Pharmacokinetics and safety of bortezomib in patients with advanced malignancies and varying degrees of liver dysfunction: phase I NCI Organ Dysfunction Working Group Study NCI-6432.

ABSTRACT:

Purpose

The proteasome inhibitor bortezomib undergoes oxidative hepatic metabolism. This study (NCI-6432; NCT00091117) was conducted to evaluate bortezomib pharmacokinetics and safety in patients with varying degrees of hepatic impairment, to inform dosing recommendations in these special populations.

Experimental design

Patients received bortezomib on days 1, 4, 8, and 11 of 21-day cycles. Patients were assigned to four hepatic function groups based on the National Cancer Institute Organ Dysfunction Working Group classification. Those with normal function received bortezomib at the 1.3 mg/m(2) standard dose. Patients with severe, moderate, and mild impairment received escalating doses from 0.5, 0.7, and 1.0 mg/m(2), respectively, up to a 1.3 mg/m(2) maximum. Serial blood sa

SUBMITTER: LoRusso PM 

PROVIDER: S-EPMC3834726 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature