A 4-DRUG COMBINATION CHEMOTHERAPY WITH CISPLATIN, MITOMYCIN, VINDESINE AND 5-FLUOROURACIL - A REGIMEN ASSOCIATED WITH MAJOR TOXICITY IN PATIENTS WITH ADVANCED NONSMALL CELL LUNG-CANCER

The purpose of this study was to determine the activity of a 4-drug co mbination chemotherapy: cisplatin, mitomycin C, vindesine and 5-fluoro uracil (5-FU) in patients with advanced non-small cell lung cancer (NS CLC). Chemotherapy consisted of the administration of cisplatin (30 mg /m(2) d 1-4), mitomycin C (10 mg/m(2) d 1), vindesine (3 mg/m(2) d 1) and 5-FU (1 g/m(2) d 1-4 by continuous intravenous infusion). In patie nts older than 70 years, and in those who received prior irradiation o r chemotherapy, cisplatin and 5-FU were omitted on day 4, Courses were repeated every 4 weeks and evaluation of response was performed after the first 2 courses. In case of response, treatment was continued unt il best response or untolerable toxicity. Among 182 eligible patients, 75% had received no prior therapy; 41% had locoregional disease and 5 9% metastatic disease; 41% lost more than 5% of their pretherapy body weight. A 34% objective response rate was observed in the 164 evaluabl e patients (31% in all the eligible patients) including 4 complete and 52 partial responses. Patients with locoregional disease had a signif icantly better response rate than those with metastases (44% vs 27%). The overall median survival was 26 weeks. Significant hematological to xicity was documented but the most serious adverse event was the occur rence of 18 (10%) cardiac or sudden deaths. These toxic deaths were si gnificantly associated with a 5% loss of body weight prior to therapy. The addition of 5-FU to combination of cisplatin, mitomycin C and vin desine does not improve antitumoral effect but results in very signifi cant cardiac toxicity.