A dose-finding, pharmacokinetic and pharmacodynamic study of a novel schedule of flavopiridol in patients with advanced solid tumors.

ABSTRACT:

Purpose

Based on the promising activity and tolerability of flavopiridol administered with a pharmacokinetically-derived dosing schedule in chronic lymphocytic leukemia (CLL), we conducted a phase I study using this schedule in patients with advanced solid tumors.

Experimental design

Flavopiridol was given IV as a 30-min loading dose followed by a 4-hr infusion weekly for 4 weeks repeated every 6 weeks. Dose-escalation was in cohorts of three patients using the standard 3+3 phase I study design. Blood samples were obtained for pharmacokinetic and pharmacodynamic studies.

Results

Thirty-four eligible patients with advanced solid tumors received a total of 208 doses (median 7, range 1-24). Total doses ranged from 40 to 105 mg/m(2). The primary dose limiting toxicity was

SUBMITTER: Ramaswamy B 

PROVIDER: S-EPMC3486515 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature