I just came across this on BCMETS:
My understanding is that there are 3 or 4 criteria that a drug must meet in order to have a good chance to successfully cross the barrier-1 of these is that its molecular weight be less than approximately 400 Daltons (IE--small molecule drug). This is not a
number set in stone but a guideline.
Herceptin, for example, is about 140,000 Daltons, and obviously much too large to cross the BBB. Avastin is about the same size.
As far as chemos go: Temodar is under 200. Gemzar is under 300 I believe, and Xeloda is about 390.
As for molecular drugs: Tarceva, Iressa, CO-501, are all around 400 or 500. GW572016 (lapatinib) is over 900
Others include Thalidomide, which is below 300 I
think. This may have angiogenesis effects and is in some trials in combination with Temodar. There is also RSR13, which is given generally in combination with whole brain radiation.
Dr Eric Winer at Dana Farber in Boston will be
starting a trial for brain mets from breast cancer in a few weeks. His trial will look at the efficacy of GW572016 on brain mets for patients who have been on Herceptin and have contained disease mostly everywhere but the brain.
There are other ways to approach brain mets. Some of which are:
1) osmotic (sp?) BBB disruption. Administration of a sugar-based solution "opens" the BBB for about 30
minutes, during which time a drug, ie chemo, is
administered. I belive the Cleveland Clinic is
involved with these trials.
2) Convection Enhanced Delivery (haven't found too
much about this)
3) There are some new approaches being researched, of
these are:
a) Molecular trojan horse (dr william pardridge, professor at UCLA and head of Armagen--"the blood brain barrier company" is leading this)
B) Gate opening/channel approach--doctor Keith
Black at Cedars Sinai's Maxine Durinz (sp??) center is leading this.
You can read about these approaches by going to
www.abc2.org, click on "what's new" and you can read up on these approaches under Vol.1, No.2, 2004 -
"Outwitting vascular barriers to effective drug
delivery"
There are other issues. Even if you can get a drug through the barrier, the drug must still (i) achieve sufficient disbursement within the brain, and (ii) be effective against your particular pathology.
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