PMID: 7023652Sep 15, 1981Paper

Modulation of 5-fluorouracil toxicity by allopurinol in man

Cancer
S B HowellJ S Romine

Abstract

Oxipurinol, the major metabolite of allopurinol, decreased the toxicity of 5-fluorouracil (5-FU) to human granulocyte colony-forming units in vitro by a factor of four. The ability of allopurinol to reduce 5-FU toxicity in vivo was studied in 23 advanced cancer patients during 42 courses of treatment. 5-FU was administered by continuous intravenous infusion for five days; allopurinol, 300 mg, po, every 8 hours was started 2 hours before and continued during and for 24 hours after 5-FU infusion. 5-FU was escalated from 1.5 to 2.25 g/m2/day on separate courses; the dose-limiting toxicity was mucositis which occurred at a level of 2.0 g/m2/day. At a 5-FU dose rate of greater than 2.0 g/m2/day 5-FU pharmacokinetics were nonlinear, reflecting saturation of catabolic pathways, and the steady-state 5-FU serum concentration was approximately 4 times that which was tolerable without allopurinol. At these concentrations of 5-FU oxipurinol significantly influenced the clearance of 5-FU. Thus concurrent allopurinol therapy permitted a doubling of the maximum tolerated dose of 5-FU and a four-fold increase in the tolerated concentration x time exposure to 5-FU.

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Citations

Aug 1, 2013·Supportive Care in Cancer : Official Journal of the Multinational Association of Supportive Care in Cancer·Siri Beier JensenUNKNOWN Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (
Jan 1, 1984·Pharmacology & Therapeutics·F Valeriote, G Santelli
Feb 28, 1985·The New England Journal of Medicine·H Garewal, F Ahmann
Oct 22, 2008·Acta Oncologica·Per AlbertssonKlas Norrby
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Nov 1, 1989·NMR in Biomedicine·P M McSheehy, J R Griffiths
Jan 17, 2019·Expert Opinion on Pharmacotherapy·Nauman S SiddiquiMuhammad Wasif Saif
Aug 27, 2005·American Journal of Health-system Pharmacy : AJHP : Official Journal of the American Society of Health-System Pharmacists·Frank G A JansmanJacobus R B Brouwers
Oct 29, 2000·Drug Safety : an International Journal of Medical Toxicology and Drug Experience·F G JansmanJ R Brouwers
Oct 1, 1995·Cancer Control : Journal of the Moffitt Cancer Center·R Quilitz
Apr 18, 2008·Anti-cancer Drugs·Muhammad Wasif SaifKostas N Syrigos

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