Combined modality therapy of non-small cell lung cancers

Lung cancer represents the leading cause of cancer mortality. Non-small cell lung cancer (NSCLC) accounts for about 75% to 80% of lung cancer cases and carries a 5-year survival of about 10% to 15% for all stages. Approximately one third of NSCLC patients present with stage III disease, which is defined as locally advanced tumour confined to the chest without distant metastasis. The traditional treatment for stage III patients has been thoracic radiotherapy (RT). However, the impact of thoracic RT alone has been minimal with published studies showing median survival < 1 year and 5-year survival of 5% to 7%. Thus, the treatment of stage III NSCLC remains a significant challenge. The metastatic nature of this disease has been responsible for the poor survival statistics and emphasises the need for effective systemic treatment. In recent years, cisplatin-containing combination chemotherapy has emerged as a viable option in the treatment of NSCLC. Combined modality therapy employing systemic (chemotherapy) and local (RT with or without surgery) approaches has shown favourable results in patients with stage III disease. Randomised studies have demonstrated the benefit of concurrent or sequential chemoradiation in selected patients with a good performance status and minimal weight loss. The exact sequence has yet to be determined. Moreover, randomised studies in stage IIIA potentially resectable disease show survival advantage for patients receiving combined modality treatment. Thus, combined modality treatment has the potential to improve overall survival by increasing both local and distal control. These recent reports of randomised clinical trials of combined modality therapy for stage III NSCLC form the basis for this report. Several new agents, like the taxanes, CPT-II and gemcitabine show promising activity in NSCLC treatment. Ongoing studies are evaluating the potential role of these new agents in combined modality treatment but since the phase III trials have not been reported yet these studies will not be discussed.