PARTIAL SUBSTITUTION OF CISPLATIN WITH CARBOPLATIN IN COMBINATION WITH ETOPOSIDE IN ADVANCED NONSMALL CELL LUNG-CANCER (NSCLC) - A MULTICENTRIC RANDOMIZED PHASE-II TRIAL

Seventy previously untreated patients with advanced NSCLC were randomi sed, after stratification for stage (IIIB vs. IV) and Performance Stat us (0-1 vs. 2), to receive either treatment A: CDDP 40 mg/m(2) + VP16 100 mg/m(2) day 1-3 (37 patients); or treatment B: CBDCA 250 mg/m(2) d ay 1 + CDDP 30 mg/m(2) day 2, 3 + VP16 100 mg/m(2) day 1-3 (33 patient s). Therapy was recycled on day 29 in both arms. The two arms were wel l balanced for the main pretreatment characteristics. Sixty-six patien ts (32 with Stage IIIB and 34 with Stage IV disease) were evaluable fo r toxicity and response (arm A = 34, arm B = 32), while four ineligibl e patients were excluded from analysis. Acute toxicity was assessed at recycling. Non-hematologic toxicity was higher in arm. A. However, th e reduction of nephrotoxicity (9% vs. 23%) in arm B was lower than exp ected. Leukopenia (15 vs. 5 patients) or thrombocytopenia (7 vs. 0 pat ients) of any grade affected more patients of arm B. Moreover, Grade 3 -4 leukopenia (six patients) or thrombocytopenia (four patients) was o bserved only in arm B. Seventeen patients responded: 11/33(32%; 95% C. I. = 17-50%) in arm A, and 6/32 (19%; 95% C.I. = 7-36%) in arm B. Medi an survival times of 40 and 34 weeks, respectively, were reported in a rm A and B. Stage IIIB and squamous cell histology were associated wit h a higher probability of response, In conclusion, the partial replace ment of CDDP with CBDCA in combination with VP16 slightly improves the tolerance of the treatment in terms of nephro- and neurotoxicity; how ever, it induces a significant increase in hematologic toxicity, In vi ew of this unfavourable toxicologic profile and of the discouraging re sponse rate observed, this regimen cannot be recommended as standard t reatment in advanced NSCLC.