Randomized Phase III Trial of Fluorouracil Alone Versus Fluorouracil Plus Cisplatin Versus Uracil and Tegafur Plus Mitomycin in Patients With Unresectable, Advanced Gastric Cancer: The Japan Clinical Oncology Group Study (JCOG9205)

PURPOSE: To compare fluorouracil (FU) alone with FU plus cisplatin (FP) and with uracil and tegafur plus mitomycin (UFTM) for patients with advanced gastric cancer in a prospective, randomized, controlled trial. PATIENTS AND METHODS: A total of 280 patients with advanced gastric cancer were randomly allocated and analyzed for survival, response, and toxicity. The survival curves were compared between groups by log-rank test on an intent-to-treat basis. RESULTS: At the interim analysis, the UFTM arm showed a significantly inferior survival with higher incidences of hematologic toxic effects than did control arm FU alone, and the registration to UFTM was terminated. Both investigational regimens, FP and UFTM, had a significantly higher incidence of hematologic toxic effects than FU alone, although the effects were manageable. The overall response rates of the FU-alone, FP, and UFTM arms were 11%, 34%, and 9%, respectively. The median progression-free survival was 1.9 months with FU alone, 3.9 months with FP, and 2.4 months with UFTM, respectively. Although FP demonstrated a higher response rate (P <.001) and longer progression-free survival than did FU alone (P <.001), no differences in overall survival were observed between the arms. The median survival times and 1-year survival rates were 7.1 months and 28% with FU, 7.3 months and 29% with FP, and 6.0 months and 16% with UFTM, respectively. CONCLUSION: Neither investigational regimen, FP nor UFTM, showed a survival advantage as compared with FU alone. FU alone will remain a reference arm in our future trial for advanced gastric cancer.