This communication represents the definitive report of a randomized phase III study comparing
cisplatin and
carboplatin, in combination with
vindesine and
mitomycin C in stage IIIB and IV squamous-cell
bronchogenic carcinoma. A total of 221 patients entered the study and were randomized into two arms. Of these, 114 patients (109 evaluable for activity) were randomized to arm A, receiving
cisplatin 120 mg/m(2),
mitomycin C 8 mg/m(2) and
vindesine 3 mg/m(2) per cycle; 107 patients (101 evaluable for activity) were randomized to arm B receiving
carboplatin 500 mg/m(2) with the same doses of
mitomycin C and
vindesine per cycle. Patients with progressive disease (PD) were excluded from the study after the 2nd cycle, and those with stable disease (SD), partial response (PR) and complete response (CR) received six cycles of
chemotherapy (or less in case of early progression). Patients were stratified according to the clinical stage (IIIB vs. IV), performance status (0+1 vs. 2+3) and
tumor histological grade (I+II
vs. III). In the
cisplatin arm two patients (1.9%) achieved a CR, 38 (34.9%) a PR, 45 (41.2%) a SD and 24 (22.0%) had PD; the overall response rate was 40/109 (36.8%). In the
carboplatin arm five patients (5.0%) achieved a CR, 31 (30.7%) a PR, 40 (39.6%) a SD, and 25 (24.7%) had PD; the overall response rate was 36/101 (35.7%). No statistically significant difference in response rate was present between the two arms, and the response rate was not influenced by performance status, histological grade or clinical stage. The Kaplan-Meyers curves displayed a significant advantage both for time to progression (P=0.005) and overall survival (P=0.008) for patients in the
carboplatin arm. The advantage for patients receiving
carboplatin instead of
cisplatin appeared evident in univariate setting for patients with a good performance status and clinical stage IV, and occurred irrespectively of
tumor histological grade; response duration and survival of responders was identical in the two arms. Patients achieving a stable disease survived longer in the
carboplatin than in the
cisplatin arm (P=0.012). Thus, substitution of
cisplatin by
carboplatin in the
combination chemotherapy regimen, although more hematologically toxic (but less emetogenic) resulted in a similar response rate, but a significantly longer time to progression and overall survival.