brain metastases leptomeningeal

[fpeter]

My friend Beatriz – also member of this group – started IT Herceptin with Methotrexate mid-October this year (via Omayya reservoir). Since Dec 2010, she had two gamma-knife treatments (after surgery and whole-brain radiation) and has done therapies with Tykerb/Lapatinib, Xeloda and Neratinib.

Last week the brain MRI showed progression. Some lesions compatible with leptomeningeal metastases have increased significantly. One of the ventricles has collapsed and the Omayya reservoir is not working anymore.
She will now get IV Herceptin with Doxil and they will also administer IT Herceptin via a new Omayya reservoir to be placed in her spine.

If anyone knows of other treatment options, we would be very grateful for information.
thanks!
Frank

[tricia keegan]

I'm sorry I have no advice to offer Frank but do wish your friend well and hope someone else can make suggestions for you.

[mamacze]

Frank
This is such a hard time for Beatriz -and for you. I am so sorry she has lepto - it seems like she is progressing and at her wits end. Her treatment has been aggressive to date and IT Herceptin via a reservoir seems like an appropriate next step. It is hard to find treatments that cross the blood brain barrier. Does she have confidence in her doctors? Has she had her tumor biopsied? She is fortunate to have you.
Kim (from CT)

[Lani]

used the search function --Lani brain mets looking for Boswellia post and others

found several including:
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10-18-2009, 11:18 AM #1
Lani
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Join Date: Mar 2006
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new taxane derivative CROSSES BLOOD-BRAIN BARRIER safe, effective for brain mets as
well as brain tumors

Angiochem crosses BBB, shows safety, efficacy in phase 1/2 brain cancer studies

ANG1005 Crosses the Blood-Brain Barrier to Reduce Tumor Size and is Effective in Resistant Tumors

Montreal, Canada, and Chicago, IL, October 19, 2009 – Angiochem, Inc. a clinical-stage biotechnology company developing drugs that are uniquely capable of crossing the blood-brain barrier to treat brain diseases, announced today that its lead drug candidate, ANG1005, has demonstrated a favorable safety and efficacy profile in more than 100 patients with brain cancer from two separate Phase 1 /2 clinical studies in patients with progressive gliomas, including recurrent glioblastoma, and in patients with progressive brain metastases. These data, which validates in humans Angiochem's peptide-based platform technology (EPiC), were presented at the Society for Neuroscience Annual Meeting in Chicago on October 18, 2009.

In the recently completed Phase 1/2 brain metastases clinical trial, greater than 70% of patients receiving therapeutic doses experienced disease control (stable disease or better) with more than half of them showing clear reduction in tumor size. Furthermore, 78% of patients with taxane resistant tumors showed responses, indicating ANG1005 has the potential to be effective against resistant tumors. Of significance, therapeutic doses of ANG1005 were present in patient brain tumor samples, indicating that the drug successfully crosses the blood-brain barrier (BBB) and concentrates in the tumor, without showing central nervous system (CNS) toxicity or immunogenicity. Similar trends in patient responses have been observed to-date in the on-going Phase 1/2 recurrent glioblastoma clinical trial with approximately 65% of patients experiencing disease control.

"It is highly encouraging to see that ANG1005 has shown the potential to be effective in metastatic brain cancers and against drug resistant tumors, that are highly aggressive and have few treatment options," commented Jan Drappatz, MD, Center for Neuro-Oncology at Dana-Farber Cancer Institute, Department of Neurology at Brigham and Women's Hospital, and, Harvard Medical School, and lead investigator for Boston-area study centers. "Furthermore, significant reductions in tumor size and reversal of neurological deficits were observed in several cases of patients with high-grade gliomas in the on-going clinical trial. We are very encouraged by these efficacy signals and look forward to learning more about the effects of ANG1005 in recurrent glioblastoma as the study progresses."

ANG1005 is a novel, next-generation taxane derivative, targeting the LRP pathway to cross the blood-brain barrier and reach therapeutic concentrations in the brain. The drug was created with Angiochem's Engineered Peptide Compound (EPiC) platform technology. Key findings to date from the clinical studies include:

71% of patients (15/ 21) demonstrated disease control at therapeutic doses including seven partial responses (PR), four minor responses (MR) and four with stable disease (SD).
78% of patients with taxane resistant tumors (7/9) demonstrated responses indicating ANG1005 is effective in resistant tumors, including three PRs and four MRs.
Similar responses were observed in metastases located in other organs such as liver, lung, lymph nodes and bone including two complete responses (CR), one in liver and one in bone.
Therapeutic concentrations of ANG1005 were present in patient brain tumor samples, indicating the drug successfully crosses the BBB and enters the tumor.
No CNS toxicity as measured by neurocognitive testing was observed.
No immunogenicity or antibody response was observed, even after repeated dosing.
Superior side-effect profile compared to other taxanes was observed based on literature references.
Similar trends in patient responses have been observed to date in the on-going recurrent glioblastoma trial with 65% of patients experiencing disease control.
In addition to the ANG1005 clinical findings, Angiochem's EPiC technology was also highlighted at the Neurosciences meeting. In a presentation entitled "Development of a New Engineered Peptide Compound (EPiC) Platform for the Transport of Small and Large Therapeutics to the CNS", Jean-Paul Castaigne, MD, discussed the science underlying the EPiC technology and disclosed evidence of its ability to increase the amount of a variety of different therapeutics to reach the brain, highlighting the potential neurological applications of this technology and speed at which new drugs could be developed.

"We are excited by our positive results to date with ANG1005, which strongly validate our platform technology in humans," commented Jean-Paul Castaigne, MD, MBA, President and CEO of Angiochem. "Through our peptide-based platform technology, called EPiC, Angiochem creates new chemical entities that can cross the human blood-brain barrier to reach therapeutic concentration in the brain. By harnessing naturally-occurring receptors at the surface of the BBB, our EPiC drugs have the potential to treat a variety of CNS diseases, including neurodegenerative and metabolic diseases, brain cancer, psychiatric disorders and many others."

###
About ANG1005 // ANG1005 is a novel, next-generation taxane derivative targeting the LRP pathway. ANG1005 was engineered with the EPiC platform which was designed to cross the BBB. Studies have shown that ANG1005 gains entry into the brain compartment by targeting the low-density lipoprotein receptor-related protein (LRP) which is one of the most highly expressed receptors on the surface of the BBB. Once inside the brain, ANG1005 enters tumor cells using the same receptor-mediated pathway through LRP, which is upregulated in various cancer cells including gliomas and metastatic brain cancers.

About Angiochem // Angiochem is a clinical-stage biotechnology company discovering and developing new breakthrough drugs that are uniquely capable of crossing the blood-brain barrier (BBB) to treat brain diseases. The company's proprietary Engineered Peptide Compounds (EPiC) technology creates drugs that cross the BBB and reach therapeutic concentration in the brain, by harnessing naturally-occurring receptors on the surface of the BBB. Angiochem's lead product candidate, ANG1005 is in two separate Phase 1/2 clinical studies in patients with brain cancers and cancer metastases. Additionally, Angiochem is developing a deep and broad product pipeline, including small and large molecules, for the potential treatment of a wide range of CNS diseases, including neurodegenerative and metabolic diseases, brain cancer, psychiatric disorders and many others. Founded in 2006, Angiochem maintains headquarters in Montreal, Canada. For additional information about the Company, please visit http://www.angiochem.com.

[Lani]

also:
07-21-2009, 02:40 AM #1
Lani
Senior Member

Join Date: Mar 2006
Posts: 4,104
for Mighty Oak and all those battling brain mets
I had heard of this research about 6 months ago--now the paper is out. I don't know when they might be trying using radioactive iodine (already FDA approved for thyroid cancer and widely used), but will try to find out if there are trials and if you have to have had a brain biopsy showing NaI symporter
present on the mets.

: J Neurooncol. 2009 Jul 19. [Epub ahead of print]

Breast cancer brain metastases express the sodium iodide symporter.

Renier C, Vogel H, Offor O, Yao C, Wapnir I.
Department of Surgery, Stanford University School of Medicine, 300 Pasteur Drive H 3625, Stanford, 94305-5655, CA, USA.
Breast cancer brain metastases are on the rise and their treatment is hampered by the limited entry and efficacy of anticancer drugs in this sanctuary. The sodium iodide symporter, NIS, actively transports iodide across the plasma membrane and is exploited clinically to deliver radioactive iodide into cells. As in thyroid cancers, NIS is expressed in many breast cancers including primary and metastatic tumors. In this study NIS expression was analyzed for the first time in 28 cases of breast cancer brain metastases using a polyclonal anti-NIS antibody directed against the terminal C-peptide of human NIS gene and immunohistochemical methods. Twenty-five tumors (84%) in this retrospective series were estrogen/progesterone receptor-negative and 15 (53.6%) were HER2+. Overall 21 (75%) cases and 80% of HER2 positive metastases were NIS positive. While the predominant pattern of NIS immunoreactivity is intracellular, plasma membrane immunopositivity was detected at least focally in 23.8% of NIS-positive samples. Altogether, these findings indicate that NIS expression is prevalent in breast cancer brain metastases and could have a therapeutic role via the delivery of radioactive iodide and selective ablation of tumor cells.
PMID: 19618116 [

[Lani]

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09-29-2006, 06:05 PM #1
Lani
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for those with brain mets (and those scared of developing brain metastases)
a most remarkable article--I felt it inappropriate to place it with interesting articles as only one tenth as many her2support readers view those posts and it is my impression that there are some out there who could definitely need this news, published in a very respectable journal

I was happy to see an email address attached to the abstract and have forwarded on more information...


1: J Neurooncol. 2006 Sep 26; [Epub ahead of print] Links
A lipoxygenase inhibitor in breast cancer brain metastases.

Flavin DF.
Foundation for Collaborative Medicine and Research, 24 Midwood Drive, Greenwich, CT, 06831, USA, Dana_FK@hotmail.com.
The complication of multiple brain metastases in breast cancer patients is a life threatening condition with limited success following standard therapies. The arachidonate lipoxygenase pathway appears to play a role in brain tumor growth as well as inhibition of apoptosis in in-vitro studies. The down regulation of these arachidonate lipoxygenase growth stimulating products therefore appeared to be a worthwile consideration for testing in brain metastases not responding to standard therapy. Boswellia serrata, a lipoxygenase inhibitor was applied for this inhibition. Multiple brain metastases were successfully reversed using this method in a breast cancer patient who had not shown improvement after standard therapy. The results suggest a potential new area of therapy for breast cancer patients with brain metastases that may be useful as an adjuvant to our standard therapy.
PMID: 17001517 [PubMed - as supplied by publisher]

[Lani]

Also it might help to go to brainmets.org and see what they are posting

[Lani]

search ROLEPAUL also--here is one of the best threads he started:


05-13-2012, 11:42 AM #1
Rolepaul
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Intrathecal Herceptin/Topotecan for Leptomeningeal Disease
My wife, Nina, was found to have Leptomeningeal Disease in the spine with too many spots to count and three active leasions in the brain Dec 15, 2011. With hard work by many people, she had ten rads of her back and spine, and started weekly 40 mg Intrathecal (IT) Herceptin on 1/12/12. 2/3/12 the dose was increased to 80 mg and 0.4 mg topotecan twice per week. IV Herceptin was added with Navelbine. Not many people thought she would be alive at the end of February. Here it is middle of May 2012 and she is celebrating Mother's Day after her mother's birthday last week. She is down to Topotecan once per week, and we are looking at getting down to Topotecan once every two weeks, as well as the IT Herceptin. The IV Herceptin and IV Naavelbine we are looking at also once every two weeks. Insurance coverage has been good from anthem Blue Cross Blue Shield, MD Anderson has been supportive of patient suggestions, and Genentech has offered to help with putting the treatment plan into more clinical trials. I hope that everyone that is having brain mets can get this information and maybe get similar results. By the way, she has been driving, walking five miles per day, Yoga, Kindle, computer searching, and looks great since the initial diagnosis. She has tightness in the lower back to the knees that we are working on. Inspiration of others is the best way to feel good about yourself.

05-14-2012, 12:48 PM #2
dchips1
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Re: Intrathecal Herceptin/Topotecan for Leptomeningeal Disease
I am so glad she is doing so well! where is she being treated, did she have an ommaya reservoir implanted?

Praying for my Mri in 2 weeks to look good with my 2 mets to be gone as well.

Darita

05-14-2012, 12:56 PM #3
Rolepaul
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Re: Intrathecal Herceptin/Topotecan for Leptomeningeal Disease
Darita,

YOur progression is very similar to Nina's! She is being treated at MD Anderson in Houston Texas. I heard UCLA might also be treating patients with IT Herceptin. She is using an ommaya reservoir. We are trying to get the topotecan reduced because I heard that only Herceptin will not cause meningitis long term. Good luck to you. MRI for brain and spine 5/30.

Paul

05-15-2012, 10:37 AM #4
StephN
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Re: Intrathecal Herceptin/Topotecan for Leptomeningeal Disease
Hello RP -
You and your Nina have an amazing story. She is a true success to keep beating back her prognosis.

This is the support group where your story is so very much appreciated. Over the years we have had a few members try the intrathecal method and a couple of the first patients were over 8 years ago right on the forefront of that treatment.

Now there are new and better drugs to insert. Nina is proof of that!

Please keep us updated on the reduction of her treating drugs and how Nina is doing generally.

05-15-2012, 12:34 PM #5
Rolepaul
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Posts: 152
Re: Intrathecal Herceptin/Topotecan for Leptomeningeal Disease
Nina gets down at times, but is now looking to go back to giving therapeutic massages or being a clinic RN. The IT Herceptin with Methotrexate was a good first thought, but the darn stuff irritated the brain surface and caused some problems. One of the contacts on this site had her daughter have an issue with insurance that got my attention and the doctor transitioned to the topotecan as that had previously been run at MD Anderson with okay results. Piggybacking the two together was the secret. I wish it had been done five years ago and saved hundreds, if not thousands, of lives. We keep spreading the information to help others. Nina is getting ready for her 53rd birthday in July and just spent Mother's Day in Washington DC with our son.

Success is not measured by the number of steps you take to your target, but by the number of ones that are past your target. We left the target from the initial assessment from Xmas 2011 back three months ago, and we are not going to look over our shoulders again.

Paul and Nina

05-15-2012, 11:29 PM #6
potra
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Location: I live in a small town (pop7,000) in rural Spain. I've been living in Spain since 1970.
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Re: Intrathecal Herceptin/Topotecan for Leptomeningeal Disease
Dear Paul and Nina, delighted to hear your story! Gives me hope. I've asked for a second opinion at MDAnderson, Madrid.

05-16-2012, 07:06 AM #7
Rolepaul
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Re: Intrathecal Herceptin/Topotecan for Leptomeningeal Disease
Potra,

Have them contact the main center in Houston Texas. Dr. Loghin is the neurooncologist and Dr. Melhem-Bertrandt is the breast oncologist. This was a compassionate care treatment, but I think they want to get a full study going. There are a tremendous number of patients and it was noted in 2007 that this was going to occur with Herceptin and brain involvement. 30% of all HER patients have your situation, and in the past there was not a good method to treat it. This appears to work for a couple of patients, now it is time for more women to be treated with this. It is not inexpensive, but it has a good chance of working based on the results I have seen with Nina and with others that are not in major publications. I hope this is a road map for many more patients that are on this blog.

05-16-2012, 09:24 PM #8
potra
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Re: Intrathecal Herceptin/Topotecan for Leptomeningeal Disease
thank you very much Paul, I have a consultation with them -next week-I'll let you know how it goes. I knew about the stats for Her2 patients and was "prepared"-also I'm a vet so it's not as scary as it might be for others, makes me very proactive-something they aren't used to here.

05-17-2012, 12:19 PM #9
Rolepaul
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Re: Intrathecal Herceptin/Topotecan for Leptomeningeal Disease
Porta,
Good luck next week. We are at MD andsrson Houston. Nina is only one in this regimen. Keep pushing as she is doing really well. Monitor spinal prptein and glucose for dffectivendss. Mlre Monday when I am back in Raldigh.
Paul

05-17-2012, 12:36 PM #10
potra
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Location: I live in a small town (pop7,000) in rural Spain. I've been living in Spain since 1970.
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Re: Intrathecal Herceptin/Topotecan for Leptomeningeal Disease
Can't thank you enough...my love to nina, Miriam

05-19-2012, 02:11 PM #11
alexandra1
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Re: Intrathecal Herceptin/Topotecan for Leptomeningeal Disease
Paul did nina have breast cancer that metastasized ?

05-19-2012, 04:49 PM #12
Lani
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Join Date: Mar 2006
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Re: Intrathecal Herceptin/Topotecan for Leptomeningeal Disease
Hot off the "press"

Reading the abstracts for the upcoming ASCO annual meeting I found this:

2015 Poster Discussion Session (Board #3), Fri, 1:00 PM-5:00 PM and 4:30 PM-5:30 PM
Intraventricular (IVe) topotecan for women with neoplastic meningitis (NM) asso- ciated with ��responsive�� malignancies.
Kurt A. Jaeckle, S. Keith Anderson, Anna Willson, Gerardo Colon-Otero, Tejal Amar Patel, Edith A. Perez; Mayo Clinic, Jacksonville, FL; Mayo Clinic, Rochester, MN; Memorial Healthcare Systems, Hollywood, FL
Background: A prior study of intra-CSF topotecan (TOPO) for unselected pts w/ NM reported PFS 6 mo of 19%, and OS of 15 wks (Groves, NeuroOncol 2008;10:208). We postulated that greater activity might occur in pts w/ malignancies considered sensitive to topoisomerase inhibitors. Methods: We reviewed outcome of women with NM and adenocarcinoma of the breast, ovary or lung receiving IVe TOPO (0.4 mg 2x/wk x 4wk, Q wk x 4, Q 2wk x 2, Q mo x 3, Q 2mo x 3, and Q 3mo x 4) until progression (PROG) or adverse events (AE). All had baseline CSF cytology, and MRI of brain and spine. CSF cytology was obtained at each treatment (Rx), and brain/spine MRI Q 3mo. Neuro-specific PROG was defined as recurrent �� CSF cytology; PROG of NM on MRI; all-cause neurologic worsening; pt refusal; or death. PFS/OS were measured from 1st TOPO Rx. All pts signed consent; the study was IRB approved. Results: 17 women (breast -12; lung-3; ovary - 2) were treated via Ommaya reservoirs; 7 (41%) had VP shunts w/ valves, adjusted for Rx. Median (med) age was 53 (41-79), and KPS 70 (50-90). At presentation, 11(65%) had �� CSF cytology and 14 (82%) had NM on MRI [brain-11 (65%); spine-10 (59%)]. 15 (88%) had no prior intrathecal Rx. 13 pts (76%) received focal RT for CNS disease, and 8 (47%), chemotherapy for extracranial disease. Med.number of Rx were 13/pt (range, 3-50); med. duration of TOPO Rx was 14 wks (range, 1-109). Med. neuro-specific PFS was 13 wks; PFS6 was 41%, and PFS12, 29 %. Med. OS was 33 wks (range, 5-180), w/ 4 alive at 13��, 30��, 33��, and 180�� wks. 4 pts (24%) lived �� 95 wks. Of 11 w/ baseline �� CSF cytology, 7 (64%) cleared CSF of malignant cells (med. duration clear �� 47 wk (range, 9-104). AE included arachnoiditis (18%), leukoencephalopathy (18%), and Ommaya infections (12%). Rx was stopped for neuro PROG (29%); systemic PROG (23%); refusal (18%); AE (12%); or persistent negative CSF (6%); 12% are still on Rx. Conclusions: Promising activity of IVe TOPO was observed in women with NM from breast, lung and ovarian cancer. PFS 6 and 12, OS and cytologic response were twice that noted in prior studies of NM pts w/ unselected malignancies. This data supports our plan for a phase II study targeting this select cohort.

05-19-2012, 05:00 PM #13
Lani
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Re: Intrathecal Herceptin/Topotecan for Leptomeningeal Disease
another pertinent ABSTRACT:

2052 General Poster Session (Board #13G), Sat, 1:15 PM-5:15 PM
Concurrent intrathecal methotrexate and liposomal cytarabine for the treatment of leptomeningeal metastasis from solid tumors.
Brian J. Scott, Homira Feely, Tiffany Brown, Vincent Van Vugt, Ryan Kim, Paul Timothy Fanta, Lyudmila Bazhenova, Santosh Kesari; University of California, San Francisco, San Francisco, CA; University of California, San Diego, La Jolla, CA; University of California, San Diego Moores Cancer Center, La Jolla, CA
Background: Leptomeningeal metastasis (LM) from solid tumors is typically a late manifestation of disease with a median survival of weeks to a few months. Treatment is palliative, with no widely accepted standard of care. Options include intrathecal (IT) or systemic chemotherapy, radiation therapy or ventriculoperitoneal shunting. Randomized trials comparing single agent IT methotrexate to liposomal cytarabine have shown similar efficacy and tolerability. There is limited data, however, on the use of combination IT chemotherapy in solid tumor LM. Methods: We conducted a retrospective cohort study of 19 subjects treated for LM from solid tumors at a single institution. In addition to therapies directed at active solid tumor sites, each subject received IT liposomal cytarabine plus IT methotrexate injections every two weeks. Survival data and treatment-related toxicities were determined by systematic chart review. Results: LM was diagnosed by CSF cytology in 12/19 (63%), while the remainder were diagnosed by clinical and MRI findings. The most common cancer types were breast 7(37%), glioblastoma 6(32%) and lung 3(16%). The majority 18(95%) had active systemic or parenchymal brain disease at the time of treatment, requiring systemic chemotherapy 18(95%) or radiation therapy 13(68%). The median number of IT treatments was 4(range 1-9). Treatment was interrupted due to toxicity in 3(17%), while 7(37%) experienced �� CTCAE grade III toxicities, most commonly meningitis 3(16%). Treatment was stopped in 7/19(37%) following complete cytologic response 6/11(55%) or radiographic clearance 1/7(14%). The median overall survival was 96 days(n��6; range 29-158), median time to neurologic progression was 46 days (n��9; range 6-101) and the most common cause of death was progression of systemic disease 4(67%). Conclusions: Combination IT chemotherapy was reasonably well-tolerated, even in a population also receiving chemotherapy for progressive systemic disease. IT-related adverse events occurred at rates similar to previously reported single agent trials. Prospective evaluation is necessary to determine whether there is a survival benefit compared to single agent IT chemotherapy.

05-19-2012, 05:08 PM #14
Lani
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Join Date: Mar 2006
Posts: 4,108
Re: Intrathecal Herceptin/Topotecan for Leptomeningeal Disease
and another:
2070 General Poster Session (Board #16A), Sat, 1:15 PM-5:15 PM
Prospective follow-up of a cohort of 112 patients with leptomeningeal metastases of breast cancer recruited from 2007 to 2011: Prognostic factors.
Fahed Zairi, Nuria Kotecki, Isabelle Rodrigues, Marie-Christine Baranzelli, Charles Andre, François Dubois, Patrick Devos, Matthieu Faivre-Pierret, Richard Assaker, Jacques Bonneterre, Emilie Le Rhun; CHRU, Lille, France; Centre Oscar Lambret, Lille, France; Université Lille Nord de France, Lille, France; Centre Oscar Lambret - Université Lille Nord de France, Lille, France
Background: Around 5% of patients with breast cancers (BC) will develop leptomeningeal metastasis (LM). The incidence may increase. Methods: We reported the description and outcome of 112 consecutive BC patients diagnosed with LM in our institution from 2007 to 2011. Correlations between characteristics and overall survival (OS) were analyzed using usual statistical methods (Kaplan Meier, Log-rank, Cox model). Results: BC were invasive ductal carcinoma in 69.7%. Estrogen and progesterone receptors were detected in respectively 61.6 and 44.6%. HER2 expression was observed in 26%. 23% were triple negative. Median time between BC diagnosis and LM diagnosis was 44 months. At LM diagnosis, median age was 54 and median Performance Status (PS) was 2. CSF cytology and cerebrospinal MRI were positive in respectively 72,5% and 87%. 103 (92%) LM patients received IT liposomal cytarabine as 1st line of treatment (ventricular device in 47%). IT therapy could be associated with systemic treatment in 58% of the cases and cerebral radiotherapy for LM in 14% of the cases. Clinical response after 1st line treatment was observed in 57%, CSF response in 30,5%, MRI response in 62,5%. 24 patients received a 2nd line of IT thiotepa, 6 a 3rd line of IT methotrexate. The more significant prognostic factors (p��0,0001) were initial PS, associated systemic treatment and triple negative BC status. Other significant predictors of OS were thiotepa as 2nd line treatment (p��0,0004), intracranial hypertension at LM diagnosis (p��0,019), associated cerebral radiotherapy (p��0,02), progesterone receptor status (p��0,04). Median OS of the 103 treated patients was 3,8 months (4,75 months for 0-2 PS and 1,6 months for 3-4 PS patients). Conclusions: Median OS was consistent those of other recent cohorts of BC LM. Our results confirm the role of a very early diagnosis, before the degradation of the general status. The association with systemic treatment or cerebral radiotherapy is indicated when possible.

05-20-2012, 12:09 PM #15
Rolepaul
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Join Date: Jan 2012
Posts: 152
Re: Intrathecal Herceptin/Topotecan for Leptomeningeal Disease
Alexandra1

Yes. Nina's was a left breast of 6.0 cm with 4 out 20 lymph nodes positive.

The 5% LMD is going to go up because of the Herceptin being able to get most everything other than brain and spine. If other areas than the cancer in the LMD was never noted, but it is estimated it would have been found in most of the patients (source not able to be cited for fear of being terminated.) We need to get positive results and get them now. The info from ASCO is great. I will start looking at this from a pharm guys viewpoint.

Paul

06-04-2012, 03:08 PM #16
Rolepaul
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Re: Intrathecal Herceptin/Topotecan for Leptomeningeal Disease
To all, there is hope with brain mets. Nina's MRIs show only normal background in the brain and spine. The PET scan came back as normal. The tumor markers are down to the normal population. There are no abnormal cells seen in the Lumbar Puncture or a vein draw. Treatment is going to nce every two weeks for the Intrathecal (and we hope the IV). TDM-1 works, but only if there is not Central Nervous System involvement. This approach will be investigated for those individuals with brain and spine mets from Herceptin based disease. We cannot thank the doctors at MD Anderson enough.

06-06-2012, 11:57 AM #17
calisa71
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Location: Miami, FL
Posts: 4

Re: Intrathecal Herceptin/Topotecan for Leptomeningeal Disease
Just got dx with lepto. I want the intrathecal Herceptin trial. Anyone with any info to expedite getting into this trial PLEASE help. I am terrified. Anyone been through this I'd love to talk.


Thank you very much

Lisa. (calisa is just an onscreen name)

06-10-2012, 06:42 AM #18
marvass
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Posts: 40
Re: Intrathecal Herceptin/Topotecan for Leptomeningeal Disease
We are doing it and rolepaul is doing it too.
Chicago are recruiting now, 10mg twice a week.
France trial are recruiting now 30mg per week.
But maybe you can get a better trial through your oncologist if you convince him. If you need more details message me or rolepaul who is more of an expert. Good luck

06-10-2012, 07:53 AM #19
Rolepaul
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Posts: 152
Re: Intrathecal Herceptin/Topotecan for Leptomeningeal Disease
Lani,

So the clinical trial shows an overall survival of 3.8 months on average. That is unacceptable! Intrathecal Herceptin has been shown to eliminate the detectable presence of Leptomeningeal disease in almost every case that has been noted in literature or on the internet if at least 50 mg per week is used. I was contacted by one gentleman whose wife died, but of liver or pancreatic cancer a few months after treatment. Most of the other patients are still alive, or passed away from other causes years after the treatment. It took four solid days of work to get all the information about this treatment method for Nina and getting treatment started was extremely difficult due to politics of not having the number of cases out there to make the doctors comfortable initially.

Dr. Raizer is struggling to get women for treatment. That is what is even more frustrating. The studies at Northwestern and in France are not well advertised, without the completion of the trial there is no documentation of positive results, without positive results there is no knowledge in the community or health industry to inform doctors and patients. Dr. Razier's study is to determine the amount of Intrathecal Herceptin that is tolerable. There are already 12 patients that have 50 mg or more per week. I would have thought that it would have been higher dosages than the 10 mg twice weekly or 20 mg twice weekly lower dosages.

Nina is already down to once per two week treatment with NED in the brain, spine, or anywhere else, Mario's wife has already started treatment, Lisa looks like she should get her treatment started within ten days, and there are other contacts I am working with to get this done through compassionate care if they can't get into the Northwestern trial. If there are the numbers of patients with Lepto disease as it sounds like, there are too many for this trial. There is talk of MD Anderson personnel getting a large scale trial started, but the provider of Herceptin, Genentech, has some reservations about providing funding for a large study. They need to have some "push" to get this concept going. I am pushing NCI, NIH, ACS, Susan B Komen, and anybody else I can to get some help for a trial.

Let me know what we need to do from your thoughts.

Mario's wife Carol is now at 50 mg per weekly dose. MRIs in three weeks to show progress. I feel like I am a one man army, but getting recruits as people find out about how to fight this war on Lepto involvemenr with HER+.

06-10-2012, 06:10 PM #20
dchips1
Senior Member

Join Date: May 2006
Location: Mesa, Az
Posts: 127
Re: Intrathecal Herceptin/Topotecan for Leptomeningeal Disease
my 6 week thoracic mri after 20 rounds of rads, showed slight reduction to my lesions. hurry up and wait for 7 more weeks for next Mri. Still on Tykerb 750mg and weekly Herceptin, tumor markers are good. i have never had any CSF samples for cells? These 2 different lesions are pretty much inoperable.It is kinda crazy that her2 + can wiggle around inside the spinal cord so crazy.

Very interested in possible treatment using Intrathecal herceptin if the radiation doesn't kill it all the way to NED!!

Barrows neurosurgeon will place omaya, but not to sure about the Herceptin use? is it the same Herceptin vials that you get IV, but use different diluent?

Can you still wear an ATV Helmet with the omaya reservoir in place? My anniversay present

Prayers and Love To all Of our warriors and Cargivers

Darita
Arizona





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06-10-2012, 07:56 PM #21
Rolepaul
Senior Member

Join Date: Jan 2012
Posts: 152
Re: Intrathecal Herceptin/Topotecan for Leptomeningeal Disease
Ommaya does not need any other protection than you normally do. They put the Ommaya into the head and it is just like a vaccine when they give the treatment. It is the same Herceptin as used via IV. They use 5 mls of sterile saline or water for injection to dissolve the amount of material targeted. Please contact me via private message and I will give you the contact information at MD Anderson and they will take your doctor's call to let you know what was done for Nina. All I want to tell you is that this will take a compassionate care protocol at the hospital there. I will do everything I can to help you.

Paul

06-11-2012, 07:23 AM #22
Rolepaul
Senior Member

Join Date: Jan 2012
Posts: 152
Re: Intrathecal Herceptin/Topotecan for Leptomeningeal Disease
By the way, yes you can still wear an ATV helmet. I did not read that carefully. You probably need to give it a few days to heal up from surgery, maybe cut just a bit of padding if there is any interference, but I think you should be okay.

Please contact Dr. Raizer at Northwestern on how he is formulating the Herceptin if you cannot get in touch with MD Anderson. See me a Private Message for contact information for me, MD Anderson, and Dr. Raizer.

06-11-2012, 08:00 AM #23
calisa71
Junior Member

Join Date: Nov 2006
Location: Miami, FL
Posts: 4

Re: Intrathecal Herceptin/Topotecan for Leptomeningeal Disease
I am in touch with Shanu modi at msk. Sent her some info from md Anderson. If Shanu and Amal could speak that could help. I am a established pt with mskcc.
Lisa

Shanu Modis email is modis@ mskcc.org.
646-888-5243

06-11-2012, 12:13 PM #24
dchips1
Senior Member

Join Date: May 2006
Location: Mesa, Az
Posts: 127
Re: Intrathecal Herceptin/Topotecan for Leptomeningeal Disease
pertuzumub has the same molecular weight as herceptin, would be interesting if we could add or use this in altering treatments with herceptin intrathecal therapy?

Darita

06-11-2012, 01:20 PM #25
calisa71
Junior Member

Join Date: Nov 2006
Location: Miami, FL
Posts: 4

Re: Intrathecal Herceptin/Topotecan for Leptomeningeal Disease
Darita. Is the cancer in your csf or just spine(bone)?

06-11-2012, 11:36 PM #26
dchips1
Senior Member

Join Date: May 2006
Location: Mesa, Az
Posts: 127
Re: Intrathecal Herceptin/Topotecan for Leptomeningeal Disease
Both of the lesions are inside the spinal canal and sitting on a nerve or two. In the thoracic area t3-4 and t-8. I have had 20 rounds of radiation to both the areas.

Darita

08-02-2012, 05:56 PM #27
evlin75
Member

Join Date: Sep 2007
Posts: 21
Re: Intrathecal Herceptin/Topotecan for Leptomeningeal Disease
My daughter is in the Chicago trial. Just had her first treatment. How long does it take to know if the medicine is working?
Thanks for any info.
Ev

08-02-2012, 07:02 PM #28
KDR
Senior Member

Join Date: Aug 2010
Posts: 854
Re: Intrathecal Herceptin/Topotecan for Leptomeningeal Disease
Calisa71,
I am Dr. Modi's patient. Are you treated on Fridays? (I've been there so long, so often, surely I must have seen you). You can PM me.
Karen

08-02-2012, 07:18 PM #29
hutchibk
Senior Member

Join Date: Oct 2005
Posts: 3,519
Re: Intrathecal Herceptin/Topotecan for Leptomeningeal Disease
If I am not misreading this (which I could be...), I believe that intrathecal Herceptin is available at every clinic as an approved treatment, as long as your Onc is doing it and insurance covers it.

08-03-2012, 07:07 AM #30
Rolepaul
Senior Member

Join Date: Jan 2012
Posts: 152
Re: Intrathecal Herceptin/Topotecan for Leptomeningeal Disease
The is a likelihood that she will have nausea and vomiting with the first treatment. That would be the best indicator it is working as it means the cancer cells have been destroyed. First MRI from now will show it is working otherwise. What was the dose? Please post what happens.

08-03-2012, 02:01 PM #31
evlin75
Member

Join Date: Sep 2007
Posts: 21
Re: Intrathecal Herceptin/Topotecan for Leptomeningeal Disease
My daughter is receiving 10 mg two times a week for the first month in the Chicago trial. She is getting herceptin only IT- no other additive. She also gets Herceptin IV - along with Tykerb that she has been on prior.

[Rolepaul]

I am sorry about not responding previously but work and personal life has been very busy. I can tell you that Nina received 1.3 mg/kg of Herceptin with 0.4 mg per dose of Topotecan via intrathecal Ommaya. The 20-40 mg dose amounts of IT Herceptin are not sufficient to stop the disease. The spinal fluid turnover is 10 times what the blood turnover is, which means the half life of drugs via Ommaya is that much shorter. There is a method in the treatment that we did for Nina, that Mario is helping get for Carol, and what the Europeans did in 2008. I would suggest that they look at 80 mg for a 132 pound bodyweight and scale the dose from that. I am sorry that the Ommaya reservoir initially failed and hope that the new one works better. Have them contact MD Anderson in Houston, Dr. Loghin in the Brain and Spine Center for more information. My thoughts are with your friend.

Nina is doing great. Next MRI between Christmas and New Year, which will be one year since the spinal lesions were found and we are four weeks passed from the anniversary of when three years since the brain lesion was found. Four miles a day walking, yoga three times per week, studying Spanish, driving, flying to Houston from Raleigh for treatment without any help, arranging her appointments, and in full recovery. Her case may be brought up at San Antonio, but I am not sure.

[NEDenise]

Frank,
I don't have any advice except...please follow Paul's suggestion and have Beatriz's doc call Dr. Loghin at MD Anderson...there's so much at stake, and what can it hurt for the two docs to compare notes! Beatriz is lucky to have you. From one brain met survivor to another...Beatriz, you are in my prayers today.

Paul,
Thanks for your post...I needed to read good news about a fellow brain met survivor. Been feeling a little down lately. Please tell Nina what an inspiration she is for me! Hope you both continue to be well, and enjoy much happiness!
Denise

[fpeter]

Thanks so much to everybody for your advice, informations and wishes! She is very happy with her medical team, but there are many things to consider now. We will follow the leads and write the doctors -- thank you!
Frank

[marvass]

Sorry to hear about Beatriz, may God help you in all these trouble days.
My wife Carol is also in same situation but 150 mg IT herceptin together with 1250mg lapatinib and steroids seem to do the job, takes time but it is working.
I suggest you take a look at my thread for all the details of the past 6 months with this desease.
Mario

[Jackie07]

The threads below contain previous postings by Beatriz:

http://her2support.org/vbulletin/sho...359#post252359

http://her2support.org/vbulletin/sho...836#post269836


Please let her know we are thinking of/praying for her.

Here's another thread on the same subject: http://her2support.org/vbulletin/showthread.php?t=54229

An abstract about the incidence and risk factors:

J Korean Neurosurg Soc. 2012 Sep;52(3):193-9. doi: 10.3340/jkns.2012.52.3.193. Epub 2012 Sep 30.
Incidence and risk factors for leptomeningeal carcinomatosis in breast cancer patients with parenchymal brain metastases.

Jung JM, Kim S, Joo J, Shin KH, Gwak HS, Lee SH.
Source

Department of Neurosurgery, Seoul National University College of Medicine, Seoul, Korea.

Abstract

OBJECTIVE:

The objective of study is to evaluate the incidence of leptomeningeal carcinomatosis (LMC) in breast cancer patients with parenchymal brain metastases (PBM) and clinical risk factors for the development of LMC.
METHODS:

We retrospectively analyzed 27 patients who had undergone surgical resection (SR) and 156 patients with whole brain radiation therapy (WBRT) as an initial treatment for their PBM from breast cancer in our institution and compared the difference of incidence of LMC according to clinical factors. The diagnosis of LMC was made by cerebrospinal fluid cytology and/or magnetic resonance imaging.
RESULTS:

A total of 27 patients (14%) in the study population developed LMC at a median of 6.0 months (range, 1.0-50). Ten of 27 patients (37%) developed LMC after SR, whereas 17 of 156 (11%) patients who received WBRT were diagnosed with LMC after the index procedure. The incidence of LMC was significantly higher in the SR group compared with the WBRT group and the hazard ratio was 2.95 (95% confidence interval; 1.33-6.54, p<0.01). Three additional factors were identified in the multivariable analysis : the younger age group (<40 years old), the progressing systemic disease showed significantly increased incidence of LMC, whereas the adjuvant chemotherapy reduce the incidence.
CONCLUSION:

There is an increased risk of LMC after SR for PBM from breast cancer compared with WBRT. The young age (<40) and systemic burden of cancer in terms of progressing systemic disease without adjuvant chemotherapy could be additional risk factors for the development of LMC.

PMID:23115660[PubMed] PMCID:PMC3483318Free PMC Article


Images from this publication.See all images (2) Free text
Fig. 1
Kaplan-Meier curve for time to development of LMC after treatment of the parenchymal brain metastases plotted for 183 patients in our study. Y-axis represents the proportion of patients without LMC at each follow-up time at the X-axis. 27 patients developed LMC (14%) during the follow-up. LMC : leptomeningeal carcinomatosis.

Incidence and Risk Factors for Leptomeningeal Carcinomatosis in Breast Cancer Patients with Parenchymal Brain Metastases
J Korean Neurosurg Soc. 2012 September;52(3):193-199.

[Jackie07]

A case report:

Breast Cancer Res Treat. 2011 Jun;127(3):841-4. doi: 10.1007/s10549-011-1417-2. Epub 2011 Mar 3.
Complete response in HER2+ leptomeningeal carcinomatosis from breast cancer with intrathecal trastuzumab.

Oliveira M, Braga S, Passos-Coelho JL, Fonseca R, Oliveira J.
Source

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.

[fpeter]

Thank you Jackie for linking the threads and for your prayers. Thanks Mario, yes i read all your posts. Beatriz got 75mg IT Herceptin plus 10mg Methotrexate (her body weight oscillates around 105lb). Treatment started mid-October, however, due to the hurricane, it was interrupted after three weeks, i e the last MRI was made after only three injections. I don't know about Topotecan, I assume that is not an option because it seems to affect the liver a lot (she has problems w liver), but I will check -- thanks!
Frank

[marvass]

After 2 months of IT herceptin the MRI showed slightly more contrast but tumors where same size, then they started to shrink after 4 months. So you have to wait to see results.

[Pray]

I'm still hoping and praying for you!

[Rolepaul]

As Mario said, it takes a bit of time for the IT Herceptin to be effective. Nina's MRI scans did not show much reduction for the first 60 to 90 days, then it was very effective. As the Demolition specialist said in Force 10 from Navaron "Give it a chance. You cannot expect immediate results every time". Trying to spread the word for this treatment.

[evlin75]

Where is the spine ommaya being placed - who is doing this procedure? My daughter needs a new point of entry for the IT treatments and any info would be helpful. Her first one became abscessed and had to be removed.

Thanks.
Ev

[Rolepaul]

Ommaya is at the hair line and not visible once the hair is more than 3/4" long. We had ours done at MD Anderson. The guy does three a week. Dr. Prabhu.