~Too Many Brain Mets To Count~Mighty Oak's Saga Continues...

[Believe51]

I was getting upset that we did not receive a return call from GammaMan's office with the results....now I know why.

He had to collect his bearings before telling me that Ed had "Numerous brain mets, too many to count or to have the Gamma Knife as an option..."

Why did this news take me for a loop? I am blown away into the darkness again and cannot digest this all right now. I am breathing but I am numb. The GammaMan already contacted the OncoMan. I asked about Whole Brain Radiation being done again. He has heard of instances but will be talking with Ed's Radiation team to consult this possibility.

In the meantime I have contacted my Nurse Advocate and asked for a phone call tonight from OncoMan. He will probally call about 8 or 9 p.m. and we will go over this situation as a whole. I want to go over my 'Last Options' folder with him and discuss where do we go from here.

Monday holds a day for calling Dana Farber and exploring in depth the other hospitals. Any suggestions or guidance you can give us right now will help. I feel lost and tired and downright numb. I know what this may all be but I refuse to give up. I do believe in miracles but I feel we have been granted so many thus far and am losing faith that there will be any more.

This news is fresh so I write in the state of mind I am in. I remind you that I am breathing and may have to take something so I can relax. My thoughts are racing through my mind and I cannot stop them. Of course I know you will pray for us and I thank you for loving us. I feel that in the entire journey I need you all the most right now and I am so blessed that you will walk besides us through this.

I am scared to death this time. You know I sit here and I give and get support.....I constantly research....I educate myself in how a gene works......but I do not know how to do the rest. I do not know how to do this, no one can prepare you for that.

Oh yeah, and this is for you cancer one more time; you are not getting it! It is The Mighty Oak and you now, head to head! Do not think he will not grab you by the throat and stare you in the eyes. He will not go down without a hell of a fight and will spend his last breathe telling you goodbye. We thought you would have gotten that by now so I guess you are not as smart as I thought. He is prepared to fight for every moment and no matter what the outcome, he will always come out the Winner!

I am lighting a candle for my boy who in his calm and journeyed voice tells me "one moment at a time, Marie." He has listened to the options I can supply right now and knows of the calls completed. I love this brave man who still continues to smile and not complain. God, how did I get so lucky?>>Marie

PS: The most ironic thing of it all is that.......I did not even think this would happen to him....Duhhh! Where was I living???

[Bill]

Marie, words escape me. Like the mighty Oak says, take one moment at a time. You guys can prevail once again. Our prayers are with you. You hang in there. Love, Bill

[juanita]

marie, i am so sorry to hear this. i will send lots of prayers and hugs your way over the next few days.

[Mary Anne in TX]

Marie, we live from truth to fantasy and back to truth again as the circumstances demand. You must sometimes live in the make believe to be able to handle the horrible ups and downs that make this disease so mean!
You have done this journey just as you should....forward, stop, back, but always forward once more. I believe it's who you are and how you live.
Why not just be right now. You'll make decisions soon. Just be and let all the love and admiration we feel for you wash over you. I can only send much love and many, many prayers for you both.
Luv and faith, sweet friend,
ma

[Believe51]

Dana Farber just called. This 'lil Darling was leaving for the weekend and seen her phone blinking. They were already closed for the evening but she could not resist listening to the message and calling me back. Here's to her giving in to tempatation, you will never know what this did for me. After the phone call from OncoMan and I think I can do the weekend without a scream ride (smiling)>>Believe51

[Lien]

Dear Marie,

Rats! S.P.F.!!!! Ofcourse you are scared and confused and oh, I don't know what you feel! It's a big blow. Somehow the two of you will face this. And you will find a way through this. Give yourself a break. You need to absorb this before moving on and dealing with this. I'm holding both of you in my heart.

Jacqueline

[Mary Jo]

Sending you guys my heartfelt love and care! I wish I could say or do more......but knowing you can make it through the weekend makes me happy for you.

Love you guys.......

Mary Jo

[pattyz]

Well hell. You know that I hate this is the latest 'news' for Ed... and for YOU.

I just this morning faxed 7 pages of detailed info my onc asked for at yest. appt. These meds are what we are looking to add in some fasion ASAP to try and control my own brain mets. They continue to grow, but slowly. Yet, he said: "at this point even if your brainstem lesion grew marginally, it could cause real trouble and symptoms right now." It will be seven years of brain mets in Sept.... that is pretty scary if I think too much.

I will be more than happy (not such a great word under circumstances) to send you any kind of info you might want. Names and /or details.

And here I sit, still keeping WBR as a very last option. call me chicken, stupid....... you'd probably be right.

Bless that ED. I've used those same words... as that's all we really can do while the river keeps on flowing.

Still hoping and wishing,

XOXOX patty

[Believe51]

OncoMan just called and first asked how we were digesting what is happening. We are okay. He will be contacting Dana Farber himself on Monday to see what they may have to offer. If they can help, he will take care of everything to get there. If they cannot, treating Ed systemically would not be a problem but he wants me to know that if he wants to stop treatment, it is understandable. This drug is not proven to pass the blood/brain barrier. He feels that the brain should be treated right now "if" we have an option to.

OncoMan tells us like it is and has always inspired some 'glimmer of hope' with each visit or call. The only hope we have now is if Dana Farber or another facility has something experimental or new. This is the only hope we have. Whole Brain Radiation for the second time is almost not an option.

We are almost out of options here. There is nothing we can add to this regime that will help. Miracles are something I would give up some of my life for right now. Hospice will be called if or when he decides to give up treatment.

I pushed the OncoMan for a projection of time and you know how I do not believe in that. Somehow, this time I needed to know.....Ed will start showing signs of disease within 3 months and it is projected that this is all the time we will have. Within 3 months. Why will I not believe that? It is only obvious.

I think part of me died today, but not the part that will continue to plead and search for that miracle. I am sorry to have to give you all this news.>>Believe51

[Pam P]

Marie I am so saddened by your latest news about Ed. I will be praying hard for one more miracle to come your way. Your strength, courage and grace through everything you are facing is beyond words.

[Lani]

here is info I just quickly gathered on Boswellia Serrata and intrathecal herceptin
from a 9/06 thread I started--I recently read a post from someone who thanked me for providing the info--she had used Boswellia and had a 40% decrease in the size of her brain mets and a long period of stable disease (couldn't find the post, but found these by putting Boswellia into the search function above). I also post my info on intrathecal (injected into the cerebrospinal fluid so it doesn't have to cross the blood-brain barrier) herceptin:
Here is the first post:

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]






hmerch
Member

Join Date: Apr 2006
Posts: 5





I contacted Dr. Flavin for my mother who has brain mets and she said that Boswellia serrata should be used right away at 800mg 3 times a day.

My understanding from my conversation with her was that those of her patients who are using this had regression of brain mets. She also has a few patients who are met free now for a few years.

This sounds pretty great and I'm going to get this for my mom if her onc allows it, but I am curious if anyone else has used this compound and if so what has been your success?

Thanks,
Hina














10-27-2006, 03:31 PM
#15
heblaj01
Senior Member

Join Date: Apr 2006
Posts: 543



Caution: possible interaction of Boswellia with some chemo drugs

In checking the pharmacokinetics of Boswellia Serrata I found this article which describes it as an iinhibitor of P450 enzymes which are required in the liver to metabolize some chemo drugs such as Navelbine.
http://www.ncbi.nlm.nih.gov/entrez/q...&dopt=Abstract
Analysis of frankincense from various Boswellia species with inhibitory activity on human drug metabolising cytochrome P450 enzymes using liquid chromatography mass spectrometry after automated on-line extraction.
The abstract does not state if the inhibition is occuring only in he gut or in the liver or both.
If the inhibition is restricted to the gut then intravenous chemo drugs would not be affected.
If however the inhibition is in the liver the consequences could be lowered effectiveness of the chemo treatment & possibly higher level of side effects due to longer persitance of the drug in the body & higher accumulation.

I hope this will turn out to be a false alert for most of those planing to use Boswellia but it needs to be clarified by someone with the right background such as Lani.


heblaj01
Senior Member

Join Date: Apr 2006
Posts: 543





This article posted by Lani is most interesting for members of this forum since it deals with metastatic brain cancer from breast.

It appears that Boswella Serrata might also be usefull for primary brain tumors since a phase 2 clinical trial is under preparation:

http://www.clinicaltrials.gov/ct/gui/show/NCT00243022
Boswellia Serrata Combined With a Low-Fat, Vegan Diet or a Standard Diet Alone in Treating Patients Who Have Undergone Surgery and Radiation Therapy for Newly Diagnosed Glioblastoma Multiforme





from my 11/06 post:



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
















11-22-2006, 03:50 PM
#9
Lani
Senior Member

Join Date: Mar 2006
Posts: 1,988



got it!

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.
















11-22-2006, 03:51 PM
#10
Lani
Senior Member

Join Date: Mar 2006
Posts: 1,988



references

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

01-07-2008, 06:08 PM #3
Lani
Senior Member

Join Date: Mar 2006
Posts: 2,762
another article I just refound:
Anticancer Drugs. 2007 Jan;18(1):23-8. Links
Ratio of trastuzumab levels in serum and cerebrospinal fluid is altered in HER2-positive breast cancer patients with brain metastases and impairment of blood-brain barrier.

Stemmler HJ, Schmitt M, Willems A, Bernhard H, Harbeck N, Heinemann V.
Medical Department III, Ludwig-Maximilians University of Munich, Clinic Grosshadern, Munich, Germany. Joachim.Stemmler@med.uni-muenchen.de
Patients receiving trastuzumab for HER2-overexpressing metastatic breast cancer seem to suffer from an increased risk of brain metastases, even in cases with responsive disease. To evaluate whether trastuzumab is able to penetrate the blood-brain barrier, we measured trastuzumab levels in the serum and in cerebrospinal fluid of metastatic breast cancer patients with brain metastases receiving trastuzumab for HER2-overexpressing metastatic breast cancer. In a pilot study, metastatic breast cancer patients with brain metastases and HER2-overexpressing tumors (HercepTest; Dako, Copenhagen, Denmark) were included. At different time points, trastuzumab levels in the serum and cerebrospinal fluid were measured using a newly developed immunoenzymatic test for trastuzumab. Six out of eight patients were evaluable for determination of trastuzumab level in the serum and cerebrospinal fluid. Before radiotherapy, median trastuzumab level in the serum was 52 054 ng/ml compared with 124 ng/ml in cerebrospinal fluid (ratio 420 : 1). After completion of radiotherapy, median trastuzumab level was 20 185 ng/ml in the serum and 226 ng/ml in cerebrospinal fluid, respectively (ratio 76 : 1). With concomitant meningeal carcinomatosis, trastuzumab level in the serum after radiotherapy was 17 431 and 356 ng/ml in cerebrospinal fluid (ratio 49 : 1). For the first time, we present clinical evidence that trastuzumab levels in cerebrospinal fluid are increased under conditions of an impaired blood-brain barrier such as meningeal carcinomatosis or radiotherapy. This evidence supports the concept of continuing trastuzumab therapy in patients with brain metastases treated by radiotherapy. Monitoring of trastuzumab levels in the serum and cerebrospinal fluid may enable individualized therapy strategies in metastatic breast cancer patients with brain metastases, and lead to a better understanding of trastuzumab pharmacokinetics in the cerebrospinal fluid and serum.
PMID: 17159499 [PubMed - indexed for MEDLINE]

[Believe51]

Patty please send. I appreciated your 'last options' folder but nothing in that or in my folder will help. For the first time ever I feel this matter is hopeless. Of all times this is not the one to lose hope. HoHum.>>Believe51

[Lani]

new drug improves survival, qual of life when combined with WBR(whole brain radiation
Am J Clin Oncol. 2007 Dec;30(6):580-7.
Improved survival, quality of life, and quality-adjusted survival in breast cancer patients treated with efaproxiral (Efaproxyn) plus whole-brain radiation therapy for brain metastases.

Scott C, Suh J, Stea B, Nabid A, Hackman J.
CBS Squared, Inc., Fort Washington, Pennsylvania 19034, USA. cbssquared@comcast.net
OBJECTIVE: To determine whether efaproxiral, an allosteric modifier of hemoglobin, improves quality of life and quality of survival in patients with primary breast cancer and brain metastases when used as an adjunct to whole-brain radiation therapy (WBRT). METHODS: Patients with brain metastases from breast cancer were randomly assigned to receive WBRT and either efaproxiral or no efaproxiral. The primary endpoint for this analysis was quality of life and quality-adjusted survival. Quality of life was assessed prior to initiation of WBRT and periodically in follow-up using the Spitzer Quality of Life Index (SQLI). RESULTS: A subgroup of 106 eligible breast cancer patients with baseline SQLI were randomized into this study and represent the target population discussed in this report. Treatment, age, and SQLI were significant predictors of survival. The addition of efaproxiral to WBRT reduced the death rate by 46% (P = 0.0086). Quality of life was improved in the WBRT + efaproxiral arm compared with the WBRT alone arm (P = 0.019). Quality-adjusted survival was statistically significantly improved by the addition of efaproxiral to WBRT (P = 0.001). CONCLUSION: Survival, quality of life, and quality-adjusted survival were all improved in breast cancer patients with brain metastases receiving efaproxiral and WBRT compared with those receiving WBRT alone.
PMID: 18091051 [PubMed - in process]

Article shows the other people involved in writing the paper were with University Cancer centers (not the drug company), that her2+ was responsible for an inordinate number of the bc brain met population due to its proclivity for the the brain, other factors.

[hutchibk]

Marie - I don't have any details, but a friend of mine was offered intrathecal treatment (a port in the head and direct delivery of chemo/targeted agent) for brain mets. She opted not to do it. Me? I probably would consider it... everyone is different. I think this is what Lani's post refers to...

love and prayers.

[Lani]

All the articles agree it is very advantageous to keep herceptin going once you have brain mets-they theorize the blood brain barrier is somewhat more permeable or some indirect effect is responsible

I also came by this (not mine) in the search function:
RTA 744 in Breast Cancer Patients With Progression of Previously Irradiated Brain Met
RTA 744 in Breast Cancer Patients With Progression of Previously Irradiated Brain Mets

RTA 744 is a novel, anthracycline that has shown the ability to circumvent ATP-binding cassette transporters (Multidrug Resistance Protein 1, Breast Cancer Resistance Protein, P-glycoprotein) in vitro. This action enables RTA 744 to penetrate across the blood brain barrier. In a Phase I safety study, RTA 744 was shown to be generally well tolerated in patients with recurrent gliolastoma multiforme (GBM). Additionally, anti-tumor activity was observed. Breast cancer is known to be sensitive to anthracycline therapy. Based on the preliminary Phase I clinical results and the sensitivity of breast cancer to anthracycline therapy, this Phase II study will investigate the safety and efficacy of RTA 744 in patients with breast cancer and metastatic disease to the brain which has progressed following whole brain irradiation.

http://www.clinicaltrials.gov/ct/sho...395112?order=2

[pattyz]

Marie... can I say more than just 'hell' here??? Pretend I did, ok.

I can't think of what I sent that must be written off if it was not tried?

My onc wants to go right to Irinotecan w/my Temodar. There is an oral Irinotecan, which I like, at a dose of about 50/60mg/m2 Dx5. It is also in trial now for 'us' this way.

Besides w/Temodar, it is also used or in trial with:
*Oral etoposide aka: VePesidR
*Avastin - yes, honest for brain mets.


There is an older chemo 'Lomustine':
Lomustine Offers Effective Low Cost Treatment for Lung and Breast Cancer Brain Metastases (Doctor's Guide)
Reports results from a small study presented at the 14th International Congress on Anti-Cancer Treatment (ICACT) of the efficacy and toxicity of lomustine in patients with lung or breast cancer brain metastases. [2/03]
What this drug is used for:Treatment of brain tumors, both primary (developed in the brain) and metastatic

*And: Temodar w/Doxil -
2004 ASCO Annual Meeting
Category: Central Nervous System Tumors
Abstract No: 1576 Two CR and two PRs was recorded in the four patients with breast tumours,
Conclusions: the schedule was a well tolerated treatment (also in elder pts.) and has suggested an encouraging activity in brain metastases from breast.

*Topotecan:
Single-agent topotecan, especially in patients with SCLC or breast cancer, has demonstrated excellent response rates against brain metastases and may be safely and effectively combined with other chemotherapeutic drugs that have the ability to pass the intact blood-brain barrier....

*And these trials:
* ZK219477 in Patients With Breast Cancer and Brain Metastases
The purpose of this Phase II clinical trial is to determine the effects, both good and bad, of a new chemotherapeutic drug called ZK219477 that appears to cross the blood-brain barrier and penetrate into the brain.
* Epothilone B in Treating Patients With CNS Metastases From Breast Cancer
This phase II trial is studying how well a new experimental treatment known as epothilone B (patupilone) works in treating patients with CNS metastases from breast cancer that have recurred after whole brain radiation. Patupilone does cross the blood-brain barrier.

However, the trial Lani posted was terminated = Business decision. ?? the RTA 744

Gd, I pray you can find something for Ed to try. I'm focused on oral at the moment. IV's next... or whatever happens.

xoxopatty

[Lani]

Please see my post in the last couple of days of a new and more effective way of taking lapatinib00ie higher dose but intermittently

J Natl Cancer Inst. 2008 Aug 6;100(15):1092-103. Epub 2008 Jul 29. Links

Effect of lapatinib on the outgrowth of metastatic breast cancer cells to the brain.

Gril B, Palmieri D, Bronder JL, Herring JM, Vega-Valle E, Feigenbaum L, Liewehr DJ, Steinberg SM, Merino MJ, Rubin SD, Steeg PS.
Women's Cancers Section, Laboratory of Molecular Pharmacology, National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Building 37, Room 1122, MSC 4254, Bethesda, MD 20892, USA.
BACKGROUND: The brain is increasingly being recognized as a sanctuary site for metastatic tumor cells in women with HER2-overexpressing breast cancer who receive trastuzumab therapy. There are no approved or widely accepted treatments for brain metastases other than steroids, cranial radiotherapy, and surgical resection. We examined the efficacy of lapatinib, an inhibitor of the epidermal growth factor receptor (EGFR) and HER2 kinases, for preventing the outgrowth of breast cancer cells in the brain in a mouse xenograft model of brain metastasis. METHODS: EGFR-overexpressing MDA-MB-231-BR (231-BR) brain-seeking breast cancer cells were transfected with an expression vector that contained or lacked the HER2 cDNA and used to examine the effect of lapatinib on the activation (ie, phosphorylation) of cell signaling proteins by immunoblotting, on cell growth by the tetrazolium salt 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay, and on cell migration using a Boyden chamber assay. The outgrowth of large (ie, >50 microm(2)) and micrometastases was counted in brain sections from nude mice that had been injected into the left cardiac ventricle with 231-BR cells and, beginning 5 days later, treated by oral gavage with lapatinib or vehicle (n = 22-26 mice per treatment group). All statistical tests were two-sided. RESULTS: In vitro, lapatinib inhibited the phosphorylation of EGFR, HER2, and downstream signaling proteins; cell proliferation; and migration in 231-BR cells (both with and without HER2). Among mice injected with 231-BR-vector cells, those treated with 100 mg lapatinib/kg body weight had 54% fewer large metastases 24 days after starting treatment than those treated with vehicle (mean number of large metastases per brain section: 1.56 vs 3.36, difference = 1.80, 95% confidence interval [CI] = 0.92 to 2.68, P < .001), whereas treatment with 30 mg lapatinib/kg body weight had no effect. Among mice injected with 231-BR-HER2 cells, those treated with either dose of lapatinib had 50%-53% fewer large metastases than those treated with vehicle (mean number of large metastases per brain section, 30 mg/kg vs vehicle: 3.21 vs 6.83, difference = 3.62, 95% CI = 2.30 to 4.94, P < .001; 100 mg/kg vs vehicle: 3.44 vs 6.83, difference = 3.39, 95% CI = 2.08 to 4.70, P < .001). Immunohistochemical analysis revealed reduced phosphorylation of HER2 in 231-BR-HER2 cell-derived brain metastases from mice treated with the higher dose of lapatinib compared with 231-BR-HER2 cell-derived brain metastases from vehicle-treated mice (P < .001). CONCLUSIONS: Lapatinib is the first HER2-directed drug to be validated in a preclinical model for activity against brain metastases of breast cancer.
PMID: 18664652

[Lani]

here is one of her paper's abstracts:
Breast Dis. 2006-2007;26:139-47. Links

Brain metastases of breast cancer.

Palmieri D, Smith QR, Lockman PR, Bronder J, Gril B, Chambers AF, Weil RJ, Steeg PS.
Women's Cancers Section, Laboratory of Molecular Pharmacology, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
Central nervous system or brain metastases traditionally occur in 10-16% of metastatic breast cancer patients and are associated with a dismal prognosis. The development of brain metastases has been associated with young age, and tumors that are estrogen receptor negative, Her-2+ or of the basal phenotype. Treatment typically includes whole brain irradiation, or either stereotactic radiosurgery or surgery with whole brain radiation, resulting in an approximately 20% one year survival. The blood-brain barrier is a formidable obstacle to the delivery of chemotherapeutics to the brain. Mouse experimental metastasis model systems have been developed for brain metastasis using selected sublines of human MDA-MB-231 breast carcinoma cells. Using micron sized iron particles and MRI imaging, the fate of MDA-MB-231BR cells has been mapped: Approximately 2% of injected cells form larger macroscopic metastases, while 5% of cells remain as dormant cells in the brain. New therapies with permeability for the blood-brain barrier are needed to counteract both types of tumor cells.
PMID: 17473372

Thinking out louad. To get rid of the dormant cells, the bc stem cells, Dr. Max Wicha has started a trial of gamma secretase inhibitor (a drug normally tried vs. Alzheimer's so it must get into the brain)

How about seeing if those trials allow brain mets (U of Michigan, Baylor and one or two other sites if I recall correctly)

It is 224 am in Denmark, so got to get some ZZZZ

Try the website brainmets.org that Dr. Steeg advocates at all the meetings

[WomanofSteel]

Marie, you already know how I feel. Holding you and Ed in prayer and a great big hug to you both.

[Lani]

9/11/08 2:10 PM
Sagopilone crosses the blood-brain barrier in vivo...[Neuro Oncol. 2008] - PubMed Result
Page 1 of 1
http://www.ncbi.nlm.nih.gov.laneprox...ubmed_RVDocSum
1: Neuro Oncol. 2008 Sep 9. [Epub ahead of print]
PMID: 18780814 [PubMed - as supplied by publisher]
Sagopilone crosses the blood-brain barrier in vivo to inhibit brain tumor
growth and metastases.
Hoffmann J, Fichtner I, Lemm M, Lienau P, Hess-Stumpp H,
Rotgeri A, Hofmann B, Klar U.
Bayer Schering Pharma AG, TRG Oncology, Müllerstrasse 172178, 13342 Berlin,
Germany.
The aim of this study was to determine the efficacy of sagopilone
(ZK-EPO), a novel epothilone, compared with other anticancer agents
in human orthotopic models of primary and secondary brain tumors.
Autoradiography and pharmacokinetic analyses were performed on
rats and mice to determine passage across the blood-brain barrier
and organ distribution of sagopilone. Mice bearing intracerebral
human tumors (U373 or U87 glioblastoma, MDA-MB-435 melanoma,
or patient-derived non-small-cell lung cancer [NSCLC]) were treated
with sagopilone 510 mg/kg, paclitaxel 812.5 mg/kg (or temozolomide
100 mg/kg), or control (vehicle only). Tumor volume was measured
to assess antitumor activity. Sagopilone crossed the blood-brain
barrier in both rat and mouse models, leading to therapeutically
relevant concentrations in the brain with a long half-life. Sagopilone
exhibited significant antitumor activity in both the U373 and U87
human glioblastoma models, while paclitaxel showed a limited effect
in the U373 model. Sagopilone significantly inhibited the growth of
tumors from CNS metastases models (MDA-MB-435 melanoma and
patient-derived Lu7187 and Lu7466 NSCLC) implanted in the brains of
nude mice, in contrast to paclitaxel or temozolomide. Sagopilone has
free access to the brain. Sagopilone demonstrated significant
antitumor activity in orthotopic models of both glioblastoma and CNS
metastases compared with paclitaxel or temozolomide, underlining the
value of further research evaluating sagopilone in the treatment of
brain tumors. Sagopilone is currently being investigated in a broad
phase II clinical trial program, including patients with glioblastoma,
NSCLC, breast cancer, and melanoma.