This comprehensive review of the management of locally advanced unresectable non-small-cell lung cancer (NSCLC) summarizes major landmark studies that have led to the current standard of care. In addition, more recent ongoing trials using altered radiation schedules and new chemotherapeutic agents are discussed.
Three randomized studies, two conducted by the Cancer and Leukemia Group B (CALGB) and one from France, all demonstrated a modest but reproducible survival advantage with cisplatin-based neoadjuvant chemotherapy followed by conventional radiation therapy.
Sequential vs concurrent chemotherapy remains the area of controversy. The potential advantage of concomitant chemoradiation is based primarily on the radiation-sensitization effect, thereby improving local control and, perhaps, survival as well. Newly updated results from the West Japan Lung Cancer Group (WJLCG) randomized trial favored concurrent to sequential chemoradiation. Five-year survival was 15.8% and 8.9%, respectively (p=0.047). The highly anticipated 3-arm study from the Radiation Therapy Oncology Group (RTOG) comparing conventionally fractionated concurrent chemoradiation Vs hyperfractionated concurrent chemoradiation vs sequential chemoradiation should have survival results available in the year 2000.
Based on the encouraging results from trials of accelerated hyperfractionated radiation therapy in NSCLC, the Eastern Cooperative Oncology Group (ECOG) has initiated a randomized trial of induction taxol and carboplatin chemotherapy followed by standard radiation Vs the same induction chemotherapy followed by hyperfractionated accelerated radiation therapy (HART).
Some novel anticancer agents with unique mechanisms of action have been tested in phase I/II trials and shown encouraging results. We expect to see more trials incorporating of these new agents into the treatment of NSCLC in the future.