A phase I study of PF-04929113 (SNX-5422), an orally bioavailable heat shock protein 90 inhibitor, in patients with refractory solid tumor malignancies and lymphomas.

ABSTRACT:

Purpose

To determine the maximum tolerated dose (MTD), toxicities, and pharmacokinetic/pharmacodynamic profile of the Hsp90 inhibitor PF-04929113 (SNX-5422) in patients with advanced solid tumors and lymphomas.

Methods

This was a single-institution, phase I, dose-escalation study of PF-04929113 administered twice weekly. Endpoints included determination of dose-limiting toxicities (DLT), MTD, the safety profile of PF-04929113, pharmacodynamic assessment of PF-04929113 on Hsp70 induction, pharmacokinetic analysis of PF-04928473 (SNX-2112) and its prodrug PF-04929113, and assessment of response.

Results

Thirty-three patients with advanced malignancies were treated. Dose escalation was continued up to 177 mg/m(2) administered orally twice a week. One DLT (nonseptic arthr

SUBMITTER: Rajan A 

PROVIDER: S-EPMC3207004 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature