The search for therapeutic gain in the combination of radiotherapy and chemotherapy.

The literature on combined treatment with radiation and cytotoxic drugs in experimental tumours and normal tissues of laboratory animals is reviewed in the context of the four previously proposed mechanisms whereby a therapeutic advantage might be gained. There is evidence for strong time-dependent processes occurring in some normal tissues. In tumours, the evidence for this is much weaker and there is considerable disparity among experimental tumours in optimum timing. This review leads to the conclusion that the clinical use of drug-radiation combinations should not be based on an anticipated beneficial interaction; gain will most probably come from the best radiotherapy and the best chemotherapy given as far as possible independently. Deleterious interactions can be reduced by allowing a gap of some weeks between chemotherapy and radiotherapy and by avoiding drugs that are known to enhance radiation damage to the normal tissues that are irradiated.