Phase I trial of BCL-2 antisense oligonucleotide (G3139) administered by continuous intravenous infusion in patients with advanced cancer.
Academic Article
Overview
abstract
PURPOSE: To evaluate the safety and pharmacokinetics of BCL-2 antisense oligonucleotide (G3139) administered by prolonged i.v. infusion in patients with advanced cancer. EXPERIMENTAL DESIGN: A total of 35 patients was treated in cohorts of 3-6 with 0.6-6.9 mg/kg/day of BCL-2 antisense oligonucleotide as a continuous infusion for 14 or 21 days. Plasma levels of intact antisense oligonucleotide were measured in all patients. RESULTS: G3139 was generally well tolerated. At the highest dose level examined in this study (6.9 mg/kg/day), fatigue and transient reversible elevations of serum transaminases (grades 2-3) became apparent after >or=7 days of treatment. Both reactions were believed to be drug related. Pharmacokinetic analyses showed that steady-state plasma concentrations of G3139 were reached approximately 10 h after starting the infusion and increased linearly across the range of doses administered
