Phase I study of gemcitabine and carboplatin in advanced non-small cell lung carcinoma

Background: This phase I study was designed to determine the maximum tolera ted dose of carboplatin with a fixed dose of gemcitabine without growth fac tor or hematopoietic precursor support, Methods: Nineteen patients with pre viously untreated non-small cell lung cancer (NSCLC) were treated at three dose levels. Initially, the gemcitabine dose was 1000 mg/m(2) given on days 1 and 8. Of the first five patients treated with carboplatin AUC 4, three experienced dose limiting toxicity (DLT). The study was: therefore, amended to decrease the dose of gemcitabine to 800 mg/m(2) given on days 1 and 8 i n a 21-day cycle. Results: Dose limiting toxicity (neutropenia and thromboc ytopenia) were seen at dose level 2A (carboplatin AUC = 5). Thus, no furthe r dose escalation was performed. Grade 3 and 4 toxicities were seen as foll ows: leukopenia in five of 18 (28%); neutropenia, four of 18 (22%); and thr ombocytopenia, four of 18 (22%) evaluable patients. Grade 3 or 4 anemia occ urred in one of 18 (6%) patients and no neutropenic fever or treatment rela ted mortality was observed. Partial responses were seen in six patients and one patient with evaluable disease had an objective response. The overall response rate was 37% (seven of 19). Six other patients had stable disease. A total of 89 courses were administered with a median of five courses per patient (range: two to six courses). The median time to progression for all patients was 3.7 months. The median overall survival was 7.4 months with f our patients still alive (median follow up 13.5 months). The survival at 6 months and 1 year is 64 and 23%, respectively. Conclusion: The maximum tole rated dose (MTD) in this group of patients was defined as carboplatin AUC 4 when administered with gemcitabine 800 mg/m(2) on days 1 and 8 of a 21-day schedule. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.