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

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 sug...

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Bibliographic Details
Published in:British journal of cancer 1997-01, Vol.76 (7), p.952-962
Main Authors: Gerrits, CJH, de Jonge, MJA, Schellens, JHM, Stoter, G, Verweij, J
Format: Article
Language:English
Subjects:
Animals
Antineoplastic agents
Antineoplastic Agents - administration & dosage
Antineoplastic Agents - therapeutic use
Biological and medical sciences
Biomedical and Life Sciences
Biomedicine
Camptothecin - administration & dosage
Camptothecin - analogs & derivatives
Camptothecin - therapeutic use
Cancer Research
Chemotherapy
Clinical Trials, Phase I as Topic
clinical-oncology
Drug Resistance
Drug Screening Assays, Antitumor
Epidemiology
Humans
Irinotecan
Medical sciences
Mice
Mice, Nude
Molecular Medicine
Neoplasms - drug therapy
Oncology
Pharmacology. Drug treatments
Topoisomerase I Inhibitors
Topotecan
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Summary: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.
ISSN:0007-0920
1532-1827
DOI:10.1038/bjc.1997.491