; Radiotherapy, Adjuvant; Stomach Neoplasms; Tegafur; Tomography, X-Ray Computed; Treatment Outcome

A 51-year-old man consulted our hospital with complaints of a headache and spasm of the left upper limbs in January 2007. He was diagnosed as left lung adenocarcinoma (c-T2N0M1, stage IV). His serum CEA level was 104.1 ng/mL. After the brain tumor extraction, CDDP (80 mg/m2) + GEM (1,000 mg/m2) were administered as first-line treatment, and the tumor response was PR (33.3% reduction rate), impaired liver function served to interrupt this regimen. Other chemotherapy was then conducted in the order of GEM (1,000 mg/m2) + VNR (25 mg/m2), and CBDCA (AUC=5) + DOC(60 mg/m2), and the tumor response was NC. As fourth-line treatment, S-1 (75 mg/m2, day 1-28, every 6 weeks) + CBDCA (AUC=5, day 8, every 6 weeks) was chosen. After 3 courses of the treatment, the serum CEA level normalized, a chest CT detected the left lung tumor size reduction (66.7% reduction rate), and an abdominal CT detected disappearance of the left adrenal gland tumor. In January 2008, left upper lobectomy and lymph node resection (ND2a) were performed. Histopathological examination of the lung tumor showed viable adenocarcinoma cells. Postoperatively, S-1+CBDCA also was administered in a 3-course treatment. This patient is currently continuing treatment with S-1 monotherapy with no recurrence. This case suggests that S-1+CBDCA may be an effective treatment in patients with advanced non-small-cell lung cancer even after multiple chemotherapy.

Topics: Adenocarcinoma; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoembryonic Antigen; Drug Combinations; Humans; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Tegafur; Tomography, X-Ray Computed

The patient was a 48-year-old female who underwent combination chemotherapy of S-1 plus CDDP after diagnosis of primary duodenal adenocarcinoma with marked lymph node metastases. The regimen was as follows: 80 mg/m2 of S-1 on days 1-21 orally and 60 mg/m2 of CDDP on day 8 intravenously. One course lasted for 5 weeks. After 5 courses, metastasized lymph nodes were remarkably reduced. This case suggests that the combination of S-1 and CDDP may be an effective regimen for advanced primary duodenal adenocarcinoma.

Topics: Adenocarcinoma; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Duodenal Neoplasms; Female; Humans; Lymphatic Metastasis; Middle Aged; Oxonic Acid; Tegafur

There is at present no defined role for S-1 chemotherapy in patients with advanced non-small cell lung cancer (NSCLC) who previously failed chemotherapy. Two cases of multidrug-resistant, NSCLC that were successfully treated with S-1 as fifth-line chemotherapy are reported. A 75-year-old man was diagnosed as having pulmonary adenocarcinoma, cT1N3M0, stage III B. He was treated with S-1 as fifth-line chemotherapy after treatment with cisplatin(CDDP)and vinorelbine(VNR), docetaxel (DOC), gemcitabine (GEM) and VNR, and amrubicin (AMR). After completing two courses, chest computed tomography(CT)showed a partial response( PR)of the recurrent tumors, and the serum carcinoembryonic antigen level decreased. Currently, seven courses have been completed, and this treatment will be continued due to the tumor response of stable disease. A 65-year-old woman was referred for treatment of recurrent pulmonary adenocarcinoma after right upper lobe resection. She was treated with S-1 as fifth-line chemotherapy after treatment with GEM and VNR, carboplatin(CBDCA) and paclitaxel ( PTX), DOC, and gefitinib. After completing five courses, chest CT showed PR of the intrapulmonary metastases. Though grade 3 toxicity-anemia in the first case and an elevated serum amylase level in the second case were observed in both cases, the patients' quality of life was preserved. S-1 could therefore be a treatment option for patients with advanced NSCLC who previously underwent chemotherapy unsuccessfully.

Topics: Adenocarcinoma; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Disease Progression; Drug Combinations; Fatal Outcome; Female; Humans; Lung Neoplasms; Male; Oxonic Acid; Quality of Life; Recurrence; Salvage Therapy; Tegafur; Tomography, X-Ray Computed; Treatment Outcome

Topics: Adenocarcinoma; Administration, Oral; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cisplatin; Disease-Free Survival; Drug Administration Schedule; Drug Combinations; Fluorouracil; Humans; Infusions, Intravenous; Irinotecan; Japan; Oxonic Acid; Patient Selection; Risk Assessment; Stomach Neoplasms; Tegafur; Time Factors; Treatment Outcome

The patient was a 55-year-old man who was treated with S-1 and paclitaxel(PTX)combination chemotherapy for inoperable advanced gastric cancer in whom an abdominal CT examination had revealed peritoneal dissemination, pancreatic invasion, and ascites. A total of 15 courses of S-1 120 mg/day for 2 weeks followed by a 2-week rest period and PTX 90 mg/ body on day 1, 8, and 15 were administered. The CT examination after the completion of chemotherapy showed resolution of the ascites, and no evidence of peritoneal dissemination was observed on the images. The tumor marker values had also decreased, but because of severe manifestations of pyloric stenosis, distal gastrectomy and D1 lymph node dissection were performed. Intraoperative exploration revealed total scarring of the peritoneal dissemination and no evidence of pancreatic invasion. We reported this case because of the long-term combination chemotherapy with no major adverse effects and the fact that resection was possible.

Topics: Adenocarcinoma; Antimetabolites, Antineoplastic; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Humans; Male; Middle Aged; Oxonic Acid; Paclitaxel; Stomach Neoplasms; Tegafur; Tomography, X-Ray Computed

A 64-year-old man underwent long-term chemotherapy for advanced gastric cancer with para-aortic lymph node metastasis (cT3 N3 M0 P0, cStage IV). S-1 (120 mg/day) was orally administered for 14 days and CDDP (60 mg/m2) was administered 10 times by intravenous drip on day 8. Next, paclitaxel (PTX 80 mg/m2) was administered 12 times by intravenous drip on days 1, 8 and 15. After 10 S-1/CDDP courses and 12 paclitaxel courses, the lymph node swelling decreased in size, but the tumor increased. CPT-11 (100 mg/m2) was administered as third-line therapy by intravenous drip on days 1, 8, 15 and 22. A partial response (PR) was obtained after 2 courses, but due to severe pyloric stenosis, a food passage disorder appeared. We performed distal gastrectomy with D2 lymph node dissection. The histological diagnosis revealed a complete disappearance of cancer cells in the stomach and lymph nodes.

Topics: Adenocarcinoma; Antimetabolites, Antineoplastic; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cisplatin; Drug Combinations; Humans; Irinotecan; Lymphatic Metastasis; Male; Middle Aged; Oxonic Acid; Paclitaxel; Stomach Neoplasms; Tegafur

The patient was a 51-year-old male diagnosed with gastric cancer in July 1999 by endoscopic examination, revealing multiple liver metastasis with abdominal computed tomography (CT). The serum levels of alpha-fetoprotein (AFP)were determined to be 91 ng/mL, and tumors were histopathologically identified as AFP-producing gastric cancer by immunohistological staining. We started combination chemotherapy with 5-fluorouracil (5-FU), Leucovorin (LV), etoposide (VP-16) and cis-diaminedichloroplatinum (CDDP) (designated as FLEP)in August 1999. The serum AFP value was normalized after two courses, and the liver metastases disappeared. The primary gastric tumor became a ulcer, and disappearance of the cancer was confirmed histologically. We continued adjuvant chemotherapy with S-1 as an outpatient. In April 2000, there was no sign of the liver metastases, but endoscopic examination showed IIc-like lesion in the stomach. We performed 2 courses of FLEP, but the tumor did not disappear. He underwent total gastrectomy with D2 dissection in June 2001. The pathological diagnosis was por 1, ss, ly2, v1, n(1+). He was still alive with no sign of recurrence 84 months after surgery. We experienced this AFP-producing gastric cancer in which CR was possible by FLEP. There was no recurrence after total gastrectomy for local recurrence.

Topics: Adenocarcinoma; alpha-Fetoproteins; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cisplatin; Drug Combinations; Etoposide; Fluorouracil; Gastrectomy; Humans; Immunohistochemistry; Leucovorin; Liver Neoplasms; Male; Middle Aged; Oxonic Acid; Remission Induction; Stomach Neoplasms; Tegafur

The patient was a 36-year-old male. He visited our department in February 2004 as a prior chest X-ray revealed multiple nodular shadows. After further examinations, he was diagnosed with stage IV adenocarcinoma of the lung. As treatment, 5 courses of carboplatin (CBDCA)+docetaxel (DOC), 3 courses of CBDCA+gemcitabine (GEM), 6 weeks of gefitinib, and 3 courses of GEM were administered. However, the tumor progressed, and S-1 (120 mg/day, 2 weeks on, 1 week off) was administered as the sixth regimen from May 2006. No severe side effects were observed, and an antitumor action was achieved over a relatively long period. Therefore, it was suggested that a single administration of S-1 for non-small cell lung cancer, which had been treated with other multiple regimens, is safe, and long-term control of the disease can be expected.

Topics: Adenocarcinoma; Adult; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Non-Small-Cell Lung; Deoxycytidine; Docetaxel; Drug Combinations; Gefitinib; Gemcitabine; Humans; Lung Neoplasms; Male; Oxonic Acid; Quinazolines; Taxoids; Tegafur

The patient was a 42-year-old female who had advanced rectal cancer(Ra, type 2)with liver metastasis. The preoperative diagnosis was T2N1H2, but the liver tumor was unresectable for hepatic vein invasion in September, 2004. She underwent low anterior resection for primary rectal cancer at first after she was given S-1 80 mg/day(14 days)for a histological effect judgment. The pathological diagnosis was moderately-differentiated adenocarcinoma, ss, n1, and the histological effect was Grade 1a. Because CT showed reduction of liver metastasis after the operation, she was treated with 2 courses of chemotherapy using S-1. Radiographic examination showed reduction of liver metastasis(36%)and improvement of hepatic vein invasion. In January, 2005, she underwent hepatectomy and the pathological diagnosis was moderately-differentiated adenocarcinoma, metastasis and the histological effect was Grade 1a. There has not been any recurrence for 48 months after hepatectomy. We experienced this case in which preoperative S-1 proved effective for liver metastasis from rectal cancer.

Topics: Adenocarcinoma; Adult; Antimetabolites, Antineoplastic; Drug Combinations; Female; Hepatectomy; Humans; Liver Neoplasms; Neoadjuvant Therapy; Oxonic Acid; Rectal Neoplasms; Tegafur

Feasibility and efficacy of S-1 and cisplatin followed by surgery was evaluated, and factors contributing to survival benefit were analyzed.. In total, 120 consecutive patients with highly advanced gastric cancer were treated with S-1 (80 mg/m(2) for 21 consecutive days) and cisplatin (50 mg/m(2) on day 8).. The response rate was 62.5% overall, and 75.7% for these with metastatic lymph nodes. Grade 3/4 adverse events were less than 10%. The median survival time was 41.9 months among 93 patients whose primary lesion was resected. Liver metastasis, R2 resection, poor performance status and lack of response were identified as independent risk factors by a multivariate analysis.. Preoperative chemotherapy with S-1 and cisplatin was effective. The results show the need for different approaches in the treatment of patients with metastases and these without.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cisplatin; Drug Combinations; Female; Humans; Liver Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Neoadjuvant Therapy; Oxonic Acid; Retrospective Studies; Stomach Neoplasms; Survival Rate; Tegafur; Treatment Outcome

The case was a 50s male with chief complaints of body weight loss and nausea. A clinical finding was Stage IV gastric cancer of poorly differentiated adenocarcinoma. We diagnosed it unresectable and started 5-FU+CDDP as the first-line chemotherapy. Partial response (PR) was observed and progression free time was 7 months. After 9 courses of 5-FU+ CDDP, the tumor grew and an oral intake was getting impossible. Gastro-jejunostomy was performed and then started a weekly PTX as the second-line chemotherapy after operation. The response was progressive disease (PD) after 4 courses of weekly PTX. Then we started S-1+CPT-11 as the third-line chemotherapy. We could continue S-1+CPT-11 for 9 courses without a severe adverse effect. Overall survival was 26.2 months.

Topics: Adenocarcinoma; Antimetabolites, Antineoplastic; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cisplatin; Drug Combinations; Fluorouracil; Humans; Irinotecan; Male; Middle Aged; Oxonic Acid; Stomach Neoplasms; Tegafur

A 58-year-old man of unresectable gastric cancer was treated with S-1 (120 mg/body/day) after gastrojejunostomy. After 5 courses of orally administration of S-1 for 4 weeks and withdrawal for 2 weeks, partial response (PR) was obtained clinically and distal gastrectomy was performed. The histological diagnosis showed no residue of carcinoma with both HE and immunohistochemical staining. The patient has been in good health and no recurrence has occurred for about 4 years and 4 months after resection.

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

A 73-year-old man underwent a distal gastrectomy with dissection of D2 lymph nodes for type 2 gastric cancer at the front wall of pyloric antrum in June 2006 (Pathological finding was moderately differentiated adenocarcinoma, T2, N0, H0, P0, M0, fStage IB). Although he was given UFT and PSK for postoperative adjuvant therapy, MRI showed a liver metastasis at segment 6 of the liver in June 2007. After 2 courses of S-1, posterior segmentectomy of the liver was performed. After hepatectomy, 5 courses of S-1 as adjuvant therapy were administered. However, another metachronous liver metastasis appeared at segment 8 in August 2008. After 3 courses of S-1 and CDDP, we performed radiofrequency ablation (RFA) therapy and a good cauterization effect was obtained. There has been no recurrence for 3 years since gastrectomy, or 2 years since the first liver metastasis. We experienced a case of metachronous liver metastasis from gastric cancer treated with multidisciplinary therapy that was beneficial for a long term survival.

Topics: Adenocarcinoma; Aged; Antimetabolites, Antineoplastic; Antineoplastic Agents; Catheter Ablation; Cisplatin; Combined Modality Therapy; Drug Combinations; Hepatectomy; Humans; Liver Neoplasms; Male; Neoplasms, Second Primary; Oxonic Acid; Stomach Neoplasms; Tegafur

We herein describe the case of a patient with advanced gastric carcinoma combined with extra-adrenal pheochromocytoma who received a radical operation after undergoing neoadjuvant chemotherapy. A 48-year-old woman was referred to our hospital for gastric carcinoma. Computed tomography revealed an enlargement of the regional lymph nodes and a para-aortic lymph node. A diagnosis of advanced gastric carcinoma was made (cT3, cN3, cM0, cStage IV according to the Japanese Classification of Gastric Carcinoma, 2nd English edition). A reduction in size was observed in both the gastric tumor and the lymph nodes around the stomach after neoadjuvant chemotherapy. However, the paraaortic lymph node showed no remarkable change. We thus suspected this para-aortic tumor not to be a lymph node, but instead to be an extra-adrenal pheochromocytoma, because of the different response from the other regional lymph nodes. An endocrinological examination confirmed the diagnosis of extra-adrenal pheochromocytoma. A gastrectomy and a resection of the pheochromocytoma were thus performed.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Female; Gastrectomy; Humans; Middle Aged; Neoadjuvant Therapy; Oxonic Acid; Pheochromocytoma; Stomach Neoplasms; Tegafur

We report on two patients, successfully treated by the combination therapy of S-1 and 24-h infusion of cisplatin (CDDP), who were initially diagnosed with unresectable stage 4 advanced gastric cancer. Each patient had a very good clinical response and underwent curative gastrectomy after completion of 14 and 10 courses of S-1/CDDP chemotherapy, respectively. A microscopically detailed examination of surgically obtained specimens showed the complete disappearance of malignant cells in the two cases. S-1/CDDP combination therapy can, therefore, be highly active in incurable advanced gastric carcinoma.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Cisplatin; Drug Combinations; Female; Humans; Infusions, Intravenous; Liver Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Oxonic Acid; Peritoneal Neoplasms; Prognosis; Remission Induction; Stomach Neoplasms; Survival Rate; Tegafur

We describe a 51-year-old man case of a huge gastric cancer with an initial presentation of isolated brain metastasis. The patient was successfully managed by gamma knife radiotherapy, followed by chemotherapy using 5-fluorouracil and cisplatin. He has continued oral administration of TS-1 on an outpatient basis with disease free survival for more than one year.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Brain Neoplasms; Cisplatin; Combined Modality Therapy; Drug Combinations; Fluorouracil; Humans; Male; Middle Aged; Oxonic Acid; Radiosurgery; Stomach Neoplasms; Tegafur; Treatment Outcome

An 81-year-old woman presented with dysphagia. Stage IV (cT3, cN3, cH0, cM1) type 4 advanced gastric cancer was diagnosed. The left adrenal gland and the paragastric, mediastinal, and abdominal para-aortic lymph nodes were enlarged. Ascites was present. The patient started to receive S-1 (100 mg/day), given orally for 4 weeks followed by 2 weeks of rest. During the first course of treatment, grade 2 anorexia, grade 2 vomiting, and grade 2 diarrhea developed. Treatment with S-1 was therefore discontinued on day 27. The tumor had shrunk and was severely deformed. There was marked narrowing of the pyloric antrum. Abdominal computed tomography revealed that ascites and enlargement of the left adrenal gland and paragastric lymph nodes had resolved. To ensure adequate oral intake and improve the patient's quality of life, a total gastrectomy with a limited (D1) lymph node dissection was performed. The primary gastric tumor, resected lymph nodes, and a peritoneal-lavage specimen were all negative for tumor. Histologically, the tumor had a complete pathological response to S-1. Two years after surgery, the patient is alive, with no evidence of metastasis or recurrence.

Topics: Adenocarcinoma; Aged, 80 and over; Drug Combinations; Female; Gastrectomy; Humans; Lymph Node Excision; Oxonic Acid; Stomach Neoplasms; Tegafur; Tomography, X-Ray Computed

In pancreatic carcinoma, vascular endothelial growth factor (VEGF) expression at the primary site has been suggested to be a prognostic parameter. We quantitatively analyzed VEGF expression in liver metastases from pancreatic carcinoma and examined the correlation among VEGF expression in liver metastases, clinicopathologic factors, and clinical outcome.. The subjects consisted of 23 patients with pancreatic adenocarcinoma who had liver metastases and were treated with S-1 and gemcitabine as the first-line treatment. VEGF expression was quantitated by enzyme immunoassay in biopsy specimens of liver metastases and nontumorous liver tissue, and in plasma. In 10 of the 23 patients, VEGF expression was also quantitated in biopsy specimens of the primary pancreatic tumor. All samples were collected before treatment.. The VEGF level in nontumorous liver tissue was 36.6 +/- 10.0 pg/mg protein versus 376.8 +/- 106.1 pg/mg protein in liver metastases (P = 0.0016). Pretreatment VEGF levels in plasma and in primary pancreatic carcinoma did not correlate with VEGF levels in the corresponding liver metastases. The median VEGF level in liver metastases (138.9 pg/mg protein) was used as the cutoff value between high and low VEGF expression in liver metastases. Patients showing high VEGF expression had a significantly longer progression-free survival and overall survival than patients showing low VEGF expression in liver metastases (P = 0.0219 and P = 0.0074, respectively).. Evaluation of VEGF levels in liver metastases might be useful in assessing the prognosis of patients with metastatic pancreatic carcinoma who are under systemic chemotherapy.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Deoxycytidine; Drug Combinations; Enzyme-Linked Immunosorbent Assay; Female; Gemcitabine; Humans; Kaplan-Meier Estimate; Liver Neoplasms; Male; Middle Aged; Oxonic Acid; Pancreatic Neoplasms; Prognosis; Tegafur; Vascular Endothelial Growth Factor A

We report a 63-year-old man with recurrent gastroesophageal junction adenocarcinoma. He underwent esophagogastrectomy in August 2004. After curative operation with Stage III (pT3N1M0), a recurrence was found at the anastomosis site in November 2004. Chemoradiotherapy with S-1 followed by chemotherapy (S-1) was performed from January 2005 to April 2006. Lymphnode metastasis to the left side of the main bronchus appeared in May 2006, and paclitaxel was used until December 2007 when PR was indicated by CT scan and GIF. Now he is receiving CPT-11. During these 3 years and 3 months, his performance status was maintained from 0 to 1.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cisplatin; Combined Modality Therapy; Drug Combinations; Esophageal Neoplasms; Humans; Irinotecan; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasms; Oxonic Acid; Paclitaxel; Quality of Life; Stomach Neoplasms; Tegafur; Time Factors; Tomography, X-Ray Computed

There is no standard treatment for peritoneal dissemination from gastric cancer. A novel combination chemotherapy has been introduced for patients with advanced gastric cancer with peritoneal metastasis.. This pilot study was performed on four patients to confirm safety and efficacy. They were diagnosed with unresectable gastric cancer with severe peritoneal dissemination by staging laparoscopy, or with metastasis to the transverse colon. We selected combined chemotherapy with both paclitaxel and S-1. Paclitaxel at 60 mg/m(2) or 60 mg/body was administered intraperitoneally on days 1 and 8 and S-1, at 80-120 mg/body, was administered orally for 14 days followed by 7 days' rest, as one course. After five courses of this therapy, the primary gastric tumors were evaluated by conventional examinations, and second-look laparoscopy was performed to assess the efficacy of the treatment against the peritoneal metastases.. After five courses, primary tumor reductions were confirmed, and no cancer cells were detected on pathocytological investigation during second-look laparoscopy in any of the patients. Three patients underwent total gastrectomy with lymph node dissection and one underwent left upper abdominal evisceration. Final histological staging showed two stage 3 and two stage 4 patients. The intraperitoneal administration of paclitaxel and the oral administration of S-1 were well tolerated. Three patients died, at 8, 15, and 29 months, respectively, after the initial treatment, and one has been alive for 54 months without recurrence.. This chemotherapy can be used in the treatment of patients with peritoneal metastasis of gastric cancer.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Female; Humans; Injections, Intraperitoneal; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Paclitaxel; Peritoneal Neoplasms; Pilot Projects; Stomach Neoplasms; Survival Rate; Tegafur; Treatment Outcome

We report a 65-year-old female case of low-grade non-intestinal type adenocarcinoma of the nasal cavity with bilateral metastases to the cervical lymph nodes(T3N2cM0: Stage IV A). Chemoradiotherapy administered as first-line therapy yielded only a partial response in the primary tumor and metastatic lesions, and subsequent chemotherapy with S-1(at a dose of 80 mg per day)alone was applied as tumor dormancy therapy(TDT)on an outpatient basis. Adverse events during S-1 medication were limited to a decrease in leukocyte count and hemoglobin level, both of which were grade 1. The tumor has not enlarged, and the patient has survived 29 months since the beginning of chemotherapy with S-1 alone without any decrease in quality of life. Although the effectiveness of S-1 for adenocarcinoma of the head and neck has not been fully demonstrated, S-1 might be useful in patients with advanced head and neck adenocarcinoma for the purpose of TDT.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Disease Progression; Drug Combinations; Female; Humans; Lymphatic Metastasis; Magnetic Resonance Imaging; Nose Neoplasms; Oxonic Acid; Tegafur; Tomography, X-Ray Computed

A 67-year-old female visited our department complaining a general fatigue. Gastrointestinal endoscopy revealed a giant ulcer at distal portion of the stomach. NSE was the only tumor marker showing an abnormal value. Pathohistology of the biopsy specimen showed a monotonus massive growth of small irregular tumor cells. Distal gastrectomy with regional lymph node dissection was carried out. Final pathology report was undifferentiated adenocarcinoma of the stomach, exposing itself to serosa with lymph node metastasis. Postoperative chemotherapy was started using S-1. However, despite NSE turning normal, CEA rose that CDDP was added to the regimen. She went into remission for several months but CEA rose again and CDDP was changed to CPT-11. To our great regret, she died six months after the operation. Undifferentiated adenocarcinoma of the stomach is rare disease. Immunohistochemical staining is useful for a differential diagnosis. Prognosis is said to be poor but S-1/CDDP may contribute to prolong prognosis.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Cell Differentiation; Chemotherapy, Adjuvant; Cisplatin; Drug Combinations; Female; Humans; Oxonic Acid; Stomach Neoplasms; Tegafur; Tomography, X-Ray Computed; Treatment Failure

Using laser-captured microdissection and a real-time RT-PCR assay, we quantitatively evaluated mRNA levels of the following biomarkers in paraffin-embedded gastric cancer (GC) specimens obtained by surgical resection or biopsy: excision repair cross-complementing gene 1 (ERCC1), dihydropyrimidine dehydrogenase (DPD), methylenetetrahydrofolate reductase (MTHFR), epidermal growth factor receptor (EGFR), and five other biomarkers related to anticancer drug sensitivity. The study group comprised 140 patients who received first-line chemotherapy for advanced GC. All cancer specimens were obtained before chemotherapy. In patients who received first-line S-1 monotherapy (69 patients), low MTHFR expression correlated with a higher response rate (low: 44.9% vs high: 6.3%; P=0.006). In patients given first-line cisplatin-based regimens (combined with S-1 or irinotecan) (43 patients), low ERCC1 correlated with a higher response rate (low: 55.6% vs high: 18.8%; P=0.008). Multivariate survival analysis of all patients demonstrated that high ERCC1 (hazard ratio (HR): 2.38 (95% CI: 1.55-3.67)), high DPD (HR: 2.04 (1.37-3.02)), low EGFR (HR: 0.34 (0.20-0.56)), and an elevated serum alkaline phosphatase level (HR: 1.00 (1.001-1.002)) were significant predictors of poor survival. Our results suggest that these biomarkers are useful predictors of clinical outcomes in patients with advanced GC.

Topics: Adenocarcinoma; Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Camptothecin; Chemotherapy, Adjuvant; Cisplatin; Dihydrouracil Dehydrogenase (NADP); Disease Progression; DNA Primers; DNA-Binding Proteins; Drug Combinations; Endonucleases; ErbB Receptors; Female; Gene Expression Regulation, Neoplastic; Humans; Irinotecan; Male; Methylenetetrahydrofolate Reductase (NADPH2); Middle Aged; Oxonic Acid; Prognosis; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Stomach Neoplasms; Survival Rate; Tegafur

Pancreatic cancer is the third most common gastrointestinal malignancy in the United States. Due to difficulty in diagnosis, 40% of patients are stage IV by the time of diagnosis and median survival is only four to six months. Current therapy for advanced pancreatic cancer focuses largely on gemcitabine. However, a relatively new drug, S-1, is showing promising results. Phase II studies of S-1 monotherapy and recent combination with gemcitabine were conducted for the treatment of metastatic pancreatic cancer. The early phase II study demonstrated a response rate approaching 20% while the combination is reaching more than 35%.. We report a 68-year-old man who presented with stage IIB pancreatic cancer which advanced to stage IV after undergoing a Whipple procedure and adjuvant treatment with gemcitabine. The patient was refractory to treatment with gemcitabine as well as irinotecan, taxotere, and cetuximab. He subsequently participated in a trial involving the drug S-1. He achieved 10-month survival with preserved quality of life: he had 14 cycles of S-1 and maintained an ECOG performance status of 0-1 throughout.. For this patient, 14 cycles of S-1 were well-tolerated for 10 months after failing two prior chemotherapeutic regimens suggesting important insight that S-1 may be active and convenient for its oral use and it may have favorable safety profile in patients with metastatic pancreatic cancer. Randomized trials are warranted to determine the effectiveness of S-1 for the treatment of pancreatic cancer.

Topics: Adenocarcinoma; Aged; Antimetabolites, Antineoplastic; Drug Combinations; Humans; Male; Neoplasm Recurrence, Local; Oxonic Acid; Pancreas; Pancreatic Neoplasms; Tegafur

S-1, a novel oral fluoropyrimidine, is an effective therapeutic agent for gastric cancer. Herein, we report a case with locally advanced gastric cancer that achieved a curative resection after S-1 monotherapy as neoadjuvant treatment. A 68-year-old man was diagnosed with gastric cancer and massive lymphadenopathy involving the perigastric, celiac axis and splenic hilum. His clinical stage was cT3N2H0P0M0. Considering his relatively poor performance (ECOG 2, severe weight loss) and advanced age, we started the patient on S-1 monotherapy at a dose of 35 mg/m2 bid for 4 consecutive weeks followed by a 2-week rest. Follow-up study after 4 treatment cycles revealed disappearance of the lymphadenopathy of the perigastric and celiac axis with diminished extension of the stomach mass. The patient had a partial response (PR) with a 72% tumor reduction, according to the Response Evaluation Criteria in Solid Tumors (RECIST). His performance status was improved to an ECOG 1 and he gained 7 kg. A curative (R0) resection was achieved with a radical total gastrectomy and D2 dissection. The pathological stage was pT3N2M0, stage IIIB. In conclusion, S-1 neoadjuvant chemotherapy aided in the treatment of gastric cancer in this patient.

Topics: Adenocarcinoma; Aged; Antimetabolites, Antineoplastic; Drug Combinations; Gastrectomy; Humans; Male; Neoadjuvant Therapy; Neoplasm Staging; Oxonic Acid; Stomach Neoplasms; Tegafur

The aim of this study was to determine the effectiveness of adjuvant gemcitabine plus S-1 chemotherapy for patients with pancreatic carcinoma.. Patients admitted for curative surgery for pancreatic adenocarcinoma received adjuvant chemotherapy with 10 cycles of gemcitabine plus S-1 every 2 weeks. Each chemotherapy cycle consisted of intravenous gemcitabine, 700 mg/m(2), on day 1 and orally administered S-1, 50 mg/m(2), for 7 consecutive days, after which there was a 1-week pause of chemotherapy.. Twenty-seven patients were entered into this study. According to the TNM system, 4 (15%), 2 (7%), 6 (22%), and 15 (56%) patients were diagnosed with stage IA, IB, IIA, and IIB disease, respectively. Overall and disease-free survival rates were 86% and 60% at 1 year, 66% and 45% at 2 years, and 33% and 45% at 3 years, respectively. Toxicity during chemotherapy was mild.. Adjuvant gemcitabine plus S-1 chemotherapy appears to be a promising treatment for patients after surgical resection of pancreatic adenocarcinoma.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Deoxycytidine; Disease-Free Survival; Drug Combinations; Female; Gemcitabine; Humans; Male; Middle Aged; Oxonic Acid; Pancreatectomy; Pancreatic Neoplasms; Pancreaticoduodenectomy; Survival Rate; Tegafur

The patient was a 54-year-old female with gastric cancer. As laparotomy showed diffuse peritoneal dissemination, only laparotomy was performed and chemotherapy was conducted with a combination of S-1 80 mg/m(2) (2 weeks administration and 1 week rest) and paclitaxel (PTX) 50 mg/m(2) (day 1, 8). After 5 courses of this regimen, endoscopy showed the tumor was reduced in size and PET-CT revealed no evidence of metastasis. She underwent total gastrectomy with D2 lymph node dissection and Roux-en Y reconstruction. Peritoneal metastasis histologically disappeared, and the final findings were T1, N0, H0, P0, CY0, M0, Stage I A, Cur A. The only adverse effect was grade 1 stomatitis during this chemotherapy. CT showed no findings of recurrence 11 months after the operation. The S-1/PTX combination chemotherapy was thought to be effective for gastric cancer with peritoneal dissemination and made curative operation possible in this case.

Topics: Adenocarcinoma; Antimetabolites, Antineoplastic; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Drug Combinations; Female; Gastrectomy; Humans; Middle Aged; Oxonic Acid; Paclitaxel; Peritoneal Neoplasms; Stomach Neoplasms; Tegafur

We described a case with recurrent gallbladder carcinoma, successfully treated by combination chemotherapy using gemcitabine, CPT-11, and S-1 that was administered as second-line chemotherapy after failure of gemcitabine monotherapy. The level of CA19-9 was normalized three months later, and metastatic tumors of the liver were calcified. She had received the combination chemotherapy for 15 months and is now alive.

Topics: Adenocarcinoma; Aged; Antimetabolites, Antineoplastic; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Calcinosis; Camptothecin; Deoxycytidine; Drug Combinations; Female; Gallbladder Neoplasms; Gemcitabine; Humans; Irinotecan; Liver Neoplasms; Neoplasm Recurrence, Local; Oxonic Acid; Tegafur

An 88-year-old man with unresectable sigmoid colon cancer due to retroperitoneal invasion and massive LN metastasis was treated with S-1 after colostomy. S-1 (80 mg/body/day) was administered for 2 weeks followed by a one week interval. Colonoscopy and abdominal CT revealed a partial response. After 5 courses, the patient underwent sigmoidectomy. S-1 was then administered for 15 courses. There was no side effect, and hospitalization was not required during the treatment. This therapy was very feasible and convenient, obtained good compliance and enhanced the quality of life of this patient. S-1 is expected to be an effective agent for the treatment of advanced colon cancer in elderly patients in days to come.

Topics: Adenocarcinoma; Aged, 80 and over; Antimetabolites, Antineoplastic; Drug Combinations; Humans; Male; Oxonic Acid; Sigmoid Neoplasms; Tegafur

We report a patient with advanced stage IV gastric cancer treated by chemotherapy for over two years. The patient was a 69-year-old man with paraaortic lymph node metastasis of gastric cancer. He underwent a distal gastrectomy in non-curative resection. After surgery, chemotherapy with TS-1 (100 mg/body/day) was performed. At 7 months after surgery, progression of lymph node metastasis in porta hepatis was recognized, and paclitaxel was administered at a weekly dose of 80 mg/m(2) for 3 weeks followed by one week rest. He remained stable for 12 months under paclitaxel treatment. At 26 months after surgery, progression of lymph node metastasis in porta hepatis was recognized again, and CPT-11 was administered at a bi-weekly dose of 80 mg/m(2). Although the patient died two years seven months after surgery, the chemotherapy with sequential administration of TS-1, paclitaxel and CPT-11 was thought to be effective for advanced gastric cancer.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Combined Modality Therapy; Drug Administration Schedule; Drug Combinations; Gastrectomy; Humans; Irinotecan; Male; Oxonic Acid; Paclitaxel; Stomach Neoplasms; Survivors; Tegafur

A 72-year-old male with advanced gastric cancer (cT3N2M0H0P0CY1, cStage IV) was treated with TS-1/CDDP as neoadjuvant chemotherapy. TS-1 (60 mg/m(2)/day) was orally administered for 3 weeks followed by 2 drug free weeks as a course, and CDDP (60 mg/m(2)) was administered by intravenous drip on day 8. After the fourth course,a significant tumor reduction was obtained. Total gastrectomy, splenectomy, and D 2 type nodal dissection were performed. The histological diagnosis revealed complete disappearance of cancer cells in the stomach and all of the lymph nodes, which is a so-called pathological complete response. The patient has now been in good health without a recurrence for 24 months after surgery. This case suggests that neoadjuvant chemotherapy with TS-1/CDDP is a potential regimen for advanced gastric cancer.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cisplatin; Drug Administration Schedule; Drug Combinations; Gastrectomy; Humans; Male; Neoplasm Staging; Oxonic Acid; Remission Induction; Stomach Neoplasms; Tegafur

Topics: Adenocarcinoma; Aged; Antimetabolites, Antineoplastic; Drug Combinations; Duodenal Neoplasms; Female; Humans; Liver Neoplasms; Oxonic Acid; Tegafur

A 72-year-old man was admitted to our hospital, complaining of exertional breathlessness. Chest radiograph revealed a right pleural effusion. Cytology for pleural effusion revealed adenocarcinoma; thus, he was diagnosed with advanced lung cancer (clinical stage T 4 N 0 M 0, Stage IIIB). Since tumor recurrence occurred despite CBDCA+gemcitabine, docetaxel, gefitinib and vinorelbine administrations, he received fifth-line oral chemotherapy using TS-1 at 120 mg/day (80 mg/m(2)/day) for 28 days, followed by withdrawal for 14 days. Chest computed tomography showed a partial response. Hematologic and non-hematologic toxicities were mild with the TS-1 administration. TS-1 could be an effective agent for treatment of multidrug-resistant non-small cell lung cancer.

Topics: Adenocarcinoma; Aged; Antimetabolites, Antineoplastic; Drug Administration Schedule; Drug Combinations; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Humans; Lung Neoplasms; Male; Neoplasm Staging; Oxonic Acid; Remission Induction; Tegafur

The patient was a 70-year-old man who was diagnosed inoperable because of liver metastases of advanced gastric cancer and his respiratory dysfunction. He received docetaxel at the starting dose of 40 mg/m(2) by iv infusion over 1 hour on day 1 and TS-1 at the full dose of 80 mg/m(2) daily for two weeks every three weeks. After 6 cycles of this combination therapy, gastric cancer with liver metastases entirely disappeared. No re-growth of gastric cancer has been seen for three years with chemotherapy of TS-1. This chemotherapy shows a high degree of safety and efficacy in this patient.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Docetaxel; Drug Administration Schedule; Drug Combinations; Humans; Liver Neoplasms; Male; Oxonic Acid; Remission Induction; Stomach Neoplasms; Taxoids; Tegafur

In recent years, a high success rate of combination chemotherapy with TS-1/CDDP has been reported against advanced gastric carcinoma. We, this time, experienced a case of advanced hemorrhagic gastric cancer with multiple hepatic metastases for which total gastrectomy was performed, followed by postoperative combination chemotherapy with TS-1/CDDP which culminated in achieving CR for the liver metastases.. The patient was a 59-year-old woman who was hospitalized for a type IV gastric carcinoma in the upper part of the gastric body. Further examination revealed liver (S 2, S 5, S 7) and lymph node metastases. Due to hemorrhage from the tumorous lesion, the treatment strategy selected was total gastrectomy followed by postoperative chemotherapy. Operative and clinicopathological findings revealed a mass lesion of MLU, type IV, 16.0x14.0 cm, sT 3 (SE), sH 1 (bilobular multiple metastases) and CY 0, and por 1, pT 2 (SS), pN 1 (+) [23/38], int, INF beta, ly 3 and v 1, respectively. Combination chemotherapy with TS-1/CDDP was instituted after surgery. As for the dosing method of combination chemotherapy,the patient was treated with a course of TS-1 80 mg daily divided into two doses over 21 days continuously, followed by a 14-day cessation of the drug,together with a dose of CDDP 70 mg on day 8. The patient received a total of four courses. At the completion of the third chemotherapy course, her multiple hepatic metastases disappeared. Further, the preoperative CA 19-9 level of 370 U/mL returned to normal after chemotherapy. Adverse events observed were leukopenia and thrombocytopenia, both of which were judged to be grade 2. At two years and nine months, the patient is being followed on an outpatient basis without any sign of postoperative recurrent disease.. We experienced a patient who was successfully treated with combination chemotherapy and demonstrated disappearance of her multiple hepatic metastases, showing a clinical response of CR lasting for more than two years against the metastases. It was inferred that this regimen of TS-1/CDDP is an effective treatment modality not only as preoperative but also postoperative chemotherapy after surgery for advanced gastric carcinoma.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Administration Schedule; Drug Combinations; Female; Gastrectomy; Humans; Liver Neoplasms; Lymph Nodes; Lymphatic Metastasis; Middle Aged; Oxonic Acid; Postoperative Period; Remission Induction; Stomach Neoplasms; Tegafur

We report a case of advanced gastric cancer that responded well to low-dosage TS-1. A 72-year-old woman was diagnosed as having unresectable advanced gastric cancer with ascites and hydronephrosis in the right kidney. She was treated with chemotherapy using a low-dosage of TS-1 (80 mg/body/day) administered perorally for 4 weeks followed by a drug-free 2 weeks, in six-week cycles. However, she developed weight loss, appetite loss, and stomatitis. We therefore reduced the dosage of TS-1 from 80 mg/body/day to 60 mg/body/day. The ascites and hydronephrosis gradually improved during the following 3 months, whereupon she could undergo total gastrectomy. The postoperative findings showed no ascites and no peritoneal dissemination. The postoperative pathological findings showed that the cancer cells were localized to within the mucosa, and there were no cancer cells in the greater and lesser omentum. Three weeks after the operation, TS-1 was resumed at 60 mg/body/day. However, 3 months later,ascites and metastasis to the abdominal skin developed, and she died 9 months after the operation.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Signet Ring Cell; Drug Administration Schedule; Drug Combinations; Female; Gastrectomy; Humans; Lymph Node Excision; Neoplasm Staging; Neoplasms, Multiple Primary; Oxonic Acid; Stomach Neoplasms; Stomatitis; Tegafur

We report on the successful treatment of advanced gastric cancer by surgical resection following neoadjuvant chemotherapy. A 67-year-old man was referred to our hospital with a diagnosis of pancreatic cancer. Meticulous examination, however, revealed the presence of gastric cancer with ascites and large lymph node metastasis adjacent to the pancreas. We selected combination chemotherapy with oral S-1 and biweekly paclitaxel. After two courses, both the primary tumor and metastatic lymph nodes were greatly reduced, and the ascites had disappeared. Using laparoscopy, there was no evidence of peritoneal metastases, and the cytological examination was negative. The patient underwent distal gastrectomy with D2 lymph node dissection. Histological examination revealed that the cancer cells were still present in part, but no lymph node metastases were found. The tumor was pathologically diagnosed as pT2, pN0, P0, M0, CY0, and p-stage II. The patient is healthy over 4 years after surgery without recurrence.

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

The patient was an 80-year-old man whose complaint was coffee-grounds vomit. He was diagnosed with advanced gastric cancer, T2N1H0P0M0, stage II. Though the curative operation was explained to the patient, he declined it because of complications of advanced age, diabetes and bronchial asthma; chemotherapy was chosen instead. TS-1 (80 mg/day) was administered for 28 days, followed by 14 days rest as one course. A partial response was observed after the first course, and no cancer cells were confirmed by endoscopic biopsy after the fifth course. Moreover, after the 14th course, CT showed a complete regression of lymph node metastasis, and no cancer cells were confirmed by endoscopic biopsy, for a complete response (CR). From now on, as society grays more and more, it is considered that elderly advanced gastric cancer patients with complications will increase. TS-1 single treatment is considered to be safe and outpatient treatment possible as one of the useful cures.

Topics: Adenocarcinoma; Aged, 80 and over; Antimetabolites, Antineoplastic; Diabetes Complications; Drug Administration Schedule; Drug Combinations; Humans; Hypertension; Male; Oxonic Acid; Remission Induction; Stomach Neoplasms; Tegafur

A 60-year-old man, who had been admitted to another hospital with complaints of constipation, abdominal fullness and appetite loss, was referred to our hospital for further examination and therapy. The patient was diagnosed as advanced gastric cancer (type-3) with multiple liver metastasis and obstructive jaundice. He was treated with combination therapy of paclitaxel and TS-1 (60 mg/m(2)/day of paclitaxel was iv administered on day 1 and 8, and TS-1 of 80 mg/m(2)/day was orally administered for 2 weeks followed by one drug-free week), and showed a remarkable response. However, because of ascites, elevated serum CEA level and resistance in the liver metastasis and gastric region, we attempted two courses of combination therapy with high-dose CPT-11 and cisplatin (70 mg/m(2)/day of CPT-11 was administered iv on day 1 and 15, and 80 mg/m(2)/day of cisplatin on day 1 followed by two drug-free weeks) which showed a remarkable response. Two courses of combination therapy with low-dose CPT-11 and cisplatin (60 mg/m(2)/day of CPT-11 and 30 mg/m(2)/day of cisplatin were administered iv on day 1 and 15 followed by two drug-free weeks) on an outpatient basis. However, the patient showed resistance to the latter combination therapy, increased ascites due to suspicious peritonitis carcinomatosa and obvious re-growth of the metastatic tumors in the liver. He died on May 23, 2006, about ten months after initial diagnosis. We reported a case of successful treatment of combination chemotherapy for advanced gastric cancer with obstructive jaundice due to progressive multiple metastatic tumors in the liver and obtained comparative long-term survival maintaining high quality of life.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cisplatin; Drug Administration Schedule; Drug Combinations; Humans; Irinotecan; Jaundice, Obstructive; Liver Neoplasms; Male; Middle Aged; Oxonic Acid; Paclitaxel; Stomach Neoplasms; Survivors; Tegafur

Gastric small cell carcinomas are rather rare. The incidence of small cell carcinomas of all histological types of gastric tumors is about 0.1%. Small cell carcinoma is a very aggressive cancer with a poor prognosis,and there is no effective chemotherapy to date. We experienced a case of small cell carcinoma of the stomach with relatively long survival from combination chemotherapy. A 75-year-old man underwent total gastrectomy, and liver metastasis was recognized 5 months postoperatively. We used combination chemotherapy with tegafur/gimeracil/oteracil potassium+cisplatin and irinotecan hydrochloride+cisplatin, and he has obtained a long survival time. We should gather more chemotherapy cases and establish some effective regimens for small cell carcinoma of the stomach.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Carcinoma, Small Cell; Chemotherapy, Adjuvant; Cisplatin; Drug Administration Routes; Drug Combinations; Gastrectomy; Humans; Irinotecan; Lymph Node Excision; Male; Oxonic Acid; Stomach Neoplasms; Survivors; Tegafur

An 85-year-old man, who had undergone right hemicolectomy and partial hepatectomy for caecum cancer with liver metastasis, was diagnosed with recurrent multiple liver metastasis 10 months after surgery. TS-1 administration at a dose of 80 mg/day induced grade 3 anorexia, and after complete recovery from the adverse reaction, it was converted to a low-dose TS-1 administration at 40 mg/day. This treatment reduced the diameter of the liver metastasis and was continued for ten months without any adverse reaction. Pharmacokinetic analysis in this patient on low-dose TS-1 showed that Cmax and AUC of 5-chloro-2,4-dihydroxypyridine (CDHP) were equivalent to the values reported in cancer patients with normal renal function receiving standard-dose administration. TS-1 therapy may provide a safe and effective alternative to chemotherapy for elderly patients with advanced colorectal carcinoma. Pharmacokinetic analysis could be useful for determining the ideal dose of TS-1.

Topics: Adenocarcinoma; Aged, 80 and over; Antimetabolites, Antineoplastic; Appendiceal Neoplasms; Colonic Neoplasms; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Humans; Liver Neoplasms; Male; Oxonic Acid; Tegafur

A 62-year-old woman with Barrett's esophageal cancer was hospitalized. Abdominal CT confirmed metastases to the liver and lymph nodes, for which surgical excision and radiotherapy were not indicated. We started chemotherapy with a course of daily oral S-1 at a dose of 80 mg/m(2) for 21 days, with a 2-hour drip of cisplatin at 60 mg/m(2) on day 8. Breaks of 14 drug-free days were given between courses. After two courses, a repeat CT confirmed that the liver and lymph node metastases had disappeared; after three courses, another CT confirmed that the metastatic foci were still absent, so we judged the disease to be in complete remission. Endoscopy and upper GI series confirmed that the primary tumor was reduced, and endoscopic mucosal resection performed using the strip biopsy method. The excision specimen was well differentiated adenocarcinoma, and mucosal invasion, and the excision stump was negative. After two more courses of S-1 + cisplatin, chemotherapy has been suspended with the patient's consent, and in the 21 months after endoscopic mucosal resection, no recurrence has been observed. This is a rare case of metastatic Barrett's esophageal cancer in which the metastases were eradicated by S-1 + cisplatin, and the primary tumor successfully excised by endoscopic mucosal resection after downstaging.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Barrett Esophagus; Cisplatin; Drug Combinations; Esophageal Neoplasms; Female; Humans; Liver Neoplasms; Lymphatic Metastasis; Middle Aged; Mucous Membrane; Oxonic Acid; Salvage Therapy; Tegafur; Tomography, X-Ray Computed

We evaluate the feasibility and efficacy of S-1 in combination with cisplatin (CDDP) for patients with colorectal cancer.. A total of 52 patients with advanced or recurrent colorectal cancer were included. S-1 was given orally twice daily for 21 days and CDDP 30 mg/m(2) on day 1 and 8, followed by a 2-week period of no treatment.. Tumor responses among patients included 18 PR, 12 SD, and 16 PD (n = 46). The overall response rate was 36.4% (18/46). The response rate of the patients with prior chemotherapy was 22.2% (4/18) and 50.0% (12/24) among the patients who had no prior therapy. The median survival periods were 555 days and the median progression free survival periods were 183 days, respectively. S-1 in combination with CDDP shows promising activity with acceptable toxicities against colorectal cancer.. A combination of S-1 and CDDP could be a standard therapy for treating colorectal carcinoma.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Colorectal Neoplasms; Disease-Free Survival; Drug Combinations; Female; Humans; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Oxonic Acid; Survival Rate; Tegafur; Treatment Outcome

Two patients with advanced gastric cancer who underwent gastrectomy and pathological examination were both diagnosed as having Stage IV gastric cancer with distant lymph-node metastases and peritoneal dissemination, respectively. The patients received S-1 and low-dose CDDP in combination therapy after reduction surgery. Each treatment course consisted of S-1 100 mg/body oral administration for 3 weeks and intravenous administration of CDDP at a dose of 25 mg/m(2) on days 7, 14 and 21. The course repeated after a two-week rest period, and the treatment was repeated every five weeks. After three courses of treatment, both patients received S-1 100 mg/body for 2 weeks on and 2 weeks off as long as possible. They remain alive 15 and 12 months after initial treatment, respectively, without any sign of recurrence. The patients did not experience grade 3 or more adverse events and received this regimen as an outpatient. These results suggest that combination therapy with S-1 and low-dose CDDP is effective against advanced gastric cancer.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Drug Administration Schedule; Drug Combinations; Female; Gastrectomy; Humans; Middle Aged; Neoplasm Staging; Oxonic Acid; Remission Induction; Stomach Neoplasms; Tegafur

We attempted S-1 administered five days a week from March, 2004 for an 84-year-old female harboring Borrmann type 1 gastric cancer because her family did not agree to her gastrectomy. After treatment for 1 month the lesion changed into a shallow ulcer. The lesion was clinically diagnosed with CR about 3 months later. As of October, 2006, 2 years after inducing CR, we have been administering S-1 to the patient, with no regrowth of the tumor.

Topics: Adenocarcinoma; Aged, 80 and over; Antimetabolites, Antineoplastic; Drug Administration Schedule; Drug Combinations; Female; Humans; Oxonic Acid; Remission Induction; Stomach Neoplasms; Tegafur

The patient was a 42-year-old female diagnosed with unresectable highly advanced gastric cancer complicated by peritoneal dissemination. We performed systemic chemotherapy with MTX+5-FU as the first-line treatment, which stabilized the disease. Since the patient initially wished a radical resection, we tried chemotherapy with weekly PTX as a second-line treatment. Her therapeutic response remained between a partial response and a stable disease for about five months, followed, however, by progressive disease. The result of the third-line treatment with CPT-11+CDDP was again a progressive disease, so we switched her regimen to single-agent S-1 as a fourth-line treatment. The ascites disappeared three months after the change in regimen. As of March 2006, the patient had survived for 17 months since diagnosis (8 months since the ongoing S-1 therapy started) and the disease is currently stabilized, and preserving a favorable performance status. However, in June 2006, the patient died of pneumonia 20 months after the diagnosis.

Topics: Adenocarcinoma; Adult; Antimetabolites, Antineoplastic; Drug Administration Schedule; Drug Combinations; Fatal Outcome; Female; Humans; Oxonic Acid; Peritoneal Neoplasms; Stomach Neoplasms; Tegafur

We report a case of multiple bone metastases from gastric cancer treated with combination chemotherapy of S-1 and CDDP. A 54-year-old man underwent distal gastrectomy for gastric cancer (Stage II) in March 2003. Multiple bone metastases complicated with DIC were diagnosed in September 2005. The patient was treated with combination chemotherapy of S-1 and CDDP. S-1 (80 mg/m2/day) was administered for 21 days followed by 14 days rest as one course. CDDP (60 mg/m2) administration was begun 8 days after the start of S-1. After one course of the treatment, DIC was resolved. The abnormal uptake at the bone metastases was found to have decreased by bone scintigraphy. Bone metastases recurred in April 2006. Although combination chemotherapy of S-1 and DOC was administered, the patient died of DIC in August 2006. Combination chemotherapy of S-1 and CDDP is considered effective treatment for prolonging survival in cases of gastric cancer with bone metastases.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Cisplatin; Drug Administration Schedule; Drug Combinations; Gastrectomy; Humans; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Oxonic Acid; Postoperative Period; Stomach Neoplasms; Tegafur

Chemotherapy (5-FU) with concurrent radiotherapy is recommended as an effective treatment for locally unresectable pancreatic cancer. A phase I study of S-1 with concurrent radiotherapy demonstrated promising results in late years. A 70-year-old man was revealed to have metastatic pancreatic cancer (T 4 N 3 M 1 (PER), Stage IVb). Since a curative operation was impossible in this case, he was treated with systemic chemotherapy using S-1 combined with irinotecan hydrochloride (CPT-11) as first-line chemotherapy. Because the primary lesion was increased in size after two courses,he was then treated by radiotherapy combined with S-1 as second-line treatment. S-1 (80 mg/body/day) was orally administered (2 consecutive weeks, 1-week break), and concurrent radiotherapy was performed at a daily fraction of 1.8 Gy, 5 days/week, total amount 45 Gy. Although in the early period of chemoradiotherapy, transfusion for anemia and morphine hydrochloride for pain control were necessary, his symptoms gradually improved by the reduction of primary lesion. The patient has been receiving systemic chemotherapy as an outpatient for 12 months without deterioration of quality of life.

Topics: Adenocarcinoma; Aged; Ambulatory Care; Antimetabolites, Antineoplastic; Camptothecin; Drug Administration Schedule; Drug Combinations; Humans; Irinotecan; Lymph Nodes; Lymphatic Metastasis; Male; Oxonic Acid; Pancreatic Neoplasms; Quality of Life; Radiotherapy Dosage; Tegafur

We investigated the clinical efficacy and safety of S-1 retrospectively for the treatment of 32 patients with advanced gastric cancer after reduction surgery (gastrectomy). S-1 was administered orally twice daily, at a standard dose of 80 mg/m(2) per day for 28 days, followed by a 14-day rest. There were 21 patients having only a single residual metastatic site and 11 with two or more metastatic sites. Major residual metastatic sites were peritoneum in 25 patients, lymph nodes in 7, liver in 4 and lung in 2. The response rate by target organ was 28.6% for lymph node metastasis, and 0% for liver and lung metastasis. Peritoneal metastasis was not considered measurable site. The median survival time (MST) after S-1 administration was 573 days (95% confidence interval, 439 to 707 days). The 1-, 2- and 3-year survival rates were 62.3%, 40.3% and 28.2%, respectively. Of the 32 patients, 14 received S-1 for more than a year, and the MST in these patients was 897 days (95% confidence interval, 255 to 1,539 days). The incidence of adverse events was 90.6%, but the incidence of grade 3 or 4 was 12.5%. Long-term administration of S-1 may serve to prolong the survival period of patients with gastric cancer after reduction surgery, particularly in peritoneal metastasis.

Topics: Adenocarcinoma; Aged; Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Drug Administration Schedule; Drug Combinations; Female; Gastrectomy; Humans; Male; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Retrospective Studies; Stomach Neoplasms; Survival Rate; Tegafur

We treated hepatic metastasis of gastric cancer with CPT-11 therapy and obtained complete remission of the hepatic tumor that has been maintained for than 2 years postoperatively. The patient was a 71-year-old man with a history of angina pectoris. In 1988, gastric cancer was diagnosed, and he underwent distal gastrectomy at another hospital. In 2003, the patient began to suffer from regurgitation symptoms and presented to our hospital in October of the year. Remnant gastric cancer was diagnosed as a result of detailed investigation. Preoperative imaging revealed the presence of a solitary tumor (6 cm in diameter) in the posterior lobe of the liver, and it was confirmed to be a hepatic metastasis from the remnant gastric cancer by needle biopsy. We decided to treat this metastasis with postoperative systemic chemotherapy. Total resection of the remnant stomach was done in November 2003 and oral S-1 therapy was started 3 weeks after surgery. When the response of the hepatic metastasis was evaluated after the completion of 3 courses, the tumor showed enlargement. Therefore, his chemotherapy was changed to CPT-11. After a total 900 mg of CPT-11 had been administered, imaging studies confirmed disappearance of the hepatic metastasis. The patient remains disease-free and has no impairment of daily activities 2 years after resection of the remnant stomach.

Topics: Adenocarcinoma; Aged; Antineoplastic Agents, Phytogenic; Camptothecin; Drug Administration Schedule; Drug Combinations; Gastrectomy; Humans; Irinotecan; Liver Neoplasms; Male; Oxonic Acid; Remission Induction; Stomach Neoplasms; Tegafur

We report a case of gastric cancer with ascites treated with chemotherapy. The patient is a 67-year-old male. Combination chemotherapy of S-1 and CDDP was given as the first-line treatment. However, the symptoms did not improve with that regimen, so we decided to change the chemotherapy to paclitaxel as second-line treatment. After 4 cycles, CT scan revealed decreasing ascites and endoscopy a reduction of the primary tumor. The patient has maintained a condition of decreasing ascites with improvement of QOL for 8 months. This regimen is considered effective treatment for unresectable gastric cancer.

Topics: Adenocarcinoma; Aged; Antineoplastic Agents, Phytogenic; Cisplatin; Drug Administration Schedule; Drug Combinations; Drug Resistance, Neoplasm; Humans; Infusions, Intravenous; Male; Oxonic Acid; Paclitaxel; Peritoneal Neoplasms; Stomach Neoplasms; Tegafur

We report a case of unresectable gastric cancer, who had been treated with S-1 alone for 3 years without cancerous symptoms. The patient was a 66-year-old male. His diagnosis was advanced gastric cancer based on gastrofiberscopy. He underwent surgery on April 15, 2003. The tumor proved to be unresectable due to direct invasion of the pancreatic head, so only gastrojejunostomy was performed. On day 14 after surgery, the administration of S-1 alone was commenced at a dose of 100 mg per day in a 4-week course of medication at 2-week intervals. No side effects were noted. Moreover, his quality of life (QOL) was not disturbed, and he led an active social life throughout the course. Long survival was achieved by S-1 alone.

Topics: Adenocarcinoma; Aged; Antimetabolites, Antineoplastic; Drug Administration Schedule; Drug Combinations; Humans; Male; Oxonic Acid; Quality of Life; Stomach Neoplasms; Survivors; Tegafur

We report a 60-year-old female with pulmonary metastasis from breast cancer who responded to S-1. In November 2001, she underwent surgery. In October 2005, relapse was detected. As there was no hormone sensitivity, chemotherapy was selected, and oral administration of S-1 at 120 mg/day (2 divided doses) was initiated. After the fourth course, the tumor marker level returned to the reference value. Thoracic CT at the end of the sixth course revealed the disappearance of the metastatic focus. Adverse reactions during the administration period were mild. S-1 showed potent antitumor effects and good tolerance, and it may be useful for treating metastatic/recurrent breast cancer.

Topics: Adenocarcinoma; Antigens, Tumor-Associated, Carbohydrate; Antimetabolites, Antineoplastic; Biomarkers, Tumor; Bone Neoplasms; Breast Neoplasms; Carcinoembryonic Antigen; Chemotherapy, Adjuvant; Combined Modality Therapy; Drug Administration Schedule; Drug Combinations; Female; Humans; Lung Neoplasms; Lymph Nodes; Lymphatic Metastasis; Mastectomy, Segmental; Middle Aged; Mucin-1; Oxonic Acid; Quality of Life; Tegafur

A 36-yr-old woman complaining of cough and body weight loss at a health checkup and referred to us after an abnormality was noted on the chest X-ray was diagnosed with clinical stage IV (cT2N3Ml) non-small-cell lung cancer (adenocarcinoma). She received three courses of chemotherapy. The response to treatment was stable disease. She was subsequently enrolled in a clinical trial of S-1, a new oral fluoropyrimidine anticancer drug, and received a total of 22 courses of S-1 over a period of 2 yr 5 mo. At the end of treatment, she was classified as having a partial response. A bronchoscopic biopsy disclosed no cancer cells. Remission continued for 1 yr 7 mo after treatment. The patient died of primary disease 8 yr after the initiation of treatment with oral S-1. Non-small-cell lung cancer was approved as a new indication of S-1 in 2004 in Japan, but the number of patients receiving it for this indication remains limited. Here, we describe our experience with a patient with adenocarcinoma of the lung who survived for a prolonged period after treatment with S-1. Our findings suggest that S-1 is effective for the treatment of non-small-cell lung cancer.

Topics: Adenocarcinoma; Adult; Antimetabolites, Antineoplastic; Drug Combinations; Female; Humans; Lung Neoplasms; Oxonic Acid; Radiography, Thoracic; Survival Rate; Tegafur; Tomography, X-Ray Computed; Treatment Outcome

We report a case of advanced gastric cancer with multiple liver metastases,in which a complete resection was performed following a bypass operation and chemotherapy. A 55-year-old man presented with vomiting and body weight loss. Gastrointestinal endoscopy revealed advanced gastric cancer with pyloric stenosis, and abdominal computed tomography showed multiple liver metastases in segments 2, 3, 5, and 6. A gastrojejunostomy was performed on August 24, 2004. The patient was then treated with 3 cycles of S-1 (120 mg/body, days 1-21) plus cisplatin (80 mg/body,day 8),followed by 8 cycles of weekly paclitaxel (wPTX; 140 mg/body, days 1,8, and 15). The primary tumor and liver tumors remained stable following the 3 cycles of S-1 plus cisplatin, but the liver tumors were considerably smaller after 3 cycles of wPTX. On August 25, 2005, a distal gastrectomy with D2 lymphadenectomy,lateral segmentectomy,and S5 partial hepatectomy was performed. The surgery was completed with no residual macroscopic or microscopic tumors. The patient received 6 cycles of wPTX as adjuvant therapy,and remained well with no evidence of tumor recurrence 28 months after the initial treatment.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Drug Administration Routes; Drug Combinations; Gastrectomy; Gastric Bypass; Humans; Liver Neoplasms; Lymph Node Excision; Male; Middle Aged; Oxonic Acid; Paclitaxel; Remission Induction; Stomach Neoplasms; Tegafur

A 65-year-old man who had AFP producing gastric cancer with massive lymph-node metastasis was admitted to our institution. Because of bulky lymph-node metastasis, the tumor was considered unresectable. He was treated with neoadjuvant chemotherapy of S-1 and cisplatin (CDDP).S-1 (80 mg/m2/day) was administered for 21 consecutive days followed by 14 days rest as one course,and CDDP (60 mg/m2) was infused over 2 hours on day 8. After 1 course, radiographic examination showed remarkable improvement in the tumor size of the stomach, and computed tomography showed markedly reduced paraaortic lymph node metastasis. However, surgery was performed after 3 weeks,because of the adverse effect of diarrhea grade 3 after one course of the chemotherapy. This is a rare case in which neoadjuvant chemotherapy of S-1 and CDDP may well be an effective treatment for unresectable AFP producing gastric cancer with bulky lymph-node metastasis.

Topics: Adenocarcinoma; Aged; alpha-Fetoproteins; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cisplatin; Drug Administration Schedule; Drug Combinations; Gastrectomy; Humans; Lymph Nodes; Lymphatic Metastasis; Male; Oxonic Acid; Preoperative Care; Stomach Neoplasms; Tegafur

Biliary tract cancers, including extrahepatic bile duct cancer, are often diagnosed at an advanced stage; however,no standard therapies have been established as yet for this disease,and new,effective chemotherapeutic agents are being sought. Recently, a late phase II study of S-1, an oral fluoropyrimidine, in 40 patients with advanced biliary tract cancer yielded a good response rate of 35.0%. In this article,we report two patients with advanced extrahepatic bile duct cancer enrolled in the study who showed a partial response to S-1 monotherapy.

Topics: Adenocarcinoma; Antimetabolites, Antineoplastic; Bile Duct Neoplasms; Bile Ducts, Extrahepatic; Drug Administration Schedule; Drug Combinations; Female; Humans; Liver Neoplasms; Male; Middle Aged; Oxonic Acid; Quality of Life; Tegafur

We report patients with advanced Stage IV gastric cancer responding to chemotherapy with S-1 or UFT. Case 1: The patient was a 59-year-old man with Stage IV gastric cancer because of CY 1. After surgery, chemotherapy with S-1 (100 mg/body/day) was performed for one year and 11 months. At present, 5 years and 5 months after surgery, this patient shows no signs of tumor recurrence. Case 2: The patient was a 68-year-old woman with Stage IV gastric cancer because of P 1. She was treated with 200 mg/day of UFT for one year and 9 months. At present, 5 years after surgery, she shows no signs of tumor recurrence. We considered that the longterm survival of such patients is attributable to chemotherapy with S-1 or UFT. The OPRT activity of the two cases was high, so chemotherapy with S-1 or UFT was thought to be effective for them.

Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Female; Humans; Male; Middle Aged; Oxonic Acid; Stomach Neoplasms; Tegafur; Uracil

The patient was a 47-year-old man who was discovered to have Borrmann type 4 cancer of the cardiac region of the stomach associated with esophageal invasion during upper GI endoscopy and was histopathologically diagnosed with poorly-differentiated adenocarcinoma. Invasion of the aorta was suspected based on a CT examination, and resection was judged to be impossible. Since the tumor was associated with impaired patency, after first inserting a metallic stent, the patient was treated with 4 cycles of S-1 100 mg/body for 2 weeks and paclitaxel (PTX) 120 mg/body by intravenous drip infusion on days 1 and 15 for 2 weeks followed by a 2-week rest period. The tumor regressed considerably, and total gastrectomy and lower esophagectomy with D1+ a lymph node resection through a left thoracolaparotomy became possible. A bypass operation or palliative resection is sometimes performed when complicated by impaired patency. In our patient, after achieving an improvement in QOL by stenting, resection became possible as a result of a response to chemotherapy with S-1. However, when considering resection after chemotherapy it seemed necessary to be careful to insert the stent as close as possible to the proximal margin of the tumor so as not to broaden the extent of the esophageal resection.

Topics: Adenocarcinoma; Antimetabolites, Antineoplastic; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Cardia; Combined Modality Therapy; Drug Combinations; Esophageal Neoplasms; Esophagectomy; Esophagus; Gastrectomy; Humans; Male; Middle Aged; Neoplasm Invasiveness; Oxonic Acid; Paclitaxel; Stents; Stomach Neoplasms; Tegafur

The patient was a 72-year-old male diagnosed with type III poorly-differentiated adenocarcinoma in the lesser curvature by gastric fiberscopy. An abdominal computed tomography (CT) scan showed the thickness of the gastric wall and the enlarged lymph node around the stomach and laparoscopic examination revealed peritoneal dissemination. The patient received neoadjuvant combined chemotherapy with S-1 and CDDP. S-1 (100 mg/day) was orally administered for 3 weeks followed by 2 drug-free weeks as a course, and CDDP (100 mg/body) was administered by intravenous drip on day 8. After the third course, significant tumor reduction was obtained. Total gastrectomy, splenectomy and D2 nodal dissection were performed. Peritoneal dissemination disappeared, and the histological diagnosis revealed complete disappearance of cancer cells in the ascites and no metastasis in all lymph nodes. The patient has now been in good health with no recurrence for 22 months after surgery. The combined neoadjuvant chemotherapy with S-1 and CDDP can be an effective treatment of choice for advanced gastric carcinoma with peritoneal dissemination.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Administration Schedule; Drug Combinations; Gastrectomy; Humans; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Oxonic Acid; Peritoneal Neoplasms; Remission Induction; Stomach Neoplasms; Tegafur

We report a recurrent case of gastric cancer with para-aortic lymph node metastasis that showed a marked response to systemic chemotherapy consisting of S-1 alone. A 70-year-old male was admitted to our hospital with appetite loss and left abdominal pain. He had a history of distal gastrectomy due to the advanced gastric cancer. Endoscopy revealed a submucosal tumor-like elevation with central ulcer, and the biopsy specimen was poorly-differentiated adenocarcinoma histologically. CT of the abdomen demonstrated a para-aortic lymph node swelling behind the remnant stomach, indicating an unresectable recurrent gastric cancer. We initially treated the patient with S-1 chemotherapy (60 mgx2/day) by oral administration. His tumor immediately responded to the chemotherapy, and restaging abdominal CT after 2 cycles of chemotherapy showed almost complete regression of lymph node metastasis. The patient has undergone S-1 chemotherapy and currently has remained in remission for more than 21 months with no severe adverse events. The S-1 regime was effective and safe, suggesting that S-1 could be the first-line chemotherapy for recurrent gastric cancer.

Topics: Adenocarcinoma; Aged; Antimetabolites, Antineoplastic; Aorta; Drug Administration Schedule; Drug Combinations; Gastrectomy; Gastric Stump; Humans; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Male; Oxonic Acid; Remission Induction; Stomach Neoplasms; Tegafur

A 68-year-old man was admitted to another hospital because of progressive weight decrease and appetite loss. Endoscopic examination revealed type 4 advanced gastric cancer at the upper body of the stomach. In February, 2003, he patient had probe laparotomy because there was a small amount of ascites in his peritoneal cavity, and intraoperative washing cytology revealed cancer cells in ascites.Subsequently, we started chemotherapy using S-1 and CPT-11. S-1 at a dose of 100 mg/day was orally administered for 2 weeks, and CPT-11 at a dose of 90 mg/body was intravenously administered once a week for 2 weeks followed by a 2-week drug-free period as 1 course. After 7 courses of the chemotherapy, the main lesion endoscopically vanished.Subsequently, the patient underwent curative total gastrectomy together with D2 lymph node dissection. Intraoperative cytology revealed no cancer cells, and histological examination of the primary lesion showed cancer cells invading the subserosa with no metastasis to any dissected lymph nodes. This therapy induced Grade 2 effect on cancer cells.Postoperatively, only S-1 was administered to the patient, who has remained alive with no recurrence for 4 years as of January, 2007.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Ascitic Fluid; Camptothecin; Drug Administration Schedule; Drug Combinations; Gastrectomy; Humans; Irinotecan; Lymph Node Excision; Male; Neoplasm Staging; Oxonic Acid; Remission Induction; Stomach Neoplasms; Tegafur

We describe two patients, who suffered from Stage IV gastric poorly differentiated adenocarcinoma and underwent palliative total gastrectomy, were treated by sequential chemotherapy and achieved long term-survival. The first patient was a 55-year-old male with peritoneal dissemination. After total gastrectomy, he was treated with methotrexate-5-fluorouracil (MTX/5-FU) sequential therapy for 5 months, S-1 single-agent therapy for 4 years and weekly paclitaxel (PTX) therapy for 9 months. He is being treated with irinotecan (CPT-11) therapy as an outpatient now, and has achieved 5 year 8-month survival. The second patient was a 60-year-old female. We observed unresectable metastases around the pancreas, aorta, and transverse mesocolon. She was treated with S-1 single-agent therapy for 1 year 10 months, MTX/5-FU sequential therapy for 9 months. She is now receiving weekly PTX therapy for 3 months as an outpatient and has achieved 2 year 11-month survival.

Topics: Adenocarcinoma; Antimetabolites, Antineoplastic; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Combined Modality Therapy; Drug Combinations; Female; Fluorouracil; Gastrectomy; Humans; Immunosuppressive Agents; Irinotecan; Male; Methotrexate; Middle Aged; Oxonic Acid; Paclitaxel; Stomach Neoplasms; Tegafur

We report a patient with type 3 gastric cancer with peritoneal dissemination and hydronephrosis who was successfully treated with intraperitoneal infusion of paclitaxel and oral administration of S-1. He was diagnosed with unresectable gastric cancer with severe peritoneal dissemination by staging laparoscopy. We selected combined chemotherapy with both paclitaxel and S-1. Paclitaxel at 60 mg/m(2) was administered intraperitoneally on days 1 and 8, and S-1 at 100 mg/body was administered orally for 14 days, followed by 7 days' rest, as one course. After five courses, primary tumor reduction was confirmed and no cancer cells were detected on pathocytological investigation at second-look laparoscopy. The patient underwent total gastrectomy with lymph node dissection. He died from liver metastasis 29 months after the initial treatment, but he had not suffered from peritoneal metastases and had kept a good quality of life (QOL) since that treatment. This chemotherapy can be applied as one of the promising candidates for the treatment of patients with peritoneal metastasis of gastric cancer.

Topics: Adenocarcinoma; Administration, Oral; Adult; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Humans; Hydronephrosis; Infusions, Parenteral; Liver Neoplasms; Male; Oxonic Acid; Paclitaxel; Peritoneal Neoplasms; Stomach Neoplasms; Tegafur

We report the case of 67-year-old man who was given a diagnosis of advanced gastric adenocarcinoma. Complete response of multiple liver and paraaortic lymph node metastases occurred in this patient after combination chemotherapy with systemic injection of paclitaxel and oral administration of novel dihydropyrimidine- dehydrogenase- inhibitory fluoropyrimidine (S-1). Following 7 courses of the biweekly paclitaxel and S-1 combination chemotherapy, the patient underwent total gastrectomy with D3 extended lymph node dissection. According to the operative findings, the tumor was curatively removed along with the liver metastases and paraaortic lymph node metastases. Biopsy of the liver was performed and the pathological diagnosis indicated no gastric adenocarcinoma cells. The pathological report showed that the lymph node metastases had completely disappeared with single exception and minute cancerous lesions were identified in the gastric mucosa and submucosa. Therefore, the histological efficacy was evaluated as Grade 2. For postoperative chemotherapy, oral S-1 administration only was chosen. However, 6 months later, biweekly paclitaxel and S-1 combination chemotherapy was administered in sequence as a second adjuvant chemotherapy because the serum level of the tumor marker was elevated. The patient is fine and has not shown any recurrence at other sites 37 months after surgery. Salvage surgery following paclitaxel and S-1 chemotherapy may be feasible for patients with advanced gastric cancer and complete regression of distant metastases. Biweekly paclitaxel and S-1 combination chemotherapy has been used safely and its administration may be continued for a long time in an outpatient clinic setting for the treatment of advanced gastric cancer.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Aorta; Drug Combinations; Endoscopy, Gastrointestinal; Humans; Liver Neoplasms; Lymphatic Metastasis; Male; Oxonic Acid; Paclitaxel; Remission Induction; Salvage Therapy; Stomach Neoplasms; Tegafur; Tomography, X-Ray Computed

A 66-year-old woman (156 cm, 58 kg) underwent sigmoid colectomy for cancer. She was found to have simultaneous liver and peritoneal metastases at operation, which had not been detected with CT examination before operation. After operation, CT showed multiple liver metastasis and a high level of CEA and CA19-9 . Pathological findings were type 3, 30 x 20 mm, poorly-differentiated adenocarcinoma, se, ly 2, v 2, n 2 (+), ow (-), aw(-), H 3, P 0 (stage IV). Treatment of the patient consisted of daily oral administration of 80 mg TS-1 for 21 days and 60 mg CPT-11 on 1 day and 15 day as one course. After 2 courses, tumor sizes of liver metastases and the level of tumor markers became reduced. The current case suggested that the administration of TS-1 and CPT-11 may have a potent therapeutic efficacy in advanced colorectal cancer.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Drug Administration Schedule; Drug Combinations; Female; Humans; Irinotecan; Liver Neoplasms; Lung Neoplasms; Oxonic Acid; Pyridines; Sigmoid Neoplasms; Tegafur; Tomography, X-Ray Computed

A 64-year-old man with unresectable sigmoid adenocarcinoma due to peritoneal dissemination (P3) and liver metastasis (H2) treated with TS-1, showed a complete response. TS-1 is an oral anticancer drug that produces biochemical modulation. It is composed of tegafur, gimestat and ostat potassium in a molar ratio of 1:0.4:1 to increase the effect of 5-FU and to decrease toxicity in the digestive canal. Treatment with TS-1 requires no hospitalization and can enhance the quality of life of the patient. TS-1 is expected to be an effective agent for the treatment of colon cancer with liver metastasis and peritoneal dissemination.

Topics: Adenocarcinoma; Antimetabolites, Antineoplastic; Biomarkers, Tumor; CA-19-9 Antigen; Carcinoembryonic Antigen; Drug Administration Schedule; Drug Combinations; Humans; Liver Neoplasms; Male; Middle Aged; Oxonic Acid; Peritoneal Neoplasms; Pyridines; Remission Induction; Sigmoid Neoplasms; Tegafur

We report a case of gastric cancer with peritoneal recurrence that responded to chemotherapy with paclitaxel and TS-1. A 62-year-old woman, who underwent total gastrectomy for advanced gastric cancer 2 years and 6 months ago, was admitted to our hospital with a chief complaint of abdominal distention and intestinal obstruction due to a large amount of ascites. Cytology of ascites revealed peritoneal dissemination, and chemotherapy with bi-weekly paclitaxel (90 mg/body) was begun. Clinical symptoms, including ascites and intestinal obstruction, were improved only after the second administration of paclitaxel. As she was able to take food orally, she was placed on combined chemotherapy consisting of tri-weekly paclitaxel (9 0 mg/body-120 mg/body: day 1) and TS-1 (80 mg/day: day 1-14) and 1 or 2 weeks rest. The patient had no signs or symptoms of peritoneal metastasis or toxicity except for general fatigue and watery eyes 1 year and 8 months after the diagnosis of peritoneal metastasis. Paclitaxel and TS-1 therapy was thought to be an effective chemotherapy against recurrent gastric cancer with peritoneal dissemination.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Drug Administration Schedule; Drug Combinations; Female; Humans; Middle Aged; Oxonic Acid; Paclitaxel; Peritoneal Neoplasms; Pyridines; Quality of Life; Stomach Neoplasms; Tegafur

A 74-year-old man was revealed to have type 3 gastric cancer with synchronous multiple liver metastases. Despite treatment with TS-1 (120 mg/body), an increase in tumor size was demonstrated by computer tomography and endoscopy. We tried a course of a combination chemotherapy consisting of paclitaxel (PTX) plus doxifluridine (5'-DFUR ) to reduce the tumor. 5'-DFUR (600 mg/m(2)) was administered day 1 to 14 followed by 7 days'rest as one course. PTX (80 mg/m(2)) was infused on days 1 and 8. After 5 courses, the tumor markers decreased markedly, and computer tomography and endoscopy revealed remarkable tumor reduction which was thought to show a partial response. After 13 courses we discontinued this chemotherapy, so increase of the tumor marker was remarkable. This case suggests that PTX/5'-DFUR protocol is effective for clinical management of gastric cancer resistant to TS-1.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Drug Administration Schedule; Drug Combinations; Drug Resistance, Neoplasm; Floxuridine; Humans; Irinotecan; Liver Neoplasms; Male; Oxonic Acid; Paclitaxel; Pyridines; Stomach Neoplasms; Tegafur

The patient was a 68-year-old woman who had cecal cancer with para-aortic lymph node metastases. Ileocecal resection was performed palliatively. Since metastasis to cervical vertebrae was detected after the operation, she received radiation therapy of 14 Gy to improve neck pain. Chemotherapy with TS-1 (80 mg/day) was started on an outpatient basis (4 weeks administration followed by a 2-week drug-free period). After 4 courses of this chemotherapy, metastases to both para-aortic lymph nodes and cervical vertebrae were remarkably reduced on CT and PET. Throughout the period of treatment, there was no adverse effect and this treatment has been maintained. In conclusion, this case seems significant from the viewpoint of achieving a partial response to TS-1 and maintaining a high quality of life. Moreover,we identified the presence of TS and DPD using an immunohistochemical staining technique. The primary tumor was positive for DPD stain test and negative for TS stain test. It was suggested that this cancer especially would respond to TS-1 chemotherapy.

Topics: Adenocarcinoma; Aged; Antimetabolites, Antineoplastic; Aorta; Cecal Neoplasms; Cervical Vertebrae; Chemotherapy, Adjuvant; Colonic Neoplasms; Combined Modality Therapy; Drug Administration Schedule; Drug Combinations; Female; Humans; Lymph Nodes; Lymphatic Metastasis; Oxonic Acid; Pyridines; Remission Induction; Spinal Neoplasms; Tegafur

The patient was a 66-year-old man who had undergone right upper lobectomy and ND 2a systematic lymph node dissection for lung cancer (M/D adenocarcinoma, p-stage IB) in March of 1999 . On November 2003, postoperative routine chest computed tomography(CT) demonstrated a mass in left S6, and pathological diagnosis revealed P/D squamous cell carcinoma (cT1N2M0, stage IIIA) by CT-guided needle biopsy and mediastinoscopy. At first, we tried two courses of a combination chemotherapy consisting of carboplatin (CBDCA) and paclitaxel every 3 weeks. After 2 courses, the regimen was stopped because of grade 3 arthritis. Then, two courses of CBDCA and gemcitabine were performed. The evaluation of the response was SD by the guidelines of Response Evaluation Criteria in Solid Tumor Groups. Next, gefitinib was orally administered for 6 months but the tumor and mediastinal lymph nodes were growing. In January 2005, oral administration of TS-1 (60 mg/1, 2 courses, 75 mg/3-6 courses) was begun twice a day for 21 consecutive days while cisplatin (60 mg/m(2)) was administered intravenously on day 8. The response was PR (the tumor decreased by 46%), no serious adverse effect was observed, and the patient maintained good quality of life throughout the chemotherapy. This case suggests that TS-1+CDDP chemotherapy may be an effective treatment in patients with advanced lung cancer even after many protocols of chemotherapy.

Topics: Adenocarcinoma; Administration, Oral; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Combined Modality Therapy; Drug Administration Schedule; Drug Combinations; Humans; Lung Neoplasms; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Male; Neoplasm Staging; Neoplasms, Second Primary; Oxonic Acid; Pneumonectomy; Pyridines; Tegafur

A 71-year-old woman was admitted for anorexia. Endoscopic findings revealed type 3 gastric cancer. Histological examination of the endoscopic biopsy revealed poorly-differentiated adenocarcinoma. We performed total gastrectomy. However, 18 days after surgery, DIC due to multiple bone metastases occurred. The patient was treated with TS-1 chemotherapy in addition to anti-DIC therapy. TS-1(100 mg/day) was administered on days 1 to 5, 8 to 12, and 15 to 19 . The DIC was resolved. She was discharged after 2 courses of this regimen. This chemotherapy can be applied for the management of DIC caused by multiple bone metastases.

Topics: Adenocarcinoma; Aged; Antimetabolites, Antineoplastic; Bone Neoplasms; Combined Modality Therapy; Disseminated Intravascular Coagulation; Drug Administration Schedule; Drug Combinations; Female; Gastrectomy; Humans; Oxonic Acid; Pyridines; Stomach Neoplasms; Tegafur

A resected case of gastric cancer is described. The patient was a 60-year-old woman who presented a type 3 gastric tumor complicated by invasion of the head of the pancreas and liver. Radical resection was not indicated, and we administered the following combination chemotherapy with TS-1 and CDDP. 120 mg/day of TS-1 was orally administered for 3 weeks followed by 2 drug-free weeks as 1 course and 9 5 mg (60 mg/m(2)) of CDDP was administered intravenously on day 8. After two courses, total gastrectomy and D2 lymph node dissection were performed. Radical surgery for cure was conducted. Microscopically, the histological effect was judged to be grade 1a. One year after the operation, the patient is still alive without recurrence and metastasis. TS-1/CDDP therapy is useful for advanced gastric cancer.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Administration Schedule; Drug Combinations; Female; Gastrectomy; Humans; Lymph Node Excision; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Oxonic Acid; Pyridines; Stomach Neoplasms; Tegafur

A 54-year-old woman with advanced gastric cancer was referred to our hospital. Because it was the yearend, we selected neoadjuvant TS-1 combined with CDDP therapy. TS-1 (60 mg bid) was administered orally for 21 consecutive days, and CDDP (60 mg/m(2)) was infused intravenously on day 8. One course was completed without serious toxicities. The primary tumor revealed partial response (PR) with no lymph node metastasis judged from barium meal study and upper GI endoscopic findings. After 3 weeks, a simple total gastrectomy with lymph node dissection was performed. The pathological diagnosis proved that there were no cancer cells in the primary lesion or regional lymph nodes, suggesting a complete response (CR) to chemotherapy. The postoperative course was uneventful, and she has been fine as an outpatient.

Topics: Adenocarcinoma; Administration, Oral; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Administration Schedule; Drug Combinations; Female; Gastrectomy; Humans; Infusions, Intravenous; Middle Aged; Neoadjuvant Therapy; Oxonic Acid; Pyridines; Remission Induction; Stomach Neoplasms; Tegafur

We report a case of recurrent advanced urachal carcinoma with right internal iliac node and left lung metastases in a 34-year-old man. After receiving partial cystectomy including en bloc resection of the urachus and with bilateral pelvic lymph node dissection, he was treated with five courses of S-1 and cisplatin combination chemotherapy. He remains free from the disease after a 30-month follow-up period. S-1/cisplatin combination chemotherapy is suggested to be a potent tool for controlling advanced urachal carcinoma.

Topics: Adenocarcinoma; Adult; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Hematuria; Humans; Iliac Artery; Lung Neoplasms; Lymph Node Excision; Lymphatic Metastasis; Male; Oxonic Acid; Tegafur; Urachus; Urinary Bladder Neoplasms

In cases with advanced/recurrent gastric cancer undergoing single therapy with TS-1, we retrospectively discussed the antitumor effects and adverse events and considered the clinical utility of TS-1. The subjects consisted of 131 cases with advanced/recurrent gastric cancer who received one or more courses of therapy with TS-1 alone between July 1999 and August 2003. We carried out 4-week administration of 80-120 mg/day of TS-1 according to body surface area, followed by a 2-week discontinuation, then repeated administration which adjusting the dosage according to the incidence of side effects, and discussed the antitumor effects and adverse events. The response rate in all cases was 21% and the median survival time (MST) was 343 days, or 25.3% and 265 days if limited to unresectable and recurrent cases. The response rates were 38.2% for unresectable cases, 16.3% for recurrent cases and 14.6% for curability C cases, and the MSTs were 250 days, 276 days and 419 days, respectively. The response rates in terms of whether or not patients had received chemotherapy were 11.6% for those who had received chemotherapy and 40.0% for those who had not, and the MSTs were 239 days and 325 days, respectively. Thus, both were significantly better in patients who had not received chemotherapy. The response rates for patients who had not received chemical therapy by target organs were favorable on the order of 50% for stomach and 33% for liver metastasis, and the MSTs were on the order of 474 days for peritoneum, 39 1 days for liver metastasis and 326 days for lymph nodes. There were 10 cases of long-term survival of 600 days or longer, but not in unresectable cases, and the target organs in many of the cases were the peritoneum and lymph nodes. Adverse reactions were observed in 34.4% of all cases and those of grade 3 or more in 9.4%, all of which were improved only by discontinuation of the drug. It was again confirmed that single therapy with TS-1 for advanced/recurrent gastric cancer is an excellent therapy providing both high antitumor effects and safety.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Drug Administration Schedule; Drug Combinations; Humans; Liver Neoplasms; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Recurrence, Local; Oxonic Acid; Retrospective Studies; Stomach Neoplasms; Survival Rate; Tegafur

A 65-year-old male showed elevated tumor marker and intra-abdominal lymph node (LN) swelling. PET revealed an accumulation of FDG at para-aortic LNs from the mediastinum to the inguinal region. Although many different examinations were performed to detect primary cancer, none was found. We diagnosed unknown primary cancer (UPC), and administered TS-1 (100 mg/day). Six months later, the tumor marker lowered and the LN swelling reduced. PET showed a little accumulation of FDG at intra-abdominal LN. An intra-abdominal LN biopsy was performed, and an adenocarcinoma was seen at a lymph vessel. Then, 15 months later, brain metastasis was recognized and 18 months later the patient died of systematic metastasis. Autopsy was not performed, and primary cancer was not seen till the end. TS-1 proved effective for the UPC.

Topics: Adenocarcinoma; Aged; Antimetabolites, Antineoplastic; Drug Administration Schedule; Drug Combinations; Fatal Outcome; Humans; Lymph Nodes; Lymphatic Metastasis; Male; Mediastinum; Neoplasms, Unknown Primary; Oxonic Acid; Tegafur

We treated a patient with multiple liver metastases arising from colon cancer in whom the metastatic tumors were responsive to treatment with the combination of TS-1 and CPT-11. The patient was a 71-year-old woman with cancer of the ascending colon and metastatic hepatic tumors. She had undergone surgery on July 28, 2004, and abdominal contrast CT scans obtained after discharge from hospital revealed numerous LDA (low-density areas) in both lobes of the liver. The patient was given ambulatory chemotherapy with TS-1 (120 mg/day on days 1-14) and CPT-11 (100 mg/day on days 1 and 8). After completion of 2 courses of chemotherapy, abdominal contrast CT scans revealed that most of the LDAs in both lobes of the liver had disappeared, and the patient was judged to have achieved PR. No adverse reactions were observed except for a slight decrease of WBC, and her chemotherapy is being continued at present. This case suggests that the combination of TS-1 and CPT-11 may be an effective form of chemotherapy for the treatment of colon cancer with multiple hepatic metastases.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colonic Neoplasms; Drug Administration Schedule; Drug Combinations; Female; Humans; Irinotecan; Liver Neoplasms; Oxonic Acid; Remission Induction; Tegafur

The case was a 54-year-old man with type-3 gastric cancer in the cardia accompanied by multiple liver metastasis. He received combination chemotherapy consisting of CPT-11 (60 mg/body, day 1 and 8)+low-dose 5-FU and CDDP (5-FU 500 mg/body/day and CDDP 5 mg/body/day, day 1-5 and 8-12, continuous infusion) every 3 weeks. The initial 2 courses were administered on an inpatient basis,and further courses as an outpatient. After 7 courses of therapy without severe adverse events, not only primary lesion but also hepatic metastasis disappeared. He has been free from disease for 4 months, and chemotherapy was further continued with TS-1 (100 mg/body, day 1-14)+CPT-11 60 mg/body, day 1, 8), every 3 weeks. CPT-11 in combination with low-dose 5-FU+CDDP can be one of the most effective regimens for unresectable advanced gastric cancer.

Topics: Adenocarcinoma; Ambulatory Care; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cardia; Cisplatin; Drug Administration Schedule; Drug Combinations; Fluorouracil; Humans; Irinotecan; Liver Neoplasms; Male; Middle Aged; Oxonic Acid; Remission Induction; Stomach Neoplasms; Tegafur

We report a case of N 3 gastric cancer successfully treated by TS-1 followed by curative resection. The patient was a 64-year-old male. Gastrointestinal endoscopic examination showed advanced gastric cancer. Examination by computed tomography revealed gastric cancer and swollen para-aortic lymph nodes. This patient was treated by neoadjuvant chemotherapy with oral administration of TS-1 (120 mg/day, day 1-28 with 2 weeks rest). After 3 courses of TS-1, the primary lesion and swollen lymph nodes were remarkably reduced. This chemotherapy enabled pancreatoduodenectomy with D 3 lymph node dissection in curative resection. The pathological diagnosis was por, pT 2, pMP and pap, pT 1, pSM 2, pPM(-), pDM(-), pN 1, pStage II and curability A. This neoadjuvant chemotherapy regimen seems to be an effective and promising therapy for patients with advanced gastric cancer.

Topics: Adenocarcinoma; Administration, Oral; Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Combined Modality Therapy; Drug Administration Schedule; Drug Combinations; Gastrectomy; Humans; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Pancreaticoduodenectomy; Stomach Neoplasms; Tegafur

A 63-year-old woman was referred to our hospital with complaints of anal pain, constipation and abdominal distention caused by a rectal tumor. After examinations, she was diagnosed as rectal cancer with multiple liver metastases. The CEA level was 70.0 ng/ml and the CA19-9 level was more than 5,000 U/ml at admission. To prevent bowel obstruction, low anterior resection of the rectum was performed. At 34 days after operation, TS-1 chemotherapy was started as outpatient treatment (each course consisted of daily oral administration of 100 mg TS-1 for 4 weeks followed by 2 drug-free weeks). After the first course, the CEA level was reduced to 3.3 ng/ml and the CA19-9 level to 15 U/ml, both under the normal value. After the second course, administration was discontinued due to diarrhea, and restarted as a daily oral administration of 80 mg TS-1. After the five courses, the CEA level was 4.0 ng/ml and the CA19-9 level was 4 U/ml, both under the normal value. Multiple liver metastases had remarkably reduced in the CT findings. The patient continues to undergo outpatient treatment with good QOL.

Topics: Adenocarcinoma; Ambulatory Care; Antimetabolites, Antineoplastic; Biomarkers, Tumor; CA-19-9 Antigen; Carcinoembryonic Antigen; Drug Administration Schedule; Drug Combinations; Female; Humans; Liver Neoplasms; Middle Aged; Oxonic Acid; Rectal Neoplasms; Tegafur

The patient was a 66-year-old male who had descending colon cancer with multiple liver metastases and paraaortic lymph node metastases. He underwent a left colectomy with lymph node dissection, but the operation resulted in curability C. The serum CEA level before the operation was 205.5 ng/ml. After 2 courses of 5-FU/LV as first-line chemotherapy, this treatment could not be continued due to grade 3 anorexia. As second-line chemotherapy, the patient was treated with daily oral administration of TS-1 (100 mg/day) for 3 weeks. Due to grade 3 anorexia, this treatment could not be continued. Tailored TS-1/CPT-11 (TS-1 80 mg/day from day 1 to day 21, CPT-11 65 mg/m(2) day 1, 15) combination therapy was then chosen as third-line chemotherapy. After 6 courses of combination therapy, the tumor marker (CEA) was decreased and para-aortic lymph nodes could not be detected by computed tomography (CT). Only grade 1 fatigue was noted as an adverse reaction to the treatment. The patient's good QOL was achieved during follow-up over 24 months with the cancer controlled. This case suggests that patients with non-curative resected colon cancer could benefit from TS-1/CPT-11 combination therapy as a second-line or third-line treatment.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Carcinoembryonic Antigen; Colectomy; Colonic Neoplasms; Drug Administration Schedule; Drug Combinations; Humans; Irinotecan; Liver Neoplasms; Lymph Nodes; Lymphatic Metastasis; Male; Oxonic Acid; Tegafur

A 75-year-old man was admitted to our hospital with hematoemesis. Gastrofiber-scopy revealed that type 3 gastric cancer was widespread in the lesser curvature. Multiple liver metastases 5 cm in diameter were shown on CT. We thought that the case was unresectable, and TS-1/CDDP chemotherapy was performed. TS-1 (80 mg/body/day) was orally administered and CDDP at 20 mg/body/day by intravenous drip infusion a week for 3 weeks followed by a drug-free 2 week period as the first course. After the third course, the primary lesion and the liver metastasis showed a partial response in terms of size. No serious drug adverse reaction was observed. Since there was no longer any reduction of the tumor, gastrectomy and coagulation therapy for liver metastasis were performed, and he has been alive for 15 months without recurrence. Combined use of TS-1 and CDDP is effective as neoadjuvant chemotherapy for advanced gastric cancer.

Topics: Adenocarcinoma; Administration, Oral; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cisplatin; Combined Modality Therapy; Drug Administration Schedule; Drug Combinations; Gastrectomy; Humans; Infusions, Intravenous; Liver Neoplasms; Male; Oxonic Acid; Remission Induction; Stomach Neoplasms; Tegafur

In two patients with advanced pancreatic cancer with cervical lymph node or liver metastasis and no indication of pancreatic resection and radiotherapy, oral treatment with S-1 (an anti-cancer agent of fluoropyrimidine derivative) exerted high anti-tumor activity on the metastatic lesions. Both cases responded well to this therapy in the late phase II study of S-1 in patients with advanced pancreatic cancer designed to evaluate efficacy and safety. In Case 1 (with cervical lymph node metastasis), the anti-tumor efficacy of this therapy was evaluated as a partial response (PR) after the first four courses of treatment. In Case 2 (with liver metastasis), the efficacy was evaluated as PR for overall response. Thus, the therapy indicated excellent efficacy in both cases. No grade 3 or severe adverse event was noted in either of the two cases. In Case 1, grade 2 anemia, stomatitis, vomiting and fatigue, and some other mild events were noted. When used as a systemic chemotherapy for metastatic pancreatic cancer, oral treatment of S-1 is highly effective, tolerable and convenient in an outpatient clinic. This drug is a promising way to improve and preserve the QOL essential to long-term home care.

Topics: Adenocarcinoma; Administration, Oral; Aged; Anemia; Antimetabolites, Antineoplastic; Drug Administration Schedule; Drug Combinations; Female; Humans; Liver Neoplasms; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neck; Oxonic Acid; Pancreatic Neoplasms; Quality of Life; Stomatitis; Tegafur; Vomiting, Anticipatory

We report a case in a late phase II clinical study investigating the efficacy and safety of the oral fluoropyrimidine anticancer drug S-1. The drug proved effective in a patient with inoperable advanced pancreatic cancer in whom radiation therapy was not indicated. The antitumor effect after 4 courses was rated excellent, with a target site (liver) evaluation of CR and overall evaluation of PR. In particular, two liver metastases, measuring 18.7 x 15.4 mm and 16.2 x 14.6 mm, respectively, both resolved, and S-1 was found to exert a potent antitumor effect against metastases. Assessment of adverse events revealed no grade 3 or 4 adverse reactions, and other adverse events were all mild. Based on the above results, S-1 appeared to be effective against advanced pancreatic cancer and showed excellent tolerability.

Topics: Adenocarcinoma; Antimetabolites, Antineoplastic; Clinical Trials, Phase II as Topic; Drug Administration Schedule; Drug Combinations; Humans; Liver Neoplasms; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Pancreatic Neoplasms; Remission Induction; Tegafur

We report two metastatic pancreatic cancer patients who showed marked tumor shrinkage following administration of the oral fluorinated pyrimidine anticancer drug, S-1. In the early phase II trial of S-1 for metastatic pancreatic cancer, both patients showed a partial response (Japan Society for Cancer Therapy Criteria): the reduction ratio of the tumor volume was 81.4% in the patient with liver metastasis (Case 1) and 86.9% in the patient with lung metastasis (Case 2). Case 1 showed grade 3 anorexia and decrease of the serum hemoglobin as severe adverse effects, but the other adverse reactions were mild. Both patients could be treated as outpatients. S-1 showed a promising antitumor effect and tolerability in patients with metastatic pancreatic cancer, and it was also considered to be beneficial for patients in terms of convenience of administration, that is, by the oral route.

Topics: Adenocarcinoma; Aged; Anorexia; Antimetabolites, Antineoplastic; Clinical Trials, Phase II as Topic; Drug Administration Schedule; Drug Combinations; Female; Hemoglobins; Humans; Liver Neoplasms; Lung Neoplasms; Middle Aged; Oxonic Acid; Pancreatic Neoplasms; Tegafur

We report a patient with chemotherapy-naïve advanced pancreatic cancer having multiple liver metastases which dramatically responded to S-1, an oral fluoropyrimidine. The patient was enrolled in the "Late Phase II Clinical Study of S-1 in Patients with Advanced Pancreatic Cancer." Anti-tumor efficacy after the first four courses of S-1 monotherapy was confirmed to be partial response (PR) in overall response by Response Evaluation Criteria in Solid Tumors (RECIST). Grade 3 neutropenia was observed, but no other severe toxicities were noted. On the basis of the results of the late phase II clinical study, S-1 is a promising agent for systemic chemotherapy against advanced pancreatic cancers because of its excellent efficacy, high tolerability, and convenient route of oral administration.

Topics: Adenocarcinoma; Antimetabolites, Antineoplastic; Clinical Trials, Phase II as Topic; Deoxycytidine; Drug Administration Schedule; Drug Combinations; Female; Gemcitabine; Humans; Liver Neoplasms; Middle Aged; Neutropenia; Oxonic Acid; Pancreatic Neoplasms; Tegafur; Tomography, X-Ray Computed

A sixty-two-year-old female presented with non-small-cell lung carcinoma with multiple bone metastasis. Combination chemotherapy with CBDCA and GEM was implemented, but as no effect was obtained, TS-1 was begun with a single course of oral administration of 100 mg/day continuously for 28 days followed by a 14-day rest. Following the start of TS-1, PR of the primary tumor was obtained, and whole-body bone scintigraphy revealed a reduction in abnormal areas of uptake. The woman continues to receive TS-1 orally as an outpatient.

Topics: Adenocarcinoma; Antimetabolites, Antineoplastic; Combined Modality Therapy; Drug Administration Schedule; Drug Combinations; Female; Humans; Lung Neoplasms; Middle Aged; Oxonic Acid; Quality of Life; Tegafur

A 49-year-old man was admitted to our hospital with vomiting. Abdominal CT revealed an avascular tumor at the uncinate process of the pancreas measuring 36x30 mm. Preoperative serum CA 19-9 was 361 U/ml. During laparotomy,the tumor was deemed unresectable (T4NXM0, Stage IVa),and duodenojejunostomy was performed. External-beam radiotherapy (EBRT) (50.4 Gy/28Fr) with concurrent twice-weekly gemcitabine (GEM) (40 mg/m(2)/day) was delivered. In the outpatient setting, and 1,000 mg/m(2) of GEM was administered intravenously on days 1, 8, and 15. Cycles were repeated every 28 days. The patient received 13 cycles of GEM chemotherapy until the appearance of a grade 2 facial rash. A decrease in tumor size was observed, and the serum CA 19-9 level dropped to 16 U/ml. He remained well without any symptoms and pursued normal activity for 33 months. He died of peritoneal dissemination 43 months after diagnosis. Gemcitabine-based chemo-radiation seems to be a safe and effective regimen for unresectable pancreatic cancer.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Deoxycytidine; Drug Administration Schedule; Drug Combinations; Gemcitabine; Humans; Male; Middle Aged; Oxonic Acid; Pancreatic Neoplasms; Quality of Life; Radiotherapy Dosage; Survivors; Tegafur; Uracil

The incidence of venous thromboembolism in cancer patients is reportedly around 15%, and a pulmonary embolism is an important cause of morbidity and mortality. We present a case of duodenal carcinoma with peritoneal carcinomatosis complicated by a pulmonary embolism. Heparin, followed by warfarin, was useful to treat the embolism. The combination chemotherapy with TS-1 and docetaxel was effective for the peritoneal carcinomatosis. The QOL of this patient was maintained for about 5 months.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Docetaxel; Drug Combinations; Drug Therapy, Combination; Duodenal Neoplasms; Female; Heparin; Humans; Middle Aged; Oxonic Acid; Peritoneal Neoplasms; Pulmonary Embolism; Quality of Life; Taxoids; Tegafur; Warfarin

A 57-year-old woman visited a physician with complaints of anorexia and pollakiuria. Because a pelvic tumor and ascites were detected, she was referred to our department. Douglas pouch puncture revealed adenocarcinoma cells. Further examination showed an advanced gastric cancer with peritoneal dissemination. The cancer was judged to be unresectable. Chemotherapy with a combination of TS-1 and CDDP was performed before the operation. After 2 courses of the chemotherapy, her complaints disappeared, although abdominal CT confirmed remaining peritoneal dissemination. After 7 courses of chemotherapy, abdominal CT showed that the peritoneal dissemination had disappeared. Total gastrectomy and lymph node dissection were performed. Histological findings of the stomach revealed complete disappearance of cancer cells in the stomach and the regional lymph nodes. We confirmed that the TS-1/CDDP therapy resulted in a complete response to advanced gastric cancer and peritoneal dissemination. We recommend that chemotherapy be continued until the peritoneal dissemination disappears.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Administration Schedule; Drug Combinations; Female; Humans; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Middle Aged; Neoadjuvant Therapy; Oxonic Acid; Peritoneal Neoplasms; Remission Induction; Stomach Neoplasms; Tegafur

A 78-year-old man was admitted to our hospital complaining of dysphagea on April 8, 2005. Upper gastrointestinal endoscopic examination showed type 2 esophageal cancer in the lower thoracic area and type 3 gastric cancer in the upper body. Computed tomography showed No. 3 lymph node swelling, but no distant metastasis. Surgery was contraindicated because of many complications, so the patient was given combined chemotherapy with TS-1 and low-dose cisplatin. Chemotherapy was started on April 18. After 2 courses of chemotherapy the esophageal lesion showed a complete response, and after 5 courses the gastric lesion evidenced a complete response.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Esophageal Neoplasms; Humans; Male; Neoplasms, Multiple Primary; Oxonic Acid; Remission Induction; Stomach Neoplasms; Tegafur

In this study, we demonstrated that chemoimmunotherapy using S-1, a novel oral fluoropyrimidine anticancer drug, combined with lentinan (LNT), a beta (1 --> 3) glucan, was effective in vivo, and we clarified the augmentation of the function of dendritic cells (DCs) in vivo and in vitro. The survival period of Colon-26-bearing mice treated with S-1 + LNT was significantly more prolonged than that of mice treated with S-1 alone (P < 0.05). On the other hand, LNT did not prolong the survival period when combined with S-1 in Colon-26-bearing athymic mice. The frequency of CD86+ DCs infiltrated into Colon-26 was increased in mice treated with S-1 + LNT, and splenic DCs harvested from mice treated with S-1 + LNT showed more potent T-cell proliferation activity than that of DCs from mice treated with S-1 alone (P < 0.05). Furthermore, the activity of cytotoxic T lymphocytes (CTLs) in splenocytes of S-1 + LNT-treated mice was specific and more potent than that of CTLs from mice treated with S-1 alone (P < 0.05). These results suggest that modulation of specific immunity with LNT has a significant role in enhanced antitumor effects through the modification of DC function. We demonstrated that DCs might play an important role in chemotherapy, and the combination therapy of S-1 and LNT presents a promising chemoimmunotherapy, which might lead to better survival for cancer patients.

Topics: Adenocarcinoma; Animals; Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Combined Modality Therapy; Dendritic Cells; Drug Combinations; Fibrosarcoma; Immunotherapy, Adoptive; Lentinan; Lung Neoplasms; Lymphoma; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Nude; Neoplasms, Experimental; Oxonic Acid; Pyridines; Rats; Rats, Inbred Strains; Spleen; Survival Rate; T-Lymphocytes, Cytotoxic; Tegafur

Case 1: A 77-year-old man was revealed to have type 3 gastric cancer with synchronous liver metastases. He underwent total gastrectomy with lymphatic dissection of D1+a and tubing of the hepatic artery. After surgery, two courses of hepatic arterial infusion of low-dose 5-FU plus CDDP were performed. The patient was discharged, and TS-1 (60 mg/day) was administered from day 1 to 14 followed by 7 days rest as one course. CDDP (10 mg/ body) was infused in the hepatic artery bolus on day 8 and 15 as outpatient treatment. After 8 months, the CEA was decreased from 3,098 ng/dl to 5.4 ng/dl, hepatic metastases were decreased by 85% assessed as a partial response. Case 2: A 71-year-old man was diagnosed with multiple liver metastases 10 months after distal gastrectomy for early gastric cancer. After tubing of the hepatic artery, three courses of hepatic arterial infusion of low-dose 5-FU plus CDDP were performed. TS-1 with hepatic arterial infusion of CDDP was administered using the same regimen as an outpatient. After 4 months, hepatic metastases decreased by 73%. These cases suggest that TS-1 with hepatic arterial infusion of CDDP in an outpatient may be an effective treatment with low toxicities and no damage to QOL in gastric cancer patients with multiple liver metastases.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Fluorouracil; Gastrectomy; Hepatic Artery; Humans; Infusion Pumps, Implantable; Infusions, Intra-Arterial; Liver Neoplasms; Lymph Node Excision; Male; Oxonic Acid; Pyridines; Quality of Life; Stomach Neoplasms; Tegafur

In general, treatment for gastric cancer with peritoneal dissemination or recurrent gastric cancer is outside the scope of surgery. The efficacy of new anti-cancer drugs such as TS-1 system was revealed in a controlled study by comparing treatment with non-treatment groups. We performed chemotherapy of TS-1 and docetaxel (TXT) in the outpatient clinic on a 72-year-old nonresected gastric cancer patient accompanied by peritoneal dissemination. Although no killer cell effect was recognized, the patient clinically achieved good QOL by this method for one year and seven months. In conclusion, we reported a treatment method for nonresected gastric cancer, which was treated only on an outpatient basis. The course of this case closely resembled the tumor dormancy therapy performed by Takahashi et al.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Docetaxel; Drug Administration Schedule; Drug Combinations; Humans; Male; Oxonic Acid; Peritoneal Neoplasms; Pyridines; Quality of Life; Stomach Neoplasms; Taxoids; Tegafur

We present a patient with multiple bone metastases who was treated successfully using only TS-1. Metastasis was diagnosed 8 years after distal gastrectomy for early gastric cancer in a woman now 61 years old. Surgery was performed on February 13, 1995. The primary tumor was located in the midportion of the gastric body, and had invaded the submucosa with metastasis to lymph nodes in the area of the lesser curvature and the left gastric artery. She was discharged from our hospital 41 days after surgery. After the 8 years of follow-up, elevation of alkaline phosphatase (ALP: 1,029 IU/l) was noted. Bone scintigraphy disclosed scattered areas of uptake in systemic bones. The biopsy specimen from the pubic bone contained metastatic adenocarcinoma, and the bone lesions were diagnosed as multiple bone metastases from gastric cancer. Chemotherapy was started with oral administration of TS-1 alone at 80 mg/day for 2 weeks, followed by 2 weeks of rest. The patient did not experience any side effects, and treatment was repeated on an outpatient basis. At 4 month after initiation of therapy, decreases in ALP and number of foci of abnormal bone uptake in scintigrams were noted. She has survived for an additional 16 months after starting TS-1, without major complications.

Topics: Adenocarcinoma; Anastomosis, Roux-en-Y; Antimetabolites, Antineoplastic; Bone and Bones; Bone Neoplasms; Disease-Free Survival; Drug Administration Schedule; Drug Combinations; Female; Gastrectomy; Humans; Middle Aged; Oxonic Acid; Pyridines; Radionuclide Imaging; Stomach Neoplasms; Tegafur

A 51-old-female patient was admitted because of dyspnea. This case was diagnosed inoperable advanced gastric cancer and pulmonary carcinomatous lymphangiosis. She was treated by combination of docetaxel (TXT) and TS-1. TXT (40 mg/m2) was administered on day 1, and TS-1 (80 mg/body/day) was then administered for 14 days followed by a 7-day interval as one course. After two courses of chemotherapy, carcinomatous lymphangiosis declined, tumor markers decreased, and dyspnea improved. Administration of oxygen was thus discontinued. No side effects appeared (hematological or non-hematological).

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Docetaxel; Drug Administration Schedule; Drug Combinations; Female; Humans; Lung Neoplasms; Lymphatic Metastasis; Middle Aged; Neoplasm Invasiveness; Oxonic Acid; Pyridines; Stomach Neoplasms; Taxoids; Tegafur

The patient was a 66-year-old man who had advanced gastric cancer with metastasis to liver and lymph nodes. He received daily oral administration of 100 mg of TS-1 for 28 days followed by 14 days rest as one treatment course. After 2 coures, regression of the primary lesion and reduction in size of the liver and lymph metastases were observed.

Topics: Adenocarcinoma; Administration, Oral; Antimetabolites, Antineoplastic; Drug Administration Schedule; Drug Combinations; Humans; Liver Neoplasms; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Pyridines; Stomach Neoplasms; Survivors; Tegafur

A 66-year-old man complained of epigastralgia and a close examination was done. A type 3 gastric carcinoma was found. The tumor invading the pancreas and swelling lymphnodes around the stomach were confirmed according to abdominal CT. We considered it difficult to resect the tumor completely, and so we used combined chemotherapy of TS-1 plus CDDP. TS-1 was taken at 120 mg/day for 28 days followed by 14 days rest. CDDP was injected at 140 mg on day 8. Because the tumor in the stomach changed to scar and swelling lymphnodes diminished after two courses of therapy, total gastrectomy was done. After operation, combined chemotherapy of LV and 5-FU resulted in no recurrence to date. Although combined chemotherapy of TS-1 plus CDDP is effective for advanced gastric carcinoma, the number of days TS-1 is taken and the duration of the preoperative chemotherapy must be investigated in forthcoming study.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Drug Administration Schedule; Drug Combinations; Gastrectomy; Gastroscopy; Humans; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Male; Neoplasm Invasiveness; Oxonic Acid; Pancreatic Neoplasms; Pyridines; Stomach Neoplasms; Tegafur

The optimum dose of TS-1 for the treatment of peritoneally disseminated gastric cancer in a patient with chronic renal failure undergoing chronic dialysis was estimated by monitoring the blood concentrations of 5-FU and gimeracil (CDHP) [therapeutic drug monitoring (TDM)] during administration of TS-1. Immediately after dialysis, 50 mg or 40 mg of TS-1, corresponding to 50% and 40% of the standard dose (100mg for this patient), respectively, was administered orally once a day every other day, and TDM was conducted. Compared with the pharmacokinetic parameters of 5-FU at the time of the initial administration of 50 mg or 40 mg of TS-1 and that of cancer patients with normal renal function, the AUC shown in the administration of 40 mg was equivalent to that observed with a single safe dose of 100 mg in patients with normal renal function. Based on this observation, the daily TS-1 dose was set at 40 mg in this patient, and TS-1 treatment was started after confirming the absence of the accumulation of 5-FU or CDHP during repeated administrations. In this treatment protocol, TS-1 was administered 11 times at a daily dose of 40 mg every other day immediately after dialysis, followed by a rest. This .administration schedule was defined as one course. Under these conditions, the patient was treated on an outpatient basis, and the treatment could be safely continued without the development of any severe adverse events, such as myelosuppression.

Topics: Adenocarcinoma; Adult; Antimetabolites, Antineoplastic; Area Under Curve; Drug Administration Schedule; Drug Combinations; Drug Monitoring; Fluorouracil; Gastrectomy; Humans; Kidney Failure, Chronic; Male; Oxonic Acid; Peritoneal Neoplasms; Pyridines; Renal Dialysis; Stomach Neoplasms; Tegafur

A 58-year-old man with gastric cancer who had undergone distal gastrectomy on February 8, 2001 was revealed to have anorexia, and was diagnosed with a local recurrence in anastomosis by upper GI examination in August 2003. In September 2003, he was given combination chemotherapy with TS-1 50 mg/m2 (days 1-14) and CPT-11 80 mg/m2 (days 1, 8) every 3 weeks. A complete response (CR) was confirmed by endoscopy in December 2003. At present, he has been receiving chemotherapy with only TS-1 50 mg/m2 as a maintenance therapy and continuing CR. However, a trial of combination therapy with TS-1 plus CPT-11 is ongoing, and this combination chemotherapy may well achieve a high response rate. Because the adverse events of this chemotherapy have been mild and tolerable in some of our cases, this regimen is considered very useful.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Combined Modality Therapy; Drug Administration Schedule; Drug Combinations; Gastrectomy; Humans; Irinotecan; Male; Middle Aged; Neoplasm Recurrence, Local; Oxonic Acid; Pyridines; Remission Induction; Stomach Neoplasms; Tegafur

A 73-year-old woman was admitted to our hospital for evaluation of hypochondralgia, and a thorough examination revealed an AFP producing gastric cancer with multiple liver metastases. One course of TS-1 100 mg/day for 4 weeks and discontinuation for 2 weeks was started from February, 2003. After 3 months, the level of AFP reduced remarkably from 53,700 ng/ml to the normal limit. The metastatic tumors in the liver showed regression, and after 14 months, CT scanning showed that the tumors had disappeared. Since the size of the original tumor showed no change, distal gastrectomy was performed, and curability A was achieved. We consider this rare case has significant value in terms of treatment of AFP producing gastric cancer with multiple liver metastases. We think the combination of surgery and chemotherapy such as TS-1 will lead to a better prognosis in such cases.

Topics: Adenocarcinoma; Aged; alpha-Fetoproteins; Antimetabolites, Antineoplastic; Combined Modality Therapy; Drug Administration Schedule; Drug Combinations; Female; Gastrectomy; Humans; Liver Neoplasms; Oxonic Acid; Preoperative Care; Prognosis; Pyridines; Stomach Neoplasms; Tegafur

The usefulness of TS-1 as second/third-line therapy was evaluated in 7 patients with stage IIIb/IV colorectal cancer in whom the response to prior 5-FU/l-LV+CPT-11 therapy administered at our hospital had been rated as progressive disease (PD). The initial dose level of TS-1 was set at 80 mg/m2. The median follow-up period was 8 months. The response rate to TS-1 therapy was 14.3% (1/7). Four cases (57.1%) were rated as showing partial response (PR) or no change (NC). The median time to treatment failure (TTF) was 117 days. Thus, relatively satisfactory tumor dormancy was achieved in IFL-resistant cases. All adverse reactions observed were grade 2 or less severe. These results suggest that TS-1 used as the second/third-line therapy will contribute to improving the prognosis of patients with advanced or recurrent colorectal cancer.

Topics: Adenocarcinoma; Aged; Antimetabolites, Antineoplastic; Colorectal Neoplasms; Drug Administration Schedule; Drug Combinations; Drug Evaluation; Female; Humans; Male; Middle Aged; Oxonic Acid; Prognosis; Pyridines; Tegafur

A 69-year-old female underwent radical surgery for advanced gastric cancer (Stage IIIA) 7 years ago. She was diagnosed as remnant gastric cancer with multiple bone metastasis and peritoneal dissemination. Treatment with docetaxel and TS-1 was started with the following regimen: daily oral administration of 100 mg/body TS-1 for 14 days, followed by a 7 day rest and infusion of 40 mg/m2 docetaxel on day 1. Two months after the initial administration of docetaxel/TS-1, the sites of the remnant gastric cancer and bone metastasis were reduced in size, and the ALP returned to almost the normal level. The site of peritoneal dissemination had disappeared. Currently (nine months after diagnosis), she is undergoing therapy with TS-1. The combination of docetaxel and TS-1 can be a new tool for the management of gastric cancer with bone metastasis.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Combined Modality Therapy; Docetaxel; Drug Administration Schedule; Drug Combinations; Female; Gastrectomy; Humans; Oxonic Acid; Peritoneal Neoplasms; Pyridines; Stomach Neoplasms; Taxoids; Tegafur

A 62-year old man had undergone total gastrectomy for Borrmann type 4 gastric cancer. No peritoneal dissemination was observed at the laparotomy. Pathological examination revealed that the tumor involved the subserosal layer, and that the lymph node metastasis extended to the left gastric nodes. Vascular and lymphatic involvement was also observed. One hundred mg/body of TS-1, an oral 5-fluorouracil (5-FU) anticancer agent, which consisted of tegafur (a prodrug of 5-FU), and two modulators (gimeracil and oteracil potassium) was given from the 16th post-operative day. A course of TS-1 consisted of consecutive administration for 4 weeks followed by 2 weeks rest. The patient complained of abdominal fullness after administration of the second course of TS-1. Computed tomography (CT) revealed massive ascites. The serum carcinoembryonic antigen (CEA) titer was elevated to 13.5 ng/ml. From these findings, the occurrence of peritoneal dissemination was suspected. Weekly docetaxel of 30 mg/m2 (40 mg/body) was given for 3 weeks followed by a week cessation. At the start of the 6th course, the serum CEA was normalized, and CT scan detected the disappearance of ascites without any new lesion. Administration of docetaxel was continued until the 10th course then stopped without relapse of the disease. No dose reduction or postponement of administration were required. The patient has survived without disease one year after cessation of the treatment. Weekly docetaxel is a safe and effective regimen for gastric cancer worth using for a second-line therapy after failure of the 5-FU-based regimen.

Topics: Adenocarcinoma; Antineoplastic Agents, Phytogenic; Carcinoembryonic Antigen; Chemotherapy, Adjuvant; Docetaxel; Drug Administration Schedule; Drug Combinations; Gastrectomy; Humans; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Oxonic Acid; Peritoneal Neoplasms; Pyridines; Stomach Neoplasms; Taxoids; Tegafur

Combined chemotherapy consisting of oral TS-1 and low-dose CPT-11 by hepatic arterial infusion is suggested to be a new effective treatment for multiple liver metastases from colorectal cancer. A 53-year-old man was diagnosed with multiple hepatic metastases from advanced colon cancer (Stage IV). The patient underwent partial resection of the colon and catheter insertion into hepatic artery for arterial infusion in November 2003. He was treated with postoperative combination chemotherapy consisting of UFT and low-dose CPT-11. UFT was administered orally at 400 mg/body/day everyday and CPT-11 was injected at 40 mg/body/week for 6 weeks, followed by a 2 weeks rest interval as 1 cycle. In spite of the reduction of metastatic liver tumors after 2 cycles of the chemotherapy, a metastatic pleural tumor appeared. Therefore, we judged the effect of the chemotherapy to be a progressive disease and changed UFT in the regimen to TS-1. TS-1 was administered orally at 80 mg/body/day under a 2-weeks-on and 1-week-off regimen for 3 times. CPT-11 was injected at 40 mg/body/week for 6 weeks, followed by a 3 weeks rest interval as 1 cycle. A stable disease was maintained for 3 months. Outpatient care was possible because no severe events were observed. Tumors showed a reduction rate of 37.4% after the combination therapy. The patient survived for 285 days after the operation.

Topics: Adenocarcinoma; Administration, Oral; Ambulatory Care; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colonic Neoplasms; Combined Modality Therapy; Drug Administration Schedule; Drug Combinations; Hepatic Artery; Humans; Infusion Pumps, Implantable; Infusions, Intra-Arterial; Irinotecan; Liver Neoplasms; Male; Middle Aged; Oxonic Acid; Pyridines; Tegafur

We report a case of peritoneal cancer dissemination with Type 4 gastric cancer, successfully treated with combination chemotherapy with TS-1. The patient was a 59-year-old female, who complained of abdominal distension with pain, weight loss, and poor appetite. She was diagnosed as unresectable Type 4 gastric cancer, T3N2MOHOP1CY1M0, Stage IV with massive ascites (cytology: Class V). After 2 courses of combined chemotherapy with TS-1 and cisplatin (CDDP), primary tumor reduction was confirmed and no cancer cells were detected from a pathological investigation with biopsied specimens by endoscopy. As additional therapy for remained ascites, intraperitoneal administration of paclitaxel and docetaxel was performed, resulting in a remarkable decrease of ascites with cytological disappearance of cancer cells. The patients underwent total gastrectomy with lymph node dissection, pathological diagnosis of primary site and lymph nodes showed grade 2 effect, and no cancer cells were detected in ascites and peritoneum, microscopically. While she died of peritoneal recurrence after the surgery, the case suggested the clinical advantage of controlling the advanced cancer-bearing state by combination chemotherapy with TS-1, instead of surgery.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Ascites; Cisplatin; Drug Administration Schedule; Drug Combinations; Female; Gastrectomy; Humans; Lymph Node Excision; Lymphatic Metastasis; Middle Aged; Oxonic Acid; Peritoneal Neoplasms; Preoperative Care; Pyridines; Stomach Neoplasms; Tegafur

The patient was a 61-year-old man who was referred to our hospital with a complaint of epigastric pain. Upper gastrointestinal endoscopy and X-ray examination of the stomach revealed type 3 cancer in the gastric antrum, extending to the middle body. It was about 9 cm in diameter, and the biopsy specimen revealed moderately differentiated tubular adenocarcinoma. Abdominal CT scan showed marked enlargement of No. 3 lymph nodes along the lesser curvature of the stomach. Examination of the blood showed a hemoglobin of 10.2 g/dl, CEA 5.8 ng/ml, CA19-9 330.5 U/ml. For this gastric cancer, clinical Stage IIIA (cT3N1HOPOMO), neoadjuvant chemotherapy with TS-1/CDDP was planned. TS-1 (120 mg/day) was orally administered for 3 weeks followed by a drug-free-2-week period as the first course, and 93 mg (60 mg/m2) of CDDP administered by intravenous drip on day 8. There were grade 2 nausea and grade 3 appetite loss by intravenous administration of CDDP in the second course. An upper GI series revealed 33% reduction of gastric cancer, and laboratory studies CEA and CA 19-9 showed normal values. One month after the second course of chemotherapy, total gastrectomy, splenectomy and lymph node dissection D2 were performed. The pathological specimens showed no cancer cells in the surgically obtained stomach and lymph nodes, so the histological effect was Grade 3. The postoperative course was satisfactory, and he now attends outpatient department without any findings of recurrence 12 months after the operation. TS-1/CDDP chemotherapy produced a high response in this case, and it may be useful as neoadjuvant chemotherapy for advanced gastric cancer.

Topics: Adenocarcinoma; Administration, Oral; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Administration Schedule; Drug Combinations; Gastrectomy; Humans; Infusions, Intravenous; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neoadjuvant Therapy; Oxonic Acid; Pyridines; Remission Induction; Stomach Neoplasms; Tegafur

We reported 2 cases with advanced gastric cancer, successfully treated with TS-1 and CDDP. Case 1 had Type 3 gastric cancer with left supra-clavicular (Virchow) and para-aortic lymph node metastases. Those distant node metastases completely disappeared after two courses of neoadjuvant chemotherapy (NAC) consisting of TS-1/ CDDP, and radical surgery for cure was conducted. The second case had Type 3 carcinoma with peritoneal dissemination. The primary lesion significantly decreased after four courses of the combination chemotherapy. The patient has been alive for 1 year and a half after 14 courses of TS-1/CDDP with stable disease. Significance of TS-1/CDDP in far advanced gastric cancer was discussed.

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

A 72-year-old female was admitted to our hospital with the complaint of left neck lymph node swelling. Abdominal computed tomography (CT) revealed wall thickening of the small intestine and multiple lymph node metastases. Barium meal study of the small intestine showed circular stenosis. The patient was operated on under a diagnosis of tumor of the small intestine and left neck lymph node swelling. Needle biopsy of the left neck lymph node and partial resection of the small intestine was done without regional lymph node dissection because of Virchow lymph node metastasis. On the resected material a 5 x 4 cm type 2 tumor was identified. Pathological findings included poorly-differentiated adenocarcinoma, si (bladder), n 4, P 0, ly 3, v 3, H 0, M(-), Stage IV. The patient received the chemotherapy with TS-1. TS-1(80 mg/body/day) orally administered for 4 weeks followed by a drug-free 2-week period as one course. CT revealed that the metastatic lesion had shrunk markedly after the second course. A complete response (CR) was observed after one year. There were no drug side effects. At present, 3 years and 9 months after the operation, cervical and abdominal CT reveals no evidence of enlargement of the cervical and intraperitoneal lymph nodes.

Topics: Adenocarcinoma; Aged; Antimetabolites, Antineoplastic; Drug Administration Schedule; Drug Combinations; Female; Humans; Intestinal Neoplasms; Intestine, Small; Lymph Nodes; Lymphatic Metastasis; Neoadjuvant Therapy; Oxonic Acid; Pyridines; Remission Induction; Tegafur

TS-1 is an antitumor drug including 5-chloro-2,4 dihydroxypyridine (CDHP), which inhibits dihydriopyrimidine dehydrogenase (DPD) activity selectively in metabolism of 5-FU. However, TS-1 therapy tends to increase adverse events for patients with impaired renal function due to excessively high blood concentration of 5-FU, because CDHP is mainly excreted into the urine. In a 67-year-old male with advanced gastric cancer, renal dysfunction occurred during TS-1 administration as its adverse event. We studied the pharmacokinetics of 5-FU, which were analyzed on the T1/2 value and the AUC (0-infinity) of 5-FU with a single and consecutive TS-1 administration, and estimated an optimal TS-1 administration regimen for this patient. The regimen is 60 mg/body/day given in one divided dose for 28 days consecutively followed by 14 days rest. This regimen enabled a continuation of TS-1 treatment for the patient. In conclusion, individual dose adjustment using pharmacokinetic study of 5-FU might be beneficial to patients with impaired renal function.

Topics: Adenocarcinoma; Aged; Antimetabolites, Antineoplastic; Drug Combinations; Humans; Kidney Diseases; Male; Oxonic Acid; Pyridines; Stomach Neoplasms; Tegafur

The patient, a 40-year-old woman, underwent total gastrectomy and excision of the pancreatic tail, spleen and gallbladder for gastric cancer in September 2000. The lesion was judged to be P1, SE, H0, N2 and Stage IV and the patient was managed on a regular schedule as an outpatient. In September 2004, she passed blood-stained feces and rectal palpation detected a hard nodule at the anterior rectal wall. A fiber optic examination of the sigmoid colon detected an ulcerous lesion with a hemorrhage at the anterior rectal wall. A biopsy revealed the lesion to be Group V poorly differentiated adenocarcinoma. Starting in October 2004, 100 mg/day of TS-1 was administered for 3 weeks; intravenous drip infusion of 100 mg/body of CDDP was conducted in the second week for a period of 24 hours. After 3 courses of this regimen, a fiber optic examination of the colon conducted in February 2005 no longer detected the rectal tumor, leaving only a cicatrix. Upon a CT examination, the para-aortic lymph nodes that had been enlarged were notably reduced in size and an improvement was eminent in the hypertrophic rectal wall. The patient no longer experienced constipation or melena. Her clinical course is being observed while an oral administration of 100 mg/day of TS-1 continues.

Topics: Adenocarcinoma; Adult; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cholecystectomy; Cisplatin; Constriction, Pathologic; Drug Combinations; Female; Gastrectomy; Humans; Oxonic Acid; Pancreatectomy; Pyridines; Rectal Diseases; Rectal Neoplasms; Splenectomy; Stomach Neoplasms; Tegafur

A 50-year-old woman visited our hospital with a chief complaint of lower abdominal mass. The patient was diagnosed with rectal cancer using colonoscopy and also diagnosed with unresectable rectal cancer because abdominal CT revealed metastases to the liver, lung and lymph node located porta hepatis. The patient was treated with TS-1 combined with CPT-11. The TS-1 (80 mg/m2) was orally administered for 2 weeks and followed by a 2 week interval, and CPT-11 (80 mg/m2) was simultaneously administered biweekly. One cycle of chemotherapy was 28 days. The patient experienced grade 1 leukocytopenia and neutropenia. Abdominal CT revealed partial response after 2 cycles. After 6 cycles, the patient was subjected to curative operation. Pathological efficacy was Grade 1a at lymph node metastasis and Grade 3 at liver metastasis. TS-1 combined with CPT-11 regimen was very feasible and convenient, and obtained a good compliance. So this regimen was promising for unresectable colorectal cancer. In the future, this regimen will be verified in phase III clinical trial and compared with FOLFIRI and FOLFOX regimens.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Drug Administration Schedule; Drug Combinations; Female; Humans; Irinotecan; Middle Aged; Oxonic Acid; Preoperative Care; Pyridines; Rectal Neoplasms; Tegafur

We report a case in which TS-1 + paclitaxel (PTX) administration was effective for gastric cancer with malignant ascites. The patient was a 66-year-old male who received total gastrectomy, distal pancreatectomy and splenectomy. He complained of abdominal fullness and ascites 18 months later. The administered regimen of chemotherapy was TS-1 100 mg/day for two weeks, and PTX 120 mg/day on day 1 and 8 of TS-1 intake, followed by 1-week rest. Computed tomography (CT) showed complete loss of malignant ascites. The toxic events were grade 2 leukopenia and grade 2 alopecia.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Ascites; Cisplatin; Combined Modality Therapy; Drug Administration Schedule; Drug Combinations; Gastrectomy; Humans; Lymph Node Excision; Male; Oxonic Acid; Paclitaxel; Pyridines; Stomach Neoplasms; Tegafur

A 62-year-old man was revealed to have type 2 gastric cancer with synchronous liver metastasis. We considered liver metastasis to be a prognostic factor, and performed two courses of combination thermochemotherapy consisting of hepatic arterial infusion of MMC and TS-1 and thermotherapy. Partial response was observed in the liver metastases,but the primary lesion showed no changes; therefore, we performed four courses of combination thermochemotherapy consisting of TS-1/CDDP therapy and thermotherapy. By the end of three courses of this therapy,the primary lesion had cicatrized,and endoscopic biopsy revealed no cancer cells. These results suggest that gastric cancer,in which liver metastasis is considered to be a prognostic factor,can be effectively treated by combination therapy with hepatic arterial infusion therapy, followed by thermochemotherapy for the primary lesion.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Drug Administration Schedule; Drug Combinations; Hepatic Artery; Humans; Hyperthermia, Induced; Infusions, Intra-Arterial; Liver Neoplasms; Male; Middle Aged; Mitomycin; Oxonic Acid; Pyridines; Remission Induction; Stomach Neoplasms; Tegafur

We report herein a case with stage IV gastric cancer previously treated with TS-1 completely responding to second-line chemotherapy with weekly paclitaxel therapy. A 65-year-old female was diagnosed as having type 3 gastric cancer with para-aortic lymph node metastases. She underwent total gastrectomy with extended lymph node dissection on March 2003. Histopathological examination revealed that the tumor was poorly-differentiated adenocarcinoma with para-aortic lymph nodes metastases and completely resected. After the operation,she was treated by adjuvant chemotherapy with TS-1. In March of 2004, she suffered from hematuria, and a CT scan revealed para-aortic lymph nodes metastases and left kidney metastasis. Then, she was treated by a weekly infusion of paclitaxel as second-line chemotherapy. After 3 courses, the tumor disappeared and efficacy was judged as CR. Moreover, CR was maintained after 7 courses. At this writing in January of 2005, she is well and has been treated with paclitaxel without any severe adverse events. Therefore, weekly paclitaxel therapy was considered to be one of the promising second-line chemotherapies for advanced or recurrent gastric cancer previously treated by TS-1.

Topics: Adenocarcinoma; Aged; Antimetabolites, Antineoplastic; Antineoplastic Agents, Phytogenic; Chemotherapy, Adjuvant; Drug Administration Schedule; Drug Combinations; Female; Gastrectomy; Humans; Kidney Neoplasms; Lymph Nodes; Lymphatic Metastasis; Neoplasm Staging; Oxonic Acid; Paclitaxel; Pyridines; Remission Induction; Stomach Neoplasms; Tegafur

Topics: Adenocarcinoma; alpha-Fetoproteins; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Humans; Liver Neoplasms; Male; Middle Aged; Oxonic Acid; Pyridines; Stomach Neoplasms; Tegafur

Since the introduction of TS-1 for clinical treatment of the progression or recurrence of stomach cancer, the effectiveness of combination therapy incorporating other agents with CDDP has been reported. Low-dose CDDP/TS-1 combination treatment was carried out in a case of Stage IV progressive stomach cancer showing multiple liver metastases and spleen metastasis. Regression of the primary carcinoma and reduction in size of liver metastases and spleen metastasis were observed. Grade 2 leukocyte decrease and grade 1 stomatitis were noted as adverse reactions to the treatment. Low-dose CDDP/TS-1 combination therapy was useful in this case of advanced gastric cancer.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Humans; Liver Neoplasms; Male; Oxonic Acid; Pyridines; Splenic Neoplasms; Stomach Neoplasms; Tegafur

We report a case of a patient with recurrent gastric cancer and lung metastasis, who responded remarkably to combination chemotherapy using TS-1 and weekly CDDP. The patient was administered 2 courses of TS-1 (80 mg/m2/day, on day 1-21) and CDDP (25 mg/m2/day, on day 8, 15, 22) every 5 weeks. The regimen was done on an outpatient basis. The treatment resulted in the metastatic tumors in the lung disappearing after 1 course. No severe side effects were observed. This combination therapy proved useful for treating lung metastasis from gastric cancer in this patient.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Administration Schedule; Drug Combinations; Humans; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Pyridines; Remission Induction; Stomach Neoplasms; Tegafur

We report a patient with unresectable advanced gastric cancer who has been being treated by TS-1 administration on alternate days for 2 years. The patient was a 50-year-old female with type 4 gastric cancer accompanied by Schnitzler metastasis and pleural effusion. TS-1 administration was initiated at a daily dose of 100 mg with a schedule of 4-week administration and 2-week suspension. However, grade 2 hepatic dysfunction and leukocytopenia developed. When the daily TS-1 administration was changed to alternate-day administration at the same dose, no side effects were observed, allowing the continuation of treatment. She has maintained a minor response (MR)-no change (NC) for 1 year and 5 months, and is still symptom-free and being treated on an outpatient basis at present, 2 years after treatment. TS-1 is an anti-cancer drug that plays a central role in chemotherapy for gastric cancer. However, in some patients, side effects sometimes develop using the routine administration method, making continuation of administration difficult. Alternate-day TS-1 administration has great potential as a protocol that produces long-term anti-tumor effects while reducing side effects.

Topics: Adenocarcinoma; Antimetabolites, Antineoplastic; Carcinoma, Signet Ring Cell; Drug Administration Schedule; Drug Combinations; Female; Humans; Middle Aged; Neoplasms, Multiple Primary; Oxonic Acid; Peritoneal Neoplasms; Pleural Effusion, Malignant; Pyridines; Stomach Neoplasms; Survivors; Tegafur

We report a case of carcinomatous lymphangitis of the lungs due to and stomach cancer showing remarkable response to TS-1. The patient was a 51-year-old man whose chest x-ray and computed tomography (CT) revealed lymphangitis, and endoscopic examination showed stomach cancer on posterior wall of stomach body. Bone marrow metastasis was suspected because platelet count was 50/microliter, and myelocytes and metamyelocytes emerged in peripheral blood. TS-1 80 mg/day was administered orally for 28 days as 1 course. After 4 courses of TS-1, chest x-ray showed remarkable improvement, and platelet count was normalized. The patient survived for 10 months after the first visit. We suggest that TS-1 is an effective therapy for carcinomatous lymphangitis of the lungs due to stomach cancer.

Topics: Adenocarcinoma; Antimetabolites, Antineoplastic; Carcinoma, Signet Ring Cell; Drug Administration Schedule; Drug Combinations; Humans; Lung Neoplasms; Lymphangitis; Male; Middle Aged; Neoplasms, Multiple Primary; Oxonic Acid; Pyridines; Stomach Neoplasms; Tegafur

An umbilical metastasis of gastric cancer is known as Sister Mary Joseph's nodule. It ordinarily indicates a poor prognosis because umbilical metastasis often develops with peritoneal dissemination. Herein, we report a case of umbilical metastasis of gastric cancer that showed good response to chemotherapy, including the oral anticancer agent TS-1. The patient was a 55-year-old man in which gastric cancer was found by upper gastrointestinal series. Physical examination revealed an umbilical nodule that had an irregular surface and a hard consistency. Ultrasonography showed a 15 x 10 mm hypoechoic mass under the umbilicus. Core needle biopsy of the umbilical mass revealed adenocarcinoma. Peritoneal dissemination was proved by diagnostic laparoscopy. Oral anticancer agent TS-1 was administered with low-dose cis-platinum. The gastric lesion and umbilical nodule showed marked response to the chemotherapy and the response continued for 20 months. The patient died of disease progression 31 months after the initiation of the treatment.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Signet Ring Cell; Cisplatin; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Humans; Male; Middle Aged; Neoplasms, Multiple Primary; Oxonic Acid; Peritoneal Neoplasms; Pyridines; Stomach Neoplasms; Tegafur; Umbilicus

We report a case of synchronous esophageal and gastric cancer in a patient with severe liver dysfunction who was treated successfully using TS-1/CDDP therapy combined with irradiation therapy. A 56-year-old man with a chief complaint of dysphagia was diagnosed with thoracic esophageal cancer by endoscopy, and was referred to our hospital. Synchronous esophageal and gastric cancer were diagnosed by endoscopy and barium swallow. The preoperative diagnosis was T3N0M0, Stage II esophageal cancer and T1N0M0, Stage I A gastric cancer, both of which were diagnosed to be resectable. However, surgery was contraindicated because of severe liver dysfunction, due to an ICG15 of 35%. TS-1 (80 mg/day) and CDDP (3 mg/day) therapy was combined with irradiation, 60 Gy given in a T-pattern to the mediastinum. The patient did not suffer any side-effects, and endoscopy performed 44 days after the start of treatment showed that the esophageal lesion was now only a scar. Only a slight elevation of the esophagus was seen by endoscopy 219 days after the start of the therapy. The patient is currently undergoing only TS-1 treatment as an outpatient and is under observation. No metastasis to the liver or any other organ has been detected. TS-1 and CDDP therapy combined with radiotherapy appears to be effective in treating thoracic esophageal cancer.

Topics: Adenocarcinoma; Administration, Oral; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Combined Modality Therapy; Drug Administration Schedule; Drug Combinations; Esophageal Neoplasms; Humans; Male; Middle Aged; Neoplasms, Multiple Primary; Oxonic Acid; Pyridines; Radiotherapy Dosage; Stomach Neoplasms; Tegafur

A 55-year-old man was referred to us after transverse colostomy for intestinal obstruction caused by descending colon cancer with peritoneal dissemination. The colon lesion was palpated as a well-defined hard mass in the left lower abdomen and the disseminated lesion as a hard mass with an unclear border in the right lower abdomen. CEA level was 917 ng/ml at admission. Left hemicolectomy was performed for tumor reduction and TS-1 of 120 mg/day was started 6 days after surgery (4 weeks administration followed by a 2-week rest period). Administration discontinued due to nausea 4 weeks after commencement of the therapy, and restarted as a 2-week administration followed by a 2-week rest period. There has been no adverse reaction since then. Twenty-seven weeks after surgery, CEA level was reduced to 47 ng/ml and peritoneal dissemination was found to have disappeared upon physical examination and computed tomograph. TS-1 is expected to be an effective agent for the treatment of colon cancer with peritoneal dissemination.

Topics: Adenocarcinoma; Administration, Oral; Antimetabolites, Antineoplastic; Colectomy; Colonic Neoplasms; Combined Modality Therapy; Drug Administration Schedule; Drug Combinations; Humans; Male; Middle Aged; Oxonic Acid; Peritoneal Neoplasms; Pyridines; Tegafur

Diagnostic imaging of a 70-year-old woman revealed widespread lymph node swelling and pyloric stenosis due to alpha fetoprotein-producing gastric cancer. Second line chemotherapy of irinotecan and mitomycin C was administered after S-1 failure. After 6 courses of 2nd line chemotherapy, pyloric stenosis was improved, and lymph node swelling disappeared. This patient has been alive without disease for more than 3 years since 2nd line chemotherapy began and for more than 4 years since her first admittance to our hospital. Second line chemotherapy may have contributed to the favorable clinical outcome in this patient.

Topics: Adenocarcinoma; Aged; alpha-Fetoproteins; Antimetabolites, Antineoplastic; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Drug Combinations; Female; Humans; Irinotecan; Mitomycin; Oxonic Acid; Pyridines; Radiography; Stomach Neoplasms; Tegafur; Treatment Failure

A 41-year-old man was found to have advanced gastric cancer with simultaneous multiple bone metastases when pyloric stenosis was being diagnosed in our hospital. We performed gastrojejunostomy from the lower third of the stomach to the upper third of the duodenum to relieve the obstruction. However, at 8 days after surgery, disseminated intra-vascular coagulation (DIC) occurred. Therefore, the patient was administered combined chemotherapy with TS-1 plus low-dose cisplatin in addition to anti-DIC therapy. TS-1 (150 mg/day) and cisplatin (10 mg/body intravenously over the course of 30 minutes) were administered on days 1 to 5, 8 to 12, and 15 to 19 (weekday-on/weekend-off schedule). There was remarkable response to this chemotherapy, and the patient was shifted from inpatient to outpatient treatment. The treatment course was repeated for 4 cycles until remission was observed. Because of hematologic relapse due to DIC at 6 months after the first treatment, he was readmitted for administration of combined chemotherapy. Fortunately, DIC once again responded to the same chemotherapy regimen. In this pathologic condition, combined chemotherapy is unavoidable when DIC occurs with cancer. Accordingly, it is necessary that an effective combined chemotherapy with mild bone marrow suppression be chosen. A companion drug should be chosen in consideration of delayed homo-toxicity and of the possibility of relapse into DIC in the drug withdrawal period. In addition, it is indispensable that careful consideration be given to the most favorable dose and regimen.

Topics: Adenocarcinoma; Adult; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Cisplatin; Combined Modality Therapy; Disseminated Intravascular Coagulation; Drug Administration Schedule; Drug Combinations; Gastrectomy; Humans; Male; Oxonic Acid; Pyridines; Stomach Neoplasms; Tegafur

A 77-year-old man diagnosed with advanced gastric cancer underwent total gastrectomy with combined splenectomy and resection of the pancreatic tails in 1996. He was treated with 400 mg/day of UFT for 2 years. Serum CEA level was found to be elevated on July 5, 2001. He complained of left chest pain in December 2001. A 4 cm-sized tumor was detected in the region extending from the subcutaneous region to the left chest wall containing the osteolytic change of the left sixth rib. He was diagnosed with a chest wall metastasis from gastric cancer. He underwent radiotherapy with thermotherapy and was also treated with chemotherapy. TS-1 was administered at 80-100 mg/body/day, twice daily for 3 weeks followed by a 2-week rest interval as 1 cycle. As a results, shrinkage of the tumor was confirmed on February 14, 2002. The tumor was confirmed to have disappeared on April 17, 2002, by chest CT. A complete response of the metastatic tumor was achieved. The patient maintained a complete response for more than 12 months, but died from the chest wall metastasis recurrence and weakness on August 13, 2003. The only observed adverse event, was grade 2 leukopenia.

Topics: Adenocarcinoma; Administration, Oral; Aged; Antimetabolites, Antineoplastic; Drug Administration Schedule; Drug Combinations; Gastrectomy; Humans; Hyperthermia, Induced; Leukopenia; Male; Oxonic Acid; Pyridines; Splenectomy; Stomach Neoplasms; Tegafur; Thoracic Neoplasms

A 69-year-old female had complaints of vomiting, appetite loss and feeling of pharyngeal obstruction. She was diagnosed with a 3'-shaped advanced cardiac cancer with esophageal invasion. A biopsy revealed poorly differentiated adenocarcinoma. The tumor was T3 (SE) N2, Stage IIIB indicating a poor prognosis. After informed consent, TS-1 was administrated as preoperative chemotherapy. Chemotherapy with TS-1 was very effective, and the tumor noticeably decreased. Next, total gastrectomy was performed. Histopathological findings revealed that the primary tumor and lymph node had become scarred and fibrous, indicating a complete response (Grade 3). In the future, TS-1 can be expected to display efficacy in neoadjuvant chemotherapy for patients with advanced gastric cancer who have poor prognoses.

Topics: Adenocarcinoma; Aged; Antimetabolites, Antineoplastic; Cardia; Chemotherapy, Adjuvant; Drug Administration Schedule; Drug Combinations; Female; Gastrectomy; Humans; Oxonic Acid; Pyridines; Remission Induction; Stomach Neoplasms; Tegafur

We report a case of a 65-year-old male with stage IV gastric cancer accompanied by liver metastases, which showed a significant response after administration of TS-1. One hundred and twenty mg/body/day of TS-1 was orally administered without hospitalization. After 3 months, upper GI endoscopy showed improvement of primary gastric lesion, and cancer cells could not be detected under biopsy. After 2 months, computed tomography (CT) showed a reduction in the multiple liver metastases. Moreover, after 15 months, CT showed a complete regression of the multiple liver metastases, for a complete response (CR). The serum level of carcinoembryonic antigen (CEA) was reduced from 115 to within normal range. Noticeable critical adverse effects did not appear. Treatment on an outpatient basis, therefore, greatly contributed to his quality of life. We judged that TS-1 might be a candidate anti-cancer drug for first-line chemotherapy for advanced gastric cancer.

Topics: Adenocarcinoma; Administration, Oral; Aged; Antimetabolites, Antineoplastic; Drug Administration Schedule; Drug Combinations; Humans; Liver Neoplasms; Male; Oxonic Acid; Pyridines; Quality of Life; Remission Induction; Stomach Neoplasms; Tegafur

Conventional gastrojejunostomy has been employed for unresectable advanced gastric cancer with pyloric stenosis; however, it is often not fully effective. We report a patient with unresectable gastric cancer who was effectively treated with an anticancer drug, S-1, after receiving an improved gastrojejunostomy. The patient was a 55-year-old woman who was referred to our hospital for epigastric pain. Upper gastrointestinal endoscopy showed a Borrmann III tumor in the antrum of the stomach, and gastric roentgenography showed pyloric stenosis. Preoperative findings were T3N2H0P0, stage III b. At operation, the tumor was found to have invaded the duodenum and the head of the pancreas, and disseminated nodules were found in the mesenterium of the small intestine, the left diaphragm, and the round ligament of the liver. A curative operation was impossible for the advanced gastric cancer. Therefore, an improved gastrojejunostomy was performed to allow oral intake. Oral intake started 7 days after the operation, and she left our hospital 20 days after the operation. She started treatment with 80 mg/day of S-1, given orally, for 28 days, followed by 14 days' rest, as 1 course. During 16 courses of the treatment, she maintained a performance status of 0 to 1 and maintained quality of life. However, she died because of pelvic dissemination and genital bleeding (caused by tumor invasion into the uterus) 2 years and 4 months after the surgery. This case suggested that the improved gastrojejunostomy was a useful method for treating unresectable gastric cancer, allowing the possibility of oral intake, and the use of S-1.

Topics: Adenocarcinoma; Anastomosis, Surgical; Antimetabolites, Antineoplastic; Drug Combinations; Female; Humans; Jejunum; Middle Aged; Oxonic Acid; Palliative Care; Pyridines; Stomach; Stomach Neoplasms; Tegafur

We report a case of advanced gastric cancer with bulky N2 lymph node metastases resected after successful treatment with novel oral anticancer drug TS-1 as a neoadjuvant chemotherapy (NAC). A 62-year-old man was admitted to our hospital complaining of epigastralgia and dysphagia. Endoscopic examination revealed type 3 advanced gastric cancer in the upper gastric body. Computed tomography (CT) showed bulky N2 lymph node metastases. He was treated with a daily dose of 120 mg of TS-1 for 4 consecutive weeks, followed by 2 weeks of rest. No serious adverse reaction was observed. After 1 course of treatment, the primary tumor and metastatic lymph nodes were reduced. Therefore, a total gastrectomy combined with splenectomy and D2 lymph node dissection was performed. Histopathologically, a few viable cancer cells remained in the resected stomach and metastatic lymph nodes were found. The histological effect of NAC was judged to be grade 2. The patient's postoperative course was uneventful, and he has been well for 11 months following surgery. TS-1 as NAC is considered to be effective for advanced gastric cancer.

Topics: Adenocarcinoma; Antimetabolites, Antineoplastic; Combined Modality Therapy; Drug Administration Schedule; Drug Combinations; Gastrectomy; Humans; Lymph Node Excision; Lymphatic Metastasis; Male; Middle Aged; Oxonic Acid; Preoperative Care; Pyridines; Remission Induction; Stomach Neoplasms; Tegafur

A 42-year-old female patient underwent total gastrectomy for gastric cancer (Borrmann's Type 3). Many rice-grain sized peritoneal metastases were observed in the transverse colon and mesenterium. The lesion was diagnosed as stage IV cancer and the degree of radical cure was determined to be C. Chemotherapy with TS-1 was administered postoperatively. In each cycle, the drug was administered at a daily dose of 100 mg for 4 weeks, followed by a drug-free period of 2 weeks. The adverse reactions were mild, and she underwent the 2nd and further courses of therapy on an outpatient basis. Since she had acute cholecystitis during the 12th course, the drug was withdrawn for 2 months. Thereafter, the drug was started again after resolution of the cholecystitis. At present, ie, 3 years and 2 months after the surgery, the patient is receiving the 23rd course of chemotherapy on an outpatient basis, and abdominal CT shows no evidence of increase in the peritoneal metastases, enlargement of the intraperitoneal lymph nodes, or ascites.

Topics: Adenocarcinoma; Adult; Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Drug Administration Schedule; Drug Combinations; Female; Gastrectomy; Humans; Oxonic Acid; Peritoneal Neoplasms; Pyridines; Stomach Neoplasms; Survivors; Tegafur

A 58-year-old man underwent distal gastrectomy with a D2 lymph adenectomy for advanced gastric cancer (pStage IIIB). Seven months later, abdominal CT revealed multiple paraaortic lymph nodes metastases. Radiation therapy was not effective, so TS-1 chemotherapy was started (each treatment course consisted of daily oral administration of 100 mg TS-1 for 4 weeks followed by 2 drug-free weeks). The CT findings revealed that the metastatic lesion had shrunk markedly after the first course. A complete response was observed after the fifth course, and was maintained thereafter. The serum level of CEA decreased from 337 to 2.7 ng/ml after the third course, but gradually rose again and stayed between 30 and 50 ng/ml. Although the re-elevation of serum CEA level suggested the existence of a recurrent lesion, no sign of recurrence was found by radiographical or endoscopic examinations. Leukocytopenia and anemia (grade 2) were the only observed adverse effects. This patient continues to undergo outpatient treatment with good QOL.

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

A 62-year-old woman was admitted because of epigastralgia and tarry stool. An endoscopic examination revealed type 3 cancer in the lower body of the stomach, and abdominal CT scan demonstrated enlarged abdominal paraaortic lymph nodes. The preoperative diagnosis was cStage IV gastric cancer (cT3, cN3, cH0, cP0, cM0). Since a curative operation was deemed impossible, we started neoadjuvant chemotherapy using TS1 plus cisplatin (CDDP) for downstaging. TS-1 (100 mg/day) was orally administered for 3 weeks, and CDDP (90 mg/body) was administered intravenously on day 8. Appetite loss of grade 3 and leucopenia of grade 1 were observed. After two courses of chemotherapy, the primary lesion was reduced in size, and the paraaortic lymph nodes disappeared on abdominal CT scan. The serum tumor marker became normal. Subsequently, she underwent curative total gastrectomy with splenectomy and lymph node dissection. Histological examination of the primary lesion revealed marked fibrosis and a small amount of residual cancer cells. The histological changes by neoadjuvant chemotherapy were judged to be grade 2 for the main tumor. It is suggested that neoadjuvant chemotherapy using TS-1 plus CDDP is effective for advanced gastric cancer with massive lymph node metastases.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Aorta, Abdominal; Cisplatin; Drug Administration Schedule; Drug Combinations; Female; Humans; Infusions, Intravenous; Lymph Nodes; Lymphatic Metastasis; Middle Aged; Oxonic Acid; Pyridines; Remission Induction; Stomach Neoplasms; Tegafur

We report a patient with multiple pulmonary metastases from rectal cancer effectively treated with TS-1 and low-dose CDDP combination chemotherapy. The patient was a 61-year-old man with rectal cancer and multiple pulmonary metastases. He had undergone abdominoperineal excision of the rectum at another hospital before this hospitalization. After the operation, we treated the patient by the combination chemotherapy of TS-1 and low-dose CDDP during his hospital stay and in the outpatient clinic after hospital discharge. After the chemotherapy was started, tumor markers decreased, and finally were in the normal range. The pulmonary metastatic lesions were remarkably reduced on CT, and the effect of this therapy was PR. No severe side effect was observed throughout the treatment. This combination chemotherapy is considered to be an effective therapy for colorectal cancer with good QOL.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Cisplatin; Combined Modality Therapy; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Humans; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Pyridines; Rectal Neoplasms; Remission Induction; Tegafur

A 69-year-old female patient underwent total gastrectomy with a D2 lymph node dissection. Her final findings were of pT2, pN0, sP0, sH0, sM0 and Stage IB. After thirty-five months from the operation, peritoneal recurrence with ascites, bilateral hydronephrosis and stenosis of colon was found. TS-1 (80 mg/day/body) was administered for four weeks followed by a 2-week rest after DJ stents were inserted into bilateral ureters. At the end of two courses of TS-1, ascites disappeared and the decrease of tumor marker was observed. During the seventh course, symptoms such as abdominal fullness and ascites became worse. She underwent a weekly administration of paclitaxel (90 mg/body) as a second-line chemotherapy. This regimen was continued for three weeks followed by a 1-week rest. After four courses of paclitaxel, ascites disappeared and the tumor marker was gradually reduced. However, multiple bone metastases were found during the eighth course, and she died about two years after the recurrence. The toxic events were mucositis (grade 1) in TS-1, and alopecia (grade 2) and leukopenia (grade 1) in paclitaxel. No major adverse effects were observed. Although the prognosis of recurrent gastric cancer with peritoneal dissemination was extremely poor, this case might suggest a possibility that intensive therapies are useful in maintaining the quality of life and improving survival.

Topics: Adenocarcinoma; Aged; Antimetabolites, Antineoplastic; Antineoplastic Agents, Phytogenic; Combined Modality Therapy; Drug Combinations; Female; Gastrectomy; Humans; Hydronephrosis; Lymph Node Excision; Neoplasm Recurrence, Local; Oxonic Acid; Paclitaxel; Peritoneal Neoplasms; Peritonitis; Pyridines; Stents; Stomach Neoplasms; Tegafur

A 53-year-old man had consulted another physician regarding his epigastralgia and anorexia. Since gastric cancer was detected, he was referred to our department. An upper gastrointestinal endoscopy revealed a type-2 gastric cancer at the upper portion of the lesser curvature of the stomach, and an abdominal CT scan showed marked swelling of periaortic lymph nodes. Since a radical resection appeared impossible, we used preoperative chemotherapy with a combination of TS-1 and CDDP. The patient was administered TS-1 for 3 weeks at 120 mg/ day, received an intravenous drip infusion of 90 mg/body of CDDP on day 8, and then discontinued chemotherapy for 2 weeks, which was regarded as one course. After 2 courses of the chemotherapy, an upper gastrointestinal endoscopy showed that the primary tumor was reduced in size, the periphery of the tumor almost flattened, and an abdominal CT scan confirmed the loss of swelling in the periaortic lymph nodes. The responsive rate was evaluated as PR. Since a radical resection was considered possible, we performed a total gastrectomy with complete D3 extirpation combined with a splenectomy. Histological efficacy was evaluated as grade 2 in primary cancer, and grade 3 in lymph nodes. Regrettably, the patient died one year and 7 months postoperatively. However, we consider the TS-1 and CDDP in combination useful as preoperative chemotherapy for advanced gastric cancer with periaortic lymph node involvement.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Aorta; Cisplatin; Combined Modality Therapy; Drug Administration Schedule; Drug Combinations; Gastrectomy; Humans; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Oxonic Acid; Pyridines; Stomach Neoplasms; Tegafur

A Case of Advanced Gastric Cancer with Multiple Liver Metastases Successfully Treated with TS-1 and CDDP: Akihiro Tsukahara, Kazuhiro Kaneko and Syuji Tanaka (Dept. of Surgery, Niigata Prefectural Koide Hospital) Summary A 70-year-old advanced gastric cancer patient with liver and lymph node metastases was treated by chemotherapy with TS-1 and CDDP. One course consisted of administration of TS-1 100 mg/body for 21 days followed by 14 days rest and infusion of CDDP 80 mg/body on day 8. At the end of 2 courses, the primary tumor showed a hypertrophic wall, but a partial response of the liver metastases (reduction ratio was 78.3%) and a complete response of the LN metastasis were achieved. PR and CR were maintained after 4 courses. There were no remarkable side effects for 4 courses. This chemotherapy may have therapeutic efficacy in cases of advanced gastric cancer with liver and lymph node metastases.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Administration Schedule; Drug Combinations; Humans; Liver Neoplasms; Lymph Nodes; Lymphatic Metastasis; Male; Oxonic Acid; Pyridines; Stomach Neoplasms; Tegafur

The patient was an 89-year-old woman whose complaints were anorexia and weight loss. As a result of various examinations, she was diagnosed with advanced gastric cancer, Borrmann 3. TS-1 was administered at 75 mg/day for two weeks followed by one-week discontinvation during hospitalization; This course was then repeated after discharge. Anorexia and weight loss improved after two weeks, and complete response (CR) was obtained after 10 months of treatment. No cancer cells were confirmed by endoscopic biopsy. During this period no severe toxicities occurred. This TS-1 administration schedule appears to be a feasible and effective therapy for elderly patients with advanced gastric cancer.

Topics: Adenocarcinoma; Administration, Oral; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Drug Administration Schedule; Drug Combinations; Female; Gastroscopy; Humans; Oxonic Acid; Pyridines; Remission Induction; Stomach Neoplasms; Tegafur

Case 1: A 62-year-old man was introduced to our hospital for Type 1 cardiac gastric cancer. On the abdominal CT, there was evidence of multiple liver metastases. The patient was treated with daily oral administration of TS-1 (120 mg/day) for 3 weeks followed by 2 weeks' rest and infusion of CDDP (60 mg/m2) on day 8 as 1 course. After completion of 1 course, partial response in the primary tumor, and complete responses in the liver and lymph node metastases had been assessed, although the primary tumor increased during the 2 months' rest after 4 courses. Case 2: A 67-year-old man was hospitalized for Type 3 cardiac gastric cancer with multiple liver and lymph node metastases. A combination of TS-1 (100 mg/day), and CDDP (60 mg/m2), and TS-1 (80-50 mg/ day) was used. After 2 courses of TS-1/CDDP and 4 courses of TS-1, the primary tumor decreased significantly in size, and complete responses in the liver and lymph node metastases had been assessed, although the primary tumor, liver and lymph node metastases increased after 6 courses of TS-1. The two cases under study suggest that the combination systemic chemotherapy of TS-1 and CDDP is an effective treatment for advanced gastric cancer with multiple liver metastases in terms of its antitumor effect and QOL of the patients.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Cardia; Cisplatin; Drug Administration Schedule; Drug Combinations; Humans; Liver Neoplasms; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Oxonic Acid; Pyridines; Quality of Life; Radiography, Abdominal; Stomach Neoplasms; Tegafur; Tomography, X-Ray Computed

A 65-year-old man was referred to our hospital because of weight loss. Endoscopic examination and computed tomography (CT) revealed an advanced gastric cancer with multiple abdominal lymph node swellings. Distal partial gastrectomy was performed but lymph node resection was not done, since it was not thought to be curative. Adjuvant chemotherapy was performed for 4 courses with a regimen of ADM 20 mg/m2 day 1, CDDP 50 mg/m2 day 1, ETP 100 mg/day days 3-7, 5-FU 600 mg/m2 every other day on days 3-29. After 3 courses of ACVF therapy, the patient's serum CEA and SCC level normalized and the lymph node metastases became undetectable by CT scan. No severe side effects were observed at any time during the administration of these medications. In this case, serum SCC level was elevated even though histologic examination did not reveal squamous cell carcinoma but poorly differentiated adenocarcinoma. On immunohistochemical analysis, these tissues were stained diffusely with CEA, locally with AE1 + 3, and partially with PAS or Alcian blue. We speculate that this tumor could have developed the potency of SCC secretions without structural change into squamous metaplasia.

Topics: Adenocarcinoma; Aged; Antigens, Neoplasm; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cisplatin; Doxorubicin; Drug Administration Schedule; Drug Combinations; Etoposide; Fluorouracil; Gastrectomy; Humans; Lymphatic Metastasis; Male; Oxonic Acid; Pyridines; Remission Induction; Serpins; Stomach Neoplasms; Tegafur

A 60-year-old female had undergone laparoscopic oophorectomy for right ovarian tumor. At the time of surgery, peritoneal dissemination and ascites was observed. Histological examination revealed that the resected ovary, peritoneal nodes and floating cells in the ascites were metastatic adenocarcinomas. Later, the primary malignant lesion was found to be a type 4 gastric carcinoma. The carcinoma was judged to be unresectable and treated by combination chemotherapy with TS-1 and CDDP every 6 weeks. After 3 courses of treatments, upper gastrointestinal series and endoscopic examinations were conducted and revealed a marked reduction of the tumor size. No carcinoma cells were detected by endoscopic biopsy. CT-scan showed complete disappearance of metastatic lesions. Staging laparoscopy was performed for evaluation of the effects of chemotherapy, and no adenocarcinoma cells at peritoneal nodes or ascites were found histologically. We performed total-gasterectomy with D1 + alpha lymph node dissection. Histopathologically, resected specimens showed severe fibrosis in most parts of the stomach. Following chemotherapy, the carcinoma was judged to be Grade 2 by histopathological examination.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Administration Schedule; Drug Combinations; Female; Gastrectomy; Humans; Middle Aged; Oxonic Acid; Peritoneal Neoplasms; Pyridines; Stomach Neoplasms; Tegafur

In the present report, we describe the treatment results of paclitaxel in patients with metastatic gastric cancer previously treated with TS-1 or combination chemotherapy of TS-1 and CDDP. Paclitaxel was administered to 4 patients at a weekly dose of 80 mg/m2/day for three weeks followed by a one week interval. Remarkable tumor reduction was observed in 2 patients. Case 1: A 52-year-old male patient with gastric cancer and multiple liver metastases was treated by weekly infusion of paclitaxel as a 2nd line chemotherapy. After 1 course, the tumor was remarkably reduced, and the reduction was judged PR. Case 2: A 31-year-old male patient presented with lymphoangitis carcinomatosa and obstructive jaundice resulting from cancerous lymphoadenopathy. After 1 course, chest radiographs and abdominal CT scan showed remarkable reduction of these lesions. The adverse effects observed with this drug were leucocytopenia and liver dysfunction, both of which improved soon. These results indicate paclitaxel is effective for advanced gastric cancer pretreated with TS-1.

Topics: Adenocarcinoma; Adult; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Signet Ring Cell; Cisplatin; Drug Administration Schedule; Drug Combinations; Humans; Liver Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Oxonic Acid; Paclitaxel; Pyridines; Remission Induction; Stomach Neoplasms; Tegafur; Treatment Outcome

Survival of patients with advanced gastric cancer with Krukenberg's tumor is poor. We report the case of a good response in a 37-year-old woman who had type 4 gastric cancer, diagnosed after the operation of Krukenberg's tumor, and then was treated with TS-1, a DPD inhibitory fluoropyrimidine, in combination with a low-dose cisplatinum (CDDP). Endoscopic gastric biopsy showed signet-ring cell adenocarcinoma and moderately differentiated tubular adenocarcinoma, and computed tomography (CT) showed the para-aortic lymph node metastasis before the chemotherapy. The patient was treated with two courses of TS-1 (100 mg/day, day 1-21) plus CDDP (10 mg/m2, day 1-5, 8-12, 15-19) with two-week interval. After the first course, gastric biopsy did not show any cancer cells and lymph node metastasis had disappeared. Serum CA19-9 decreased gradually week by week during the chemotherapy, even during the washout period after the first course, and was normalized after two courses. This case suggests that the combination of TS-1 and low-dose CDDP is effective against type 4 advanced gastric cancer.

Topics: Adenocarcinoma; Adult; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Signet Ring Cell; Cisplatin; Drug Administration Schedule; Drug Combinations; Female; Humans; Infusions, Intravenous; Krukenberg Tumor; Lentinan; Neoplasms, Multiple Primary; Ondansetron; Ovarian Neoplasms; Oxonic Acid; Pyridines; Stomach Neoplasms; Tegafur

The prognosis and QOL of unresectable pancreatic cancer are very poor. A symptomless 60-year-old male was admitted for examination of a high serum CA19-9 level. Following ultrasound and abdominal CT, we diagnosed unresectable advanced pancreatic cancer with multiple liver metastasis. After we obtained his informed consent, we administered continuous infusion of 5-FU and low-dose cisplatin (CDDP) infusion (low-dose FP therapy) for 3 weeks. He then underwent combination chemotherapy with low-dose CDDP and TS-1 on an outpatient basis. During the chemotherapy, he did not experience any major adverse event and his QOL was relatively good. On follow-up CT 3 months later, the primary tumor in the pancreas was found to be stable. However, the size and number of liver tumors were remarkably reduced. The serum CA19-9 level had also remarkably decreased from 48,300 U/ml to 1,480 U/ml. In conclusion, the combination chemotherapy using low-dose CDDP and TS-1 can be effective in cases of unresectable pancreatic cancer with multiple liver metastasis.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Fluorouracil; Humans; Infusions, Intravenous; Liver Neoplasms; Male; Middle Aged; Oxonic Acid; Pancreatic Neoplasms; Pyridines; Quality of Life; Tegafur

A 44-year-old male patient underwent total gastrectomy for gastric cancer with peritoneal dissemination and direct invasion into the pancreas. After the operation, the patient received daily oral administration of TS-1, a novel oral anticancer agent. Each treatment course consisted of four-week administration of 120 mg TS-1 daily followed by two drug-free weeks. The patient was confirmed to be cancer-free by abdominal CT from the eighth course. With this chemotherapy, slight decrease of WBC (grade 1 or 2) and mild bowel obstruction appeared as the side effects of TS-1, but no other serious effects were observed. (A dose reduction of TS-1 from 120 mg to 100 mg per day was done at the beginning of the fifth course.) This patient could return to his work (physical labor) in the sixth month after the operation. The cancer-free period has persisted for sixteen months since the operation, and a good quality of life has been maintained simultaneously. TS-1 revealed a high effectiveness without deteriorating the patient's quality of life.

Topics: Adenocarcinoma; Administration, Oral; Adult; Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Drug Administration Schedule; Drug Combinations; Gastrectomy; Humans; Male; Oxonic Acid; Pyridines; Quality of Life; Stomach Neoplasms; Tegafur

The clinical efficacy and safety of TS-1 therapy were studied retrospectively in patients with inoperable and recurrent gastric cancer. The subjects were 45 patients who were treated with TS-1 for more than 4 weeks at our center between May 1999 and July 2002. The objective overall response rate was 32% (14/44; 95% confidence interval, CI, 19-48). The response rate in the chemo-naive patients was 44% (11/25; 95% CI, 24-65), and that in the patients with previous chemotherapy was 16% (3/19; 95% CI, 3.4-40). Although doses or durations of TS-1 administration were reduced in 22 patients (reduction group) due to adverse effects or poor performance status, they achieved a fairly high response rate of 38% (8/21). For primary lesions, the response rate was 30% (8/27). The prevalence of adverse reactions with a grade of 3 or 4 was 36%. However, the prevalence of each grade 3 or 4 adverse effect was relatively low, at 13% for neutropenia, and around 5% for anorexia, nausea, vomiting, and diarrhea. The median administration period was 10 weeks (4-47 weeks) in all patients and 11 weeks (6-47 weeks) in the reduction group. The relative dose intensity was 0.89 in all patients and 0.81 in the reduction group. In patients who were treated until August 2001, the median survival time (MST) was 13 months with 1-year and 2-year survival rates of 53% and 14%, respectively. These results were similar to those reported in the phase II study for the new drug approval. This study demonstrated the reproducible activity and safety of TS-1 in practice.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Drug Administration Schedule; Drug Combinations; Female; Humans; Male; Middle Aged; Oxonic Acid; Pyridines; Retrospective Studies; Stomach Neoplasms; Survival Rate; Tegafur

We report a case of advanced gastric cancer resected after successful treatment with the novel oral anticancer drug TS-1. The patient was a 52-year-old male. Gastrointestinal fiberscopy showed advanced gastric cancer. Examinations by computed tomography revealed gastric cancer invasion of the pancreas and swollen para-aortic lymph nodes. This patient was treated by preoperative chemotherapy with oral administration of TS-1 (120 mg per day). After 3 courses of treatment of TS-1, the primary lesion and swollen lymph nodes were remarkably reduced. This chemotherapy enabled total gastrectomy in curative resection. The pathological effectiveness of chemotherapy was Grade 1b in the primary lesion and Grade 2 or 3 in the lymph nodes. The patient sustained few side effects. This preoperative chemotherapy regimen seems to be an effective and promising therapy for patients with advanced gastric cancer.

Topics: Adenocarcinoma; Administration, Oral; Antimetabolites, Antineoplastic; Drug Administration Schedule; Drug Combinations; Gastrectomy; Humans; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Pyridines; Stomach Neoplasms; Tegafur

S-1(TS-1), a novel oral fluoropyrimidine, has been commercially available for gastric cancer in Japan. A nationwide post-marketing survey for safety was carried out after its approval. The aim of this analysis was to evaluate the efficacy and safety profile of this agent in clinical practice for patients with advanced gastric cancer registered in the postmarketing survey from our institution.. Between April 1999 and April 2000, a total of 51 chemo-naive patients were registered in the survey from the National Cancer Center Hospital East. S-1 was administered at 80 mg/m2/day for 4 weeks, followed by a 2-week rest, repeated every 6 weeks until disease progression, unacceptable toxicity, or the patient's refusal.. Of the 51 patients, 41 (80%) fulfilled the criteria of the guidelines determined by the company as appropriate patients for the drug administration. The median number of treatment courses was five. Toxicities were generally mild: grade 3 or 4 toxicities were seen in 10% or fewer patients, and no treatment-related deaths occurred. In the 47 patients with evaluable lesions, there were 2 complete responses and 18 partial responses, with a response rate of 43%. With a minimum follow-up of 2 years, median survival time and 2-year survival were 11.1 months and 33%, respectively. The majority of the 17 2-year survivors had diffuse-type histology and peritoneal metastasis and achieved an objective response.. S-1 appears to be safe and highly active, with favorable longterm survival in patients with metastatic gastric cancer, particularly in those with diffuse-type histology and peritoneal metastasis.

Topics: Adenocarcinoma; Adult; Aged; Antimetabolites, Antineoplastic; Drug Combinations; Drug Evaluation; Female; Humans; Japan; Liver Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Peritoneal Neoplasms; Product Surveillance, Postmarketing; Pyridines; Stomach Neoplasms; Survival Analysis; Tegafur; Time Factors; Treatment Outcome

A no change (NC) status could be maintained in a patient with remnant gastric cancer for more than 500 days with low-dose TS-1. The patient was a 68-year-old woman who was found to have remnant gastric cancer during an endoscopic examination in follow-up on an outpatient basis after surgery for hepatocellular carcinoma in our department. Surgery was rejected as a treatment option because of severe liver dysfunction, and the patient was started on oral TS-1 80 mg/day. Both AST and ALT levels increased immediately after the start of TS-1, and TS-1 was discontinued until these levels improved. It was resumed at 50 mg/day, and there were no subsequent adverse reactions. Endoscopic examination on day 69 after the start of TS-1 showed that a partial response (PR) had not been achieved, but the lesion had shrunk. Endoscopy on day 454 after the start of TS-1 showed it had been possible to maintain a similar state. This was a rare case in which it was possible to achieve prolonged same status with low-dose TS-1.

Topics: Adenocarcinoma; Administration, Oral; Aged; Antimetabolites, Antineoplastic; Carcinoma, Hepatocellular; Drug Administration Schedule; Drug Combinations; Female; Humans; Liver Neoplasms; Neoplasm, Residual; Neoplasms, Multiple Primary; Oxonic Acid; Pyridines; Stomach Neoplasms; Tegafur

Hand-foot syndrome (HFS) is a rare adverse reaction to oral fluoropyrimidine TS-1, which contains the dihydropyrimidine dehydrogenase (DPD) inhibitor. We treated a recurrent gastric cancer patient with chronic renal failure who developed grade 2 HFS, grade 2 conjunctivitis and grade 3 stomatitis soon after TS-1 administration. Those symptoms improved with the administration of vitamin B6, topical emollient therapy, and so on. We thought that the continuous elevation of serum 5-FU concentration, due to the accumulation of DPD inhibitor from the renal dysfunction, led to the development of HFS, although the participation of 5-FU metabolites such as F-beta-alanine cannot be ruled out.

Topics: Adenocarcinoma; Aged; Antimetabolites, Antineoplastic; Conjunctivitis; Drug Combinations; Foot Dermatoses; Hand Dermatoses; Humans; Male; Neoplasm Recurrence, Local; Oxonic Acid; Prodrugs; Pyridines; Stomach Neoplasms; Stomatitis; Syndrome; Tegafur; Vitamin B 6

A 62-year-old man with carcinomatous ascites more than 5 years after early gastric cancer operation was admitted to our hospital because of suspected pancreatic cancer, and was diagnosed with a relapse of the gastric cancer. TS-1 was administered at a dose of 120 mg/day. At the end of 1 course a partial response of a decrease of tumor markers and ascites and improvement of QOL was achieved, and the patient was followed in the outpatient clinic. The current case suggests that TS-1 may have a potent therapeutic efficacy in cases of gastric cancer relapse with carcinomatous ascites.

Topics: Adenocarcinoma; Antimetabolites, Antineoplastic; Ascites; Drug Administration Schedule; Drug Combinations; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Oxonic Acid; Peritonitis; Pyridines; Stomach Neoplasms; Tegafur

A 63-year-old man who had suffered from anorexia and body weight loss was admitted to the hospital. Upper GI series and an endoscopic examination revealed type 3 cancer in the posterior wall of the cardia. Abdominal CT scan showed enlargement of No. 16 lymph nodes. Preoperative diagnosis was stage IV gastric cancer (T3 (SE) H0 P0 N3), and we considered a curative operation impossible. Therefore, neoadjuvant chemotherapy with TS-1 and low-dose cisplatin (CDDP) was planned. After 4 weeks of administration, the primary lesion was reduced in size and the No. 16 lymph nodes were shrunken remarkably. Therefore, a total gastrectomy with a splenectomy, a distal pancreatectomy, and D3 lymph node dissection was performed. Histological findings demonstrated the degeneration of cancer cells and fibrosis in the primary tumor and metastatic regional lymph nodes. There were no viable cancer cells in the No. 16 lymph nodes. The histological changes against neoadjuvant chemotherapy were judged to be Grade 1b for the main tumor and Grade 3 for the No. 16 lymph nodes. Neoadjuvant chemotherapy with TS-1 and low-dose cisplatin is so effective in a short period that can be adapted to advanced gastric cancer for downstaging.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Aorta, Abdominal; Cisplatin; Drug Administration Schedule; Drug Combinations; Gastrectomy; Humans; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neoadjuvant Therapy; Oxonic Acid; Pyridines; Stomach Neoplasms; Tegafur

We treated a patient with gastric cancer considered to be unresectable due to peritoneal metastasis, who responded remarkably to treatment with TS-1. The patient was a 62-year-old male. His diagnosis was gastric cancer, for which he underwent surgery on February 22, 2001. Laparotomy disclosed many nodules measuring 2-3 mm in diameter in the abdominal cavity, so rapid pathological tests were conducted during the operation. The test results indicated peritoneal metastasis from gastric cancer. Therefore, simple laparotomy was employed as the best option. On day 13 after surgery, oral administration of TS-1, bid., at a daily dose of 120 mg was commenced. In our outpatient clinic, he was given 3 courses, each comprising 4 weeks' medication and 2 weeks' discontinuation. Subsequently, upper digestive tract endoscopy was performed but only scars in the gastric vestibular area were observed. Biopsy could not detect any malignant findings. Medication was discontinued due to the patient's preference and he died of gastric cancer 10 months after operation.

Topics: Adenocarcinoma; Administration, Oral; Antimetabolites, Antineoplastic; Drug Combinations; Humans; Male; Middle Aged; Oxonic Acid; Peritoneal Neoplasms; Pyridines; Stomach Neoplasms; Tegafur

A total of 40 patients with advanced and recurrent gastric cancer in our hospital were treated with TS-1 alone, and the efficacy of treatment, survival time, and adverse effects were examined. TS-1 was administered with the usual dosage and dose regimen. Response to treatment included a complete response (CR) in 3 cases, partial response (PR) in 8 cases, no change (NC) in 10 cases, and progressive disease (PD) in 7 cases. The response rate was 39.3%, and among the 28 patients with evaluable lesions TS-1 produced a high response rate of 56.3% in 16 patients who had undergone prior therapy. The median survival time (MST) was 478 days in the 28 patients with evaluable lesions, excluding patients with peritoneal dissemination, and 283 days in the 12 patients with peritoneal dissemination. The outcome was markedly poorer in the patients with peritoneal dissemination than in the patients with evaluable lesions. The incidence of grade 3 or higher adverse effects was 20%, including two cases in which decreased dihydropyrimidine dehydrogenase (DPD) activity was suspected, and one case in which decreased dihydropyrimidinase (DHP) was suspected. Although the effect of TS-1 alone on gastric cancer is significantly superior to that of any conventional cancer drugs, the results of this study suggest that the antitumor effect varies with the site of the target lesions and according to whether the lesion is a remnant or recurrence.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Drug Administration Schedule; Drug Combinations; Female; Humans; Leukopenia; Male; Middle Aged; Neoplasm Recurrence, Local; Oxonic Acid; Pyridines; Stomach Neoplasms; Survival Rate; Tegafur

We treated a patient with inoperable advanced gastric cancer and malignant ascites by combination chemotherapy of TS-1 and biweekly paclitaxel (TXL). After two courses the ascites had disappeared and the primary tumor was reduced. TS-1 (80 mg/body/day) was administered for 21 days followed by 7 days rest and TXL (100 mg/body) was administered on days 1 and 14 as one course. The patient could not eat at the time of hospitalization, but at the time of the second course he could eat a full serving of rice porridge. Grade 2 anemia and leukopenia were the only adverse reactions observed; no major adverse reactions were observed. These results suggest that with TS-1 and TXL combination chemotherapy, patients with advanced gastric cancer can achieve a marked improvement in quality of life.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Ascites; Drug Administration Schedule; Drug Combinations; Esophageal Neoplasms; Humans; Male; Neoplasm Invasiveness; Oxonic Acid; Paclitaxel; Pyridines; Quality of Life; Stomach Neoplasms; Tegafur; Treatment Outcome

We report two head and neck cancer patients who responded to TS-1. Case 1, a 52-year-old man was admitted to our department a diagnosis of supraglottic laryngeal cancer (T3N2cM0) on January 25, 2000. Concurrent chemoradiotherapy consisting of 2 courses of chemotherapy and radiation therapy at 70.2 Gy was administered. After the treatment, a biopsy showed a remaining cancer in the primary lesion. Since the patient refused to undergo surgery, the patient was followed up at the outpatient clinic using UFT at 400 mg/day. Because pulmonary metastasis was detected by chest CT, administration of TS-1 was started. TS-1 was administered at the conventional dose of 120 mg/day for 4 weeks followed by a 2-week rest. According to a CT conducted after 2 courses, the mass in the lung field disappeared and the clinical outcome was judged to be a CR. The TS-1 administration is still continuing, and the patient's condition also remains a CR. Case 2 was a patient with highly-differentiated adenocarcinoma in the ethmoid sinus (T3N2bM0). The patient was inoperable and was given radiation therapy of 64.8 Gy. Because of no change of the tumor after radiotherapy, TS-1 was administered at 60 mg x 2/day for 4 weeks followed by a 2-week rest. After TS-1 was administered for 3 courses, a CT showed a remarkable regression of the tumor resulting in a PR for the primary and the neck lesion. Upper gastrointestinal endoscopy during the 4th course detected a gastric ulcer of the A1 stage, and the patient was immediately admitted to the hospital. The ulcer was an adverse reaction of grade 3, which was improved by conservative therapy. TS-1 was restarted with a dose of 100 mg/day on April 11. No particular adverse reaction has been observed since then. The patient has received 13 courses of TS-1 and is still receiving TS-1. No clear tumor has been observed, and the clinical outcome is considered to be a CR. TS-1 is considered to be an excellent oral anticancer drug in terms of its anti-tumor effect and the patient's QOL.

Topics: Adenocarcinoma; Antimetabolites, Antineoplastic; Drug Administration Schedule; Drug Combinations; Head and Neck Neoplasms; Humans; Laryngeal Neoplasms; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Pyridines; Quality of Life; Remission Induction; Tegafur

A 62-year-old advanced gastric cancer patient with bulky N2 lymph node metastases was treated by neoadjuvant chemotherapy with TS-1 and CDDP. TS-1 (100 mg/body/day) was orally administered for 3 weeks followed by a drug-free 2-week period as 1 course, and 75 mg/body/day of CDDP was administered by intravenous drip on day 8. After the first course, the primary lesion and the regional lymph node metastases showed partial response in terms of size. No serious drug adverse reaction was observed. During the second course, urgent total gastrectomy with distal pancreatectomy and splenectomy was performed for massive bleeding from a deep gastric peptic ulcer. The histopathological findings showed complete response of the carcinoma as primary lesion except for two sites of minimal lymphatic permeation and one lymph node (No. 8a) metastasis. The combined use of TS-1 and CDDP is useful as neoadjuvant chemotherapy for advanced gastric cancer.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cisplatin; Drug Administration Schedule; Drug Combinations; Female; Humans; Lymph Nodes; Lymphatic Metastasis; Middle Aged; Oxonic Acid; Pyridines; Stomach Neoplasms; Tegafur

A 74-year-old male underwent left upper abdomen excision (LUAE) and D3 lymph node dissection for type 4 gastric cancer. Nine months after the surgery, abdominal computed tomography (CT) revealed paraportal lymph node recurrence (#8p), 22 mm in size. One hundred mg/body/day of TS-1 was administrated for 14 days, followed by 7 days rest, as one course. A complete response was obtained after the second course. This treatment was stopped after the 11 course because the patient suffered prolonged grade 1 fatigue. The patient has been in good health without a recurrence for 1 year and 5 months after the recurrence. Adverse effects included rash (grade 1), diarrhea (grade 2), fatigue (grade 2) and neutrophils neutropenia (grade 2).

Topics: Adenocarcinoma; Aged; Antimetabolites, Antineoplastic; Drug Administration Schedule; Drug Combinations; Gastrectomy; Humans; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Male; Oxonic Acid; Pyridines; Remission Induction; Stomach Neoplasms; Tegafur

We encountered a case of effective response to TS-1 of inoperable gastric cancer, in the course of chemotherapy for malignant lymphoma. A 78-year-old man, in the course of chemotherapy for malignant lymphoma, complained of appetite loss. A biopsy from gastric endoscopy indicated gastric carcinoma. This was diagnosed as inoperable gastric cancer, and gastro-jejunostomy was performed. After administration of TS-1 orally for 4 courses, it was observed to be effective with no severe adverse events.

Topics: Adenocarcinoma; Aged; Antimetabolites, Antineoplastic; Drug Administration Schedule; Drug Combinations; Humans; Lymphatic Metastasis; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Male; Oxonic Acid; Pyridines; Stomach Neoplasms; Tegafur

Topics: Adenocarcinoma; Administration, Oral; Antimetabolites, Antineoplastic; Ascitic Fluid; Drug Combinations; Fluorouracil; Humans; Male; Middle Aged; Oxonic Acid; Peritoneal Neoplasms; Pyridines; Stomach Neoplasms; Tegafur

The patient was a 64-year-old male. On November 21, 1991, he underwent gastric resection on the pyloric side for early gastric cancer in the authors' hospital, and did not experience recurrence for many years thereafter. However, endoscopic examination of the upper gastrointestinal tract performed on June 11, 1999 revealed advanced cancer in the posterior wall of the residual stomach which was accompanied by invasion of the esophagus. Thus, the residual stomach was completely removed on July 5, 1999. The histopathological findings were tub1, se, ly3, v2, aw(-), ow(+) and ew(+), and a portion of the esophageal stump and the serosa of the lesser curvature were positive for cancerous tissue. Endoscopic examination was performed one month after the operation, on August 7, 1999. A forceps biopsy taken from an elevated lesion of the esophagus at the posterior wall of the anastomosis revealed adenocarcinoma cells in the lower layer of the squamous epithelium. A residual esophageal lesion was thus diagnosed. Beginning on August 9, 1999, TS-1 was administered in a dosage of 50 mg bid, but it was later learned that the patient had ingested only half of that TS-1 dosage (i.e., 50 mg/day). After completion of one course of this therapy, endoscopy was again performed. It was found that the prominence on the esophageal mucosa at the anastomosis, which had been diagnosed as being cancerous tissue, had shrunk in size, while a forceps biopsy taken from the same site yielded no findings of malignancy. The patient was followed for 18 months thereafter, and endoscopy was performed three times during that interval but continued to yield no evidence of malignancy. As of February 2001, this patient had completed 12 courses of TS-1 at one-half its usual dosage. There have been no findings of recurrence, and the patient's course continues to be good. In summary, this was an interesting case in which residual cancer was detected in the esophageal stump following resection for gastric cancer, and it can be concluded that TS-1 therapy was effective in spite of being incomplete (i.e., half-dose), eradicating the residual cancer tissue.

Topics: Adenocarcinoma; Antimetabolites, Antineoplastic; Drug Combinations; Esophageal Neoplasms; Gastrectomy; Gastric Stump; Humans; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Invasiveness; Oxonic Acid; Pyridines; Stomach Neoplasms; Tegafur

A 64-year-old male visited our hospital with complaints of epigastric pain. Computed tomography (CT) showed gastric cancer with extensive paraaortic lymph node metastasis. We decided that a curative operation was impossible, and administered the following chemotherapy. After 120 mg/day of TS-1 was orally administered for 3 weeks followed by 2 drug-free weeks with 90 mg of CDDP was administered intravenously on day 8, CT showed a 90.6% reduction in the paraaortic lymph node metastasis. No serious adverse reaction was observed. After 2 courses of this chemotherapy, surgery was performed after informed consent was obtained from the patient. Histrogical result showed PR. The patient is now healthy and no sign of recurrence has been observed. TS-1/CDDP therapy is useful for advanced gastric cancer.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Aorta; Cisplatin; Drug Administration Schedule; Drug Combinations; Humans; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Neoadjuvant Therapy; Oxonic Acid; Preoperative Care; Pyridines; Remission Induction; Stomach Neoplasms; Tegafur

We report the case of 72-year-old man with recurrent gastric cancer who was successfully treated with TS-1. We performed only non-curative operation because the tumor had infiltrated the pancreas head and aspiration pneumonia complications developed under the anesthetic. Abdominal CT revealed local recurrence and metastasis of the paraaortic lymph node after 3 months, so we started TS-1 chemotherapy. One course consisted of daily oral administration of 100 mg TS-1 for 4 weeks and withdrawal for 2 weeks. The recurrent lesions disappeared completely after 1 course. Furthermore, this therapy was continued for 3 courses without any side effects.

Topics: Adenocarcinoma; Administration, Oral; Aged; Antimetabolites, Antineoplastic; Drug Administration Schedule; Drug Combinations; Humans; Lymphatic Metastasis; Male; Neoplasm Recurrence, Local; Oxonic Acid; Pyridines; Stomach Neoplasms; Tegafur

TS-1, a novel oral formation of 5-fluorouracil that consists of 1 M tegafur (FT), 0.4 M gimeracil and 1 M otacil potassium, was reported to achieve a relatively high response rate of 49% in patients with advanced gastric cancer in a late phase II study. We report a case of inoperable gastric cancer with multiple liver metastases, which responded significantly to the short-term administration of TS-1 following intravenous FMP therapy. A 79-year-old man, who had nothing of note in his past or family history, presented with multiple liver tumors and type 3 gastric tumor. His diagnosis was inoperable gastric cancer with liver metastases, and he underwent outpatient treatment of oral administration of TS-1, following FMP therapy under hospitalization. The main and metastatic lesions shrunk dramatically with the two courses of the chemotherapy. There were no noticeable adverse effects. QOL has been maintained and the patient remains in good condition. TS-1 can be considered well-tolerable and quite effective for inoperable gastric cancer, especially if preceding therapy with 5-FU shows significant efficacy. TS-1 may therefore be a new candidate as a first line drug in outpatient cancer treatment.

Topics: Adenocarcinoma; Administration, Oral; Adult; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Administration Schedule; Drug Combinations; Fluorouracil; Hospitalization; Humans; Infusions, Intravenous; Liver Neoplasms; Male; Mitomycin; Oxonic Acid; Pyridines; Stomach Neoplasms; Tegafur; Treatment Outcome

S-1 is an anticancer drug in which tegafur is combined with modulators, gimeracil and oteracil potassium. We encountered a patient with gastric cancer for whom oral administration of S-1 was effective, and we report this case. A 79-year-old woman visited our hospital with a major complaint of anorexia. Tests revealed severe anemia, with a hemoglobin (Hb) level of 6.5 g/dl, and the patient was admitted to the hospital for treatment. The primary lesion was a large type-1 gastric cancer (poorly differentiated adenocarcinoma) in the middle gastric body. In addition, a lesion with a diameter of 50 mm was observed in the left hepatic lobe and small metastatic lesions were also scattered in the right lobe. When a performance status (PS) of 0 was obtained after her systemic condition had been improved, S-1 was started, at a dose of 80 mg/day (with one course consisting of administration for 4 weeks, followed by 2 weeks' rest). No severe adverse drug reaction was observed. After one course of administration was completed, the patient received administrations at the outpatient clinic. Upon the completion of two courses, computed tomography (CT) showed disappearance of the metastatic lesions and marked regression of the primary lesion. At present, upon completion of the sixth course, no hepatic metastasis is observed and the primary gastric lesion shows a tendency to regress. Her PS is maintained at 0.

Topics: Adenocarcinoma; Aged; Antimetabolites, Antineoplastic; Drug Combinations; Female; Humans; Liver Neoplasms; Oxonic Acid; Pyridines; Stomach Neoplasms; Tegafur

A 60-year-old man was admitted to our hospital suffering from discomfort in the epigastrium. Endoscopic examination revealed stenosis from the fornix to the body of the stomach. The lesion had invaded the lower esophagus. Biopsy specimens confirmed poorly differentiated adenocarcinoma. An abdominal CT scan showed the lesion was a single mass in the stomach and swollen lymph nodes at the fornix, and revealed slight ascites and left hydronephrosis. The patient received oral administration of TS-1. No adverse effect was seen after 3 courses of treatment, and the lesion was reduced so that it was only found in the fornix. During the 1 year and 3 months of treatment with TS-1, this patient worked as mountain guide in the Hida area and was able to travel to the Himalayas in Nepal for the New Year of 2001. To preserve the quality of life of cancer patients, it is worth considering outpatient treatment with TS-1.

Topics: Adenocarcinoma; Antimetabolites, Antineoplastic; Drug Administration Schedule; Drug Combinations; Humans; Male; Middle Aged; Oxonic Acid; Pyridines; Quality of Life; Stomach Neoplasms; Tegafur

The patient, a 53-year-old male, underwent radical surgery for advanced gastric cancer (stage IV). On the second day after surgery, adjuvant chemotherapy consisting of 250 mg/day 5-FU (i.v.) for 14 days, followed by 450 mg/day of UFT-E for about 12 months, was initiated. About 21 months after surgery (7 months after cessation of medication), the CA19-9 level had risen (136 U/ml). After 26 months, the patient experienced a backache and his CEA and CA19-9 levels had risen 11.7 ng/ml and 869 U/ml, respectively. The results from an imaging examination were suggestive of multiple bone metastases and para-aortic lymphatic metastasis. Chemotherapy was resumed with only TS-1 (100 mg/day). Because the tumor markers (TM) continued to rise, he was hospitalized and the medication was combined with daily administration of 10 mg of CDDP (TS-1 + CDDP protocol). When the total dose of CDDP reached 160 mg, there was a dramatic drop in the TM (surrogate marker) level. The patient was discharged and medication of TS-1 and 10 mg/day of CDDP twice a week was continued on an outpatient basis. Five months after the initial administration of FP, the CEA and CA19-9 returned to normal levels (4.3 ng/ml and 33 U/ml, respectively). Metastases to the para-aortic lymph nodes had disappeared and the sites of bone metastases were reduced in size. The patient was able to resume his full social activities. Since that time, a second-line therapy has been added. Currently (about two years after the recurrence), he is still undergoing therapy with TS-1 + CDDP.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Aorta; Bone Neoplasms; Chemotherapy, Adjuvant; Cisplatin; Drug Combinations; Humans; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Oxonic Acid; Pyridines; Remission Induction; Stomach Neoplasms; Survivors; Tegafur

A 64-year-old man had undergone subtotal gastrectomy with a D2 lymphadenectomy for advanced carcinoma of the stomach with paraaortic lymph nodes metastases 12 months earlier. The histopathological findings revealed a well differentiated adenocarcinoma [type 2 macroscopic findings, SE, INF beta, ly2, v1, N2, M1 (LYM)]. On admission, biochemical investigations showed an elevation of CEA, CA19-9, and CA 125. An abdominal ultrasonography and a computed tomography (CT) revealed lymph node swelling of the paraaorta. After non-curative operation, he has received adjuvant chemotherapy with TS-1 plus CDDP. At first, 100 mg/day of TS-1 was orally administered for three weeks followed by two drug-free weeks, with CDDP (60 mg/m2/day) infused on day 8. Next, the treatment course consisted of four-week consecutive administration of TS-1 (80 mg/day) followed by two drug-free weeks, with biweekly infusion of CDDP at a dose of 15 mg/m2. The CT findings revealed that an almost complete reduction of the metastatic paraaortic lymphnodes was obtained after completion of course 1, and was maintained thereafter. No noteworthy adverse reactions were observed and the patient has a good QOL. The patient is now in a good health and continues to undergo low dose TS-1 plus CDDP chemotherapy as an outpatient.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Aorta; Chemotherapy, Adjuvant; Cisplatin; Drug Administration Schedule; Drug Combinations; Gastrectomy; Humans; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Oxonic Acid; Pyridines; Remission Induction; Stomach Neoplasms; Tegafur

A case of an unresected, advanced gastric cancer with Sister Mary Joseph nodule was presented. It was treated with new combination chemotherapy of low-dose S-1 and cisplatin producing complete response of periumbilical metastasis. Few treatments are efficacious for umbilical invasion of peritoneal dissemination. A complete response for Sister Mary Joseph nodule from gastric adenocarcinoma has not been ever reported.

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

A patient with advanced gastric cancer complicated with liver and lymph node metastases was successfully treated with a novel oral anticancer drug, TS-1, TS-1 was administered at a dose of 100 mg/day. One course consisted of consecutive administration of TS-1 for 28 days and withdrawal for 14 days. At the end of 3 courses a partial response of the liver metastases was achieved. Although the patient has had complications with ascites collection due to hypoalbuminemia, he has been well without regrowth of any metastases for over 8 months.

Topics: Adenocarcinoma; Antimetabolites, Antineoplastic; Drug Combinations; Humans; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Oxonic Acid; Pyridines; Stomach Neoplasms; Tegafur

TS-1, a DPD inhibitory fluoropyrimidine, is a novel oral formation of 5-fluorouracil (5-FU). In patients with advanced gastric cancer, the response rate was reportedly over 40%. We report three cases of advanced gastric cancer treated using TS-1 in combination with a low-dose of cisplatinum (CDDP) that well responded. Case 1: A 62-year-old women underwent total gastrectomy. Ten weeks later, she suffered intestinal obstruction due to peritoneal recurrence of gastric cancer. Eighty mg of TS-1 in combination with bi-weekly administration of CDDP (10 mg) improved her intestinal obstruction. Case 2: A 50-year-old man suffered peritoneal recurrence of gastric cancer. Computed tomography (CT) showed intestinal obstruction, ascites, and hydronephrosis. After 100 mg of TS-1 in combination with bi-weekly administration of CDDP (20 mg) for 1 year, CT showed almost complete improvement of peritonitis carcinomatosa. Case 3: A 58-year-old man, who suffered advanced gastric cancer with peritonitis carcinomatosa, was administrated 100 mg of TS-1 in combination with bi-weekly administration of CDDP (20 mg). After 2 months of administration, remarkable improvement was observed in the upper gastrointestinal series. Adverse reactions, which were grade 1 for stomatitis, were observed only in case 1. All three patients are alive (case 1 and 2 have survived more than one year) and therapy is continuing. In conclusion, combined chemotherapy of TS-1 and low-dose CDDP was effective and well tolerable for advanced gastric cancer patients. It was suggested that effective biochemical modulation might be achieved by these two drugs.

Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Administration Schedule; Drug Combinations; Female; Fluorouracil; Humans; Male; Middle Aged; Oxonic Acid; Pyridines; Stomach Neoplasms; Tegafur

We present the case of a 72-year-old man with gastric tube cancer accompanied by multiple liver metastases, after esophagectomy for esophageal cancer, whose quality of life (QOL) was improved with a small dosage of TS-1. The patient's high serum AFP level suggested alpha-fetoprotein-producing gastric cancer. He was treated with half the standard dose of TS-1, because the patient's poor general condition necessitated chemotherapy with low toxicity and high efficacy. The daily dose was 40 mg for the first three courses and 50 mg for the last two. Each treatment course consisted of a four-week administration followed by two drug-free weeks. The patient received five courses of chemotherapy at our outpatient clinic before his death from re-progression of liver metastasis. No serious side effect except temporary stomatitis was observed. A decrease in tumor markers, alpha-fetoprotein and carcinoembryonic antigen, was obtained after 4 weeks. After 2 cycles, computed tomography and endoscopy examinations showed regression of the primary tumor and liver metastases, and tumor markers were decreased remarkably. The patient's QOL improved gradually after the treatment. His performance status before the chemotherapy was 3, and improved to 1 after two cycles. The small dosage of TS-1 was effective without any adverse effects, and improved the patient's QOL, for 6 months.

Topics: Adenocarcinoma; Aged; Antimetabolites, Antineoplastic; Drug Administration Schedule; Drug Combinations; Humans; Liver Neoplasms; Male; Oxonic Acid; Pyridines; Quality of Life; Stomach Neoplasms; Tegafur

The patient was a 65-year-old woman who came to our hospital because she had noticed swelling of a left supraclavicular lymph node. Endoscopy revealed an ulcerous lesion in the L chain region, and poorly differentiated adenocarcinoma of the stomach was diagnosed as a result of a biopsy. Oral therapy was impossible because of pyloric stenosis, and a gastrojejunal bypass operation was performed. Serious hepatic dysfunction occurred postoperatively due to swelling that was suspected of being due to lymph node metastasis in the porta hepatis. For this reason, the TS-1 therapy that had been initially scheduled was abandoned, and low-dose FP therapy was instituted for 4 weeks. Afterward, the swelling resolved and the patient's hepatic disorder and systemic condition improved. Administration of TS-1, 80 mg/day (bid), was started in the outpatient clinic 4 weeks after the completion of FP therapy. Administration had to be discontinued after the first course of TS-1 therapy because of grade 3 thrombocytopenia and neutropenia. However, since marked decreases in tumor markers were observed, TS-1 administration was resumed after recovery. After completion of the second course of TS-1 therapy, a decrease in size of the Virchow lymph node was noted, and PR was diagnosed. TS-1 as initial chemotherapy had to be abandoned for this patient because of a serious hepatic disorder, in which TS-1 administration is contraindicated. However, a favorable response was obtained by concomitant use of FP therapy.

Topics: Adenocarcinoma; Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Female; Fluorouracil; Humans; Liver Diseases; Lymphatic Metastasis; Oxonic Acid; Pyridines; Stomach Neoplasms; Tegafur

Hand-foot syndrome (HFS) is a relatively common side effect of fluorouracil (5-FU) chemotherapy that has also been associated with the oral fluoropyrimidine capecitabine. Interestingly, HFS is virtually unknown to result from treatment with UFT, a combination of tegafur and uracil. Tegafur is a prodrug of 5-FU and is a component of S-1, another oral fluoropyrimidine active in a variety of solid tumors. We know of only one previously described case of S-1-induced HFS and the case reported here is the first to provide full documentation of this occurrence. The pathophysiology of chemotherapy-induced HFS remains unknown and very little pathological information is available. Treatment consists of topical emollient therapy, although pyridoxine has occasionally been beneficial. The study of HFS may provide an important insight into the pharmacology of fluoropyrimidines and allow for effective preventive strategies for this side effect of chemotherapy.

Topics: Adenocarcinoma; Administration, Oral; Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Drug Administration Schedule; Drug Combinations; Female; Humans; Keratoderma, Palmoplantar; Middle Aged; Oxonic Acid; Pyridines; Sigmoid Neoplasms; Tegafur

A newly approved oral fluoropyrimidine, TS-1, is a dihydropyrimide dehydrogenase (DPD)-inhibiting fluoropyrimidine (DIF) drug. We describe a case of interstitial pneumonia probably caused by TS-1. A peripheral blood lymphocytes stimulating test (DLST) with TS-1 demonstrated a substantial positive reaction. So far only three cases of TS-1-induced interstitial pneumonia have been reported but the relationship between interstitial pneumonia and TS-1 was demonstrated only in this case. Considering that interstitial pneumonia has also been reported with 5-FU, it is necessary in the future to clarify which component of this drug is directly related to interstitial pneumonia.

Topics: Adenocarcinoma; Aged; Antimetabolites, Antineoplastic; Drug Combinations; Humans; Lung Diseases, Interstitial; Male; Oxonic Acid; Pyridines; Stomach Neoplasms; Tegafur

TS-1(S-1) has been developed as a new oral anticancer drug based on the biological modulation of 5-fluorouracil. We treated a patient with highly advanced gastric carcinoma with a new combination chemotherapy of S-1 and low-dose cisplatin. Remarkable tumor reduction was observed after two cycles of this therapy in the primary tumor and metastatic lymph nodes, and the ascites disappeared. This was concluded to be a partial response. The only adverse effect was skin pigmentation of the fingers (grade 1), leading to early timing of operation after chemotherapy. The gastric tumor showed evident invasion to the serosa. Lymph nodes around the stomach were swollen. Peritoneal dissemination was also recognized in the omentum and mesocolon. Total gastrectomy with regional lymph node dissection was performed. Disseminated tumors were all resected. Histological examination showed that no tumor cells were detected in the gastric primary lesion, metastatic lymph nodes or disseminated peritoneal tumors, suggesting pathological complete remission. It was suggested that this regimen could be a potent combined therapy for the treatment of patients with highly advanced gastric carcinoma, and it could be useful as neoadjuvant chemotherapy. Further studies are necessary to evaluate the efficacy of this therapy.

Topics: Adenocarcinoma; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Gastrectomy; Gastroscopy; Humans; Male; Middle Aged; Neoadjuvant Therapy; Oxonic Acid; Peritoneal Neoplasms; Pyridines; Stomach Neoplasms; Tegafur; Tomography, X-Ray Computed; Treatment Outcome

Recently, as society ages there have become more elderly gastric cancer patients with/without several complications(cerebrovascular diseases, cardiac diseases, atherosclerosis, DM, etc.), that were non-resected and require highly effective chemotherapy and good QOL. We report two elderly gastric cancer patients responding to chronomodulation chemotherapy (tegafur + cisplatin + Isovorin) based on circadian rhythms plus a new antitumor drug, S-1. The treatment protocol was tegafur 800 mg/body, days 1-7 (continuing 16 h, intravenously with 500 mg/body from 16 to 0 h, 300 mg/body from 0-8 h, for non-uniform administration), cisplatin 10 mg/body, days 1-5, (16 h), Isovorin 25 mg/body, days 1-5, (16 h, oneshot infusion, for 4 courses followed by a week rest. Next was S-1 120 mg/body x 2 times orally for 28 days, followed by 2 weeks rest, the administered for another 28 days. The first patient was 74 years of age, with advanced type 3 plus early type IIc gastric cancers with liver metastasis (H1). After chemotherapy the liver metastasis disappeared, there was a 70% reduction in the advanced cancer and the early cancer disappeared. The second patient was 84 years of age, with advanced type 3 gastric cancer invading the esophagus. After chemotherapy, the primary lesion was reduced 80% and the esophageal invasion mass shrunk. The only adverse effect was grade 2 pancytopenia. In conclusion this regimen resulted in good intrachemotherapeutic QOL and highly effective performance in elderly advanced gastric cancer patient.

Topics: Adenocarcinoma; Administration, Oral; Aged; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Signet Ring Cell; Chronotherapy; Circadian Rhythm; Cisplatin; Drug Administration Schedule; Drug Combinations; Humans; Leucovorin; Male; Neoplasms, Multiple Primary; Oxonic Acid; Pyridines; Stomach Neoplasms; Tegafur

TS-1, a novel oral formation of 5-fluorouracil that consists of 1M tegafur (5-FU), 0.4M CDHP and 1M Oxo, is reported to achieve a higher response rate of 49% in patients with advanced gastric cancer in a late phase II study. We report a case of recurrent gastric cancer that responded significantly to the short-term administration of TS-1. A 73-year-old man, who had undergone a curative distal gastrectomy with D2 lymphadenectomy 2 years earlier, had presented with obstructive jaundice resulting from cancerous lymphadenopathy. PTCD was performed for drainage, but cholestasis disappeared completely through the two courses of oral administration of TS-1. The serum level of transaminase and bilirubin remained within normal limits, even with PTCD unequipped, until the patient died of the original disease. The adverse effects observed with the drug were anemia (grade 1) and skin pigmentation (grade 2), both of which improved soon after discontinuing the medication. In conclusion, TS-1 may be well-tolerable and effective in some cases of terminal-stage and/or recurrent gastric cancer, especially those associated with obstructive jaundice arising from the cancerous lymphadenopathy, in that patient QOL can be maintained to a much greater extent.

Topics: Adenocarcinoma; Administration, Oral; Aged; Antimetabolites, Antineoplastic; Cholestasis; Drug Combinations; Humans; Lymphatic Diseases; Male; Oxonic Acid; Pyridines; Quality of Life; Stomach Neoplasms; Tegafur

TS-1 is an oral anticancer drug that produces biochemical modulation. TS-1 is composed of FT (tegafur), CDHP (gimestat), and Oxo (ostat potassium), in a molar ratio of 1:0.4:1. We administered TS-1 to a patient with liver and pulmonary metastasis of rectal cancer (phase II study). Each treatment course consisted of a four-week administration followed by two drug-free weeks. The daily dose was 120-150 mg/day. Before the administration, hepatic metastasis was 30 x 20 mm. After 2 courses, it was reduced to 20 x 15 mm (reduction rate: 50%). Three pulmonary metastases that were recognized in chest radiographs before the administration tended to reduction after 3 courses. The reduction rate after 4 courses was 42.5%. The reduction was judged PR for the hepatic metastasis and MR for pulmonary metastases. There was no side effect and hospitalization was not required during the treatment. Thus, the administration of TS-1 enhanced the quality of life of this patient.

Topics: Adenocarcinoma; Administration, Oral; Antimetabolites, Antineoplastic; Drug Administration Schedule; Drug Combinations; Humans; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Pyridines; Rectal Neoplasms; Tegafur

We report a case of advanced gastric cancer producing Alpha Fetoprotein (AFP) with multiple liver metastases in which TS-1 is effective. Prognosis of gastric cancer producing AFP is well known to poor. A 74-year-old female was admitted complaining of anemia. She was diagnosed as having advanced gastric cancer with multiple liver metastases producing AFP by endoscopy, computed tomography and angiography. Her serum AFP level was 17,666 ng/ml and her serum CEA level was 5-2 ng/ml. After transarterial embolization (TAE), her family rejected her operation because it would not be curative. So, she was treated with TS-1, 40 mg, administered orally every day, followed by 14 days rest, as the first course. The next was TS-1, 80 mg orally administered for 6 courses. Her serum AFP level was down from 17,666 ng/ml to 94 ng/ml after 6 courses of TS-1. CT revealed that liver metastases did not change and endoscopy showed the primary lesion has diminished. Our report is the first to demonstrate that TS-1 is effective for patients with advanced gastric cancer producing AFP with multiple liver metastases.

Topics: Adenocarcinoma; Aged; alpha-Fetoproteins; Antimetabolites, Antineoplastic; Drug Administration Schedule; Drug Combinations; Female; Humans; Liver Neoplasms; Oxonic Acid; Pyridines; Stomach Neoplasms; Tegafur

We report the case of an unresected, metastatic gastric cancer, which was treated with a very short course of the oral 5-fluorouracil (5-FU) prodrug S-1. The patient had to discontinue chemotherapy during the first treatment cycle due to severe toxicity, but achieved a pathologically confirmed, long-term complete response of her primary tumour, a diffuse-type poorly differentiated adenocarcinoma.

Topics: Adenocarcinoma; Aged; Antimetabolites, Antineoplastic; Drug Combinations; Female; Fluorouracil; Humans; Oxonic Acid; Prodrugs; Pyridines; Remission Induction; Stomach Neoplasms; Tegafur

The purpose of this study was to establish a nude rat orthotopic (organ-specific) human colorectal cancer model as an in vivo secondary screen for general evaluation of new anticancer agents against colorectal cancer and to evaluate practically the antitumor activity of 1 M tegafur-0.4 M 5-chloro-2,4-dihydroxypyridine-1 M potassium oxonate (S-1), a new p.o. fluoropyrimidine, in comparison to 1 M tegafur-4 M uracil [(UFT) effective on colorectal tumor in clinical]. After implantation of KM12C, a human colorectal cancer cell line, into the subserosal layer of the colon as a single-cell suspension, extensive local tumor growth and invasion to both the mucosal and the serosal sides were observed in all rats. Metastatic foci were also formed in both lymph nodes and lungs following local tumor growth in all of them. Using this method, an equitoxic dose of S-1 (15 mg/kg/day) and UFT (30 mg/kg/day) was administered p.o. for 14 consecutive days from 7 days after tumor cell implantation. S-1 showed a higher tumor growth inhibition than UFT did [S-1, 57% (significantly different from the tumor weight of the untreated group at P < 0.05) and UFT, 18% (P > 0.05)]. When both drugs were administered to nude rats bearing KM12C injected into the cecal wall for 28 consecutive days at equitoxic doses, the mean survival in the S-1 group was 16 days longer than that in the untreated group (P < 0.01) but that in the UFT group was only 8 days longer (P > 0.05). After the administration of an equitoxic dose of both drugs, S-1 gave the higher levels than UFT in various pharmacokinetic parameters as follows: area under the curve 0-24 h of 5-fluorouracil in plasma (3.5-fold), area under the curve 0-24 h of 5-fluorouracil incorporated into RNA in the tumor (1.3-fold), and thymidylate synthase inhibition rate (percentage) in the tumor (about 20%). Collectively, these findings suggested that this orthotopic human colorectal tumor model in nude rats is useful to evaluate the clinical therapeutic efficacy of drugs or therapies for colorectal cancer, and that S-1 had a higher therapeutic effect on human colorectal tumor than UFT did.

Topics: Adenocarcinoma; Animals; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cell Division; Colonic Neoplasms; Drug Combinations; Fluorouracil; Humans; Neoplasm Metastasis; Neoplasm Transplantation; Oxonic Acid; Prodrugs; Pyridines; Rats; Rats, Nude; RNA; Tegafur; Transplantation, Heterologous