14083 Background: S-1, a fourth generation oral fluoropyrimidine that mimics infusional 5-fluorouracil, has demonstrated activity against advanced gastric cancer. Based on a single agent activity and in vitro synergy between mitomycin C (MMC) and 5-fluorouracil, we conducted a phase II study to assess the efficacy and tolerability of the combination of S-1 and MMC as second-line chemotherapy for previously treated, advanced gastric cancer. Methods: Patients with measurable gastric cancer, progressive after at least one prior chemotherapy for metastatic disease, were treated with MMC 7 mg/m2 on day 1 and S-1 40 mg/m2 twice daily as an intermittent regimen of 4 weeks of treatment followed by a 2-week rest. Treatment was repeated every 6 weeks, for up to 4 cycles. Objective response rate was the primary endpoint and was evaluated every 2 cycles of chemotherapy. With a single-stage phase II design, at least 25 patients were required. Results: Of the 26 patients registered, 24 patients were evaluable for response and 26 for safety. Eighteen patients (69%) were previously treated with 5-fluorouracil-based chemotherapy, and 10 (39%) were treated with taxanes. The patients’ median age was 55 years (range, 38–73) and 7 (27%) had an ECOG performance status of 2. A total of 64 chemotherapy cycles were delivered (median, 2; range, 1–4). In an intent-to-treat analysis, 6 patients (23%) achieved a partial response, which maintained for 3.5 months. The median progression-free and overall survivals were 4.4 months (95% CI, 1.7–7.2) and 5.4 months (95% CI, 3.4–7.4), respectively. Major toxic effects included stomatitis, diarrhea and fatigue, but were generally mild and manageable. No patient developed hemolytic reaction. Conclusions: Second-line chemotherapy with MMC and S-1 is an effective regimen for advanced gastric cancer with an acceptable toxicity profile and a convenient administration schedule. No significant financial relationships to disclose.
Randomized phase II study of second-line chemotherapy with the best available 5-fluorouracil regimen versus weekly administration of paclitaxel in far advanced gastric cancer with severe peritoneal metastases refractory to 5-fluorouracil-containing regimens (JCOG0407)
