Chemoradiation for locally advanced, unresectable NSCLC - New standard of care, emerging strategies

The optimal therapy for locally advanced, unresectable, stage III nonsmall- cell lung cancer (NSCLC) continues to evolve. The critical determinants of overall survival include local tumor control and the eradication of subclin ical micrometastatic disease. Historically, standard radiation therapy resu lted in a median survival of 7 to 10 months. In a randomized trial, the Can cer and Leukemia Group B (CALGB) established the superiority of induction c isplatin (Platinol) and vinblastine chemotherapy followed by radiation ther apy. Additional studies revealed that induction chemotherapy improved survi val rates by decreasing metastatic disease progression. Three independent m eta-analyses confirmed the survival benefit afforded by cisplatin-based ind uction chemotherapy followed by radiotherapy, and helped to establish this as the new standard of care, Other investigators have demonstrated improvem ents in focal tumor control and survival with either concurrent chemoradiot herapy or hyperfractionated radiotherapy. Most recently, attention has focu sed on radiation dose intensity and the utilization of newer, highly active chemotherapeutic agents with concurrent or sequential radiation therapy. T hese newer drugs, including paclitaxel (Taxol), docetaxel (Taxotere), gemci tabine (Gemzar), vinorelbine (Navelbine), and irinotecan (Camptosar), enhan ce radiation cytotoxicity and, when administered in systemically active dos ages, may also control micrometastatic disease. Phase I and II studies of n ovel chemoradiation regimens continue to demonstrate encouraging results, a nd several large randomized clinical trials are currently enrolling patient s.