Phase I study of panobinostat and imatinib in patients with treatment-refractory metastatic gastrointestinal stromal tumors.

ABSTRACT:

Background

Panobinostat, a pan-deacetylase inhibitor, overcomes imatinib resistance in preclinical models of gastrointestinal stromal tumours (GIST). Here we determined the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT) of panobinostat in combination with imatinib (IM) for treatment of patients with refractory GIST.

Methods

Following a 7-day run-in phase of IM (400 mg per day), escalating doses of panobinostat were added following a '3 plus 3' design. Twelve heavily pretreated GIST patients were enrolled in two dose levels.

Results

Most common adverse events were thrombocytopenia, anaemia, fatigue, creatinine elevation, nausea, emesis and diarrhoea. Twenty micrograms of panobinostat and 400 mg IM were declared the MTD. Pharmacologically active concent

SUBMITTER: Bauer S 

PROVIDER: S-EPMC3950855 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature