[Chronobiology and cancer]

Circadian rhythms characterize murine tolerance for 18 anticancer agents, including radiations and chemotherapeutic drugs. Such rhythms usually exhibit a large amplitude. Moreover, the circadian time of highest host tolerance for several cytostatics was similar to that of their optimal antitumor effectiveness in four different experimental models. Mechanisms of such rhythms involve predictable temporal changes in drug pharmacokinetics as well as rhythms in the susceptibility of both tumor and host tissues. Studies performed in mice or rats led to an adequate prediction of the optimal time to administer adriamycin, 4'tetrahydropyranyl-adriamycin and cis-dichlorodiammine platinum, provided that the rest-activity cycle of either species be considered. Since the dosing time of these agents also influenced largely the extent of human tolerance for these drugs, the extension of circadian timed therapy appears as inescapable. Programmable delivery systems have been developed to render such goal feasible, and their need has been emphasized in preliminary studies. Since interindividual differences may characterize, to some extent, host chronotolerance, and to a larger extent, tumor chronosusceptibility, a circadian monitoring of marker variables ("marker rhythms") constitutes a further challenge for individualizing cancer chronotherapy.