CHEMOTHERAPEUTIC TREATMENTS - A STUDY OF THE INTERPLAY AMONG DRUG-RESISTANCE, TOXICITY AND RECUPERATION FROM SIDE-EFFECTS

A system of differential equations for the control of tumor growth cel ls in a cycle nonspecific chemotherapy is analyzed. Spontaneously acqu ired drug resistance is taken into account, and a criterion for the se lection of chemotherapeutic treatment is used. This criterion purports to describe the possibility of improvement of the patient's health wh en treatment is discontinued. Contrary to our early results which also take drug resistance into account, in this context strategies of cont inuous chemotherapy in which rest periods take part may be better than maximum drug concentration throughout the treatment (which appears to be in accordance with clinical practice). This bears out our previous conjecture that when drug resistance is accounted for, the imperfecti ons in the usual modelling of treatment criteria, which in general do not allow for patient recuperation, ruled out the possibility of rest periods in optimal continuous chemotherapy. (C) 1997 Society for Mathe matical Biology.