{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T09:04:23Z","timestamp":1791191063386,"version":"4.1.0"},"reference-count":324,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2002,8,1]],"date-time":"2002-08-01T00:00:00Z","timestamp":1028160000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2002,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Learning Objectives<\/jats:title>\n                    <jats:p>After completing this course, the reader will be able to:<\/jats:p>\n                    <jats:p>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.<\/jats:p>\n                    <jats:p>Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.com<\/jats:p>\n                    <jats:p>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.<\/jats:p>\n                    <jats:p>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.<\/jats:p>\n                    <jats:p>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.<\/jats:p>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1634\/theoncologist.7-4-288","type":"journal-article","created":{"date-parts":[[2004,8,24]],"date-time":"2004-08-24T17:38:39Z","timestamp":1093369119000},"page":"288-323","source":"Crossref","is-referenced-by-count":326,"title":["Clinical Studies of Three Oral Prodrugs of 5-Fluorouracil (Capecitabine, UFT, S-1): A Review"],"prefix":"10.1093","volume":"7","author":[{"given":"M.","family":"Malet-Martino","sequence":"first","affiliation":[{"name":"Groupe de RMN Biom\u00e9dicale, Laboratoire des IMRCP, Universit\u00e9 Paul Sabatier, Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Martino","sequence":"additional","affiliation":[{"name":"Groupe de RMN Biom\u00e9dicale, Laboratoire des IMRCP, Universit\u00e9 Paul Sabatier, Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2002,8,1]]},"reference":[{"key":"2021122216222551100_R1","first-page":"119","article-title":"Studies in 2-acetylaminofluorene carcinogenesis. 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