Topoisomerase I inhibition with topotecan: pharmacologic and clinical issues

Expert Opin Pharmacother. 2001 Mar;2(3):491-505. doi: 10.1517/14656566.2.3.491.


Topoisomerase I (topo-I) inhibitors are a new class of anticancer agents with a mechanism of action aimed at interrupting DNA replication in cancer cells, the result of which is cell death. Most, if not all, topo-I inhibitors are derivatives of the plant extract camptothecin. Topotecan is a derivative of camptothecin which has been structurally modified to increase water solubility. The pharmacokinetic profile of topotecan is usually characterised by a two-compartment model and is linear in the dose range of 0.5 - 3.5 mg/m(2). Current clinical trials suggest antitumour activity against a variety of human tumour types, including ovarian cancer, non-small cell lung cancer (NSCLC) and non-lymphocytic haematologic malignancies. The main dose-limiting toxicity (DLT) is non-cumulative myelosuppression. Non-haematologic toxicities are usually mild. Based on several Phase I studies, the recommended Phase II dose was 1.5 mg/m(2)/day iv. for 5 days. Current Phase I and Phase II trials are evaluating the combination of topotecan with other chemotherapeutic agents to increase the therapeutic benefits of topotecan. The DLT in these trials is mainly myelosuppression.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • Clinical Trials as Topic
  • Drug Resistance, Multiple
  • Drug Resistance, Neoplasm
  • Enzyme Inhibitors / therapeutic use*
  • Humans
  • Topoisomerase I Inhibitors*
  • Topotecan / therapeutic use*


  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Topoisomerase I Inhibitors
  • Topotecan