Intrathecal (IT) Herceptin for brain mets

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I do not know how to post links with my ipad yet and was only able to copy the first message from the discussion thread on the site.

complete response of leptomeningeal her2+ bc to intrathecal herceptin (case report

other than our member Courtney)



Complete response in HER2+ leptomeningeal carcinomatosis from breast cancer with intrathecal trastuzumab

Mafalda Oliveira • Sofia Braga • Jose ́ Lu ́ıs Passos-Coelho • Ricardo Fonseca • Joa ̃o Oliveira

Received: 15 February 2011 / Accepted: 16 February 2011 / Published online: 3 March 2011 Ó Springer Science+Business Media, LLC. 2011



M. Oliveira (&) 􏰀 J. L. Passos-Coelho 􏰀 J. Oliveira Medical Oncology Department, Instituto Portugueˆs de Oncologia de Lisboa Francisco Gentil, Rua Professor Lima Basto, 1099-023 Lisbon, Portugal e-mail: mafalda.moliveira@gmail.com

S. Braga Instituto Gulbenkian de Cieˆncia, Rua da Quinta Grande, 6, P-2780-156 Oeiras, Portugal

R. Fonseca Pathology Department, Instituto Portugueˆs de Oncologia de Lisboa Francisco Gentil, Rua Professor Lima Basto, 1099-023 Lisbon, Portuga



BRIEF REPORT

Abstract



Introduction

Leptomeningeal carcinomatosis (LC) is a rare but rapidly fatal event in the natural history of breast cancer [1]. HER2? breast cancer has an increased risk of central nervous system (CNS) metastases [2] but there are little data on LC frequency in these tumors [3]. Trastuzumab, a monoclonal antibody against the extracellular domain of the HER2 receptor, is highly effective in systemic control of HER2? metastatic breast cancer [4] but it is not clear if it can penetrate the intact blood brain barrier (BBB) [5]. We report the case of a patient who received weekly intrathecal (IT) trastuzumab for LC from HER2? breast cancer for 18 months, with impressive neurological benefit.

Case report

A 40 year-old woman presented in April 2003 with a left- sided cT4bN1M0 estrogen receptor (ER) positive (70% of cells) invasive ductal carcinoma. She received six cycles of neoadjuvant chemotherapy (5-FU 500 mg/m2, epirubicin 100 mg/m. Trastuzumab, a monoclonal antibody against the HER2 receptor, is a major breakthrough in the treat- ment of HER2? breast cancer. However, its high molec- ular weight precludes it from crossing the intact blood– brain barrier, making the central nervous system a sanc- tuary to HER2? breast cancer metastases. We prospec- tively 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, anthracy- clines, 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 admin- istration should be prospectively evaluated to confirm clinical activity and optimize dose, schedule, and duration of treatment.

Keywords Intrathecal trastuzumab 􏰀 Leptomeningeal carcinomatosis 􏰀 HER2? breast cancer

My oncologist at UCSF has mentioned it as an option and there was a woman from the HER2 support board who had it done there.  Good luck to you and your wife!  This is one hard road.

I know one of my breast cancer friends' oncologist gave her intrathecal Herceptin for suspected leptominingeal metastases.  It was not in a trial.  The doctor was Dr. Garrett Smith in San Francisco. 

I hope this helps.

Just to follow up on my previous post. . . . Many women in my support group see Dr. Smith, and they all love him.  He is from all accounts very compassionate and caring.  However, I personally have not been impressed by some of his treatment recommendations (for others), which did not seem consistent with evidence-based medicine.  Second opinions also have disagreed with his recommendations.  If you have other choices with respect to doctors that will administer intreathecal Herceptin, I would choose someone else, if you can get into see that person in a timely maner.  You should know that Dr. Slamon, who was the force behind Herceptin is at UCLA.  Although it is almost impossible to see him, his protegee, Dr. Hurvitz (spelling?) is more available.  The medical oncologists at UCSF, where I am treated, are excellent.  Getting in to see them, however, may be difficult.   

No, luckily (knock wood) I do not need it at this time.  Just IV Herceptin for me. 

Good luck! 

You might also try posting on the Her2 support board -- www.her2support.org   People have posted there about intrathecal Herceptin.  If you indicate where you are located geographically, that might be helpful, too.   

If you need further info about UCSF or Dr. Smith, I am happy to try and help. 

You also might try Dr. Nancy Lin at Dana Farber in Boston.  She has done a lot of research on brain metastases, and also specializes in Her2 positive disease.  (I also have heard that she is very nice.)  I have no idea, however if she would give intrathecal Herceptin.  Her research abstract and link to her profile are below. 

Research Abstract

Dr. Lin is a medical oncologist at Dana-Farber Cancer Institute focusing on the care of women with breast cancer. Her research focuses upon developing novel therapies for women with brain metastases, and upon exploring mechanisms of resistance and response to HER2-based therapy.

Publications

View All Publications  

http://www.dfhcc.harvard.edu/membership/profile/member/599/0/

Bumping for Janette

Marvass, I'm glad you were able to get this treatment, and I'm also glad to hear that it seems to be working.

All the best.

Leah