Reversal of 5-fluorouracil-induced toxicity by oral administration of uridine.
BACKGROUND
Previous preclinical and clinical investigations have shown that the combined administration of 5-fluorouracil (5-FU) with delayed uridine can reverse side effects induced by 5-FU. This biochemical modulation-based combination may increase the therapeutic index of 5-FU.


METHODS
Seven patients with advanced cancer were treated weekly with 5-FU at increasing dosages starting at a dose of 600 mg/m2. Five patients developed dose-limiting leukopenia, and two patients developed thrombocytopenia. At the dose-limiting toxicity level, 5-FU treatment was repeated and followed after 3 hours by oral uridine (5 g/m2 q 6 hr) during 72 hours.


RESULTS
5-FU-induced leukopenia was reversed for several weeks after the administration of oral uridine. However, thrombocytopenia was not reversed. Side effects of the combined treatment consisted of mild diarrhea in five of the seven patients.


CONCLUSIONS
These data indicate that oral uridine can reduce the severity of 5-FU-induced myelosuppression.
Department of Medical Oncology, Free University Hospital, Amsterdam, The Netherlands.
C J
CJ
van Groeningen
G J
GJ
Peters
H M
HM
Pinedo
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D004359:Drug Therapy, Combination; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects* / Q000037:antagonists & inhibitors; D006801:Humans; D007970:Leukopenia / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D013921:Thrombocytopenia / Q000139:chemically induced / Q000517:prevention & control*; D014529:Uridine / Q000008:administration & dosage* / Q000009:adverse effects
D005472:Fluorouracil; D014529:Uridine