On the importance of sensitivity to the dose-effect relationship in chemotherapy

The dose effect relationship of cytostatics is discussed from a theoretical point of view. Assuming tumour cell sensitivity as a continuum and an exponential distribution of cell probability density as a function 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 probability density according to sensitivity and finally the product of dose and (minimum) sensitivity. The model demonstrates that the fractional tumour reduction intended is of major importance for the resulting curves. Dose effect curves describing a small fractional cell kill (0.5) are much steeper than curves describing a high one (to 10(-3)). Possible clinical implications of the model are discussed.