SURVIVAL AND CURE OF LEUKEMIC MICE AFTER CIRCADIAN OPTIMIZATION OF TREATMENT WITH CYCLOPHOSPHAMIDE AND 1-BETA-D-ARABINOFURANOSYLCYTOSINE

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  • 1 January 1977
    • journal article
    • research article
    • Vol. 37  (10) , 3648-3655
Abstract
When cyclophosphamide and 1-.beta.-D-arabinofuranosylcytosine [ara-C] were administered to mice previously given injections of L1210 leukemia cells, the combination was more effective than either drug given alone. The effectiveness of the 2 drugs in combination was strongly influenced by the stage of the circadian system at which the drugs were administered. With the use of a chronobiological (sinusoidal) approach, in comparison with 1 or 2 conventional treatment schedules, it was possible to demonstrate an overall lower toxicity as monitored by death or weight loss. Mean survival times and cures (when obtained) were circadian stage dependent. In 1 study the cure rate was 94% in mice treated at 1 circadian stage, but only 44% in those treated at another stage. It cannot be overemphasized that just as the right timing can enhance (with statistical significance) tolerance to chemotherapeutic agents and the rate of cure in leukemic mice, so can wrongly timed (wrongly placed) ara-C sinusoid or wrongly timed cyclophosphamide enhance toxicity and host death rate.

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