Background:Combination therapy with oxaliplatin,irinotecan,fluorouracil,and leucovorin(FOLFIRINOX)chemotherapy drastically improves survival of advanced pancreatic cancer patients.However,the efficacy of FOLFIRINOX as...Background:Combination therapy with oxaliplatin,irinotecan,fluorouracil,and leucovorin(FOLFIRINOX)chemotherapy drastically improves survival of advanced pancreatic cancer patients.However,the efficacy of FOLFIRINOX as a second-line treatment after gemcitabine failure has not been tested prospectively.We investigated the feasibility and safety of attenuated FOLFIRINOX in patients with gemcitabine-refractory advanced pancreatic cancer.Methods:A multicenter phase II prospective open-label,single-arm study was conducted at 14 hospitals.Patients with histologically proven invasive ductal pancreatic adenocarcinoma,a measurable or evaluable lesion,Eastern Cooperative Oncology Group performance status 0 or 1,adequate organ function,and aged 19 years or older were eligible.Attenuated FOLFIRINOX consisted of oxaliplatin 65 mg/m2,irinotecan 135 mg/m2,and leucovorin 400 mg/m2 injected intravenously on day 1 and 5-fluorouracil 2000 mg/m2 continuously infused intravenously over 46 h on days 1-2,repeated every 2 weeks.The primary endpoint was progression-free survival from the initiation of FOLFIRINOX.Secondary endpoints were the objective response rate,disease control rate,overall survival,safety,and tolerability.We estimated overall survival and progression-free survival using the Kaplan-Meier methods.Results:We enrolled 39 patients from 14 institutions.The objective response rate was 10.3%,while the disease control rate was 64.1%.The 6-month and 1-year overall survival rates were 59.0%and 15.4%,respectively.Median progression-free survival and overall survival were 3.8 months(95%confidence interval[CI]1.5-6.0 months)and 8.5 months(95%CI 5.6-11.4 months),respectively.Grade 3 or 4 adverse events were neutropenia(41.0%),nausea(10.3%),anorexia(10.3%),anemia(7.7%),mucositis(7.7%),pneumonia/pleural effusion(5.1%),and fatigue(5.1%).One treatment-related death attributable to septic shock occurred.Conclusion:Attenuated FOLFIRINOX may be promising as a second-line therapy for gemcitabine-refractory pancre-atic cancer.展开更多
基金study was supported by a research Grant from Hanmi Pharmaceutical Co.Ltd.,and the Soonchunhyang University Research fund.
文摘Background:Combination therapy with oxaliplatin,irinotecan,fluorouracil,and leucovorin(FOLFIRINOX)chemotherapy drastically improves survival of advanced pancreatic cancer patients.However,the efficacy of FOLFIRINOX as a second-line treatment after gemcitabine failure has not been tested prospectively.We investigated the feasibility and safety of attenuated FOLFIRINOX in patients with gemcitabine-refractory advanced pancreatic cancer.Methods:A multicenter phase II prospective open-label,single-arm study was conducted at 14 hospitals.Patients with histologically proven invasive ductal pancreatic adenocarcinoma,a measurable or evaluable lesion,Eastern Cooperative Oncology Group performance status 0 or 1,adequate organ function,and aged 19 years or older were eligible.Attenuated FOLFIRINOX consisted of oxaliplatin 65 mg/m2,irinotecan 135 mg/m2,and leucovorin 400 mg/m2 injected intravenously on day 1 and 5-fluorouracil 2000 mg/m2 continuously infused intravenously over 46 h on days 1-2,repeated every 2 weeks.The primary endpoint was progression-free survival from the initiation of FOLFIRINOX.Secondary endpoints were the objective response rate,disease control rate,overall survival,safety,and tolerability.We estimated overall survival and progression-free survival using the Kaplan-Meier methods.Results:We enrolled 39 patients from 14 institutions.The objective response rate was 10.3%,while the disease control rate was 64.1%.The 6-month and 1-year overall survival rates were 59.0%and 15.4%,respectively.Median progression-free survival and overall survival were 3.8 months(95%confidence interval[CI]1.5-6.0 months)and 8.5 months(95%CI 5.6-11.4 months),respectively.Grade 3 or 4 adverse events were neutropenia(41.0%),nausea(10.3%),anorexia(10.3%),anemia(7.7%),mucositis(7.7%),pneumonia/pleural effusion(5.1%),and fatigue(5.1%).One treatment-related death attributable to septic shock occurred.Conclusion:Attenuated FOLFIRINOX may be promising as a second-line therapy for gemcitabine-refractory pancre-atic cancer.