Therapeutic ratio of reirradiation with cytotoxic drugs and other response-modifying agents

Abstract

The introduction of combined modality approaches was a highly significant step in the evolution of curative radiation treatment. Achieving a favorable balance between tumor cell kill and normal tissue toxicity is important, especially in the context of reirradiation. As a result of previous treatments, which often include surgery and chemotherapy, function and reserve capacity of tissues and organs are impaired. Therefore, strategies that could increase the tumor cell kill of reirradiation without increasing serious toxicities would improve the therapeutic index. Two major examples where reirradiation often is combined with concomitant chemotherapy are head and neck tumors and rectal cancer. Compared with the systematic experimental models used for development of first-line combinations and their evaluation through a classic series of clinical trials including randomized phase III studies, development of sound combination regimens for reirradiation is still in its infancy. The clinical situation is complicated by more heterogeneous tumors with changes in physiological and microenvi-ronmental parameters over time and quite variable pretreatment approaches, time intervals, irradiated volumes, etc. This chapter summarizes the principles of combined modality treatment and studies performed in the reirradiation setting.