HER2 Support Group Forums - View Single Post - ~Too Many Brain Mets To Count~Mighty Oak's Saga Continues...

Lani · 06-12-2009, 04:26 PM

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]

06-12-2009, 04:26 PM	#11
Lani Senior Member Join Date: Mar 2006 Posts: 4,778	I quickly put Lani brain met into the search above and found 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]