Incorporation of paclitaxel and carboplatin in combined-modality therapy for locally advanced non-small cell lung cancer

Combined chemotherapy and thoracic radiation therapy has emerged as a primary treatment option for locally advanced, unresectable non-small cell lung cancer (NSCLC). Randomized trials and subsequent meta-analyses have shown a clear survival benefit with platinum-based combination chemotherapy administered sequentially or concurrently with hyperfractionated thoracic radiation over radiation alone. Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and carboplatin recently have been evaluated in numerous phase I/II trials at various doses in both sequential and concurrent schedules with thoracic radiation in patients with locally advanced and unresectable NSCLC. The patterns of failure in patients treated with concurrent paclitaxel/carboplatin and thoracic radiation suggest the need for additional chemotherapy either at the front end or after completion of the concurrent regimen. A large multicenter randomized study (Locally Advanced Multimodality Protocol) has been initiated to address these issues of improvement in distant control and to further refine the combined-modality approach for patients with locally advanced NSCLC. Several other combined- modality regimens incorporating a platinum compound and a novel agent like gemcitabine, vinorelbine, paclitaxel, or docetaxel have been recently completed or are in progress. The hope for the immediate future is to define an 'effective' and 'optimal' regimen that can be given simultaneously with thoracic radiation and can result in improved local and systemic control in patients with regionally advanced NSCLC. Numerous phase II and III trials are currently planned or under way to further define the efficacy of this novel combination of paclitaxel/carboplatin in combined-modality programs in an attempt to determine the optimal administration sequence of chemotherapy and thoracic radiation. These combined-modality programs are now being integrated into trials for early stage, potentially resectable disease. Thus, NSCLC is in fact a systemic disease requiring a multidisciplinary approach for optimal management.