Quantification of sodium thiosulphate protection on cisplatin-induced toxicities.
OBJECTIVE
To quantify the amount of protection from cisplatin (CDDP)-induced mortality and toxicity provided by sodium thiosulphate (STS).


METHODS
Prospective controlled animal study.


METHODS
Animal research facility.


METHODS
Nephrotoxicity, myelotoxicity, and auditory/neurotoxicity were studied in guinea pigs. Total CDDP doses of 15, 21, 25, 35, and 45 mg/kg were administered to animals in groups of five. In some groups, STS (8000 mg/kg) was given. Animals underwent bloodwork and auditory brainstem response (ABR) testing to estimate toxicity before and 1 month after treatment.


METHODS
Blood urea nitrogen, creatinine, and white blood cell count were used to assess renal and myelotoxicity. Hearing was assessed with ABR thresholds to click stimuli. Survival was an overall measure of toxicity.


RESULTS
Forty guinea pigs in six treatment groups were studied. Animals given 21 mg/kg CDDP all died within 1 month and showed evidence of severe toxicity. Eighty percent of subjects treated with CDDP 15 mg/kg survived and showed evidence of nephrotoxicity and ototoxicity. Subjects treated with STS and CDDP showed survival comparable to the control group treated with CDDP 15 mg/kg. Under STS protection, CDDP was tolerated in doses three times the toxic dose without protection. Without STS, the maximum dose of CDDP tolerated for a month was 15 mg/kg.


CONCLUSIONS
STS protects against mortality owing to CDDP by reducing toxicity. Under STS protection, the maximum tolerated dose of CDDP is greatly increased in guinea pigs.
Leitao
Darren J
DJ
Department of Otolaryngology, University of Manitoba, Winnipeg, Manitoba.
Blakley
Brian W
BW
D000818:Animals; D000931:Antidotes / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000633:toxicity*; D002945:Cisplatin / Q000493:pharmacokinetics / Q000633:toxicity*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D064420:Drug-Related Side Effects and Adverse Reactions / Q000517:prevention & control*; D006168:Guinea Pigs; D007674:Kidney Diseases / Q000139:chemically induced / Q000401:mortality / Q000517:prevention & control; D008297:Male; D020258:Neurotoxicity Syndromes / Q000209:etiology / Q000401:mortality / Q000517:prevention & control; D011446:Prospective Studies; D013118:Spinal Cord Diseases / Q000139:chemically induced / Q000401:mortality / Q000517:prevention & control; D013885:Thiosulfates / Q000008:administration & dosage* / Q000493:pharmacokinetics
D000931:Antidotes; D000970:Antineoplastic Agents; D013885:Thiosulfates; C017717:sodium thiosulfate; D002945:Cisplatin