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Comparative Antitumor Activity of 5-Fluorouracil (5-FU) Prodrugs in Preclinical Model Systems

Role of Leucovorin and Dihydropyrimidine Dehydrogenase Inhibitors

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Fluoropyrimidines in Cancer Therapy

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

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Abstract

Over the last two decades, attempts have been made to improve the efficacy of 5-fluorouracil (5-FU) by either schedule or biochemical modulation. Among the changes of particular importance in schedule of administration has been the use of prolonged infusion (1). Several studies have investigated different schedules for 5-FU administration including bolus administration up to 5 d, protracted infusion over weeks, continuous infusion over a period of 24 h, or a combination of both continuous and bolus administration (2). A meta-analysis was carried out on all randomized trials and have shown that if 5-FU is used alone, continuous infusion induces more tumor regression than bolus regimens, prolongs the time to disease progression, but the difference on the impact on survival is not significant (3). Clinical data, however, demonstrated similar results when protracted infusion of 5-FU was compared (historically) with 5-FU modulated by leucovorin (LV).

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Authors
  1. Shousong Cao MD
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  2. Gunnar Hapke PhD, MD
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  3. Youcef M. Rustum PhD
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Editors and Affiliations

  1. Roswell Park Cancer Institute, Buffalo, NY, USA

    Youcef M. Rustum

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Cao, S., Hapke, G., Rustum, Y.M. (2003). Comparative Antitumor Activity of 5-Fluorouracil (5-FU) Prodrugs in Preclinical Model Systems. In: Rustum, Y.M. (eds) Fluoropyrimidines in Cancer Therapy. Cancer Drug Discovery and Development. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-337-8_10

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  • DOI: https://doi.org/10.1007/978-1-59259-337-8_10

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-61737-274-2

  • Online ISBN: 978-1-59259-337-8

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