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Phase I Trial of the Combination of Irinotecan, Paclitaxel, and Carboplatin in Patients With Advanced Non–Small-Cell Lung Cancer

From the University of North Carolina, Chapel Hill, NC; Indiana University, Indianapolis, IN; Pharmacia Corp, Peapack, NJ; University of Southern California/Norris Cancer Center, and Cedars-Sinai Medical Center, Los Angeles, CA; and Pharmacia Corp, Milan, Italy.

Address reprint requests to Mark A. Socinski, MD, Director, Multidisciplinary Thoracic Oncology Program, University of North Carolina at Chapel Hill, 3009 Old Clinic Building, CB# 7305, Chapel Hill, NC 27599; email: socinski{at}med.unc.edu

PURPOSE: To determine the maximum-tolerated dose, toxicities, and dose suitable for phase II/III trials of irinotecan (CPT-11) combined with paclitaxel and carboplatin in patients with advanced non–small-cell lung cancer (NSCLC).

PATIENTS AND METHODS: Patients with stage IIIB/IV NSCLC were enrolled to this multicenter, phase I study. The initial regimen was paclitaxel 225 mg/m²/3 h, followed by carboplatin area under the curve (AUC) 6 over 30 minutes on day 1, and CPT-11 starting at 40 mg/m² over 90 minutes, days 1 and 8, every 3 weeks. Dose-limiting toxicity occurred in three of seven patients. The regimen was amended, with doses reduced to paclitaxel 175 mg/m²/3 h, carboplatin AUC 5 and CPT-11 at 40 mg/m², all on day 1 every 3 weeks. Dose escalation of CPT-11 proceeded to 80 mg/m² then 125 mg/m² before dose-limiting toxicities were experienced. Subsequent patients received an intermediate CPT-11 dose of 100 mg/m².

RESULTS: Thirty-three patients were enrolled; 32 patients were assessable for safety, and 31 were assessable for tumor response. The primary first-cycle dose-limiting toxicities were neutropenia and diarrhea. The most common grade 3/4 toxicity observed during all cycles was neutropenia (16 patients [50%], with six [19%] developing neutropenic fever). Objective tumor response was observed in 39% (12/31, 95% confidence interval, 22% to 58%). The median time to tumor progression was 6.8 months, median survival 11.0 months, and 1-year survival probability 0.46.

CONCLUSION: CPT-11 100 mg/m², paclitaxel 175 mg/m², and carboplatin AUC 5 given every 3 weeks can be safely administered in patients with advanced NSCLC. Neutropenia and diarrhea are the dose-limiting toxicities. The combination shows appreciable activity, and survival data are favorable.

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				M. A. Socinski, D. E. Morris, J. S. Halle, D. T. Moore, T. A. Hensing, S. A. Limentani, R. Fraser, M. Tynan, A. Mears, M. P. Rivera, et al. Induction and Concurrent Chemotherapy With High-Dose Thoracic Conformal Radiation Therapy in Unresectable Stage IIIA and IIIB Non-Small-Cell Lung Cancer: A Dose-Escalation Phase I Trial J. Clin. Oncol., November 1, 2004; 22(21): 4341 - 4350. [Abstract] [Full Text] [PDF]