Jackson D V, Sethi V S, Spurr C L, White D R, Richards F, Stuart J J, Muss H B, Cooper M R, Castle M C
Cancer Treat Rep. 1981 Nov-Dec;65(11-12):1043-8.
Using a sensitive radioimmunoassay, serial blood concentrations of vincristine were measured in 11 patients with refractory malignancies receiving infusions of vincristine at three dose levels: 0.5, 0.75, and 1.0 mg/m2 daily for 5 days. The pharmacokinetics of vincristine infusion were compared to pharmacologic data obtained from four patients who received conventional iv bolus injections of 2 mg of vincristine. Whereas rapid decline of blood levels was seen following iv bolus injection, with concentrations of vincristine approaching 10(-9) M by 48-72 hours, vincristine infusions of 0.5, 0.75, and 1.0 mg/m2 daily for 5 days consistently resulted in blood concentrations greater than 10(-9) M during the treatment period. Similarly, areas under the concentration curve were greater in patients receiving infusions compared to bolus injections of vincristine. Antitumor responses in patients receiving vincristine infusions were observed after failure to respond to iv bolus injections. These data demonstrate the ability of infusion therapy to sustain blood concentrations of vincristine in man beyond that seen with conventional administration and suggest the possibility of improved therapeutic efficacy with this agent by use of infusion techniques.
