TREATMENT OF PATIENTS WITH ADVANCED GASTRIC-CARCINOMA WITH A 5-FLUOROURACIL-BASED OR A CISPLATIN-BASED REGIMEN - 2 PARALLEL RANDOMIZED PHASE-II STUDIES

BACKGROUND, Although many drug combination therapies have been propose d, there is no standard therapy for patients with advanced gastric car cinoma. The superiority of combination therapy over monochemotherapy h as not been demonstrated convincingly. To explore the role of monochem otherapy, the authors evaluated 5-fluorouracil (5-FU), modulated by GS -leucovorin (GS-LV) and a cisplatin-containing regimen, which was comp rised of epirubicin, etoposide, and cisplatin with the addition of the reversal agent lonidamine (EEP-L). METHODS, After stratification acco rding to performance status (PS) and resection of the primary tumor, 7 2 patients with advanced gastric carcinoma were randomized to 2 parall el Phase II trials with 5-FU/6S-LV and EEP-L, respectively. Thirty-six patients in Study A received bolus GS-LV, 100 mg/m(2), followed by bo lus 5-FU, 370 mg/m(2), on Days 1-5 and 36 others in Study B received e pirubicin, 30 mg/m(2), on Days 1 and 5; etoposide, 100 mg/m(2), on Day s 1, 3, and 5; cisplatin, 30 mg/m(2), on Days 2 and 4; and lonidamine, 150 mg/day. RESULTS. There were 6 partial responses (18.2%) (95% conf idence interval [CI] +/- 13.2) in Study A and 7 partial responses (21. 9%) (95% CI +/- 14.3) in Study B. Partial responses were more frequent in patients with resected tumors or with an Eastern Cooperative Oncol ogy Group PS of 0-1. The median duration of response was 8.8 and 8.3 m onths, respectively, in Study A and Study B. The median survival reach ed 8 months in Study A and 9 months in Study B. In the whole populatio n of patients survival was significantly higher in patients with a PS of 0-1 (P < 0.05). Patients with a PS of 0-1 and a resected tumor had the significantly longest survival both in EEP-L treated patients and in all evaluable patients in the two studies. The most frequent World Health Organization Grade 3-4 toxic effects were gastrointestinal in S tudy A and hematologic in Study B. No treatment-related death was obse rved. CONCLUSIONS. The efficacy of 5-FU, modulated with GS-LV, is mode rate in patients with advanced gastric carcinoma, similar to cisplatin -containing regimens. PS and other prognostic factors could influence the response rate, which does not appear to be a reliable parameter fo r evaluating the outcome of chemotherapy trials. (C) 1998 American Can cer Society.