gimeracil and Neutropenia

Standardized adjuvant therapy is not performed after major hepatectomy for biliary tract cancer (BTC) because of frequent adverse events, which may be caused by insufficient liver function. Therefore, the aim of this multicenter study (KHBO1003) was to determine the safety protocol for adjuvant chemotherapy after major hepatectomy.. Within 12 weeks of R0 or R1 major hepatectomy (hemihepatectomy or trisectionectomy) for BTC, the following adjuvant chemotherapy was performed for 6 months: 800-1,000 mg/m(2) gemcitabine on days 1, 8, and 15 and then every 3-4 weeks or 40-80 mg/m(2)/day S-1 on days 1-28 and every 3-6 weeks. Major dose-limited toxicity (DLT) was defined as grade 4 hematotoxicity, grade 3/4 febrile neutropenia, grade 3/4 non-hematotoxicity, skipped gemcitabine on days 8 and 15, or halting the course at or after 14 days. Dose-escalation and de-escalation decisions were based on the continual reassessment method. Every three patients were alternately assigned to each arm.. Thirty-three patients (14 intrahepatic bile duct, 1 gall bladder, 18 extrahepatic bile duct) were enrolled in this study from February 2011 to July 2012 (n = 18 gemcitabine, n = 15 S-1). At 10% of DLT, the recommended dose was 1,000 mg/m(2) gemcitabine biweekly and 80 mg/m(2)/day S-1 on days 1-28 and every 6 weeks. Major DLT and adverse drug reactions were neutropenia. No grade 3 or 4 non-hematological adverse events were noted.. We determined RDs for gemcitabine and S-1 adjuvant chemotherapy after major hepatectomy with a DLT that does not exceed 10%.

Topics: Aged; Antimetabolites, Antineoplastic; Biliary Tract Neoplasms; Chemotherapy, Adjuvant; Deoxycytidine; Dose-Response Relationship, Drug; Drug Combinations; Drug Monitoring; Drug Screening Assays, Antitumor; Female; Gemcitabine; Hepatectomy; Humans; Male; Neutropenia; Postoperative Care; Pyridines; Tegafur; Treatment Outcome

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

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