A PHASE-III RANDOMIZED STUDY OF 5-FLUOROURACIL AND CISPLATIN VERSUS 5-FLUOROURACIL, DOXORUBICIN, AND MITOMYCIN-C VERSUS 5-FLUOROURACIL ALONE IN THE TREATMENT OF ADVANCED GASTRIC-CANCER

Background. With the introduction of cisplatin-containing regimens in the treatment of advanced gastric cancer, promising clinical results h ave been reported. A 61.5% response rate was observed with a combinati on of 5-fluorouracil (5-FU) infusion and bolus cisplatin; however, the superiority of cisplatin-containing regimens to other regimens has no t been clearly verified in any randomized controlled studies. A prospe ctive, randomized study of 5-FU and cisplatin (FP) versus 5-FU, doxoru bicin and mitomycin C (FAM) versus 5-FU alone (FU) in previously untre ated patients with advanced gastric cancer is reported. Methods. A tot al of 324 patients were entered into the trial and 295 patients (103 f or FP, 98 for FAM, 94 for FU) were evaluable. The patients were random ized to receive FP, FAM, or FU after stratifying by the following fact ors: performance status, presence of measurable disease, and resection of the primary tumor. Results. The overall response rate for patients with measurable disease in the FP arm was significantly higher than i n the FAM and FU arms (51% for FP; 25% for FAM; 26% for FU). The durat ions of response for each arm, however, were not significantly differe nt. Even though the median time to progression for the FP arm (21.8 we eks) was longer than that for the FAM arm (12 weeks; P < 0.05) and for the FU arm (9.1 weeks; P < 0.005), there was no statistical differenc e in overall survival among the three arms. Toxicity for all three reg imens was moderate and consisted primarily of myelosuppression, nausea , vomiting, and alopecia. Conclusions. Although the FP regimen showed a significantly higher response rate and a longer time to progression than the FAM or FU regimens, a survival benefit was not observed.