A PHASE-II STUDY OF WEEKLY HIGH-DOSE 5-FRUOROURACIL AND LEUCOVORIN PLUS BIWEEKLY ALTERNATING DOXORUBICIN AND CISPLATIN FOR ADVANCED GASTRIC-CARCINOMA

On the basis of recent clinical data suggesting that high-dose continu ous 5-fluorouracil (5-FU) is able to overcome resistance to 5-FU bolus application in gastric carcinoma, a phase II study was performed to e valuate the activity and toxicity of weekly high-dose 5-FU and leucovo rin plus biweekly alternating doxorubicin and cisplatin as the first-l ine treatment in patients with advanced gastric carcinoma. Between Oct ober 1995 and September 1997, 24 consecutive patients with locally adv anced (n = 4) or metastatic (n = 20) gastric carcinomas were treated w ith a combination of 500 mg/m(2) leucovorin as a 2-h infusion, followe d by 2.0 g/m(2) 5-FU as a 24-h continuous infusion once weekly for 6 w eeks, plus 20 mg/m2 doxorubicin as a bolus application and 50 mg/m(2) cisplatin as a l-h infusion, week 1, 3 and 5 (FLAP regimen). Response, toxicity and survival data were evaluated. A total of 20 patients wer e evaluable for response and 24 for toxicity. Objective responses were observed in Il patients (55%) with no complete remission. Four patien ts (20%) showed stabilization and 5 patients (25%) experienced progres sive disease. The median time to disease progression was 8 months and the overall duration of survival was 14 months. Myelosuppression was s ignificant. In 2 patients, grade 4 WHO thrombocytopenia and leukopenia /anaemia respectively were registered, but there were no treatment-rel ated deaths. We conclude that the weekly alternating FLAP regimen is e ffective in advanced gastric carcinoma with tolerable toxicity. Howeve r, significant myelotoxicity and frequent hospitalization suggest that FLAP should not be preferred to other regimens used in metastatic dis ease. Currently we intend to establish this regimen in the neoadjuvant setting in patients with primary unresectable localized gastric carci nomas.