Abstract
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 on two administration sequences in chemotherapyβnaive patients with NSCLC.
METHODS
Eighty eligible patients were assigned randomly to receive 1 of 2 irinotecan and cisplatin administration sequences on Day 1: irinotecan followed by cisplatin (IβP) (n = 39 patients) or cisplatin followed by irinotecan (PβI) (n = 41 patients). Treatment was comprised of irinotecan at a dose of 80 mg/m^2^ intravenously on Days 1 and 8 and cisplatin at a dose of 60 mg/m^2^ intravenously on Day 1 of a 21βday cycle for a maximum of 6 cycles. For PK analysis, serial plasma samples were obtained on Day 1 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 PβI (54%) compared with IβP (39%). In multivariate logistic regression analysis, the PβI 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 in both arms.
CONCLUSIONS
IP chemotherapy showed promising activity with a favorable 1βyear 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. Cancer 2006. Β© 2006 American Cancer Society.