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Preclinical and Clinical Development of Exatecan (DX-951f)

A Hexacyclic Camptothecin Analog

  • Chapter
Book cover Camptothecins in Cancer Therapy

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

Abstract

The principal rationale for synthesizing exatecan (DX-8951f, Daiichi Pharmaceutical Co., Ltd, Japan) was to exploit physicochemical features of the camptothecins (CPTs) anticipated to yield an increased therapeutic advantage compared with currently available CPT analogs such as topotecan and irinotecan. The overall therapeutic profile sought in these efforts was greater and broader antitumor activity, decreased toxicity, and intrinsic activity without requiring metabolic activation, which may accentuate the fundamentally large interindividual variability in the pharmacologic behavior of the CPT analogs and consequently in their antitumor and toxicologic profiles. Exatecan has completed Phase I clinical development on a broad range of schedules and is currently undergoing more focused disease-directed Phase II and Phase III evaluations. Additionally, DE-310, a unique polymer prodrug of exatecan, which was developed to achieve protracted systemic exposure to the active drug after a single dose, is also undergoing early clinical development.

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Author information

Authors and Affiliations

  1. Institute for Drug Development, Cancer Therapy and Research Center, University of Texas Health Science Center, San Antonio, TX

    Eric K. Rowinsky MD (Director of Clinical Research)

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  1. Eric K. Rowinsky MD
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Editor information

Editors and Affiliations

  1. Department of Pharmacy Practice and Science, College of Pharmacy, University of Kentucky, Lexington, KY

    Val R. Adams PharmD

  2. Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY

    Thomas G. Burke PhD

  3. Experimental Therapeutics Program, Lucille P. Markey Cancer Center, University of Kentucky Medical Center, University of Kentucky, Lexington, KY

    Thomas G. Burke PhD

  4. Tigen Pharmaceuticals Inc., Lexington, KY

    Thomas G. Burke PhD

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© 2005 Humana Press Inc., Totowa, NJ

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Rowinsky, E.K. (2005). Preclinical and Clinical Development of Exatecan (DX-951f). In: Adams, V.R., Burke, T.G. (eds) Camptothecins in Cancer Therapy. Cancer Drug Discovery and Development. Humana Press. https://doi.org/10.1385/1-59259-866-8:317

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  • DOI: https://doi.org/10.1385/1-59259-866-8:317

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-027-4

  • Online ISBN: 978-1-59259-866-3

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