Phase I and Pharmacological Study of Vinblastine by Prolonged Continuous Infusion

摘要: Vinblastine is an antimitotic plant alkaloid with elimination half-life of about 24 h. The cytotoxicity vinblastine against solid tumor cell lines in vitro markedly increased prolonged exposure. Therefore, patients advanced malignancy were treated a continuous i.v. infusion given via implantable pump. received for median 12 wk (range, 2 to 36 wk), at dosages ranging from 0.5 0.9 mg/m2/day. steady-state serum concentration (VLBss) was determined 2- 3-wk intervals each patient correlation toxicity. dose-limiting toxicity leukopenia nine and peripheral neuropathy one patient. Thirteen developed progressive disease prior reaching toxicity, withdrew the study because severe local injection site. There only mild rates ≤0.65 mg/m2/day, but no dosage did reproducible occur. maximum VLBss significantly higher those than nontoxic (1.91 versus 1.00 ng/ml; P = 0.001), there significant difference between two groups (0.76 0.74 mg/m2/day). Our results demonstrate that infusions are feasible, achieving >1 ng/ml, drug which cytotoxic . recommended starting dose Phase II studies 0.7 adjustments every 4 based on white blood count VLBss. Prospective monitoring VLBss, adjustment maintain <1.5 2.0 may avoid unexpected occurrence myelosuppression.