progression on lapatinib for us

[mkrny]

Trial appears to have failed for my Maryann. She is completing second cycle while we start planning to have IT herceptin. Local neuro-onc will administer this. Only 4 patients known worldwide to have tried this. I've seen the study from Europe on this (2 patients), the local guy has one patient on it and I don't know where the 4th is. Waiting for more info on how they are doing with it and where they were when starting.

Anyone else out there investigating IT herceptin or doing it?

[sarah]

I send you love, hope and prayers. Miracles happen. It may take a while for the drug to have its effect.
big hug and love
sarah

[Lolly]

Ken, I'm sorry to hear this news, but it sounds as if you're ready to move to the next attack. But what is IT Herceptin? Is that the protocol whereby Herceptin is administered directly into the spinal fluid in order to bypass the BBB? I've heard of this; please keep us posted on the next plan of attack so we can keep the prayers coming.

<3 Lolly

[Bev]

Saying a prayer for your Maryann. Keep us updated. This sounds like new and exciting treatment and we need to know if it works. Sorry if life has you on a roller coaster now. Best wishes. BB

[heblaj01]

Ken,
I hope that intrathecal Herceptin is going to work as well with Marryann as for the german patient previously reported in the medical press.
Here are a few of the other possible options that you may want to look into:

-RTA744 phase I clinical trial
http://72.14.207.104/search?q=cache:...n&ct=clnk&cd=1

-Boswellia Serrata
http://www.her2support.org/vbulletin...ad.php?t=25524

-Dr Keith Black: for second opinion (also other info links)http://her2support.org/a/newher2_002.htm

-current guidelines for brain mets (all types, not just br cancer)
http://www.her2support.org/vbulletin...ad.php?t=25685

[mkrny]

All,
Thanks for the words of support.

Lolly,
Yes herceptin injected into the cerebral spinal fluid (CSF) either via lumbar puncture (ouch) or Ommaya reservior (port through skull). Genetech's standard formula must be changed though. Our neuro-onc is trying to get Genetech to reformulate it and back a clinical trial for IT use or at least endorse IT use. Right now they aren't too interested. As our neuro-onc explained Genetech delivers the drug in a box with two jars, one with powder (the drug) and the other is water with something in it that will kill patient if used IT. So they open the box and throw out the water and reformulate it at their pharmacy using the receipe from the European study.

Maybe Joe can work on them Genetech his side.

heblaj01,
Thanks for the references,
1- I'll discuss the RTA744 trial w/ oncs, I haven't seen that before
2- I've discussed the Boswellia Serrata with our neuro-onc (he came from Sloan but didn't work w/ it there so he didn't have too much to say about it). I'll need to look into that more.
3- Unfortunately the current guidelines for brain mets doesn't cover leptomenengeal decease.

Thanks again,

[StephN]

Dear Ken and Maryann -
I am distressed to hear that Tykerb has not had the desired effect. It seems to be like all the other drugs that work well in some patients and not in others. I am sure there will be some interesting reports from San Antonio in a couple of weeks that may shed some light on what is going on in your case.

I wanted to let you know that I have had two lumbar drains placed since June of this year. Very few people have a reason to need such a thing, but I wanted to let you know that I had virtually NO discomfort and no trouble after the removal with the insertion site healing properly.

In my case they went in between L3 and L4 with a tiny needle to allow the excess CSF to slowly drain so the leak area in the back of my head could clear. The first time I was fully awake and had no calming or pain meds. The Chinese resident who did it was excellent. The second time the drain was part of my surgery to repair the leak, so I woke up with it. For giving you something (the reverse), I am not sure they would need anything much bigger.

One bit of cerebral/spinal fluid trivia. It may surprise you to learn that our bodies make about 2 cups per day of this fluid. It circulates around the brain and through the spine and the excess is removed in a natural process as it is not needed. It is a closed system, but not completely closed.

Let us know how the whole process goes, or with the Omaya reservoir as well. I can only recall one member here who had the Omaya placed and she seemed OK with it.

KEEP AFTER GENENTECH on the reformulation.

[Lani]

treatment purposes, it is good to know that the smaller the needle the less the chance for a post-puncture headache. They are extremely rare when pediatric sized needles are used. Just saw a recent article--let me know if you need it. Depending on how much they need to take/drain, smaller needles are a bit less practical as it takes a bit longer to get the same amount of fluid through a smaller needle (think of a garden hose vs. a fire department hose--the one with the larger diameter can transport more liquid faster). Since patient comfort should outweigh a tiny amount of additional time, inform those you know who need these procedures to ask--it is seldom offered. The easiest way is to say: if you yourself needed this procedure what size needle would you want--a pediatric or an adult. Sometimes they have to special order the needle from the hospital stores and it takes a few more minutes. (I had dye injected for imaging studies on two occasions and had to ask just these questions)

Here are two articles on IT herceptin--the latest(hot-off-the-press) I do not yet have access to:
1: Lancet Oncol. 2006 Nov;7(11):888. Links
Care with intrathecal trastuzumab.

Siderov J.
PMID: 17081914 [PubMed - in process]

Related Links
Application of intrathecal trastuzumab (Herceptintrade mark) for treatment of meningeal carcinomatosis in HER2-overexpressing metastatic breast cancer.[Oncol Rep. 2006]

Hope this helps!

PS I have very little internet access at the moment(visiting for the holidays), so sorry not to post more info on this

[Lani]

The Lancet Oncology
Volume 7 • Number 11 • November 2006
Copyright © 2006 Elsevier






Reflection and Reaction
Care with intrathecal trastuzumab


Jim Siderova
a Cancer Services, Austin Health, Studley Road, Heidelberg, VIC, Australia 3084

E-mail address: jim.siderov@austin.org.au




PII S1470-2045(06)70917-2

I read with interest the Case Report on the use of intrathecal trastuzumab published in The Lancet Oncology because it is an uncommon method of administration for a monoclonal antibody.[1] I wish to point out a potential issue with the intrathecal administration of trastuzumab.

In Australia and the UK, trastuzumab is supplied in vials of 150 mg powder,2, 3 which contains histidine, trehalose dihydrate, and polysorbate, among other excipients. Once reconstituted with water for injection, the resultant solution is free of preservatives. In the USA, trastuzumab is supplied in vials of 440 mg powder,[4] together with 20-mL bacteriostatic water for reconstitution. This bacteriostatic water contains 1·1% benzyl alcohol—a preservative.

Products that contain preservatives, particularly benzyl alcohol, should not be administered intrathecally because of the risks of anaphylaxis and potential for neurotoxicity from the preservative agent.[5] Reported events include paraparesis, fibrosis of the cauda equina, and segmental demyelination of the dorsal and ventral roots.[5]

Thus, colleagues in the USA who might consider treatment with trastuzumab intrathecally should do so without the use of the diluent provided.

Intrathecal administration is an important component of the management of malignant disease, but products injected in this way should not contain preservatives, especially benzyl alcohol. Physicians, pharmacists, and nurses involved in the preparation or administration of intrathecal treatment should ensure that preservative-free products are used.

I declare no conflicts of interest.

[Lani]

REFERENCES:

1 Platini C, Long J, Walter S: Meningeal carcinomatosis from breast cancer treated with intrathecal trastuzumab. Lancet Oncol 7. 778-780.2006; Full Text
2 Roche products Pty Ltd: Herceptin (trastuzumab) Australian approved product information. Therapeutic Goods Administration approved amendment, Roche products Pty Ltd Sydney 21 April, 2006.
3 Electronic Medicines Compendium: (accessed Sept 20, 2006) http://emc.medicines.org.uk/emc/indu...ocumentid=3567
4 In: McEvoy GK, ed. American Hospital Formulary Service (AHFS) Drug Information, American Society of Health-System Pharmacists Bethesda 2006: 1209-1215.
5 Hetherington NJ, Dooley MJ: Potential for patient harm from intrathecal administration of preserved solutions. Med J Aust 173. 141-143.2000; Abstract

[Kim in CA]

Saying a prayer for you both, and hoping the Lapatinib will start showing results soon. Do keep us posted as you can. Kim in CA

[aviv]

dear mkrny,

I'm also looking at IT Herceptin- it looks pretty far from where I'm standing now, but it may be an option for us - pls, share us with anything you'll find.

thanks!

[aviv]

I also wanted to ask you all about IT Herceptin-
My mom has 8 brain lesion (~1.5cm) - probably more, since we ran CAT scan, rather than MRI.
Some of them are deep in the brain (frontal, perietal, temporal and occipital areas).
Is there any knowledge if IT Herceptin would fit that condition- would it reach these deep mets- or, would it only work for the areas nearby the intrathecal fluid, and the mets that are on the surface of the brain?
Also, I've checked around here- as expected, no one is conducting trials/treatments on IT Herceptin around.
I tried to get Dr Stemmler (the one who ran this trial), got no response thus far-
Has anyone found a place other than Germany that runs these treatments?

Thanks!!!

[mkrny]

From what I see any work w/ IT herceptin is pre-trial. Very experimental at this point w/ unknown end results from a statistical perspective (4 patients isn't enough for oncs to hang their hat on performance).

We have a neuro-onc on Long Island in NY (Dr Demopoulos) that is giving it to one patient currently and my Maryann is likely to be his second patient on it. I can provide contact info if desired.

Is radio surgery (e.g. Gamma-knife, Cyberknife, ...) an option to attack the multiple brain met spots you mom has?

[aviv]

mkrny: she had already gone through WBR on May.
Our radiology doc carefully checked her images from the past few months (CTs, MRI), and concluded that since the lesions are growing fast, it's useless to try stereotactic radiation- since while concetrating radiation on individual tumors, others would rapidly grow, and eventually she'll get the same amount of radiation as if she would in the case of repetitive WBR- so he suggests only second WBR.
I fear from additional WBR, as it may severly affect her- so as long as she can bear the pain with steroids, we'll postpone the second WBR.

Please, do forward the contact of Dr Demopoulos.

[mkrny]

Here's his contact info:

Dr Alexis Demopoulos
Director, Neuro-Oncology
North Shore/LIJ - North Shore University Hospital
300 Community Dr
Manhasset, NY 11030
516.562.3065

Our prayers are with you,

[aviv]

thanks! already contacted him and he referred me to someone in the area. i'll keep you posted if there's any progress on the IT Herceptin area with us.