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

[Lani]

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

[hutchibk]

and our Courtney will be another case report... this is fantastic!

Courtney showed the path to treatment. My wife just got results from four weeks at 40 mg Herceptin IT, then four weeks at 80 mg IT with Topotecan IT, as well as 120 mg Herceptin IV with Navelbine. The last is the same ass TDM-1 without it being conjugated. The December 17 2011 MRI showed 30 or so spots in the spine and two new ones in the brain. On March 9, thee ones in the spine were not showing contrast uptake, and neither was one of the two in the brain. The other in the brain only showed faintly, indicating it too had been attacked. This board gave me the hope, guidance, and perserverance to get this treatment plan approved. The posters on this board should be proud about the help they give to others.

[Lani]

Wonderful news!! Thank you so much for sharing it. Glad to have been of help.

[Laurel]

Wow!!!!!!! I'm jazzed by this update!

[Rolepaul]

I posted as a guest about a month ago. My wife is still having the IT Herceptin and topotecan. She also is receiving IV Herceptin and Navelbine. She needs neupogen to get her White blood count up the two days following the Navelbine. In otherwords, she says she feels like she had a fight with a cactus. The results are continuing to improve. None of the spine spots are active, nor are the brain spots that were there previously. It looks real good for right now so the drug frequency is being backed off to once per weeke topo and once per two weeks Navelbine. The insurance agency will pay for the intravenous Herceptin, but they called the intrathecal herceptin experimental. After negotiating (mafia style by me), the decision was made to pay for both methods of administration which meant that I was not out $25K so far. The goal is to get to once per four weeks of IT and IV of Herceptin on the same day with the IV being TDM-1 Herceptin (perhaps Navelbine and Herceptin). Nina is walking five miles per day, playing cards, will go to yoga this week (port installation required a three week stoppage), driving, etc. She looks good, although her posterior has lost fat and muscle from the radiation. She is getting Massage and will start acupuncture for the pain

Let's hope this was the secret to treatment for many others.

[Lani]

Great news!

Thanks for posting-- we are unaware if it has been the secret for many others as only a few post who have had IT perception

Your wife is a pioneer and I hope by sharing her experiences, we open up the opportunity for others to be treated this way, the results shared and the opening of clinical trials so others may benefit

Congratulations on convincing the insurance company

All the best!