title: Cisplatin chronotherapy and disulfiram rescue reduce toxicity without interfering with anticancer activity: animal findings and preliminary clinical experiences.
abstract: Cisplatin-induced mortality and nephrotoxicity are each predictably worse when the drug is given at certain points within the circadian schedule. Oral disulfiram protects rats from toxic effects at some circadian stages but not others. This manuever does not diminish the anticancer activity of cisplatin in these rats. Human beings given 2 g of oral disulfiram and high doses of cisplatin at the circadian stage associated with least cisplatin nephrotoxicity (prospectively determined potassium excretion acrophase) suffer little or no kidney damage. Disulfiram administration apparently does not interfere with the antineoplastic activity of cisplatin in humans. This is the first demonstration of the feasibility of assignment of treatment time according to a measure of the patient's 'internal clock' as assessed by pretreatment marker rhythmometry. It also establishes the feasibility of giving disulfiram to human beings.
authors: Department of Medicine, University of Minnesota, Minneapolis 55455.
authors: R V
authors: RV
authors: Roemeling
authors: R
authors: R
authors: Olshefski
authors: T
authors: T
authors: Langevin
authors: J
authors: J
authors: Berestka
authors: J J
authors: JJ
authors: Reusch
authors: J E
authors: JE
authors: Reusch
authors: D
authors: D
authors: Lakatua
authors: M R
authors: MR
authors: Wick
authors: W J
authors: WJ
authors: Hrushesky
mesh_terms: D000368:Aged; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002940:Circadian Rhythm; D002945:Cisplatin / Q000008:administration & dosage / Q000633:toxicity; D004221:Disulfiram / Q000008:administration & dosage; D004334:Drug Administration Schedule; D004341:Drug Evaluation; D004353:Drug Evaluation, Preclinical; D005260:Female; D006801:Humans; D007668:Kidney / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D002945:Cisplatin; D004221:Disulfiram