ON THE IMPORTANCE OF SENSITIVITY TO THE DOSE-EFFECT RELATIONSHIP IN CHEMOTHERAPY

The dose-effect relationship of cytostatics is discussed from a theore tical point of view. Assuming tumour cell sensitivity as a continuum a nd an exponential distribution of cell probability density as a functi on of sensitivity the 'log kill' concept has been extended to a model describing the relation between dose and effect in malignant tumours. The model is based on only 3 parameters: The ratio between maximum and minimum sensitivity, the ratio between maximum and minimum cell proba bility density according to sensitivity and finally the product of dos e and (minimum) sensitivity. The model demonstrates that the fractiona l tumour reduction intended is of major importance for the resulting c urves. Dose-effect curves describing a small fractional cell kill (0.5 ) are much steeper than curves describing a high one (to 10(-3)). Poss ible clinical implications of the model are discussed.