Safety and efficacy of sequential chemotherapy with carboplatin plus gemcitabine followed by weekly paclitaxel in advanced non-small cell lung cancer

Abstract

Improving survival in non-small cell lung cancer (NSCLC) will require new strategies or new drugs. Sequential administration of conventional non-cross-resistant cytotoxic drugs offers an opportunity to increase drug diversity while maintaining dose intensity. This Phase II trial was designed to assess the efficacy and feasibility of such a regimen in advanced NSCLC. Patients with NSCLC stage IIIB or IV received as first-line treatment four cycles of carboplatin (AUC 5) (day 1) plus gemcitabine 1000mg/m(2) (days 1 and 8) every 3weeks. Thereafter, treatment continued with 12 weekly cycles of paclitaxel 80mg/m(2). In total, 46 patients were included. Median age was 59.6years (range 41.3-74.3years) and 93.5% (n=43) had Eastern Cooperative Oncology Group performance score of 0 or 1. All but 6 had stage IV disease, and 13 (28.3%) had squamous cell carcinomas. Thirty-six (78%) patients completed 4 cycles of carboplatin-gemcitabine and 35 patients received at least 1 cycle of paclitaxel, of whom 16 (46% of total) patients completed 12 cycles of paclitaxel. The overall objective response rate was 49%. Sixteen (37%) patients had a response to carboplatin-gemcitabine, increasing to 21 (49%) patients after administration of paclitaxel. Of the 13 assessable patients who showed a partial response (PR) on carboplatin-gemcitabine, 12 (92%) patients showed also a PR on paclitaxel. Of 19 assessable patients with stable disease (SD) on carboplatin-gemcitabine, 4 (21%) had a PR and 13 (68%) SD on paclitaxel. Toxicity was moderate: 24% stopped because of toxicity. Sequential chemotherapy with carboplatin-gemcitabine and weekly paclitaxel is active and feasible in advanced NSCLC patients.