Sequential Chemotherapy with Combination Irinotecan and Cisplatin Followed by Docetaxel for Treatment-Naïve Patients with Advanced Non-small Cell Lung Cancer

BackgroundSequential administration of platinum-based doublet therapy and then a taxane may reduce the risk of drug resistance and, therefore, improve treatment outcome. This study was designed to evaluate the efficacy and tolerability of sequential administration of irinotecan and cisplatin and then docetaxel in patients with advanced non-small cell lung cancer (NSCLC).MethodsEligible patients received irinotecan in 60-mg/m2 infusions for 30 to 60 minutes on days 1, 8, and 15, and cisplatin in 75-mg/m2 infusions for 60 minutes on day 1 every 28 days for four cycles (IC). Regardless of the response, patients received up to four cycles of sequential docetaxel in 75-mg/m2 infusions for 60 minutes.ResultsForty-six patients with histologically confirmed chemotherapy-naïve stage IIIB or IV NSCLC were enrolled, of whom 42 were evaluable. The response rate at completion of chemotherapy with IC was 45.2% (95% confidence interval [CI]: 30.2%–60.3%). Five patients had improvement of disease status during sequential docetaxel, and seven patients had disease progression. Progression-free survival was 8.0 months (95% CI: 5.4–9.9 months), and the overall median survival was 14.6 months (95% CI: 9.8–17.9 months). The 1-, 2-, and 3-year survival rates were 54.3%, 22.6%, and 12.1%, respectively. The incidence of severe (≥CTC V2 grade 3) neutropenia during IC was 23.9% compared with 95.7% for sequential docetaxel (p < 0.0001).ConclusionSequential administration of IC and then docetaxel is feasible and is associated with a prolonged progression-free survival, but the current data do not confirm an improvement in treatment outcome by the sequential approach.