Exploitable mechanisms in combined radiotherapy-chemotherapy: the concept of additivity.

Abstract There are a number of different mechanisms that can lead to an improved therapeutic result by the combination of radiotherapy and chemotherapy. Some require interaction between the effects of the two modalities; others require independence of effect. Enhanced killing of tumor cells is only one possible mechanism. There are serious conceptual problems in demonstrating greater-than-additive cell kill whenever dose-response curves are nonlinear. An approach to this problem is suggested, based on an "envelope of additivity" in an iso-effect plot.