Combined chemotherapy and radiation in locally advanced non-small cell lung cancer

The majority of patients with locally advanced, unresectable, non-small cell lung cancer (NSCLC) treated with conventional radiation therapy develop distant metastases and succumb to the disease. Thus, NSCLC should be viewed as a systemic disease, and attempts to control micrometastatic disease with chemotherapy should have a greater impact on survival. This does not eliminate the role of radiation therapy, as locoregional control is equally important. Combined chemoradiotherapy has become the major area of clinical research to improve long-term outcomes in patients with locally advanced NSCLC. The optimal chemoradiotherapy sequence is yet to be determined. Several randomized studies have demonstrated that sequential chemotherapy followed by definitive thoracic irradiation is superior to the same radiation therapy alone. The overall impact has been on both survival and incidence of distant metastasis. A number of pilot studies (phase II) have tested concurrent chemoradiotherapy in patients with locally advanced NSCLC. At the University of Maryland Cancer Center, we are evaluating the efficacy of thoracic radiation (60 Gy) with concurrent weekly carboplatin, which has known activity in NSCLC and also has radiosensitizing effects. Preliminary results show that the combination is feasible and well tolerated; median survival rates compare favorably to those seen in the combined-modality arms of the randomized, sequential studies. Definitive conclusions based on the results of the reported studies are not possible, yet there seems to be a potential benefit to adding chemotherapy to radiation therapy. These trials need to be confirmed before they can be used to define a "standard of care" for patients with locally advanced, unresectable NSCLC.