Randomized phase II study of two opposite administration sequences of irinotecan and cisplatin in patients with advanced nonsmall cell lung carcinoma

BACKGROUND. Combined chemotherapy with irinotecan and cisplatin (IP) is active in patients with nonsmall cell lung carcinoma (NSCLC). However, the optimal administration schedule needs to be defined to maximize its synergic effect. The authors evaluated the efficacy, toxicity, and pharmacokinetics (PK) of IP chemotherapy given oil two administration sequences in chemotherapy-naive patients with NSCLC. METHODS. Eighty eligible patients were assigned randomly to receive 1 of 2 irinotecan and cisplatin administration sequences oil Day 1: irinotecan followed by cisplatin (I-P) (n = 39 patients) or cisplatin followed by irinotecan (P-I) (it = 41 patients). Treatment was comprised of irinotecan at a dose of 80 mg/m(2) 2 intravenously oil Days I and 8 and cisplatin at a dose of 60 mg/m(2) intravenously Oil Day I of a 21-day cycle for a maximum of 6 cycles. For PK analysis, serial plasma samples were obtained oil Day I of the first cycle. RESULTS. In total, 77 patients were assessable for efficacy. The overall response rate was 47%, and there was a trend in favor of P-I (54%) compared with I-P (39%). In multivariate logistic regression analysis, the P-I sequence and female gender were found to be significant predictors of a better response (P = 0.047 and P = 0.011, respectively). Overall toxicity profiles and PK parameters were similar ill both arms. CONCLUSIONS. IP chemotherapy showed promising activity with a favorable I-year survival rate. For future clinical Use, the authors recommend administering cisplatin first and then irinotecan, because that sequence was associated with a higher response rate.