15. Combined chemotherapy and radiation in locally advanced inoperable NSCLC

Abstract

Lung cancer is the leading cause of cancer death around the world. Non-small cell lung cancer (NSCLC) accounts for three quarters of all lung tumors. Surgery is the cornerstone of treatment in localized NSCLC but only 20% of patients are considered surgical candidates at presentation. The vast majority of patients cannot be subjected to surgery either because of tumor advancement or poor medical condition. Radiation therapy has traditionally been considered the mainstay of treatment in inoperable stage III disease. Irradiation, however, is in principle used for palliation since in most instances this method does not allow for eradication of bulky disease in the thorax. Moreover, radiotherapy does not prevent uncontrolled systemie disease, which is the major cause of death in locally advanced NSCLC. In consequence, the prognosis of patients with locally. advanced tumoursis dismal and has remained essentially unchanged within the last decades. The five-year survival rates after irradiation vary between 3 and 6%. One of the attempts to improve the outcome is combining radiation with chemotherapy. This strategy seems to be particularly interesting as it may potentially increase the cure rate not only by improved locoregional tumour controi butaiso by elimination of micrometastases outsidethe radiotherapy field. Chemotherapy and radiation may be applied in sequence ar concurrently. The results of phase III triais of radiation alone vs combined therapy using platinum based regimens demonstrated some survival benefit. The positive impact of chemotherapy was also demonstrated in the metaanalysis. Of the two strategies (chemotherapy followed by radiotherapy or concurrent chemoradiotherapy, the latter was found to be superior to sequential application but at the expense of increased early toxicity. The value of new agents (taxanes, vinorelbine, gemcitabine and topoisomerase inhibitors) in combined modality therapy of NSCLC seems to be promising, but warrants further clinical evaluation. In conclusion, chemotherapy may be usetul as an adjunct to radiation in locally advanced NSCLC. However, the benefit of combined approach, in particular concomitant chemoradiation, should be balanced against increased toxicity.