s-1-(combination) and Lung-Neoplasms

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

Lung cancer is the leading cause of cancer-related deaths in the world, and non-small cell lung cancer accounts for > 75% of all lung cancer cases. Cisplatin-based concurrent chemoradiotherapy has become the standard treatment for locally advanced non-small cell lung cancer (NSCLC). Third-generation chemotherapy agents plus cisplatin have been most commonly used in concurrent chemoradiotherapy, which is also associated with more adverse effects and acute toxicities. S-1 as an oral chemotherapeutic agent exhibits higher antitumor activity, less adverse effects, and better biological availability. Recently, studies illustrated S-1-based concurrent chemoradiotherapy also had excellent effects in the treatment of locally advanced NSCLC.. A systematic literature search will be performed through February 2018 using MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, and Google Scholar for relevant articles published in any language. Randomized controlled trials and prospective comparative studies will be included. All meta-analyses will be performed using Review Manager software. The quality of the studies will be evaluated using the guidelines listed in the Cochrane Handbook. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses statements will be followed until the findings of the systematic review and meta-analysis are reported.. The results of this systematic review and meta-analysis will be published in a peer-reviewed journal.. Our study will draw an objective conclusion of the efficacy and safety of S-1-based chemoradiotherapy in the treatment of locally advanced unresectable NSCLC and provides level I evidence for clinical decision makings.

Topics: Antimetabolites, Antineoplastic; Carcinoma, Non-Small-Cell Lung; Chemoradiotherapy; Combined Modality Therapy; Disease-Free Survival; Drug Combinations; Humans; Lung Neoplasms; Neoplasm Staging; Oxonic Acid; Pneumonectomy; Randomized Controlled Trials as Topic; Systematic Reviews as Topic; Tegafur

We performed a meta-analysis to evaluate the efficacy and safety for S-1-based regimens as the first-line treatment in Asian chemotherapy-naive patients with advanced non-small-cell lung cancer.. Eligible randomized clinical trials (RCTs) were included, of which data were extracted by inclusion criteria and exclusion one. Odds ratio and hazard ratio (HR) of outcomes including objective response rate (ORR), progression-free survival (PFS), overall survival (OS) and adverse effects (AEs) were explored for the final analysis.. Twenty-one RCTs including 3263 patients were fit into the analysis. Pooled HR for PFS was 1.01 (95% CI: 0.92-1.10; p = 0.88), the pooled HR for OS was 0.95 (95% CI: 0.85-1.06; p = 0.33) and the pooled odds ratio for ORR was 0.74 (95% CI: 0.61-0.90; p = 0.003). S-1-based regimens showed milder AEs in high-grade nausea/vomit, anorexia, leukopenia, neutropenia and febrile neutropenia (all p < 0.05).. The present study has revealed that S-1-based regimens are accompanied by the similar efficacy and slighter AEs compared with standard regimens as the first-line treatment in Asian chemotherapy-naive patients with advanced non-small-cell lung cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; Asian People; Carcinoma, Non-Small-Cell Lung; Clinical Trials as Topic; Drug Combinations; Humans; Lung Neoplasms; Neoplasm Metastasis; Neoplasm Staging; Odds Ratio; Oxonic Acid; Randomized Controlled Trials as Topic; Tegafur; Treatment Outcome

S-1 is a new oral fluoropyrimidine formulation that comprises tegafur, 5-chloro-2,4-dihydroxypyridine, and potassium oxonate. S-1 is designed to enhance antitumor activity and to reduce gastrointestinal toxicity. Several studies have demonstrated that both S-1 monotherapy and S-1 combination regimens showed encouraging efficacies and mild toxicities in the treatment of lung squamous cell carcinoma and adenocarcinoma. However, it is unclear whether S-1 can be used as standard care in advanced non-small cell lung cancer (NSCLC). The purpose of this meta-analysis was to assess the efficacy and safety of S-1-based chemotherapy, compared with standard chemotherapy, in patients with locally advanced or metastatic NSCLC. Thirteen randomized controlled trials (RCTs) involving 2,134 patients with a similar ratio of different pathological types were included. In first-line or second-line chemotherapy, compared with standard chemotherapy, S-1-based chemotherapy showed similar efficacy in terms of median overall survival (mOS), median progression free survival (mPFS), and objective response rate (ORR) (all P > 0.1), and significantly reduced the incidence of grade ≥ 3 hematological toxicities. In patients with locally advanced NSCLC receiving concurrent chemoradiotherapy, compared with standard chemoradiotherapy, significantly improved survival in the S-1-based chemotherapy was noted in terms of mOS and mPFS (risk radio [RR] = 1.289, P = 0.009; RR = 1.289, P = 0.000, respectively) with lower incidence of grade ≥ 3 neutropenia (RR = 0.453, P = 0.000). The present meta-analysis demonstrates that S-1-based chemotherapy shows similar benefits in advanced NSCLC and improves survival in locally advanced NSCLC, compared with standard treatment.

Topics: Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Chemoradiotherapy; Drug Combinations; Humans; Lung Neoplasms; Oxonic Acid; Publication Bias; Tegafur; Treatment Outcome

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

We performed a meta-analysis of S-1-containing regimens versus control in the management of locally advanced/metastatic non-small-cell lung cancer.. Eligible studies included randomized studies evaluating S-1-containing regimens in the settings of locally advanced, first-line metastatic or second-line metastatic non-small-cell lung cancer.. Pooled odds ratio for overall response rate was 1.09 (95% CI: 0.85-1.38; p = 0.2), the pooled hazard ratio for progression-free survival was 0.98 (95% CI: 0.88-1.09; p = 0.69) and the pooled hazard ratio for overall survival was 0.98 (95% CI: 0.88-1.10; p = 0.75) for S-1-based regimens versus control. Moreover, the relative risk of febrile neutropenia was 0.34 (95% CI: 0.20-0.59; p = 0.0001).. Our meta-analysis has demonstrated that S-1-based regimens are associated with similar efficacy outcomes and better hematological tolerability.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Drug Combinations; Humans; Lung Neoplasms; Neoplasm Metastasis; Neoplasm Staging; Odds Ratio; Oxonic Acid; Tegafur; Treatment Outcome

Gemcitabine-based chemotherapy is widely used for unresectable advanced pancreatic cancer which contains locally advanced and metastatic pancreatic cancer. We performed meta-analysis to examine whether gemcitabine plus S-1 could improve treatment efficacy as first-line chemotherapy for those patients when compared with gemcitabine alone.. STATA was used to estimate the summary hazard ratios or odds ratios and their 95% confidence intervals. Heterogeneity among trials was examined by Cochran's χ(2) test. Publication bias was evaluated by Begg's and Egger's tests. Subgroup analysis based on the extent of disease was performed.. Four randomized controlled trials including 878 Asian patients were analyzed. In total meta-analysis, gemcitabine plus S-1 significantly improved overall survival (hazard ratio, 0.82; 95% confidence interval, 0.70-0.96; P = 0.015), progression-free survival (hazard ratio, 0.64; 95% confidence interval, 0.55-0.74; P < 0.001), overall response rate (odds ratio, 3.00; 95% confidence interval, 2.04-4.41; P < 0.001) and disease control rate (odds ratio, 1.78; 95% confidence interval, 1.32 to 2.39; P < 0.001), and was associated with more but manageable hematologic (leukocytopenia, neutropenia, thrombocytopenia) and non-hematologic (diarrhea, stomatitis, nausea, rash) adverse events. In subgroup analysis, gemcitabine plus S-1, comparing with gemcitabine, significantly improved overall survival in locally advanced patients (hazard ratio, 0.69; 95% confidence interval, 0.48 to 0.99; P = 0.022) but not in metastatic patients (hazard ratio, 0.75; 95% confidence interval, 0.46-1.23; P = 0.256).. This meta-analysis confirmed the survival benefits of gemcitabine plus S-1 as first-line treatment for unresectable advanced pancreatic cancer at least in Asia, while good Eastern Cooperative Oncology group performance status was warranted. Importantly, we highlighted the significant overall survival benefit of gemcitabine plus S-1 in locally advanced patients but not in metastatic patients.

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Asian People; Deoxycytidine; Disease-Free Survival; Drug Administration Schedule; Drug Combinations; Female; Gemcitabine; Humans; Kaplan-Meier Estimate; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Odds Ratio; Oxonic Acid; Pancreatic Neoplasms; Peritoneal Neoplasms; Randomized Controlled Trials as Topic; Research Report; Tegafur; Treatment Outcome

S-1 is an oral fluoropyrimidine derivative, including three pharmacological compounds: tegafur, gimeracil and oteracil, in a molar ratio of 1: 0.4: 1.. This review addresses the clinical evidence of S-1 in NSCLC in various clinical settings. Currently, S-1 for NSCLC is approved only in Japan. Prospective studies of S-1 as front-line and second-line chemotherapy with or without other agents and concurrent chemoradiotherapy are mainly reviewed. Only two Phase III clinical trials were published or presented for advanced NSCLC. S-1 and cisplatin is an active first-line chemotherapy regimen for advanced NSCLC and S-1 and carboplatin is noninferior to a carboplatin and paclitaexel regimen. The combination of S-1 and a platinum agent is active against NSCLC, regardless of tumor histology.. It is becoming possible to design effective regimens with S-1 against NSCLC in various clinical settings considering the ethnic differences in pharmacokinetics and a greater understanding of the underlying molecular pathways or biomarkers of NSCLC. Further Phase III studies with S-1 for both early and advanced NSCLC are warranted worldwide.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Non-Small-Cell Lung; Chemoradiotherapy; Cisplatin; Clinical Trials as Topic; Combined Modality Therapy; Drug Combinations; Humans; Lung Neoplasms; Oxonic Acid; Tegafur

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

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

A 7 4-year-old male was referred to our hospital for an abnormal chest shadow pointed out by a medical examination. A chest computed tomography revealed a tumor shadow 39 X 32mm in size in his left upper lobe in January, 2010. Pathological examination of biopsy specimens showed squamous cell carcinoma of the lung. Although there was no distant metastasis, multiple metastases to mediastinal lymph nodes was noted. He was diagnosed as Stage III A(cT2aN2M0). Considering his age and the histology of the disease, systemic chemotherapy with nedaplatin and S-1 was performed. The diameter of the primary lesion was decreased from 39mm to 18mm after 4 courses of chemotherapy, and was considered as partial response (PR)according to the RECIST criteria. The adverse events were grade 2 appetite loss, grade 3 neutropenia, and grade 2 thrombocytopenia. Recently, various new agents for treating non-squamous cell lung carcinoma have been developed, but there has been little progress in the treatment of squamous cell lung carcinoma. We experienced a patient with advanced squamous cell lung carcinoma who responded with CDGP/S-1 combination chemotherapy. We are now conducting a phase I / II clinical study to verify the usefulness of this regimen against advanced squamous cell lung carcinoma.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Drug Combinations; Humans; Lung Neoplasms; Male; Neoplasm Staging; Organoplatinum Compounds; Oxonic Acid; Tegafur; Tomography, X-Ray Computed

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

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

A 57-year-old man was admitted to our hospital for hepatocellular carcinoma (HCC). He underwent right hepatectomy with preoperative adjuvant transcatheter arterial chemoembolization. A follow-up computed tomography scan revealed a single pulmonary metastasis. After 2 courses of S-1 administration, he underwent left lower lobectomy, and a pathological specimen taken at the time was diagnosed as pulmonary metastasis of HCC. Although adjuvant chemotherapy with S-1 resulted in relapse-free survival for 2 years after pulmonary resection, he was found to have recurrence of liver cancer and underwent partial hepatectomy. This case report suggests that surgical resection and S-1 administration would be a useful treatment option for hepatocellular carcinoma with distant metastasis.

Topics: Antimetabolites, Antineoplastic; Carcinoma, Hepatocellular; Combined Modality Therapy; Drug Combinations; Hepatectomy; Humans; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Tegafur

The prognosis for hepatocellular carcinoma with extrahepatic metastasis or vascular invasion is very poor. We treated a case successfully by combining chemotherapy and liver resection for hepatocellular carcinoma with multiple pulmonary metastases and vascular invasion. A 56-year-old man who complained of abdominal pain in his right side was transported to the hospital by ambulance. Because CT scan revealed the rupture of hepatocellular carcinoma, he underwent emergency transcatheter arterial embolization (TAE). A close examination revealed tumor thrombus in the inferior vena cava and posterior segment of the portal vein branch, with multiple pulmonary metastases. We conducted right hepatic lobectomy and removal of the inferior vena cava tumor thrombus. After the operation, pulmonary metastatic lesions gradually grew larger, so the oral administration of S-1 at 120 mg per day was started. At the end of the first course, the CT scan revealed that multiple pulmonary metastases were significantly reduced, and treatment was maintained until the end of 4 courses. A prolongation of survival could be expected by combining systemic chemotherapy and liver resection for advanced hepatocellular carcinoma such as the present case.

Topics: Antimetabolites, Antineoplastic; Carcinoma, Hepatocellular; Combined Modality Therapy; Drug Combinations; Humans; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Neoplasm Metastasis; Neovascularization, Pathologic; Oxonic Acid; Prognosis; Tegafur

UFT and S-1 are oral 5-fluorouracil (5-FU) derivative drugs containing an inhibitor of dihydropyrimidine dehydrogenase (DPD); they are defined as DPD-inhibitory fluoropyrimidine (DIF). Because DPD is the key enzyme of 5-FU degradation, 5-FU is not active in primary lung cancers with high DPD activity, which causes rapid degradation of 5-FU. Thus, theoretically, a DIF can overcome a cancer's resistance to 5-FU through inhibiting the enzyme activity of DPD, with the result that 5-FU may be active in primary lung cancer. In fact, UFT has proved to be effective in a postoperative adjuvant setting for early non-small-cell lung cancer (NSCLC) in several randomized controlled studies (RCTs). S-1, in which a more potent DPD inhibitor is combined, is active in advanced NSCLC regardless of the histological cell subtype, and its clinical efficacy in first-line therapy for unresectable advanced disease as well as in postoperative adjuvant therapy for resected disease is now being examined in a variety of RCTs. In the present review, the mechanism of action of UFT and S-1 as well as clinical evidence regarding their use in the treatment of NSCLC are summarized.

Topics: Administration, Oral; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Chemotherapy, Adjuvant; Dihydrouracil Dehydrogenase (NADP); Drug Combinations; Drug Resistance, Neoplasm; Enzyme Inhibitors; Evidence-Based Medicine; Humans; Lung Neoplasms; Oxonic Acid; Radiotherapy, Adjuvant; Tegafur; Time Factors; Treatment Outcome; Uracil

S-1 (also known as TS-1; Taiho Pharmaceutical Co. Ltd.; Tokyo, Japan) is a new oral fluoropyrimidine formulation that combines tegafur, 5-chloro-2,4-dihydroxypyridine (CDHP), and potassium oxonate in a molar ratio of 1:0.4:1. Single-agent S-1 has demonstrated marked activity against non-small-cell lung cancer (NSCLC) as well as a broad array of other solid tumors, including gastric, colorectal, breast, cervical, and pancreatic cancers. This comprehensive review summarizes the results of previous clinical studies and describes ongoing clinical trials of S-1 in advanced NSCLC. S-1 combined with platinum compounds, irinotecan, and gemcitabine has produced promising results in terms of feasibility, safety, and effectiveness. Available data have stimulated further research, including phase III trials for the first-line treatment of advanced NSCLC.

Topics: Administration, Oral; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Clinical Trials as Topic; Drug Combinations; Humans; Japan; Lung Neoplasms; Oxonic Acid; Tegafur

S-1 is a newly developed oral anti-tumor agent, which contains 5-chloro-2, 4-dihydroxypyridine and potassium oxonate to strengthen biological activities of 5-fluorouracil. Response rate of S-1 for advanced non-small cell lung cancer was reported to be 12.5-22%. Response rate of combination chemotherapy with S-1 plus cisplatin (CDDP) was reported to be 47%, and the median survival time was 11 months. Adverse events of the combination chemotherapy were milder than other combination chemotherapy described before. Therefore, S-1 plus CDDP combination chemotherapy is a future candidate for phase III clinical study.

Topics: Administration, Oral; Anemia; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Cisplatin; Drug Administration Schedule; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Neutropenia; Oxonic Acid; Remission Induction; Tegafur

The present paper presents a review of the second-line treatment of non-small cell lung cancer (NSCLC) and reports a phase I study of the combination chemotherapy of docetaxel (DOC) and S-1 as second-line chemotherapy. Current options for the second-line treatment of NSCLC include cytotoxic drugs, such as DOC, pemetrexed, and targeted therapies. However, single-agent chemotherapy has shown limited activities. A new treatment approach is needed for this patient population. We hypothesized that combination chemotherapy of DOC and S-1 would be effective through the additive and synergistic activities. We performed a phase I clinical trial of this combination chemotherapy. S-1 was administered orally at a dose of 80 mg/m2 for 14 days, followed by a drug-free interval of a week (one cycle). The starting dose level (level 1) of DOC was set to 40 mg/m2, until a dose of 60 mg/m2 was reached at level 3. Three patients were treated with level 2, in which the dose of DOC was increased up to 50 mg/m2. Two of 3 patients had grade 4 neutropenia, which was determined as dose-limiting toxicity. The dose level of DOC 40 mg/m2 on day 1 in combination with S-1 80 mg/m2 for 14 days of a three week cycle was recommended for a phase II study. Partial response was achieved in 4 of the 9 patients. This combined chemotherapy consisting of S-1 and DOC may prove effective for treating recurrent cases of NSCLC. A phase II study is ongoing.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Docetaxel; Drug Administration Schedule; Drug Combinations; Humans; Lung Neoplasms; Maximum Tolerated Dose; Oxonic Acid; Randomized Controlled Trials as Topic; Taxoids; Tegafur

A 68-year-old man underwent subtotal esophagectomy with two fields lymphadenectomy and postoperative chemotherapy so called low dose FP therapy for advanced esophageal cancer (Stage IIIa, pT 3, pN 1, M 0) in October 1999. As he was diagnosed with a recurrence of esophageal cancer as metastatic lymph node tumors which were placed in the right anterocervical and supraclavicular region in March 2001, he underwent enucleation of metastatic lymph node tumors and postoperative chemoradiation therapy, so-called low-dose FP-R therapy. Recently, since other metastatic lymph node tumors in the neck appeared again in August 2001, he underwent radical neck lymph node dissection and postoperative chemoradiation treatment, so-called FAP-R therapy. In October 2003, a chest CT showed multiple lung tumors. He was diagnosed with multiple metastatic lung tumors originating from esophageal cancer. Then, two courses of a combined chemotherapy consisting of TS-1 and CDDP were administered at an interval of one month. We judged the effect of this chemotherapy to be a partial response (PR), because the largest metastatic lung tumor 18 mm in diameter showed a reduction rate of 81.9%, and other tumors had almost disappeared in the chest CT after the combined therapy. No severe adverse effects of more than grade 3 were observed during this combined therapy. This combined chemotherapy consisting of TS-1 and CDDP may prove effective for treating recurrent cases of esophageal cancer.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cisplatin; Drug Administration Schedule; Drug Combinations; Esophageal Neoplasms; Esophagectomy; Humans; Lung Neoplasms; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Male; Oxonic Acid; Pyridines; Tegafur

Lung cancer is the leading cause of cancer-related death throughout the world including Japan. During the 1990s, new cytotoxic agents such as irinotecan, paclitaxel, docetaxel, vinorelbine, gemcitabine, and amrubicin showed impressive single-agent activity in patients with lung cancer. To date, clinical research has defined the current standard chemotherapy for advanced non-small cell lung cancer (NSCLC) as modern platinum-based doublets considered more efficacious than any single regimen and with no added benefit to triplet therapies. However, we have reached an efficacy plateau with these agents. Rearrangement of the drug combination or change of the drug doses and schedules will not result in significant further progress. New, less toxic agents that improve survival and quality of life are clearly needed. In the last three decades, we have gained a growing understanding of the molecular biologic changes and the complex series of cellular signals that allow cancer cells to manifest behavior. This provides an opportunity to develop novel therapies aimed at inhibiting some of these changes and signals. Targeted agents, primarily the epidermal growth factor receptor inhibitors, have led to a new era in the treatment of NSCLC. This paper will review the current status of cytotoxic agents and molecular targeted therapy in lung cancer potential useful in the treatment of the patients.

Topics: Anthracyclines; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Bevacizumab; Boronic Acids; Bortezomib; Camptothecin; Carcinoma, Non-Small-Cell Lung; Cetuximab; Clinical Trials as Topic; Deoxycytidine; Drug Combinations; Erlotinib Hydrochloride; Furans; Gefitinib; Gemcitabine; Glutamates; Guanine; Humans; Irinotecan; Lung Neoplasms; Oxonic Acid; Pemetrexed; Pyrazines; Pyridines; Quinazolines; Tegafur; Vinblastine; Vinorelbine

Topics: ADP Ribose Transferases; Animals; Antineoplastic Agents; Benzamides; Cisplatin; Drug Combinations; Fluorouracil; Genes, ras; Humans; Imatinib Mesylate; Insect Proteins; Lung Neoplasms; Mice; Neoplasms; Neoplastic Syndromes, Hereditary; Oxonic Acid; Piperazines; Protein-Tyrosine Kinases; Pyridines; Pyrimidines; Signal Transduction; Tegafur; Tumor Cells, Cultured

Cisplatin-based chemoradiotherapy is considered standard treatment for unresectable locally advanced non-small-cell lung cancer (LA-NSCLC). This study examined two regimens of chemotherapy in concurrent chemoradiation. Eligible patients with unresectable, radically irradible LA-NSCLC were randomized to either the SP (S-1 and cisplatin) or DP (docetaxel and cisplatin) arms with concurrent thoracic radiotherapy of 60 Gy, comprising 2 Gy per daily fraction. The primary endpoint was the overall survival (OS) rate at 2 years (the 2-year OS rate). From May 2011 to August 2014, 110 patients were enrolled. Of 106 eligible patients, the 2-year OS rates were 79% (95% CI: 66%-88%) and 69% (95% CI: 55%-80%) the SP and DP arms, respectively. The median progression-free survival was 11.6 months for the SP arm and 19.9 months for the DP arm, while the median survival time was 55.2 months for the SP arm and 50.8 months for the DP arm. Grade 3/4 leukopenia were more frequent in DP arm. The incidences of febrile neutropenia and pneumonitis tended to be higher in DP arm. There were no treatment-related deaths in either arm. The primary endpoint was met in both arms. The SP arm as a future reference regimen will be chosen due to fewer toxicities and better OS.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Chemoradiotherapy; Cisplatin; Docetaxel; Drug Combinations; Female; Follow-Up Studies; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Recurrence, Local; Oxonic Acid; Prognosis; Survival Rate; Tegafur; Thoracic Neoplasms

Combination carboplatin and S-1 is active in the treatment of non-small cell lung cancer (NSCLC). However, data on this combination for elderly patients with NSCLC are insufficient.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Area Under Curve; Carboplatin; Carcinoma, Non-Small-Cell Lung; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Neutropenia; Oxonic Acid; Survival Rate; Tegafur; Thrombocytopenia; Treatment Outcome

A randomized phase 3 study was performed to investigate the efficacy and safety of maintenance therapy with S-1 after induction therapy with carboplatin plus S-1 in patients with advanced squamous non-small cell lung cancer (NSCLC).. Chemotherapy-naive patients with advanced or relapsed squamous NSCLC were treated with carboplatin (area under the curve of 5 on day 1 every 3 weeks) plus S-1 (40 mg/m. Of the 365 patients enrolled in the study, 347 participated in the induction phase, and 131 of these individuals were randomized to receive S-1 plus BSC (n = 67) or BSC alone (n = 64). The risk of disease progression was significantly lower for patients in the S-1 plus BSC arm than those in the BSC-alone arm (hazard ratio, 0.548; 95% confidence interval, 0.374-0.802; P = .0019). The most common toxicities during maintenance therapy with S-1 included anorexia, anemia, and fatigue, but most cases were not severe.. Continued maintenance with S-1 plus BSC is an effective and well-tolerated treatment option for patients with advanced squamous NSCLC previously treated with carboplatin plus S-1.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Squamous Cell; Cisplatin; Drug Combinations; Humans; Induction Chemotherapy; Lung; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Pemetrexed; Progression-Free Survival; Proportional Hazards Models; Tegafur; Treatment Outcome

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Non-Small-Cell Lung; Chemotherapy, Adjuvant; Disease-Free Survival; Drug Combinations; Feasibility Studies; Female; Humans; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Tegafur

A proportion of patients with stage IV non-small-cell lung cancer (NSCLC) is predicted to receive third-line treatment. However, currently no standard third-line treatment for NSCLC is available. Anlotinib is an oral, multi-targeted tyrosine kinase (TK) receptor inhibitor, which was approved as a third-line treatment for stage IV NSCLC in China on May 9, 2018. Nevertheless, The objective response rate of patients treated with anlotinib was merely 9.2% and the overall survival was only 3 months compared with the patients treated with placebo. Previous studies have shown that cancer treatment with a combination of chemotherapy with TK receptor inhibitors is effective and safe well tolerated. Therefore, the combination of anlotinib with other chemotherapeutic agents may be an effective treatment strategy for patients with stage IV NSCLC. Oral S-1 is a third-generation fluorouracil derivative; it showed good efficacy and caused relatively low toxicity in patients with NSCLC.. The purpose of this trial is to evaluate the efficacy and safety of anlotinib combined with S-1 as the third-line treatment for patients with stage IV NSCLC. This is a prospective, phase II clinical trial. We will enroll29 patients with stage IV NSCLC treated with anlotinib plus S-1. Tumors will be assessed using computed tomography prior to treatment, after two, four, and six cycles of treatment, and during follow-up every 3 months until disease progression or death. The primary endpoint is the objective response rate (ORR). The secondary endpoints are progression-free survival, duration of response, proportion of disease control, and safety.. The expected outcome of this study is that anlotinib combined with S-1 has tolerable toxicity and better ORR than anlotinibmonotherapy. The results may indicate additional treatment options for patients with stage IV NSCLC.
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Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Drug Combinations; Female; Follow-Up Studies; Humans; Indoles; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Prognosis; Prospective Studies; Quinolines; Randomized Controlled Trials as Topic; Research Design; Survival Rate; Tegafur; Young Adult

Purpose Our previous phase I trial suggested feasibility of addition of leucovorin (LV) to S-1 and gemcitabine therapy in advanced pancreatic cancer. The aim of this phase II trial was to assess the efficacy and toxicity of gemcitabine, S-1 and LV (GSL) combination therapy for advanced pancreatic cancer. Methods Chemotherapy-naïve patients with histologically or cytologically proven advanced pancreatic cancer were enrolled. Gemcitabine was administered at a dose of 1000 mg/m2 by 30 min infusion on days 1, S-1 40 mg/m2 orally twice daily and LV 25 mg orally twice daily on days 1 to 7 every 2 weeks. Primary end point was progression free survival (PFS). Results A total of 49 patients with advanced pancreatic cancer (19 locally advanced and 30 metastatic) were enrolled. Overall response rate and disease control rate were 32.7% and 87.8%. The median PFS and overall survival (OS) were 10.8 (95% confidence interval [CI], 7.4-13.5) and 20.7 (95% CI 13.0-NA) months with 1-year survival rate of 73.4%. Major Grade 3-4 toxicities were neutropenia (22.4%) and stomatitis (14.3%). No toxicity related death was observed. Conclusions In this single center, phase II trial, gemcitabine, S-1 and LV combination therapy was tolerable and can potentially be a treatment option for advanced pancreatic cancer.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Deoxycytidine; Drug Combinations; Female; Follow-Up Studies; Gemcitabine; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Pancreatic Neoplasms; Peritoneal Neoplasms; Prognosis; Survival Rate; Tegafur

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

Because chemoradiotherapy using cisplatin and S-1, an oral fluoropyrimidine, is effective for unresectable non-small cell lung cancer (NSCLC), an induction setting was used in a multicenter phase II study (Clinical trial number: UMIN000008205). The correlations of relapse and clinicopathological factors were analyzed.. We defined locally advanced NSCLC as pathologically proven chest wall invasion or hilar and/or mediastinal lymph node metastases by endobronchial ultrasound-guided transbronchial needle aspiration. The patients received two courses of S-1 administration for 14 days and intravenous cisplatin injection on day 8. A total dose of 40 Gy radiotherapy was concurrently received. Surgical resection was performed after completion of the treatment.. Of the 23 eligible patients, 18 had stage IIIA and 5 had stage IIB NSCLC. Twenty of the eligible patients (87.0%) completed the regimen. Six (26.1%) complete responses were identified and 12 cases (52.2%) were histopathologically downstaged by induction chemoradiotherapy (ICRT). The 3-year overall survival rate was 58.1% and relapse-free survival (RFS) rate was 52.0%, respectively. Among several clinicopathological parameters, univariate RFS analysis identified that only downstaging was significantly associated with longer RFS times (p = 0.003). The radiological response did not reflect pathological response. When the variables of preoperative pathologically proven N2 metastasis, pathological ICRT effectiveness, and downstaging were included in the Cox proportional hazard modes, only the parameter of downstaging displayed significant hazard ratio (hazard ratio 0.13, p = 0.010).. This protocol is considered an option among preoperative therapies and has obvious benefits for pathologically downstaged cases.. UMIN000008205.. June 19, 2012.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Chemoradiotherapy; Cisplatin; Drug Combinations; Female; Humans; Lung Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Oxonic Acid; Survival Rate; Tegafur

Background Optimal maintenance therapy for lung squamous cell carcinoma (SCC) has not been established. The aim of this study was to evaluate the efficacy and safety of switch maintenance therapy with S-1, an oral fluoropyrimidine, after induction therapy with carboplatin and nanoparticle albumin-bound paclitaxel (nab-paclitaxel) in chemotherapy-naïve patients with advanced SCC. Methods Chemotherapy-naïve patients with advanced SCC received induction therapy with four cycles of carboplatin (at an area under the curve of 6, day 1 of a 28-day cycle) and nab-paclitaxel (100 mg/kg, days 1, 8, and 15). Patients who achieved disease control after induction therapy received maintenance therapy with S-1 (80 mg/m

Topics: Adult; Aged; Aged, 80 and over; Albumins; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Brain Neoplasms; Carboplatin; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Drug Combinations; Female; Follow-Up Studies; Humans; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Maintenance Chemotherapy; Male; Middle Aged; Nanoparticles; Oxonic Acid; Paclitaxel; Prognosis; Survival Rate; Tegafur

The East Asia S-1 Trial in Lung Cancer (EAST-LC) was a randomized phase III study conducted in East Asia that demonstrated the non-inferiority of S-1 to docetaxel in previously treated patients with advanced non-small cell lung cancer (NSCLC). Here, we reported the results of the Japanese subgroup treated with docetaxel 60 mg/m. Patients were randomized 1:1 to receive either S-1 or docetaxel. The primary endpoint was overall survival (OS); the secondary endpoints included progression-free survival (PFS), response rate (RR), quality of life (QOL), and safety.. Patient characteristics in the Japanese subgroup (n = 724) were similar to those in the overall EAST-LC population. Median OS was 13.4 months in the S-1 group and 12.6 months in the docetaxel group. In pemetrexed-pretreated patients, OS with S-1 was similar to that with docetaxel. Median PFS was 2.9 and 3.0 months in the S-1 and docetaxel groups, respectively. RR was 9.4% and 10.3% in the S-1 and docetaxel groups, respectively. The QOL of patients treated with S-1 was better compared with that of patients treated with docetaxel. Decreased appetite and diarrhea were more common in the S-1 group, whereas the frequency of neutropenia and febrile neutropenia was markedly higher in the docetaxel group.. This Japanese subgroup analysis showed that S-1 had similar efficacy to docetaxel in patients with previously treated advanced NSCLC. These results are similar to those of the overall EAST-LC population.

Topics: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Carcinoma, Non-Small-Cell Lung; Disease-Free Survival; Docetaxel; Drug Combinations; Female; Humans; Japan; Lung Neoplasms; Male; Middle Aged; Neutropenia; Oxonic Acid; Quality of Life; Tegafur; Treatment Outcome

We conducted a Phase I/II study of carboplatin, S-1 and concurrent thoracic radiotherapy (TRT) for elderly patients (71 years or older) with unresectable stage III non-small cell lung cancer (NSCLC).. Patients received carboplatin (AUC 3-5) on Day 1 and S-1 (30-40 mg/m2 two times daily) on Days 1-14, every 2 weeks, for up to four cycles, plus concurrent TRT at a total dose of 60 Gy. The primary endpoint for the Phase II study was the 1-year progression-free survival (PFS) rate.. Eighteen patients were enrolled in the Phase I study. Febrile neutropenia, a decreased platelet count and esophagitis were dose-limiting toxicities. The recommended doses for the Phase II study were determined to be an AUC of 3 for carboplatin, 40 mg/m2 twice daily for S-1. Twenty-eight patients were evaluated in the Phase II study. The 1-year PFS rate was 57.1% (90% CI 41.6-71.4%), and the median PFS was 16.8 months (95% CI 7.8-not assessable [NA]). The lower limit of the 90% CI for 1-year PFS exceeded the prespecified threshold value of 30%; therefore, the primary endpoint was met. Grades 3-4 toxicities included thrombocytopenia (21%) and hyponatremia (11%). Grade 3 radiation pneumonitis was observed in 18% of patients. No treatment-related deaths were observed.. Combination chemotherapy consisting of carboplatin plus S-1 and concurrent TRT had a promising efficacy in elderly patients with locally advanced NSCLC; however, radiation pneumonitis was frequently observed.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Non-Small-Cell Lung; Chemoradiotherapy; Drug Combinations; Female; Humans; Leukopenia; Lung Neoplasms; Male; Neoplasm Staging; Oxonic Acid; Paclitaxel; Progression-Free Survival; Radiation Pneumonitis; Tegafur; Treatment Outcome

S-1 plus cisplatin is a standard chemotherapy regimen for advanced non-small cell lung cancer (NSCLC). The addition of bevacizumab has been shown to significantly improve overall survival (OS) in patients with advanced non-squamous (NSq) NSCLC who received carboplatin plus paclitaxel, however, failed to show an OS advantage in patients who received cisplatin plus gemcitabine.. Chemotherapy-naive patients with Stage IIIB, IV or recurrent non-SQ NSCLC were treated with a 3-week cycle of S-1 80 mg/m2 on days 1-14, cisplatin 60 mg/m2 on day 8 and bevacizumab 15 mg/kg on day 8 for 4-6 cycles. Patients without progressive disease (PD) received maintenance bevacizumab 15 mg/kg on day 1 with a 3-week cycle and S-1 80 mg/m2 every other day. The primary endpoint was progression-free survival (PFS). Secondary endpoints were objective response rate (ORR), OS, toxicity profile and Quality of life (QOL).. From June 2013 to January 2015, 39 eligible patients were enrolled from eight institutions. Thirty-one patients (79%) completed four cycles of induction chemotherapy, and maintenance chemotherapy was initiated in 23 patients (59%). Median PFS, OS and ORR were 7.3 months (95% CI: 5.9-8.7), 21.4 months (95% CI: 14.7-not reached) and 64%, respectively. The most common grade 3/4 toxicities were leukopenia (12.8%), neutropenia (23.0%) and hypertension (28.2%). QOL analyses showed detrimental effects after initiation of the regimen.. S-1 plus cisplatin in combination with bevacizumab met the primary endpoint in patients with advanced NSq-NSCLC. RR was anticipated to be high with acceptable toxicities.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Carcinoma, Non-Small-Cell Lung; Cisplatin; Drug Combinations; Female; Humans; Kaplan-Meier Estimate; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Patient Compliance; Quality of Life; Survival Analysis; Tegafur

S-1 is an oral fluoropyrimidine that is active in the treatment of non-small cell lung cancer (NSCLC); however, an optimal treatment schedule and appropriate dose adjustments of S-1 in elderly patients have not yet been established.. We conducted a phase II trial to evaluate the efficacy and safety of a 2-week S-1 monotherapy treatment followed by a 1-week interval as a first-line treatment of elderly NSCLC patients, by adjusting the dose based on the individual creatinine clearance (Ccr) and body surface area (BSA). The primary endpoint was the disease control rate.. Forty patients were enrolled. The disease control and response rates were 89.5% (95% confidence interval [CI] = 79.8-99.2) and 7.9% (95% CI = 0.0-16.4), respectively. The median progression-free survival and overall survival times were 4.4 months (95% CI = 4.2-8.5) and 17.0 months (95% CI = 11.2-18.7), respectively. Neutropenia, anorexia, hyponatremia, hypokalemia, and pneumonia of grade ≥ 3 occurred in 5.0%, 7.5%, 5.0%, 2.5%, and 2.5% of patients, respectively. Among the patient-reported outcomes, most of the individual factors in the patients' quality of life, including upper intestine-related symptoms improved with the treatment, except for dyspnea, which slightly albeit continuously worsened throughout the study.. In elderly patients with previously untreated advanced NSCLC, a 2-week S-1 monotherapy treatment, tailored to both the Ccr and BSA, with a 1-week interval was well tolerated and demonstrated promising efficacy. This study was registered at the University Hospital Medical Information Network (UMIN) Center (ID: UMIN000002035), Japan.

Topics: Administration, Oral; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Body Surface Area; Carcinoma, Non-Small-Cell Lung; Creatinine; Drug Administration Schedule; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Metabolic Clearance Rate; Oxonic Acid; Precision Medicine; Survival Rate; Tegafur; Treatment Outcome

EGFR-tyrosine kinase inhibitors (TKIs) combined with TS-1 might overcome EGFR-TKI resistance, which has been indicated by several preclinical studies. We investigated the synergistic efficacy and safety of the combination therapy of EGFR-TKIs and TS-1 in non-small cell lung cancer (NSCLC) patients with acquired resistance to previous EGFR-TKI therapy.. This was a phase II, single-arm and single-center prospective study. Stage IIIB-IV NSCLC patients with acquired resistance to prior EGFR-TKI treatment were enrolled. All patients were administered combination therapy of TS-1 and continuing EGFR-TKIs in this study. The primary endpoints were progression-free survival (PFS), while overall survival (OS), disease control rate (DCR), and safety were secondary endpoints.. A total of 42 patients with acquired resistance to EGFR-TKIs were eligible for this study. The median PFS for all patients was five months (95% confidence interval [CI] 3.6-5.4). The OS and DCR were 31.9 (95% CI 17.8-46.0) months and 69.0% (29/42), respectively. No grade 4 toxicity or grade 3 hematologic toxicity was observed in this study. One patient (2%) experienced grade 3 elevated total serum bilirubin.. The combination treatment of TS-1 and EGFR-TKIs was effective and well tolerated by patients who had experienced prior EGFR-TKI treatment failure. Our results need to be validated by larger prospective clinical trials.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Disease-Free Survival; Drug Combinations; Drug Resistance, Neoplasm; ErbB Receptors; Humans; Lung Neoplasms; Middle Aged; Oxonic Acid; Protein Kinase Inhibitors; Tegafur; Treatment Outcome

Cisplatin-based chemoradiotherapy is the standard treatment for unresectable, locally advanced non-small-cell lung cancer (NSCLC). This trial evaluated two experimental regimens that combine chemotherapy with concurrent radiotherapy.. Eligible patients with unresectable stage III NSCLC were randomised to either the SP arm (S-1 and cisplatin) or VP arm (vinorelbine and cisplatin), with early concurrent thoracic radiotherapy of 60 Gy, comprising 2 Gy per daily fraction. The primary endpoint was the overall survival rate at 2 years (2-year overall survival (OS)) (Study ID: UMIN000002420).. From September 2009 to September 2012, 112 patients were enroled. Of the 108 eligible patients, the 2-year OS was 75.6% (80% confidence interval (CI), 67-82%) in the SP arm and 68.5% (80% CI: 60-76%) in the VP arm. The hazard ratio (HR) for death between the two arms was 0.85 (0.48-1.49). The median progression-free survival was 14.8 months for the SP arm and 12.3 months for the VP arm with an HR of 0.92 (0.58-1.44). There were four treatment-related deaths in the SP arm and five in the VP arm.. The null hypotheses for 2-year OS were rejected in both arms. The West Japan Oncology Group will employ the SP arm as the investigational arm in a future phase III study.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Chemoradiotherapy; Cisplatin; Dose Fractionation, Radiation; Drug Combinations; Female; Humans; Japan; Lung Neoplasms; Male; Neoplasm Staging; Oxonic Acid; Survival Analysis; Tegafur; Treatment Outcome; Vinorelbine

Platinum-based combination chemotherapy is the standard postoperative adjuvant treatment for pathological stage II/III non-small cell lung cancer (NSCLC). Oral S-1 therapy has good efficacy and relatively low toxicity for the treatment of advanced NSCLC. We investigated whether long-term S-1 monotherapy is also useful as an adjuvant therapy after surgery in patients with NSCLC.. We conducted a phase II randomized open-label multi-institutional study in patients with pathological stage II/IIIA NSCLC (7. A total of 70 and 71 patients were enrolled in S-1 arm and S-1 plus cisplatin arm, respectively. The 2-year DFS rates were 52% (95% confidence interval [CI], 0.40-0.63) and 61% (95% CI, 0.48-0.70) for S-1 arm and S-1 plus cisplatin arm, respectively. Both arms met the primary endpoint. Neither DFS nor OS was significantly different between the arms (log-rank test: P =  0.1695 and P =  0.8684, respectively). The main G3/4 adverse events were loss of appetite and anemia (S-1 vs. S-1 plus cisplatin: 4.3% vs. 11.6% and 0% vs. 5.8%, respectively). The treatment completion rate did not differ between the two arms (S-1 vs. S-1 plus cisplatin: 45.7%, 95% CI, 41.9-66.3% vs. 43.5% 95% CI, 44.0-68.4%).. Long-term adjuvant chemotherapy with S-1 was a feasible and promising treatment for patients with completely resected NSCLC, regardless of cisplatin addition. S-1 monotherapy should be investigated further, based on its low toxicity and practical convenience.

Topics: Aged; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Chemotherapy, Adjuvant; Cisplatin; Drug Combinations; Female; Follow-Up Studies; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Pneumonectomy; Postoperative Period; Tegafur

The clinical benefit of chemotherapy and the appropriate regimen for non-small-cell lung cancer (NSCLC) patients with interstitial lung disease (ILD) remain unclear. To fulfill this unmet medical need, we conducted a phase II study to elucidate the efficacy of S-1 in combination with carboplatin (CBDCA) in NSCLC patients with ILD.. A total of 33 advanced or recurrent NSCLC patients with ILD were prospectively enrolled in this multicenter, open-label, phase II study. Every 4 weeks, CBDCA at a dose of AUC 5 on day 1 and S-1 at a dose of 80 mg/m. The median age at initiating chemotherapy was 70. Sixteen patients (48.5%) had squamous cell carcinoma histology. With respect to the types of ILD, the usual interstitial pneumonia pattern was dominant (66.7%). The median number of cycles administered was 3, and the overall response rate and disease control rate were 33.3% and 78.8%, respectively. The median progression-free survival, the median survival time and the 1-year survival rate were 4.8 months, 12.8 months and 51.4%, respectively. Acute exacerbation of ILD caused by chemotherapy was noted in 2 patients (6.1%).. This is the first prospective study designed to evaluate the efficacy of a specific chemotherapeutic regimen as the primary endpoint in patients with advanced NSCLC with ILD. The combination of S-1 with CBDCA may be a treatment option for advanced NSCLC patients with ILD (The clinical trial registration number: UMIN000011046).

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Disease-Free Survival; Drug Combinations; Female; Humans; Lung Diseases, Interstitial; Lung Neoplasms; Male; Middle Aged; Neoplasm Recurrence, Local; Oxonic Acid; Prospective Studies; Survival Rate; Tegafur

To assess the efficacy and toxicity of S-1 and bevacizumab combination therapy for patients previously treated for advanced non-squamous non-small cell lung cancer (NSCLC).. This was a prospective, multi-center, single-arm phase II study. Patients with non-squamous NSCLC who had experienced progression after cytotoxic chemotherapy were enrolled. Oral S-1 was administered on days 1-14 of a 21-day cycle, and bevacizumab (15 mg/kg) was given intravenously on day 1. Patients received S-1 adjusted on the basis of their creatinine clearance and body surface area. The primary endpoint was response rate (RR); secondary endpoints were progression-free survival (PFS), overall survival (OS), and safety.. We enrolled 30 patients. One patient had never received platinum-based therapy. Five patients had activating mutations of the epidermal growth factor receptor gene, of whom four had received tyrosine kinase inhibitors before this study. The RR was 6.7% [95% confidence interval (CI) 1.8-21.3%], and the disease control rate (DCR) was 80% (95% CI 62.7-90.5%). Median PFS was 4.8 months (95% CI 2.7-6.4 months], and median OS was 13.8 months (95% CI 8.4 months-not applicable). Patients did not experience any Grade 4 toxicity or treatment-related death. Grade 3 hematologic toxicity (anemia) occurred in one patient (3.3%). The main Grade 3 non-hematologic toxicities were anorexia (10%), infection (10%), and diarrhea (6.7%).. The addition of bevacizumab to S-1 was tolerable, but not beneficial for patients with previously treated non-squamous NSCLC. We do not recommend further study of this regimen.

Topics: Adult; Aged; Angiogenesis Inhibitors; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Carcinoma, Non-Small-Cell Lung; Disease-Free Survival; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Prospective Studies; Tegafur; Treatment Outcome

We conducted this single-institute; prospective, non-randomized parallel two-arm phase II study to evaluate the efficacy and safety of switch maintenance chemotherapy with S-1 after induction therapy with a platinum-based regimen in patients with advanced non-small cell lung cancer (NSCLC).. Between July 2010 and January 2014, 79 patients were enrolled, of which 78 were found to be eligible for inclusion in this study. The treatment success rate at three months was 28.2% (90% confidence interval (CI), 7.1-17.1%) in the S-1 group and 64.1% (90% CI, 50.0-76.8%) in the S-1+Bev group. The primary endpoint was met in the S-1+Bev group. The median PFS and OS were 2.6 months and 11.0 months in the S-1 group, and 4.6 months and 19.9 months in the S-1+Bev group, respectively. The most common grade three toxicity was neutropenia (10% incidence in the S-1+Bev group). There were no cases of febrile neutropenia.. Switch maintenance chemotherapy with S-1 in combination with continuation maintenance chemotherapy with bevacizumab yielded modest efficacy with mild and acceptable toxicities.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Biomarkers, Tumor; Carcinoma, Non-Small-Cell Lung; Drug Combinations; Drug Substitution; Female; Humans; Lung Neoplasms; Maintenance Chemotherapy; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Retreatment; Survival Analysis; Tegafur; Treatment Outcome

We conducted a multicenter randomized study of adjuvant S-1 administration schedules for surgically treated pathological stage IB-IIIA non-small cell lung cancer patients.. Patients receiving curative surgical resection were centrally randomized to arm A (4 weeks of oral S-1 and a 2-week rest over 12 months) or arm B (2 weeks of S-1 and a 1-week rest over 12 months). The primary endpoints were completion of the scheduled adjuvant chemotherapy over 12 months, and the secondary endpoints were relative total administration dose, toxicity, and 3-year disease-free survival.. From April 2005 to January 2012, 80 patients were enrolled, of whom 78 patients were eligible and assessable. The planned S-1 administration over 12 months was accomplished to 28 patients in 38 arm A patients (73.7%) and to 18 patients in 40 arm B patients (45.0%, p = 0.01). The average relative dose intensity was 77.2% for arm A and 58.4% for arm B (p = 0.01). Drug-related grade 3 adverse events were recorded for 11% of arm A and 5% of arm B (p = 0.43). Grade 1-3 elevation of bilirubin, alkaline phosphatase, aspartate aminotransferase, and alanine transaminase were more frequently recorded in arm A than in arm B. The 3-year disease-free survival rate was 79.0% for arm A and 79.3% for arm B (p = 0.94).. The superiority of feasibility of the shorter schedule was not recognized in the present study. The conventional schedule showed higher completion rates over 12 months (p = 0.01) and relative dose intensity of S-1 (p = 0.01). Toxicity showed no significant difference among the shorter schedule and the conventional schedule, except for grade 1-3 elevation of bilirubin.. This randomized multicenter study was retrospectively registered with the UMIN-CTR (UMIN000016086, registration date December 30, 2014).

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Carcinoma, Adenosquamous; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Disease-Free Survival; Drug Administration Schedule; Drug Combinations; Feasibility Studies; Female; Humans; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Patient Compliance; Prospective Studies; Tegafur; Treatment Outcome; Young Adult

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

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

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

Postoperative 1-year administration of S-1, an oral derivative of 5-fluorouracil (5-FU), was shown to be feasible in lung cancer. The 5-year survival rates of postoperative patients treated with S-1 adjuvant chemotherapy and the prognostic impact of clinicopathological factors were examined.. The data of 50 patients with curatively resected pathological stage IB to IIIA non-small cell lung cancer, who were treated with S-1 postoperatively, were analyzed. The prognostic impacts of 22 clinicopathological factors including expressions of the 5-FU pathway enzymes were evaluated. A single-nucleotide polymorphism (SNP), i.e. 538G>A (rs17822931), of ABCC11/MRP8, which encodes a 5-FU excretion enzyme that is known as an earwax type determinant, was also evaluated.. The 5-year overall and relapse-free survival rates were 72.5 and 67.5%, respectively. A performance status ≥ 1, lymphatic vessel invasion, blood vessel invasion, and the A/A type of SNP538, which is responsible for the dry earwax type, were significantly associated with shorter relapse-free survivals. In 34 patients who showed a relative performance of 70% or more for chemotherapy, multivariate survival analysis indicated significant hazard ratios only for the A/A type of SNP538 (p = 0.007).. S-1 has sufficient power as adjuvant chemotherapy. However, its effect might be small in the dry earwax type patient group in an adjuvant setting.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; ATP-Binding Cassette Transporters; Carcinoma, Non-Small-Cell Lung; Chemotherapy, Adjuvant; Disease-Free Survival; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Polymorphism, Single Nucleotide; Prognosis; Survival Analysis; Tegafur

S-1, a novel oral fluoropyrimidine, is active in the treatment of non-small cell lung cancer (NSCLC). However, data on S-1 for elderly patients with NSCLC are insufficient.. Eligibility criteria were no prior chemotherapy, stage IIIB or IV NSCLC, performance status 0-1, age >70 years, and adequate hematological, hepatic, and renal functions. Patients received S-1 (40 mg/m(2) twice a day) for 28 consecutive days. This schedule was repeated every 6 weeks. The primary end point was the tumor response rate.. Thirty-two patients were enrolled and 31 patients were evaluable for response. The patients' median age was 80 years (range: 71-88). The response rate was 22.6% (95% CI: 11-38). Neutropenia, anemia, thrombocytopenia, febrile neutropenia, and diarrhea of grade ≥ 3 occurred in 6, 6, 10, 3, and 3%, respectively.. In elderly patients with previously untreated advanced NSCLC, S-1 appears to be well tolerated and demonstrates encouraging activity.

Topics: Aged; Aged, 80 and over; Anemia; Antimetabolites, Antineoplastic; Carcinoma, Non-Small-Cell Lung; Drug Administration Schedule; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Nausea; Neutropenia; Oxonic Acid; Tegafur; Treatment Outcome; Vomiting

In the CATS (Cisplatin And TS-1) randomized trial comparing cisplatin plus either docetaxel (DP arm) or TS-1 (SP arm) in lung cancer, efficacy was found to be equivalent but the global quality of life (QOL) score was higher in the SP arm. The purpose of the current study was to identify which of the adverse events (AEs) contributed to the deterioration of QOL.. QOL and AE data from the CATS trial were used to quantitatively analyze the relationship between deterioration of QOL score and occurrence of AEs. Subtracted values of the QOL score from post-chemotherapy to pre-chemotherapy were fully compared between patients with or without each AE (Student's t test, significance level = 0.001). Multivariate linear regression analysis was also performed. Analysis of variance was performed to identify whether grade of AE(s) might be significantly correlated with the deterioration of the QOL score (significance level of 0.05).. As expected, gastrointestinal (GI) toxicities were associated with worsening of a variety of QOL items in both trial arms, detected by both univariate and multivariate analysis (p < 0.001 and p < 0.0001, respectively). Multivariate analysis unpredictably indicated that an increase in serum bilirubin level was the only AE that was uniquely associated with worsening of physical functioning (p = 0.0002), cognitive functioning (p < 0.0001), and financial problems (p = 0.0005) in the DP arm, although not in the SP arm. GI toxicities tended to be prolonged in the SP arm.. An increase in serum bilirubin level may contribute to the worse global QOL of subjects in the DP arm in the CATS trial. The method we used here may be a unique approach to identify unpredictable AE(s) that worsen the QOL of patients treated by chemotherapy.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bilirubin; Carcinoma, Non-Small-Cell Lung; Cisplatin; Cognition Disorders; Docetaxel; Drug Combinations; Gastrointestinal Diseases; Humans; Lung Neoplasms; Oxonic Acid; Quality of Life; Taxoids; Tegafur

Objectives Maintenance therapy is a standard therapeutic strategy in non-squamous non-small-cell lung cancer. However, there is no consensus regarding the benefit of maintenance therapy for patients with squamous cell lung cancer. We assessed maintenance therapy with S-1, an oral fluoropyrimidine agent, following induction therapy with carboplatin and S-1 in patients with squamous cell lung cancer. Methods In this phase II trial, chemotherapy-naïve patients with squamous cell lung cancer were enrolled to induction therapy with four cycles of carboplatin (at an area under the curve of 5 on day 1) and S-1 (80 mg/m(2)/day on days 1-14) in a 28-day cycle. Patients who achieved disease control after induction therapy received maintenance therapy with S-1 in a 21-day cycle until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival after administration of maintenance therapy. Results Fifty-one patients were enrolled in the study. The median progression-free survival from the start of maintenance therapy was 3.0 months (95 % confidence interval, 2.5-3.5). The most common toxicities associated with maintenance therapy were anemia, thrombocytopenia, and fatigue, but they were not severe. Conclusion S-1 maintenance therapy might be a feasible treatment option in patients with squamous cell lung cancer.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Squamous Cell; Disease-Free Survival; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Tegafur; Treatment Outcome

This phase II trial investigated the efficacy and safety of S-1 plus bevacizumab (SB) after failure of platinum-based chemotherapy in patients with non-squamous non-small cell lung cancer (non-sq NSCLC).. Patients with non-sq NSCLC who had undergone prior platinum-based chemotherapy, regardless of the use of bevacizumab, were eligible. S-1 (80 mg/m(2)) was administered orally twice daily for 14 days, and bevacizumab (15 mg/kg) on day 1 every 3 weeks until disease progression or unacceptable toxicity occurred. The primary endpoint was progression-free survival (PFS).. Twenty-eight patients (14 males and 14 females; median age 62 years; performance status 0/1/2: 21/7/0) were accrued from 4 centers. Almost half (n = 15, 53.6 %) of these had received prior bevacizumab therapy. The median PFS and overall survival were 3.2 months [95 % confidence interval (CI) 2.2-4.0 months] and 11.4 months (95 % CI 8.9-13.9 months), respectively. Prior exposure to bevacizumab did not affect the PFS. An objective response was observed in 4 patients, the response rate and disease control rate being 14.3 and 85.7 %, respectively. The treatment was well tolerated, the most common treatment-related side effects being anorexia (75 %) and fatigue (68 %).. Although SB was well tolerated, this combination did not provide any additional benefit in terms of PFS for patients with non-sq NSCLC after failure of platinum-based chemotherapy. It will be important to clarify the most suitable agent for use with bevacizumab, and the optimal timing of bevacizumab therapy for lung cancer.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Carcinoma, Non-Small-Cell Lung; Disease-Free Survival; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Platinum Compounds; Survival Rate; Tegafur; Treatment Failure; Treatment Outcome

The aim of this study was to investigate the efficacy and safety of S-1 plus cisplatin combined with concurrent radiotherapy (SCCCR) versus cisplatin alone combined with concurrent radiotherapy (CCCR) in Chinese patients with unresectable stage III nonsmall-cell lung cancer (NSCLC).. Between January 2012 and December 2014, 72 eligible Chinese patients with NSCLC were included and randomly divided into 2 groups, each having 36 patients. Patients in the SCCCR group received S-1 plus cisplatin with concurrent, radiotherapy. The other 36 patients in the CCCR group were administered cisplatin with concurrent radiotherapy. The primary outcome was the overall response rate. The secondary outcomes were overall survival (OS), progression-free survival (PFS), and adverse events.. The 3-year overall response rates for the SCCCR and CCCR groups were 60.1% and 53.3%, respectively (P = 0.041). The median OS was 35.1 (range, 6.5-47.2) months and 24.6 (range, 2.8-24.3) months for the SCCCR and CCCR groups, respectively (P = 0.016). The median PFS for the SCCCR and CCCR groups was 31.4 (range, 5.6-39.3) months and 22.3 (range, 2.4-36.5) months, respectively (P = 0.023). The toxicity profiles were similar for both groups.. The efficacy and safety of SCCCR was more encouraging compared to those of CCCR in Chinese NSCLC patients. In addition, the toxicities in both groups were tolerable.

Topics: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Carcinoma, Non-Small-Cell Lung; Cisplatin; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Tegafur

Although cisplatin-based chemotherapy combined with thoracic irradiation (TRT) is a standard treatment for unresectable, locally advanced non-small cell lung cancer (NSCLC), this treatment outcome has remained unsatisfactory. We had previously conducted a phase I trial of cisplatin plus S-1, an oral 5-fluorouracil derivative, and TRT, which were safe and effective.. In this phase II trial, 48 patients with stage III NSCLC received cisplatin (40mg/m(2) on days 1, 8, 29 and 36) and S-1 (80mg/m(2) on days 1-14 and 29-42) and TRT (60Gy). The primary endpoint was the response rate.. A partial response was observed in 37 patients (77%; 95% confidence interval: 63-88%). At a median follow up of 54 months, the median progression-free survival and median survival time were 9.3 and 31.3 months, respectively. No difference in efficacy was observed when the patients were stratified by histology. Toxicities were generally mild except for grade 3 or worse febrile neutropenia and pneumonitis of 8% and 4%, respectively. No patient developed severe esophagitis. At the time of this analysis, 35 (73%) of the 48 patients recurred; 15 (31%) showed distant metastasis, 17 (35%) had loco-regional disease, and 2 (4%) showed both loco-regional disease and distant metastasis.. This chemoradiotherapy regimen yielded a relatively favorable efficacy with mild toxicities in patients with locally advanced NSCLC.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Chemoradiotherapy; Cisplatin; Disease Progression; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Oxonic Acid; Radiotherapy; Radiotherapy Dosage; Retreatment; Survival Analysis; 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

This Phase II study was conducted to evaluate the efficacy and safety of S-1 and irinotecan combination therapy as a second-line treatment in patients with advanced non-small cell lung cancer.. Irinotecan was administered at 60 mg/m(2) on Days 1 and 8. Oral S-1 was administered on Days 1-14 every 3 weeks at 80 mg/day for patients with a body surface area of <1.25 m(2), 100 mg/day for patients with a body surface area of 1.25-1.5 m(2) and 120 mg/day for patients with a body surface area of >1.5 m(2). The primary endpoint was response rate, while the secondary endpoints were progression-free survival, overall survival and safety.. Thirty-one patients were enrolled in this study. The response and disease control rates were 6.5 and 58.1%, respectively. Progression-free survival and median survival time were 2.8 and 12.6 months, respectively. Grade 3-4 adverse events were reported for 29.0% of the patients. Hematological toxicities of Grade 3 or 4 included leukopenia (9.7%), neutropenia (9.7%), febrile neutropenia (3.2%), thrombopenia (3.2%) and anemia (6.5%). Non-hematological toxicities of Grade 3 or 4 included pneumonitis (6.5%), diarrhea, colitis, dyspnea, rash, oral mucositis, anorexia and pulmonary thromboembolism/deep vein thrombosis (3.2% each).. S-1 and irinotecan combination therapy at the present dose and schedule exhibited only modest efficacy with mild toxicities in previously treated patients with non-small cell lung cancer. No further clinical investigation with current dose and schedules is warranted for patients with non-small cell lung cancer who failed first-line platinum-based doublet chemotherapy.

Topics: Adult; Aged; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Carcinoma, Non-Small-Cell Lung; Drug Combinations; Female; Humans; Irinotecan; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Survival Analysis; Tegafur; Young Adult

Gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), is an effective treatment for advanced non-small cell lung cancer (NSCLC) in patients with activating EGFR mutations. However, there have been little evidence-based studies of gefitinib in combination with platinum-doublet therapy in these patients. We performed a phase II trial to determine the efficacy and safety of triplet chemotherapy with gefitinib, carboplatin, and S-1 as a first-line treatment. This was a multicentre, single-arm, phase II trial of carboplatin, S-1, and gefitinib in advanced NSCLC patients with activating EGFR mutations. Patients received four courses of these drugs in 3-4 week cycles. In each cycle, carboplatin (area under curve = 5) was administered on day 1, S-1 (80 mg/m(2)) on days 1-14, and gefitinib (250 mg) every day. Subsequently, the same regimen without carboplatin was administered until disease progression or unacceptable toxicity occurred. The 1-year progression-free survival (PFS) was the primary endpoint, while response rate (RR), PFS, overall survival (OS), and safety were secondary endpoints. Thirty-five patients were enrolled into this study. The 1-year PFS was 74.3% and the overall RR was 85.7%. The median PFS for all patients was 17.6 months (95% confidence interval 15.5-∞), but the median OS was not reached, because 28 patients were still alive after a median follow-up time of 21.4 months. Haematological adverse events (grade 3 or higher) included neutropaenia (17.1%), thrombocytopenia (14.3%), and anaemia (5.7%), while non-haematological adverse events (grade 3 or higher) included elevated aminotransferase (20.0%), diarrhoea (14.3%), and febrile neutropaenia (2.9%). No interstitial lung disease or treatment-related deaths occurred. Combination chemotherapy with carboplatin, S-1, and gefitinib is efficacious and well tolerated as a first-line treatment in advanced NSCLC patients with activating EGFR mutations.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Non-Small-Cell Lung; Disease-Free Survival; Drug Combinations; ErbB Receptors; Female; Gefitinib; Humans; Lung Neoplasms; Male; Middle Aged; Mutation; Oxonic Acid; Quinazolines; Tegafur; Treatment Outcome

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

This randomized phase II trial investigated the efficacy and safety of docetaxel plus bevacizumab and S-1 plus bevacizumab in the second-line treatment of non-squamous (non-Sq) non-small-cell lung cancer (NSCLC).. Patients with non-Sq NSCLC who experienced disease progression after prior platinum-based chemotherapy with or without bevacizumab were randomly assigned to receive docetaxel plus bevacizumab (DB) once every 3 weeks or S-1 orally twice daily on days 1-14 plus bevacizumab (SB) on day 1 every 3 weeks until disease progression.. Ninety patients were randomized. The median progression-free survival (PFS) was 3.9 months (95% confidence interval [CI]=3.0-6.5) in DB and 3.5 months (95% CI=2.9-5.9) in SB. The objective response rate was significantly higher in DB than in SB (22.2% vs. 2.2%; P=0.004), whereas the disease control rates of the arms were identical (62.2% vs. 62.2%; P=1.00). Patients receiving DB were more likely to have ≥grade 3 neutropenia (93.4% vs. 4.4%) and febrile neutropenia (33.3% vs. 0%) than SB. In DB, PFS and overall survival (OS) were significantly longer among bevacizumab-naïve patients than among bevacizumab-experienced patients (median PFS: 7.2 vs. 2.9 months; P=0.004; and median OS: 21.3 vs. 14.1 months; P=0.012).. DB and SB produced modest PFS benefits in the second-line treatment of patients with advanced non-Sq NSCLC. Because of the toxicity of DB and the low response rate of SB, neither regimen warrants further investigation, excluding DB in bevacizumab-naïve patients with advanced non-Sq NSCLC.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Carcinoma, Non-Small-Cell Lung; Docetaxel; Drug Combinations; Female; Humans; Kaplan-Meier Estimate; Lung Neoplasms; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Oxonic Acid; Platinum; Retreatment; Taxoids; Tegafur; Treatment Outcome

The aims of this study were to evaluate the efficacy and safety of S-1 versus cisplatin (CDDP)+S-1 in patients with completely resected stage II and IIIA non-small cell lung cancer, and to identify predictive biomarkers whose expression in the tumors was significantly associated with patient outcome.. A total of 200 patients were randomly assigned to receive either S-1 (40 mg/m(2) twice per day) for 2 consecutive weeks repeated every 3 weeks for 1 year (S group) or CDDP (60 mg/m(2)) on day 1 plus oral S-1 (40 mg/m(2) twice per day) for 2 consecutive weeks repeated every 3 weeks for four cycles (CS group) within 8 weeks after surgery. The primary endpoints were relapse-free survival (RFS) at 2 years and identification of predictive biomarkers whose expressions have been reported to be associated with CDDP or fluoropyrimidine sensitivity.. The RFS rate at 2 years was 65.6% (95% confidence intervals; CI, 55.3-74.0%) in the S group and 58.1% (95% CI, 47.7-67.2%) in the CS group. The only gene with interaction of P < 0.05 was uridine monophosphate synthase (UMPS; P = 0.0348). The benefit that members of the S group had over members of the CS group was higher expression of UMPS. In vitro and in vivo experiments confirmed that overexpression of UMPS enhanced the antitumor effect of fluoropyrimidine.. Adjuvant S-1 monotherapy might be preferable to CDDP+S-1 for patients with completely resected NSCLC. UMPS expression may define a patient subset that would benefit from long-term postoperative S-1 monotherapy.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Biomarkers; Carcinoma, Non-Small-Cell Lung; Chemotherapy, Adjuvant; Cisplatin; Combined Modality Therapy; Drug Combinations; Drug Resistance, Neoplasm; Female; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Prognosis; Tegafur; Treatment Outcome; Young Adult

This study was conducted to evaluate the efficacy and safety of S-1 in patients with advanced non-small-cell lung cancer (NSCLC), receiving two or more prior chemotherapy regimens.. S-1 was administered orally for 14 consecutive days, followed by a 7-day rest period. This treatment course was repeated until disease progression or intolerable toxicity occurred.. From 2010 to 2012, 45 patients were enrolled in this study. Of the 45 patients, 4 patients [8.9 %, 95 % confidence interval (CI) 0.6-17.2 %] exhibited a partial response and 24 patients (53.3 %) exhibited stable disease. The disease control rate was 62.2 % (95 % CI 48.1-76.4 %). Median progression-free survival was 71 days, and median survival time was 205 days. Four patients had grade 3 hematological toxicities, but toxicities of grade 4 were not observed in this study.. Although S-1 monotherapy as third-line treatment or beyond was well tolerated, the response rate for this regimen did not demonstrate sufficient activity for patients with advanced NSCLC.

Topics: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Carcinoma, Non-Small-Cell Lung; Disease-Free Survival; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Tegafur

Archival formalin-fixed, paraffin-embedded (FFPE) tumor specimens were collected from advanced NSCLC patients enrolled in LETS phase III trial comparing first-line S-1/carboplatin with paclitaxel/carboplatin and subjected to multiplex genotyping for 214 somatic hotspot mutations in 26 genes (LungCarta Panel) and 20 major variants of ALK, RET, and ROS1 fusion genes (LungFusion Panel) with the Sequenom MassARRAY platform. MET amplification was evaluated by fluorescence in situ hybridization. A somatic mutation in at least one gene was identified in 48% of non-squamous cell carcinoma and 45% of squamous cell carcinoma specimens, with EGFR (17%), TP53 (11%), STK11 (9.8%), MET (7.6%), and KRAS (6.2%). Mutations in EGFR or KRAS were associated with a longer or shorter median overall survival, respectively. The LungFusion Panel identified ALK fusions in six cases (2.5%), ROS1 fusions in five cases (2.1%), and a RET fusion in one case (0.4%), with these three types of rearrangement being mutually exclusive. Nine (3.9%) of 229 patients were found to be positive for de novo MET amplification. This first multiplex genotyping of NSCLC associated with a phase III trial shows that MassARRAY-based genetic testing for somatic mutations and fusion genes performs well with nucleic acid derived from FFPE specimens of NSCLC tissue.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Non-Small-Cell Lung; DNA Mutational Analysis; Drug Combinations; Female; Gene Expression Profiling; Humans; In Situ Hybridization, Fluorescence; Kaplan-Meier Estimate; Lung Neoplasms; Male; Mass Spectrometry; Middle Aged; Multiplex Polymerase Chain Reaction; Mutation; Oxonic Acid; Paclitaxel; Tegafur

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

Although thoracic irradiation (TRT) is a standard treatment for elderly patients with locally advanced non-small-cell lung cancer (LA-NSCLC), treatment outcomes are poor. We previously reported a phase I trial combining S-1, an oral 5-fluorouracil derivative, and thoracic radiation, which yielded safe and effective outcomes.. In this phase II trial, 30 patients aged 76 years or older with LA-NSCLC received S-1 (80 mg/m(2) on days 1-14 and 29-42) and TRT (60Gy). The primary end-point was the response rate.. The median age and pre-treatment Charlson score were 79 years and 1, respectively. The mean proportions of the actual doses of S-1 and TRT delivered relative to the planned doses were 95% and 98%, respectively. Partial responses were observed in 19 patients (63%; 95% confidence interval: 45-82%), which did not attain the end-point. At a median follow-up time of 23.7 months, the median progression-free survival and median survival times were 13.0 months and 27.9 months, respectively. No difference in efficacy was observed upon stratification by tumour histology. Toxicities were generally mild, except for grade 3 or greater febrile neutropenia and pneumonitis in 7% and 10% of patients, respectively. No patient developed severe oesophagitis.. Although the primary end-point was not met, concurrent S-1 chemotherapy and radiotherapy yielded favourable survival data. Also, the combined treatment was well-tolerated in elderly patients with LA-NSCLC.

Topics: Aged; Aged, 80 and over; Carcinoma, Non-Small-Cell Lung; Disease Progression; Disease-Free Survival; Drug Combinations; Female; Fluorouracil; Humans; Lung Neoplasms; Male; Neoplasm Metastasis; Oxonic Acid; Recurrence; Tegafur; Tomography, X-Ray Computed; 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

A previous phase 3 trial demonstrated noninferiority in terms of overall survival for combined S-1 (an oral fluoropyrimidine) and carboplatin compared with combined paclitaxel and carboplatin as first-line treatment for advanced non-small cell lung cancer (NSCLC). In the current study, the authors evaluated the efficacy and safety of combined S-1, carboplatin, and bevacizumab followed by maintenance with S-1 and bevacizumab in chemotherapy-naive patients with advanced nonsquamous NSCLC.. Patients received carboplatin (area under the concentration-time curve, 5 mg mL(-1) per minute) and bevacizumab (15 mg/kg) on day 1 plus oral S-1 (80 mg/m2 per day) on days 1 through 14 every 21 days for up to 6 cycles. For patients without disease progression, S-1 and bevacizumab were continued until disease progression or unacceptable toxicity developed.. Forty-eight patients were enrolled in the phase 2 study; of these, 35 patients (72.9%) completed at least 4 cycles. Most toxicities of grade ≥3 were hematologic, and no increase in relative incidence associated with maintenance with S-1 and bevacizumab was observed. The objective response rate was 54.2% (95% confidence interval, 39.2%-68.6%), and the median progression-free survival was 6.8 months (95% confidence interval, 4.3-8.2 months).. The regimen of combined S-1, carboplatin, and bevacizumab followed by maintenance with S-1 and bevacizumab was active and feasible as first-line treatment for advanced nonsquamous NSCLC.

Topics: Adult; Aged; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Carboplatin; Carcinoma, Non-Small-Cell Lung; Disease-Free Survival; Drug Administration Schedule; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Tegafur; Treatment Outcome

The purpose of this study was to evaluate the feasibility and compliance of adjuvant chemotherapy of S-1 plus carboplatin for patients with completely resected non-small cell lung cancer (NSCLC) of pathological stage IB-IIIB.. S-1 was given orally at a dose of 80 mg/m²/day for 2 weeks, followed by a 2-week period of no treatment. Carboplatin was given intravenously on day 8 at an area under the curve of 6. This regimen was repeated for four to six 28-day courses.. Seventeen patients were enrolled in this study. Fourteen of them completed at least 4 cycles of chemotherapy. Nine patients had grade 2 and three patients had grade 3 thrombocytopenia, respectively. Severe nonhematologic toxicities were uncommon. Treatment was delayed in a few patients because of prolonged thrombocytopenia.. We concluded that the regimen was feasible and tolerable for patients with completely resected NSCLC as adjuvant chemotherapy.

Topics: Aged; Antineoplastic Agents; Area Under Curve; Carboplatin; Carcinoma, Non-Small-Cell Lung; Chemotherapy, Adjuvant; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; ROC Curve; Tegafur; Thrombocytopenia; Treatment Outcome

We conducted a multicentre feasibility study for single agent long-term S-1 chemotherapy following docetaxel plus cisplatin in patients with curatively resected stage II-IIIA non-small cell lung cancer.. Patients received three cycles of docetaxel (60 mg m(-2)) plus cisplatin (80 mg m(-2)) and then received S-1 (40 mg m(-2) twice daily) for 14 consecutive days with a 1-week rest for >6 months (maximum, 1 year). The primary end point was feasibility, which was defined as the proportion of patients who completed eight or more cycles of S-1 chemotherapy. If the lower 95% confidence interval (CI) of this proportion was 50% or more, then the treatment was considered as feasible. The sample size was set at 125 patients.. One hundred and thirty-one patients were enrolled, of whom 129 patients were eligible and assessable. In all, 109 patients (84.5%) completed 3 cycles of docetaxel plus cisplatin and 66 patients (51.2%, 95% CI: 42.5-59.8) completed 8 or more cycles of S-1 treatment. Grade 3/4 toxicities during the S-1 chemotherapy included anaemia (7.3%), neutropaenia (3.7%), and anorexia (3.7%).. The toxicity level was acceptable, although the results did not meet our criterion for feasibility. Modification of the treatment schedule for S-1 chemotherapy might improve the treatment compliance.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Chemotherapy, Adjuvant; Cisplatin; Docetaxel; Drug Administration Schedule; Drug Combinations; Feasibility Studies; Female; Humans; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Taxoids; Tegafur; Young Adult

To determine the efficacy and safety of oral S-1 in combination with cisplatin and thoracic radiotherapy in patients with unresectable stage III non-small-cell lung cancer (NSCLC).. S-1 (50mg/m(2)) was administered orally twice daily for 14 days, with cisplatin (40 mg/m(2)) on days 1 and 8 of each cycle every 3 weeks, for 2-4 cycles. Thoracic radiation therapy was administered in 2 Gy fractions five times weekly for a total dose of 60 Gy. The primary endpoint was the response rate, and secondary endpoints included progression-free survival, overall survival and safety.. Forty-one patients were enrolled in this study. The objective response rate was 87.8% (98% CI: 77.8-97.8%). The median progression-free survival was 467 days (15.4 months), and the median survival time was 904 days (29.7 months). The overall survival rates at 1- and 2-years were 85.7% and 52.9%, respectively. Hematological toxicities included grade 3/4 neutropenia (17%) and grade 3/4 leukopenia (27%). No grade 3 febrile neutropenia was detected, and grade 3/4 non-hematological toxicities were also mild. A grade 3 gastrointestinal hemorrhage was observed in one patient.. The combination of oral S-1 plus cisplatin with concurrent radiotherapy is a promising treatment with a high efficacy and lower toxicity in patients with locally advanced NSCLC.

Topics: Adult; Aged; Carcinoma, Non-Small-Cell Lung; Chemoradiotherapy; Cisplatin; Disease-Free Survival; Drug Combinations; Female; Humans; Leukopenia; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Neutropenia; Oxonic Acid; Tegafur

A phase I study was performed to evaluate dose-limiting toxicity and the recommended dose for the oral fluoropyrimidine S-1 administered concurrently with thoracic radiotherapy (TRT) in elderly (≥ 70 years of age) patients with locally advanced non-small cell lung cancer.. S-1 was administered on days 1 to 14 and 22 to 35 at oral doses of 65 or 80 mg m(-2) day(-1). TRT was administered in 2-Gy fractions five times weekly for a total dose of 60 Gy. Twelve previously untreated patients were treated with S-1 at 65 (n=6) or 80 (n=6) mg m(-2) day(-1).. All patients completed the planned 60 Gy of TRT. Dose-limiting toxicity included pneumonitis (n=2), infection (n=1), and stomatitis (n=1), each of grade 3, but each event was reversible. The recommended dose for S-1 was determined to be 80 mg m(-2) day(-1). No patient experienced toxicity of grade 4. The dose intensity of S-1 was well maintained and the combination of S-1 plus TRT was well tolerated overall. The overall response rate was 83.3 %, with a median survival time of 34.0 months.. Administration of S-1 at 80 mg m(-2) day(-1) on days 1 to 14 and 22 to 35 can be safely combined with concurrent TRT in elderly patients with locally advanced non-small cell lung cancer.

Topics: Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Carcinoma, Non-Small-Cell Lung; Dose-Response Relationship, Drug; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Maximum Tolerated Dose; Oxonic Acid; Tegafur

A phase III study (Lung Cancer Evaluation of TS-1) previously demonstrated noninferiority in terms of overall survival (OS) at interim analysis for carboplatin-S-1 compared with carboplatin-paclitaxel for first-line treatment of advanced non-small-cell lung cancer (NSCLC).. A total of 564 patients were randomly assigned to receive either carboplatin on day 1 plus oral S-1 on days 1-14 or carboplatin-paclitaxel on day 1 every 21 days. Updated results and post hoc subgroup analysis according to tumor histology are presented.. The updated analysis revealed a median OS of 15.2 months in the carboplatin-S-1 arm and 13.1 months in the carboplatin-paclitaxel arm, with a hazard ratio (HR) of 0.956 [95% confidence interval (CI) 0.793-1.151], consistent with the previous primary analysis. Median OS was 14.0 months in the carboplatin-S-1 arm and 10.6 months in the carboplatin-paclitaxel arm (HR 0.713; 95% CI 0.476-1.068) for patients with squamous cell carcinoma (SCC), with corresponding values of 15.5 and 13.9 months (HR 1.060; 95% CI 0.859-1.308) for those with non-SCC.. These results establish the efficacy and safety of carboplatin-S-1 in patients with advanced NSCLC regardless of tumor histology.

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Non-Small-Cell Lung; Cross-Linking Reagents; Disease-Free Survival; Drug Combinations; Female; Humans; Japan; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Paclitaxel; Tegafur; Treatment Outcome; Young Adult

Both amrubicin (Am) and S-1 are effective against non-small-cell lung cancer (NSCLC), and preclinical studies have demonstrated that the effect of tegafur/uracil, the original compound of S-1, in combination with Am significantly inhibits tumor growth.. We conducted a phase I/II study of Am and S-1 against pretreated NSCLC without EGFR mutation. We fixed the dose of S-1 at 40 mg/m(2) on days 1-14 and escalated the Am dose in increments of 5 mg/m(2) from a starting dose of 30 mg/m(2)/day on days 1-3 and repeated the cycle every 4 weeks.. Twenty-six patients were registered. In phase I, at an Am dose of 35 mg/m(2)/day, three patients experienced grade 2 leukopenia during S-1 administration, and S-1 was withdrawn. Another patient developed grade 2 serum bilirubin in the first cycle. DLTs were observed in four of six patients at this dose level, and therefore, 30 mg/m(2)/day was set as the recommended dose for Am. Twenty patients received this recommended Am dose. Febrile neutropenia was observed in two patients, and one patient developed a grade 4 increase in serum creatinine. Grade 3 vomiting, infection, hypotension, and urinary retention were observed in one patient each, respectively. Other toxicities were mild, and there were no treatment-related deaths. Two patients showed a CR, three showed a PR, and the overall response rate was 25.0%. The median progression-free and the median survival times were 3.8 and 15.6 months, respectively, and the 1-year survival rate was 60%.. Am and S-1 every 4 weeks is an effective combination for pretreated NSCLC without EGFR mutation.

Topics: Adult; Aged; Anthracyclines; Antibiotics, Antineoplastic; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Disease-Free Survival; Dose-Response Relationship, Drug; Drug Combinations; ErbB Receptors; Female; Humans; Kaplan-Meier Estimate; Lung Neoplasms; Male; Middle Aged; Mutation; Oxonic Acid; Survival Analysis; Tegafur

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

S-1, an oral fluoropyrimidine derivative, has previously demonstrated anticancer efficacy in pancreatic cancer (PC), predominantly in Asian populations. This study evaluated the antitumor effect and safety of S-1 in Caucasian patients with metastatic PC.. Chemotherapy-naïve patients received S-1 orally at 30 mg/m(2) twice daily (BID) for 2 weeks, repeated every 3 weeks. Primary endpoint was ORR. Secondary endpoints included PFS, OS and safety assessment. The trial had a Simon's two-stage design with 22 patients evaluable for efficacy in stage 1 and an additional 18 patients in stage 2, if ≥3/22 patients had a confirmed response at the first stage.. Three out of 27 patients showed PR, however, detection of asymptomatic brain metastases in one of them prevented this study from proceeding to stage 2. The median PFS and OS for all patients was 3.5 and 9.1 months, respectively. The median duration of disease control for patients with SD or PR (n = 17) was 4.3 months. S-1 was well tolerated; fatigue was the most frequent grade 3/4 adverse event.. Efficacy data of PFS and OS are at least comparable to gemcitabine, the current standard of care. S-1 is active in Caucasian patients with metastatic PC.

Topics: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Bone Neoplasms; Drug Combinations; Female; Humans; Liver Neoplasms; Lung Neoplasms; Lymph Nodes; Male; Middle Aged; Oxonic Acid; Pancreatic Neoplasms; Tegafur

In this phase II clinical trial, we evaluated the efficacy and safety of S-1 monotherapy in patients with previously treated advanced non-small-cell lung cancer (NSCLC). We also measured plasma concentrations of 5-fluorouracil (5-FU) and 5-chloro-2,4-dihydroxypyridine components of S-1 and examined correlation with effectiveness and toxicity.. S-1 was given orally at a dose of 80 mg/m(2)/day for 14 consecutive days, followed by a 7-day rest period. This treatment course was repeated until disease progression or intolerable toxicity.. We enrolled 30 patients. The response rate was 26.7% (8/30), and the disease control rate was 70% (21/30). Median progression-free survival (PFS) was 3.1 months, and median overall survival (OS) was 11.2 months. Mutations in the epidermal growth factor receptor (EGFR) gene were analyzed in 27 patients. The response rate was higher in patients with mutant EGFR (50.0%) than in those with wild-type EGFR (11.8%, P = 0.0288). Median PFS was 4.8 and 2.5 months (P = 0.038), and median OS was 22.4 and 8.4 months (P = 0.071). There was no grade 4 toxicity in this study. Five patients had grade 3 non-hematologic toxicity, and there was a trend toward higher plasma concentrations of 5-FU in those patients than in another patients.. S-1 monotherapy is effective and well-tolerated treatment for previously treated advanced NSCLC.

Topics: Aged; Antimetabolites, Antineoplastic; Carcinoma, Non-Small-Cell Lung; Disease Progression; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Survival Rate; Tegafur; Treatment Outcome

To evaluate the efficacy and feasibility of the consolidation therapy of the oral fluoropyrimidine agent S-1 after concurrent chemoradiotherapy for unresectable stage III non-small cell lung cancer (NSCLC).. Eligible patients had unresectable stage III NSCLC with performance status of 0 or 1. Chemoradiotherapy at a total dose of 60 Gy consisted of cisplatin (80 mg/m(2)) on days 1 and 29, vinorelbine (20 mg/m(2)) on days 1, 8, 29 and 36. Sequential consolidation S-1 therapy was commenced at a dose of 80-120 mg twice daily on day 57 with two cycles of 4 weeks administration and 2 weeks withdrawal.. Of the 66 patients, 65 were evaluated. Chemoradiotherapy was completed in 57 (87.7%) patients, and S-1 consolidation therapy was administered in 45 (69.2%) and completed in 31 (47.6%). Grade 3 pneumonitis developed in three patients with one dying of it. The response rate was 61.5% (95% confidence interval [CI], 48.6-73.3%). The median progression-free survival was 10.2 (95%CI, 8.6-13.7) months and median survival time 21.8 (95%CI, 15.6-27.6) months. The 1- and 3-year survival rates were 73.9% and 34.0%, respectively.. Chemoradiotherapy with cisplatin and vinorelbine followed by S-1 consolidation demonstrated a reasonable overall survival in patients with stage III NSCLC. However, less than half of the patients completed this regimen, and the additional effect of S-1 was marginal compared with historical control. We concluded that chemoradiotherapy alone is still the recommended standard treatment for patients.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Chemoradiotherapy; Cisplatin; Combined Modality Therapy; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Grading; Neoplasm Staging; Oxonic Acid; Tegafur; Treatment Outcome; Vinblastine; Vinorelbine

S-1, an oral fluoropyrimidine, is usually given for 4 weeks (80 mg/m2/day) followed by a 2-week rest. However, compliance with this regimen is unsatisfactory because of adverse events such as leukopenia, anorexia, and nausea. To reduce adverse effects and improve compliance, we studied a "5-day on/2-day off" low-dose regimen of S-1 and evaluated pharmacokinetics in patients with non-small-cell lung cancer (NSCLC).. Twelve patients with NSCLC were divided into 2 groups and received S-1 in a dose of 25 mg twice daily (level 1, n = 6) or 40 mg twice daily (level 2, n = 6) for 5 consecutive days followed by a 2-day rest (5 days on/2 days off) every week. Plasma 5-fluorouracil (5-FU) concentrations were measured.. The maximum concentration in plasma and the area under the plasma concentration-time curve from 0 to 9 h were respectively 55.3 ± 21.1 ng/ml and 290.2 ± 95.7 ng·hr/ml for level 1, as compared with 104.2 ± 33.5 ng/ml and 541.9 ± 232.3 ng·hr/ml for level 2. These values were similar to those previously reported for a continuous intravenous infusion of 5-FU. Adverse events were grade 1 fatigue (n = 1 in each group) and anorexia (n = 1 in each group).. A "5-day on/2-day off" low-dose (40 mg twice daily) regimen of S-1 is feasible for the treatment of NSCLC, with acceptable plasma 5-FU concentrations and minimal adverse effects. A phase II or III trial of this regimen in an adjuvant setting is warranted in patients with NSCLC.

Topics: Administration, Oral; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Carcinoma, Non-Small-Cell Lung; Drug Combinations; Female; Follow-Up Studies; Gas Chromatography-Mass Spectrometry; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Patient Compliance; Pyridines; Tegafur; Treatment Outcome

Oral adjuvant chemotherapy without hospitalization might reduce the physiological and psychological burden on patients if effectiveness could be guaranteed. We conducted a multicenter feasibility study using S-1, an oral derivative of 5-fluorouracil, as postoperative adjuvant chemotherapy in patients with curatively resected pathologically stage IB-IIIA non-small-cell lung cancer.. Adjuvant chemotherapy comprised 8 courses (4-week administration, 2-week withdrawal) of S-1 at 80-120 mg per day. Fifty-one patients from 7 institutions were enrolled in this pilot study, from June 2005 to March 2007. The primary end point was the completion rate of scheduled adjuvant chemotherapy. Secondary end points were the incidence and grade of adverse reactions.. Fifty patients were eligible. The completion rate for the planned 8 courses of S-1 administration was 72.0% (36 patients). Total percentage administration amount was 71.1%. Grade 3 adverse reactions such as neutropenia (4.0%), anorexia (4.0%), thrombopenia (2.0%), anemia (2.0%), elevated total bilirubin (2.0%), hypokalemia (2.0%), nausea (2.0%), and diarrhea (2.0%) were observed, but no grade 4 adverse effects were encountered. Overall and relapse-free survival rates at 3 years were 87.7% and 69.4%, respectively.. Postoperative 1-year administration of S-1 seems feasible as oral adjuvant chemotherapy for lung cancer. The oral formulation and low incidence of adverse reactions permit treatment on an outpatient basis. The present study would be reasonable to follow up with a properly powered phase III trial.

Topics: Administration, Oral; Aged; Ambulatory Care; Antimetabolites, Antineoplastic; Carcinoma, Non-Small-Cell Lung; Chemotherapy, Adjuvant; Combined Modality Therapy; Dose-Response Relationship, Drug; Drug Combinations; Feasibility Studies; Female; Follow-Up Studies; Humans; Incidence; Lung Neoplasms; Male; Middle Aged; Neoplasm Recurrence, Local; Oxonic Acid; Tegafur; Treatment Outcome

This phase I/II study was designed to evaluate a combination of irinotecan and S-1 a new regimen for salvage chemotherapy in patients with advanced or metastatic non-small cell lung cancer (NSCLC).. The study group comprised patients with advanced or metastatic NSCLC who had previously received at least one platinum-containing chemotherapy. Patients received irinotecan on days 1, 15 and oral S-1 (40 mg/m(2) twice daily as a fixed dose) on day 1 to 14 of a 28-day cycle.. In the phase I part, irinotecan was given in escalating doses of 70 (Level 1), 80 (Level 2), and 90 mg/m(2) (Level 3). Three of the 5 patients given Level 3 had dose-limiting toxicity, and Level 2 (80 mg/m(2) of irinotecan) was designated as the recommended dose. In phase II, 38 patients received a median of 7.4 cycles of irinotecan at the recommended dose. The overall response rate was 15.8 % (90 % confidence interval (CI): 6.1-25.5 %), and the median progression-free and overall survival times were 4.5 months (95 % CI: 3.5-5.0) and 15.0 months (95 % CI: 9.5-20.6) months, respectively. Toxicity was generally mild. Grade 3 or higher toxicity included neutropenia in 17.9 % of the patients, thrombocytopenia in 5.1 % and nausea in 7.7 %.. Combination chemotherapy with S-1 and irinotecan was considered an effective salvage regimen in patients with advanced or metastatic NSCLC.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Carcinoma, Non-Small-Cell Lung; Disease-Free Survival; Dose-Response Relationship, Drug; Drug Combinations; Female; Humans; Irinotecan; Lung Neoplasms; Male; Maximum Tolerated Dose; Middle Aged; Oxonic Acid; Salvage Therapy; Survival Rate; Tegafur; Treatment Outcome

We investigated the efficacy and toxicity of a novel oral 5-fluorouracil (5-FU) formulation (S-1), administered according to a tailored dose regimen.. S-1 was administered orally for 28 days, followed by 14 days of no treatment, in 23 patients who received a tailored dose of S-1, adjusted on the basis of individual creatinine clearance and body surface area. In 8 of the patients, pharmacokinetic study was performed on the 6 points on 7th day after S-1 administration.. Of the 23 patients enrolled in this study, 2 (8.7 %) had a partial response and 14 (60.9 %) had stable disease. The disease control rate was 69.6 % (16/23) (95 % confidence interval, 50.8-88.4 %). Grade 3/4 hematologic and non-hematologic toxicities were minor. In the pharmacokinetic study group, the maximum plasma concentration (C (max)) and the area under the plasma concentration curve of 5-FU at all 6 points after administration of the tailored S-1 dose regimen were similar to the values reported in a previous study describing cancer patients with normal renal function who received a standard dose of S-1 (80 mg/m(2)/day).. Our results suggest that tailored S-1 monotherapy is safe and therapeutically useful as first-line treatment for elderly patients with advanced and recurrent non-small cell lung cancer.

Topics: Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Body Surface Area; Carcinoma, Non-Small-Cell Lung; Creatinine; Disease-Free Survival; Drug Administration Schedule; Drug Combinations; Female; Fluorouracil; Humans; Lung Neoplasms; Male; Oxonic Acid; Tegafur; Treatment Outcome

Combination of S-1, an oral fluorouracil derivative, plus docetaxel against non-small cell lung cancer (NSCLC) showed promising efficacy but clinically problematic emesis. A phase I/II study utilising a new schedule for this combination was conducted.. A biweekly regimen of docetaxel on day 1 with oral S-1 on days 1-7 was administered to previously treated NSCLC patients. Doses of docetaxel/S-1 were escalated to 30/80, 35/80, and 40/80 mg m(-2), respectively, and its efficacy was investigated at the recommended dose below maximum tolerated dose (MTD).. In phase I study employing 13 patients, dose-limiting toxicities were febrile neutropenia and treatment delay, with the respective MTDs for docetaxel 40 mg m(-2)/S-1 80 mg m(-2). In the phase II study, 34 patients were treated with docetaxel 35 mg m(-2)/S-1 80 mg m(-2) for a median cycle of 6. The response and disease control rates were 34.3% (95% confidence interval (CI), 18.6-50.0%) and 62.9% (95% CI, 46.8-72.9%), respectively. Median progression-free survival was 150.5 days. Haematologic grade 4 toxicities were observed in neutropenia (11.8%) and thrombocytopenia (2.9%). Regarding non-haematologic toxicities, including emesis, there were no grade 3/4 side effects.. Combination of 1-week administration of S-1 with biweekly docetaxel is safe and active for NSCLC.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Disease-Free Survival; Docetaxel; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Humans; Lung Neoplasms; Oxonic Acid; Taxoids; Tegafur

S-1, an oral 5-fluorouracil derivative, is effective against advanced non-small cell lung cancer (NSCLC) with mild toxicity and synergistic effects with radiation in preclinical trials. In this phase I study, we evaluated the dose-limiting toxicity and recommended dose of S-1 for a future phase II study when administered concurrently with thoracic radiation (total dose of 60 Gy at 2 Gy per daily fraction) in elderly patients (>75 years old) with localized advanced NSCLC. S-1 was administered on days 1-14 and 29-42 at the following dosages: 60, 70, and 80 mg/m(2)/day. Twenty-two previously untreated patients were enrolled in this study. Dose-limiting toxicity included febrile neutropenia, thrombocytopenia, stomatitis, and pneumonitis. One patient had grade 5 radiation pneumonitis. No other patient experienced radiation pneumonitis or esophagitis exceeding grade 2. The recommended dose for S-1 was determined to be 80 mg/m(2)/day, which produced an overall response rate of 75% (n=12). The median progression-free survival time was 11.5 months (95% confidence interval: 7.1-15.8 months) with a median follow-up time of 27.9 months. These results indicate that concurrent treatment with S-1 and thoracic radiation is a feasible option for NSCLC in the elderly. A phase II study is currently under way.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Combined Modality Therapy; Dose-Response Relationship, Drug; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Oxonic Acid; Survival Rate; Tegafur

We examined the safety and efficacy of the combination of S-1 and biweekly docetaxel in patients with previously treated advanced non-small-cell lung cancer (NSCLC).. Patients with previously treated advanced NSCLC were eligible if they had a performance status of 2 or less, were 80 years or younger, and had adequate organ function. Forty-nine patients (38 men and 11 women; median age, 66 years; range 43-79 years) were enrolled. Patients were treated with the combination of 80 mg/m(2) per day of S-1 for 14 consecutive days and 35 mg/m(2) of docetaxel on days 1 and 15 every 4 weeks.. The overall response rate was 16.3% (95% confidence interval, 7.6-30.5%). The disease-control rate was 49.0% (95% confidence interval, 34.4-63.7%). The median survival time after this treatment was 9 months (range 1-22 months). The median progression-free survival time was 3 months (range 1-11 months). Response rates and survival times did not differ significantly according to the histological type. Grade 3-5 toxicities included neutropenia in 51.0% of patients, thrombocytopenia in 2.0%, anemia in 20.4%, infection in 24.5%, anorexia in 12.2%, diarrhea in 14.3%, nausea in 6.1%, and dehydration in 4.2%. There was 1 treatment-related death due to severe anorexia, stomatitis, diarrhea, and, as consequence, dehydration.. The combination of S-1 and biweekly docetaxel is an acceptable therapeutic option in patients with previously treated advanced NSCLC regardless of the histological type.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Disease-Free Survival; Docetaxel; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Survival Rate; Taxoids; Tegafur; Treatment Outcome

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 phase I study was conducted to evaluate the feasibility and to determine the recommended doses of the combination therapy of S-1 and irinotecan (CPT-11) in patients with advanced non-small cell lung cancer (NSCLC) as second-line treatment.. Patients with NSCLC who were previously treated with one chemotherapy regimen and had a performance status of 0 or 1 were eligible. CPT-11 was administered at 60 mg/m² (level 1), 80 mg/m² (level 2) on days 1 and 8, and oral S-1 was administered at 80 mg/day for body surface area (BSA) less than 1.25 m², 100 mg/day for BSA 1.25-1.5 m², and 120 mg/day for BSA more than 1.5 m² on days 1-14 every 3 weeks. The dose-limiting toxicity (DLT) was defined as grade 4 leukocytopenia or neutropenia, grade ≥ 3 neutropenia with fever over 38°C, grade ≥ 3 thrombocytopenia, or grade ≥ 3 major nonhematological toxicities.. Nine patients were enrolled in the study. None of 3 patients enrolled in level 1 had any DLT. Of 6 patients in level 2, 2 patients had grade 3 diarrhea and one had grade 3 interstitial pneumonia. Level 1 was declared as the recommended dose.. The feasibility of the combination therapy of S-1 and CPT-11 was shown in the second-line setting for the treatment of advanced NSCLC. The recommended dose of CPT-11 was 60 mg/m² combined with standard dose of S-1 for phase II trials of pretreated advanced NSCLC patients.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Carcinoma, Non-Small-Cell Lung; Dose-Response Relationship, Drug; Drug Combinations; Female; Humans; Irinotecan; Lung Neoplasms; Male; Maximum Tolerated Dose; Middle Aged; Oxonic Acid; Tegafur

Although S-1 has been shown to have activity against advanced nonsmall-cell lung cancer (NSCLC), its efficacy for elderly patients remains unclear. This phase II study evaluated the efficacy and safety of S-1 as a first-line treatment for elderly patients. Chemotherapy-naïve patients aged 70 years or older with stages IIIB to IV or postoperative NSCLC and performance status 1 or lower were eligible. Patients received S-1 approximately equivalent to 80 mg/m/day for 2 weeks followed by a 1-week rest period every 3 weeks. The primary end point was the response rate. Secondary end points were toxicity, disease control rate, progression-free survival, and overall survival. Twenty-nine patients were eligible. The median age was 78 years (range, 70-85 years). The overall response rate and the disease control rate were 27.6 [95% confidence interval (CI), 11.3-43.9%] and 65.5% (95% CI: 48.2-82.8%), respectively. The median progression-free survival time was 4.0 months (95% CI: 4.0-9.8 months). The median overall survival was 12.1 months (95% CI: 13.8-25.5 months) and the 1-year survival rate was 53.6%. No grade 4 toxicities were observed. The only hematological toxicity of grade 3 was anemia in 6.9% of patients. The grade 3 nonhematological toxicities included hyponatremia, anorexia, nausea, oral mucositis, and diarrhea in 3.4% of patients and infection in 6.9% of patients. S-1 monotherapy was effective and well tolerated as a first-line treatment for elderly patients with advanced NSCLC. The results of this study warrant further investigations of this regimen, including a randomized controlled trial.

Topics: Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Carcinoma, Non-Small-Cell Lung; Disease-Free Survival; Drug Combinations; Female; Follow-Up Studies; Humans; Lung Neoplasms; Male; Neoplasm Staging; Oxonic Acid; Prospective Studies; Survival Rate; 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

The aim of this study was to evaluate the efficacy and toxicity of a novel oral 5-fluorouracil formulation (S-1) as second-line therapy after platinum agent chemotherapy for advanced non-small cell lung cancer (NSCLC).. S-1 was administered orally at a dose of 80 mg/m(2) for 28 days, followed by 14 days of rest (1 cycle); treatment was repeated until disease progression, unacceptable toxicity, or patient refusal.. Of the 46 patients enrolled in this study, 44 were evaluable. Six patients (14%) exhibited a partial response and 28 (64%) showed stable disease. Disease-control rate was 77.3% (34/44) (95% CI, 64.9-89.7%). The overall response rate was 14% (6/44) (95% CI, 3.5-23.8%). Median progression-free survival was 4.2 months. The median survival time was 16.4 months, and the one-year survival rate 60.3%. Grade 3/4 hematological toxicities were minor. All of those adverse reactions were tolerable and reversible.. This study demonstrated the efficacy of S-1 monotherapy as second-line treatment for advanced NSCLC.

Topics: Administration, Oral; Aged; Carcinoma, Non-Small-Cell Lung; Disease Progression; Disease-Free Survival; Drug Combinations; Drug Resistance, Neoplasm; Female; Follow-Up Studies; Hematologic Diseases; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Platinum Compounds; Recurrence; Tegafur; Treatment Outcome

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

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

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

Platinum-free regimens can represent an alternative for advanced non-small cell lung cancer (NSCLC) if similar efficacy is provided with better tolerability. This study evaluated the efficacy and safety of combined irinotecan and S-1 for chemotherapy-naïve advanced NSCLC.. Chemotherapy consisted of 4-week cycles of intravenous irinotecan (100 mg/m(2), days 1 and 15) and oral S-1 (80 mg/m(2), days 1-14). The primary endpoint was response rate, while secondary endpoints were overall survival, progression-free survival (PFS), and safety.. A total of 112 cycles was administered to 40 patients (median 3 cycles; range 1-6 cycles). Twelve patients showed partial response and 17 patients had stable disease, representing a response rate of 30% and a disease control rate of 72.5%. Median survival time and median PFS were 16.1 and 4.8 months, respectively. Hematological toxicities of grade 3 or 4 were neutropenia (32.5%) and anemia (5.0%). The most common nonhematological toxicities of grade 3 or 4 included diarrhea (15.0%) and anorexia (17.5%). Patients homo- or heterozygous for UGTA1A*6 tended to show a higher incidence of grade 3 diarrhea (p = 0.055).. The combination of irinotecan and S-1 offers good efficacy and tolerability for previously untreated advanced NSCLC.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Carcinoma, Non-Small-Cell Lung; Drug Combinations; Female; Genotype; Glucuronosyltransferase; Humans; Irinotecan; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Tegafur

To evaluate the combination chemotherapy using oral antimetabolite S-1 plus cisplatin (SP) with concurrent thoracic radiotherapy (RT) followed by the consolidation SP for locally advanced non-small cell lung cancer.. Patients with stage III non-small cell lung cancer, 20 to 74 years of age, and Eastern Cooperative Oncology Group performance status 0 to 1 were eligible. The concurrent phase consisted of full dose S-1 (orally at 40 mg/m/dose twice daily, on days 1-14) and cisplatin (60 mg/m on day 1) repeated every 4 weeks for two cycles with RT delivered beginning on day 1 (60 Gy/30 fractions over 6 weeks). After SP-RT, patients received an additional two cycles of SP as the consolidation phase.. Fifty-five patients were registered between November 2006 and December 2007. Of the 50 patients for efficacy analysis, the median age was 64 years; male/female 40/10; Eastern Cooperative Oncology Group performance status 0/1, 21/29; clinical stage IIIA/IIIB 18/32; and adenocarcinoma/others 20/30. There were 42 clinical responses including one complete response with an objective response rate of 84% (95% confidence interval [CI], 71-93%). The 1- and 2-year overall survival rates were 88% (95% CI, 75-94%) and 70% (95% CI, 55-81%), respectively. The median progression-free survival was 20 months. Of the 54 patients for safety analysis, common toxicities in the concurrent phase included grade 3/4 neutropenia (26%), thrombocytopenia (9%), and grade 3 esophagitis (9%) and febrile neutropenia (9%). In one patient, grade 3 pneumonitis was observed in the consolidation phase. There were two treatment-related deaths caused by infection in the concurrent phase.. SP-RT showed a promising efficacy against locally advanced NCSLC with acceptable toxicity.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Chemoradiotherapy; Cisplatin; Disease-Free Survival; Dose Fractionation, Radiation; Drug Combinations; Esophagitis; Female; Fever; Humans; Japan; Kaplan-Meier Estimate; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Neutropenia; Oxonic Acid; Tegafur; Thrombocytopenia; Treatment Outcome

The feasibility of using S-1, a novel oral dihydropyrimidine dehydrogenase (DPD)-inhibitory 5-fluorouracil, as postoperative adjuvant chemotherapy for completely resected non-small cell lung cancer (NSCLC) was analyzed.. Adjuvant chemotherapy consisted of eight courses (2-week administration and 1-week withdrawal) of S-1, at 80-120 mg/body per day in an outpatient setting. From July 2006 through March 2007, 30 patients were enrolled in this multi-institutional trial.. The planned eight courses of S-1 administration were accomplished to 17 patients (56.7%; 95% confidence interval 37.4-74.5%). Two patients discontinued the treatment due to the disease recurrence, and therefore the completion rate was calculated to be 60.7%. The completion rate in patients younger than 70 years old was 78.6% while it was 42.9% in those of 70 years old or older. In seven patients including five elderly patients (> or =70 years old), S-1 administration was discontinued due to subjective symptoms, such as anorexia, during the early courses. The rate of patients with mild renal impairment (60< or =creatinine clearance<80 ml/min) tended to be higher in the elderly patients than that in the younger patients. Although grade 3 neutropenia (6.7%), anemia (6.7%), thrombocytopenia (3.3%) and digestive hemorrhage (3.3%) were observed, no grade 4 adverse events occurred.. Postoperative long-term administration of S-1 seems feasible as adjuvant chemotherapy for NSCLC, with few adverse events except for the early development of anorexia, especially in the elderly patients.

Topics: Aged; Carcinoma, Non-Small-Cell Lung; Chemotherapy, Adjuvant; Combined Modality Therapy; Drug Combinations; Feasibility Studies; Female; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Tegafur

We conducted a phase II study of S-1 and carboplatin combination regimen in the treatment of patients with advanced non-small cell lung cancer (NSCLC). Chemotherapy-naïve patients with advanced NSCLC were treated with S-1 and carboplatin. S-1 was administered orally twice daily for 14 days and carboplatin AUC 5 on day 1 of each cycle, and this was repeated every 4 weeks. Twenty-nine patients were enrolled in this study. The main grade 3 or 4 toxicities observed during the first cycle were neutropenia (10.3%), thrombocytopenia (41%), and transaminase elevation. Objective responses were seen in 9 patients (response rate 31.0%). The median survival time and median progression-free survival were 16.0 months (95% CI, 12.1-19.0 months) and 4.5 months (95% CI, 3.2-6.1 months), respectively. Hematological adverse events reaching grade 3 or 4 were neutropenia (10.3%), anemia (3.4%), and thrombocytopenia (3.4%). No febrile neutropenia was detected. Nonhematological toxicities were also mild. Although grade 3 infection was observed in 1 patient, the patient improved without intervention. The combination of S-1 plus carboplatin is an active and well-tolerated regimen for the treatment of patients with advanced NSCLC. Further investigations are required to confirm our results in randomized trials.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Non-Small-Cell Lung; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Neutropenia; Oxonic Acid; Tegafur; Thrombocytopenia

The purpose of this phase I/II study is to evaluate a new combination chemotherapy consisting of docetaxel and S-1 as front-line therapy for patients with untreated advanced non-small cell lung cancer (NSCLC). The treatment included docetaxel on day 1 and oral S-1 at a fixed dose of 40mg/m(2) administered twice daily on days 1-14 and repeated every 3 weeks. In phase I, docetaxel at escalating doses of 40 (level 0), 50 (level 1) and 60mg/m(2) (level 2) was administered starting from level 1. Because only one patient among the 6-patient cohort at level 1 and no patient among the 3-patient cohort at level 2 experienced defined dose-limiting toxicity (DLT), level 2 was determined as the recommended dose. In phase II, 60 patients were treated at the recommended dose for median 3 cycles, and the overall response rate was 30% (95% confidence interval [CI], 18.9-43.2%), and the median overall and progression-free survival times were 15.2 (95% CI: 10.5-17.7) and 4.9 (95% CI: 3.5-5.6) months, respectively. The most frequent toxicities experienced were neutropenia, febrile neutropenia and appetite loss; all toxicities were however well manageable. The present regimen showed a potent activity with mild toxicity in untreated NSCLC.

Topics: Administration, Oral; Adult; Aged; Carcinoma, Non-Small-Cell Lung; Disease Progression; Docetaxel; Drug Combinations; Drug Dosage Calculations; Drug Therapy, Combination; Female; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Neutropenia; Oxonic Acid; Survival Analysis; Taxoids; Tegafur

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

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

The objectives of this study were to determine the maximum tolerated dose (MTD) and recommended dose (RD) of S-1 plus cisplatin (CDDP) and to evaluate safety and efficacy using the defined RD in advanced/recurrent head and neck cancer (HNC).. S-1 was administered orally at 40 mg/m(2) twice daily for 14 consecutive days, and CDDP was infused on day 8 at a dose of 60 and 70 mg/m(2). Each course was repeated every 4 weeks.. A total of 38 patients were registered, 10 patients for the Phase I study and an additional 28 patients for the Phase II study. Although no dose-limiting toxicity (DLT) was observed in the CDDP 60 mg/m(2) (Level 1) group, two of six patients in the CDDP 70 mg/m(2) (Level 2) group exhibited DLT (fatigue/diarrhea). The MTD was not achieved in the Phase I study. Level 2 was therefore determined as the RD. In the Phase II study, 34 patients, including 6 patients from the Phase I study, were evaluated. At the termination of treatment, the confirmed response rate was 44.1% (15/34, 95% CI: 27.4-60.8). The best response rate without an adequate duration time was 67.6% (95% CI: 51.9-83.4). The median survival period was 16.7 months, and the 1-year survival rate was 60.1%. The main toxicities of Grade 3 or above were anorexia (26.5%), nausea (14.7%), neutropenia/thrombocytopenia (11.8%) and anemia/fatigue (8.8%).. This is considered to be an effective regimen with acceptable toxicities for HNC.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Carcinoma, Squamous Cell; Cisplatin; Drug Combinations; Female; Follow-Up Studies; Head and Neck Neoplasms; Humans; Infusions, Intravenous; Liver Neoplasms; Lung Neoplasms; Male; Maximum Tolerated Dose; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Oxonic Acid; Prognosis; Survival Rate; Tegafur; Treatment Outcome; Young Adult

The purpose of the present phase II study was to evaluate both the efficacy and toxicity of the combination of S-1 and docetaxel in previously treated patients with locally advanced or metastatic non-small cell lung cancer.. Thirty-eight previously treated patients with non-small cell lung cancer were treated with S-1 (80 mg/m(2), days 1-14, oral) and docetaxel (40 mg/m(2), day 1, intravenous) every 3 weeks.. No complete response was observed, and seven patients had a partial response, yielding an overall response rate of 18.4% (95% CI, 7.7-34.3%). The median overall survival time and 1-year overall survival rate were 16.1 months and 60%, respectively. The median progression-free survival time was 4.4 months. Myelosuppression was the main toxicity with grade 3 or 4 neutropenia and leukopenia in 50 and 21%, respectively. There was no irreversible toxicity in this study.. The combination of S-1 and docetaxel is well tolerable and has substantial activity for patients with locally advanced or metastatic non-small cell lung cancer. A phase III trial comparing docetaxel with or without S-1 would warrant further investigation.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Disease-Free Survival; Docetaxel; Drug Combinations; Female; Follow-Up Studies; Humans; Leukopenia; Lung Neoplasms; Male; Middle Aged; Neoplasm Metastasis; Neutropenia; Oxonic Acid; Survival Rate; Taxoids; 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

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

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

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

The antimetabolic agent S-1 inhibits thymidylate synthase similar to pemetrexed, but through a different mechanism of action. Whether the antitumour activity of S-1 depends on histological type remains unclear. We analysed pooled data from 2 phase II clinical studies of cisplatin and S-1 in patients with previously untreated advanced non-small cell lung cancer.. We comprised 110 patients with stage IIIB or IV non-small cell lung cancer. Univariate and multivariate analyses were performed to determine the effects of histological type on progression-free survival and response rates.. On pooled analysis of the data, according to histological type, median progression-free survival was 3.8 months in patients with squamous cell carcinoma and 4.4 months in those with non-squamous cell carcinoma. Both analyses showed that progression-free survival and response rate did not differ significantly.. Unlike molecular targeted agents and pemetrexed, a combination of cisplatin and S-1 may be no difference in response according to histological type.

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Carcinoma, Non-Small-Cell Lung; Disease-Free Survival; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Survival Rate; Tegafur

The primary goal of this open-label, multicenter, randomized phase III trial was to determine whether treatment with carboplatin plus the oral fluoropyrimidine derivative S-1 was noninferior versus that with carboplatin plus paclitaxel with regard to overall survival (OS) in chemotherapy-naive patients with advanced non-small-cell lung cancer (NSCLC).. A total of 564 patients were randomly assigned to receive either carboplatin (area under the curve, 5) on day 1 plus oral S-1 (40 mg/m2 twice per day) on days 1 to 14 or carboplatin (area under the curve, 6) plus paclitaxel (200 mg/m2) on day 1 every 21 days.. At the planned interim analysis, with a total of 268 death events available, the study passed the O'Brien-Fleming boundary of 0.0080 for a positive result and noninferiority of carboplatin and S-1 compared with carboplatin and paclitaxel was confirmed for OS (hazard ratio, 0.928; 99.2% CI, 0.671 to 1.283). Median OS was 15.2 months in the carboplatin and S-1 arm and 13.3 months in the carboplatin and paclitaxel arm, with 1-year survival rates of 57.3% and 55.5%, respectively. Rates of leukopenia or neutropenia of grade 3/4, febrile neutropenia, alopecia, and neuropathy were more frequent in the carboplatin and paclitaxel arm, whereas thrombocytopenia, nausea, vomiting, and diarrhea were more common in the carboplatin and S-1 arm. The carboplatin and S-1 arm had significantly more dose delays than the carboplatin and paclitaxel arm.. Oral S-1 with carboplatin was noninferior in terms of OS compared with carboplatin and paclitaxel in patients with advanced NSCLC, and is thus a valid treatment option.

Topics: Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Non-Small-Cell Lung; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Paclitaxel; Survival Analysis; Tegafur

It is extremely difficult to bring about a complete cure of metastatic breast cancer: the purpose of treatment is to prolong the patient's survival while maintaining their quality of life (QOL). The current retrospective study was conducted to find whether S-1, an orally administered 5-FU agent, can produce a therapeutic result in patients with recurrent metastatic breast cancer while maintaining their QOL.. Among the patients who were diagnosed at our institution to have recurrent metastatic breast cancer between November 2001 and December 2008, those who were treated with S-1 were selected and their records retrospectively reviewed.. The analysis was conducted on 33 patients. The median number of regimens that these patients underwent was 2 (range 0-6). The overall response rate (ORR), clinical benefit rate (CBR), median time to treatment failure and overall survival were 30%, 42%, 152 days and 338 days, respectively. Among the 11 patients who were treated with S-1 in the first or the second line, ORR and CBR were 45.5 and 63.6%, respectively. Toxicity more than grade 3, leucopenia, neutropenia diarrhea, mucositis, and hand-foot syndrome were found in only 3%.. S-1 is well-tolerated by patients, promising a therapy while maintaining their QOL. When applied in the early stage of a disease in particular, the agent promises a very effective anti-tumor effect.

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Bone Neoplasms; Breast Neoplasms; Drug Combinations; Female; Humans; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Middle Aged; Oxonic Acid; Retrospective Studies; Survival Rate; Tegafur; Treatment Outcome

We aimed to evaluate the efficacy and safety of combination chemotherapy with S-1 and low-dose weekly cisplatin in patients with advanced non-small cell lung cancer (NSCLC). In this phase II trial, previously untreated patients with stage IIIB/IV NSCLC were treated with oral administration of S-1 at 80 mg/m(2) for 21 days and three consecutive weekly low doses of cisplatin (25 mg/m(2)) followed by a 2-week rest period. Twenty-six patients were eligible for the assessment of efficacy and safety. Six partial responses were observed with an overall response rate of 23.1% (95% confidence interval: 12.3-31.6%). The median survival time and median progression-free survival were 13.4 months and 5.4 months, respectively. Grade 3/4 hematologic toxicities were observed in 9 patients (34.6%), including one grade 4 neutropenia and thrombocytopenia. As for non-hematologic adverse reactions, although grade 3 events were observed in 4 patients (15.3%), no severe renal toxicity or vomiting was found. S-1 and weekly low-dose cisplatin combination chemotherapy in patients with advanced NSCLC showed an acceptable response rate, overall survival time, and toxicity. Because this regimen can be performed in an outpatient setting, it might be an alternative useful and convenient option. Further investigations with a large population are required to confirm our results.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Cisplatin; Disease-Free Survival; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Tegafur; Time Factors; Treatment Outcome

To determine the maximum tolerated dose (MTD) and recommended dose (RD) of S-1 in combination with cisplatin and thoracic radiotherapy in patients with unresectable Stage III non-small-cell lung cancer (NSCLC).. S-1 was administered orally twice daily for 14 days and cisplatin on Days 1 and 8 of each cycle; this was repeated every 3 weeks. Doses of each drug were planned as follows: level 0, 50/40; level 1, 60/40; level 2, 70/40; level 3, 80/40 (S-1 [mg/m(-2)/day(-1)]/cisplatin [mg/m(-2)/day(-1)]). Thoracic radiation therapy was administered in 2 Gy fractions five times weekly to a total dose of 60 Gy.. Ten patients were enrolled in this study. All patients received 60 Gy of thoracic radiotherapy and 7 (70%) patients received four cycles of chemotherapy. At level 1, 2 of 3 patients experienced a delay exceeding 10 days in the cisplatin administration of Day 29. Grade 4 neutropenia and Grade 3 fever occurred in 1 and 1 patients, respectively. Nonhematologic toxicities were mild. None developed >or=Grade 3 esophagitis or lung toxicity. At level 0, 2 of 7 patients developed dose-limiting toxicity. Thus, level 1 was considered the MTD and Level 0 was selected as the RD. Objective responses were seen in all patients.. The RD is the level 0 dose, and this regimen is a feasible and well-tolerated regimen for the treatment of patients with Stage III NSCLC.

Topics: Administration, Oral; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Cisplatin; Combined Modality Therapy; Dose Fractionation, Radiation; Drug Administration Schedule; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Maximum Tolerated Dose; Middle Aged; Oxonic Acid; Tegafur

A combination of S-1, a newly developed oral 5-fluorouracil derivative, and cisplatin is reported to show anti-tumour activity against advanced non-small cell lung cancer (NSCLC). Because S-1 shows synergistic effects with radiation, we conducted a phase I study to evaluate the maximum tolerated doses (MTDs), recommended doses (RDs), and dose-limiting toxicities (DLTs) of cisplatin and S-1 when combined with concurrent thoracic radiation (total dose of 60 Gy with 2 Gy per daily fraction) in patients with locally advanced NSCLC. Chemotherapy consisted of two 4-week cycles of cisplatin administered on days 1 and 8, and S-1 administered on days 1-14. S-1/cisplatin dosages (mg/m(2)/day) were escalated as follows: 60/30, 60/40, 70/40, 80/40 and 80/50. Twenty-two previously untreated patients were enrolled. The MTDs and RDs for S-1/cisplatin were 80/50 and 80/40, respectively. DLTs included febrile neutropaenia, thrombocytopaenia, bacterial pneumonia and delayed second cycle of chemotherapy. No patient experienced radiation pneumonitis>grade 2 and only one patient experienced grade 3 radiation oesophagitis. The overall response rate was 86.4% with a median survival time of 24.4 months. These results indicate that combination cisplatin-S-1 chemotherapy with concurrent thoracic radiation would be a feasible treatment option and a phase II study is currently under way.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Cisplatin; Combined Modality Therapy; Dose-Response Relationship, Drug; Dose-Response Relationship, Radiation; Drug Administration Schedule; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Tegafur

S-1 is a novel oral fluorouracil prodrug active against non-small cell lung cancer (NSCLC). To determine the feasibility of S-1 combined with weekly irinotecan for patients with advanced NSCLC, we performed a phase I study to determine the maximum tolerated dose (MTD) and the recommended dose (RD) of irinotecan.. Patients with advanced NSCLC received S-1 (80 mg/m(2)) on days 1-14 and irinotecan (50-80 mg/m(2)) on days 1, 8, and 15 of each 28-day cycle. Three to six patients were treated with each dose of irinotecan, with the MTD defined as the dose at which dose-limiting toxicity (DLT) appeared in 33% of patients.. At doses of 50-70 mg/m(2), no patients experienced any DLT, whereas, at a dose of 80 mg/m(2), two of four patients experienced DLTs. Two patients experienced grade 3 toxicities - neutropenia and diarrhea.. The MTD of weekly irinotecan was 80 mg/m(2), making its RD for phase II trials 70 mg/m(2).

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Carcinoma, Non-Small-Cell Lung; Drug Administration Schedule; Drug Combinations; Feasibility Studies; Female; Humans; Irinotecan; Lung Neoplasms; Male; Maximum Tolerated Dose; Middle Aged; Neoplasm Staging; Oxonic Acid; Tegafur; Treatment Outcome

TS-1 is a novel oral anticancer agent comprised of tegafur, a prodrug of 5- flurouracil, and two modulators. A phase i study of tS-1 plus carboplatin combination therapy was conducted to determine the maximum tolerated dose (MTD), recommended dose (RD), and dose limiting toxicities (DLT) in advanced non-small-cell lung cancer (NSClC). TS-1 was given orally at a dose of 80 mg/m(2)/day for 2 weeks, followed by a 2-week rest. Carboplatin was given intravenously on day 8 at a dose of 4.0, 5.0, 6.0 area under the curve (AUC) values. Fifteen patients with advanced NSClC were analyzed. the grade 3-4 toxicities observed during the first cycle were febrile neutropenia (6%), anemia (6%), anorexia (6%), and diarrhea (6%). these toxicities were reversible and manageable. The MTD for carboplatin was evaluated to be more than 6.0 AUC values, as one of six patients developed Dlt at this dose. the RD for carboplatin was estimated as 6.0 AUC values. Objective responses were seen in five patients (response rate 33%).

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Area Under Curve; Carboplatin; Carcinoma, Non-Small-Cell Lung; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Maximum Tolerated Dose; Middle Aged; Oxonic Acid; Tegafur

The objective of this phase I/II study was to determine the recommended dose (RD) of S-1 and carboplatin (CBDCA), and to evaluate the efficacy and safety of this combination in the treatment of patients with advanced non-small cell lung cancer (NSCLC). Chemotherapy-naïve patients were treated with S-1 given orally on days 1-14, and CBDCA infused intravenously on day 1, repeated every 3 weeks. RD was AUC5 of CBDCA and 80 mg/m(2) of S-1. Nineteen patients were treated at the RD. The overall response was 30.8% (95% confidence interval: 17.1-58.3%). The response rate in the RD was 36.8% (95% CI: 16.3-61.6%). The median overall survival time was 11.1 months (95% CI: 8.1-15.3 months) and the median progression-free survival time was 5.0 months (95% CI: 3.6-6.0 months). Major grades 3-4 toxicities were thrombocytopaenia (47%), anaemia (26%) and infection (16%). This is the first report to show promising activity of this combination in phase II, including survival data and manageable toxicity, especially in outpatients receiving treatment for advanced NSCLC.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Non-Small-Cell Lung; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Maximum Tolerated Dose; Middle Aged; Oxonic Acid; Tegafur

To assess the efficacy and safety of S-1 and cisplatin with concurrent thoracic radiation for unresectable stage III non-small-cell lung cancer (NSCLC).. Eligible patients were 20-74 years old and had histologically or cytologically confirmed NSCLC, a performance status of 0-1, and no prior chemotherapy. Patients were treated with cisplatin (60 mg m(-2) on day 1) and S-1 (orally at 40 mg m(-2) per dose, b.i.d., on days 1-14), with the treatment repeated every 4 weeks for four cycles. Beginning on day 2, a 60-Gy thoracic radiation dose was delivered in 30 fractions.. Of 50 patients, 48 were eligible. Partial response was observed in 42 patients (87.5%; 95% CI: 79.1-96.9%). This regimen was well tolerated. Common toxicities included grade 3/4 neutropenia (32%), grade 3/4 leukopenia (32%), grade 3/4 thrombocytopenia (4%), grade 3 febrile neutropenia (6%), grade 3 oesophagitis (10%), and grade 3 pneumonitis (5%). Median progression-free survival was 12.0 months and median overall survival was 33.1 months. The 1- and 2-year survival rates were 89.5 and 56%, respectively.. This chemotherapy regimen with concomitant radiotherapy is a promising treatment for locally advanced NSCLC because of its high response rates, good survival rates, and mild toxicities.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Cisplatin; Combined Modality Therapy; Disease-Free Survival; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Survival Rate; Tegafur

We conducted a phase I study to determine the maximum tolerated dose, the recommended dose and the safety profile of S-1 and gemcitabine combination regimen in the treatment of elderly patients (> or = 70 years) with advanced nonsmall cell lung cancer (NSCLC). Chemotherapy-naive patients with advanced NSCLC were treated with S-1 and gemcitabine. S-1 was administered orally twice daily for 14 days and gemcitabine on days 1 and 15 of each cycle, and this was repeated every 4 weeks. Doses of each drug were planned as follows: level 1, 800/60; level 2, 1000/60; level 3, 1000/70; and level 4, 1000/80 [gemcitabine (mg/m2/ day)/S-1 (mg/m2/day)]. The dose-limiting toxicity (DLT) of the regimen was assessed during the first chemotherapy cycle. Sixteen patients were enrolled in this study. The main grade 3 toxicities observed during the first cycle were neutropenia (43.7%), leukopenia (18.7%), and hyperglycemia. One of six patients in level 3 had DLT. Although no patients in level 4 experienced DLT, this level was considered the maximum tolerated dose. Level 4 was selected as the recommended dose. Objective responses were seen in four patients (response rate, 42.9%). The combination of S-1 plus gemcitabine is a feasible and well-tolerated regimen for the treatment of elderly patients with advanced NSCLC.

Topics: Administration, Oral; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Deoxycytidine; Dose-Response Relationship, Drug; Drug Combinations; Female; Gemcitabine; Humans; Hyperglycemia; Leukopenia; Lung Neoplasms; Male; Maximum Tolerated Dose; Neutropenia; Oxonic Acid; Tegafur; Treatment Outcome

To evaluate the efficacy and toxicity of combination therapy with the oral fluoropyrimidine formulation S-1 and irinotecan for patients with advanced NSCLC.. Chemotherapy-naive patients with advanced NSCLC were treated with i.v. irinotecan (150 mg/m2) on day 1 and with oral S-1 (80 mg/m2) on days 1 to 14 every 3 weeks.. Fifty-six patients (median age, 63 years; range, 40-74 years) received a total of 286 treatment cycles (median, 5; range, 1-15). No complete responses and 16 partial responses were observed, giving an overall response rate of 28.6% [95% confidence interval (95% CI), 17.3-42.2%]. Twenty-four patients (42.9%) had stable disease and 12 patients (21.4%) had progressive disease as the best response. The overall disease control rate (complete response + partial response + stable disease) was thus 71.4% (95% CI, 57.8-82.7%). Median progression-free survival was 4.9 months (95% CI, 4.0-6.4 months), whereas median overall survival was 15 months. Hematologic toxicities of grade 3 or 4 included neutropenia (25%), thrombocytopenia (3.6%), and anemia (3.6%), with febrile neutropenia being observed in four patients (7.1%). The most common nonhematologic toxicities of grade 3 or 4 included anorexia (14.3%), fatigue (8.9%), and diarrhea (8.9%). There were no deaths attributed to treatment.. The combination of S-1 and irinotecan is a potential alternative option with a favorable toxicity profile for the treatment of advanced NSCLC. This nonplatinum regimen warrants further evaluation in randomized trials.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Carcinoma, Non-Small-Cell Lung; Disease-Free Survival; Drug Combinations; Female; Humans; Irinotecan; Japan; Kaplan-Meier Estimate; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Tegafur; Treatment Outcome

The aim of this study was to determine and evaluate the recommended dose of docetaxel in combination with a novel oral 5-fluorouracil analogue S-1 and evaluate the efficacy and safety in patients with previously treated non-small cell lung cancer.. In phase I, patients with previously treated non-small cell lung cancer were treated with docetaxel (starting dose 40 mg/m) intravenously on day 1 and oral administration of S-1 at a fixed dose of 80 mg/m on days 1 to14 every 3 weeks. The recommended dose was the dose level preceding the maximum tolerated dose; once determined, patients were enrolled in phase II.. The recommended dose of docetaxel was 40 mg/m in combination with S-1 80 mg/m/d. Of 30 patients enrolled in phase II part, 29 patients were eligible and analyzed. No complete response and 7 (24.1%) partial responses were observed, for an overall response rate of 24.1% (95% confidence interval, 10.3-43.5%). Median overall survival was 11.8 months. The 1-year survival rate was 42%. The grade 3 to 4 hematologic toxicities were neutropenia (34.5%), leukopenia (20.6%), and anemia (10.3%). The grade 3 to 4 nonhematological toxicities included fever 2 (6.9%), diarrhea 1 (3.4%), stomatitis 1 (3.4%), cerebral infarction 1 (3.4%), and pneumonitis 1 (3.4%). There was one treatment-related death due to relapse of drug induced pneumonitis.. This combination chemotherapy is highly active and well tolerated in previously treated patients with non-small cell lung cancer. These results are encouraging and warrant additional investigation.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Docetaxel; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Prognosis; Salvage Therapy; Survival Rate; Taxoids; 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

Treatment of patients with unresectable recurrent oral cancer is quite difficult. In particular,there is no scientific evidence to select anti-cancer drugs for patients who were given previous radiation therapy. To select optional chemotherapy regimens, we have employed a new chemosensitivity testing method, a collagen gel droplet embedded culture sensitivity test (CD-DST) for patients with unresectable oral cancer. Six oral cancer patients with recurrence and/or metastatic disease were treated with the optional chemotherapy based on the results of CD-DST. No result was obtained due to a problem of poor growth of tumor cells in one case. In another case, we could not find a sensitive anti-cancer drug among the agents we examined. These 2 patients were treated with selected palliative pain control therapy. Optional chemotherapy based on the results of CD-DST was given to 4 patients showing sensitivity to the anti-cancer drugs examined. Tumor recession or tumor dormancy was observed clinically during a definite period. Toxicity was mild and the median survival was 10.9 months. We therefore conclude that the examination with CD-DST may provide important scientific evidence to determine a suitable chemotherapy for patients with advanced oral cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Drug Administration Schedule; Drug Combinations; Drug Screening Assays, Antitumor; Humans; Lung Neoplasms; Mitomycin; Mouth Neoplasms; Neoplasm Recurrence, Local; Oxonic Acid; Pyridines; Tegafur

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

Various kinds of combination chemotherapies with 5-FU as a base agent have been performed for patients with advanced or recurrent colorectal cancer. S-1 was a newly developed 5-FU derivative and was orally administered. One of the combination therapies with S-1 plus irinotecan (CPT-11) has also been expected to have a better therapeutic value. Recently this combination therapy has been undertaken by our department, and its clinical use and toxicities are described in this article.

Topics: Administration, Oral; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colorectal Neoplasms; Drug Administration Schedule; Drug Combinations; Humans; Infusions, Intravenous; Irinotecan; Leukopenia; Lung Neoplasms; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Oxonic Acid; Tegafur; Vomiting, Anticipatory

The purpose of this study was to evaluate the efficacy and safety of a novel oral anticancer fluoropyrimidine derivative, S-1, in patients receiving initial chemotherapy for unresectable, advanced non-small-cell lung cancer (NSCLC). Between June 1996 and July 1998, 62 patients with NSCLC who received no previous chemotherapy for advanced disease were enrolled in this study. Fifty nine patients (22 in stage IIIB and 37 in stage IV) were eligible for the evaluation of efficacy and safety. S-1 was orally administered twice daily after meals. Three doses of S-1 were prescribed according to body surface area (BSA), so that they would be approximately equivalent to 80 mg/m2/day. One cycle of S-1 consisted of consecutive administration for 28 days followed by a 2-week rest, and the cycle was repeated up to 4 times. The partial response (PR) rate of the eligible patients was 22.0% (13/59) (95% confidence interval: 12.3-34.7%). Grade 4 neutropenia was observed in one of the 59 patients (1.7%). There were no irreversible, severe or unexpected toxicities. The median survival time (MST) of all of the patients was 10.2 months (95% confidence interval: 7.7-14.5 months), and the one-year survival rate was 41.1%. S-1 was considered to be an active single agent against NSCLC.

Topics: Administration, Oral; Adult; Aged; Anorexia; Antimetabolites, Antineoplastic; Carcinoma, Non-Small-Cell Lung; Drug Administration Schedule; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Middle Aged; Neutropenia; Oxonic Acid; Quality of Life; Remission Induction; Tegafur

Early and late phase II studies of S-1 were conducted for the treatment of metastatic pancreatic cancer. In both trials, S-1 was administered at a dose of 80 mg/m2/day. One course consisted of consecutive administration of S-1 for 28 days, followed by 14 days of rest. This regimen was repeated every 6 weeks until the occurrence of progressive disease or unacceptable toxicities. The early phase II study demonstrated a response rate of 21.1% with a median survival time of 5.6 months in 19 patients. The major drug-related adverse events were gastrointestinal toxicities like nausea, and anorexia, though most of them were tolerable and reversible. Other treatment-related adverse events, like ileus, colitis, and abdominal distension, were less frequent. The late phase II study confirmed favorable responces with a mild toxicity profile in 40 evaluable patients. S-1 is active and well tolerated in patients with metastatic pancreatic cancer. Randomized trials are warranted to determine the effectiveness of S-1 for the treatment of pancreatic cancer.

Topics: Administration, Oral; Aged; Anorexia; Antimetabolites, Antineoplastic; Drug Administration Schedule; Drug Combinations; Female; Humans; Liver Neoplasms; Lung Neoplasms; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Nausea; Oxonic Acid; Pancreatic Neoplasms; Tegafur

This is the first phase II study of S-1 monotherapy for patients with metastatic colorectal cancer after failure of both irinotecan- and oxaliplatin-containing regimens. The initial dose of S-1 was 35 mg m-2, administered twice daily for 14 days every 3 weeks. Treatment was repeated until the occurrence of disease progression. Twenty-eight patients were enrolled. S-1 was administered to 21 patients as third-line therapy and to the remaining seven patients as fourth-line therapy. Of 26 evaluable patients, the overall response rate was 14.3% (95% CI, 0.4-28.1), and the disease control rate was 42.9% (95% CI, 23.3-62.4). With a median follow-up period of 227 days, median time to progression and overall survival duration were 91 and 414 days, respectively. The 1-year survival rate of all patients was 60.7%. There was no grade 4 toxicity. Grade 3 haematological toxicities were documented only in two patients. In conclusion, S-1 shows potential as a salvage regimen in heavily pretreated colorectal cancer patients. The twice-daily dose of 35 mg m-2 was well tolerated and can be used in designing further combination chemotherapy.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colorectal Neoplasms; Drug Combinations; Female; Humans; Irinotecan; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Recurrence, Local; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Salvage Therapy; Survival Rate; Tegafur; Treatment Outcome

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

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

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

The purpose of this study was to evaluate the efficacy and safety of a novel oral anticancer fluoropyrimidine derivative, S-1, in patients receiving initial chemotherapy for unresectable, advanced non-small-cell lung cancer (NSCLC). Between June 1996 and July 1998, 62 patients with NSCLC who had not received previous chemotherapy for advanced disease were enrolled in this study. 59 patients (22 stage IIIB and 37 stage IV) were eligible for the evaluation of efficacy and safety. S-1 was administered orally, twice daily, after meals. 3 dosages of S-1 were prescribed according to body surface area (BSA) so that they would be approximately equivalent to 80 mg m(-2)day(-1): BSA < 1.25 m(2), 40 mg b.i.d.; BSA> or =1.25 but <1.5 m(2); 50 mg b.i.d., and BSA> or =1.5 m(2): 60 mg b.i.d. One cycle consisted of consecutive administration of S-1 for 28 days followed by a 2-week rest period, and cycles were repeated up to 4 times. The partial response (PR) rate of the eligible patients was 22.0% (13/59); (95% confidence interval: 12.3-34.7%). A PR was observed in 22.7% (5/22) of the stage IIIB patients and 21.6% (8/37) of the stage IV patients. The median response duration was 3.4 months (1.1-13.7 months or longer). Grade 4 neutropenia was observed in one of the 59 patients (1.7%). The grade 3 or 4 toxicities consisted of decreased haemoglobin level in 1.7% of patients (1/59), neutropenia in 6.8% (4/59), thrombocytopenia in 1.7% (1/59), anorexia in 10.2% (6/59), diarrhoea in 8.5% (5/59), stomatitis in 1.7% (1/59), and malaise in 6.8% (4/59), and their incidences were relatively low. There were no irreversible, severe or unexpected toxicities. The median survival time (MST) of all patients was 10.2 months (95% confidence interval: 7.7-14.5 months), and the one-year survival rate was 41.1%. The MST of the stage IIIB patients was 7.9 months, and that of the stage IV patients was 11.1 months. The one-year survival rates of the stage IIIB and IV patients were 30.7% and 47.4%, respectively. S-1 was considered to be an active single agent against NSCLC. Further study of S-1 with other active agents is warranted.

Topics: Administration, Oral; Adult; Aged; Antimetabolites, Antineoplastic; Carcinoma, Non-Small-Cell Lung; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Middle Aged; Neutropenia; Oxonic Acid; Pyridines; Survival Analysis; Tegafur; Treatment Outcome

The efficacy and safety of S-1, a new oral fluoropyrimidine, were evaluated in patients with non-small-cell lung cancer (NSCLC). The objective of this study was to determine whether the drug should be investigated in a late phase II study.. Each treatment course consisted of an oral dose of S-1, 50 mg/body or 75 mg/body, twice a day for 28 days followed by a 2-week washout period.. Fifty-six eligible patients were enrolled. Five of the 40 previously untreated patients (12.5%; 90% confidence interval, 6.2%-23.5%) showed a partial response (PR), and no tumor response was observed in the 16 previously treated patients. The median survival duration in all eligible patients was 8.4 months, with a 1-year survival rate of 27.3%. The incidences of grade 3 or more severe adverse effects were: anemia, 5.4%; leukopenia, 5.4%; neutropenia, 5.4%; thrombocytopenia, 1.8%; anorexia, 3.6%; diarrhea, 3.6%; and general fatigue, 5.4%. These effects disappeared after cessation of the drug or appropriate treatment. One patient died as a result of aggravated interstitial pneumonitis, but the relationship of this event to S-1 was not clear.. S-1 showed modest activity with mild toxicity in the treatment of non-small-cell lung cancer. Based on this result, we will progress to the next stage of a late phase II study for advanced NSCLC, and a phase II study of S-1 and cisplatin for advanced gastric cancer. Final results will be reported as they are obtained.

Topics: Administration, Oral; Adult; Aged; Antimetabolites, Antineoplastic; Carcinoma, Non-Small-Cell Lung; Confidence Intervals; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Pyridines; Tegafur

Squamous cell lung cancer is one of the major pathological types in patients with non-small cell lung cancer. Since treatment with angiogenic agents and target drugs in patients with advanced squamous cell lung cancer is not promising, there are limited strategies to improve the outcome in such patients. Herein, we report a pretreated patient with advanced squamous cell lung cancer, who received low-dose of apatinib combined with S-1 as salvage treatment, with good long-term response.. The patient complained of dry cough for one month without any relief by medication. Otherwise, she denied any other medical or family history.. According to the chest computed tomography, and pathologic findings from biopsy for lesion in lung, the patient was diagnosed with lung squamous cell lung cancer with enlargement of bilateral supraclavicular lymph nodes suggesting metastasis, staged as IIIb.. The patient received gemcitabine plus cisplatin as first line treatment, and gemcitabine as maintenance therapy. After progression, she received vinorelbine as second line treatment. After progression again, she received low-dose apatinib combined with S-1 as third line treatment.. With the follow-up period from October 21, 2014, to April 6, 2019, there were 15 months, 9 months, and 24 months of progression-free survival time for first line (including maintenance therapy), second line, and third line treatment, respectively. The only adverse event was neutropenia at grade 2 (CTC AE) occurring during the maintenance treatment.. This case indicated that low-dose apatinib combined with S-1 might be effective and safe in selected pretreated patients with advanced squamous cell lung cancer. It might be worthy to conduct further researches to investigate the efficacy and safety of the combination therapy in such patients.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Disease Progression; Drug Combinations; Female; Humans; Lung Neoplasms; Middle Aged; Oxonic Acid; Pyridines; Tegafur

S-1 and pemetrexed (PEM) are key treatments for non-small cell lung cancer (NSCLC). However, the mechanism of anticancer activity of S-1 and PEM is similar. Cross-resistance between S-1 and PEM is of concern. This exploratory study was designed to evaluate the treatment effect of S-1 following PEM-containing treatment.. This retrospective study included patients with advanced (c-stage III or IV, UICC seventh edition) or recurrent NSCLC who received S-1 monotherapy following the failure of previous PEM-containing chemotherapy at six hospitals in Japan. The primary endpoint of the study was the overall response rate (ORR). The secondary endpoint was the disease control rate (DCR), time to treatment failure (TTF), progression-free survival (PFS), and overall survival (OS).. A total of 53 NSCLC patients met the criteria for inclusion in the study. Forty-six patients had adenocarcinoma (88.7%) and no patients had squamous cell carcinoma. Thirty-one patients (58.5%) received the standard S-1 regimen and 18 patients (34.0%) received the modified S-1 regimen. ORR was 1.9% (95% confidence interval [CI]: 0.00%-10.1%). Median TTF, PFS, and OS were 65, 84, and 385 days, respectively.. Although there were several limitations in this study, the ORR of S-1 after PEM in patients with nonsquamous (non-SQ) NSCLC was low compared to the historical control. One of the options in the future might be to avoid S-1 treatment in PEM-treated patients who need tumor shrinkage.

Topics: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Disease-Free Survival; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Pemetrexed; Retrospective Studies; Tegafur

S-1 combined with cisplatin is known to be noninferior to taxanes plus platinum as the first-line treatment for patients with advanced nonsmall cell lung cancer (NSCLC) in the Japanese population. This study aimed to evaluate the efficacy and safety profiles of oral S-1 plus cisplatin (SP) in Taiwanese patients.. Patients with previously untreated stage IIIB or IV NSCLC were prospectively recruited to receive 40-60 mg of S-1 twice daily on days 1-21 plus 60 mg/m. A total of 55 patients from five cancer centers in Taiwan were enrolled. Among the 46 evaluable patients, those administered with SP achieved disease control rate of 69.6% (partial response, 19.6%; stable disease, 50.0%), with median overall survival and progression-free survival (PFS) of 15.1 and 5.7 months, respectively. Moreover, a better survival trend was observed in epidermal growth factor receptor mutation-positive patients versus mutation-negative patients treated with SP (PFS, 8.6 vs 5.6 months). The most commonly observed treatment-related adverse events (AEs) were nausea (41.8%), followed by decreased appetite, anemia, and diarrhea. Grade of ≥3 AEs related to the study treatment occurred in 11 patients (20.0%). No febrile neutropenia or treatment-related death was found in this study.. This study demonstrated that SP is an effective and safe first-line regimen for Taiwanese patients with advanced NSCLC.

Topics: Adult; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Cisplatin; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Survival Analysis; Taiwan; Tegafur

Studies have suggested that chemotherapy after immune checkpoint inhibitors may confer an improved response for non-small cell lung cancer (NSCLC). However, potential selection bias in such studies has not been addressed. We therefore applied propensity score analysis to investigate the efficacy of chemotherapy after PD-1 inhibitor treatment (CAP) compared with chemotherapy alone.. We conducted a retrospective observational cohort study for patients treated at 47 institutions across Japan between April 1, 2014 and July 31, 2017. Eligible patients had advanced or recurrent NSCLC who have undergone chemotherapy. Patients subsequently treated with chemotherapy (docetaxel with or without ramucirumab, S-1 or pemetrexed) either after PD-1 inhibitor therapy (CAP cohort) or alone (control cohort) were included. The primary end point was objective response rate (ORR). Inverse probability weighting (IPW) was applied to adjust for potential confounding factors.. A total of 1439 patients (243 and 1196 in the CAP and control cohorts, respectively) was available for unadjusted analysis. Several baseline characteristics-including age, histology,. After accounting for selection bias by propensity score analysis, CAP showed a significantly higher ORR compared with chemotherapy alone, with the primary end point of ORR being achieved. However, these results did not translate into a PFS or OS advantage, suggesting that prior administration of PD-1 inhibitors may result in a synergistic antitumor effect with subsequent chemotherapy, but that such an effect is transient. CAP therefore does not appear to achieve durable tumor control or confer a lasting survival benefit.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Docetaxel; Drug Combinations; Drug Synergism; Female; Humans; Immune Checkpoint Inhibitors; Kaplan-Meier Estimate; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Pemetrexed; Programmed Cell Death 1 Receptor; Progression-Free Survival; Propensity Score; Ramucirumab; Retrospective Studies; Tegafur

The purpose of this study was to analyze the safety and feasibility of low-dose apatinib combined with S-1 as a second-line therapy or beyond in Chinese patients with pulmonary and/or hepatic metastases of nasopharyngeal carcinoma (NPC).. Forty-one Chinese NPC patients with pulmonary and hepatic metastases were treated with low-dose apatinib plus S-1. The S-1 dose was determined according to each patient's body surface area (BSA): 40 mg twice a day for BSA <1.25 m. Treatment efficacy was evaluated in all 41 patients after four courses of chemotherapy. The objective response rate was 34.1%, and the disease control rate was 80.4%. The median progression-free survival was 9.7 months (95% confidence interval, 6.2-13.8 months), and the median overall survival was 22.1 months (95% confidence interval, 15.1-28.9 months). The 2-year survival rate was 41.5%. The most common toxicities included loss of appetite in 39.0% of patients, dyslipidemia in 34.1%, hypertension in 31.7%, myelosuppression in 24.4%, fatigue in 21.9%, and hand-foot syndrome in 17.1%. Seven patients received dose adjustment of apatinib due to side effects.. In patients with pulmonary and/or hepatic metastases of NPC, low-dose apatinib plus S-1 yielded an excellent survival benefit, and the toxicities were mild and tolerable.

Topics: Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Asian People; Carcinoma, Non-Small-Cell Lung; Combined Modality Therapy; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Feasibility Studies; Female; Humans; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Oxonic Acid; Pyridines; Survival Rate; Tegafur; Young Adult

Adjuvant chemotherapy with platinum-based regimens for completely resected early-stage non-small cell lung cancer (NSCLC) provides overall survival benefit in several clinical trials.. We conducted this prospective study to evaluate the efficacy and safety of adjuvant chemotherapy with carboplatin and S-1 for patients with completely resected stage II to IIIA NSCLC.. Patients with completely resected stage IIA to IIIA NSCLC were treated with four cycles of carboplatin with area under the concentration time curve of 5 mg/mL/min on day 1 plus S-1 at 80-120 mg/bodyweight per day for two weeks, followed by one-week rest as adjuvant chemotherapy. The primary endpoint was the completion rate of three cycles of the treatment. The secondary endpoints were safety and two-year survival rate.. A total of 19 patients were enrolled, until the study was terminated prematurely because of fatal pulmonary embolism in two patients. The median number of treatment cycles was three (range: 1-4). The completion rate of three cycles was 78.9% (95% confidence interval [CI]: 56.6-91.4%). Two-year disease-free survival rate was 57.8%. Grade 3 or 4 hematological toxicities included neutropenia (26.2%), anemia (5.2%), and thrombocytopenia (15.7%). Grade 3 or 4 nonhematological toxicities were anorexia (10.5%) and nausea (10.5%). Febrile neutropenia developed in 5.2%. In two patients (10.5%), grade five pulmonary embolism was observed, and the causal relationship with treatment could not be denied.. Carboplatin and oral S-1 had modest survival benefit, but this regimen was not tolerable in an adjuvant setting because fatal pulmonary embolism occurred in two patients.. Carboplatin and oral S-1 had modest survival benefit but this regimen was not tolerable. Fatal pulmonary embolism occurred in this regimen.

Topics: Adenocarcinoma of Lung; Administration, Oral; Aged; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Drug Combinations; Female; Follow-Up Studies; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Pilot Projects; Prospective Studies; Survival Rate; Tegafur

Herein, we report a case of unresectable lung cancer in which S-1 monotherapy contributed to an improvement in the patient's quality of life and to prolonged survival. A 44-year-old man with primary pulmonary adenocarcinoma(negative driver mutation and a PD-L1 tumor proportion score of 1-24%)of clinical stage ⅢA(cT4N0M0)underwent multidisciplinary treatment as follows: 1 ) weekly carboplatin and paclitaxel plus radiotherapy as induction chemoradiotherapy, 2 ) surgery that revealed that the lesion was unresectable, 3 ) cisplatin plus pemetrexed as second-line treatment, and 4 ) pembrolizumab as third-line treatment. However, the disease progressed after 19 courses of pembrolizumab, and the patient developed cachexia due to esophageal stenosis caused by tumor enlargement. He underwent percutaneous gastrostomy and was fed via a gastrostomy tube. S-1 monotherapy(2-week administration every 3 weeks)was introduced as fourth-line treatment. After 3 courses of S-1 monotherapy, the patient complained of regurgitation of stomach fluid. Computed tomography( CT)revealed that the primary tumor had decreased in size, and he developed the ability to drink water. After 6 courses of S-1, CT revealed progressive disease, so atezolizumab was administered as fifth-line treatment. However, after 2 courses, mediastinitis due to esophageal penetration into the mediastinum occurred. The patient died 28 months after the initial treatment.

Topics: Adenocarcinoma of Lung; Adult; Antimetabolites, Antineoplastic; Drug Combinations; Humans; Lung Neoplasms; Male; Oxonic Acid; Quality of Life; Tegafur

S-1 monotherapy is effective and feasible for previously treated patients with advanced non-small cell lung cancer (NSCLC). However, it is not clear whether its effectiveness and tolerability in elderly patients are equivalent to those in younger patients. Hence, this study aimed to evaluate the efficacy and feasibility of S-1 monotherapy in elderly patients with NSCLC who had previously received other treatments.. We included 96 elderly patients (aged ≥75 years) with advanced NSCLC treated with S-1 alone as a subsequent-line treatment at 12 medical facilities between January 2005 and March 2018 in this study. The baseline characteristics of the patients, response to S-1 monotherapy, and adverse events (AEs) were investigated, retrospectively.. A total of 68 male and 28 female patients (median age, 78 [range: 75-86] years) were analyzed. In elderly patients who were treated with S-1 monotherapy as a subsequent-line treatment, the objective response rate, disease control rate, median progression-free survival (PFS), and overall survival (OS) were 8.3%, 43.8%, 3.4 months, and 9.6 months, respectively. Observed AEs included anorexia, anemia, nausea, fatigue, reduced platelet count, and skin hyperpigmentation. Treatment-related death was observed in one patient because of pneumonitis. In patients who experienced no progressive disease, subsequent-line S-1 alone was associated with longer PFS and OS.. S-1 monotherapy is effective and feasible as a subsequent-line treatment in elderly patients who were previously treated for NSCLC, and it produces results. S-1 monotherapy could be one of the treatment choices for elderly patients with previously treated NSCLC.

Topics: Aged; Aged, 80 and over; Carcinoma, Non-Small-Cell Lung; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Oxonic Acid; Retrospective Studies; Tegafur

Topics: Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Non-Small-Cell Lung; Chemotherapy, Adjuvant; Drug Combinations; Humans; Lung Neoplasms; Oxonic Acid; Tegafur

A 68-year-old man underwent a subtotal stomach-preserving pancreatoduodenectomy(SSPPD)for a distal bile duct carcinoma(BDC)pT3aN1M0, pStage ⅡB and adjuvant chemotherapy with gemcitabine. One year 7 months after the initial surgery, CT revealed a nodule with an increasing tendency in the left lung. As it was difficult to distinguish primary lung cancer from BDC lung metastasis, we performed a thoracoscopic left wedge resection. The histopathology of the resected specimen was BDC lung metastasis. In the follow-up with adjuvant chemotherapy with S-1 for 10 months, 2 nodules were found in the right lung, and we performed thoracoscopic right S6 segmentectomy. Eight months later, another nodule was found in the left lung, and we performed thoracoscopic left wedge resection. The histopathology was BDC lung metastasis for all the resected specimens. The patient is alive with no evidence of recurrence after 9 months of the latest surgery(4 years 11 months after the initial surgery). Although the standard treatment for metastatic recurrence of BDC is systemic chemotherapy, some cases treated with surgical resection had relatively good prognosis, such as the present case. Surgical resection might be feasible as a treatment option for metastatic recurrence of BDC.

Topics: Aged; Antimetabolites, Antineoplastic; Bile Duct Neoplasms; Bile Ducts; Drug Combinations; Humans; Lung Neoplasms; Male; Neoplasm Recurrence, Local; Oxonic Acid; Pancreaticoduodenectomy; Pneumonectomy; Tegafur

Objective A subset analysis of the LETS study suggested that S-1 plus carboplatin was more beneficial than paclitaxel plus carboplatin in terms of the overall survival (OS) in squamous cell lung cancer. However, the benefit of maintenance therapy for squamous cell non-small cell lung cancer (NSCLC) patients is still unknown. We herein report a phase II study to evaluate the efficacy and safety of a tailored dose of S-1 plus carboplatin followed by maintenance S-1 in chemotherapy-naive advanced squamous cell NSCLC. Methods Patients received carboplatin on day 1 plus S-1 on days 1 to 14 every 21 days. The dose of S-1 was determined by the body surface area and creatinine clearance. After four cycles of induction, non-progressive patients continued to receive S-1 until disease progression or unacceptable toxicity occurred. The primary endpoint was an objective response rate (RR) with a threshold value of 15%. The secondary endpoints were the progression-free survival (PFS) and OS from enrollment, the PFS in the maintenance phase, and safety. Results In the 33 patients analyzed, the rate of patients who met the primary endpoint was 30.3% (95% confidence interval: 15.6-48.7%), and the disease control rate was 75.8%. The median PFS and OS were 3.5 and 11.3 months, respectively. Ten patients received maintenance S-1, and the median PFS from the beginning of induction treatment was 5.3 months. Grade 3/4 toxicities with a frequency of more than 5% were all controllable. Conclusion Tailored-dose S-1 plus carboplatin followed by maintenance S-1 is an effective and feasible treatment for advanced squamous cell NSCLC.

Topics: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Drug Combinations; Epithelial Cells; Female; Humans; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Paclitaxel; Tegafur

Cytotoxic chemotherapy for advanced non-small cell lung cancer (NSCLC) as second-line or subsequent treatment generally results in a poor treatment outcome. Several reports have indicated that subsequent cytotoxic chemotherapy in patients who have received immune checkpoint inhibitors (ICIs) might have relatively better efficacy.. The clinical data of advanced NSCLC patients treated with nivolumab during clinical practice at the National Cancer Center Hospital between 17 December 2015 and 31 August 2017 were consecutively reviewed, and the treatment outcomes of docetaxel-based chemotherapy (docetaxel +/- ramucirumab) or S-1 after nivolumab were analyzed. The results were then compared with those of advanced NSCLC patients treated with docetaxel or S-1 but not ICIs during clinical practice between 17 December 2014 and 16 December 2015.. Thirty patients were administered docetaxel-based chemotherapy and 21 patients were administered S-1 in any line after nivolumab. Twenty-four patients were administered docetaxel-based chemotherapy and 15 patients were administered S-1 immediately after nivolumab. Sixty-six patients were administered docetaxel and 23 patients were administered S-1 without ICIs. The objective response rate, disease control rate, and median progression-free survival duration were 28.6%, 53.6%, and 5.26 months for patients receiving docetaxel-based chemotherapy or S-1 immediately after nivolumab treatment; 24.3%, 51.4%, and 3.88 months for patients receiving docetaxel-based chemotherapy or S-1 in any line after nivolumab; and 16.4%, 56.7%, and 2.74 months, for patients receiving docetaxel or S-1 without ICIs, respectively.. Subsequent cytotoxic chemotherapy, especially immediately after nivolumab, has better treatment efficacy than that of regimens without ICI pretreatment.

Topics: Adult; Aged; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Docetaxel; Drug Combinations; Female; Humans; Kaplan-Meier Estimate; Lung Neoplasms; Male; Middle Aged; Nivolumab; Oxonic Acid; Ramucirumab; Retreatment; Tegafur; Treatment Outcome

Non-small cell lung cancer (NSCLC) is the most common lung cancer. Numerous clinical studies have reported that the combination of carboplatin and S-1 (CS) can be used to treat NSCLC effectively. However, no systematic review has been conducted to assess its efficacy and safety for NSCLC. This systematic review aims to evaluate the efficacy and safety of CS for treatment of patients with NSCLC.. This study will retrieve the following electronic databases from inception to the February 1, 2019: Cochrane Library, EMBASE, MEDILINE, CINAHL, AMED, and 4 Chinese databases without any language limitations. This systematic review will include randomized controlled trials (RCTs) and case-control studies for assessing the efficacy and safety of CS for the treatment of NSCLC. Cochrane risk of bias will be used as methodological quality assessment for each qualified study. The RevMan V.5.3 software will be utilized to synthesize the data and conduct the meta-analysis if it is allowed. The data will be pooled by using the random-effects model or fixed-effects model.. The primary outcome is overall response rate. The secondary outcomes are overall survival, progression-free survival, the disease control rate, and any adverse events.. It will provide latest evidence to determine the efficacy and safety of CS for treatment of patients with NSCLC.. No research ethic approval is needed in this study because this study will not analyze individual patient data. The results are expected to disseminate through peer-reviewed journals.. PROSPERO CRD42019124860.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Non-Small-Cell Lung; Drug Combinations; Humans; Lung Neoplasms; Meta-Analysis as Topic; Oxonic Acid; Randomized Controlled Trials as Topic; Systematic Reviews as Topic; Tegafur

Colorectal cancer is a common malignancy and a major health issue in geriatrics. Systemic chemotherapy should be considered for elderly patients. We report an 85-year-old man with metastatic cecal cancer who has achieved long-term survival following single-agent chemotherapy with S-1. His fecal occult blood test results were positive; he then underwent colonoscopy and was diagnosed with cecal cancer. Chest CT revealed multiple metastases in both lungs. Since radical excision was infeasible, we performed right hemicolectomy to prevent bowel obstruction. Histological examination revealed a T3, N0, M1a (PUL2), Stage IV tumor. After discharge from the hospital, the patient preferred receiving chemotherapy that would have fewer side effects. S-1 monotherapy was administered. Despite increased progression of the pulmonary metastases, he experienced no subjective symptoms, his QOL remained consistent, and he completed 42 cycles of chemotherapy in total. The patient is currently being managed on an outpatient basis. In conclusion, elderly patients with cancer should be carefully evaluated according to both disease control and individual circumstances, such as patient's tolerability, QOL, and preference.

Topics: Aged, 80 and over; Antimetabolites, Antineoplastic; Cecal Neoplasms; Drug Combinations; Humans; Lung Neoplasms; Male; Neoplasm Staging; Oxonic Acid; Tegafur; Tomography, X-Ray Computed; Treatment Outcome

A patient in his 70s was diagnosed with sigmoid colon cancer[pT3pN1cM1(PUL1), pStage IV ]for which he underwent sigmoid colectomy and received S-1 adjuvant therapy for the lung metastases. The patient received a total of 10 courses of S- 1, administered orally on days 1-14 of a 21-day cycle. The lung metastases showed a complete response, and the patient completed the S-1 chemotherapy. No recurrence of lung metastases was detected up to 6 months later.

Topics: Aged; Antimetabolites, Antineoplastic; Colectomy; Drug Combinations; Humans; Lung Neoplasms; Male; Oxonic Acid; Sigmoid Neoplasms; Tegafur; Treatment Outcome

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

To investigate the potential radiosensitization of S-1 and gefitinib in human non-small cell lung cancer (NSCLC) in vitro and in vivo.. The impact of radiation, 5-fluorouracil (5-Fu), and gefitinib on the proliferation and apoptosis of human NSCLC A549, H1299, H1975, and HCC827 cells was examined by MTT and flow cytometry. The effect of radiation, 5-Fu, and gefitinib on the clonogenicity of H1975 and HCC827 cells was determined by colony formation assay. The effect of radiation, 5-fluorouracil (5-Fu), and gefitinib on the EGFR, AKT, and ERK1/2 activation in H1975 cells was determined by Western blot. The therapeutic efficacy of radiation, S-1, and gefitinib in the growth of implanted H1975 tumors and the AKT activation in the tumors were examined in vivo and immunohistochemistry, respectively.. Combination of radiation, 5-Fu, and gefitinib significantly inhibited the proliferation of H1975 cells and triggered their apoptosis, but not other NSCLC cells tested. The combination therapy significantly mitigated the clonogenicity and attenuated the activation of EGFR and AKT signaling in H1975 cells. Furthermore, combination of S-1, gefitinib, and radiation significantly inhibited the growth of implanted H1975 tumors in mice and remarkably reduced the AKT phosphorylation in the tumors.. Our data indicated that combination of S-1 and gefitinib significantly increased radiosensitivity of H1975 cells. The triple combination therapies may benefit patients with the EGFR T790M mutant NSCLC.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Carcinoma, Non-Small-Cell Lung; Cell Proliferation; Chemoradiotherapy; Drug Combinations; Drug Resistance, Neoplasm; Gamma Rays; Gefitinib; Humans; Lung Neoplasms; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Oxonic Acid; Phosphorylation; Radiation-Sensitizing Agents; Tegafur; Tumor Cells, Cultured; Xenograft Model Antitumor Assays

The patient was a 78-year-old man with resection of distal pancreatectomy for pancreatic cancer with simultaneous multiple lung metastasis. They were papillary and tubular adenocarcinoma, Pt, TS3, infiltrative type, ly0, v0, pT3, CH0, DU0, S1, RP1, PV0, A1(Asp), PL0, OO0 and pN0, M1(PUL), pStage IV. He was received gemcitabine after the surgery. S-1 was added because of lung metastasis progression. Chemotherapy was continued for about 10 years from resection, and intra-abdominal recurrence was not observed and good performance status was maintained. 5-year survival rate of pancreatic cancer is as low as about 6.5%in Stage IV. There are cases where lung resection to isolated lung metastasis are performed after resection of pancreas and long-term-survival are obtained. A resected case of long-term-survival of pancreatic cancer with simultaneous multiple lung metastasis is rare, so we will report with a few literature considerations.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Deoxycytidine; Drug Combinations; Gemcitabine; Humans; Lung Neoplasms; Male; Oxonic Acid; Pancreatectomy; Pancreatic Neoplasms; Prognosis; Tegafur; Time Factors

Topics: Adenocarcinoma of Lung; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Docetaxel; Drug Combinations; Humans; Lung Neoplasms; Male; Oxonic Acid; Paget Disease, Extramammary; Pneumonectomy; Positron-Emission Tomography; Skin Neoplasms; Tegafur; Treatment Outcome

Adjuvant chemotherapy with uracil tegafur (UFT) improved survival among patients with completely resected stage I lung adenocarcinoma. S-1, an oral dihydropyrimidine dehydrogenase (DPD)-inhibitory 5-fluorouracil, is a more potent DPD inhibitor than UFT;therefore, we hypothesized that postoperative adjuvant chemotherapy with S-1 would be effective for advanced non-small cell lung cancer (NSCLC). We conducted a feasibility study of S-1 as postoperative adjuvant chemotherapy in patients with curatively resected pathological stage bold I back 10 bold I and bold I back 10 bold I back 20 bold I A NSCLC.. Adjuvant chemotherapy consisted of 9 courses (4-week administration, 2-week withdrawal) of S-1 at 80-120 mg/body per day. Twenty-four patients with completely resected NSCLC were enrolled in this study from November 2007 through December 2010. The primary endpoint was the rate of completion of the scheduled adjuvant chemotherapy. The secondary endpoints were safety, overall survival, and relapse-free survival.. Five patients were censored because of disease recurrence. The planned 9 courses of S-1 were administered to completion in 8 patients. Twelve patients completed more than 70% of the planned courses. Grade 3 adverse reactions, such as elevated total bilirubin (4.2%) and pneumonitis (4.2%), were observed, but there were no Grade 4 adverse reactions. Patients who completed more than 70% of the 9 courses demonstrated better overall survival than those who completed less than 70%.. Postoperative administration of S-1 may be possible with few severe adverse events as adjuvant chemotherapy for patients with curatively resected pathological stage bold I back 10 bold I -bold I back 10 bold I back 20 bold I A NSCLC. J. Med. Invest. 65:90-95, February, 2018.

Topics: Aged; Carcinoma, Non-Small-Cell Lung; Chemotherapy, Adjuvant; Drug Combinations; Feasibility Studies; Female; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Tegafur

Brain metastasis (BM) is a rising challenge in forward-looking oncology, as its treatment choices are very limited, especially, after the failure of local treatment schemes.. We report on a 39-year-old Chinese woman who was diagnosed with stage IV triple-negative breast cancer(TNBC) with multiple brain, lung, and bone metastases. She had previously, undergone whole-brain radiation therapy. Paclitaxel, platinum, UTD1, capecitabine, gemcitabine, vinorelbine, and single-agent apatinib were then administered as first- to fifth-line therapies. She exhibited progression each time after a short period of disease stabilization.. Triple-negative breast cancer.. The patient chose treatment with apatinib+CPT-11+S-1 as the sixth-line therapy.. A remarkable response of the brain, and lung metastases, and alleviation of the brain edema were achieved, and these effects persisted for 7 months.. We describe the significant anti-tumor effect of apatinib + CPT-11 + S-1 against BMs from breast cancer. This report is the first to suggest potential approaches to BM treatment using this scheme and describes the effects of an apatinib-containing regimen on BMs.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Brain Edema; Brain Neoplasms; Camptothecin; Disease Progression; Drug Combinations; Female; Humans; Irinotecan; Lung Neoplasms; Neoplasm Staging; Oxonic Acid; Pyridines; Tegafur; Triple Negative Breast Neoplasms

We investigated the efficacy of concurrent radiotherapy plus S-1 (CRS) for treating unresectable stage III advanced non-small-cell lung cancer (ANSCLC).Seventy five ANSCLC patients were included in this retrospective study. Of those, 40 patients were assigned to an intervention group, and received S-1 (orally at 40 mg/m) twice daily for 14 consecutive days. Then, concurrent radiotherapy was administered in 2 Gy fractions, 5 times weekly for a total dose of 60 Gy. The other 35 patients were assigned to a control group, and underwent concurrent radiotherapy (the same as the intervention group) and cisplatin (60 mg/m on day 1 (CRC). The outcome measurements included overall response rate (ORR), overall survival (OS), progression-free survival (PFS), and toxicity.The 3-year ORR was 60.7% and 43.9% for intervention group and control group, respectively (P = .031). The median OS was 34.1 months and 25.3 months in the intervention and control groups, respectively (P = .041). The median PFS was 31.5 months for intervention group, while it was 22.4 months for control group (P = .048). No significant difference in toxicity was found between the 2 groups.The results demonstrated that the efficacy of CRS was superior to the CRC in ANSCLC patients with similar toxicity.

Topics: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Chemoradiotherapy; China; Cisplatin; Combined Modality Therapy; Disease-Free Survival; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Retrospective Studies; Tegafur; Treatment Outcome

There is no standard treatment for advanced non-small cell lung cancer (NSCLC) after the failure of two lines of chemotherapy, S-1 as the third generation of fluorouracil derivate with well safety and low toxicity, presented some efficacy in lung cancer treatment. The aim of this study is to explore the efficacy of S-1 for advanced NSCLC patients treated with two or more prior chemotherapy regimens.. We performed a retrospective analysis of 105 NSCLC patients treated with S-1 monotherapy or S-1 contained chemotherapy as the third or more line of treatment in our hospital from January 2014 to April 2017. S-1 was administrated orally twice daily for 2 weeks, followed by one week of rest, the dose of drug was determined by body surface area (<1.25 m2, 80 mg/d; 1.25 m2-1.5 m2, 100 mg/d; ≥1.5 m2, 120 mg/d), platinum or the third-generation chemotherapy drugs could be combinedly used. Clinical response was assigned every cycle according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, Kaplan-Meier analysis was used to estimate progression-free survival (PFS).. 42 patients received S-1 monotherapy, the other 63 patients received combined regimens, the median treatment line was 4 (3-11) and the median treatment cycle was 2 (1-14). No complete response (CR) were observed, there were 4 patients with partial response (PR), 34 patients with stable disease (SD) and 67 patients with progressive disease (PD), the objective response rate (ORR) was 3.81%, disease control rate (DCR) was 36.19%. The median PFS was 1.90 months (0.67 months-10.83 months), no difference between monotherapy and combined group (DCR: 28.56% vs 41.27%, P=0.185), the liver metastasis showed poorer PFS (1.40 months vs 1.93 months , P=0.042).. S-1 presented some activity in advanced NSCLC treated with more than two lines of treatment. The addition of other drugs cannot improve efficacy. S-1 monotherapy can be used as a choice for heavily-treated patients.. 【中文题目：替吉奥治疗晚期非小细胞肺癌三线及以上
患者的疗效分析】 【中文摘要：背景与目的 晚期非小细胞肺癌一二线治疗后进展，目前尚无标准的治疗方案，替吉奥作为安全低毒的第三代氟脲嘧啶衍生物，对肺癌具有一定疗效，本研究旨在探讨替吉奥在晚期三线及以上非小细胞肺癌患者中的疗效。方法 回顾性分析105例2014年1月-2017年4月我院收治的使用替吉奥单药或联合方案治疗三线及以上晚期非小细胞肺癌患者的临床资料，替吉奥使用方法：体表面积<1.25 m2，每日80 mg；1.25 m2-1.5 m2，每日100 mg；≥1.5 m2，每日120 mg，分2次口服，连续使用1 d-14 d，21 d为1个周期。可联合铂类或其他第三代化疗药物。每周期根据实体瘤疗效评价标准（Response Evaluation Criteria in Solid Tumors, RECIST）1.1标准评价近期疗效，采用Kaplan-Meier方法统计生存数据。结果 替吉奥单药治疗42例，联合用药63例，中位治疗线数4（3-11），中位周期数2（1-14）。无完全缓解患者，部分缓解患者4例，疾病稳定患者34例，疾病进展患者67例。客观有效率3.81%，疾病控制率36.19%。中位无进展生存期1.90个月（95%CI: 0.67-10.83），单药或联合治疗疗效相似（疾病控制率：28.56% vs 41.27%，P=0.185），肝转移患者预后更差（中位无进展生存期：1.40个月 vs 1.93个月，P=0.042）。结论 在晚期非小细胞肺癌患者三线及以上抗肿瘤治疗中，替吉奥具有一定疗效，联合用药不能进一步提高疗效，替吉奥单药可作为多程治疗后患者的选择之一。】 【中文关键词：替吉奥；肺肿瘤；化疗；药物耐药】.

Topics: Adult; Aged; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Drug Combinations; Female; Fluorouracil; Humans; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Retrospective Studies; Safety; Survival Analysis; Tegafur; Treatment Outcome

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

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

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

Interstitial lung disease (ILD) is commonly concomitant with lung cancer, and its acute exacerbation (AE) is the most serious complication in patients receiving treatment for lung cancer.. To investigate the incidence and characteristic features of AE of ILD, we conducted a retrospective study of 665 consecutive patients with lung cancer who were treated at our institute between 2008 and 2014.. Among the 665 patients, 74 (11.1%) had preexisting ILD, and 64 of them received chemotherapy. Four of the 64 patients (6.3%) had experienced AE of ILD, and two (3.1%) died of respiratory failure during first-line chemotherapy. The use of a combination of carboplatin with tegafur-gimeracil-oteracil potassium (S-1) or paclitaxel as a first-line chemotherapy for non-small cell lung cancer led to a lower frequency of AE, at 8.3% (1/12) and 9.1% (1/11), respectively. The incidence of AE rose to 12.8% (5/39) during second-line treatment, and 14 (total: 15 times) of the 64 patients (21.9%) experienced AE from the time of diagnosis to the end of treatment. The incidence of AE was 17.7% (6/34), 15.8% (3/19), 5.0% (2/40), and 4.2% (1/24) in the paclitaxel-, vinorelbine-, etoposide-, and S-1-containing regimens, respectively. No difference in clinical features and laboratory data was detected between the AE and non-AE groups.. Although this was a small retrospective study, its findings showed that S-1 and etoposide may be relatively safe options for the treatment of patients with lung cancer and concomitant ILD.

Topics: Acute-Phase Reaction; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Disease Progression; Drug Combinations; Etoposide; Feasibility Studies; Female; Humans; Incidence; Lung Diseases, Interstitial; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Paclitaxel; Respiratory Insufficiency; Retrospective Studies; Tegafur

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

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Colitis; Drug Combinations; Escherichia coli Infections; Escherichia coli O157; Female; Humans; Lung Neoplasms; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Rectal Neoplasms; Tegafur; Tomography, X-Ray Computed

Pre-existing interstitial lung disease (pre-ILD) increases the risk of chemotherapy-related lung injury (CRLI). However, whether the risk varies by type of anti-cancer cytotoxic agent in patients with pre-ILD is unknown. In this study, we hypothesized that S-1, an oral fluoropyrimidine agent, is associated with a smaller CRLI risk than docetaxel (DTX) and investigated these agents together with radiological evaluations of pre-ILD via pre-treatment chest computed tomography (CT).. After reviewing 234 and 352 patients who underwent evaluable chest CT within 6 months prior to the administration of S-1 or DTX, respectively, from January 2006 to October 2014, 60 and 89, respectively, of these patients with pre-ILD were retrospectively analysed.. In total, 2 persons administered S-1 (3 %) and 16 treated with DTX (18 %) developed CRLI (p = 0.007) after the initial treatment (mean, 61 days), of whom 1 and 7, respectively, died because of respiratory failure. Pre-treatment CT revealed that 9 S-1-treated patients (16 %) and 15 DTX-treated patients (17 %) had pre-ILD occupying more than 25 % of the lung field. Multivariate analysis demonstrated that DTX administration increased the risk of CRLI by 6.47-fold versus S-1 therapy (p = 0.016). Of note, the area occupied by pre-ILD was also associated with the risk of CRLI (<25 %; odds ratio 0.309, p = 0.045).. Our results indicated that S-1 is associated with a smaller risk of CRLI than DTX. The area occupied by pre-ILD should also be noted when administrating anti-cancer agents.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Docetaxel; Drug Combinations; Female; Humans; Logistic Models; Lung Diseases, Interstitial; Lung Injury; Lung Neoplasms; Male; Medical Records; Middle Aged; Oxonic Acid; Predictive Value of Tests; Retrospective Studies; Risk; Taxoids; Tegafur; Tomography, X-Ray Computed

The recommended regimen for S-1 internal use is 4 weeks of daily medication and 2 weeks of drug holiday. However, we experience many cases where changing the regimen is ineffective because of adverse events. This time, we report a favorable case of alternate-day treatment with S-1 in an elderly patient with multiple lung metastases of colon cancer. An 84-year-old woman, performance status 2, was diagnosed as having colon cancer and multiple lung metastases. After operation of the colon, she received chemotherapy with the S-1 alternate-day treatment. The lung metastases decreased remarkably, and she was able to continue the treatment without significant adverse events. She has been receiving the treatment without progression for more than 18 months now. The alternate-day treatment with S-1 is reported as a cure with anticancer efficacy and few adverse events. This treatment seems to be a useful chemotherapy for elderly patients with colon cancer.

Topics: Aged, 80 and over; Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Colonic Neoplasms; Drug Combinations; Female; Humans; Lung Neoplasms; Oxonic Acid; Tegafur; Treatment Outcome

There is no established standard regimen for non-small cell lung cancer (NSCLC) patients with interstitial lung disease (ILD). For them, we performed a pilot study to evaluate the feasibility of chemotherapy with carboplatin and S-1, which are known as cytotoxic drug with rare development of ILD as adverse event.. A total of 21 chemotherapy-naive NSCLC patients with ILD were prospectively enrolled between March 2009 and September 2011. Every 3 weeks, carboplatin at a dose of AUC 5 on day 1 and S-1 at a dose of 80 mg/m2 daily for 14 days were administered.. The median age at initiating chemotherapy was 67. Histological examination revealed 10 patients (48 %) with adenocarcinoma. Before chemotherapy, partial pressure of arterial O2 (PaO2) was low with a median of 71 Torr on room air. The median number of cycles administered was four, and the overall response rate and disease control rate were 33 and 67 %, respectively. At the time of data cut-off, all patients were deceased. The median progression-free survival (PFS) and median overall survival (OS) periods were 4.2 and 9.7 months. There was no significant difference of PFS and OS according to tumor histology. Acute exacerbation (AE) of ILD following S-1 plus carboplatin occurred in two patients (10 %, 2/21) within first course treatment. However, they were successfully managed with steroid therapy and survived for 7.0 and 8.8 months, respectively, after AE-ILD development.. This is the first prospective study to evaluate the safety and efficacy of S-1 plus carboplatin treatment for NSCLC patients with ILD. This regimen could be a feasible option for NSCLC patients with ILD, regardless of tumor histology. Our results would support to carry out a large-scale clinical trial to confirm the feasibility of this regimen.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Non-Small-Cell Lung; Disease-Free Survival; Drug Combinations; Female; Humans; Kaplan-Meier Estimate; Lung Diseases, Interstitial; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Pilot Projects; Prospective Studies; Tegafur

Concurrent chemoradiotherapy (CCRT) is the preferred treatment for stage III unresectable non-small cell lung cancer (NSCLC). However, there have been few reports on combination chemotherapy with radiation for second- and third-generation antitumor drugs, although clinical guidelines have recommended the use of these drugs along with platinum agents.. We retrospectively analyzed the efficacy and toxicity of cisplatin and either S-1 or vinorelbine for treating stage III unresectable NSCLC patients who were treated with CCRT.. Between September 2006 and May 2014, 56 patients with unresectable stage III NSCLC were treated with CCRT with S-1 and cisplatin (median age: 63 years) and 58 patients were treated with CCRT with vinorelbine and cisplatin (median age: 61 years). The median follow-up time was 14.6 months in the S-1 arm and 28.0 months in the vinorelbine arm. We found no significant difference in progression-free survival (15.8 months vs. 10.1 months; p=0.15) and overall survival (33.7 months vs. 31.1 months; p=0.63) between the S-1 and vinorelbine arms, respectively. Severe (more than grade 3) leukopenia (35.7% vs. 98.2%; p<0.01), neutropenia (44.6% vs. 98.2%; p<0.01), and febrile neutropenia (1.8% vs. 46.6%, p<0.01) were significantly less frequent in the S-1 arm than in the vinorelbine arm. Treatment-related deaths were not observed in either arm.. CCRT with both S-1 or vinorelbine with cisplatin appears feasible based on their efficacy and toxicity profiles. Both treatments may be recommended as treatment options for patients with stage III unresectable NSCLC.

Topics: Adult; Aged; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Chemoradiotherapy; Cisplatin; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Retrospective Studies; Tegafur; Vinblastine; Vinorelbine

A 50-year-old woman with a chief complaint of bloody stools was diagnosed with rectal cancer via colonoscopy. Laparoscopic rectal anterior resection with D3 lymph node dissection was performed in June 2014. The pathological diagnosis was pStage III a(Ra, pT3, N1)cancer, and the patient received 8 courses of XELOX as postoperative adjuvant chemotherapy. During follow-up at 12 months after surgery, chest computed tomography revealed a mass in the left lingular segment measuring 25mm in diameter and multiple small nodules in both the lungs, indicating lung metastases. We found several subcutaneous nodules with a maximum diameter of 10mm in her abdomen and the back of head. We removed 3 subcutaneous nodules for the purpose of diagnosis and treatment in June of 2015. The pathological findings were consistent with cutaneous metastases of rectal cancer. The patient received a 1 course of IRIS and 5 courses of IRIS plus bevacizumab. Subsequently, the lung metastases disappeared and no new skin lesions were detected. We suggest that this case could be a good reference in determining the appropriate treatment for rectal cancer having lung or cutaneous metastases.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Chemotherapy, Adjuvant; Drug Combinations; Female; Humans; Irinotecan; Lung Neoplasms; Middle Aged; Oxonic Acid; Rectal Neoplasms; Skin Neoplasms; Tegafur; Treatment Outcome

A woman in her 70's presented with the predominant complaint of bloody stools. She was diagnosed with rectal cancer, and bilateral lymph node and pulmonary metastases were detected on computed tomography(CT). The patient was diagnosed with cT3N3M1a, cStage IV disease. After undergoing a colostomy, the patient was treated with S-1 plus oxaliplatin (SOX), and bevacizumab(Bev). A second CT scan obtained after completion of 7 courses of chemotherapy revealed that the lung metastases had significantly reduced or disappeared. Approximately 7 months after initial treatment, the patient underwent a laparoscopic Hartmann procedure to remove the tumor. The patient is currently under observation while being administered postoperative adjuvant chemotherapy as an outpatient in our department. There is currently no evidence of the safety of laparoscopic-assisted rectal cancer surgery for first-time Stage IV cases. However, when tumor regression has been achieved with chemotherapy, it may be an effective option.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Colostomy; Drug Combinations; Female; Humans; Laparoscopy; Lung Neoplasms; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Rectal Neoplasms; Tegafur

S-1 is a newly developed dihydropyrimidine dehydrogenase inhibitory fluoropyrimidine that exhibits high clinical efficacy against non-small cell lung cancers. To identify genes that may be associated with chemosensitivity to the antitumor drug S-1, we used a low density array representing 93 genes to analyze expression profiles in 4 orthotopically implanted lung cancers derived from human lung cancer cell lines (Lu99, Lu130, LC6 and A549). The tumor growth inhibition (TGI) rates of S-1 in orthotopically implanted tumors of the Lu99, Lu130, LC6 and A549 cell lines were 34.6, 37.5, 32.1 and 3.6%, respectively. The expression of the PRSS3, ABCC4, TXN, SHMT1 and CMPK genes was significantly promoted in the orthotopically implanted SCID mouse model of the 4 lung cancer cell lines by the administration of S-1, while the expression of the LMO7 and FOLH1 genes was significantly suppressed. The expression of the ABCC1, 2 and TST genes was negatively correlated with TGI. The expression of the TK1 and ERCC2 genes was positively correlated with TGI. The results of the present study suggest that the expression of the ABCC1, 2, TST, TK1 and ERCC2 genes is related to resistance to the antitumor drug S-1.

Topics: Animals; Antineoplastic Agents; Cell Line, Tumor; Drug Combinations; Gene Expression Regulation, Neoplastic; Humans; Lung Neoplasms; Mice; Microarray Analysis; Neoplasm Proteins; Oxonic Acid; Tegafur; Xenograft Model Antitumor Assays

Post-operative adjuvant chemotherapy has been considered an effective strategy to reduce cancer recurrence and improve survival for resected non-small-cell lung cancer. The Japan Clinical Oncology Group has completed patient accrual for a randomized Phase III study (JCOG0707), which compares the survival benefit of UFT and S-1 for completely resected pathological Stage I (T1 >2 cm and T2 in TNM classification version 6) non-small-cell lung cancer. However, there is a growing concern that those who participated in clinical trials are highly selected patients and do not represent the 'real-world' population. This multicenter observational cohort study aims to analyze the backgrounds, pattern of care and outcomes of the patients who were excluded from the JCOG0707 study during the accrual period. The results of this cohort study will be useful for external validity of the results of clinical trial such as JCOG0707.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Chemotherapy, Adjuvant; Cohort Studies; Disease-Free Survival; Drug Combinations; Female; Fluorouracil; Humans; Kaplan-Meier Estimate; Lung Neoplasms; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Oxonic Acid; Patient Selection; Postoperative Period; Prodrugs; Proportional Hazards Models; Tegafur; Uracil

We report 3 cases of long-term control achieved via S-1 monotherapy in elderly patients with advanced non-small-cell lung cancer. In case 1, a 75-year-old man clinically diagnosed with stage IIIA lung adenocarcinoma received S-1 as fourthline chemotherapy. PR was achieved, and PFS was 8 months. In case 2, a 78-year-old woman clinically diagnosed with stage IV lung squamous cell carcinoma received S-1 as third-line chemotherapy. A PR was achieved, and PFS was 14 months. In case 3, an 83-year-old man clinically diagnosed with stage IV lung squamous cell carcinoma received CBDCA plus PTX, followed by S-1 on alternate days. Although tumor size was not reduced, SD was maintained for 11 months.

Topics: Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Carcinoma, Non-Small-Cell Lung; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Neoplasm Staging; Oxonic Acid; Tegafur; Tomography, X-Ray Computed

The prognosis of Stage IV b pancreatic cancer is extremely poor; the mean survival time is 2-4 months. However, new anticancer agents can improve the outcome of advanced pancreatic cancer. We present the case of a 50-year-old female patient with Stage IV b pancreatic head cancer with invasion to the superior mesenteric vein(SMV)and multiple liver metastases. The patient received S-1 as first-line chemotherapy. Three months later, a further CT scan showed reduction of the pancreatic tumor, disappearance of the liver metastases, and reduction in SMV invasion. Therefore, a subtotal stomach-preserving pancreatoduodenectomy with partial SMV resection was performed. Following surgery, the patient received S-1 chemotherapy again. However, lung metastasis appeared. Despite the initiation of gemcitabine(GEM)treatment, the patient developed metastases in other parts of the lung and the abdominal wall. She died 46 months after surgery, but it is noteworthy that the liver metastases were manageable. The combination of chemotherapy and surgery was effective in prolonging survival in this patient with Stage IV b pancreatic head cancer.

Topics: Antimetabolites, Antineoplastic; Deoxycytidine; Drug Combinations; Fatal Outcome; Female; Gemcitabine; Humans; Liver Neoplasms; Lung Neoplasms; Middle Aged; Neoplasm Invasiveness; Neoplasm Staging; Oxonic Acid; Pancreatic Neoplasms; Pancreaticoduodenectomy; Tegafur

S-1 is one of the effective chemotherapy regimens for treating non-small cell lung cancer. We report of an elderly patient with non-small cell lung cancer who responded to S-1 monotherapy following gefitinib therapy. An 83-year-old woman was diagnosed with advanced adenocarcinoma of the lungs (cT3N3M1a, Stage IV). Considering her age, monotherapy with vinorelbine was administered as first-line chemotherapy. Despite the completion of four courses, she was diagnosed with progressive disease. Thereafter, after considering her status as a non-smoking woman, gefitinib was introduced as second-line chemotherapy, which resulted in significant tumor size reduction.Tumor regrowth was identified 16 months later, and gefitinib was switched to erlotinib, but the tumor kept increasing in size.S -1 monotherapy was introduced as fourth-line chemotherapy, and the tumor began to decrease in size again. A partial response was obtained after 10 months, without serious adverse effects. Gefitinib following S-1 monotherapy resulted in long-term tumor size control for a total of 27 months in an elderly patient with advanced non-small cell lung cancer.S -1 monotherapy might be one of the options for salvage therapy after gefitinib treatment becomes ineffective.

Topics: Aged, 80 and over; Antimetabolites, Antineoplastic; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Disease Progression; Drug Combinations; Fatal Outcome; Female; Gefitinib; Humans; Lung Neoplasms; Oxonic Acid; Quinazolines; Salvage Therapy; Tegafur

We report of a patient with 3-year relapse-free survival after surgical resection for lung and liver metastases of distal cholangiocarcinoma (DCC). A quinquagenarianman was taken to a local hospital in October 2009 for yellow urine. He was diagnosed with DCC and was referred to our hospital for surgery. Pancreaticoduodenectomy was performed, and there was no residual tumor on histological examination. He did not receive any adjuvant therapy. One year 7 months after surgery, an isolated lung metastasis was identified on CT and was surgically removed. Six months after resection of the lung metastasis, a solitary liver metastasis was detected. Although systematic chemotherapy (gemcitabine plus S-1; 2 weeks treatment, 1 week drug free) was administered, the treatment was abandoned because of grade 3 (CTCAE v4.0) of skin disorders during the third course. Partial resection of the liver was performed in April 2012. Alternate-day treatment with S-1 was performed after resection of liver metastasis and is ongoing without adverse events. He has survived for more than 3 years without recurrence after liver resection. In this case of DCC metastasis, prognosis improved with surgical resection.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bile Duct Neoplasms; Cholangiocarcinoma; Deoxycytidine; Drug Combinations; Gemcitabine; Hepatectomy; Humans; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Pancreaticoduodenectomy; Recurrence; Tegafur

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

Unresectable metastatic colorectal cancer with very slow tumour growth rate does not necessarily require for strong short-interval chemotherapy. In the present study, we administered monthly chemotherapy and aimed to evaluate the usefulness of the specific treatment schedule in patients with unresectable metastatic colorectal cancer with slow tumour growth rate.. Since 2009, at our Institution, patients' whose serum carcinoembryogenic antigen (CEA) values on the treatment day were not higher than those before initial chemotherapy, and patients who did not wish to undergo intensive chemotherapy, were prospectively scheduled for specific chemotherapy. Between January 2009 and December 2011, 10 patients with unresectable metastatic colorectal cancer who received monthly chemotherapy were enrolled in the current study. During the same period, 14 patients with unresectable metastatic colorectal cancer were administered conventional-interval chemotherapy, oxaliplatin with oral S-1 (SOX) or capecitabine (XELOX), and comprised the control group.. Three patients received first-line, four patients received second-line, and three patients received third-line treatment. All patients were able to receive a single-regimen of chemotherapy for more than a year. The survival of patients who received monthly chemotherapy was significantly better than survival of those who received SOX or XELOX within 30 months after starting chemotherapy (p<0.05).. For patients with very slow tumour growth rates, our monthly chemotherapy may be beneficial.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Colorectal Neoplasms; Deoxycytidine; Drug Combinations; Female; Fluorouracil; Follow-Up Studies; Humans; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Peritoneal Neoplasms; Prognosis; Survival Rate; Tegafur

An 80-year-old man presenting with abdominal distension was admitted to our hospital. He was diagnosed with sigmoid cancer with multiple liver and lung metastases. We first performed a sigmoidectomy to avoid obstruction, and then initiated chemotherapy with S-1(120mg/day). The tumor showed a complete clinical response after 10 courses, but we had to change the regimen after 18 courses because of growth of the lung metastases. After 10 courses of capecitabine(4,200mg/ day)treatment, we again observed growth of the lung metastases; a new nodule, which was also considered to be a metastasis, appeared on the abdominal wall. We then decided to administer mFOLFOX6(5-fluorouracil+Leucovorin+oxaliplatin) after the patient had received oral anticancer drugs for 3 years 4 month. In conclusion, oral chemotherapy drugs may prevent tumor growth over a long period and improve quality of life(QOL)in elderly patients with Stage IV colon cancer.

Topics: Administration, Oral; Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Capecitabine; Combined Modality Therapy; Deoxycytidine; Drug Combinations; Fluorouracil; Humans; Liver Neoplasms; Lung Neoplasms; Male; Neoplasm Staging; Oxonic Acid; Sigmoid Neoplasms; Tegafur; Time Factors

A 72-year-old woman was admitted to our hospital with bloody stools and constipation. She was diagnosed with advanced lower rectal cancer with multiple liver and pulmonary metastases. Because the rectal cancer was located 2 cm from the anal verge, we suggested she undergo an abdominoperineal resection(Miles operation), but she refused to undergo a colostomy. Then, 6 courses of chemotherapy with S-1/oxaliplatin(SOX)were administered, and the local tumor, liver metastases, and pulmonary metastases were all significantly decreased in size(reduction rate 60%). After chemotherapy, she chose to undergo low anterior resection(LAR), D2. Postoperative recovery was uneventful, and she currently has stable disease with adjuvant SOX chemotherapy. Induction SOX chemotherapy was considered to be useful for maintaining the quality of life(QOL) in a patient with advanced rectal cancer.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Colostomy; Drug Combinations; Female; Humans; Liver Neoplasms; Lung Neoplasms; Neoplasm Staging; Organoplatinum Compounds; Oxaliplatin; Oxonic Acid; Rectal Neoplasms; Tegafur; Treatment Outcome

The prognosis of patients with advanced gastric cancer is poor. The goal of this study was to evaluate the efficacy and safety of combination therapy of cetuximab and S-1 combined with oxaliplatin (SOX) in Chinese patients with advanced gastric cancer.. For patients in the experimental group (cetuximab in combination with SOX (Ce-SOX), 30 patients), once-weekly cetuximab (400 mg/m2 at the first infusion then 250 mg/m2 every week) was administered. For patients in both the control (SOX alone, 26 patients) and experimental groups, oxaliplatin (100 mg/m2) was administered intravenously on day 1, while S-1 (80 mg/m2/day) was given orally twice daily for 14 days. The endpoints of this study included progression-free survival, response rate, and disease-control rate.. There was no statistically significant difference in response rate between the Ce-SOX and SOX groups (54.8% versus 44%, P=0.225). The difference in disease-control rate was also statistically insignificant between the two groups (87.1% versus 76%, P=0.162). Median progression-free survival in the Ce-SOX group was significantly higher than that in the SOX group (12.8 versus 10.1 months, P=0.007). The median overall survival of the Ce-SOX group and SOX group was 14.0 and 12.2 months, respectively (P=0.043). The one-year survival rate for the Ce-SOX group was 57% compared to 40% in the SOX group. There was no statistical difference in the grade 3 or 4 adverse effects between the two groups.. These findings suggest that the cetuximab combined with SOX regimen is feasible and shows promising efficacy with tolerable adverse effects in Chinese patients with advanced gastric cancer.

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

A 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

Colorectal cancer (CRC) is among the most common cancers worldwide, but marked epidemiological differences exist between Asian and non-Asian populations. Hence, a consensus meeting was held in Hong Kong in December 2012 to develop Asia-specific guidelines for the management of metastatic CRC (mCRC). A multidisciplinary expert panel, consisting of 23 participants from 10 Asian and 2 European countries, discussed current guidelines for colon or rectal cancer and developed recommendations for adapting these guidelines to Asian clinical practice. Participants agreed that mCRC management in Asia largely follows international guidelines, but they proposed a number of recommendations based on regional 'real-world' experience. In general, participants agreed that 5-fluorouracil (5-FU) infusion regimens in doublets can be substituted with UFT (capecitabine, tegafur-uracil) and S1 (tegafur, 5-chloro-2,4-dihydroxypyridine and oxonic acid), and that the monoclonal antibodies cetuximab and panitumumab are recommended for KRAS wild type tumors. For KRAS mutant tumors, bevacizumab is the preferred biological therapy. FOLFOX (folinic acid, 5-FU, and oxaliplatin) is preferred for initial therapy in Asian patients. The management of mCRC is evolving, and it must be emphasized that the recommendations presented here reflect current treatment practices and thus might change as more data become available.

Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Asia; Bevacizumab; Camptothecin; Capecitabine; Cetuximab; Colonic Neoplasms; Combined Modality Therapy; Deoxycytidine; Drug Combinations; ErbB Receptors; Fluorouracil; Guideline Adherence; Humans; Leucovorin; Liver Neoplasms; Lung Neoplasms; Magnetic Resonance Imaging; Metastasectomy; Neoplasm Staging; Organoplatinum Compounds; Oxaloacetates; Oxonic Acid; Panitumumab; Practice Guidelines as Topic; Proto-Oncogene Proteins; Proto-Oncogene Proteins p21(ras); ras Proteins; Rectal Neoplasms; Tegafur; Tomography, X-Ray Computed

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

The aim of the present study was to analyze factors that affect progression-free survival (PFS) of patients with previously treated advanced non-small cell lung cancer (NSCLC) after S-1 therapy, in particular epidermal growth factor receptor (EGFR) mutation status.. Between October 2009 and June 2013, 56 patients with advanced NSCLC were analyzed for EGFR somatic mutations and treated with S-1 with or without bevacizumab. Risk factors associated with PFS were evaluated using a Cox proportional hazards regression model with a step-down procedure. Proportional hazards assumptions were checked and satisfied and only variables with statistical significance in univariate analysis were included in multivariate analysis.. The median PFS of patients with EGFR mutations who received S-1 therapy was significantly longer than that of patients with wild-type EGFR. The median PFS of patients with good performance status (PS) was significantly longer than that of patients with poor PS. In multivariate analysis, wild-type EGFR and poor PS were significant and independent negative factors that affect PFS after S-1 therapy.. EGFR mutation and good PS were positive predictive factors for PFS after S-1 therapy, suggesting that S-1 therapy is efficacious for patients with EGFR-activating mutations even in a multi-line setting.

Topics: Aged; Aged, 80 and over; Angiogenesis Inhibitors; Antibodies, Monoclonal, Humanized; Antimetabolites, Antineoplastic; Bevacizumab; Carcinoma, Non-Small-Cell Lung; Disease-Free Survival; Drug Combinations; ErbB Receptors; Female; Humans; Lung Neoplasms; Male; Middle Aged; Multivariate Analysis; Mutation; Oxonic Acid; Retrospective Studies; Tegafur; Vascular Endothelial Growth Factor A

Stage IV gastric cancer has poor prognosis, and median survival time (MST) is reported to range from 6 to 13 months. We report a case of long-term survival in a Stage IV gastric cancer patient who was successfully treated with multi combination chemotherapy with S-1. A 73-year-old woman presenting with gastric cancer with pyloric stenosis and peritoneal dissemination at the sigmoid colon underwent distal gastrectomy with D2 lymphadenectomy and sigmoidectomy. She received adjuvant chemotherapy with S-1 and CDDP after surgery. During the twelfth administration of S-1 and CDDP, she developed an anaphylactic reaction against CDDP; therefore, only S-1 was administered for the next 6 courses. Thirty one months postgastrectomy, a left ovarian metastasis (about 4 cm) was detected by computed tomography. Two courses of S-1 and CPT-11 were administered; however, the ovarian metastasis grew to twice its initial size. She underwent hysterectomy and bilateral ovariectomy. The pathological diagnosis was metastatic tumors in the uterus and ovary(Krukenberg tumor). After the second surgery, S-1 and docetaxel therapy was initiated. A metastasis (S2, 5mm diameter) appeared in the right lung around 65 months after the gastrectomy. The patient received a total of 28 courses, up until 69 months post-gastrectomy. At present, she hopes to finish the chemotherapy and is consulting a palliative care facility. At 80 months post-gastrectomy, she has no symptoms because the lung metastasis exhibits slow growth (15 mm diameter), and is maintaining her quality of life (QOL).

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Female; Gastrectomy; Humans; Lung Neoplasms; Neoplasm Staging; Ovarian Neoplasms; Oxonic Acid; Stomach Neoplasms; Tegafur

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

Concurrent chemoradiotherapy using S-1 containing tegafur, an oral 5-FU prodrug, plus cisplatin has been reported to show promising efficacy against locally advanced non-small cell lung cancer with acceptable toxicity. The purpose of this study is to assess the impact of this induction treatment followed by surgery on survival for those patients.. Potentially resectable locally advanced non-small cell lung cancer patients were eligible. The concurrent phase consisted of S-1 (orally at 40 mg/m² twice a day on days 1 to 14 and 22 to 36) and cisplatin (60 mg/m² on days 1 and 22) with radiation of 40 Gy/20 fractions beginning on day 1 followed by surgical resection.. Forty-two consecutive patients, between June 2005 and February 2011, were retrospectively analyzed. The median age was 59 (42 to 77) years, there were 34 males and 8 females, 26 cStage IIIA and 16 IIIB, each 21 adenocarcinomas and others. There were 26 partial responses and 16 stable disease cases after current induction treatment without uncontrollable toxicity. Of the 42 patients, 39 underwent surgical resection; 27 underwent a lobectomy and 12 pneumonectomies. One patient died due to thoracic empyema 65 days after surgery. The median follow-up time was 32.0 months. Three- and 5-year disease-free survival rates in all 39 resected patients were 52.0% and 44.0%, respectively, and 3- and 5-year overall survival rates were 77.4% and 61.7%, respectively.. Concurrent chemoradiotherapy using S-1 plus cisplatin followed by surgery may provide a better prognosis for locally advanced non-small cell lung cancer patients. Further prospective clinical investigation should be required.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Chemoradiotherapy; Cisplatin; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Preoperative Care; Retrospective Studies; Tegafur

An 80-year-old man with no complaint was referred to our department because of high serum CEA level. He was diagnosed as non-small cell lung cancer(adenocarcinoma)of the left lower lobe(c-T2aN0M0, stage I B), and therefore the left lower lobectomy with lymph node dissection was performed. Pathological staging was p-T2aN1(#10)M0, stage II A, and EGFR mutation was negative. Adjuvant chemotherapy with UFT was started, but multiple hilar and mediastinal lymph nodes metastases soon appeared. Carboplatin(CBDCA)+paclitaxel(PTX), erlotinib, and docetaxel(DOC)were attempted after that, but the lymph nodes increased in size and the CEA level was up to 159.8 ng/mL. At about the same time, brain and pulmonary metastases were recognized. After radiation for the chest lymph nodes and stereotactic radiosurgery(SRS)for the brain metastasis, oral S-1 monotherapy was introduced. Soon after, the lymph nodes shrinked and the CEA level decreased. Also, the pulmonary metastasis disappeared. Although a right supraclavicular lymph node metastasis was resected during the clinical course, the S-1 monotherapy has been continued with no serious adverse event. He is well(PS 0)without recurrent lesion, and his serum CEA level is within the normal limit.

Topics: Aged, 80 and over; Carcinoma, Non-Small-Cell Lung; Combined Modality Therapy; Drug Combinations; Humans; Lung Neoplasms; Male; Oxonic Acid; Recurrence; Tegafur

We report a case of a 64-year-old man with multiple lung metastases after gastric cancer surgery. This patient was initially treated with S-1. However, he experienced adverse effects, and subsequently, he was effectively treated with cisplatin (CDDP) and irinotecan (CPT-11). In July 2010, the patient experienced a decrease in appetite and underwent a detailed examination. He also underwent distal gastrectomy in the same month. The postoperative diagnosis was T4a( SE), N2, M0, Stage IIIB. In November 2010, adjuvant chemotherapy with S-1 was initiated. In February 2011, the patient developed a skin disorder( grade 3) and generalized edema along with walking difficulty, which were identified as adverse effects of S-1. Evidently, S-1 was contraindicated for this patient, and adjuvant therapy was discontinued. In September 2011, contrast -enhanced thoracoabdominal computed tomography( CT) was performed and para-aortic lymph node metastasis and multiple lung metastases were detected. CDDP+CPT-11 therapy was initiated. By June 2012, 8 courses had been administered, and the patient had a good partial response. With regard to chemotherapy for advanced or recurrent gastric cancer, there is no consensus on a treatment policy for cases in which S-1 cannot be used owing to adverse effects. CDDP+CPT-11 therapy is considered a safe and effective choice.

Topics: Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cisplatin; Contraindications; Drug Combinations; Humans; Irinotecan; Lung Neoplasms; Male; Middle Aged; Neoadjuvant Therapy; Oxonic Acid; Recurrence; Stomach Neoplasms; Tegafur

Pulmonary injuries due to S-1 have been reported, and these reports have shown an increase in lung cancer following the increased usage of S-1 in treating lung cancer. We report the first case of lung injury due to S-1 in combination with pneumocystis pneumonia (PCP), because the radiological findings and clinical courses were compatible with S-1-induced lung injury combined with PCP. We should consider that S-1 might induce lung injuries which might occur with PCP, especially with a history of drug-induced or radiation-induced lung injuries.

Topics: Aged; Antimetabolites, Antineoplastic; Drug Combinations; Humans; Lung Injury; Lung Neoplasms; Male; Oxonic Acid; Pneumonia, Pneumocystis; Tegafur

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

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

Based on the results of phase I/II studies, S-1 plus cisplatin (CDDP) and vinorelbine (VNR) plus CDDP are commonly used chemoradiotherapeutic regimens for the treatment of non-small cell lung cancer(NSCCLC) in Japan. However, there have been no studies that have compared S-1 and CDDP combined with thoracic radiotherapy (TRT) with VNR and CDDP combined with TRT.. A total of 39 and 50 patients with stage III non-small cell lung cancer (NSCLC) were treated with S-1 and CDDP plus concurrent TRT, or with VNR and CDDP plus concurrent TRT, respectively, between 2002 and 2010.. In the S-1 plus CDDP plus TRT group, the median progression-free survival (PFS) and the median overall survival (OS) were 327 days and 1012 days, respectively. In the VNR plus CDDP plus TRT group, the median PFS and the median OS were 328 days and 905 days, respectively. The differences in the PFS and OS were not statistically significant. Grade 3 or more leukopenia and neutropenia were significantly more common in the VNR plus CDDP plus TRT group. Grade 3 or more thrombocytopenia, esophagitis and eruption tended to be more common in the S-1 plus CDDP plus TRT group.. Due to the difference in the toxicity profiles of the two combinations, S-1 plus CDDP plus TRT or VNR plus CDDP plus TRT should be selected depending on each patient's baseline characteristics.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Chemoradiotherapy; Cisplatin; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Retrospective Studies; Survival Rate; Tegafur; Treatment Outcome; Vinblastine; Vinorelbine

To report dacryoendoscopic observations and the incidence of lacrimal obstruction/stenosis associated with S-1, an oral anticancer drug.. Retrospective, nonrandomized clinical trial.. A total of 52 patients (41 men, 11 women; age 42-93 years) who were prescribed the anticancer drug S-1 were studied. Patients who suffered eye complaints following S-1 treatment underwent ophthalmic examination, probing and lacrimal irrigation. Patients whose tear meniscus was high or had abnormal lacrimal irrigation were evaluated by dacryoendoscopy.. Overall, 5 of 52 S-1-treated patients (9.6%) experienced lacrimal passage stenosis/obstruction. One patient had punctal stenosis, and four patients had canalicular obstruction/stenosis. The onset of epiphora ranged from 2 to 8 months (4.4 ± 2.2 months, mean ± SD) after the initiation of chemotherapy.. Patients receiving S-1 treatment should be evaluated for potential lacrimal disorders, particularly canalicular obstruction/stenosis. Dacryoendoscopic observation is effective for the diagnosis of this side effect.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Colonic Neoplasms; Drug Combinations; Endoscopy; Female; Humans; Incidence; Lacrimal Duct Obstruction; Lung Neoplasms; Male; Middle Aged; Nasolacrimal Duct; Oxonic Acid; Pancreatic Neoplasms; Retrospective Studies; Stomach Neoplasms; Tegafur

A 70-year-old female patient underwent pylorus-preserving pancreaticoduodenectomy for carcinoma of the ampulla of Vater in March 2007. In April 2009, multiple lung metastases were detected by CT scanning. The patient was treated with S-1 (80mg/day, day 1-28, followed by 2-weeks withdrawal)from April 2009. The shrinkage of lung metastases was diagnosed as a complete response based on the Response Evaluation Criteria in Solid Tumors(RECIST). No severe toxicities were observed. S-1 is an effective and safe anti-cancer agent available for lung metastases of carcinoma of the ampulla of Vater.

Topics: Aged; Ampulla of Vater; Antimetabolites, Antineoplastic; Common Bile Duct Neoplasms; Drug Combinations; Duodenal Neoplasms; Female; Humans; Lung Neoplasms; Oxonic Acid; Pancreatic Neoplasms; Tegafur; Tomography, X-Ray Computed

Pleomorphic carcinoma is a rare malignancy of the lung. Here we present a 68-year-old man who was admitted to our hospital for examination of an abnormal radiogram of the chest. The radiogram revealed a large mass in the right lung field. A chest computed tomographic (CT) scan demonstrated a nonsegmentalmass like consolidation. Percutaneous CT-guided fine-needle needle biopsy from the lung was performed, and the specimen demonstrated pulmonary pleomorphic carcinoma. The patient was initially treated with two courses of cisplatin (CDDP) and docetaxel (DOC), and still showed progressive disease (PD). Therefore, we administered S-1 following radiotherapy. The chest CT revealed partial response after 4 months. We experienced a pulmonary pleomorphic carcinoma which showed a response to salvage chemotherapy with S-1.

Topics: Aged; Antimetabolites, Antineoplastic; Biopsy; Chemoradiotherapy; Drug Combinations; Fatal Outcome; Humans; Lung Neoplasms; Male; Oxonic Acid; Salvage Therapy; Tegafur

A 30-year-old man underwent a left lobectomy and S5/6 partial hepatectomy in August 2001 for hepatocellular carcinoma (HCC). A lung tumor was detected by positron emission tomography (PET-CT) 8 years after the surgery. In May 2010, he received pulmonary tumor resection and the histopathological findings revealed metastasis of HCC. However a metastatic brain tumor was detected by computed tomography (CT) in September 2010, therefore surgery and radiation therapy were subsequently performed. Thereafter, metastatic hilar lymph node appeared in December 2010, therefore we performed systemic chemotherapy using S-1/cisplatin combined with radiation therapy for the metastatic tumor. The tumor was markedly decreased and no shadow was detected by PET-CT. He has been followed up in the outpatient clinic with no recurrence.

Topics: Adult; Antimetabolites, Antineoplastic; Brain Neoplasms; Carcinoma, Hepatocellular; Combined Modality Therapy; Drug Combinations; Hepatectomy; Humans; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Male; Oxonic Acid; Tegafur

A 29-year-old man developed a persistent dry cough. Chest high-resolution computed tomography (HRCT) revealed centrilobular ultrafine granular shadows scattered in all lung fields. A lung biopsy with video-assisted thoracoscopic surgery revealed findings compatible with pulmonary tumor thrombotic microangiopathy (PTTM). However, the primary tumor was not identified. Combination chemotherapy with S-1 and cisplatin decreased his cough and improved the chest HRCT findings. The illness, however, gradually became difficult to control. He eventually developed pulmonary hypertension and died. Typically, an antemortem diagnosis of PTTM cannot be made. In this case, the diagnosis of PTTM and combination chemotherapy improved the chest HRCT findings, respiratory symptoms, and prognosis.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Biopsy; Carcinoma, Signet Ring Cell; Cisplatin; Drug Combinations; Fatal Outcome; Humans; Hypertension, Pulmonary; Lung Neoplasms; Male; Neoplasms, Unknown Primary; Oxonic Acid; Pulmonary Artery; Tegafur; Thoracic Surgery, Video-Assisted; Thrombotic Microangiopathies; Tomography, X-Ray Computed

In a previous study, we reported a patient who responded to non-small cell lung cancer treatment with S-1 and concurrent radiotherapy over an extended period. This time, we report a long-term follow-up of the same case, and a new case which had a complete response to S-1 and concurrent radiotherapy. Case 1 is a 35-year-old woman with a pathological diagnosis of stage T2N2M0 lung adenocarcinoma. This case was already reported till 36 months postoperatively. 71 months postoperatively, PET-CT inspection revealed no obvious metastasis, unusual accumulations of FDG, or unusual shadows which may suggest recurrence. Case 2 is a 37-year-old woman with a pathological diagnosis of stage T2N2M0 right lung adenocarcinoma. After CBDCA/GEM and gefitinib were used as anterior chemotherapies, the right lung was partially resected. However, since the metastasis was developed, a total amount of 60 Gy/30 Fr was used to irradiate the mediastinum of the right cervix. Around the same time, S-1 treatment was started[a dose of 50mg/day(35m2/day)in two divided doses for 2 weeks, followed by 1 week of rest). As a result of S-1 treatment with concurrent radiotherapy, the patient had a long-term response. Sixteen months postoperatively, there has been no observable recurrence by CT inspection.

Topics: Adult; Antimetabolites, Antineoplastic; Carcinoma, Non-Small-Cell Lung; Chemoradiotherapy; Drug Combinations; Female; Humans; Lung Neoplasms; Lymphatic Metastasis; Neoplasm Staging; Oxonic Acid; Tegafur; Time Factors; Tomography, X-Ray Computed

About 30% of patients with non-small cell lung cancer (NSCLC) have locally advanced cancer (stage IIIA or IIIB) at the time of presentation. Many institutions have reported treatment with preoperative chemoradiotherapy (PCRT) followed by curative resection in patients with stage III NSCLC, but the optimal therapeutic protocol for this group has not been established.. Nineteen patients with stage III NSCLC were treated with PCRT, followed by surgery at the Hamanomachi Hospital, Fukuoka, Japan from May 2000 to November 2011. We evaluated the effectiveness of PCRT for inducing downstaging using mainly three chemoradiotherapy regimens; cisplatin plus Tegafur-Gimeracil-Oteracil Potassium (S-1), cisplatin plus Tegafur-Uracil (UFT), or 1,1'cyclobutanedicarboxylate (Carboplatin, CBDCA) plus paclitaxel, with concurrent radiation therapy in 19 patients with stage III NSCLC.. The overall 5-year survival rate was 57.1%, which is higher than the average survival rate for patients with stage III NSCLC in Japan. Among the regimens used, only cisplatin plus S-1 with concurrent radiation therapy significantly induced downstaging. There was a significant difference in survival time between the downstaged and non-downstaged groups. However, there was no significant difference in survival time between the S-1 plus cisplatin group and the other groups combined, because of the short observation period for the S-1 plus cisplatin group.. PCRT using cisplatin plus S-1 with concurrent radiation therapy is useful for inducing downstaging in patients with locally advanced stage III NSCLC.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Chemoradiotherapy; Cisplatin; Drug Combinations; Female; Humans; Kaplan-Meier Estimate; Lung Neoplasms; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Staging; Oxonic Acid; Retrospective Studies; Tegafur

Recently, multiple-line chemotherapy has become popular for non-small cell lung cancer (NSCLC). The survival time of patients is influenced by patient characteristics and subsequent treatments.. The usefulness of paclitaxel plus S1 (PTX+S1) was evaluated in 46 pretreated NSCLC patients. Time from the start of individual regimens till the start of the next one (TNR) was calculated for regimens administered to the study population including PTX+S1 and analyzed by the shared frailty Cox model.. The response rate and the median progression-free survival time of PTX+S1 were 32.6% and 253 days, respectively. Substantial difference in TNR was observed in epidermal growth factor receptor mutation status and in line and type of regimens, but not in stage, age, sex, performance status and histology, by univariate analysis. Multivariate analysis revealed that PTX+S1 was only one factor to prolong TNR.. Because of long progression-free survival and long TNR, further evaluation of PTX+S1 is necessary.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Disease-Free Survival; Drug Administration Schedule; Drug Combinations; ErbB Receptors; Female; Humans; Lung Neoplasms; Male; Middle Aged; Multivariate Analysis; Mutation; Oxonic Acid; Paclitaxel; Proportional Hazards Models; Retrospective Studies; Survival Rate; Tegafur; Time Factors; Treatment Outcome

S-1 is an oral fluoropyrimidine derivative that is active against non-small cell lung cancer (NSCLC). Development of S-1 combination chemotherapy for advanced NSCLC is under way. Given the importance of designing therapeutic strategies based on specific tumor biology, we have evaluated the relation between immunohistochemical expression levels of thymidylate synthase (TS), orotate phosphoribosyltransferase (OPRT), or dihydropyrimidine dehydrogenase (DPD) and the response to treatment with S-1 plus carboplatin in patients with advanced NSCLC. Chemotherapy-naïve patients with advanced (stage IIIB or IV) NSCLC, an Eastern Cooperative Oncology Group performance status of 0 or 1, adequate organ function, and archival tumor tissue were assigned to receive S-1-carboplatin (n=22). The predictive or prognostic relevance of the molecular markers was also examined by their evaluation in patients treated with paclitaxel plus carboplatin (n=25). Expression levels of TS, OPRT, or DPD in tumor specimens did not differ significantly between patients treated with S-1-carboplatin and those treated with paclitaxel-carboplatin. A low expression level of TS or of DPD was associated with a better response and longer survival in patients treated with S-1-carboplatin but not in those treated with paclitaxel-carboplatin. Tumor expression levels of TS and DPD are predictive of response to S-1-carboplatin chemotherapy in patients with advanced NSCLC.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Carboplatin; Carcinoma, Non-Small-Cell Lung; Dihydrouracil Dehydrogenase (NADP); Disease-Free Survival; Drug Combinations; Female; Humans; Kaplan-Meier Estimate; Lung Neoplasms; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Orotate Phosphoribosyltransferase; Oxonic Acid; Paclitaxel; ROC Curve; Tegafur; Thymidylate Synthase; Treatment Outcome

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

Metronomic chemotherapy involves frequent, regular administration of cytotoxic drugs at nontoxic doses, usually without prolonged breaks. We investigated the therapeutic efficacies of metronomic S-1, an oral 5-fluorouracil prodrug, and vandetanib, an epidermal growth factor receptor and vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitor, in models of hepatocellular carcinoma (HCC).. We compared anti-HCC effects and toxicity in the six treatment groups: control (untreated), maximum tolerated dose (MTD) S-1, metronomic S-1, vandetanib, MTD S-1 with vandetanib, and metronomic S-1 with vandetanib. Tumor microvessel density (MVD) and tumor apoptosis were evaluated by immunohistochemistry. The expression of VEGF and thrombospondin-1, an endogenous inhibitor of angiogenesis, was analyzed by Western blot.. Metronomic S-1 significantly inhibited tumor growth, which was enhanced by combination with vandetanib. With respect to toxicities, MTD S-1 caused severe body weight loss and myelosuppression, whereas metronomic S-1 did not cause any overt toxicities. Moreover, metronomic S-1 or metronomic S-1 with vandetanib prolonged survival, the latter treatment providing the greatest benefit. Metronomic S-1 and metronomic S-1 with vandetanib decreased MVDs and increased apoptosis in tumor tissues. The expression of VEGF in tumor tissues was upregulated by vandetanib and metronomic S-1 with vandetanib, whereas the expression of thrombospondin-1 was upregulated by metronomic S-1 and metronomic S-1 with vandetanib.. Metronomic S-1 with an antiangiogenic agent seems to be an effective and safe therapeutic strategy for HCC.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Blotting, Western; Carcinoma, Hepatocellular; Cell Proliferation; Drug Combinations; ErbB Receptors; Fluorouracil; Humans; Immunoenzyme Techniques; Lung Neoplasms; Male; Maximum Tolerated Dose; Mice; Mice, Inbred BALB C; Mice, Nude; Oxonic Acid; Piperidines; Quinazolines; Tegafur; Tumor Cells, Cultured

Topics: Aged; Antimetabolites, Antineoplastic; Conjunctival Diseases; Corneal Diseases; Drug Combinations; Epithelium, Corneal; Humans; Lung Neoplasms; Male; Oxonic Acid; Pigmentation Disorders; Tegafur

We report a 50-year-old female with pulmonary metastases from breast cancer who responded to S-1. In September 2003, she underwent surgery for breast cancer. Four years 8 months after the operation, lung relapse was detected. After the treatment failure of FEC60 (5-FU 500 mg/m², epirubicin 60 mg/m², cyclophosphamide 500 mg/m²) and taxane antitumor drugs, oral administration of S-1 80 mg/body/day was initiated. At the end of three courses, thoracic CT revealed the disappearance of the lung metastasis. Advanced reactions during the administration period were mild. After 14 courses of S-1 therapy (during 11 months), a complete response was clinically maintained. S-1 showed a good antitumor effect and tolerance, and it might be useful for treating metastatic and recurrent breast cancers.

Topics: Antimetabolites, Antineoplastic; Breast Neoplasms; Drug Combinations; Female; Humans; Lung Neoplasms; Middle Aged; Oxonic Acid; Tegafur; Tomography Scanners, X-Ray Computed

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

Our patient was a 57-year-old male with a history of esophageal cancer. He was referred to our hospital for squamous cell lung carcinoma(SCC). Chest computed tomography identified a mass in the left lung field, which was suspected to be invading the reconstructed gastric tube, left subclavian artery, common carotid artery, and distal aortic arch. He was diagnosed as primary pulmonary squamous cell carcinoma(SCC)because six years had already passed since a previous surgery for early esophageal cancer. He received three courses of induction chemotherapy including S-1/CDDP. We evaluated the therapy as a partial response. He underwent an extended resection of distal aortic arch and left subclavian artery with left upper lobectomy, and those vessels were reconstructed using prosthetic grafts. Pathological findings showed the tumor as a well differentiated SCC of pT4N0M0 at stage III A, with a residual tumor on the reconstructed gastric tube, even though the effect of induction chemotherapy was Ef2. He received three courses of S-1/CDDP after surgery. The patient has been well without recurrence for 31 months after surgery.

Topics: Antineoplastic Combined Chemotherapy Protocols; Aorta, Thoracic; Carcinoma, Non-Small-Cell Lung; Cisplatin; Drug Combinations; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Staging; Neovascularization, Pathologic; Oxonic Acid; Tegafur; Time Factors

This single-institutional study was designed to determine whether S-1, an oral fluoropyrimidine, plus cisplatin with concurrent radiotherapy is feasible as an induction treatment for locally advanced non-small cell lung cancer (NSCLC).. Eighteen patients were analyzed in this study from July 2005 to March 2008. The patients received 40 mg/m(2) S-1 orally twice per day on days 1 through 14 and 22 through 35, and cisplatin (60 mg/m(2)) was injected intravenously on days 8 and 29. The patients also underwent radiotherapy, and received a total dose of 40 Gy in 20 fractions beginning on day 1. Surgical resection was performed from 3 to 6 weeks after completing the induction treatment.. Nine (50%) of the 18 patients who received the induction treatment achieved a partial response. One patient refused to undergo surgery. The remaining 17 patients underwent a complete surgical resection. There were no deaths nor any major morbidities during the perioperative period. The recurrence-free survival and overall survival rate at 2 years for the patients who underwent resection were 63.3% and 88.2%, respectively.. Induction treatment using S-1 plus cisplatin and concurrent radiotherapy and surgical resection for selected patients with stage III NSCLC is a feasible and promising new treatment modality.

Topics: Administration, Oral; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Chemoradiotherapy; Cisplatin; Cohort Studies; Combined Modality Therapy; Disease-Free Survival; Drug Combinations; Feasibility Studies; Female; Humans; Infusions, Intravenous; Kaplan-Meier Estimate; Lung Neoplasms; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Invasiveness; Neoplasm Staging; Oxonic Acid; Patient Selection; Pneumonectomy; Prognosis; Risk Assessment; Survival Analysis; Tegafur; Treatment Outcome

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Docetaxel; Drug Combinations; Drug Resistance, Neoplasm; Humans; Lung Neoplasms; Lymphatic Metastasis; Male; Oxonic Acid; Paget Disease, Extramammary; Skin Neoplasms; Taxoids; Tegafur; Tomography, X-Ray Computed; Urinary Bladder Neoplasms

We report a case of anal cancer in a 58-year-old woman who complained of narrow, bloody stools and anal pain. Physical examination revealed anal stenosis associated with a circular mass arising in the anal canal. Histological examination of biopsy specimens confirmed a diagnosis of moderately differentiated squamous cell carcinoma. Enhanced computed tomography revealed anal cancer invading the levator ani and the vagina, with lymph-node, multiple hepatic, and pulmonary metastases. The patient received two cycle of chemoradiotherapy with S-1 plus low-dose cisplatin with rest for 4 weeks, leading to complete response of the primary lesion and a partial response of the metastatic lesions. Each cycle included oral S-1 (120 mg/body; day 1-21), cisplatin (10 mg/body; day 1-5, 8-12) and radiotherapy (2 Gy/day; day 1-5, 8-12, 15-19). Adverse effects of treatment were mild perineal skin erosion and mild appetite loss, but no hematologic toxicity. Although the patient died 16 months after first admission, chemoradiotherapy with S-1 plus cisplatin is potentially effective for the management of advanced anal cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; Anus Neoplasms; Chemoradiotherapy; Cisplatin; Drug Combinations; Female; Gamma Rays; Humans; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Middle Aged; Neoplasm Staging; Oxonic Acid; Tegafur; Treatment Outcome

A 77-year-old man was diagnosed as hepatocellular carcinoma, and was referred to our hospital. After he was treated by transcatheter chemoembolization, he underwent a left hepatic lobectomy of the liver and cholecystectomy. Serum AFP and PIVKA-II remarkably elevated 7 months after surgery, and CT scan revealed multiple metastatic nodules in bilateral lungs. The nodules were diagnosed as lung metastasis of HCC. Because the lesions grew larger, S-1/IFN was administered. Diagnostic imaging and tumor markers showed a marked improvement after 4 courses of S-1/IFN therapy, and he is still alive with good condition without recurrence and progression of tumors.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Hepatocellular; Drug Combinations; Embolization, Therapeutic; Hepatectomy; Humans; Interferon-alpha; Liver Neoplasms; Lung Neoplasms; Male; Oxonic Acid; Recurrence; Remission Induction; Tegafur; Tomography, X-Ray Computed

A case of a 68-year-old man with hepatocellular carcinoma (HCC) is presented. He underwent partial liver resection for three times and transcatheter arterial chemoembolization (TACE) for three times. Follow-up CT revealed a recurrent hepatic surface mass with malignant extended into the inferior vena cava (IVC) and right atrium (RA). CT scan also revealed multiple metastatic nodules in bilateral lungs. The tumor thrombus into the RA and the hepatic surface mass were successfully treated with surgical resection. Pathological specimen allowed the diagnosis of poorly-differentiated HCC. Adjuvant chemotherapy with S-1 resulted in complete remission of lung metastases. Tumor markers showed a significant improvement after S-1 administration. This case report suggests that a surgical resection followed by S-1 administration would be effective for a patient with lung metastases and a tumor thrombus into IVC or RA.

Topics: Aged; Antimetabolites, Antineoplastic; Carcinoma, Hepatocellular; Chemoembolization, Therapeutic; Drug Combinations; Humans; Liver Neoplasms; Lung Neoplasms; Male; Neoadjuvant Therapy; Oxonic Acid; Recurrence; Tegafur; Tomography, X-Ray Computed

The patient was a 63-year-old man, who had been suffering from lung cancer with left chest wall invasion and contralateral pulmonary metastases. Due to the severe pain caused by this advanced lung cancer with poor performance status (PS), oxycodone was administered for treatment. Radiotherapy was used for local tumor control and oral S-1 was given as systemic chemotherapy. The local control rate (near CR) and the PS were improved effectively by this combination of palliative treatment. As a result, he was allowed to return home and followed as an outpatient. Our experience suggests that positive palliative treatment improves the quality of life (QOL) of patients and provides survival benefits.

Topics: Antimetabolites, Antineoplastic; Combined Modality Therapy; Drug Combinations; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Invasiveness; Oxonic Acid; Quality of Life; Tegafur; Thoracic Neoplasms; Thoracic Wall

A 35-year-old woman with a clinical diagnosis of stage T2N2M0 lung adenocarcinoma received 3 courses of preoperative chemotherapy with cisplatin and docetaxel. The treatment response was no change. A left inferior lobectomy with mediastinal and hilar lymph-node dissection (ND2a) was performed. The pathological diagnosis was stage T2N2M0 lung cancer. Gefitinib was administered postoperatively. After 2 months of oral treatment, gefitinib was discontinued because of enlarged subcarinal lymph nodes and an elevated level of serum Sialyl LewisX-i antigen (SLX). Starting 4 months after surgery, the mediastinum was irradiated with a total dose of 50 Gy. Chemotherapy with S-1 was started 5 months after surgery. S-1 was administered in a dose of 100 mg/day in two divided doses for 4 weeks, followed by 2 weeks of rest. The patient received 6 courses of chemotherapy with S-1, without increasing the dose. The enlarged mediastinal lymph nodes disappeared, and the serum SLX level returned to normal. The patient had a complete response, and was subsequently followed on an outpatient basis while receiving oral UFT. More than 36 months have elapsed since surgery, with no evidence of recurrence.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Combined Modality Therapy; Drug Combinations; Drug Resistance, Neoplasm; Female; Gefitinib; Humans; Lung Neoplasms; Oxonic Acid; Positron-Emission Tomography; Quinazolines; Remission Induction; Tegafur; Tomography, X-Ray Computed

A 73-year-old woman was admitted to our hospital for hemorrhagic shock due to HCC rupture and treated by transcatheter arterial chemoembolization (TACE) in July 2007, followed by partial hepatic resection two months later. Multiple pulmonary and remnant liver metastases were detected by CT six months after the surgery. Since treatment with UFT for two months was not effective, the chemotherapy was changed to S-1 100 mg/body/day in June 2008. After S-1 treatment for three months, lung metastases remarkably diminished, as did the serum AFP level. Meanwhile, although the S-1 dose was gradually reduced to 50 mg/body/day due to adverse effects, pulmonary lesions and serum AFP level remained stationary for five months. While there is no established regimen for distant metastases of HCC, S-1 may be effective even at a reduced dose.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Hepatocellular; Drug Combinations; Female; Humans; Liver Neoplasms; Lung Neoplasms; Oxonic Acid; Tegafur; Tomography, X-Ray Computed

No investigation of S-1 monotherapy in previously treated advanced non-small-cell lung cancer (NSCLC) patients has yet been reported. We conducted a retrospective study to evaluate the efficacy and tolerability of S-1 in patients with failure of second- or further-line chemotherapy.. The records of NSCLC patients who had received S-1 monotherapy between January 2005 and November 2006 with the following eligibility criteria were reviewed: previously treated with at least two regimens including platinum and docetaxel in the case of nonadenocarcinoma patients, and including platinum, docetaxel and epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI) in the case of adenocarcinoma patients. S-1 was administered for 28 consecutive days, followed by a 14-day drug-free period (42 days in one course). The drug was administered in two divided doses daily at 80 mg/day for patients with a body surface area <1.25 m(2), 100 mg/day for those with a body surface area of 1.25-1.5 m(2), and 120 mg/day for those with a body surface area > or = 1.5 m(2).. Thirty-five patients were registered. The median number of courses administered per patient was 2 (range 1-9). The toxicity profile was mild, and grade 3 or more severe toxicity was rare. The overall response and disease control rates were 5.7% and 40%, respectively. The median survival time was 208 days.. S-1 exhibits modest activity and acceptable toxicity when used as a third or subsequent line of chemotherapy in patients with advanced NSCLC.

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Carcinoma, Non-Small-Cell Lung; Disease-Free Survival; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Retrospective Studies; Salvage Therapy; Survival Analysis; Tegafur; Time Factors; Treatment Outcome

The combination therapy of CPT-11, a prodrug of SN-38, with S-1, a dihydropyrimidine dehydrogenase inhibitory fluoropyrimidine, shows a high clinical response rate in non-small cell lung cancer (NSCLC). However, this combination causes severe toxicities such as diarrhea. Here, we investigated the advantages of treatment with the SN-38-incorporating polymeric micelles NK012 over CPT-11 in combination with S-1 in mice bearing a NSCLC xenograft in terms of antitumor activity and toxic effects, particularly intestinal toxicity. In vitro cytotoxic effects were examined in human NSCLC cell lines (A549, PC-9, PC-14, EBC-1 and H520). In vivo antitumor effects were evaluated in PC-14- and EBC-1-bearing mice after NK012 or CPT-11 administration on Days 0 and 7 and S-1 administration on Days 0-13. Pathological changes in the small intestine were also investigated. The in vitro growth inhibitory effects of NK012 were 56.8- to 622-fold more potent than those of CPT-11. NK012/S-1 treatment showed significantly higher antitumor activity both in PC-14-bearing (p = 0.0007) and EBC-1-bearing mice (p < 0.0001) than CPT-11/S-1 treatment. The deformity and decrease in the density of intestinal villi were more severe in CPT-11/S-1-treated mice than in NK012/S-1-treated mice. NK012/S-1 combination is a promising candidate regimen against NSCLC without inducing toxicities such as severe diarrhea and therefore warrants clinical evaluation.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Dihydrouracil Dehydrogenase (NADP); Drug Combinations; Drug Delivery Systems; Drug Synergism; Female; Humans; Intestinal Mucosa; Irinotecan; Lung Neoplasms; Mice; Mice, Inbred BALB C; Mice, Nude; Micelles; Oxonic Acid; RNA, Messenger; Tegafur; Thymidylate Synthase; Xenograft Model Antitumor Assays

The treatment for hepatocellular carcinoma with distant metastasis remains unclear. We experienced a successful case of S-1 chemotherapy for bilateral pulmonary recurrence of hepatocellular carcinoma following hepatectomy after gaining chemoresistance through pretreatment. A 62-year-old man underwent extended right hepatectomy for hepatocellular carcinoma occupying the whole right lobe. CT scan 15 months after hepatectomy revealed bilateral multiple pulmonary recurrence. Pharmacokinetic modulation chemotherapy (PMC) was performed after treatment of UFT, and stable disease status for 24 months was achieved. Pulmonary metastatic lesions gradually became larger, so oral administration of 100 mg per day of S-1 was followed by stable disease status for 9 months. The present case suggests that S-1 chemotherapy may be useful for hepatocellular carcinoma with distant metastasis.

Topics: Administration, Oral; Carcinoma, Hepatocellular; Drug Combinations; Hepatectomy; Humans; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Neoplasm Recurrence, Local; Oxonic Acid; Tegafur; Time Factors

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Basal Cell; Cisplatin; Combined Modality Therapy; Drug Combinations; Female; Humans; Lung Neoplasms; Middle Aged; Oxonic Acid; Radiotherapy Dosage; Salvage Therapy; Tegafur; Thymectomy; Thymus Neoplasms

It is desirable to find more appropriate therapeutic opportunities in non-small-cell lung cancer (NSCLC) due to the current poor prognosis of affected patients. Recently, several histone deacetylase (HDAC) inhibitors, including suberoylanilide hydroxamic acid (SAHA), have been reported to exhibit antitumor activities against NSCLC. S-1, a novel oral fluorouracil anticancer drug, has been developed for clinical use in the treatment of NSCLC in Japan. Using an MTT assay, we analyzed the growth-inhibitory effect of 5-fluorouracil (5-FU), S-1, and SAHA against three NSCLC cell lines, as well as the breast cancer cell line MCF7 which is known to be highly sensitive to 5-FU. Combined treatment with low-dose SAHA enhanced 5-FU- and S-1-mediated cytotoxicity and resulted in synergistic effects, especially in 5-FU-resistant cells. Both the mRNA and protein expression levels of thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), and orotate phosphoribosyltransferase (OPRT), which are associated with 5-FU sensitivity/response, were analyzed in the cells undergoing treatment. 5-Fluorouracil-resistant lung cancer cells displayed high expression of TS mRNA and protein. Suberoylanilide hydroxamic acid down-regulated TS mRNA and protein expression, as well as repressed the rapid induction of this factor during 5-FU treatment, in all examined cell types. We also examined the status of the Rb-E2F1 pathway, with SAHA up-regulating p21(waf1/cip1) expression via promoter histone acetylation; this, in turn, blocked the Rb-E2F1 pathway. We conclude that combination therapy with SAHA and S-1 in lung cancer may be promising due to its potential to overcome S-1 resistance via modulation of 5-FU/S-1 sensitivity-associated biomarker (TS) by HDAC inhibitor.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Cyclin-Dependent Kinase Inhibitor p21; Drug Combinations; E2F1 Transcription Factor; Fluorouracil; Gene Expression Regulation; Histone Deacetylase Inhibitors; Humans; Hydroxamic Acids; Lung Neoplasms; Oxonic Acid; Retinoblastoma Protein; RNA, Messenger; Tegafur; Thymidylate Synthase; Vorinostat

A 70-year-old man was referred to our hospital with bowel obstruction because of rectal cancer. High anterior resection of rectum and lymph node dissection was performed. The rectal cancer was in stage III, and the patient selected no adjuvant chemotherapy. At 1-year follow-up, the CEA level was 17. 6 ng/mL, and CT revealed multiple lung metastases and paraaortic and parailiac lymph node metastases. S-1, 100 mg/body, was administered for 4 weeks followed by 2 drug-free weeks. After 3 courses, the CEA level was 4. 5 ng/mL, and metastatic lesions were remarkably reduced in the CT findings. After 10 courses, the CEA level was hovering around 6 ng/mL, and CT showed no recurrent foci. The effect of S-1 treatment was PR, and no severe side effect was observed throughout the treatment.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Humans; Lung Neoplasms; Lymphatic Metastasis; Male; Oxonic Acid; Rectal Neoplasms; Tegafur; Tomography, X-Ray Computed

Most non-small cell lung cancer (NSCLC) tumors with activating mutations of the epidermal growth factor receptor (EGFR) are initially responsive to first-generation, reversible EGFR tyrosine kinase inhibitors (TKI) such as gefitinib, but they subsequently develop resistance to these drugs through either acquisition of an additional T790M mutation of EGFR or amplification of the proto-oncogene MET. We have now investigated the effects of combination treatment with thymidylate synthase (TS)-targeting drugs and the second-generation, irreversible EGFR-TKI BIBW2992 on the growth of NSCLC cells with the T790M mutation. The effects of BIBW2992 on EGFR signaling and TS expression in gefitinib-resistant NSCLC cells were examined by immunoblot analysis. The effects of BIBW2992 and the TS-targeting agents S-1 (or 5-fluorouracil) or pemetrexed on the growth of gefitinib-resistant NSCLC cells were examined both in vitro and in vivo. The combination of BIBW2992 with 5-fluorouracil or pemetrexed synergistically inhibited the proliferation of NSCLC cells with the T790M mutation in vitro, whereas an antagonistic interaction was apparent in this regard between gefitinib and either of these TS-targeting agents. BIBW2992 induced downregulation of TS in the gefitinib-resistant NSCLC cells, implicating depletion of TS in the enhanced antitumor effect of the combination therapy. The combination of BIBW2992 and either the oral fluoropyrimidine S-1 or pemetrexed also inhibited the growth of NSCLC xenografts with the T790M mutation to an extent greater than that apparent with either agent alone. The addition of TS-targeting drugs to BIBW2992 is a promising strategy to overcome EGFR-TKI resistance in NSCLC with the T790M mutation of EGFR.

Topics: Afatinib; Amino Acid Substitution; Animals; Antineoplastic Agents; Apoptosis; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Cell Proliferation; Drug Combinations; Drug Resistance, Neoplasm; Drug Synergism; E2F1 Transcription Factor; ErbB Receptors; Fluorouracil; Gefitinib; Glutamates; Guanine; Humans; Lung Neoplasms; Mice; Mutation; Oxonic Acid; Pemetrexed; Phosphatidylinositol 3-Kinases; Protein Kinase Inhibitors; Proto-Oncogene Mas; Quinazolines; Tegafur; Thymidylate Synthase; Xenograft Model Antitumor Assays

A 7 0-year-old female underwent distal gastrectomy for gastric cancer in November 2001. She did not wish to receive postoperative adjuvant chemotherapy. In May 2002, her serum carcinoembryonic antigen(CEA)level rose. CT demonstrated liver(S5/6)and lung(S9)metastases in August 2002. We started to treat her with S-1(100mg/day day 1-14 orally), and restaging CT showed complete regression of liver and lung metastases in August 2003. In spite her complete response(CR), we continued S-1 treatment for the successive two years. No adverse reaction to chemotherapy occurred. Although CR was maintained for about 4 years, she was found to have a 9-mm solitary lesion in the upper pole of the spleen in June 2007. After 6 months, this tumor increased to 15mm in size, and we considered it as a solitary metastasis to the spleen from gastric cancer. S-1 chemotherapy was restarted, but tumor size gradually increased. Tumor size finally reached 25mm in December 2008. She underwent splenectomy in January 2009. From then until now, she has not received any chemotherapy, and has been followed well without any recurrence.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Drug Combinations; Female; Gastroenterostomy; Humans; Liver Neoplasms; Lung Neoplasms; Neoplasm Metastasis; Oxonic Acid; Remission Induction; Splenectomy; Splenic Neoplasms; Stomach Neoplasms; Tegafur; Time Factors; Tomography, X-Ray Computed

A 71-year-old woman was admitted to our hospital, because of an abnormality on her chest radiograph findings. After extensive examination, she was diagnosed with primary lung adenocarcinoma (cT4N2M1, stage IV). She was treated by carboplatin+gemcitabine, gefitinib and docetaxel and the responses were stable disease in any treatment. As the fourth-line treatment, she received oral chemotherapy using S-1 at 100 mg/day (80 mg/m2 day) for 28 days, followed by withdrawal for 14 days. Tumor size was reduced 29.2% after 1 course, 62.5% after 5 courses and 83.3% after 10 courses (14 months). Hematologic and non-hematologic toxicities were mild with the S-1 administration. We experienced a case of continuation of tumor shrinkage over a year without serious adverse events by S-1 treatment. Therefore, oral administration of S-1 could be useful for the treatment of recurrent non-small cell lung cancer over a long time.

Topics: Administration, Oral; Aged; Antimetabolites, Antineoplastic; Carcinoma, Non-Small-Cell Lung; Drug Combinations; Female; Humans; Lung Neoplasms; Oxonic Acid; Radiography; 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

It is not clear what the optimal treatment of chemotherapy is for patients with heavily treated metastatic breast cancer (MBC). We have retrospectively examined the efficacy and safety of S-1 in patients with MBC who had been previously treated with anthracycline, taxane, and capecitabine.. Patients with MBC who had been administered S-1, an oral modulated compound containing a fluoropyrimidine derivative, between November 2001 and June 2003 at the Cancer Institute Hospital were retrospectively reviewed. S-1 at a standard dose of 50 mg/body was administered twice daily for four weeks, followed by a two-week rest period. This was repeated every six weeks until disease progression or unacceptable toxicity.. Thirty-five patients were assessed. The patients were heavily pretreated with anthracycline (100%), taxane (paclitaxel or docetaxel) (100%), capecitabine (100%), vinorelbine (71%), and mitomycin (69%). Median follow-up time of patients was 9.6 months (range, 1.2-26.6). ORR was 3% (95% confidence interval: 0-9%), and CBR was 20% (95% confidence interval: 6-33%). Time to treatment failure was 2.8 months. Overall survival was 21.4 months. Grade 1 or 2 adverse events were observed in 17% and 13%, respectively. Grade 3 events occurred as anorexia (9%), nausea (9%), vomiting (9%), diarrhea (14%), fatigue (3%), and elevation of AST/ALT (3%). No grade 3 was seen as hand-foot syndrome. Neither grade 3 nor 4 was observed in bone marrow suppression.. S-1 was fairly well tolerated, but demonstrated very limited activity in capecitabine-pretreated patients who had already been exposed to anthracycline and taxane. It was suggested that S-1 clinically exhibited cross-resistance to capecitabine.

Topics: Adult; Aged; Aged, 80 and over; Anthracyclines; Antimetabolites, Antineoplastic; Bone Neoplasms; Breast Neoplasms; Bridged-Ring Compounds; Capecitabine; Deoxycytidine; Drug Combinations; Drug Resistance, Neoplasm; Female; Fluorouracil; Humans; Liver Neoplasms; Lung Neoplasms; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Oxonic Acid; Pleural Neoplasms; Prognosis; Retrospective Studies; Survival Rate; Taxoids; Tegafur; Treatment Outcome

Most non-small cell lung cancer (NSCLC) tumors with activating mutations in the epidermal growth factor receptor (EGFR) are initially responsive to EGFR tyrosine kinase inhibitors (EGFR-TKI) such as gefitinib and erlotinib, but they almost invariably develop resistance to these drugs. A secondary mutation in EGFR (T790M) and amplification of the MET proto-oncogene have been identified as mechanisms of such acquired resistance to EGFR-TKIs. We have now investigated whether addition of the oral fluoropyrimidine derivative S-1 to gefitinib might overcome gefitinib resistance in NSCLC cell lines.. The effects of gefitinib on EGFR signaling and on the expression both of thymidylate synthase and of the transcription factor E2F-1 in gefitinib-resistant NSCLC cells were examined by immunoblot analysis. The effects of S-1 (or 5-fluorouracil) and gefitinib on the growth of NSCLC cells were examined in vitro as well as in nude mice.. Gefitinib induced down-regulation of thymidylate synthase and E2F-1 in gefitinib-resistant NSCLC cells with MET amplification but not in those harboring the T790M mutation of EGFR. The combination of 5-fluorouracil and gefitinib synergistically inhibited the proliferation of cells with MET amplification, but not that of those with the T790M mutation of EGFR, in vitro. Similarly, the combination of S-1 and gefitinib synergistically inhibited the growth only of NSCLC xenografts with MET amplification.. Our results suggest that the addition of S-1 to EGFR-TKIs is a promising strategy to overcome EGFR-TKI resistance in NSCLC with MET amplification.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Drug Combinations; Drug Resistance, Neoplasm; Drug Screening Assays, Antitumor; E2F1 Transcription Factor; ErbB Receptors; Fluorouracil; Gefitinib; Gene Amplification; Genes, erbB-1; Humans; Lung Neoplasms; Male; Mice; Mice, Nude; Mutation; Oxonic Acid; Proto-Oncogene Mas; Proto-Oncogene Proteins c-met; Quinazolines; Tegafur; Thymidylate Synthase

An 81-year-old man presented with right shoulder pain 10 months after surgery for non-small cell lung cancer (p- T3N0M0, Stage II b). FDG-PET revealed an increased uptake in the multiple bone and mediastinal lymph nodes, suggestive of recurrence of lung cancer. He was given combined chemotherapy of gemcitabine plus S-1 as first-line treatment. This regimen was performed as a phase I trial for an elderly patient with advanced non-small cell lung cancer, and the treatment proved effective. No toxic events were observed due to this therapy, so he was treated as an outpatient for one year. He was considered to have good quality of life.

Topics: Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Carcinoma, Non-Small-Cell Lung; Deoxycytidine; Drug Combinations; Gemcitabine; Humans; Lung Neoplasms; Male; Oxonic Acid; Positron-Emission Tomography; Tegafur

A 78-year-old man had underwent right upper lobectomy for lung adenocarcinoma in July 1998(pT1N0M0, pStage Ia). In January2003, computed tomography showed a tumor in right lower lobe of lung, which grew slowly. He was treated with UFT. In April 2004, computed tomographyshowed multiple nodules in both lung, which was considered of metastasis of lung cancer. The increase of the nodules were observed, and treatment with gefitinib was started. Insertion mutation at EGFR in exon 20 was seen from the primarylung cancer. Since tumor growth occurred despite gefitinib administration, we converted gefitinib into S-1 using 80 mg/day for 28 days, followed by 14 days rest. Chest computed tomographyshowed a partial response. No side effect was observed, and continued internal use of S-1 until January 2007 when it was impossible to continue, and meanwhile, the increase of the tumor was not seen.

Topics: Aged; Carcinoma, Non-Small-Cell Lung; Drug Combinations; Drug Resistance, Neoplasm; ErbB Receptors; Gefitinib; Humans; Lung Neoplasms; Male; Mutation; Oxonic Acid; Quinazolines; Tegafur; Tomography, X-Ray Computed

We evaluated retrospectively single-agent S-1 chemotherapy in non-small cell lung cancer patients in clinical practice.. Sixteen consecutive patients treated with single-agent S-1 for NSCLC between July 2005 and June 2007 at the Department of Thoracic Surgery, Tsuchiura Kyodo General Hospital. The treatment schedule comprised oral administration of S-1 at 80-120 mg/day. One cycle of S-1 consisted of consecutive administration to 14 (10 cases)or 28(6 cases)days followed by a 14-day rest.. Patients profiles were: M/F: 11/5, median age 68 years old(range 51-83), PS 0/1/2/3: 2/6/5/3, adeno/squamous/large: 13/2/1, clinical stage 3A/3B/4: 3/4/9, prior chemotherapy regimens 0/1/2/3/4: 2/3/4/5/2, prior surgery/radiation: 12/5 were performed. Median number of delivered cycles was 5 cycles(range 1-13). Grade 3 hematological toxicities were anemia(6%)and thrombocytopenia(6%). Grade 3 non-hematological toxicities were nausea(6%)and vomiting(6%). Response of 13 patients could be evaluated after 2-4 cycles of S-1. Four partial responses were observed, for a response rate of 31%. The survival time was 67-852 days(average 14.0 months), 1-year survival rate was 74.0%, median time to progression was 4.6 m, and 1- year progression free survival was 25.0%.. Single-agent S-1 chemotherapy has modest activity and is the one of the important regimens and tolerable for elderly, poor-PS, recurrent patients with NSCLC in clinical practice.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Disease Progression; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Survival Rate; Tegafur

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

The objective of this study was to evaluate the efficacy and toxicity of S-1 monotherapy in patients with pretreated advanced non-small cell lung cancer(NSCLC).. We prospectively analyzed patients previously treated with a platinum-containing regimen or monotherapy with a third-generation chemotherapeutic drug. S-1 was orally administered at approximately 80 mg/m / 2day for 28 days followed by a 2-week rest period. We evaluated the efficacy and toxicities.. A total of 15 patients received S-1 monotherapy. Three partial responses were observed among them with an overall response rate of 20%. Toxicities of grade 3 or higher included anemia(13%), thrombocytopenia( 6%), fatigue(6%), anorexia(13%), diarrhea(13%), interstitialpneumonitis(6%)and infection(6%). The ratio of outpatient treatment period was 73.5%. The median time to progression, median survivaltime and 1-year survival rate were 4.2 months, 7.8 months and 27.8% respectively.. S-1 monotherapy was suggested to be effective and tolerable in patients with pretreated advanced NSCLC.

Topics: Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Carcinoma, Non-Small-Cell Lung; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Prospective Studies; Survival Rate; Tegafur

A 73-year-old man was referred to our hospital with complaints of constipation and defecation caused by a sigmoid colon tumor. After examination, he was diagnosed as sigmoid colon cancer with lung metastasis, peritoneal dissemination and early gastric cancer. To prevent bowel obstruction, a sigmoid colon resection was performed. On postoperative day 20, S-1 (100 mg/body for 4 weeks followed by 2 drug-free weeks) treatment was started. After 13 courses of treatment, gastrointestinal fiberscope revealed that the gastric cancer was remarkably reduced, and after 16 courses, computed tomography revealed that the lung metastasis was remarkably reduced. Although after 12 courses, elevation of bilirubin, the treatment could be possible to continued on a lowered dose of S-1 from 100 mg to 80 mg/body. Twenty-four months after the operation, good control of cancer has been maintained, and the treatment is continuing. S-1 treatment was proved effective for double cancer of the advanced colorectal cancer and the gastric cancer.

Topics: Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Humans; Lung Neoplasms; Male; Neoplasms, Multiple Primary; Oxonic Acid; Peritoneum; Sigmoid Neoplasms; Stomach Neoplasms; Tegafur

Bronchioloalveolar carcinoma (BAC) is a distinct subtype of non-small cell lung cancer for which there is no optimal therapy for non-resectable or recurrent disease. This report describes a patient with BAC refractory to conventional chemotherapy but with a partial response to S-1, oral fluoropyrimidine, resulting in symptom improvement and weaning from oxygen supplementation. Our observation suggests that S-1 is a novel option for the treatment of advanced BAC.

Topics: Adenocarcinoma, Bronchiolo-Alveolar; Antimetabolites, Antineoplastic; Carcinoma, Non-Small-Cell Lung; Drug Combinations; Female; Humans; Lung Neoplasms; Middle Aged; Oxonic Acid; Tegafur; 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

We report two successful remnant and recurrent cases of head and neck cancer treated with S-1. Case 1, a 52-year-old man, was diagnosed as supraglottic laryngeal carcinoma (T3N2cM0, squamous cell carcinoma: SCC) on January 25, 2000, and concurrent chemoradiotherapy (CCRT) was applied. After the treatment, a remnant tumor in the larynx was found by biopsy. He was followed using UFT at 400mg/day because he had refused surgery. Pulmonary metastasis was detected by chest CT on June 14, 2001, and the administration of S-1 was started. After 2 courses, the mass in the lung disappeared, and the primary lesion was also judged to be a complete response(CR). The administration of S-1 is still continuing and remnant tumors have not been found. Case 2, a 76-year-old man, was diagnosed with hypopharyngeal carcinoma (T3N2bM0, SCC) on December 14, 2001, and CCRT was applied resulting in CR in the hypopharynx and the neck. He was followed using UFT at 300 mg/day after discharge. A supraclavicular lymph node became palpable on March 27, 2003. Pathological examination by fine needle aspiration cytology showed SCC, class V. After 2 courses administering S-1 at 100mg/day, the supraclavicular lymph node disappeared. S-1 was changed to UFT at 300 mg/day on July 31, 2003, because adverse events of grade 3 appeared. Administration of UFT was continued for one year. No recurrence has been found for 5 years.

Topics: Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Drug Combinations; Head and Neck Neoplasms; Humans; Hypopharyngeal Neoplasms; Laryngeal Neoplasms; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Tegafur; Tomography, X-Ray Computed; Treatment Outcome

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

We report a case of recurrent rectal cancer with multiple lung metastases successfully treated with S-1 and CPT-11 combination chemotherapy. Rectal amputation was carried out on the rectal cancer patient, a 63-year-old man. CT scan revealed multiple lung metastases after 20 months of surgery. The patient was treated with S-1 and CPT-11 combination chemotherapy. S-1(100mg/body/day)was orally administered for 2 weeks followed by a 1-week interval, and CPT-11 (120 mg/body on day 1)was simultaneously administered. After completion of 8 courses, CT scan showed no lung metastases, and the patient was judged to have achieved a complete response (CR). The CR interval was maintained for twelve months until 20 courses of chemotherapy had been completed. This chemotherapy was expected to have a potent therapeutic efficacy for recurrent rectal cancer, considering the convenience, cost benefit and no severe adverse event.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Drug Combinations; Humans; Irinotecan; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Rectal Neoplasms; Recurrence; Tegafur; Tomography, X-Ray Computed; Treatment Outcome

The patient was a 54-year-old male. In July 2004, he underwent resection of the pancreatic body tail region to treat pancreatic body tail cancer. On histopathological examination, the stump of the extirpated specimen was positive for tumor cells. After surgery, 10 courses of therapy with gemcitabine hydrochloride(GEM, 1, 000 mg/m(2), 3-week administration followed by 1-week discontinuation)were performed, and follow-up was continued. In February 2006, local relapse was detected. Chemotherapy with GEM was administered for 1 year and 9 months. However, in November 2007, an increase in the recurrent lesion size and right lung metastasis were noted. The regimen was switched to combination therapy with S-1 and GEM(S-1 60 mg/m(2) day, continuous administration on days 1 to 14 and 2-week discontinuation; and GEM 1, 000 mg/ m(2), administered on days 8 and 15). After the end of the 11th course, PET-CT revealed the disappearance of FDG accumulation in the recurrent and metastatic lesion sites. During the treatment period, there were no grade 3 or higher adverse reactions. The patient is being treated at the outpatient clinic (as of January 2009).

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Deoxycytidine; Drug Combinations; Gemcitabine; Humans; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Pancreatic Neoplasms; Positron-Emission Tomography; Recurrence; Tegafur; Tomography, X-Ray Computed

A57 -year-old man. Though chronic hepatitis C was pointed out before, it had been left untreated for about 5 years. He was hospitalized because many venereal diseases had been pointed out in the liver by abdomen ultrasonography. Results of close examination revealed stage IV B with bone metastases, and pulmonary metastases was diagnosed. After consultation, whole-body chemotherapy combining S-1 and PEG-IFN was attempted as of June 26, 2007. S-1 (80 mg/day) was then administered every day for two weeks with drug withdrawal for one week. PEG-IFNalpha-2a (180 microg)was administered once a week. We set three weeks as one course. The liver tumor was markedly reduced, and the pulmonary metastases were also reduced at the completion of 5 courses. The therapeutic effectiveness of this chemotherapy was confirmed by imaging test. The course was favorable, and whole-body chemotherapy was discontinued on January 29, 2008. At this writing in October of 2008, the course has been uneventful. This treatment method is a promising choice for whole-body chemotherapy for advanced hepatocarcinoma in the future. We have added some review of the literature, and the S-1+PEG-IFN combination chemotherapy is reported.

Topics: Angiography; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Carcinoma, Hepatocellular; Drug Combinations; Hepatitis C, Chronic; Humans; Interferon alpha-2; Interferon-alpha; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Oxonic Acid; Polyethylene Glycols; Recombinant Proteins; Tegafur; Tomography, X-Ray Computed

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

A male patient in his seventies presented at our hospital with a chief complaint of an abnormal shadow on a chest scout film. We suspected non-small cell carcinoma of the right upper lobe on computed tomography (CT). The patient underwent partial resection of the right upper lobe by video-assisted thoracoscopic surgery in May 2004, frozen sections of which showed poorly differentiated squamous cell carcinoma, consistent with the tumor size 2.5 x 1.7 cm. We performed right upper lobectomy and lymphadenectomy. Final pTNM was T1N0M0, stage IA. The patient had been followed every three months until a coin lesion appeared in the right lower lobe in April 2007. He chose radiation therapy of 48 Gy in total at another hospital with the result that the lesion disappeared. However, the disease recurred in May 2008. Bilateral multiple lung metastases and mediastinal lymph nodes involvement were confirmed by CT. Two courses of docetaxel 60 mg/m(2) (90 mg/body) and cisplatin 80 mg/m / 2 (120 mg/body) were not effective with adverse reaction grade 3. Less docetaxel and cisplatin resulted in a grade 4 reaction. The regimen was changed to S-1 60 mg per day with three weeks on and two weeks off. After two courses complete remission was confirmed at a chest X-ray examination. He has been free of disease with tegafur/uracil 600 mg per day for 4 months.

Topics: Aged; Antimetabolites, Antineoplastic; Carcinoma, Squamous Cell; Drug Combinations; Humans; Lung Neoplasms; Lymph Node Excision; Male; Neoplasm Recurrence, Local; Oxonic Acid; Pneumonectomy; Remission Induction; Tegafur

A 40s male was performed proximal gastrectomy with D1+alpha dissection and interposition reconstruction for type 1 esophago-gastric junctional cancer in January 2002. Pathological findings were as follows: pap, se, ly0, v0, n1 (#3, 1/9) stage IIIA, curability B. Adjuvant chemotherapy by 5'-DFUR (800 mg/day) was done for 1 year. Bilateral pulmonary metastasis was detected in left S6 (3.8 cm) and right S10 (3 cm) in February 2006. After S-1 (120 mg/day) was administered for 4 courses, right pulmonary metastasis had become scar, and the other was remained and growing. S-1 (100 mg/ day 1-21)+CPT-11 (120 mg div day 1, 15) was done for 6 courses. However, the tumor was growing. As no other lesions but left pulmonary metastasis in S10, radical thoracoscopic left lower lobectomy with ND1 lymph node dissection was performed. Pathological finding was pulmonary metastasis from gastric cancer with no lymph node metastasis. There were no recurrences observed in May 2009 since gastrectomy was done 7 years ago, and 3 years since pulmonary metastasis was detected.

Topics: Adult; Antimetabolites, Antineoplastic; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Drug Combinations; Gastrectomy; Humans; Irinotecan; Lung Neoplasms; Male; Neoadjuvant Therapy; Oxonic Acid; Pneumonectomy; Stomach Neoplasms; Tegafur; Thoracoscopy

A 68-year-old man lost in unconscious and was diagnosed as ruptured hepatocellular carcinoma (HCC) in a local emergency hospital. He was treated by transcatheter arterial embolization, and further investigation revealed simultaneous cancer in rectum. He was referred to our institute, and admitted in June 2005. He underwent lateral segment and S8 partial resection of the liver, cholecystectomy, anterior resection of rectum, and D3 lymphadenectomy in August 2005. Multiple HCC recurrences in the remnant liver appeared in December 2005. He was subsequently treated with transcatheter chemoembolization four times. In May 2006, CT scan revealed multiple metastatic nodules in bilateral lungs with remarkably elevated serum AFP and PIVKA-II. The nodules were diagnosed as lung metastasis of the HCC. Because the lesions grew larger, S-1 was started in February 2007. Diagnostic imaging and tumor markers showed a marked improvement 2 months after S-1 administration, and no recurrence has been found since then. This case illustrates that S-1 may be an effective treatment for HCC with extrahepatic metastasis.

Topics: Aged; Antimetabolites, Antineoplastic; Carcinoma, Hepatocellular; Drug Combinations; Hepatectomy; Humans; Liver Neoplasms; Lung Neoplasms; Male; Neoplasm Recurrence, Local; Neoplasms, Multiple Primary; Oxonic Acid; Rectal Neoplasms; Tegafur

A 78-year-old woman underwent gastrectomy for type 3 gastric cancer with pyloric stenosis, which was detected in November 1997. Thoracic and abdominal CT and other diagnostic procedures were conducted regularly for 5 years after surgery. The patient was recurrence-free and her clinical course was satisfactory. Starting in early May 2005, however, she began to experience respiratory difficulty at exertion, which exacerbated rapidly thereafter. Examination at a department of respiratory physiology led to a diagnosis of a recurrence of stomach cancer and carcinomatous lymphangiosis+lymphatic metastasis to the peritoneal cavity. She was referred to us for palliative care. The accentuated respiratory difficulty was eased with oxygen inhalation and opioid administration. With improvement in her respiratory condition, a combination of S-1 80 mg/day, CDDP 10 mg x once/week and Lentinan 1 mg x twice/week, was initiated. Within about 2 weeks, her respiratory difficulty was eliminated and after 4 weeks x 2 courses, the tumor images were no longer recognized in the thoracic and abdominal CTs. The combination therapy of S-1/low-dose CDDP/Lentinan is free of evident adverse effects and may be a potent therapeutic alternative as a palliative therapy for malignant stomach cancers in elderly patients or those in a poor systemic condition.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Female; Humans; Lentinan; Lung Neoplasms; Lymphatic Metastasis; Oxonic Acid; Recurrence; Stomach Neoplasms; Tegafur; Time Factors; Tomography, X-Ray Computed

A 72-year-old male had suffered from a recurrent pulmonary squamous cell carcinoma. He had a history of systemic chemotherapy including carboplatin+paclitaxel(CBDCA+PTX)and docetaxel(DOC). As third-line chemotherapy, this patient was treated with 100 mg of S-1 daily for 4 weeks followed by 2 weeks of rest. Maximal effect was acquired 3.5 months after start of S-1 and resulted in partial response. Since tumors re-grew, S-1 was stopped and other chemotherapies including gemcitabine+vinorelbine(GEM+VNR)and gefitinib were tried but proved ineffective. The tumors gradually grew and, subsequently, right total atelectasis occurred. Re-administration of S-1 showed tumor regression and atelectasis improved. Now this patient is continuing treatment with S-1 monotherapy.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Carcinoma, Squamous Cell; Drug Combinations; Humans; Lung Neoplasms; Male; Neoplasm Recurrence, Local; Oxonic Acid; Tegafur; Tomography, X-Ray Computed

A 77-year-old man was admitted to our hospital complaining of general malaise, loss of appetite and hemoptysis. Chest X-ray film and computed tomography (CT) scan showed right-sided pleural effusion with lung tumor. Succeeding upper gastro-intestinal fiberscopy and cystoscopy revealed poorly-differentiated adenocarcinoma of the stomach and urothelial carcinoma of the bladder. Repeated treatment with 100 mg/body of S-1 on day 1 followed by 60 mg/m(2) of cisplatin on day 8 was effective in this patient.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Gastroscopy; Humans; Lung Neoplasms; Magnetic Resonance Imaging; Male; Neoplasm Staging; Neoplasms, Multiple Primary; Oxonic Acid; Stomach Neoplasms; Tegafur; Tomography, X-Ray Computed; Urinary Bladder Neoplasms

A 70-year-old woman with pulmonary carcinomatous lymphangitis and paraaortic lymph node metastases due to gastric cancer, was treated by combination chemotherapy of S-1 and irinotecan (CPT-11). After one course of the chemotherapy, pulmonary carcinomatous lymphangitis and paraaortic lymph node metastases were remarkably improved. Diet intake was improving and cancer pain remarkably declined. Because the origin of gastric cancer was not improved, total gastrectomy, distal pancreatectomy and splenectomy were performed. After surgery, relapse of pulmonary carcinomatous lymphangitis caused death of the patient. The combination chemotherapy of S-1 and CPT-11 was effective for pulmonary carcinomatous lymphangitis and paraaortic lymph nodes metastases due to gastric cancer. However, careful consideration is required since surgery is performed on a patient who had suffered pulmonary carcinomatous lymphangitis.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Aorta; Camptothecin; Drug Combinations; Female; Gastroscopy; Humans; Irinotecan; Lung Neoplasms; Lymphangitis; Lymphatic Metastasis; Neoplasm Staging; Oxonic Acid; Stomach Neoplasms; Tegafur; Tomography, X-Ray Computed; Treatment Failure

The patient was an 86-year-old female who suffered from advanced non-small cell-lung cancer (cT4N3M1, Stage IV). She was treated with combined chemotherapy of gemcitabine and S-1 as first-line therapy. This regimen was performed as a phase I trial for elderly patients with advanced non-small cell lung cancer. The treatment assessment was evaluated as partial response. No toxic events were observed due to this therapy, so she was treated as an outpatient. She was considered to have good quality of life.

Topics: Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Deoxycytidine; Drug Combinations; Female; Gemcitabine; Humans; Lung Neoplasms; Oxonic Acid; Positron-Emission Tomography; Tegafur; Tomography, X-Ray Computed

The therapeutic effect of concurrent chemoradiotherapy with TS-1 has been confirmed in various solid tumors; however, the detailed mechanism of action has not yet been fully elucidated. In the present study, we identified hypoxia-inducible factor-1 (HIF-1) as one of the targets of TS-1 in chemoradiotherapy. In growth delay assays using a tumor xenograft of non-small-cell lung carcinoma, H441, TS-1 treatment enhanced the therapeutic effect of single gamma-ray radiotherapy (14 Gy) and significantly delayed tumor growth by 1.58-fold compared to radiotherapy alone (P < 0.01). An optical in vivo imaging experiment using a HIF-1-dependent 5HRE-luc reporter gene revealed that TS-1 treatment suppressed radiation-induced activation of HIF-1 in the tumor xenografts. The suppression led to apoptosis of endothelial cells resulting in both a significant decrease in microvessel density (P < 0.05; vs radiation therapy alone) and a significant increase in apoptosis of tumor cells (P < 0.01; vs radiation therapy alone) in tumor xenografts. All of these results indicate that TS-1 enhances radiation-induced apoptosis of endothelial cells by suppressing HIF-1 activity, resulting in an increase in radiosensitivity of the tumor cells. Our findings strengthen the importance of both HIF-1 and its downstream gene, such as vascular endothelial cell growth factor, as therapeutic targets to enhance the effect of radiotherapy.

Topics: Animals; Antimetabolites, Antineoplastic; Apoptosis; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Combined Modality Therapy; Drug Combinations; Endothelial Cells; Humans; Hypoxia-Inducible Factor 1; Immunohistochemistry; Lung Neoplasms; Mice; Mice, Inbred BALB C; Oxonic Acid; Tegafur; Vascular Endothelial Growth Factor A

A 31-year-old woman suffering from stomach pain was admitted to our hospital, and diagnosed with unresectable advanced gastric cancer. She was initially treated with combination therapy of S-1 and CDDP, and a partial response was achieved. After two courses of the chemotherapy, however, she complained of dyspnea, and pulmonary carcinomatous lymphangitis was confirmed by computed tomography. As second-line chemo-therapy, we attempted combination therapy with docetaxel, CDDP and S-1(DCS). After one course of the combination therapy, a remarkable response in the pulmonary carcinomatous lymphangitis was achieved. Treatment of patients with advanced gastric cancer associated with pulmonary carcinomatous lymphangitis is quite difficult and there is no scientific evidence to select anti-cancer drugs for these patients. We concluded that DCF could be a useful regimen for patients with gastric cancer associated with pulmonary carcinomatous lymphangitis.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Docetaxel; Drug Combinations; Female; Gastroscopy; Humans; Lung Neoplasms; Lymphangitis; Neoplasm Staging; Oxonic Acid; Stomach Neoplasms; Taxoids; Tegafur; Tomography, X-Ray Computed; Treatment Failure

A 65-year-old male underwent a curative distal gastrectomy for advanced gastric cancer in June 2000. S-1 mono- therapy (80 mg/m2, day 1-28/42 days) for liver metastasis in S6 started as the first-line chemotherapy in October 2004. After 3 courses, complete response (CR) was observed for liver metastasis which had continued until January 2007. During the first-line chemotherapy, grade 2 non-hematological toxicities occurred and the S-1 dose reduction was required. Thereafter, no more grade 2 non-hematological toxicities were observed. Paclitaxel mono-therapy (80 mg/m2, day 1, 8, 15/28 days) for multiple lung metastases started as the second-line chemotherapy in February 2007. After 4 courses, complete response (CR) was observed for lung metastasis which has continued until now, May 2008. During the second- line chemotherapy, grade 3 neutropenia and grade 2 leukopenia occurred and a 10% dose reduction of paclitaxel was required three times. Consequently, the hematological toxicities have not occurred.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Drug Combinations; Humans; Liver Neoplasms; Lung Neoplasms; Magnetic Resonance Imaging; Male; Oxonic Acid; Paclitaxel; Radiography; Stomach Neoplasms; Tegafur

An 82-year-old female with unresectable colon cancer accompanied by multiple lung metastasis was treated with S-1. Our course consisted of S-1(80 mg/body)from day 1 to 5 followed by 2 days rest. After 14 courses, multiple lung metastasis decreased in size. After 20 courses, the multiple lung metastasis disappeared and local recurrence of colon cancer decreased. Weekly S-1 leads to a partial response. Our chemotherapy showed simple and good compliance for a patient over 80 years old.

Topics: Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colonic Neoplasms; Drug Combinations; Female; Humans; Irinotecan; Lung Neoplasms; Neoplasm Recurrence, Local; Oxonic Acid; Tegafur; Tomography, X-Ray Computed; Treatment Failure

S-1 is an oral fluorouracil anticancer drug that contains the 5-FU prodrug tegafur. Tegafur has been shown to be converted enzymatically to 5-FU to exert its antitumor effect, and this conversion is principally catalyzed by CYP2A6. Forty-six non-small-cell lung cancer patients were enrolled. The frequencies of the CYP2A6*4C, CYP2A6*7, and CYP2A6*9 alleles were 17.4, 19.6, and 15.2%, respectively. In the S-1 pharmacokinetic analysis, the area under the concentration-time curve from 0 to 10 h (AUC(0-10)) ratios of 5-FU/tegafur showed large interindividual variabilities, ranging from 5.14 to 112.6. The AUC(0-10) for tegafur was 1.5-fold higher in patients with the CYP2A6*4C allele than in patients without the CYP2A6*4C allele P < 0.05). Furthermore, patients with the CYP2A6*4C allele had a significantly lower maximum plasma concentration (102.6 +/- 32.9 ng/ml) for 5-FU than patients without the CYP2A6*4C allele (157.0 +/- 65.5 ng/ml, P < 0.05). Genotyping of CYP2A6 polymorphisms may provide vital information for effective cancer therapy using S-1.

Topics: Adult; Aged; Alleles; Antimetabolites, Antineoplastic; Area Under Curve; Aryl Hydrocarbon Hydroxylases; Asian People; Carcinoma, Non-Small-Cell Lung; Cytochrome P-450 CYP2A6; Drug Combinations; Female; Fluorouracil; Genotype; Humans; Lung Neoplasms; Male; Middle Aged; Mixed Function Oxygenases; Oxonic Acid; Smoking; Tegafur

We report two cases with recurrent non-small cell lung cancer (NSCLC) successfully treated with cisplatin and S-1 after multiple chemotherapy. A 64-year-old woman was diagnosed with adenocarcinoma, yield-T4N2M1, stage IV. She was treated with cisplatin 60 mg/m(2) (day 8) and S-1 80 mg/m(2) (days 1-21) as sixth-line chemotherapy after treatment with paclitaxel and irinotecan, cisplatin and gemcitabine, docetaxel, gefitinib, and vinorelbine. Chest computed tomography (CT) showed partial response of recurrent tumors. Another woman (56 years old) was diagnosed with adenocarcinoma, yield-T0N1M1, stage IV. She was also treated with cisplatin and S-1 as fourth-line chemotherapy after treatment with nedaplatin and gemcitabine, docetaxel and irinotecan, and gefitinib. Chest CT showed a partial response of recurrent tumors. Additionally, we retrospectively reviewed 10 cases with recurrent NSCLC treated with cisplatin and S-1 during the same period. Grade 3 to 4 hematologic toxicity included neutropenia in 30% of these 10 patients, thrombocytopenia in 20%, and anemia in 60%. Grade 3 non-hematologic toxicity included hyperglycemia and hyponatremia in 20% of the 10 patients. All side effects were manageable and there was no case of treatment-related death. Cisplatin combined with S-1 could be an option for recurrent NSCLC.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Cisplatin; Drug Combinations; Female; Humans; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Recurrence; Tegafur; Tomography, X-Ray Computed

The patient was a 63-year-old man who consulted our hospital with complaints of a cough and breathing difficulties. His chest CT revealed a 25-mm mass in his right S1 hilar area with spiculation, disseminated nodule in right lung, and pericardial effusions. Also, bronchoscope and TBLB revealed squamous cell carcinoma. This patient was diagnosed as lung cancer (cT4N3M1, stage IV), and chemotherapy was initiated. The chemotherapy was given in the order of CBDCA (AUC3) +GEM (1,000 mg/m(2)), DOC (60 mg/m(2)), and VNR (25 mg/m(2)), and the tumor response was PD. S- 1 (120 mg/body/day, continuous administration for 2 weeks followed by 1 week of rest) was chosen as fourth-line treatment, and a breast CT detected tumor size reduction following completion of the first course. However, after completion of three courses, the breast CT found tumor-enlargement again. Then the chemotherapy was changed to amrubicin (35 mg/m(2)), but the treatment was discontinued due to skin rash. We once experienced a size reduction with S-1, so S-1 (100 mg/body/day, day 1-14) plus CPT-11 (60 mg/m(2), day 1, 7, 14) combination chemotherapy was conducted at 4-week intervals. After two courses were completed, tumor size reduction was observed by breast XP and CT. The response rate was 40.0%. Currently, seven courses were completed, and we will continue this treatment due to the tumor response of SD. The S-1 single treatment and S-1+CPT-11 combination chemotherapy showed efficacy for this difficult case of NSCLC with refractoriness to multiple cancer drug chemotherapy. This combination treatment should be investigated further for its therapeutic benefit.

Topics: Antigens, Neoplasm; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Camptothecin; Carcinoma, Squamous Cell; Drug Combinations; Drug Resistance, Neoplasm; Humans; Irinotecan; Keratin-19; Keratins; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Tegafur; Tomography, X-Ray Computed

A 71-year-old man underwent right hemicolectomy for an ascending colon cancer (stage II, Cur A) in September 2001. Adjuvant chemotherapy with tegafur/uracil was performed, but CT scans and FDG-PET, conducted in May 2003, revealed cancerous pleuritis and lung metastasis. Although 2 courses of the chemotherapy with LV+5-FU (RPMI regimen) were completed, progressive disease was confirmed. Therefore, the chemotherapy with CPT-11 (100 mg/ day; day 1, 15)+S-1 (100 mg/day; day 1-21) was started in May 2004. After completion of 6 courses, CT scan showed a partial response. Only grade 2 vomiting was noted as an adverse reaction to the treatment, however, the patient has been managed on an outpatient basis for the last 3 years with good QOL and the cancer under control. This case suggests that this combination therapy can be expected to be highly effective as a safe approach for continuously maintaining the QOL of patients with advanced or recurrent colorectal cancer.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colonic Neoplasms; Drug Combinations; Humans; Irinotecan; Lung Neoplasms; Male; Neoplasm Staging; Oxonic Acid; Pleurisy; Positron-Emission Tomography; Tegafur; Time Factors; Tomography, X-Ray Computed

Topics: Alleles; Antimetabolites, Antineoplastic; Aryl Hydrocarbon Hydroxylases; Asian People; Body Size; Carcinoma, Non-Small-Cell Lung; Cytochrome P-450 CYP2A6; Drug Combinations; Fluorouracil; Humans; Lung Neoplasms; Oxonic Acid; Tegafur

The patient was a 44-year-old male in whom low anterior resection of the rectum, partial pneumonectomy, and liver biopsy were performed because of suspicion of synchronous liver and pulmonary metastases of rectal cancer which caused familial adenomatous polyposis. Because anticancer drug sensitivity testing by the HDRA method performed on tissue collected from the cancer immediately postoperatively revealed sensitivity to 5-FU and CPT-11, and measurement of nucleic acid metabolizing enzymes showed a high level of DPD, a 5-FU metabolizing enzyme, combination therapy with TS-1 and CPT-11 was started. TS-1, 120 mg/body, was administered on 14 consecutive days followed by a 7-day rest period, and CPT-11, 120 mg/body, was administered on day 1 and day 8. One cycle was defined as 3 weeks,and cycles were repeated. Grade 2 diarrhea occurred, but the CPT-11 dose was reduced to 100 mg/body, and treatment was continued. CR was achieved when the 4th course had been completed. Thoracic and abdominal CT was performed after 4 courses, but no recurrent foci were detected in the residual lung tissue, and all of the metastatic liver foci had resolved. To date 6 courses have been completed, and no relapses have been detected by thoracic CT. We report a case in which it was possible to predict efficacy as a result of treatment based on anticancer drug sensitivity testing and measurements of nucleic acid metabolizing enzymes.

Topics: Adenomatous Polyposis Coli; Adult; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Combined Modality Therapy; Diabetes Complications; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Combinations; Humans; Irinotecan; Liver Neoplasms; Lung Neoplasms; Male; Neoplasms, Multiple Primary; Oxonic Acid; Rectal Neoplasms; Remission Induction; Tegafur

A 56-year-old Japanese man who was suffering from dry cough and right neck mass visited our hospital. Chest X-ray revealed a lung mass shadow in the lower left lung field. We diagnosed it as an advanced large cell carcinoma after conducting transbronchial lung biopsy and neck lymphnode biopsy. A right neck mass enlarged after three chemotherapy regimens of carboplatin and vinorelbine for first-line, docetaxel for second-line, and TS-1 and cisplatin for third-line. Finally, cisplatin (80 mg/m(2), day 1) and gemcitabine (800 mg/m(2), day 1, 8) were administered as fourth-line therapy. Partial response was observed after completing four chemotherapy cycles.. In this case, the fourth-line chemotherapy, consisting of cisplatin and gemcitabine, proved effective for refractory NSCLC. Further research should be conducted regarding third-line chemotherapy for NSCLC patients with good performance status.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Large Cell; Cisplatin; Deoxycytidine; Docetaxel; Drug Administration Schedule; Drug Combinations; Gemcitabine; Humans; Lung Neoplasms; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Oxonic Acid; Remission Induction; Taxoids; Tegafur; Vinblastine; Vinorelbine

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

Advanced hepatocellular carcinoma (HCC) with distant metastases, in particular to the lung, has a poor prognosis. This study was undertaken to evaluate the effectiveness of TS-1 as chemotherapy in advanced HCC with lung metastases. Between January 2004 and October 2005, 8 patients with advanced HCC with lung metastasis were enrolled. All patients received systemic chemotherapy with TS-1. The drug was administered at a dose of 80 mg/m(2)/day for four weeks, followed by a two-week rest, repeated every six weeks until disease progression, unacceptable toxicity, or the patient's refusal. Median age of the patients was 59 years (range, 44 to 79 years). All patients were in Child-Pugh class A. A total of 22 cycles were administered to each patient (range, 1 to 5). No complete or partial responses were observed. There were two patients (25%) with decreasing tumor marker. Median progression-free survival was 79.5 days (range, 29 to 225). The median overall survival was 257 days (95% confidence interval, 191 to 323 days). TS-1 as chemotherapy was well tolerated when administered in the schedule used in this study. Some patients achieved stable disease and clinical benefits, though this regimen has limited activity in HCC with lung metastases. Randomized controlled trials are necessary to clarify survival benefits in patients with advanced HCC with lung metastasis.

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Carcinoma, Hepatocellular; Drug Administration Schedule; Drug Combinations; Female; Humans; Infusions, Intra-Arterial; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Prognosis; Retrospective Studies; Survival Rate; Tegafur; Treatment Outcome

We report a case of TS-1-resistant recurrent gastric cancer with lung metastasis responding to TS-1 and irinotecan (CPT-11) combination therapy. A 72-year-old man underwent total gastrectomy with pancreaticosplenectomy for advanced gastric cancer on October 18, 2001, and partial hepatectomy for postoperative liver metastasis on August 22, 2002. In March 2004, a chest computed tomography scan revealed metastatic lesions in the bilateral lungs, and he received a single administration of TS-1, resulting in partial response. After 13 courses, this therapy was discontinued due to progressive disease. Then,TS-1 and CPT-11 combination therapy was chosen as the second-line chemotherapy. After 4 courses, a partial response was obtained in lung metastasis, and thereafter has been maintained. He has been treated on an outpatient basis because of no grade 3 or severer adverse reactions. TS-1 and CPT-11 combination therapy could be a promising regimen as the second-line chemotherapy for gastric cancer resistant to TS-1.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Combined Modality Therapy; Drug Administration Schedule; Drug Combinations; Drug Resistance, Neoplasm; Gastrectomy; Humans; Irinotecan; Liver Neoplasms; Lung Neoplasms; Male; Oxonic Acid; Pancreas; Splenectomy; Stomach Neoplasms; Tegafur

The patient is a 65-year-old man, who underwent curative resection for maxillary sinus carcinoma after chemoradiation. Lung metastases were observed two months following resection, and were treated with S-1 at a dose of 120 mg/day. One course of the S-1 administration regimen consisted of 2 weeks and a 1-week interval. The patient achieved long survival for 527 days with no adverse reaction. Therefore, this treatment on an outpatient basis greatly contributed to his quality of life. We consider S-1 as a first-line anti-cancer drug for tumor dormancy therapy.

Topics: Aged; Antimetabolites, Antineoplastic; Carcinoma, Squamous Cell; Combined Modality Therapy; Drug Administration Schedule; Drug Combinations; Humans; Lung Neoplasms; Male; Maxillary Sinus Neoplasms; Oxonic Acid; Survivors; Tegafur

The patient was an 84-year-old male. About 7 months after surgery for a non-small cell lung cancer StageIII B, granular shadows were noted on his bilateral lungs on CT; and the level of CA 19-9 , a tumor marker, had increased. These findings led to a diagnosis of intrapulmonary tumor metastasis. Treatment with a platinum-based antineoplastic agent was recommended,but the patient refused it because of his age. The patient was thus placed under observation. Because the tumor appeared to increase in size, treatment was initiated using S-1 capsules (hereafter abbreviated to S-1) alone. Each course consisted of S-1 at a dosage of 100 mg/body/day, twice daily for 21 days, followed by 14 days of drug withdrawal. After the completion of one course, the level of the tumor marker was reduced to normal. After 6 courses were completed, CT indicated a marked reduction or elimination of the intrapulmonary metastatic foci. Malignant phenomenon exceeding grade 3 was no longer recognized,and it was possible to deliver the scheduled dosage of S-1 throughout the entire series of courses. At the end of the 14th course, no signs of exacerbation or recurrence were recognized. It has been about 18 months after the S-1 single therapy was started. This therapy is still being continued.

Topics: Aged, 80 and over; Antimetabolites, Antineoplastic; Carcinoma, Non-Small-Cell Lung; Drug Administration Schedule; Drug Combinations; Humans; Lung Neoplasms; Male; Oxonic Acid; Quality of Life; Tegafur; Tomography, X-Ray Computed

We report a case of postoperative multiple pulmonary metastases of NSCLC successfully treated with S-1. A 72-year-old man underwent rt. lower lobectomy + ND 2 a by VATS. The histopathological examination showed squamous cell carcinoma, pT4 (satellite nodules in same lobe) N0M0. Multiple pulmonary metastases appeared 3 months after operation. We started combination chemotherapy with S-1 and CBDCA. S-1 (100 mg/body) was administered on days 1-21. CBDCA (AUC=5.0) was administered on day 8. Multiple pulmonary metastases almost disappeared after 2 courses of combination chemotherapy. After 6 courses of combination chemotherapy with S-1 and CBDCA, we then converted to S-1 only. Every cycle was repeated every 5 weeks. One year later, there was no sign of disease progression. S-1 is considered to be effective and safely administered in patients with NSCLC.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Squamous Cell; Combined Modality Therapy; Drug Administration Schedule; Drug Combinations; Humans; Lung Neoplasms; Lymph Node Excision; Male; Neoplasm Staging; Oxonic Acid; Pneumonectomy; Postoperative Period; Quality of Life; Tegafur; Thoracic Surgery, Video-Assisted

We report a case with gastric cancer and lung metastasis,who responded remarkably to combination chemotherapy using S-1 and weekly CDDP. A 59-year-old man was hospitalized for aphagia. Based on upper GI endoscopy and CT,type 3 gastric cancer associated with lung metastases was diagnosed. Cardiac gastrectomy, D 1 dissection, intermittented small intestine were performed. At 18 days postoperatively,the patient was administered 3 courses of S-1 (100 mg/body, on day 1-21) and CDDP (30 mg/body, on day 8, 15, 22) every 5 weeks. The treatment resulted in the metastatic tumors in the lung disappearing after 1 course. No severe adverse effects were observed. This combination chemotherapy proved useful for treating lung metastasis from gastric cancer in this patient.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Signet Ring Cell; Cisplatin; Drug Administration Schedule; Drug Combinations; Gastrectomy; Humans; Lung Neoplasms; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Oxonic Acid; Remission Induction; Stomach Neoplasms; Tegafur

A 61-year-old male had undergone distal gastrectomy followed by right hepatectomy for alpha-fetoprotein-producing gastric cancer and liver metastasis. Subsequently, multiple lung metastases were detected by follow-up chest examinations. Despite treatment with TS-1/Irinotecan (CPT-11)/Cisplatin (CDDP) combination therapy, the metastases increased gradually in size and number. Combination therapy with TS-1/Paclitaxel (TXL)/CDDP was effective, as confirmed by marked reduction in tumor size on chest computed tomography. TS-1/TXL/CDDP chemotherapy was administered repeatedly for relapse of lung metastases. The relapse was controlled twice with this chemotherapy regimen, and the patient remains alive at 52 months after gastrectomy without pulmonary symptoms such as hemosputum. Although patients with postoperative lung metastases from AFP-producing gastric cancer have a dismal prognosis, our clinical experience suggests that TS-1/TXL/CDDP combination therapy may be a useful regimen for such conditions.

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

High-dose toremifene therapy (120 mg/day) is useful for the recurrence of receptor-positive breast cancer. However, some reports show that combination therapy of high-dose toremifene and chemotherapy exhibits additive effects. Twelve patients were given oral chemotherapy (capecitabine, 5'-DFUR+CPA, S-1) with high-dose toremifene. The overall response rate was 41.7%, in addition to 58.3% with no change beyond three months. Adverse events were restricted to headache, stomatitis and nausea. Average time to progressive (TTP) was 5.8 months. It was shown that high-dose toremifene and oral chemotherapy were useful for breast cancer recurrence without severe side effects.

Topics: Administration, Oral; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Capecitabine; Cyclophosphamide; Deoxycytidine; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Female; Floxuridine; Fluorouracil; Humans; Liver Neoplasms; Lung Neoplasms; Lymph Nodes; Lymphatic Metastasis; Middle Aged; Neoplasm Recurrence, Local; Oxonic Acid; Quality of Life; Skin Neoplasms; Tegafur; Toremifene

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 recurrent carcinoma of the ampulla of Vater with multiple lung and abdominal lymph node metastases that well responded to S-1, an oral fluoropyrimidine. A 56-years-old woman underwent a pylorus-preserving pancreaticoduodenectomy for carcinoma of the ampulla of Vater in October 2003. Multiple lung metastases were detected by chest X-ray as a post operative screening a year after surgery. Computed tomography showed multiple abdominal lymph node metastases. The patient was treated with S-1 (80 mg/day, day 1-28, followed by 2 weeks rest) from November 2003. Anti-tumor efficacy was confirmed to be partial response by Response Evaluation Criteria in Solid Tumors (RECIST). Leukocytopenia, anemia, and mucositis were observed. Every toxicity was mild to moderate, and no other severe toxicities were noted. S-1 might be an effective and safe agent for carcinoma of the ampulla of Vater.

Topics: Ampulla of Vater; Antimetabolites, Antineoplastic; Common Bile Duct Neoplasms; Drug Combinations; Female; Humans; Lung Neoplasms; Lymphatic Metastasis; Middle Aged; Neoplasm Recurrence, Local; Oxonic Acid; Pancreaticoduodenectomy; Tegafur

We herein report a case of long-term surviving patient who was treated with intravenous administration of activated autologous lymphocytes and low-dose chemotherapy. The patient was an 82-year-old female. She underwent radical resection for sigmoid colon cancer in 1998 and right lobectomy of the liver for metastatic liver tumor in 2001. A follow up CT revealed the metastasis to the bilateral lung on November 2003. Then she received a treatment with UFT plus low-dose CPT-11/CDDP and activated autologous lymphocytes. Although the response of the treatment was SD, the serum CEA level decreased to a normal range. The treatment continued with delayed administration for 30 months while CEA and the size of the tumors increased very slowly. After that, her treatment was changed with a single administration of S-1. She obtained a 3.5 year survival with an inhibition of fast tumor growth by chemo-immunotherapy.

Topics: Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Cisplatin; Drug Combinations; Female; Humans; Immunotherapy; Injections, Intravenous; Irinotecan; Lung Neoplasms; Lymphocyte Activation; Lymphocyte Transfusion; Lymphocytes; Oxonic Acid; Sigmoid Neoplasms; Tegafur; Time Factors; Tomography, X-Ray Computed; Transplantation, Autologous; Uracil

There are numerous reports on the subject of effectiveness in radio-chemotherapy with regard to esophageal cancer, suggesting especially the combination therapy of 5-FU + CDDP aimed for recovery. Treatment becomes difficult when distal metastases appear during an adjuvant therapy followed by surgery. Our report here is a case in which a complete recovery was obtained after changing to S-1, a prodrug of 5-FU, in response to multiple lung metastases which appeared during the combined 5-FU + CDDP therapy followed by surgery for esophageal cancer.. The patient was a 71-year-old male. Endoscopy during a physical examination showed a Type 1 tumor 27-30 cm from the anterior teeth. Detailed tests provided a preoperative diagnosis of esophageal cancer: Ut Type 1, T2-T3, N2, MO, IMO. A right thoracolaparotomic subtotal esophagectomy and retrosternal reconstruction were performed. Pathological findings showed well-differentiated squamous cell carcinoma, pT1b (sm), pN1 (106-rec R), pStage II. Postoperative combination of 5-FU + CDDP (day 1-5, 5-FU 500 mg; CDDP 10 mg/body) was started. Because of the appearance of multiple lung metastases after the completion of 3 courses, 2 courses of S-1 + CDDP (S-1 120 mg/body day 1-14; CDDP 5 mg/body day 1-5, day 8-12) were performed. After completing the chemotherapy, CT revealed the resolution of the lung metastases and complete recovery was diagnosed. Following this, a treatment with S-1 alone was continued until the appearance of bone metastases at which time radiotherapy was performed. The treatment is currently ongoing and no recurrence of the lung metastases has been shown.. There have been numerous reports of the combination of S-1 + CDDP in esophageal cancer for NAC or in inoperable cases. However, our report suggests that this method may be effective in cases of recurrence or distal metastases.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Esophageal Neoplasms; Follow-Up Studies; Humans; Lung Neoplasms; Male; Oxonic Acid; Prognosis; Tegafur; Tomography, X-Ray Computed; Treatment Outcome

The patient was a 59-year-old woman. We performed chemotherapy using S-1 after resection of sigmoid carcinoma because the patient was diagnosed with metastatic lung tumor. The mass was regarded as metastases and reduced in size. We performed pulmonary segmentectomy. Frozen section pathological diagnosis revealed that it was primary lung cancer.

Topics: Colonic Neoplasms; Colonoscopy; Drug Combinations; Female; Humans; Lung Neoplasms; Middle Aged; Neoplasms, Multiple Primary; Oxonic Acid; Tegafur; Tomography, X-Ray Computed

A 78-year-old female underwent a curative total gastrectomy with D2 lymphandectomy for advanced gastric cancer in March 2003. S-1 mono-therapy (80 mg/m2, day 1-28/42 days) began as the first-line chemotherapy from October 2004 when multiple lung metastases were detected by CT. Paclitaxel mono-therapy (80 mg/m2, days 1, 8, 15/28 days) began as the second-line chemotherapy from April 2005 when prior S-1 mono-therapy judged as progressive disease (PD) by CT. Paclitaxel mono-therapy judged it as partial response (PR) in June, but the final judgement was as PD in September 2005. S-1 + CPT-11 combination therapy (S-1: 80 mg/m2, day 1-21, CPT-11: 80 mg/m2, days 1, 15/35 days) began as the third-line chemotherapy from September 2005. After 10 courses, multiple lung metastases were judged as complete response (CR) in September 2006. During the third-line chemotherapy, any adverse event of grade 2 or more did not occur. After judgment of CR, the patient has been followed without chemotherapy due to patient's desire, and is still alive without any recurrence in July 2007.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Carcinoembryonic Antigen; Drug Combinations; Drug Resistance, Neoplasm; Female; Gastrectomy; Humans; Irinotecan; Lung Neoplasms; Oxonic Acid; Stomach Neoplasms; Tegafur; Time Factors; Tomography, X-Ray Computed

5-FU plus Cisplatin combination therapy had been employed against primary liver carcinomas for years. S-1 is a fourth-generation oral fluoropyrimidine and attracts considerable interest for the activity against gastric cancer. We herein examined the effect and adverse effects of S-1 plus Cisplatin combination therapy for primary liver carcinomas.. 4 patients with hepatocellular carcinoma (HCC) and 3 with cholangiocellular carcinoma (CCC) were employed for this study. They all had far-advanced diseases in and/or out of the liver at the time of the therapy initiation. They were 4 men and 3 women. Their ages were in the range of 42-73 (58 +/- 9.73, mean +/- SD) years old. The protocol of the therapy is a 3-week period of S-1 (70-80 mg/m2/day) oral administration combined with 2 intravenous administration of CDDP (20-35 mg/m2) during the period. With two weeks of intermission, the therapy was repeatedly performed 2-11 times for each patient.. Three patients had PR and 2 had NC response with the therapy. Two patients with HCC and pre-treatment with 5-FU had PD response. Although the patients developed leukopenia and thrombocytopenia, the therapy was well tolerable also in the outpatient basis.. S-1 plus Cisplatin combination therapy is a potential therapy for advanced primary liver carcinomas.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Hepatocellular; Cisplatin; Drug Combinations; Female; Humans; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Prognosis; 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 68-year-old woman was referred to our hospital with an abnormal shadow on her chest CT, which showed a mass lesion 3.5 cm in diameter at segment 7 in the right lung. At thoracotomy, a curative operation could not be performed because of pleural dissemination, so a partial resection was done for the histopathological examination. It showed papillary adenocarcinoma and clinical Stage IIIB. Her family hoped not to inform her that a curative operation was impossible. We explained the necessity of adjuvant chemotherapy to her, and she consented to UFT. However, the level of CEA gradually elevated, and pleural effusion on the right side appeared 2 years after operation. We converted UFT into TS-1. The level of CEA gradually reduced, and pleural effusion disappeared. We conclude that oral administration of UFT or TS-1 is useful as palliative chemotherapy for advanced non-small cell lung cancer without serious adverse events and worsening of quality of life.

Topics: Adenocarcinoma, Papillary; Aged; Antineoplastic Combined Chemotherapy Protocols; Drug Administration Schedule; Drug Combinations; Female; Humans; Lung Neoplasms; Oxonic Acid; Pleural Effusion, Malignant; Pyridines; Quality of Life; Tegafur; Uracil

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 65-year-old female with unresectable advanced gastric cancer accompanied by multiple lung metastases underwent jejunostomy and was treated with TS-1 and CDDP. One course consisted of TS-1 (80 mg/day) via an intestinal fistula tube from days 1 to 14 followed by 14 days rest and CDDP (80 mg/day) was administered by 24-hour continuous intravenous infusion on day 8. After 3 courses, the primary tumor and lymph node metastases decreased in size (PR), and CT scan showed the multiple lung metastases had disappeared. Total gastrectomy (D 2) and splenectomy were performed after chemotherapy. The final diagnosis was Stage IIIA and the pathological response to chemotherapy was Grade 2. The patient has survived for over 14 months after surgery and has presented no signs of recurrence.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cisplatin; Drug Administration Schedule; Drug Combinations; Female; Gastrectomy; Humans; Infusions, Parenteral; Jejunostomy; Lung Neoplasms; Lymph Nodes; Lymphatic Metastasis; Neoplasm Invasiveness; Oxonic Acid; Pyridines; Remission Induction; Splenectomy; Stomach Neoplasms; Tegafur

In December 2002, a 67-year-old man underwent right colectomy (stage IIIa, cur B) for cancer of the ascending colon. Chemotherapy with 5'-DFUR and PSK was performed after surgery, but was discontinued due to grade 3 diarrhea. The patient refused treatment with other drugs. An increased CEA level was observed in July 2004, and metastasis of his colon cancer to the liver, lungs, and supraclavicular lymph nodes was confirmed. The patient agreed to resume chemotherapy in December 2004, and received outpatient treatment with CPT-11 (70 mg/m(2) on days 1 and 8) and TS-1 (100 mg/day on days 1-14). There was a significant decrease of tumor markers and a decrease in the size of the metastatic tumors, with these findings being judged as PR. Diarrhea (grade 1) and oral ulceration (grade 2) were observed during treatment. However, these side effects were transient and resolved temporarily without suspending therapy. Although hepatic dysfunction (grade 2) was observed after the completion of cycle No.5, the patient decided to discontinue treatment. CPT-11/TS-1 chemotherapy seems to be useful for maintaining the QOL of patients with metastatic colon cancer.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colectomy; Colonic Neoplasms; Combined Modality Therapy; Drug Administration Schedule; Drug Combinations; Humans; Irinotecan; Liver Neoplasms; Lung Neoplasms; Lymph Nodes; Lymphatic Metastasis; Male; Oxonic Acid; Pyridines; Quality of Life; Tegafur

A 76-year-old male patient was diagnosed with advanced double cancer of the lung and stomach. He had also been suffering from interstitial pneumonitis for several years. He was treated with combination of cisplatin and TS-1. TS-1 (120 mg/body/day) was administered for 21 days from day 1, and cisplatin (60 mg/m(2)) was given on day 8 followed by a 14-days interval. After two courses of chemotherapy,the dose of cisplatin was reduced to 48 mg/m(2) because of grade 1 serum creatinine elevation. The lesions of the lung and stomach were improved significantly without exacerbation of the interstitial pneumonitis.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Drug Administration Schedule; Drug Combinations; Humans; Lung Diseases, Interstitial; Lung Neoplasms; Male; Neoplasms, Multiple Primary; Oxonic Acid; 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

We need more effective treatments for refractory non-small cell lung cancer.. A 61-year-old man had a recurrence in the left ninth rib invading the chestwall 4 years after resection of squamous cell lung cancer. The metastatic lesion grew larger even after 3 different regimens of systemic chemotherapy and local irradiation. Then he started to receive 120 mg of TS-1 daily for 28 days followed by 14 days of rest (1 course). A partial response was achieved after 2 courses of the treatment and continued for 6 weeks. Doses of oxycodone hydrochloride could be reduced to one-sixth of the initial dose according to tumor regression.. This is the first report to show the effectiveness of TS-1 for a refractory recurrence of lung cancer to the bone.

Topics: Administration, Oral; Antimetabolites, Antineoplastic; Bone Neoplasms; Carcinoma, Squamous Cell; Combined Modality Therapy; Drug Administration Schedule; Drug Combinations; Humans; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Pneumonectomy; Postoperative Period; Quality of Life; Ribs; Tegafur

A 55-year-old-male patient underwent subtotal esophagectomy for esophageal cancer (pT1b, N0, M0, stage II) in April 2005. The patient received postoperative chemotherapy (docetaxel 40 mg/body, 5-fluorouracil 750 mg/body, cisplatin 10mg/body: administered every 4 weeks) for 3 months. Six months postoperatively, routine follow up CT demonstrated multiple metastatic tumors in the bilateral lungs. Under the diagnosis of multiple lung metastases, the patient was hospitalized and received intensive chemotherapy with docetaxel 40 mg/week (day 1), 5-fluorouracil 500 mg/day (days 1-5), cisplatin 10 mg/day (days 1-5). After two weeks administration, the patient eagerly hoped for outpatient treatment. The treatment was changed to outpatient chemotherapy with S-1 100 mg/day (continuous administration for 3 weeks followed by rest for 1 week) and cisplatin 20 mg/every week. The treatment enabled the patient to keep working. Follow up CT showed disappearance of all tumors two months after TS-1/cisplatin chemotherapy. There were no obvious signs of recurrence 5 months after chemotherapy. The S-1/cisplatin therapy in the outpatient was thought to be one of the effective treatments in maintaining quality of life for the patient.

Topics: Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Docetaxel; Drug Combinations; Esophageal Neoplasms; Esophagectomy; Fluorouracil; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Metastasis; Oxonic Acid; Recurrence; Taxoids; Tegafur

This study was designed to examine the efficacy and compliance of S-1 for the patients with peritoneal metastasis of gastric cancer.. Sixteen consecutive patients with peritoneal metastasis of gastric cancer were treated with S-1. Their survival was compared with that of the historical control group (25 patients). Thymidylate synthase, dihydropyrimidine dehydrogenase, thymidine phosphorylase and orotate phosphoribosyl transferase mRNA expression in the tumor were evaluated.. The median survival time of S-1-treated patients was 550 days, which was significantly longer than that of the historical control group (215 days). We elucidated some factors to prolong the survival of the patients treated with S-1 for peritoneal metastasis: peritoneal metastasis without other distant metastases, the combination of S-1 treatment and gastrectomy, and low expression of thymidine phosphorylase mRNA in primary tumors.. S-1 showed a surprisingly long-term survival with minimum toxicity in patients with peritoneal metastasis of gastric cancer.

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Biomarkers, Tumor; Dihydrouracil Dehydrogenase (NADP); Drug Combinations; Female; Gastrectomy; Humans; Intestinal Neoplasms; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Orotate Phosphoribosyltransferase; Oxonic Acid; Patient Compliance; Peritoneal Neoplasms; Stomach Neoplasms; Survival Rate; Tegafur; Thymidine Phosphorylase; Thymidylate Synthase; Time Factors; Treatment Outcome

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

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 76-year-old man had complained of hoarseness, productive cough and left chest pain in June 2005. Chest radiograph and computed tomography showed a tumor 7.5x5 cm in size which contacted the aortic arch, some nodules in left upper lobe and right lower lobe of lung and left pleural effusion. The broncho-fiberscopic biopsy histologically proved the tumor to be moderately differentiated squamous cell carcinoma in the left upper lobe of lung. The patient was diagnosed as a non-resectable lung cancer with clinical stage IV (c-T4N2M1). In July 2005, he was treated with oral administration of TS-1 (120 mg/day) and Jyu-zen daiho toh (7.5 g/day). After one week, he complained of grade 2 leukopenia and grade 1 skin rash. Then TS-1 was reduced to 100 mg/day. After this modulation of the treatment, he could take TS-1 and Jyu-zen daiho toh days 1-14, every 3 weeks. The patient then received 17 courses until June 2006. The left pleural effusion and left chest pain disappeared only 2 weeks after taking TS-1. In June of 2006, central necrosis of the left lung tumor was confirmed by positron emission computed tomography. No serious adverse effect was observed, and the patient maintained good quality of life. This case suggests that TS-1 with Jyu-zen daiho toh may be an effective treatment for elderly advanced lung cancer.

Topics: Aged; Antimetabolites, Antineoplastic; Carcinoma, Squamous Cell; Drug Administration Schedule; Drug Combinations; Drugs, Chinese Herbal; Humans; Lung Neoplasms; Male; Neoplasm Staging; Oxonic Acid; Quality of Life; Tegafur

A 54-year-old man was admitted Osaka University Hospital for hepatocellular carcinoma (HCC) with portal vein thrombus and multiple intrahepatic metastases that extended to the bilateral lobes of the liver. He underwent multimodal therapy, including extended left lobectomy followed by intra-arterial 5-fluorourcil (5-FU) infusion chemotherapy combined with subcutaneous interferon-alpha (IFN-alpha) to treat the lesions in the residual liver. Seven months after the initial resection, recurrent tumors in the spleen, lung, and residual liver were detected by follow-up examination. We started a new regimen of per oral administration of S-1 and subcutaneous IFN-alpha injection, because the combined therapy with intra-arterial 5-FU infusion was not considered effective for distant metastases. After two cycles of S-1 and IFN-alpha, the metastatic tumor in the spleen and the recurrence in the residual liver had disappeared, and the diagnosis was complete remission with no adverse effect; the pulmonary metastasis showed a partial response, and was finally resected. This patient is still alive with no recurrence 32 months after initial hepatic resection. This outcome suggests that combination therapy with S-1 and IFN-alpha may be a promising treatment modality against advanced HCC with distant metastasis.

Topics: Administration, Oral; Antimetabolites, Antineoplastic; Carcinoma, Hepatocellular; Dihydrouracil Dehydrogenase (NADP); Drug Combinations; Drug Therapy, Combination; Follow-Up Studies; Hepatectomy; Humans; Immunologic Factors; Injections, Subcutaneous; Interferon-alpha; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Neoplasm Recurrence, Local; Oxonic Acid; Splenic Neoplasms; Tegafur; Tomography, X-Ray Computed

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

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

A 61-year-old man with multiple liver and lung metastases from advanced gastric cancer was admitted to our hospital. We selected the patient from the outpatient department and started a single administration of TS-1 as a first line chemotherapy. TS-1 was markedly effective and the CEA level decreased 4,528 ng/ml to 44 ng/ml only in three months. The clinical response was assessed to be partial response (PR) comparable to complete response (CR) according to the tumor regression effect. The effect had been continued for almost six months. Because the CEA level elevated again, we estimated that the tumor acquired a drug tolerance to TS-1. Therefore, we applied CDDP with TS-1 as a second line chemotherapy. Unfortunately, it was not effective. Then we combined paclitaxel (PTX) to TS-1. The CEA level was remarkably reduced again, but transiently. Thereafter, we continued a sequential administration of TS-1 plus other drugs (CPT-11, docetaxel and MMC). Over 2 years, the patient is alive with a good quality of life.

Topics: Antibiotics, Antineoplastic; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Carcinoembryonic Antigen; Cisplatin; Docetaxel; Drug Administration Schedule; Drug Combinations; Humans; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Mitomycin; Oxonic Acid; Paclitaxel; Pyridines; Remission Induction; Taxoids; Tegafur

A 56-year-old male was admitted to our hospital for hepatoma with portal vein thrombus and multiple intrahepatic metastases. He underwent an extended left lobectomy and a partial resection of the liver in May 2002. After two weeks from the surgery, he received intra arterial 5-FU infusion chemotherapy combined with subcutaneous interferon-alpha injection to treat the lesions in the residual liver. Four months after the surgery, hepatic vein tumor thrombus appeared in the remnant liver and it extended to the inferior caval vein. And another 4 months later, multiple pulmonary metastases were detected with computed tomography and they grew rapidly in the view of their sizes and numbers. Because the combined therapy of 5-FU/interferon-alpha was not effective to distant metastases, we started a new regimen of oral administration of TS-1 and a subcutaneous interferon-alpha injection. After 1 treatment cool, hepatic vein thrombus was markedly reduced the size and vascularity in the CT. Multiple pulmonary metastases also decreased in their sizes and numbers. No adverse effect was seen during this treatment. It was suggested that a combination therapy of TS-1 and interferon-alpha may be one of the most effective treatment modalities against advanced HCC with distant metastasis.

Topics: Administration, Oral; Antimetabolites, Antineoplastic; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Hepatocellular; Combined Modality Therapy; Drug Combinations; Hepatectomy; Humans; Infusions, Intra-Arterial; Injections, Subcutaneous; Interferon-alpha; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Neoplastic Cells, Circulating; Oxonic Acid; Pneumonectomy; Pyridines; Tegafur; Thrombectomy; Vena Cava, Inferior

A patient with lung metastasis of breast cancer was reported. The patient underwent surgery in December, 1999. Her breast cancer then recurred in December, 2000. After treatment failure with anthracycline and taxane antitumor drugs,she participated in a phase II study of S-1, a fluorinated pyrimidine anticancer drug, which was given orally at 80 mg/m2/day (2 doses). After completion of 4 courses of treatment,the target lesions of the lung metastasis markedly shrunk by 47.5% as compared with the pretreatment. Because salvage therapy with S-1 alone showed good antitumor efficacy and beneficial tolerability when the standard dosage was maintained, it was considered that this home therapy was effective for advanced/recurrent breast cancer that was resistant to anthracycline and taxane antitumor drugs.

Topics: Administration, Oral; Anthracyclines; Antimetabolites, Antineoplastic; Breast Neoplasms; Bridged-Ring Compounds; Carcinoma, Ductal, Breast; Clinical Trials, Phase II as Topic; Drug Administration Schedule; Drug Combinations; Drug Resistance, Neoplasm; Female; Humans; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Middle Aged; Oxonic Acid; Pyridines; Quality of Life; Salvage Therapy; Taxoids; Tegafur

Cardiotoxicity is a rare complication occurring during 5-fluorouracil (5-FU) treatment for malignancies. We herein report the case of a 70-year-old man with 5-FU-induced cardiotoxicity, in whom a high serum level of alpha-fluoro-beta-alanine (FBAL) was observed. The patient, who had unresectable colon cancer metastases to the liver and lung, was referred to us for chemotherapy from an affiliated hospital; he had no cardiac history. After admission, the patient received a continuous intravenous infusion of 5-FU (1000 mg/day), during which precordial pain with right bundle branch block occurred concomitantly with a high serum FBAL concentration of 1955 ng/ml. Both the precordial pain and the electrocardiographic changes disappeared spontaneously after the discontinuation of 5-FU. As the precordial pain in this patient was considered to have been due to 5-FU-induced cardiotoxicity, the administration of 5-FU was abandoned. Instead, oral administration of S-1 (a derivative of 5-FU), at 200 mg/day twice a week, was instituted, because S-1 has a strong inhibitory effect on dihydropyrimidine dehydrogenase, which catalyzes the degradative of 5-FU into FBAL. The serum FBAL concentration subsequently decreased to 352 ng/ml, the same as the value measured on the first day of S-1 administration. Thereafter, no cardiac symptoms were observed. The patient achieved a partial response 6 months after the initiation of the S-1 treatment. The experience of this case, together with a review of the literature, suggests that FBAL is related to 5-FU-induced cardiotoxicity. S-1 may be administered safely to patients with 5-FU-induced cardiotoxicity.

Topics: Aged; Antimetabolites, Antineoplastic; beta-Alanine; Cardiovascular Diseases; Colonic Neoplasms; Drug Combinations; Electrocardiography; Fluorouracil; Heart; Humans; Liver Neoplasms; Lung Neoplasms; Male; Oxonic Acid; 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 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

S-1 is an oral fluoropyrimidine reported to be most active for gastric cancer. However, few studies have documented a complete response (CR) of lung metastasis to S-1 treatment. We describe a 66-year-old woman in whom S-1 induced complete regression of lung metastasis from gastric cancer, that had been refractory to another oral fluoropyrimidine, 5'-deoxy-5-fluorouridine (5'-DFUR). After preoperative chemotherapy with a combination of etoposide, adriamycin and cisplatin and with methotrexate plus 5-fluorouracil, the patient underwent a total gastrectomy with lower esophagectomy for advanced diffuse-type gastric cancer with invasion of the esophagus in May 1993. She received postoperative adjuvant chemotherapy with 5'-DFUR (600 mg/day) for 3 years. However, a solitary metastasis to the left lung was detected in November 1996 and she underwent partial resection of the left lung. Chemotherapy with 5'-DFUR was reinitiated after operation, but re-metastasis to the left lung with elevation of the serum carcinoembryonic antigen (CEA) level was diagnosed in June 1999. Treatment with S-1 was started in August. S-1 was given orally in a dose of 100 mg/day for 28 consecutive days, followed by a 14-day recovery; treatment was repeated every 6 weeks. The metastatic lesion in the left lung completely regressed after two courses of S-1 and the serum CEA level returned to the normal range. The patient received a total of 10 courses of S-1. The dose of S-1 was reduced to 80 mg/day from the sixth course because of grade 2 skin rash. Pharmacokinetic studies after administration of S-1 revealed high and prolonged plasma 5-FU levels. Nearly 4 years have passed since complete regression of the lung metastasis. This may be the first report to document a prolonged complete response of lung metastasis from gastric cancer induced by single-agent chemotherapy with S-1.

Topics: Adenocarcinoma, Mucinous; Administration, Oral; Antimetabolites, Antineoplastic; Chemotherapy, Adjuvant; Drug Administration Schedule; Drug Combinations; Esophagectomy; Female; Floxuridine; Fluorouracil; Gastrectomy; Humans; Lung Neoplasms; Middle Aged; Oxonic Acid; Pyridines; Radiography, Thoracic; Remission Induction; Stomach Neoplasms; Tegafur; Tomography, X-Ray Computed

The patient, a 67-year old man, was referred to us with refractory otorrhea of the left ear. The diagnosis was adenoid cystic carcinoma of the external auditory meatus, so the primary focus was excised. During the postoperative observation period, multiple metastases to the lung were noted, for which TS-1 (120 mg/day, given for 28 consecutive days, each course followed by a discontinuation of 14 days) was administered. After the completion of 2 courses, reductions in the metastatic pulmonary lesions and the amount of pleural effusion were noted, while adverse effects were limited to mild anorexia. Thus, it was possible to continue medication for 15 months on an ambulatory basis. It was indicated that TS-1 may be effective in the treatment of multiple pulmonary metastases of adenoid cystic carcinoma.

Topics: Aged; Antimetabolites, Antineoplastic; Carcinoma, Adenoid Cystic; Drug Administration Schedule; Drug Combinations; Ear Canal; Ear Neoplasms; Humans; Lung Neoplasms; Male; Oxonic Acid; Pyridines; Tegafur

A 56-year-old gastric cancer patient with multiple lung metastases and dilated cardiomyopathy was treated by chemotherapy with TS-1. This case was judged to be unresectable. TS-1 (100 mg/body/day) was orally administered for 4 weeks followed by a drug-free 2-week period as 1 course. At the completion of 3 courses, the multiple lung metastases were assessed to show a complete response (CR). There were no side effects and no hospitalization. This chemotherapy is being continued, and a CR in the lung and no change of the gastric cancer have been maintained for 15 months (10 courses).

Topics: Administration, Oral; Antimetabolites, Antineoplastic; Carcinoma, Signet Ring Cell; Cardiomyopathy, Dilated; Drug Administration Schedule; Drug Combinations; Humans; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Pyridines; 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 52-year-old male was admitted to our hospital with huge hepatoma of the right lobe. He underwent a right lobectomy of the liver in July 1999. After five months from the surgery, multiple recurrences in the liver and lung were revealed with Computed tomography (CT). TAE was performed for intrahepatic recurrence and a combination therapy, consisting of UFT and interferon-alpha, was started for pulmonary metastasis. Then 5-FU/CDDP/interferon-alpha therapy was given in 2001 and TS-1/interferon-beta therapy was given thereafter in 2002. Consequently, the patient survived for 31 months with no disturbance in quality of life. No intrahepatic recurrence was also detected during the survival period. It was suggested that a good prognosis may be expected, even in the HCC case with distant metastasis after hepatic resection, if the primary cite was curatively treated.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Hepatocellular; Cisplatin; Drug Combinations; Fluorouracil; Hepatectomy; Humans; Interferon-alpha; Interferon-beta; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Neoplasm Recurrence, Local; Oxonic Acid; Pyridines; Tegafur; Time Factors; Uracil

The patient was a 61-year-old man who had gastric cancer with metastasis to cervical lymph nodes and pulmonary lymphangitis carcinomatosa. He received daily oral administration of 120 mg of TS-1 (day 1-21) and systemic administration of 100 mg of CDDP (day 8) as one treatment course. As the metastatic lesions had disappeared after chemotherapy, he underwent total gastrectomy. Histopathological examination of resected regional lymph nodes revealed marked fibrosis and a small amount of scattered cancer cells. Although much peritoneal dissemination was observed macroscopically, histopathological examination of these tumors revealed only fibrosis with no cancer cells. These findings supported the effect of this neoadjuvant chemotherapy. He died of recurrence of the carcinoma 203 days after surgery, without any sign of recurrence of metastasis to cervical lymph nodes or pulmonary lymphangitis carcinomatosa.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Cisplatin; Drug Combinations; Gastrectomy; Humans; Lung Neoplasms; Lymphangitis; Lymphatic Metastasis; Male; Middle Aged; Oxonic Acid; Pyridines; Stomach Neoplasms; Tegafur

A 65-year-old man, who had been admitted to another hospital with complaints of severe cough and dyspnea, was transferred to our hospital for the further examination and therapy. The patient was diagnosed with advanced gastric cancer (type-3) with lymphangitis carcinomatosa of the lung. He was treated with combination therapy of 5-FU and cisplatin, and showed a complete response. However, because resistance was seen in the lymphangitis of the lung and the gastric lesion; and a liver metastasis was also seen, we attempted combination therapy with paclitaxel and TS-1. Sixty mg/m2/day of paclitaxel was administered intravenously on day 1 and 8, and TS-1 of 60-80 mg/m2/day was administered orally for 2 weeks followed by one drug-free week. After 2 courses of the combination therapy, the patient achieved a remarkable response in the lymphangitis carcinomatosa of the lung, but a slight response in the liver metastasis and gastric lesion.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Drug Resistance, Neoplasm; Fluorouracil; Humans; Liver Neoplasms; Lung Neoplasms; Lymphangitis; Male; Oxonic Acid; Paclitaxel; Pyridines; Stomach Neoplasms; Tegafur

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

TS-1 is a new, oral anticancer agent composed of two modulators, gimeracil (CDHP) and oteracil potassium (Oxo) are mixed with tegafur in a ratio of 1:0.4:1. We report one case of advanced gastric cancer with lung and lymph node metastases that completely responded to TS-1. A 71-year-old woman was admitted to our hospital because of breathlessness. A diagnosis of advanced gastric cancer with extensive lymph node metastases and multiple pulmonary metastases was made. One hundred mg/body/day of TS-1 was orally administrated for 4 weeks. A partial response (PR) was obtained after the first course with regression of multiple pulmonary metastases. After 1 drug-free week, the second course was administered with 120 mg/body/day of TS-1 for 4 weeks. After two courses, the primary tumor was reduced to an ulcer scar with pathological confirmation of a complete disappearance of the cancer tissue. Moreover, computed tomography (CT) showed a complete regression of the extensive lymph node and diffuse lung metastases, for a complete response (CR). The serum level of CEA was reduced from 172.7 ng/ml to 8.1 ng/ml after TS-1 treatment. As for adverse events, only pigmentation of the skin and Grade 2 oral aphta were observed.

Topics: Adenocarcinoma, Papillary; Administration, Oral; Aged; Antineoplastic Agents; Carcinoembryonic Antigen; Drug Combinations; Female; Humans; Lung Neoplasms; Lymphatic Metastasis; Oxonic Acid; Pyridines; 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

1 M Tegafur (FT)-0.4 M 5-chloro-2,4-dihydroxypridine (CHDP)-1 M potassium oxonate (Oxo) (S-1), was developed as a new oral antineoplastic agent based on biochemical modulation of fluorouracil (5-FU) by CHDP and Oxo. The antitumor effect of S-1 on human head and neck squamous carcinoma cells was evaluated in xenografts and a metastasis model, in comparison with combined drug of 1 M FT and 4 M uracil (UFT). Mice treatment with S-1 showed a significant higher concentration of 5-FU in the tumor and the serum than UFT treated mice. S-1 showed higher tumor growth inhibition and metastasis inhibition than UFT. The mice in which metastasis was inhibited lived more than twice as long as the control mice. These results suggest that S-1 will have a higher clinical therapeutic effect against advanced squamous cell carcinoma of the head and neck in humans.

Topics: Administration, Oral; Animals; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Dose-Response Relationship, Drug; Drug Combinations; Female; Fluorouracil; Head and Neck Neoplasms; Humans; Lung Neoplasms; Mice; Mice, Inbred BALB C; Mice, Nude; Mice, SCID; Neoplasm Transplantation; Oxonic Acid; Pyridines; Survival Rate; Tegafur; Transplantation, Heterologous; Tumor Cells, Cultured; Uracil