To determine the feasibility and toxicity of combining leucovorin (CF) with a 5fluorouracil(5-FU) combination chemotherapy regimen currently accepted by many as standard treatment for gastric cancer, CF (500 mg/m') was administered in combination with the Georgetown S-FU, doxorubicin, and mitomycin C (FAM) regimen. Thirty-two patients with advanced adenocarcinoma of the stomach were evaluable for toxicity and 26 patients with measurable disease were evaluable for response. Fifty-four percent of patients were previously treated with chemotherapy or radiation therapy. The response rate was 38% (95% confidence interval, 21% to 59%). The median duration of response was 6 months (range, 2 to 23+ months). The estimated median survival time was 6.8 months for patients with measurable disease and 11.5 months for all 32 patients. Although diarrhea is dose limiting when 5-FU and CF are administered weekly for 6 of 8 weeks, diarrhea occurred rarely on this combination regimen with 5-FU and CF administered only 4 of every 8 weeks. The dose-limiting toxicity of FAM-CF was cumulative myelosuppression, which also occurs with the standard FAM regimen. As a result, the administered dose intensity of 5-FU decreased as patients continued on study. Thus, a randomized comparison of FAM with FAM-CF would not determine whether CF modulation increases the efficacy of 5-FU when it is administered in optimal doses to patients with gastric cancer. Cancer 65: 2442-2445,1990. WENTY THOUSAND new cases of gastric cancer will T be diagnosed in 1989, making it the sixth most common cause of cancer death in the US.' Unfortunately, only 25% of newly diagnosed patients are candidates for curative surgery and only 25% of these survive more than Presented in part at the Symposium on the Expanding Role of Folates and Fluoropyrimidines in Cancer Chemotherapy,