The role of chemotherapy in the treatment of unresectable stage III and IV nonsmall cell lung cancer.

Modern platinum-based combination chemotherapy has played a major role in the therapeutic approach to unresectable stage III and IV NSCLC. Randomized phase III trials clearly documented a survival as well as palliative benefit to treatment in patients with stage IV NSCLC who have a good PS (PS 0-1). The optimal therapeutic approach in patients with poor PS (PS 2) has not yet been defined. Recent trials that focused on the elderly suggested that they receive benefits from chemotherapy that are similar to their younger counterparts. The benefit from chemotherapy seems to occur early (initial 3 to 4 cycles) and prolonged therapy is not indicated. Second-line therapy that is administered upon progression was shown to provide survival and palliative benefits. In unresectable stage III NSCLC, the addition of chemotherapy to TRT improves long-term survival and has the potential to cure a minority of patients. Although sequential and concurrent chemoradiotherapy approaches have improved survival in phase III trials, concurrent strategies seem superior in comparative trials. New techniques in radiation therapy, such as three-dimensional treatment planning, may allow safer administration of both modalities concurrently and allow higher doses of TRT to be delivered. In unresectable stage III and stage IV NSCLC, the role of the new "targeted" therapies is currently being defined in several randomized, phase III trials. It is imperative that physicians who care for patients with advanced NSCLC be aware of these trials and attempt to enroll their patients, if possible. It is only through the successful and timely completion of well-designed clinical trials that we will advance our knowledge of improved treatment options for our patients with this disease.