Resonance in periodic chemotherapy: a case study of acute myelogenous leukemia.

The effects of periodic chemotherapy administration are evaluated within the context of a G(0)model of the cell cycle. Parameters are estimated for normal bone marrow cells and malignant cells in acute myelogenous leukemia (AML). This model explicitly includes the resting G(0)phase and the feedback mechanism that recruits the cells back into the cell cycle. Periodic chemotherapy administration can induce resonance within our model under high cell kill rate where the average cell cycle times may change during the course of treatment, and therapeutic benefits from these resonances cannot be solely based on cell cycle times in untreated tissue. The depletion rate under chemotherapy and the regrowth rate may differ between the cell populations, and our analysis suggests that this favors the tumour cells. We were able to distinguish between the effects of cycle-non-specific, S -phase-specific and M -phase-specific drugs, and found that these can show differences in sharpness and location of the resonance phenomenon. We conclude that resonance chemotherapy (chronotherapy) is unlikely to be efficacious in the treatment of AML. Copyright 2001 Academic Press.