intrathecal herceptin for leptomeningeal carcinomatosis (too many mets to count) --

Lani · 03-04-2011, 03:55 PM

report of complete response that lasted 27 months until death of the patient for other reasons and no evidence of LC mets on autopsy!!

Breast Cancer Res Treat. 2011 Mar 3. [Epub ahead of print]
Complete response in HER2+ leptomeningeal carcinomatosis from breast cancer with intrathecal trastuzumab.
Oliveira M, Braga S, Passos-Coelho JL, Fonseca R, Oliveira J.

Medical Oncology Department, Instituto Português de Oncologia de Lisboa Francisco Gentil, Rua Professor Lima Basto, 1099-023, Lisbon, Portugal, mafalda.moliveira@gmail.com.
Abstract
Trastuzumab, a monoclonal antibody against the HER2 receptor, is a major breakthrough in the treatment of HER2+ breast cancer. However, its high molecular weight precludes it from crossing the intact blood-brain barrier, making the central nervous system a sanctuary to HER2+ breast cancer metastases. We prospectively assessed functional outcome and toxicity of administering trastuzumab directly into the cerebrospinal fluid of a patient with leptomeningeal carcinomatosis (LC) and brain metastases from HER2+ breast cancer that had already been treated with other intrathecal chemotherapy, with no benefit. Upon signed informed consent, weekly lumbar puncture with administration of trastuzumab 25 mg was begun to a 44 year-old women with metastatic breast cancer (lymph node, bone, lung, and liver involvement) previously treated with tamoxifen, letrozole, anthracyclines, taxanes, capecitabine, intravenous trastuzumab, and lapatinib. She received 67 weekly administrations of intrathecal trastuzumab with marked clinical improvement and no adverse events. She survived 27 months after LC diagnosis. A complete leptomeningeal response, with no evidence of leptomeningeal metastasis at necropsy, was achieved. We believe that intrathecal trastuzumab administration should be prospectively evaluated to confirm clinical activity and optimize dose, schedule, and duration of treatment.

PMID: 21369716 [P

chrisy · 03-04-2011, 05:54 PM

wow. interesting.

Soccermom · 03-04-2011, 06:10 PM

Fabulous news!

krisvell · 03-05-2011, 01:54 PM

Lani,
That is good news. I seem to recall that Joan mentioned a clinical trial coming up in March that was doing the same thing. It sounds like intrathecal treatment is rare and very scary to administer. I wonder if this is an initial option for someone like me. It seems like the Herceptin has kept things at bay for me from the neck down.Wouldn't mind getting it for my brain. I meet with my oncolgist on Tuesday to see what if anything she wants to give me. One option is to wait and only treat me if mets return. That scares me.
Kris..

Soccermom · 03-05-2011, 11:55 PM

I had a friend who was triple negative and was on intrathecal for leptomeningeal mets. It was successful for quite a while and in her case bought her about 1 1/2 years. She did have some complications ( meningitis) and the port in her skull was uncomfortable ,but she was determined to fight as hard as she could and managed to remain very active,

Marcia

Lani · 03-06-2011, 06:30 AM

I think I might have confused some people

leptomeningeal carcinomatosis are too many to count mets on the linings of the brain, not the brain tissue itself

It is a rare complication so it is nice to see a report of a successful treatment

I think some interpreted my "translation" of carcinomatosis as too many mets to count as being too many brain mets to count.

This article applies to leptomeningeal (lining tissue of the brain) metastasis NOT brain parencyma (brain tissue itself) metastasis as the way the intrathecal therapy works is to mix with the CSF (cerebrospinal fluid) and bathe the lining tissue of the brain and thus have access to it.

Brain mets are as I understand it usually within the parenchyma (brain tissue itself) not near the surface or the linings of the brain and so the herceptin might not be able to penetrate to get access to the met and work

Hope this helps

krisvell · 03-06-2011, 07:36 AM

Lani,
I think it's my understanding not you confusing me. So it looks like there's no way to get Herceptin to treat a brain tumor. (:
Kris....

Jackie07 · 03-06-2011, 08:46 AM

Found an interesting 'illustration' in Wikipedia on CSF flow:

http://en.wikipedia.org/wiki/Cerebrospinal_fluid

The molecule of Herceptin is too big to cross the blood-brain barrier. But Tykerb is small enough to get to the tumor cells. There are also ways to use extra pressure to 'force' certain drugs to cross the barrier...

Lani · 03-06-2011, 09:49 AM

they have also shown that those with brain tumors who stay on herceptin and add other things too it ie, lapatinib do better (whether because the BBB gets interrupted by the growth of the mets or something else) or because keeping the other non-brain mets at bay helps keep the brain mets from growing...

A lot we don't know yet

Joan M · 03-08-2011, 07:14 AM

I'm wondering whether Dr. Black started his intrathecal Herceptin trial for brain mets, as Kris mentioned.

Other than the obvious potential benefit for survivors with brain mets, what I think interesting about this trial (if it gets off the ground) is how they would determine whether a brain met is HER2+. My brain met was removed by surgery and tested HER2-, which can happen in about 30% of cases, I believe (that is, in general, the chemistry of the secondary tumor does not exactly match the primary tumor). I wonder how they would account for that in a trial.

Joan

Lani · 03-08-2011, 09:22 AM

Don't have time to look up now, but it seems possible they might be able to do a lumbar puncture to look for cancer cells and characterize them for leptomeningeal tumor as it is on the lining outside the brain and spinal cord so cells could be floating around in the cerebrospinal fluid that bathes these linings

Those cells could be individually characterized--they have the technology

Need to find out if this is just conjectural or actually turns out to be the case.

I usually only post article or presentations/posters from meetings, so am warning what I posted above has not be verified yet to actually be the case,
just my supposition.

SilentBob · 03-30-2011, 01:52 PM

My wife is currently undergoing treatment for LC using herceptin plus methotrexate intrathecally using an Ommaya reservior. The LC diagnosis came immediately after the completion of WBR as she began falling while at the hospital.

This treatment began mid-February and we saw immediate positive results as she was steadily declining beforehand. After several weeks in the hospital, she was finally able to return home. The last MRI showed improvement in the spine, brain and CSF. Since she had just completed WBR, the tumor within the brain can be attributed to that.

12-27-2011, 10:38 AM

Silentbob,

Which hospital or medical center did the the Intrathecal Herceptin? I know that Northwestern in Chicago Illinois has a clinical trial going. My wife just found out 12/14/2011 that the brain responded to the Xeloda/Tykerb/Radiation and is NED, but constellations in the spinal cavity were found. She is being evaluated for same type of treatment as your wife, but we do not want to travel to Chicago with her treatment ongoing in Houston, while I stay at home in the Raleigh area. It sounded like the treatment was working from your response. I would just like to hear what the follow up was.

AirplanePaul

SilentBob · 12-27-2011, 11:19 AM

AirplanePaul,

My wife ultimately ended up passing in July. The imaging showed that it had kept things at least at bay up until the point she had her last MRI in April.

Sign up for an account and I will send you a private message going through the detail.

evlin75 · 09-16-2012, 06:12 PM

my daughter has leptomeningeal mets and was in the trial in Chicago. Now at MD Anderson in Orlando getting IT of 40.
I would appreciate the information if you would consent to share per private message also. Thanks in advance for that if it is possible
Ev