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Phase II Study of Irinotecan Plus Cisplatin in Patients With Advanced Non–Small-Cell Lung Cancer

From the Vanderbilt University, Nashville, TN; Duke University, Durham, NC; University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, CA; The Cancer Treatment and Research Center, San Antonio, TX; and Pharmacia & Upjohn, Kalamazoo, MI.

Address reprint requests to Russell F. DeVore III, MD, Vanderbilt University Medical Center, 1956 TVC, Nashville, TN 37232; email russell.devore{at}mcmail.vanderbilt.edu

PURPOSE: To evaluate the antitumor efficacy and safety of a combination of irinotecan (CPT-11) and cisplatin in patients with inoperable non–small-cell lung cancer (NSCLC). A secondary objective was to characterize the pharmacokinetics and pharmacodynamics of CPT-11 and its active metabolite, SN-38.

PATIENTS AND METHODS: Patients with stage IIIB or IV NSCLC were treated with repeated 4-week courses comprising CPT-11 (60 mg/m²) administered on days 1, 8, and 15, and a single dose of cisplatin (80 mg/m²) after CPT-11 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 1-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-11 dose attenuations to 40 mg/m² in the majority of patients (31 of 52; 60%), whereas dose reductions of cisplatin were uncommon. CPT-11 pharmacokinetic parameters were comparable to those reported previously in single-agent studies.

CONCLUSION: CPT-11/cisplatin is an active 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 to exploit more directly the therapeutic synergy of these agents.

Presented in part at the Thirty-Third Annual Meeting of the American Society of Clinical Oncology, Denver, CO, May 17-20, 1997 (abstr 1674).

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