New perspectives in combined radiotherapy and chemotherapy treatment

Strategies for developing combined modality treatment for lung cancer have, until now, depended largely on empirical approaches whereby drugs with some activity against advanced disease have been combined with radiation. Survival gains have been modest. The present article emphasizes the need for new approaches that are based on mechanisms of interaction or cooperation between radiation and drugs, such that there is a selective increase in killing of tumour cells. Potential interactions include the use of radiation and drugs to eliminate cell populations which are shown in predictive assays to have differing mechanisms of resistance to the two modalities, selective inhibition of repopulation of tumour cells during radiotherapy by using drugs or biological agents, and selective killing of cells in hypoxic or acidic regions of tumours. The feasibility and potential of such approaches should be evaluated initially in small single-arm studies where outcome in individual patients is related to biological studies of mechanism. Such treatment may need to be individualized (e.g. depending on markers of drug resistance or growth factor receptors). Ultimately, the value of such treatments will need to be evaluated (whether individualized or generic) against standard treatment in large randomized trials. Guidelines for the conduct of such trials are indicated with emphasis on quality of life, assessment of costs and benefits, and involvement of patients in clinical decision making.