Preclinical evaluation of CPT-11 and its active metabolite SN-38

Semin Oncol. 1996 Feb;23(1 Suppl 3):11-20.

Abstract

CPT-11 (irinotecan) is a water-soluble analogue of camptothecin (CPT), an antitumor drug extracted from the Chinese tree Camptotheca acuminata. SN-38 is an active metabolite of CPT-11 that contributes significantly to its activity. The antitumor effects of CPT-11 and SN-38 are exerted through a novel mechanism of action; inhibition of DNA topoisomerase I. CPT-11 and its metabolite have demonstrated potent inhibitory activity against a variety of cancer cell lines in vitro and against several murine and human tumors grafted in mice in vivo, including those that express multidrug resistance. CPT-11 has also shown synergistic activity in combination with 5-fluorouracil and cisplatin in vitro. No irreversible or unusual toxicities were observed with CPT-11 in animal toxicity studies. In summary, the preclinical profile of CPT-11 confirmed this drug to be an attractive candidate for clinical development.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Camptothecin / administration & dosage
  • Camptothecin / analogs & derivatives*
  • Camptothecin / pharmacology
  • Camptothecin / toxicity
  • DNA Damage
  • Drug Resistance
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Irinotecan
  • Neoplasms, Experimental / drug therapy
  • Topoisomerase I Inhibitors*

Substances

  • Antineoplastic Agents, Phytogenic
  • Enzyme Inhibitors
  • Topoisomerase I Inhibitors
  • Irinotecan
  • Camptothecin