Selumetinib and brain mets - 1262526

Hello,

I couldn't find a specific reference to it crossing the blood-brain barrier, but there are at least three trials listed on clinicaltrials.gov that are testing it in children with gliomas, so there must be a thought that it does cross the barrier. As a small molecule drug, it is somewhat more likely to do so, although often the problem is whether the concentration of a drug which reaches the cancer cells in the brain is high enough to be effective. That is the theory behind pulsed Tarceva - trying to increase the amount that gets to the cancer cells in the brain. If only ten percent of the drug crosses the barrier, then it is thought that a higher dosage is the way to get an effective amount through.

JImC
Forum moderator

I'm sorry that I don't have any further information. These drugs are all pretty new, and I think there's very little experience to guide any expectations here. As a practical matter, untreated and/or symptomatic brain metastases are usually an exclusion criterion for clinical trials in lung cancer (except those specifically looking at treatment of brain metastases), so I suspect it may be necessary to treat brain metastases with radiation before it would be feasible to enroll on a trial of a MEK inhibitor. In addition, they would not allow for different dosing and schedules for it, so it wouldn't be possible to just try "pulsed" treatment instead of the prescribed daily dose in the protocol.

Good luck.

-Dr. West

This class of drugs, like selumetinib, does not penetrate the brain tissue under normal conditions at regular doses. They are actively prevented from entering the brain by transport proteins. As Dr West says, most clinical trials will want your brain metastases controlled first before enrollment.