Larry...did you see this??

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.

Patty,

Thanks. I will do some further research on some of the things you mentioned. I'm sure they will come up with some ways to deliver drugs to the brain or drugs that are small enough molecules to get through the barrier at some point in the future. Unfortunately for my wife and I it will be too late.

As for Thalidomide, we did look into getting Barb into a clinical trial at Moffitt Cancer Center in Tampa where they were using Temodar and Thalidomide in combination but the Thalidomide dose was so large that it was scary. So I asked her medical onc's opinion and he said "Oh my god, that will kill her or damage her significantly within a week or will make her a zombie, it will be a nightmare!" Everyone should always evaluate any clinical trial very carefully even though it is sponsored by a major and respected cancer center, no matter how desparate you may be at the time. So we opted for the Temodar treatments only without the Thalidomide. When you get to the end stages the quality of life becomes a major issue even if you were willing to put up with a lot of side-effects as you were fighting or struggling with the cancer.

Thanks again for the info.

Larry

ok....

I didn't write that myself, not that smart ) It is from a brother of a gal with brain mets.

I was excited for a minute when I posted, thinking one of those bits might be of help. It is me in denial of what you have so eloquently written of your wife's aggressive disease....

But I really should have known you have researched and looked at possibilites until exausted and ultimately left with so little hope.

You also expressed beautifully the difference between the quality of life issues as opposed to aggressive treatment choices, disease progression and time wise.

Thank you for always taking YOUR precious time to communicate so deeply and thoroughly.

Warmest regards and appreciation,
pattyz