Resonance in periodic chemotherapy: A case study of acute myelogenous leukemia

The effects of periodic chemotherapy administration are evaluated within th e context of a G(0) model of the cell cycle. Parameters are estimated for n ormal bone marrow cells and malignant cells in acute myelogenous leukemia ( AML). This model explicitly includes the resting G(0) phase and the feedbac k mechanism that recruits the cells back into the cell cycle. Periodic chem otherapy administration can induce resonance within our model under high ce ll kill rate where the average cell cycle times may change during the cours e of treatment, and therapeutic benefits from these resonances cannot be so lely based on cell cycle times in untreated tissue. The depletion rate unde r chemotherapy and the regrowth rate may differ between the cell population s, and our analysis suggests that this favors the tumour cells. We were abl e to distinguish between the effects of cycle-non-specific, S-phase-specifi c and M-phase-specific drugs, and found that these can show differences in sharpness and location of the resonance phenomenon. We conclude that resona nce chemotherapy (chronotherapy) is unlikely to be efficacious in the treat ment of AML. (C) 2001 Academic Press.