CLINICAL PHARMACOLOGIC EFFECTS OF THYMIDINE PLUS 5-FU

  • 1 January 1980
    • journal article
    • research article
    • Vol. 64  (12) , 1169-1177
Abstract
Ten patients with advanced cancer were given 24 courses of thymidine (TdR) plus 5-FU [5-fluoruracil]. In the initial part of the study, TdR was given by continuous infusion at a dose of 8 g/m2 every 24 h .times. 5 days, 5-FU was given as an i.v. bolus daily .times. 5. During the continuous TdR infusion, TdR serum levels ranged from 10-6 to 10-5 M; thymine serum levels ranged from 10-5 to 10-4 M. 5-FU serum decay on Day 1 was rapid; serum decay on Day 5 was slightly prolonged in 2 of 3 patients studied. The optimal dose of 5-FU was continuous infusion of TdR seemed to be between 200 and 400 mg/m2 daily .times. 5 in heavily pretreated patients. Rapid infusion of TdR at a dose of 8 g/m2 every 2 1/2 h followed by 5-FU resulted in markedly prolonged 5-FU serum decay (initial serum half-life, .apprx. 240 min) and definite increase in clinical toxicity. The dose-limiting toxic effect of both schedules was myelosuppression. Administration of TdR in 1/10 the initial infusion time resulted in a nearly 100-fold increase in peak TdR levels. Thymine was the major metabolite of TdR. 5-FU did not influence TdR blood levels. The protracted 5-FU serum decay appears to account at least in part for the increased toxicity of 5-FU when administered following TdR.