A Phase 1 study of UCN-01 in combination with irinotecan in patients with resistant solid tumor malignancies.

ABSTRACT:

Purpose

UCN-01 (7-hydroxystaurosporine) is a multi-targeted protein kinase inhibitor that exhibits synergistic activity with DNA-damaging agents in preclinical studies. We conducted a Phase I study to determine the maximum-tolerated dose (MTD), dose-limiting toxicity (DLT), pharmacokinetic, and pharmacodynamic effects of UCN-01 and irinotecan in patients with resistant solid tumors.

Experimental design

Patients received irinotecan (75-125 mg/m(2) IV on days 1, 8, 15, 22) and UCN-01 (50-90 mg/m(2) IV on day 2 and 25-45 mg/m(2) on day 23 and subsequent doses) every 42 days. Blood for pharmacokinetics of UCN-01 and irinotecan, and blood, normal rectal mucosa, and tumor biopsies for pharmacodynamic studies were obtained.

Results

Twenty-five patients enrolled to 5 dose lev

SUBMITTER: Fracasso PM 

PROVIDER: S-EPMC3102212 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature