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Cited by 382Colorectal Cancer Treatments and StudiesCancer therapeutics and mechanismsCancer Treatment and Pharmacology

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Clinical Studies of Three Oral Prodrugs of 5-Fluorouracil (Capecitabine, UFT, S-1): A Review

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Malet-Martino, M., Martino, R.·2002·The Oncologist
DOI 10.1634/theoncologist.7-4-288
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Abstract

Learning Objectives: After completing this course, the reader will be able to: Define the main oral prodrugs of fluorouracil. Know the indications of the new oral prodrugs of fluorouracil. Review the main toxicities and drug interactions of oral prodrugs of fluorouracil. Evaluate the benefit(s) of using an oral prodrug of fluorouracil compared with classical treatments. Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.com Although 5-fluorouracil (5-FU) was first introduced in 1957, it remains an essential part of the treatment of a wide range of solid tumors. 5-FU has antitumor activity against epithelial malignancies arising in the gastrointestinal tract and breast as well as the head and neck, with single-agent response rates of only 10%-30%. Although 5-FU is still the most widely prescribed agent for the treatment of colorectal cancer, less than one-third of patients achieve objective responses. Recent research has focused on the biomodulation of 5-FU to improve the cytotoxicity and therapeutic effectiveness of this drug in the treatment of advanced disease. As all the anticancer agents, 5-FU leads to several toxicities. The toxicity profile of 5-FU is schedule dependent. Myelotoxicity is the major toxic effect in patients receiving bolus doses. Hand-foot syndrome (palmar-plantar erythrodysesthesia), stomatitis, and neuro- and cardiotoxicities are associated with continuous infusions. Other adverse effects associated with both bolus-dose and continuous-infusion regimens include nausea and vomiting, diarrhea, alopecia, and dermatitis. All these reasons explain the need for more effective and less toxic fluoropyrimidines. In the first part of this review, we briefly present the metabolic pathways of 5-FU responsible for the efficacy and toxicity of this drug. This knowledge is also necessary to understand the target(s) of biomodulation. The second part is devoted to a review of the literature on three recent prodrugs of 5-FU, i.e., capecitabine, UFT (ftorafur [FTO] plus uracil), and S-1 (FTO plus 5-chloro-2,4-dihydroxypyridine plus potassium oxonate). The pharmacological principles that have influenced the development of these new drugs and our current knowledge of the clinical pharmacology of these new agents, focusing on antitumor activity and toxicity, are presented. The literature was analyzed until March 2002. This review is intended to be as exhaustive as possible since it was conceived as a work tool for readers wanting to go further.

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Authors
Malet-Martino, M., & Martino, R.
Affiliations
  • Groupe de RMN Biomédicale, Laboratoire des IMRCP, Université Paul Sabatier, Toulouse, France
  • Université Toulouse III - Paul Sabatier (FR)
ORCID
Martino, R.
Venue
The Oncologist
Publisher
Oxford University Press (OUP)
Published
2002-08-01
Volume
7
Issue
4
Pages
288-323
ISSN
  • 1083-7159 (ISSN-L)
  • 1549-490X
DOI
10.1634/theoncologist.7-4-288
OpenAlex
W2103359811
Cited by
382
References
228
Citations by year
2026: 7 · 2025: 13 · 2024: 11 · 2023: 18 · 2022: 19 · 2021: 15 · 2020: 14 · 2019: 15 · 2018: 20 · 2017: 20 · 2016: 24 · 2015: 20 · 2014: 23 · 2013: 21 · 2012: 18
FWCI
4.88
Type
journal article
Language
en
Open access
Licence
academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
Locations
  • The Oncologist (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer therapeutics and mechanisms
  • Health Sciences › Medicine › Oncology › Cancer Treatment and Pharmacology
Keywords
5-fluorouracil, oral prodrug, capecitabine, UFT, S-1, fluoropyrimidine, 5-fluorouracil metabolism, drug toxicity, drug interactions, myelosuppression, hand-foot syndrome, stomatitis, cardiotoxicity, neurotoxicity, colorectal cancer, breast cancer, solid tumors
MeSH terms
Capecitabine, Administration, Oral, Antineoplastic Agents, Deoxycytidine, Fluorouracil, Tegafur, Humans, Neoplasms, Prodrugs, Pyridines, Uracil, Treatment Outcome

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