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Topoisomerase I inhibitors: the relevance of prolonged exposure for present clinical development.
- Source :
-
British journal of cancer [Br J Cancer] 1997; Vol. 76 (7), pp. 952-62. - Publication Year :
- 1997
-
Abstract
- 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.
- Subjects :
- Animals
Antineoplastic Agents therapeutic use
Camptothecin therapeutic use
Clinical Trials, Phase I as Topic
Drug Screening Assays, Antitumor
Humans
Irinotecan
Mice
Mice, Nude
Neoplasms drug therapy
Topotecan
Antineoplastic Agents administration & dosage
Camptothecin administration & dosage
Camptothecin analogs & derivatives
Topoisomerase I Inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 0007-0920
- Volume :
- 76
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- British journal of cancer
- Publication Type :
- Academic Journal
- Accession number :
- 9328159
- Full Text :
- https://doi.org/10.1038/bjc.1997.491