Blood Brain Barrier Program - Anyone have info?
 

Hi Ladies,

I am still waiting to see if Tykerb is going to be enough to do the trick to eliminate the six small tumors in my brain as I am NED everywhere else. If Tykerb isn't effective enough, we are going forward with Gamma Knife to blast the suckers.

In doing research on these topics, my husband Jay came across a program at Oregon Health & Science University called the "Blood Brain Barrier Program" where they apparently have a technology that temporarily suspends the BBB's function to allow medication to reach the brain. I was wondering if anyone knows anything about this and whether or not this is a possible treatment option for those of us with brain mets. It seems that if we could just get some of these amazing drugs into our brains, perhaps we could fight and beat these brain mets more easily.

Thoughts? I am going to ask my doctor about this at my next meeting. I am also wondering why drugs such as Herceptin can't be injected into the cerebral fluid and thus given access to the brain that way. I am no medical expert but was just wondering if any of you had any insight.

The website for the Oregon program is : www.ohsu.edu/bbb/

Any info on your personal experiences in treating brain mets is greatly appreciated. I am feeling scared and need something to hope for.

Courtney,

I saw your post over on YSC. I know someone will chime in for you! Good luck!!!

Take care,

"I am also wondering why drugs such as Herceptin can't be injected into the cerebral fluid and thus given access to the brain that way. I am no medical expert but was just wondering if any of you had any insight. "

There was a study several years ago in Germany of this procedure. I found the following article which describes that study: Intrathecal Herceptin

Data was also released at this years San Antonio meeting from a phase II study of a drug being developed by Wyeth - Neratinib which is a small molecule drug similar to Tykerb and also crosses the BBB.

Regards
Joe

Cancer Centers of America do inject chemo and other therapeutics (possibly Herceptin) into a CNS port. I know of someone doing this that goes to the Philadelphia location (but this woman is triple negative so Herceptin wouldn't be considered). Is there a Cancer Center of America close to you to consult with? They do cool and radical therapies there.

Intrathecal Herceptin - hmmm, that sounds promising. Thank you Joe and Becky! I will keep my fingers crossed that Tykerb and Gamma do the trick for my brain mets but it is interesting to know that there are people doing alternative therapies.

If anyone here on the her2support site has had intrathecal herceptin injections, I would be interested in knowing how that worked out? Any major side effects? Was it effective? Herceptin has worked incredibly well for me and has allowed me to reach NED status in body. I am suspecting that it could do the same for my brain if only it could get there.

Hi

Even though I have no experience with what you are seeking, I do have a good memory of the board. We do have a member who posts every so often, Johanna Johanndotter (Iceland) who did have intracranial/CNS Herceptin injections that worked well. Look up her posts and perhaps privately contact her for more information. She is the only one who got someone to do this for her and it worked out well for her. If what you are doing now doesn't work out, I bet Cancer Center of America would try it since they do try chemo this way.

Good luck and please keep us posted.

here are ten articles, only one of which addresses bc brain mets
 

the others being meningiomatous or leptomeningiomatous involvement rather than mets within the brain tissue proper

Will try to forward on to you 1. and 6.

Good luck!

oops! I forgot to post the ten abstracts. Here they are:
 

Items 1 - 10 of 10
One page.
1:
Extended survival of a HER-2-positive metastatic breast cancer patient with brain metastases also treated with intrathecal trastuzumab.
Colozza M, Minenza E, Gori S, Fenocchio D, Paolucci C, Aristei C, Floridi P.
Cancer Chemother Pharmacol. 2008 Nov 6. [Epub ahead of print] No abstract available.
PMID: 18987856 [PubMed - as supplied by publisher]



2:
High-dose intrathecal trastuzumab for leptomeningeal metastases secondary to HER-2 overexpressing breast cancer.
Mir O, Ropert S, Alexandre J, Lemare F, Goldwasser F.
Ann Oncol. 2008 Nov;19(11):1978-80. Epub 2008 Oct 9. No abstract available.
PMID: 18845838 [PubMed - indexed for MEDLINE]



3:
Intrathecal trastuzumab (Herceptin) and methotrexate for meningeal carcinomatosis in HER2-overexpressing metastatic breast cancer: a case report.
Stemmler HJ, Mengele K, Schmitt M, Harbeck N, Laessig D, Herrmann KA, Schaffer P, Heinemann V.
Anticancer Drugs. 2008 Sep;19(8):832-6.
PMID: 18690096 [PubMed - indexed for MEDLINE]


4:
[Two cases treated with trastuzumab as primary chemotherapy]
Murakami K, Sakata H, Miyazawa Y, Matsushita K, Akutsu Y, Nishimori T, Yoneyama Y, Usui A, Kano M, Matsubara H, Ochiai T.
Gan To Kagaku Ryoho. 2007 Oct;34(10):1683-7. Japanese.
PMID: 17940391 [PubMed - indexed for MEDLINE]



5:
CNS complications of breast cancer: current and emerging treatment options.
Kaal EC, Vecht CJ.
CNS Drugs. 2007;21(7):559-79. Review.
PMID: 17579499 [PubMed - indexed for MEDLINE]



6:
Care with intrathecal trastuzumab.
Siderov J.
Lancet Oncol. 2006 Nov;7(11):888. No abstract available.
PMID: 17081914 [PubMed - indexed for MEDLINE]



7:
Meningeal carcinomatosis from breast cancer treated with intrathecal trastuzumab.
Platini C, Long J, Walter S.
Lancet Oncol. 2006 Sep;7(9):778-80. No abstract available.
PMID: 16945774 [PubMed - indexed for MEDLINE]



8:
Application of intrathecal trastuzumab (Herceptintrade mark) for treatment of meningeal carcinomatosis in HER2-overexpressing metastatic breast cancer.
Stemmler HJ, Schmitt M, Harbeck N, Willems A, Bernhard H, Lässig D, Schoenberg S, Heinemann V.
Oncol Rep. 2006 May;15(5):1373-7.
PMID: 16596213 [PubMed - indexed for MEDLINE]



9:
Intrathecal therapy with trastuzumab may be beneficial in cases of refractory schizophrenia.
Sastry PS, Sita Ratna W.
Med Hypotheses. 2004;62(4):542-5.
PMID: 15050103 [PubMed - indexed for MEDLINE]


10:
Use of intrathecal trastuzumab in a patient with carcinomatous meningitis.
Laufman LR, Forsthoefel KF.
Clin Breast Cancer. 2001 Oct;2(3):235. No abstract available.
PMID: 11899418 [PubMed - indexed for MEDLINE]

The knowledge of the women and men on this website never ceases to amaze me. Thank you so much for the info Lani. I am going to bring some of these articles to my onc to see what he thinks. I am praying that the Tykerb will do the trick but I always like to be two steps ahead in anticipating what my next move will be if things fail. Blessings to you all!

No side effects to speak of - I was a little worried because I'd read that a lot of women do not tolerate it well and have indigestion issues. But so far it has been smooth sailing. Now I just have to hope that it is doing something. I go for a follow-up MRI in a few weeks to see if the brain mets have shrunk or (miracle of miracles) are gone completley. My onc has seen this happen before!

Hi Courtney-There is a girl in my UCLA group who gets intrathecal herceptin at UCLA. She has been fighting stage 4 for quite some time - she's VERY young - maybe 30ish and now has to use a wheel chair due to multiple mets in her CNS. I know she's had gamma as well. Send me a pm with your email info and I'll forward it to her.
Flori

Courtney,

I'll see whether I can get some information about Herceptin and intrathecal catheter from a neuro-oncologist that I'm scheduled to meet with in early February. He's at a major cancer research hospital.

In October I had a bc met removed from my left frontal lobe which was followed by stereotatic radiotherapy that ended on Dec. 12, and I'm supposed to follow up with a neuro-oncologist.

I'll let you know.

Joan

Lani - Thank you so much for these abstracts and the ones you sent to my personal email. I am hopeful that there are going to be many options available for treating these brain mets if the Tykerb doesn't do the job. Thank you again!

Thank you, Joan. Keep me posted. You will be in my thoughts and prayers as you wait for your follow-up.

posted this earlier for those with brain mets making decisions
 

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]

You might want to go up to the Search function on the yellow bar above and put in Lani and brain mets..I have posted on various treatments

here is just one from I thread I found I contributed to
 

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, 07:08 PM #3
Lani
Senior Member

Join Date: Mar 2006
Posts: 2,508
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]

Boswellia Information
 

I read the article from Dr. Flavin regarding Boswellia with great interest. I recently wrote Dr. Flavin to ask if there were any counterindications to taking Boswellia with Tykerb and here is what she wrote back:

"We find that the boswelli will reduce tumors in the brain in 3 months but if the patients stay on tykerb or trastuzamab, the tumors then return in 3 more months. We have seen when the patients are not on a HER2 blocker, the Boswellia keeps the tumors regressed as long as the patients take the 1 gram of Boswellia 3 x/day. There are no side effects with this drug."

Has anyone on this site had positive results with Boswellia? Negative results? Any results? I am wondering if I should supplement my treatment with it.

Courtney
 

I see that you are from San Francisco. Have you consulted with the gamma/cyberknife people at UCSF as to whether your tumors are too numerous or large to consider treating them that way.

I have met Penny Sneed,MD a radiation oncologist who I believe specializes in the gamma/cyberknife treatment of brain mets from primarily breast cancer among other metastatic diseases and is listed with Breast Cancer Clinic at UCSF. Perhaps she could also discuss with you whether any of her her2+ patients have been treated with intrathecal herceptin and/or Boswellia and/or Tykerb either before or after her treatments and how they have fared.

I am also following this very closely for personal reasons - 2 mets growing in my brain and 2 new mets/one in each lung and trying to make the right decisions. Thanks for all the info that is getting provided by you - all of you. I do not have to post but I am following up on the info provided.

More Info
 

Scientists Develop a New Drug Delivery System for Brain Cancers

EORTC-NCI-AACR Press Release. 2008 Oct 22


GENEVA, SWITZERLAND - Scientists have developed a new drug delivery system that is capable of crossing the blood-brain barrier to reach and kill cancer cells in the brain, according to research presented at the 20th EORTC-NCIAACR Symposium on Molecular Targets and Cancer Therapeutics in Geneva October 22. Following successful preclinical studies, the technology is being evaluated in two phase I clinical trials in patients with malignant glioma and brain metastases.
The blood-brain barrier is formed by a network of closely sealed endothelial cells in the brain’s capillaries, and it expresses a high level of proteins that pump foreign molecules away from the brain, while allowing others (such as glucose and insulin) that are necessary to the functioning of the brain cells to cross the barrier. This makes it very difficult for molecules, including anti-cancer drugs, to cross the blood-brain barrier and reach tumor cells in the brain. Currently, less than five per cent of drugs (made up of very small molecules) are able to cross the barrier; one example is temozolomide, which is the only chemotherapy available for treating brain tumors such as glioblastoma multiform and progressive anaplastic astrocytoma. These tumors have a poor prognosis and continue to grow, even after treatment with temozolomide. Therefore, new therapies for these hard-to-treat brain tumors are needed urgently.
In four related presentations to the symposium, scientists from Canada, the USA and France described how they are investigating a new drug delivery technology that provides a non-invasive and flexible way of transporting different drugs (for example, antibodies, proteins, peptides, siRNA, small molecules, etc.) across the blood-brain barrier and into the central nervous system.
The drug being evaluated in the four abstracts is called ANG1005. It is made up of one molecule of a peptide called Angiopep-2 joined together with three molecules of paclitaxel, a taxane chemotherapy drug.
Dr Reinhard Gabathuler, author of one of the abstracts and chief scientific officer at Angiochem Inc (Montreal, Canada) – the company that is developing the Angiopep technology and ANG1005 – explained: “Unlike invasive or pharmacological approaches to deliver drugs to the brain, the Angiopep technology utilizes the physiological approach by making use of the receptors on the surface of the blood-brain barrier that are responsible for actively transporting necessary molecules across the barrier to the brain. The family of Angiopeps (including Angiopep-2) has been designed to interact with a specific receptor, Low Density Lipoprotein Receptor Related Protein-1 (LRP- 1). This receptor has many functions, binds over 30 ligands [molecules] of various sizes, and is highly expressed at the blood-brain barrier.”
In laboratory-based tests of ANG1005 on mice and rats, Dr Gabathuler, other scientists in the company and collaborators in the US and Canada found that the drug was transported rapidly across the blood-brain barrier and into the functional part of the brain, the parenchyma.
“In contrast to free paclitaxel, which is normally prevented from reaching the brain by the P-glycoprotein efflux pump, ANG1005 is efficiently transported across the blood-brain barrier, with approximately 100-fold higher transport rate compared to free paclitaxel and 10-fold higher transport rate than temozolomide,” he said.
In addition, the drug resulted in a significant, 27% increase of survival of mice with glioblastoma tumors and a shrinking of glioblastoma tumors in rats.
A second study, led by Dr Francis Bichat, head of the scientific platform at Oncodesign (Dijon, France), evaluated the anti-cancer properties of the drug in cancer cell lines and mice, as well as investigating its toxicity and what happened to the drug in mice.
He found that ANG1005 had the same anti-cancer properties as did free paclitaxel (paclitaxel on its own) in cancer cell lines. Speaking before the conference, he said: “The anti-tumor activity of paclitaxel was maintained with ANG1005 compared with free paclitaxel. There was no loss of activity.” He also found a significant inhibition of brain tumor growth in rats when they were treated with ANG1005, whereas tumors in rats that were treated with paclitaxel did not have their growth inhibited. “This is probably because free paclitaxel is not able to enter the brain,” he said.
“The most interesting finding from this study is the potency of ANG1005 to bypass the blood-brain barrier and to allow paclitaxel into the brain where it shows anti-tumor activity,” said Dr Bichat.
The success of these pre-clinical studies enabled Angiochem Inc to start two phase I clinical trials at cancer centers in the US: one in patients with advanced cancer and brain metastases, and the second in patients with recurrent malignant glioma.
These trials are still being conducted, but, as of 23 September 2008, 22 patients with advanced solid tumors (including breast cancer, melanoma, liver cancer and 15 patients with brain metastases) have been treated with ANG1005 in the first trial. The drug is given by intravenous infusion for one hour, every 21 days. At doses up to 500 mg/m2 the drug appears to be safe and well tolerated and no patient has discontinued due to adverse side effects. The researchers are continuing to increase the dose.
Dr Jean-Paul Castaigne, president and chief executive officer of Angiochem Inc, who presented the clinical trials results, said: “To date, the safety and tolerability of ANG1005 has been excellent in patients with advanced solid tumors and brain metastases.”
In the second trial in patients with recurrent malignant glioma, 12 patients had been treated by 23 September 2008 – eight with glioblastoma multiform, one with anaplastic astrocytoma and three with anaplastic oligondendrocytoma.
Dr Castaigne said: “We have demonstrated that the drug is safe and tolerable up to and including doses of 75 mg/m2 and we are currently evaluating doses of 105 mg/m2. No patient has discontinued due to drug-related adverse side-effects. So far, all patients (with the exception of one) dosed up to 50 mg/m2 have had their disease progress following two cycles of treatment at six weeks. However, it should be noted that 50 mg/m2 of ANG1005 has an equivalent paclitaxel dose of only about 25 mg/m2, which is still quite low for appreciable cytotoxic effects.”
He continued: “To date, treatment options for patients with recurrent malignant glioma are limited and prognosis is bleak because of the brain’s highly evolved physiological structure. Results from both these trials show that Angiopep conjugates may provide a potentially safe and effective way to treat gliomas and other currently unmanageable diseases of the central nervous system. The Angiopep technology is well tolerated, since most of the side-effects observed to date with ANG1005 are caused by paclitaxel, the active drug component.”
Both trials will be reporting their most important results by the end of 2008, and researchers are planning a continuation of the trial in patients with brain cancer in 2009.
Dr Castaigne said: “Angiochem's intention is to continue the early development of ANG1005 until proof-of efficacy is obtained in either progressive malignant gliomas or brain metastases. We will seek to find a partner with significant oncology experience to carry forward the later development stages and marketing of ANG1005.
“Although other technologies have demonstrated abilities to cross the blood-brain barrier, we believe that the Angiopep technology is the furthest developed of the physiological approach and has significant advantages. ANG1005 is the company’s first compound in clinical development using the Angiopep technology. We have been successful in conjugating other chemotherapeutics (e.g. doxorubicin and etoposide) to our technology; preclinical data have demonstrated success in delivering these compounds into the brain and retaining cytotoxic activities. Angiochem is also focusing considerable effort on the conjugation and delivery of other drug classes (including monoclonal antibodies, proteins, peptides, siRNA, etc.) to treat other CNS disorders.”




Regards
Joe

I will be asking my doctor about this tomorrow. Interestingly enough, I can remember about 3 1/2 years ago an acquaintance telling me of women flying in and out for putting the Herceptin treatments where she was. Sometimes it just seems like things move too slow in regards to that.

OK, a question for a propellor head... all this talk of Boswellia Serrata is confusing me, but I am interested.

I have had IMRT and my brain mets are gone. I am now on Tykerb with Herceptin to keep me stable in the brain (LOL) and in the torso, and it is working well in all regards.

Am I a candidate for Boswellia Serrata? Would it do me any good?

Hi Brenda - I can't answer your question about whether or not you are a good candidate but I can share my experience with you and tell you what my doctor said. I am NED in body and have 6 small spots on my brain. I added Tykerb in January to see what kind of an effect it would have by itself on the brain mets (before we do Gamma or WBR we wanted to see if Tykerb could do the trick alone). So far Tykerb is stabalizing things and I asked my onc if I could add Boswellia to the mix to see what it can do too. He read the literature and whole heartedly agreed to let me try it. I go for a follow-up scan in 4 weeks to see if the brain mets are gone, shrinking, or the same. Then we'll decide which radiation treatment to proceed with. However, I am totally optomistic that Tykerb and Boswellia will be enough to have gotten rid of the little buggers. I will keep you posted on what kinds of success I have with it. Definitely ask your doctor about supplementing with Boswellia. I am thrilled that you are doing so well!!!

That's good news Courtney. I was put on Tykerb with Xeloda for a year and a half when I was dxed with 5 small brain mets (ranging in size from 1mm - 9mm) almost 2 years ago. My spots shrunk within 3 months and went dormant for a year and a half while I remained on T/X. It was heavenly! Then, this past August, they started to shine/wake-up again on my MRI (no new ones, just the old ones), so we quickly scheduled me for IMRT brain radiation to zap them before they had a chance to grow or take hold again. They are now gone, daddy, gone, and we changed my treatment to Tykerb/Herceptin, which is also heavenly as far as treatments go, and now I think I might want to consider Boswellia. Wonder if it comes with a protective action once mets have existed or disappeared, or does it just have a "mets zapping" action?
Will mention to my onc and see what he says. I can probably guess, though...

That is great news, Brenda! I am hoping for a similar outcome. Sounds like we are on similar treatment regimens. I am currently on Tykerb/Herceptin/Zometa too. Good luck to you and keep me posted on your status! You are in my thoughts and prayers!