circadian rhythm in tolerance of mice for etoposide etoposide 40 mgkgday x 3 days and 60 mgkgday x 3 days was best tolerated by male b6d2f1 mice when given in the second half of the rest span of their sleepwake circadian cycle such a timequalified treatment resulted in increased longterm survival rate highest peripheral leukocyte count at nadir and lowest body weight loss as compared to results from drug dosing in the activity span assuming that such results may be extrapolated to human beings the treatment time of etoposide associated with an optimal tolerance would be located in the second half of the sleeping span usually near 500 hrs