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  lüll Clinical studies of three oral prodrugs of 5-fluorouracil (capecitabine, UFT,  S-1): a review Malet-Martino M; Martino ROncologist  2002[]; 7 (4): 288-323Although 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.|Administration, Oral[MESH]|Antineoplastic Agents/metabolism/*therapeutic use/toxicity[MESH]|Capecitabine[MESH]|Deoxycytidine/*analogs & derivatives/metabolism/*therapeutic use/toxicity[MESH]|Fluorouracil/metabolism/*therapeutic use/toxicity[MESH]|Humans[MESH]|Neoplasms/drug therapy[MESH]|Prodrugs/metabolism/*therapeutic use/toxicity[MESH]|Pyridines/metabolism/*therapeutic use/toxicity[MESH]|Tegafur/metabolism/*therapeutic use/toxicity[MESH]|Treatment Outcome[MESH]|Uracil/metabolism/*therapeutic use/toxicity[MESH] |