THE ROLE OF INDUCTION CHEMOTHERAPY BEFORE RADIATION-THERAPY IN NONOPERATIVE MANAGEMENT OF STAGE-III NSCLC

Radiation therapy alone has been 'standard' management of patients with Stage III non-small cell lung cancer for several decades. Palliative benefits are routinely achieved but significant survival benefits have not been documented. Patterns of failure in Stage III patients emphasize the need to pursue better treatment for both local macroscopic disease and distant micrometastatic sites. Improved control in both areas will be necessary to meaningfully enhance outcome for the universe of Stage III NSCLC patients. Several randomized trials show a significant survival benefit when cisplatin-containing induction chemotherapy is administered prior to locoregional treatment. In the favorable subset of Stage III patients selected for study by CALGB, the surviving fraction at 2-5 years post-therapy was ≥ 2-fold larger in the chemoradiation group than in the cohort treated with radiation alone. The French trial documented a significant decrease in distant metastases rate among the chemotherapy treated patients. In all the trials where patterns of failure are discussed, local disease persistence is the overwhelming rule. Future trials must evaluate improved induction chemotherapy approaches. Stage III patients are an ethical population in which to test induction therapy with new drug combinations randomized against already 'active' regimens for comparative efficacy. End points would be initial response rates, patterns of failure, and overall survival. The feasibility of high-dose chemotherapy regimens with growth factor and hematopoietic support followed by aggressive radiation must be tested. If feasible, trials randomizing high dose versus conventional dose induction programs within the context of sequential multimodality therapy should follow. Intensified radiation approaches such as hyperfractionation or CHART should be paired with active concurrent chemotherapy following induction chemotherapy alone. Pursuit of these approaches over the next several years will hopefully produce major improvements in treatment efficacy and lead to enhanced survival expectations for the large group of patients worldwide with Stage III NSCLC. © 1994.