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.