Phase I-II study of gemcitabine and carboplatin in stage IIIB-IV non-small-cell lung cancer

Purpose: platinum-based chemotherapy currently represents standard treatmen t for advanced non-small-cell lung cancer. Gemcitabine is one of the most i nteresting agents currently in use in advanced non-small-cell lung cancer, and high response rates have been reported when it is administered in combi nation with cisplatin. The aim of the present study was to evaluate the com bination of gemcitabine and carboplatin in a phase I-II study. Patients and Methods: Chemotherapy-naive patients with stage IIIB-IV non-sm all-cell lung cancer received carboplatin art area under the concentration- time curve (AUC) 5 mg/ml/min and gemcitabine at an initial dose of 800 mg/m (2), subsequently escalated by 100 mg/m(2) per step. Gemcitabine was admini stered on days 1 and 8 and carboplatin on day 8 of the 28-day cycle. Dose e scalation proceeded up to dose-limiting toxicity (DLT), which was defined a s grade 4 neutropenia or thrombocytopenia or grade 3 nonhematalogic toxicit y. Results: Neutropenia was DLT, inasmuch as it occurred in three of five pati ents receiving gemcitabine 1,200 mg/m(2). Nonhematologic toxicities were mi ld. Gemcitabine 1,100 mg/m(2) plus carboplatin AUC 5 was recommended for ph ase II studies. An objective response war observed in 13 (50%) of 26 patien ts, including four complete responses (15%) and nine partial responses (35% ). Median duration of response was 13 months (range, 3 to 23 months). Media n overall survival was 16 months (range, 3 to 26 months). Conclusion: The combination of gemcitabine and carboplatin is well tolerate d and active. Neutropenia was DLT. The observed activity matches that obser vable in cisplatin-gemcitabine studies, whereas duration of response and su rvival are even higher. A phase II trial is under way. (C) 1999 by American Society of Clinical Oncology.