title: A phase I study of doxifluridine as a five-day stepped-dose continuous infusion.
abstract: Doxifluridine (5'-dFUR) is a prodrug of 5 fluorouracil (5-FU) synthesized in an attempt to improve the therapeutic index compared with 5-FU. In this phase I study, cohorts of three patients were treated by a 5-day continuous infusion with the dose increased daily, total doses ranging from 3.75 g/m2 to 20 g/m2/120 h. Twenty-nine patients received 54 courses (median 2, range 1-4). The dose-limiting toxicities were mucositis (Miller grade 3 in three patients and grade 4 in another) and grade 4 neutropenia and thrombocytopenia in two patients. Other toxicities included nausea, vomiting, and diarrhea, rash, and fever. Neurological toxicity was mild and no cardiovascular toxicity was recorded. Plasma and urine levels of 5'-dFUR and 5-FU were quantitated by high-performance liquid chromatography. Steady-state plasma levels between 167 ng/ml and 6,519 ng/ml were recorded and at these levels there was no evidence of saturation of doxifluridine metabolism. One patient at the maximum tolerated dose of 20 g/m2/120 h had a complete response in a nasopharyngeal carcinoma.
authors: Department of Cancer Medicine, Peter MacCallum Cancer Institute, Melbourne, Victoria, Australia.
authors: I N
authors: IN
authors: Olver
authors: P A
authors: PA
authors: Reece
authors: J F
authors: JF
authors: Bishop
authors: R G
authors: RG
authors: Morris
authors: B L
authors: BL
authors: Hillcoat
authors: T W
authors: TW
authors: Guentert
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use* / Q000633:toxicity / Q000652:urine; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004341:Drug Evaluation; D005260:Female; D005467:Floxuridine / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use* / Q000633:toxicity / Q000652:urine; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D012074:Remission Induction
chemical_list: D000970:Antineoplastic Agents; D005467:Floxuridine; C025034:doxifluridine