Clinical pharmacologic effects of thymidine plus 5-FU.
Ten patients with advanced cancer were given 24 courses of thymidine (TdR) plus 5-FU. In the initial part of the study, TdR was given by continuous infusion at a dose of 8 g/m2/24 hrs x 5 days, and 5-FU was given as an iv bolus daily x 5. During the continuous TdR infusion, TdR serum levels ranged from 10(-6) to 10(-5) M, and thymine serum levels ranged from 10(-5) to 10(-4) M. 5-FU serum decay on Day 1 was rapid, and serum decay on Day 5 was slightly prolonged in two of three patients studied. The optimal dose of 5-FU with continuous infusion of TdR seemed to be between 200 and 400 mg/m2 daily x 5 in heavily pretreated patients. In the second part of the study, rapid infusion of TdR at a dose of 8 g/m2/2 1/2 hrs followed by 5-FU resulted in markedly prolonged 5-FU serum decay (initial serum half-life, approximately 240 mins) and definite increase in clinical toxicity. The dose-limiting toxic effect of both schedules was myelosuppression. Administration of TdR in one tenth of 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.
D000328:Adult; D004334:Drug Administration Schedule; D004341:Drug Evaluation; D004359:Drug Therapy, Combination; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D006801:Humans; D007958:Leukocyte Count / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D010976:Platelet Count / Q000187:drug effects; D013936:Thymidine / Q000008:administration & dosage* / Q000097:blood; D013941:Thymine / Q000097:blood; D013997:Time Factors
D013941:Thymine; D005472:Fluorouracil; D013936:Thymidine