title: Other fluorinated pyrimidines in the treatment of solid tumors.
abstract: Researchers, primarily in Japan, Europe, and the United States, have evaluated several new fluorinated pyrimidines in recent years. Most of these drugs are orally active prodrugs of fluorouracil (5-FU), and some also contain modulators of its pharmacological properties. S-1 is a rationally developed combination of tegafur, a prodrug of 5-FU; CDHP, an inhibitor of 5-FU catabolism; and potassium oxonate, an inhibitor of 5-FU-induced diarrhea. S-1 underwent phase I and II trials in Japan, where it is now approved for use in the treatment of advanced gastric cancer. Two phase I studies conducted recently in Europe and the United States identified diarrhea as the dose-limiting toxicity of S-1. BOF-A2, which contains a 5-FU prodrug and CNDP, an inhibitor of 5-FU catabolism, demonstrated clinical activity in preliminary studies in Japan. This article summarizes the preclinical and clinical development of S-1 and BOF-A2.
authors.affiliation: Department of Oncology, Albert Einstein Hospital, Sao Paulo, Brazil.
authors.forename: E D
authors.initials: ED
authors.lastname: Saad
authors.forename: P M
authors.initials: PM
authors.lastname: Hoff
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D004338:Drug Combinations; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D010094:Oxonic Acid / Q000008:administration & dosage / Q000627:therapeutic use*; D011725:Pyridines / Q000008:administration & dosage / Q000627:therapeutic use*; D005641:Tegafur / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D000964:Antimetabolites, Antineoplastic; D004338:Drug Combinations; D011725:Pyridines; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; C053194:Emitefur; D005472:Fluorouracil