Pharmacokinetics and toxicity of continuous infusion (6S)-folinic acid and bolus 5-fluorouracil in patients with advanced cancer.

摘要: Twenty-seven patients with advanced cancer were entered in a phase I study of bolus i.v. 5-fluorouracil at dose 370 mg/m2/day for 5 days combined continuous infusion (6 S )-folinic acid 5.5 days, starting 24 h advance the first dose. The was escalated cohorts from 250 to maximum 1000 mg/m2/day. pharmacokinetics studied 3 given and 6 mean steady-state plasma concentrations its principal metabolite )-5-methyltetrahydrofolate 2.7 5.1 µm, respectively. Both comparable produced when administered as half R,S mixture (E. M. Newman et al. , Cancer Res., 49: 5755–5760, 1989). At acid, concentration 15.3 more than 4-fold increase predicted by linear pharmacokinetics, while only 16.5 µm. change ratio parent compound accounted decrease nonrenal clearance probably indicating saturation metabolism. toxicities observed this trial, including stomatitis, diarrhea, neutropenia, anemia, did not differ nature or severity those on same schedule. Finally, degree toxicity appear depend over range doses tested.