Reduction of cytotoxicity to normal tissues by new regimens of cell-cycle phase-specific drugs

Abstract A new policy for minimizing cytotoxicity to normal tissues of cell-cycle phase-specific drugs is suggested. This policy is based on short drug pulses and on an integer relation between the period of drug application and the cell-cycle length of the host susceptible tissue. The new protocol is expected to be effective even if the cell-cycle parameters of the malignant population have the same mean as those of the host cells but their variance is larger, and as long as the variance in the duration of the drug pulse is not too large. Under these conditions protocols can be determined by the host temporal parameters alone. The method has been verified in vitro , treating a leukemic cell line with cytosine arabinoside (Ara-C).