A phase I clinical-pharmacodynamic study of the farnesyltransferase inhibitor tipifarnib in combination with the proteasome inhibitor bortezomib in advanced acute leukemias.

ABSTRACT:

Purpose

To determine the safety, target inhibition, and signals of clinical activity of tipifarnib in combination with bortezomib in patients with advanced acute leukemias.

Experimental design

In a "3 + 3" design, patients received escalating doses of tipifarnib (days 1-14) and bortezomib (days 1, 4, 8, 11) every 3 weeks until maximum tolerated dose was reached. Peripheral blood mononuclear cells (PBMC) were collected at days 1, 8, and 22 for measurement of chymotrypsin-like and farnesyltransferase activity. Purified bone marrow leukemic blasts were collected at baseline and at day 8 for measurement of NF-κB activity.

Results

The combination was well-tolerated, and maximum tolerated dose was not reached. Dose-limiting toxicities included diarrhea, fatigue, and sensori

SUBMITTER: Lancet JE 

PROVIDER: S-EPMC3049960 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature