Docetaxel in combination with platinum compounds for non small-cell lung cancer

Assessing the combination of docetaxel with cisplatin or carboplatin was based on their activity as single agents, their nonoverlapping toxicity profiles, and their lack of cross-resistance. Phase I studies of docetaxel in combination with cisplatin established that 75 mg/m2 of each agent could be administered with reasonable safety and appeared to be active in non small-cell lung cancer (NSCLC). We evaluated the docetaxel/cisplatin combination in patients with advanced NSCLC. The response rate was 32%, and the median survival was 11.5 months. Efficacy was comparable to that observed in the Australian and French trials with the same combination. This is now being evaluated further in two large randomized trials for patients with advanced NSCLC and has been incorporated into the combined modality programs for early-stage disease. Carboplatin, devoid of the nephrotoxicity and neurotoxicity associated with the parent cis-platin, was then combined with docetaxel. The recommended dose of docetaxel for further evaluation in combination with carboplatin (AUC=6 mg/mL.min) was 90 mg/m2 with filgrastim support and 80 mg/m2 without filgrastim support. Our phase II trial of the combination of docetaxel and carboplatin in advanced NSCLC demonstrated an overall response rate of 36%; median survival was 13.9 months, and 1-year survival was 52%. Comparable activity has been seen by other investigators, and the regimen is being evaluated in two randomized trials. The combination of docetaxel with either of the two platinum agents has reasonable activity in NSCLC, though the carboplatin/docetaxel doublet appears to have a better therapeutic index.