Drug Detail

Information about Gleevec

Generic Name
Imatinib + Midostaurin
Imatinib + PKC412
Brand Name (US)
Drug Type
Tyrosine Kinase Inhibitor
Approval Status
Gleevec is approved for GIST. This combination was evaluated in a phase 1/2 trial for GIST.
GIST, CML, others
Overall Strategy
KIT Protein Based + Oncogenic Signal Path Based
Block KIT + Block related tumor signal paths
Drug Category
KIT/PDGFRA inhibitor

A phase I/II trial testing this combination has completed. Drug interactions appeared to be a concern.
Nineteen patients were given 200 mg. per day of PKC combined with Gleevec at doses ranging from 600 mg. to 1000 mg. Using this combination, Gleevec exposure (blood concentrations) decreased ~70 percent after one month on the combination, either due to enzyme induction (liver enzymes metabolize Gleevec), or protein binding interactions.
At the same time, PKC levels increased ~twofold by day 28 over those that were expected from previous studies of PKC alone in AML. The study was therefore amended to allow for dose escalation of Gleevec and temporary dose reduction of PKC. This resulted in reduced toxicity and increased levels of Gleevec in the blood equal to 600 mg. of Gleevec alone.
Two of five patients evaluable for response had stable disease at four months.