Additivity versus repair inhibition in fractionated treatments combining drugs and X rays: a theoretical analysis.

Abstract

Drugs which inhibit the repair of radiation damage could potentially be useful for enhancing the effects of radiotherapy. In pre-clinical combined modality studies, however, it is often difficult to state with certainty whether or not a drug has inhibited radiation damage repair. This paper shows that several commonly used parameters for assessing repair can give the wrong answer regarding the presence of drug-induced repair inhibition. These parameters are; the difference in radiation dose between 1 and n fractions to give the same effect, the fractional recovered dose per fraction interval, FR, and the related parameter FREC. A further parameter used for treatment comparisons is the enhancement ratio for the drug (D.E.R.; ratio of radiation doses, with and without drug, to cause a given effect). An increasing D.E.R. with increasing number of radiation fractions has been taken as an indication that the drug inhibited repair. The present report demonstrates that this, too, can be misleading. From an analysis based on a linear-quadratic survival curve for X rays, it is suggested that deriving and comparing alpha/beta ratios (ratio of the linea to quadratic coefficients) gives the best indication of drug-induced changes in survival curve shape which may reflect underlying changes in repair capacity.