5-FLUOROURACIL, EPIRUBICIN, AND MITOMYCIN-C VERSUS 5-FLUOROURACIL, EPIRUBICIN, MITOMYCIN-C, AND LEUCOVORIN IN ADVANCED GASTRIC-CARCINOMA - A RANDOMIZED TRIAL

Leucovorin (LV) enhances the activity of 5-fluorouracil (5FU). Based o n these data, we performed a randomized trial with 5FU, epirubicin (EP I), mitomycin C (MMC) with/without LV in advanced gastric cancer (AGC) . The purpose of our study was to investigate if the addition of LV im proved the response rate of the combination 5FU EPI, MMC (FEM) over FE M. From January 1988 until April 1994, 88 patients with recurrent or m etastatic AGC were randomly received 5FU, EPI, MMC with (group A) or w ithout (group B) LV. Between the two arms of the study no difference w as noticed in sex, performance status, primary site of tumor, and lymp h node metastases. Therapy included group A (5FU 600 mg/m(2)/day, i.v. bolus, on days 1, 8, 29, 36, and EPI 45 mg/m(2)/day, i.v. bolus, on d ays I and 29, MMC 10 mg/m(2)/day, i.v, bolus, on day 1) and group B (t he same as group A plus LV 200 mg/m(2)/day by 2 h intravenous infusion with 5FU intravenous push at midinfusion). No significant difference in response rate was noticed between the two treatment arms; there wer e two (5%) patients with complete response in group A, and five (12%) in A and 11 (26%) partial responders in group B (p < 0.1). A significa ntly higher number of patients achieving stable disease was observed i n group B; 19 (44%) in comparison to group A 10 (24%) (p < 0.048). The re were more patients with progressive disease in group A 25 (59%) tha n in group B 12 (28%) (p < 0.003) (Table 2). No difference was noted i n mean duration of response: group A, 15.8 (6-31) weeks; acid group B, 17.6 (6-28) weeks. The mean time to progression was for group A [11.4 (6-35) weeks] and for group B [17.6 (8-33) weeks]. Mean survival was for group A [27.4 (12-59) weeks] and for group B [30.6 (17-53) weeks], for 50% of patients. Causes of death were, for group A, 40 patients f rom disease progression and two sudden deaths; for group B, causes of death were for 41 patients disease progression and two sudden deaths. There were two patients in group A and one in group B that were not ev aluable because they abandonded therapy after the first cycle. Toxicit y was increased in group B; anemia, nausea and vomiting, and alopecia (p < 0.055) were more severe in group B, but not statistically differe nt when compared to group A. Neutropenia, thrombocytopenia, mucositis, and fatigue of any grade were significantly more common and severe in group B. Significant dose reductions due to toxicity were required mo re commonly in group B. We conclude that the response rate was increas ed in the schedule with the addition of LV, at the cost of increased t oxicity and with no difference in survival. A randomized trial compari ng FEM-LV with new generation regimens would determine whether the add ition of LV qualifies FAM equally active with these.