High-dose therapy with carboplatin and paclitaxel in non-small cell lung cancer

Abstract

Non-small cell lung cancer (NSCLC) remains the leading cause of cancer deaths in the United States. The combination of more active agents like vinorelbine and paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) with cisplatin has led to improved survival for patients with advanced metastatic disease. The ability to escalate the dose of cisplatin-based regimens is limited by nonhematologic toxicities and is especially difficult in the population of patients with advanced NSCLC. However, the development of new agents with significant activity against NSCLC as well as new strategies for high-dose therapy have made it possible to examine the potential of dose-intense therapy in this population. A phase I trial performed at the University of North Carolina was designed to evaluate paclitaxel 250 mg/m2 given over 24 hours plus escalating doses of carboplatin starting at an area under the concentration-time curve (AUC) dose of 8 supported by peripheral blood stem cells and filgrastim in the treatment of advanced NSCLC. The AUC dose of carboplatin was escalated in increments of 2. The maximum tolerated dose of carboplatin combined with paclitaxel 250 mg/m2 administered over 24 hours was defined at an AUC of 18. In this study, six of seven patients with advanced NSCLC had major responses. This regimen is currently being tested in patients with locally advanced NSCLC by the Cancer and Leukemia Group B: patients receive two cycles of induction therapy with paclitaxel 250 mg/m2 over 3 hours followed by carboplatin at an AUC of 18 supported by peripheral blood stem cells and filgrastim. Depending on response to induction therapy, patients then receive surgical resection, thoracic radiation therapy, or both. This phase II trial will examine clinical and pathologic responses and the toxicity of this high-dose regimen in patients with locally advanced NSCLC. Ultimately, phase III trials will be needed to establish the role of this approach in NSCLC.