A phase I dose-escalation study of danusertib (PHA-739358) administered as a 24-hour infusion with and without granulocyte colony-stimulating factor in a 14-day cycle in patients with advanced solid tumors.

ABSTRACT:

Purpose

This study was conducted to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of the i.v. pan-aurora kinase inhibitor PHA-739358, danusertib, in patients with advanced solid tumors.

Experimental design

In part 1, patients received escalating doses of danusertib (24-hour infusion every 14 days) without filgrastim (granulocyte colony-stimulating factor, G-CSF). Febrile neutropenia was the dose-limiting toxicity without G-CSF. Further dose escalation was done in part 2 with G-CSF. Blood samples were collected for danusertib pharmacokinetics and pharmacodynamics. Skin biopsies were collected to assess histone H3 phosphorylation (pH3).

Results

Fifty-six patients were treated, 40 in part 1 and 16 in part 2. Febrile neutropenia was the dose-limi

SUBMITTER: Cohen RB 

PROVIDER: S-EPMC2826106 | biostudies-literature | 2009 Nov

REPOSITORIES: biostudies-literature