Blood Brain Barrier Penetration on EGFR mutant patients - 1266921

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njliu
Blood Brain Barrier Penetration on EGFR mutant patients - 1266921

I have read that Tarceva and Iressa as well as Chemo drugs in general do not have significant enough penetration into the CNS. However, I would appreciate some updates if the followings have good efficacy in the brain :
1. Alimta and/or Avastin,
2. 2nd generation TKI, Afatinib in conjunction with Cetuximab.
3. 3rd generation TKI's like CO-1686 and AZD9291.
3. Immunotherapy like Anti PD-1 and Anti PDL-1.
Thank you.
NJ

JimC
Hi NJ,

Hi NJ,

Regarding the ability of chemo to penetrate the blood brain barrier, Dr. West has said:

“It’s not very well studied, but the idea that chemotherapy can’t get into the brain because of the blood-brain barrier is oversimplified. There’s actually evidence that the response rate of metastases in the brain is in the same ballpark as that of measured disease outside of the brain:

http://cancergrace.org/lung/2007/10/24/chemo-for-brain-mets/

There have been some vague hints that Alimta (pemetrexed) and Camptosar (irinotecan) may be particularly effective for brain metastases, but frankly I’d say that the amount and quality of that evidence isn’t enough for me to be at all inclined to make clinical decisions on the basis of that work. There’s really no meaningful work to suggest that one lung cancer treatment is significantly more effective against brain metastases compared with others.” – http://cancergrace.org/forums/index.php?topic=11255.msg92631#msg92631

Dr. West also stated:

"Some chemo agents, ranging from Temodar (temazolamide), Camptosar (irinotecan), and Alimta (pemetrexed) have all had a few reports of inducing responses in the brain more commonly than some others, but that's pretty scant evidence, frankly. If there were a situation in which I think there would be more hope for pulsed Tarceva (erlotinib) to treat disease in the central nervous system, it would be in someone with an activating EGFR mutation, but especially in someone who has already been on Tarceva, we just don't know." - http://cancergrace.org/forums/index.php?topic=9788.msg77732#msg77732

Most recently, Dr. West confirmed his previous statements and said: "the only other thing I’d add is that Avastin (bevacizumab) is not generally recommended for people with untreated and/or symptomatic brain metastases from lung cancer." - http://cancergrace.org/topic/chemos-that-can-cross-the-blood-brain-barri...

JimC
Forum moderator

<p>I began visiting GRACE in July, 2008 when my wife Liz was diagnosed with lung cancer, and became a forum moderator in January, 2010. My beloved wife of 30 years passed away Nov. 4, 2011 after battling stage IV lung cancer for 3 years and 4 months</p>

njliu
Hi Jim, thanks. That

Hi Jim, thanks. That clarifies the role of chemo drugs in this setting. Any idea if the new generation TKIs like Afatinib in combination with Cetuximab, CO1686 or AZD9291, as well as Anti PD1/PDL1 hold better promise?
NJ

catdander
So far all the combos have

So far all the combos have shown cancer eventually able to workaround the defenses. There's not enough data yet to say what the other combos are able to provide.

Dr West
Unknown/unpublished

Unknown/unpublished/unreported, on all fronts. None of these approaches is being advertised as a treatment for disease in the CNS.

-Dr. West

+++++++++++++++++++++++++
Dr. Howard (Jack) West
Associate Clinical Professor
Medical Oncology
City of Hope Cancer Center
Duarte, CA

Founder & President
Global Resource for Advancing
Cancer Education