Optimization of the chronotherapeutic index in the experimental animal laboratory.
Large animal studies show that the effects of fixed doses of anticancer drugs vary predictably with multi-frequency rhythms' stages--components of a genetically--anchored, habitat synchronized, cosmically influenced time structure--the chronome. Both the tolerance by the host of the toxic drugs and the treatment's efficacy in killing cancer cells contribute to these changes. Chronotherapy, timing treatment according to the chronome, attempts to first maximize treatment efficacy while also minimizing toxicity, so as to optimize the therapeutic ratio. Outcomes have been improved by several hundred per cent by treating rodents at the "right" time with single or multiple agents under controlled laboratory conditions, and by chronoradiotherapy of human perioral tumors, using tumor temperature as a marker rhythm.
Halberg
E
E
Chronobiology Laboratories, University of Minnesota, Minneapolis 55455.
Cornélissen
G
G
Halberg
F
F
D000818:Animals; D000830:Animals, Laboratory; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use / Q000633:toxicity; D001853:Bone Marrow / Q000528:radiation effects; D002940:Circadian Rhythm; D004334:Drug Administration Schedule; D051379:Mice; D008954:Models, Biological; D009374:Neoplasms, Experimental / Q000188:drug therapy*
D000970:Antineoplastic Agents