Partial substitution of cisplatin with carboplatin in combination with etoposide in advanced non-small cell lung cancer (NSCLC): a multicentric randomised Phase II trial

Abstract

Seventy previously untreated patients with advanced NSCLC were randomised, after stratification for stage (IIIB vs. IV) and Performance Status (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 day 1 + CDDP 30 mg/m 2 day 2, 3 + VP16 100 mg/m 2 day 1–3 (33 patients). Therapy was recycled on day 29 in both arms. The two arms were well balanced for the main pretreatment characteristics. Sixty-six patients (32 with Stage IIIB and 34 with Stage IV disease) were evaluable for toxicity and response (arm A = 34, arm B = 32), while four ineligible patients were excluded from analysis. Acute toxicity was assessed at recycling. Non-hematologic toxicity was higher in arm A. However, the reduction of nephrotoxicity (9% vs. 23%) in arm B was lower than expected. Leukopenia (15 vs. 5 patients) or thrombocytopenia (7 vs. 0 patients) of any grade affected more patients of arm B. Moreover, Grade 3–4 leukopenia (six patients) or thrombocytopenia (four patients) was observed only in arm B. Seventeen patients responded: 11 34 (32%; 95% C.I. = 17–50%) in arm A, and 6 32 (19%; 95% C.I. = 7–36%) in arm B. Median survival times of 40 and 34 weeks, respectively, were reported in arm A and B. Stage IIIB and squamous cell histology were associated with a higher probability of response. In conclusion, the partial replacement of CDDP with CBDCA in combination with VP16 slightly improves the tolerance of the treatment in terms of nephro- and neurotoxicity; however, it induces a significant increase in hematologic toxicity. In view of this unfavourable toxicologic profile and of the discouraging response rate observed, this regimen cannot be recommended as standard treatment in advanced NSCLC.