Increasing the dosage of vincristine: a clinical and pharmacokinetic study of continuous-infusion vincristine in children with central nervous system tumors

摘要

BACKGROUND: Vincristine (VCR) is widely used to treat patients with malignant disease; among the patients treated with VCR are children with brain tumors. In vitro studies have demonstrated that the cytotoxic activity of VCR is related to both extracellular concentration and duration of exposure. The attainment of higher plasma concentrations by injecting larger bolus doses of VCR has been limited by concerns about neurotoxicity. One possible alternative strategy for enhancing the antitumor efficacy of VCR involves prolonging the duration of in vivo exposure. Therefore, the authors explored the neurotoxicity and pharmacokinetics of VCR administered via a 96hour continuous infusion after administration of a conventional bolus dose in a pediatric population. METHODS: The current study included 16 patients, 11 of whom were males. The median age of the study population was 4. 8 years (range, 1.7-15. 8 years).