Randomized Phase II trial of sequential chemotherapy in advanced non-small cell lung cancer (SWOG 9806): Carboplatin/gemcitabine followed by paclitaxel or cisplatin/vinorelbine followed by docetaxel

Purpose: Improving chemotherapeutic efficacy in non-small cell lung cancer (NSCLC) will require the development of new drugs or new strategies to better use currently available agents. Sequential administration offers an opportunity to increase drug diversity while maintaining dose intensity. On the basis of the data indicating the activity of taxanes as second-line therapy and the lack of efficacy for more than three cycles of platinum-based therapy, this randomized Phase II study tested the concept of planned sequential chemotherapy in advanced NSCLC. Experimental Design: Patients with selected stage IIIb (pleural effusion)/stage IV NSCLC, performance status of 0-1 and normal organ function were eligible. Therapy: arm 1, carboplatin (area under the curve = 5.5 mg/ml × min day 1) and gemcitabine (1000 mg/m² days 1 and 8 every 21 days × 3) followed by paclitaxel (225 mg/m² every 21 days × 3) or arm 2, cisplatin (100 mg/m² day 1), vinorelbine (25 mg/m² days 1 and 8 every 21 d × 3) followed by docetaxel (75-100 mg/m² every 21 days × 3). Results: Two-hundred four patients were accrued, of whom, 178 were eligible and evaluable. Eighty percent of patients were stage IV on arm 1 and 85% on arm 2. Response rates were 21 and 28% on arms 1 and 2, respectively. Median, 1-year and 2-year survivals were 9 months, 34 and 13%, and 9 months, 36 and 8%, on arms 1 and 2, respectively. Conclusions: Sequential therapy, as used in this study, resulted in comparable efficacy to previous Southwest Oncology Group trials of two drug combinations in this population; however, it failed to meet criteria for further study.