OBJECTIVE: The aim of this study was to determine the maximum-tolerated dose and dose-limiting toxicity (DLT) of combination therapy with gemcitabine and S-1 in patients with advanced pancreatic cancer. METHODS: Chemotherapy-naive patients with histologically or cytologically proven unresectable or metastatic pancreatic cancer were enrolled. The patients received gemcitabine intravenously over 30 min on days 1 and 8 and S-1 orally twice daily from days 1 to 14. Cycles were repeated every 21 days until disease progression. Patients were scheduled to receive gemcitabine (mg/m(2)/week) and S-1 (mg/m(2)/day) at four dose levels: 800/60 (level 1), 1,000/60 (level 2), 1,000/70 (level 3) and 1,000/80 (level 4). RESULTS: Eighteen patients were enrolled in this study. The maximum-tolerated dose was not reached even at the highest dose level (level 4) because only 2 of the 6 patients at this level experienced DLT. The DLTs were neutropenia and rash. Six (33%) of the 18 patients achieved a partial response and median overall survival time was 7.6 months. CONCLUSIONS: Combination chemotherapy with gemcitabine and S-1 was well tolerated and showed good antitumor activity in the treatment of pancreatic cancer. We recommend a gemcitabine dose of 1,000 mg/m(2)/week and an S-1 dose of 80 mg/m(2)/day in further studies with this schedule.
OBJECTIVE: The aim of this study was to determine the maximum-tolerated dose and dose-limiting toxicity (DLT) of combination therapy with gemcitabine and S-1 in patients with advanced pancreatic cancer. METHODS: Chemotherapy-naive patients with histologically or cytologically proven unresectable or metastatic pancreatic cancer were enrolled. The patients received gemcitabine intravenously over 30 min on days 1 and 8 and S-1 orally twice daily from days 1 to 14. Cycles were repeated every 21 days until disease progression. Patients were scheduled to receive gemcitabine (mg/m(2)/week) and S-1 (mg/m(2)/day) at four dose levels: 800/60 (level 1), 1,000/60 (level 2), 1,000/70 (level 3) and 1,000/80 (level 4). RESULTS: Eighteen patients were enrolled in this study. The maximum-tolerated dose was not reached even at the highest dose level (level 4) because only 2 of the 6 patients at this level experienced DLT. The DLTs were neutropenia and rash. Six (33%) of the 18 patients achieved a partial response and median overall survival time was 7.6 months. CONCLUSIONS: Combination chemotherapy with gemcitabine and S-1 was well tolerated and showed good antitumor activity in the treatment of pancreatic cancer. We recommend a gemcitabine dose of 1,000 mg/m(2)/week and an S-1 dose of 80 mg/m(2)/day in further studies with this schedule.
Authors: Y Nakai; H Isayama; T Sasaki; N Sasahira; T Tsujino; N Toda; H Kogure; S Matsubara; Y Ito; O Togawa; T Arizumi; K Hirano; M Tada; M Omata; K Koike Journal: Br J Cancer Date: 2012-05-03 Impact factor: 7.640