PHASE-I EVALUATION AND PHARMACOKINETIC STUDY OF WEEKLY IV THYMIDINE AND 5-FU IN PATIENTS WITH ADVANCED COLORECTAL-CARCINOMA

  • 1 January 1985
    • journal article
    • research article
    • Vol. 69  (2) , 179-184
Abstract
A phase I study of weekly i.v. thymidine (TdR) and 5-FU [5-fluorouracil] was carried out in patients with advanced colorectal carcinoma using 2 dosage schedules. Schedule 1 employed a 3-h infusion of TdR (6-8 g/m2 per h) followed immediately by a bolus of 5-FU (100-200 mg/m2). Schedule 2 used a slightly larger dose of TdR (18 g/m2 per h for 1.5 h), with 5-FU given 30 min after the TdR infusion was started. Myelosuppression was observed erratically at the higher doses of 5-FU. Diarrhea and severe fatigue were seen frequently with Schedule 1. CNS effects were the dose-limiting effects for both schedules. For long-term use the maximally tolerated 5-FU doses were 100 mg/m2 per wk for Schedule 1 and 175 mg/m2 per wk for Schedule 2. In pharmacokinetic studies in 5 patients, both schedules produced prolonged plasma .beta.-half-lives of 5-FU (96-189 min). Extensive formation of floxuridine was seen with both schedules. It appears that CNS toxic effects are characteristic of TdR-containing 5-FU regimens and would limit the therapeutic potential of this approach.