Combined Modality Trials in Unresectable Stage III Non-Small Cell Lung Cancer: The Cancer and Leukemia Group B Experience

Lung cancer remains the leading cause of cancer-related mortality in the United States and 30% to 40% of newly diagnosed patients with non-small cell lung cancer present with regionally advanced and unresectable stage III disease. Combined-modality therapy is the current standard of care in patients with good performance status at the time of diagnosis and recent trials have suggested a survival advantage for the concurrent use of chemotherapy and thoracic radiation therapy at the risk of increased toxicity (mainly esophagitis and myelosuppression). The Cancer and Leukemia Group B has been instrumental in shaping the standard of care in the combined-modality approach to unresectable stage III non-small cell lung cancer. Currently, Cancer and Leukemia Group B is conducting trials evaluating novel thoracic radiation therapy strategies as well as the incorporation of molecularly targeted agents, yielding encouraging preliminary data. In addition, a change in the therapeutic platform is planned that explores a full-dose systemic approach with the antifolate pemetrexed that possesses radiosensitizing properties.