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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Camptothecins: a review of their development and schedules of administration.

Used for centuries in traditional Chinese medicine, camptothecin was rediscovered in the 1950s during a search for compounds that could be used as a source for steroid synthesis. Due to its limited water solubility, a sodium salt was used in the early clinical trials. The severe toxicity and erratic absorption relegated this compound to the research laboratory until the 1980s when the topoisomerase enzyme was identified as the cellular target of camptothecin, the topoisomerase enzyme was found to be overexpressed in cancer cells and a structure-activity relationship was determined for camptothecin. These new developments brought the camptothecins back to the clinical setting for further testing. The various analogues that have been most studied to date include: irinotecan (CPT-11), and its derivative SN-38, topotecan, and 9-aminocamptothecin. Numerous trials have been conducted in an attempt to establish the efficacy in various tumour types, to determine the dose-limiting toxicity and to define the optimal schedule of administration. It seems that large doses of these drugs given on intermittent schedules are not effective. Our hypothesis is that the camptothecins require a prolonged schedule of administration given continuously at low doses or frequent intermittent dosing schedules to be most effective. With these schedules, normal haematopoietic cells and mucosal progenitor cells with low topoisomerase I levels may be spared, while efficacy is preserved.[1]


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