Journal article
A phase I and pharmacokinetic study of oral uracil, ftorafur, and leucovorin in patients with advanced cancer
Cancer chemotherapy and pharmacology, Vol.37(6), pp.581-586
1996
DOI: 10.1007/s002800050432
PMID: 8612313
Abstract
A phase I and pharmacokinetic study of oral uracil, ftorafur, and leucovorin was performed in patients with advanced cancer. Uracil plus ftorafur (UFT) was given in a 4:1 molar ratio in three divided doses for 28 consecutive days. Patient cohorts were treated at 200, 250, 300, and 350 mg/m2 of UFT daily. For all patients, 150 mg of leucovorin was given daily in three oral doses. A 1-week rest period followed each 28-day treatment course. Gastrointestinal toxicity, characterized by diarrhea, nausea, and vomiting, was dose-limiting at 350 mg/m2 UFT in patients who had received prior chemotherapy. Mild fatigue and transient hyperbilirubinemia were also common. In previously untreated patients, UFT at 350 mg/m2 was well-tolerated, suggesting this as an acceptable phase II dose in this schedule with leucovorin. Two of eight previously untreated patients with advanced colorectal cancer had partial responses with UFT (350 mg/m2) plus leucovorin. Pharmacokinetic parameters [ftorafur, uracil, 5-fluorouracil (5-FU), 5-methyltetrahydrofolate] showed wide interpatient variations. Plasma levels of 5-FU (Cmax 1.4±1.9 μM) were comparable to those achieved with protracted venous infusions, and folate levels (Cmax 6.1±3.6 μM) were sufficient for biochemical modulation. Ongoing study will determine if this convenient oral regimen will compare favorably in terms of efficacy, toxicity, and cost with intravenous fluoropyrimidine programs.
Details
- Title: Subtitle
- A phase I and pharmacokinetic study of oral uracil, ftorafur, and leucovorin in patients with advanced cancer
- Creators
- N. J Meropol - Roswell Park Cancer InstituteY. M Rustum - Roswell Park Cancer InstituteN. J Petrelli - Roswell Park Cancer InstituteM RODRIGUEZ-BIGAS - Roswell Park Cancer InstituteC Frank - Roswell Park Cancer InstituteD. H HO - The University of Texas MD Anderson Cancer CenterM Kurowski - Roswell Park Cancer InstituteP. J Creaven - Roswell Park Cancer Institute
- Resource Type
- Journal article
- Publication Details
- Cancer chemotherapy and pharmacology, Vol.37(6), pp.581-586
- Publisher
- Springer
- DOI
- 10.1007/s002800050432
- PMID
- 8612313
- ISSN
- 0344-5704
- eISSN
- 1432-0843
- Language
- English
- Date published
- 1996
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984359813502771
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