Topoisomerase I inhibitors: the relevance of prolonged exposure for present clinical development

Br J Cancer. 1997;76(7):952-62. doi: 10.1038/bjc.1997.491.


Topoisomerase I inhibitors constitute a new class of anti-cancer agents. Recently, topotecan and irinotecan were registered for clinical use in ovarian cancer and colorectal cancer respectively. Cytotoxicity of topoisomerase I inhibitors is S-phase specific, and in vitro and in vivo studies have suggested that, for efficacy, prolonged exposure might be more important than short-term exposure to high concentration. Clinical development of those topoisomerase I inhibitors that have reached this stage is also focused on schedules aiming to achieve prolonged exposure. In this review, we summarize all published preclinical studies on this topic for topoisomerase I inhibitors in clinical development, namely 20-S-camptothecin, 9-nitro-camptothecin, 9-amino-camptothecin, topotecan, irinotecan and GI147211. In addition, preliminary data on clinical studies concerning this topic are also reviewed. The data suggest that prolonged exposure may indeed be relevant for anti-tumour activity. However, the optimal schedule is yet to be determined. Finally, clinical data are yet too immature to draw definitive conclusions.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / therapeutic use
  • Camptothecin / administration & dosage*
  • Camptothecin / analogs & derivatives*
  • Camptothecin / therapeutic use
  • Clinical Trials, Phase I as Topic
  • Drug Screening Assays, Antitumor
  • Humans
  • Irinotecan
  • Mice
  • Mice, Nude
  • Neoplasms / drug therapy
  • Topoisomerase I Inhibitors*
  • Topotecan


  • Antineoplastic Agents
  • Topoisomerase I Inhibitors
  • lurtotecan
  • Irinotecan
  • Topotecan
  • Camptothecin