Background: The purpose of this study was twofold: (1) to compare S-1 with infusional 5-fluorouracil (FU) to determine which would be a better partner of paclitaxel (PTX), and (2) to compare a concurrent strategy with a sequential one, the latter strategy being the one that is widely used in Japanese general practice.
Methods: The 161 eligible patients were randomized into four arms to receive the following regimens: A (sequential), intravenous 5-FU at 800 mg/m(2) for 5 days every 4 weeks followed by weekly PTX at 80 mg/m(2); B (sequential), S-1 at 80 mg/m(2) for 4 weeks and 2-week rest followed by PTX; C (concurrent), intravenous 5-FU at 600 mg/m(2) for 5 days and weekly PTX at 80 mg/m(2) every 4 weeks; and D (concurrent), S-1 for 14 days and PTX at 50 mg/m(2) on days 1 and 8 every 3 weeks. The primary endpoint was the overall survival (OS) rate at 10 months.
Results: The ten-month OS rates in arms A, B, C, and D were 63, 65, 61, and 73%, respectively. The OS was best in the concurrent S-1/PTX arm, with a mean survival time of 15.4 months, but no significant difference was observed between the four arms. Response rates were higher in the concurrent arms than in the sequential arms.
Conclusion: Our study did not show sufficient prolongation of survival with the concurrent strategy to proceed to a phase-III trial; however, the sequential arms showed survival comparable to that in the concurrent arms, with less toxicity. In patients who are ineligible for cisplatin (CDDP), sequential treatment starting with S-1 and proceeding to PTX would be a good alternative strategy, considering quality of life (QOL) and the cost-benefits of an oral agent as first-line treatment.