A phase 1 dose-escalation study of irinotecan in combination with 17-allylamino-17-demethoxygeldanamycin in patients with solid tumors.

ABSTRACT:

Purpose

Both heat shock protein 90 (Hsp90) and checkpoint kinase 1 (Chk1) have emerged as novel therapeutic targets. We conducted a phase I study of irinotecan and the Hsp90 inhibitor 17AAG, which can also down-regulate Chk1, in patients with solid tumors.

Experimental design

During the dose escalation phase, patients received i.v. irinotecan followed by 17AAG once weekly for 2 weeks in a 21-day cycle. At the maximum tolerated dose (MTD), additional patients were enrolled to undergo pre- and post-17AAG tumor biopsies for pharmacodynamic evaluation. The pharmacokinetics of irinotecan, 17AAG, and their metabolites were characterized. Tumor p53 status as determined by immunohistochemistry was correlated with antitumor activity.

Results

Twenty-seven patients with a variet

SUBMITTER: Tse AN 

PROVIDER: S-EPMC3996559 | biostudies-literature | 2008 Oct

REPOSITORIES: biostudies-literature