Phase II study of irinotecan plus cisplatin in patients with advanced non-small-cell lung cancer

Purpose: To evaluate the antitumor efficacy and safety of ct combination of irinotecan (CPT-11) and cisplatin in patients with inoperable nan-small-cell lung cancer (NSCLC). A secondary objective was to characterize the pharmacokinetics and pharmacodynamics of CPT-11 and its active metabolite, SN-38. Patient and Methods: Patients with stage IIIB or IV NSCLC were treated with repeated 4-week courses comprising CPT-11 (60 mg/m(2)) administered on days 1, 8, and 15, and a single dose of cisplatin (80 mg/m2) after CPT-I 1 administration on day 1. Results: Fifty-two patients were enrolled, including 33 men and 19 women. The median age was 61 years (range, 29 to 79 years). Southwest Oncology Group performance status was 0 in 12 patients, 1 in 32 patients, and 2 in eight patients. Eleven and 41 patients had stage IIIB and IV disease, respectively. Objective responses occurred in 28.8% of patients (15 of 52; 95% confidence interval, 16.5% to 41.2%). The median survival duration was 9.9 months (range, 1.6 to 30.8 months). The I-year survival rate was 37%. Grade 3/4 adverse events consisted primarily of nausea (32.7%) or vomiting (13.5%), late-onset diarrhea (17.3%), and neutropenia (46.1%), the study design led to preferential modification of CPT-11 doses, resulting in CPT-II dose attenuations to less than or equal to 40 mg/m(2) in the majority of patients (31 of 52; 60%), whereas dose reductions of cisplatin were uncommon. CPT-II pharmacokinetic parameters were comparable to those reported previously in single-agent studies. Conclusion: CPT-11/cisplatin is an derive combination regimen with manageable toxicity in the therapy of stage IIIB/IV NSCLC. Future studies should be designed with schedules and dose modification provisions that avoid unnecessary CPT-11 dose reductions ta exploit more directly the therapeutic synergy of these agents. (C) 1999 by American Society of Clinical Oncology.