Chemotherapy and radiation in the nonoperative management of stage III non-small-cell lung cancer: the right chemotherapy works in the right setting.

Approximately one-quarter of all American patients with NSCLC present with stage III disease. At least to this juncture, standard management for the large majority of these patients is nonoperative, except for staging mediastinoscopy. Radiation therapy alone to 6000 cGy or above given in once-daily fractions 5 days per week is usually considered "standard" therapy. While this approach causes disease shrinkage in one-third to two-thirds of patients treated, long-term local control with this benchmark radiotherapy is poor, the median time to progression is less than 6 months, and median survival for treated patients is less than 1 year. Combination CT is more effective in inducing tumor regression in stage III than in stage IV NSCLC patients. The administration of a short course of induction CT (two to three cycles) prior to definitive XRT improves median and overall survival among stage III patients. In individuals with stage III disease selected for good performance status (0 to 1), minimum weight loss (< 5%), and no supraclavicular node involvement, sequential CT/XRT is associated with a survival plateau above 20% at 2 years, 3 years, and beyond. Local failure and distant failure both remain as problems despite the survival improvements produced by sequential CT/XRT. Concurrent chemoradiation, especially utilizing daily low-dose cisplatin, improves local control significantly and lengthens survival. Increased intensity of TRT using multifraction-per-day schedules or more active induction CT programs also may improve local control and perhaps affect overall survival. Trials now underway are testing sequences of induction CT followed by concurrent CT/XRT or rapid fractionation schemes and concurrent cisplatin-based combination CT. These strategies will hopefully produce yet another step up for the plateau phase of the survival curve for patients with stage III NSCLC.