A multicentre randomised trial comparing weekly paclitaxel + S-1 with weekly paclitaxel + 5-fluorouracil for patients with advanced gastric cancer

PurposeThis study aimed to compare the efficacy and toxicity of weekly paclitaxel plus S-1 with weekly paclitaxel plus 5-fluorouracil in treating advanced gastric cancer as first line regimen. The primary end-point was disease control rate (DCR).MethodsPatients with advanced or recurrent gastric cancer were randomly assigned to an experimental arm or a control arm. The experimental arm’s dosage schedule was paclitaxel 60 mg/m2 (intravenous infusion) on days 1, 8 and 15 and S-1 80–120 mg/d (oral administration) on days 1–14. Control arm patients were given the same paclitaxel, combined with 5-fluorouracil 500 mg/m2 (continuous intravenous infusion) on days 1–5; and leucovorin 20 mg/m2 (intravenous infusion) on days 1–5. All schedules were repeated every 28 d.ResultsA total of 240 patients were enrolled and equally randomised into two arms. The overall response rate and DCR of the experimental arm was non-inferior to that of the control arm both in the per-protocol set and the full analysis set. The secondary end-point median progression-free survival (PFS) of the experimental and control arms was 153 and 129 d, with the hazard ratio of 0.641 (95% CI: 0.473–0.868, P = 0.004). The hazard ratio of the time to treatment failure of the two arms was 1.449 (95% CI: 0.705–2.980, P = 0.229). The six-month PFS rates of both arms were similar (31.3% versus 31.8%, P = 0.94). Cox regression analysis indicated that only treatment regimen and age were independent predictive factors for PFS. The most common adverse events were haematological and gastrointestinal. The rates of grade 3–4 adverse events were not significantly different between the two study arms and were mostly lower than 5%.ConclusionWeekly paclitaxel combined with S-1 is an active and well-tolerated regimen, supporting the view that S-1 can be an alternative for infusional 5-fluorouracil for advanced gastric cancer.