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Effect of allopurinol on the toxicity of high‐dose 5‐fluorouracil administered by intermittent bolus injection
Author(s) -
Howell Stephen B.,
Pfeifle Craig E.,
Wung Wally E.
Publication year - 1983
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/1097-0142(19830115)51:2<220::aid-cncr2820510209>3.0.co;2-w
Subject(s) - medicine , allopurinol , toxicity , bolus (digestion) , fluorouracil , mucositis , anesthesia , chemotherapy , pharmacology , gastroenterology , urology , surgery
The effect of allopurinol pretreatment on the toxicity of 5‐fluorouracil (5‐FU) was examined in a clinical trial. Twenty‐three patients were given bolus infusions of 5‐FU every two weeks in doses that produced mild toxicity (0.8–1.9 g/m 2 ). On alternate courses patients were pretreated with allopurinol either 300 mg two hours prior to and 10 hours after 5‐FU, or 300 mg every 8 hours for 4 doses starting 24 hours before 5‐FU. Seventeen and 20 pairs of courses were evaluable from the 2‐ and 24‐hour pretreatment groups, respectively. Allopurinol did not produce a significant degree of protection against 5‐FU‐induced myelosuppression or mucositis on either dose schedule. Neurotoxicity manifesting as both cerebellar and encephalopathic signs and symptoms was the most important toxicity encountered and was dose‐limiting for 5‐FU on this schedule. Mean oxipurinol serum concentrations at the time of 5‐FU administration were 24 uM and 104 uM for the 2‐ and 24‐hour allopurinol pretreatment schedules respectively. Allopurinol increased the T 1/2 of 5‐FU by a mean of 67% in three of the four patients studied. Pretreatment with allopurinol did not reduce the toxicity of 5‐FU administered as an intravenous bolus.