chemo and Blood Brain Barrier (BBB)

Portal Forums Lung/Thoracic Cancer Lung Cancer Complications Brain Metastases chemo and Blood Brain Barrier (BBB)

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December 3, 2012 at 1:45 pm  #1250910    

slimer

From my reading, it appears that the oncological/hemotological world still does not know if chemos, particularly small molecule chemos like Alimta and Gemzar, pass the BBB to combat brain mets. Are autopsies not done on lung cancer patients? Can’t an autopsy and chemical analysis of the brain reveal whether or not a chemo passes the BBB? What about all those who die during clinical trials, are they not autopsied to find out the role of chemo in the death, and to examine the brain and BBB to see if the chemo passed through? Why can’t this question be answered definitively at this point of cancer research? When someone dies suspiciously and drugs are suspected, an autopsy is ordered by law enforcement authorities. And most of the time they get definitive answers. Is this not done when chemos are in clinical trials, or on those patients being followed for OS statistics later die? What am I missing here? When my mother died of cancer, clearly of cancer, her HMO still asked if we wanted an autopsy.

December 3, 2012 at 2:50 pm  #1250915    

Dr West

First, actually autopsies are not generally done for someone who died of a progressing cancer. It’s a reasonable thing to do, but most often, it isn’t a major mystery when someone with a known cancer dies — it certainly doesn’t tend to qualify as a suspicious case. So autopsies of cancer patients are rare, and they’re actually not done very often in general in our health care system compared to the past, in part because I don’t think they’re routinely paid for and are quite time consuming for pathologists (though I’ve heard pathologists say that you can learn a lot from the exercise).

Second, the question you ask is one that is not really relevant to the question of why a person died, but it’s more of a research question. That means that it really only makes sense to evaluate the question in people who have been treated in a uniform way, such as all being lung cancer patients who receive gemcitabine and then die within a short time of their last chemo infusion. In fact, today it’s considered to be an indicator of poor quality care to have a patient with cancer receiving chemotherapy within their last few weeks of life, when it’s far more likely to be harmful than helpful for them.

So yes, we still don’t know as much as we’d like to about penetration of chemo drugs in the central nervous sytem, but that would really need to be studied in a dedicated trial and not just hoping to glean useful information from the tiny subset of very heterogeneous people with cancer who have an autopsy.

-Dr. West


Howard (Jack) West, MD
Medical Oncologist

Views expressed here represent my opinion, not those of GRACE or Swedish Cancer Institute. This information does not constitute medical advice and is intended to supplement and not replace medical information provided by your doctor.

December 3, 2012 at 4:22 pm  #1250922    

slimer

Thanks for the prompt reply, Dr. West.

If you had a patient who is NED and then develops brain mets (does happen), receives, let’s say, Gammaknife treatment for them, would you recommend adjuvant therapy, and if so, which chemos would you choose among since the question of BBB penetration has not yet been answered definitively through clinical trial and autopsy?

December 3, 2012 at 6:31 pm  #1250927    

cards7up

When my mom passed of ext SCLC in 2009, they did ask us if we wanted an autopsy and we refused knowing it was the cancer that killed her. I’ll be donating my body to our medical school when I pass hoping it might help someone else down the line. They then cremate you and return the cremains to your family and this is at their expense. This might be something you could check into if you’re interested.

Dr. West, are you aware of any clinical trials using chemo to treat brain mets?

Take care, Judy


Stage IIIA adeno, dx 7/2010. SRS then chemo carbo/alimta 4x. NED as of 10/2011. Local recurrence, surgery to remove LRL 8/29/13. Chemo carbo/alimta x3.

December 3, 2012 at 8:12 pm  #1250931    

Dr West

I’m not aware of clinical trials to treat brain metastases.

I don’t know that it can really be called adjuvant therapy in the setting of known brain metastases. I’d likely favor the treatment approach that I would also use in the setting of adjuvant therapy, which is a combination of cisplatin/Alimta (pemetrexed) for an adenocarcinoma, or cisplatin/gemcitabine for a squamous NSCLC. And I don’t think we know enough about penetration into the CNS to customize the chemo on the basis of this question.

Importantly, though, knowing that gamma knife leaves a much higher risk of future brain metastases, I would say that gamma knife alone isn’t the most definitive treatment for brain metastases. If we’re going for an aggressive approach and even talking about the potential for cure, I tend to favor whole brain radiation (WBR) in someone with brain metastases, since I’d really think of this as the highest risk setting to suggest a potential value of something akin to prophylactic cranial irradiation (PCI). I don’t see a lot of value in aggressively treating the rest of the body if you’re going to undertreat the brain. I’d be far more confident about PCI/WBR being effective against future brain metastases than I would be about chemotherapy serving in that capacity.

-Dr. West


Howard (Jack) West, MD
Medical Oncologist

Views expressed here represent my opinion, not those of GRACE or Swedish Cancer Institute. This information does not constitute medical advice and is intended to supplement and not replace medical information provided by your doctor.

December 3, 2012 at 11:15 pm  #1250939    

slimer

Thank you Dr. West for your strategically expansive yet concise response. Very informative.

December 4, 2012 at 6:52 pm  #1250964    

Dr West

I actually just saw a patient today who is newly diagnosed with an advanced lung adenocarcinoma, multiple brain metastases, and has an EGFR mutation. Given the risk for cognitive side effects, particularly over a longer term, the pretty good probability that she’ll respond to the Tarceva (erlotinib) I’m starting on her, including in the brain, and the significant chance that someone with a driver mutation will do well for a very long time, my inclination was to start with the Tarceva. We can use WBR as the fall-back option if she doesn’t show convincing symptomatic improvement of her neurologic symptoms (arm numbness and weakness) quickly.

I did a brief video discussion about this topic earlier today, and it should be posted on the GRACE site in the next day or two.

-Dr. West


Howard (Jack) West, MD
Medical Oncologist

Views expressed here represent my opinion, not those of GRACE or Swedish Cancer Institute. This information does not constitute medical advice and is intended to supplement and not replace medical information provided by your doctor.

December 6, 2012 at 1:39 am  #1250988    

certain spring

Good luck to your patient, Dr West. It’s frightening to be in her position. When I argue with you about first-line Tarceva vs chemotherapy, this is the kind of scenario I have in mind.


49-year-old non-smoker, dx stage IV NSCLC May 2010 (squamous tumour of the left lung with multiple brain metastases). Radiotherapy to chest and brain; progressed through two cycles carbo/gemcitabine. Repeated lung collapses; pneumonia in collapsed lung, Nov 2010; bronchial stent placed, Dec 2010. Declined second-line Taxotere. Mutation testing Feb 2011, surprise EGFR exon deletion 19. Started Tarceva (150mg), Feb 2011. Progression in liver and elsewhere, May 2013.

December 6, 2012 at 12:38 pm  #1250998    

Dr West

Will try to remember to update as we see how things go.

One concern is the delay that often intervenes as an insurer drags its feet on providing Tarceva. We routinely expect a 1-2 week interval while the insurer sends forms and dithers, and that’s getting into a range where we’d really rather have someone on treatment. Often WBR can be initiated within a day or two after brain metastases being identified…

-Dr. West


Howard (Jack) West, MD
Medical Oncologist

Views expressed here represent my opinion, not those of GRACE or Swedish Cancer Institute. This information does not constitute medical advice and is intended to supplement and not replace medical information provided by your doctor.

December 6, 2012 at 3:55 pm  #1251011    

certain spring

Well, there are many things wrong with the NHS, but once my oncologist got the EGFR test result, she had me on Tarceva within a matter of days. She had to get permission from the local health trust to prescribe such an expensive drug, but that was it. When I read about what people have to go through – like aunttootsie with her crizotinib delays – I realise how lucky I have been. I suppose every healthcare system has its own advantages and its own flaws.


49-year-old non-smoker, dx stage IV NSCLC May 2010 (squamous tumour of the left lung with multiple brain metastases). Radiotherapy to chest and brain; progressed through two cycles carbo/gemcitabine. Repeated lung collapses; pneumonia in collapsed lung, Nov 2010; bronchial stent placed, Dec 2010. Declined second-line Taxotere. Mutation testing Feb 2011, surprise EGFR exon deletion 19. Started Tarceva (150mg), Feb 2011. Progression in liver and elsewhere, May 2013.

December 6, 2012 at 4:54 pm  #1251017    

slimer

This is sort of off the subject, but I have been a fan of the NHS ever since my wife and I found ourselves freezing in Manchester around Xmas about 20 years ago. My wife had a high fever, flushed face and sweating, and felt very weak. I asked a woman in the street if she knew where a hospital was. She said there is a GP right around the corner, and took us there. I had no idea what a GP was. It turned out it was a medical office tucked in among apartment bldgs.

When we entered there were 4 women waiting, and I said to myself, Oh no, a long wait. One of the women said to my wife, dear you look like you are suffering so, you go in first, and the other women nodded. The Dr. saw her, took care of her, and sent us off with a bottle labled “the Elixir” whose mysterious contents cured her within two days. I asked what I owed and the Dr. said “nothing, you are guests in our country and under the care of the NHS.” Wow, can you imagine such a civilized medical experience happening anywhere in the USA! I hope the NHS’s neighborhood GPs still exist.

December 6, 2012 at 9:44 pm  #1251019    

catdander forum moderator

Imagine? Why yes I can, John Lennon taught me that. That wild hopeful Brit.

Certain Spring, yes I suppose we do have good and bad in both systems. I really enjoy reading about and learning when different healthcare systems work well. As they do mostly.

I wish the US healthcare system didn’t cost so much more without adding anything to our healthcare. I’m just breathing a sigh of relief that I can count on being able to continue to buy my pre existing illness insurance through the new US healthcare act. My story isn’t anything special, I’ve always had health insurance but when I lost my job of 12 years, (11 months ago), I found myself unable to buy individual care. Ridiculous!

There you go slimer I really went off subject. :evil: I get my buttons pushed sometimes and it appears it just happened.

Hope and Imagine, It’s the impetus of innovation and change.


My husband, 53 @ dx of stage 3 squam nsclc R. pancoast tumor 8/09 caused destruction of 3 ribs, touching brachial plexus. 2 core and 1 VATS undx biopsies. Open thoracotomy for 1 positive biopsy (unresectable). Chemorads, 9/09. MRI by pancoast specialty surgeon 11/09 spine met found, stage IV, Rad to spine, Chemo changed from cis/etop to navelbine/carbo. 6 cycles total. Tarceva 2/10-11/10. 3cm tumor L lung, biopsy undx w/collapsed lung. Gemzar, 12/10 through 7/12. NED 3/12, stop tx 7/12. Remains NED as of 8/14.

December 6, 2012 at 10:10 pm  #1251023    

Jazz

Janine,
On the eve of the deadline to make Medicare decisions, I’ve just realized I’ll never be able to get Medigap insurance because I chose to continue with an individual plan that my husband’s employer paid for at the time I became eligible for Medicare. Now that he’s self-employed, I’m stuck with an astronomical premium… I feel your pain!

Anyway, sorry for the off-topic outburst. Wonderful story, Slimer. I was not aware that any of the traditional chemos crossed the BBB, although I vaguely recall something about Alimta having some possible connection to preventing or delaying brain mets.

Jazz


Non-smoker, Dx 6/06 Stage IV Adeno. EGFR+ (exon 19 del), T790m+. Trial: 2cyc Carbo/Doce/Avastin + 2 w/Gem 8 – 12/06; Avastin maint. 1 – 4/07. Alimta + Tarceva 5/07 – 2/09. NED to 8/09. Tarceva 150 9/09-5/11, SBRT/XRS to lung & spine met 2/11. Trial MK2206 (AKT inhibitor) + Tarceva 5 – 12/11. Afatinib+cetuximab trial 2/12 -2/13. LL collapsed. 1/13 PET – new bone & adrenal mets. 4 cyc Carbo-Gem-Tarceva 5/13. Brain MRI 10/13 – clear. Lost Dad to LC 5/13.Anti-PDL1@Angeles Clinic?

December 6, 2012 at 10:22 pm  #1251024    

catdander forum moderator

Hi Jazz, I think you know about all that’s known about chemo and the BBB.

My husband is new to medicare (it kicks in 2 years into disability no matter what your age). He hit the doughnut hole a few months ago and sent us for a loop. The enrollment period ends the end of today Dec. 7. I suppose it’s time to do some work.

How are you? We are pretty good.


My husband, 53 @ dx of stage 3 squam nsclc R. pancoast tumor 8/09 caused destruction of 3 ribs, touching brachial plexus. 2 core and 1 VATS undx biopsies. Open thoracotomy for 1 positive biopsy (unresectable). Chemorads, 9/09. MRI by pancoast specialty surgeon 11/09 spine met found, stage IV, Rad to spine, Chemo changed from cis/etop to navelbine/carbo. 6 cycles total. Tarceva 2/10-11/10. 3cm tumor L lung, biopsy undx w/collapsed lung. Gemzar, 12/10 through 7/12. NED 3/12, stop tx 7/12. Remains NED as of 8/14.

December 6, 2012 at 10:41 pm  #1251025    

Jazz

Janine,

I’m so thrilled your Hubby is NED! He set the record for being on Gemzar in my book (a doc at UCSF called it “the new water”).

The donut hole is a drag but not as bad as it used to be. I chose to stay on private insurance because I was on Tarceva when I became eligible and the donut hole didn’t have the 50% break it does now. Anyway, if you can get a good Medigap plan, that might be the way to go. Not sold on those Advantage plans but maybe there’s something I’m missing. Just remember that if M-care doesn’t approve something, neither will the gap insurer. And M-care doesn’t pay travel for treatment (the only way I break even right now with my exhorbitant plan).

I suppose I should post on the Afatinib thread since I’m still on the trial. Next scan on the 12th and if it passes muster, it’s on to the 12th cycle (12-12-12-12!!). I’m going to buy a Lotto ticket just in case!

Jazz


Non-smoker, Dx 6/06 Stage IV Adeno. EGFR+ (exon 19 del), T790m+. Trial: 2cyc Carbo/Doce/Avastin + 2 w/Gem 8 – 12/06; Avastin maint. 1 – 4/07. Alimta + Tarceva 5/07 – 2/09. NED to 8/09. Tarceva 150 9/09-5/11, SBRT/XRS to lung & spine met 2/11. Trial MK2206 (AKT inhibitor) + Tarceva 5 – 12/11. Afatinib+cetuximab trial 2/12 -2/13. LL collapsed. 1/13 PET – new bone & adrenal mets. 4 cyc Carbo-Gem-Tarceva 5/13. Brain MRI 10/13 – clear. Lost Dad to LC 5/13.Anti-PDL1@Angeles Clinic?

December 7, 2012 at 1:48 am  #1251034    

certain spring

Slimer, you will be happy to hear that GPs still exist. Some are good and some are bad, but all are free. My current GP is particularly wonderful, and has made my life easier in lots of ways. But she’s never offered me anything called “the Elixir”!
BTW we had an epic discussion about chemo and the blood-brain barrier the other day:

http://cancergrace.org/topic/wbrt-does-it-actually-do-what-is-says-on-the-wrapper

It seems as though in some patients, brain mets do respond to chemo; the worry is how to detect who those patients are. For myself, I’ve not yet had any cause to regret having had WBR: on the contrary, I’m very glad I did. Glad to see you are doing so well – all best.


49-year-old non-smoker, dx stage IV NSCLC May 2010 (squamous tumour of the left lung with multiple brain metastases). Radiotherapy to chest and brain; progressed through two cycles carbo/gemcitabine. Repeated lung collapses; pneumonia in collapsed lung, Nov 2010; bronchial stent placed, Dec 2010. Declined second-line Taxotere. Mutation testing Feb 2011, surprise EGFR exon deletion 19. Started Tarceva (150mg), Feb 2011. Progression in liver and elsewhere, May 2013.

December 7, 2012 at 12:33 pm  #1251063    

Dr West

Here’s the post with the video that describes my thought process on this case I was describing of why I might favor a trial of systemic therapy before WBR in a specific scenario.

http://cancergrace.org/radiation/2012/12/07/video-on-systemic-rx-for-brain-mets/

-Dr. West


Howard (Jack) West, MD
Medical Oncologist

Views expressed here represent my opinion, not those of GRACE or Swedish Cancer Institute. This information does not constitute medical advice and is intended to supplement and not replace medical information provided by your doctor.

December 7, 2012 at 2:55 pm  #1251064    

catdander forum moderator

Excellent, thanks.


My husband, 53 @ dx of stage 3 squam nsclc R. pancoast tumor 8/09 caused destruction of 3 ribs, touching brachial plexus. 2 core and 1 VATS undx biopsies. Open thoracotomy for 1 positive biopsy (unresectable). Chemorads, 9/09. MRI by pancoast specialty surgeon 11/09 spine met found, stage IV, Rad to spine, Chemo changed from cis/etop to navelbine/carbo. 6 cycles total. Tarceva 2/10-11/10. 3cm tumor L lung, biopsy undx w/collapsed lung. Gemzar, 12/10 through 7/12. NED 3/12, stop tx 7/12. Remains NED as of 8/14.

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