The effects of co-administration of selenium and cis-platin (CDDP) on CDDP-induced toxicity and antitumour activity.
The therapeutic antitumour activity and host toxicity of cis-platin (CDDP), which was administered with selenium (sodium selenite) was studied on the growth of a human yolk sac tumour grown in nude mice. Treatment consisted of CDDP single agent chemotherapy (3 weeks) or preliminary PVB combination chemotherapy (CDDP + vinblastine + bleomycin, 2 weeks). Selenium was co-administered from day 1 to 5 with each therapeutic regimen. The administration of CDDP alone caused significant reduction in tumour burden but at higher doses there was significant host toxicity. The co-administration of selenium together with CDDP (CDDP: selenium, molar ratio = 3.5:1) did not affect the anti-tumour activity of CDDP but it did cause a decrease of parameters of host toxicity including lethality, increasing the 50% lethal dose (LD50) from 9.3 mg kg-1 to 17.5 mg kg-1. The parameters of host toxicity which were altered by selenium co-administration were nephrotoxicity, myeloid suppression and weight loss. Our study suggested that selenium co-administration allows higher doses of CDDP with reduction of apparent toxicity, resulting in a higher therapeutic index and possibly indicating a potential increase in the utilization of CDDP in clinical cancer chemotherapy.
Ohkawa
K
K
Department of Biochemistry, Jikei University School of Medicine, Tokyo, Japan.
Tsukada
Y
Y
Dohzono
H
H
Koike
K
K
Terashima
Y
Y
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002945:Cisplatin / Q000627:therapeutic use* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D005260:Female; D007928:Lethal Dose 50; D008649:Mesonephroma / Q000097:blood / Q000188:drug therapy*; D051379:Mice; D008819:Mice, Nude; D010051:Ovarian Neoplasms / Q000188:drug therapy; D020887:Selenious Acid; D012643:Selenium / Q000627:therapeutic use*; D000509:alpha-Fetoproteins / Q000378:metabolism
D000509:alpha-Fetoproteins; D020887:Selenious Acid; D012643:Selenium; D002945:Cisplatin