Send to

Choose Destination
Br J Cancer. 1997;76(7):952-62.

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

Author information

Department of Medical Oncology, Rotterdam Cancer Institute (Daniel den Hoed Kliniek) and University Hospital, The Netherlands.


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.

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for PubMed Central
Loading ...
Support Center