The effects of co-administration of selenium and cis-platin (CDDP) on CDDP-induced toxicity and antitumour activity

Br J Cancer. 1988 Jul;58(1):38-41. doi: 10.1038/bjc.1988.157.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Cisplatin / therapeutic use*
  • Cisplatin / toxicity
  • Dose-Response Relationship, Drug
  • Female
  • Lethal Dose 50
  • Mesonephroma / blood
  • Mesonephroma / drug therapy*
  • Mice
  • Mice, Nude
  • Ovarian Neoplasms / drug therapy
  • Selenious Acid
  • Selenium / therapeutic use*
  • alpha-Fetoproteins / metabolism

Substances

  • alpha-Fetoproteins
  • Selenious Acid
  • Selenium
  • Cisplatin