Combining Systemic Therapies with Radiation in Non-Small Cell Lung Cancer

Abstract

Radiotherapy has been the mainstay of the treatment of stage III non-small cell lung cancer (NSCLC) patients. In the early nineties, combined treatment with chemotherapy was introduced. In 1995, a meta-analysis showed improved treatment outcome of the sequential use of cisplatin-based chemotherapy and radiotherapy (RCT) compared to radiotherapy alone. Subsequent randomized studies and the two meta-analyses demonstrated that concurrent radiochemotherapy (RCT) is superior (local control and overall survival) to sequential used both method. However, several questions remain unanswered concerning the optimal chemotherapy regimen and radiotherapy doses and techniques in terms of treatment outcome and toxicity profile. Targeted therapies represent a new class of drugs which interfere with specific molecular targets (typically proteins) playing critical roles in tumor growth and progression. Some combinations appear to be too toxic like the vascular epithelial growth factor antibody bevacizumab. The feasibility of adding the epidermal growth factor receptor inhibitor cetuximab has been recently reported for NSCLC patients. Strategies to safely incorporate novel antiangiogenic agents into combined-modality therapy in lung cancer are needed. The rapid development of molecular oncology will hopefully contribute to a better patient selection to particular strategies and to treatment optimization. Increasing radiotherapy doses applied according to up-to-date techniques and combinations with new biologicals might lead to further treatment improvements.