A randomized phase II study comparing two schedules of the 21-day regime of Gemcitabine and Carboplatin in advanced NSCLC

Purpose: Carboplatin area under the curve (AUC) 5 ml/min on day 1 with gemcitabine 1,250 mg/m2 on day 1 and day 8 is a widely used regimen in advanced non-small cell lung cancer. Grade 3–4 thrombocytopenia and neutropenia are frequent. The aim of this study is to investigate whether tox- icity of gemcitabine/carboplatin could be reduced by ad- ministering carboplatin on day 8 instead of day 1 without a decrease in response rate (RR). Methods: Patients received gemcitabine 1,250 mg/m2 on days 1 and 8, carboplatin AUC 5 on day 1 (arm A) or day 8 (arm B). Drugs were administered over a 21-day cycle. Toxicity and RR were evaluated weekly and every second cycle, respectively. Results: 71 patients were enrolled into the study. We found 79% (95% CI 61–91%) grade 3–4 toxicity (neutropenia and thrombocytopenia) in arm A and 50% (95% CI 32–68%) in arm B; 66% grade 3–4 thrombocytopenia in arm A and 26% in arm B. We observed 30% grade 4 hematological toxicity in arm A and 3% in arm B. In arm A an overall RR of 20% (95% CI 7.7–38.6%) was seen, and 18.2% (95% CI 7–35.5%) in arm B. Conclusions: Although the study was prematurely closed, the current data are of interest. The schedule with carboplatin on day 8 is associated with substantially lower grade 3–4 neutropenia and throm- bocytopenia with comparable dose intensity and RR