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info. more brain mets help!

Forums General Melanoma Community info. more brain mets help!

  • Post
    Tracey FL
    Participant

    I have not been on for a few months.  Mom has been going to Moffitt for two different trials PD-1 and fluradarbine (sp) they failed.  The tumors have spread to the brain.  She had the radio knife done two weeks ago on three of her small brain tumors.  We just found out that she has more brain tumors.  She has more tumors in the body cavity and on the neck rather large ones.  The Drs want to do whole brain radiation now, 5 days a week for 4 weeks.  She is now on Chemo and no longer at Moffitt, they sent her home for the chemo since it can be done

    I have not been on for a few months.  Mom has been going to Moffitt for two different trials PD-1 and fluradarbine (sp) they failed.  The tumors have spread to the brain.  She had the radio knife done two weeks ago on three of her small brain tumors.  We just found out that she has more brain tumors.  She has more tumors in the body cavity and on the neck rather large ones.  The Drs want to do whole brain radiation now, 5 days a week for 4 weeks.  She is now on Chemo and no longer at Moffitt, they sent her home for the chemo since it can be done in South Florida She is still doing rather well but I have started to see her get weak  not in to much pain (most of the pain is from some back problems).  Her hair is gone and she has lost 20 lbs.  I don't know what to do.  Mom has been fighting this stage lV since March.  I want to do the best thing for her, and it seems that her options are running out.  Has anyone been at this stage and been able to go back to some trials?  Has anyone done a BRAF or any of the others I see on this web site talked about at this stage.  I feel that I am loosing hope.  She says that she just does not want to travel any more.  I think that is why I feel helpless.  I am sorry that I am rambling on.

    I pray for everyone with this.

    Tracey

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      EricNJill
      Participant

      Tracey,

      I'm so sorry for all that you and your family are going through.  I know that they opened a Compassionate Use Trial for PLX4032 (BRAF Positive) and I did not remember seeing that Brain Mets were an exclusion.  My husband had a brain met in November that was removed and he had radiosurgery as well so we are looking into that trial too.

      My advice would be to read this article.  http://www.internalmedicinenews.com/single-view/brief-decline-in-quality-of-life-seen-after-brain-radiotherapy/751443a3b9.html

      It's a tough decision and there isn't one answer for everyone.  I think you are doing the right thing, asking questions here on the board.  I'm sure you will get some good information from others who have had WBR. 

      I hope everything works out for you mom and you can have a Merry Christmas.

      JillNEric in OH

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      EricNJill
      Participant

      Tracey,

      I'm so sorry for all that you and your family are going through.  I know that they opened a Compassionate Use Trial for PLX4032 (BRAF Positive) and I did not remember seeing that Brain Mets were an exclusion.  My husband had a brain met in November that was removed and he had radiosurgery as well so we are looking into that trial too.

      My advice would be to read this article.  http://www.internalmedicinenews.com/single-view/brief-decline-in-quality-of-life-seen-after-brain-radiotherapy/751443a3b9.html

      It's a tough decision and there isn't one answer for everyone.  I think you are doing the right thing, asking questions here on the board.  I'm sure you will get some good information from others who have had WBR. 

      I hope everything works out for you mom and you can have a Merry Christmas.

      JillNEric in OH

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      LynnLuc
      Participant

      The idea of whole brain radiation scares the crap out of me, but I know of one lady who had stage 4 melanoma and went thru it…it took care ofall  her melanoma mets..and she recovered ok  just took awhile to come back …I think the idea of getting my head bolted down so I don't move…I just couldn't do it unless they put me to sleep before they do that…just not being able to move is a scary concept to me. I had a couple weeks of radiation but it was to my chest…they said not to move and I didn't…but I wasn't restrained.

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      LynnLuc
      Participant

      The idea of whole brain radiation scares the crap out of me, but I know of one lady who had stage 4 melanoma and went thru it…it took care ofall  her melanoma mets..and she recovered ok  just took awhile to come back …I think the idea of getting my head bolted down so I don't move…I just couldn't do it unless they put me to sleep before they do that…just not being able to move is a scary concept to me. I had a couple weeks of radiation but it was to my chest…they said not to move and I didn't…but I wasn't restrained.

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      Sharyn
      Participant

      Hi Tracey,

      I have been Stage IV for almost 2 years, and I have failed every treatment until now. I was diagnosed with brain mets in Oct/09, (2 at 5mm and a dozen or more at 1mm), had WBR and went on Temodar, had 2 more 5mm brain mets in spring 2010, and had gamma knife SRS on the 4 (5mm) mets in May. Then I had a mastectomy for breast mets in Aug, and I'm now on the ipilimumab compassionate use trial since Sept. I don't have my latest CT results yet, but I can tell you that my sub-qs have all but melted away. This is the best response I've ever had to any treatment. 

      I can tell you from experience that your Mom is feeling weak and disinterested because of the chemo. I went through the same thing last Christmas when I did Temodar. Whatever chemo does to the patient, it makes them feel like this is it, this is the beginning of the end. That's how I felt last year. I remember thinking, and even saying, that it was my last Christmas. But once I stopped chemo last year, those thoughts went away as well. So here I am still, with yet another Christmas under my belt and feeling absolutely wonderful!  

      If you are considering a B-RAF inhibitor, your mom will have to first have genetic profiling done to see if she has the B-RAF V600E mutation. Ask her doctor about that.  I wish you both the best of luck with treatments. Merry Christmas, and a healthy, happy New Year.

      Hugs

      Sharyn, Stage IV

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      Sharyn
      Participant

      Hi Tracey,

      I have been Stage IV for almost 2 years, and I have failed every treatment until now. I was diagnosed with brain mets in Oct/09, (2 at 5mm and a dozen or more at 1mm), had WBR and went on Temodar, had 2 more 5mm brain mets in spring 2010, and had gamma knife SRS on the 4 (5mm) mets in May. Then I had a mastectomy for breast mets in Aug, and I'm now on the ipilimumab compassionate use trial since Sept. I don't have my latest CT results yet, but I can tell you that my sub-qs have all but melted away. This is the best response I've ever had to any treatment. 

      I can tell you from experience that your Mom is feeling weak and disinterested because of the chemo. I went through the same thing last Christmas when I did Temodar. Whatever chemo does to the patient, it makes them feel like this is it, this is the beginning of the end. That's how I felt last year. I remember thinking, and even saying, that it was my last Christmas. But once I stopped chemo last year, those thoughts went away as well. So here I am still, with yet another Christmas under my belt and feeling absolutely wonderful!  

      If you are considering a B-RAF inhibitor, your mom will have to first have genetic profiling done to see if she has the B-RAF V600E mutation. Ask her doctor about that.  I wish you both the best of luck with treatments. Merry Christmas, and a healthy, happy New Year.

      Hugs

      Sharyn, Stage IV

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      jim Breitfeller
      Participant

      Tracey,

      You may want to look into this.

       

      Antifolate Activity of Pyrimethamine Enhances Temozolomide-Induced Cytotoxicity in Melanoma Cells.

      Authors

      Chen M, Osman I, Orlow SJ 

      Institution

      Departments of Medicine and Cell Biology, and the New York University Cancer Institute Clinical Cancer Center, New York, New York.

      Source

      Mol Cancer Res 2009 May 12.

      Abstract

      Most metastatic melanoma patients fail to respond to available therapy, underscoring the need to develop more effective treatments. We screened 2,000 compounds from the Spectrum Library in human melanoma cell lines to identify compounds that enhanced the cytotoxic effect of temozolomide, a drug used to treat metastatic melanoma. Screening was done with the temozolomide-resistant melanoma cell line SK-MEL-19, and six compounds were identified that had little or no inherent cytotoxicity but significantly enhanced growth-inhibition by temozolomide. These compounds were tested in five additional melanoma cell lines. Cell proliferation and death assays were used to compare the efficacy of single agent temozolomide versus combination treatments. Effects of combination treatment on levels of DNA double-strand breaks, the DNA repair protein O(6)-methylguanine-DNA-methyltransferase, apoptosis [measured by cleaved caspase-3 and poly(ADP-ribose) polymerase], and cell cycle were examined. Pyrimethamine, an antiparasitic, sensitized melanoma cells to temozolomide. Temozolomide combined with Pyrimethamine synergistically inhibited cell proliferation in melanoma cells with combination index values of 0.7 or less. In addition, combination treatment induced cell cycle arrest and increased both DNA damage and apoptosis. The increase in cell death due to combination treatment was rescued by leucovorin. Other folate antagonists were also effective enhancers of temozolomide-induced cytotoxicity, and the effects of antifolates were also evident in gliomas. Our screening approach led to the identification of Pyrimethamine, an orally available drug that efficiently crosses the blood-brain barrier, as a potent enhancer of the efficacy of temozolomide as an antineoplastic agent via inhibition of folate metabolism.(Mol Cancer Res 2009;7(5):703-12).

       

      Dying Tumor Cells Attracts Dendritic Cells That Activates T cells

      More interestingly, the researchers discovered that tumors cells dying from the viral attack secreted a protein called HMGB1. This protein is specifically recognized by the receptor TLR2 present at the surface of another particular class of white blood cells called myeloid dendritic cells. The presence of HMGB1 attracts and activates the dendritic cells into the brain which, in turn, activate the T lymphocyte cells essential in killing other tumors growing in the brain.

      New Treatment for Brain Tumors ?

      While the effectiveness of such an immunotherapy approach still needs to be proven in humans as a potential treatment against cancer, this study presents a very elegant demonstration of using the specialized mechanisms of the immune system in conjunction with chemotherapy to deliver effective treatment against cancer. It would be interesting to know if such approach could ultimately be considered for the eradication of other types of cancer.

      Read more at Suite101: Anti-Tumor Immunotherapy for Brain Cancer: HMGB1 from Tumor Cells Activates TLR2 Signaling in Dendritic Cells http://www.suite101.com/content/antitumor-immunotherapy-for-brain-cancer-a90636#ixzz1946SNsts

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      jim Breitfeller
      Participant

      Tracey,

      You may want to look into this.

       

      Antifolate Activity of Pyrimethamine Enhances Temozolomide-Induced Cytotoxicity in Melanoma Cells.

      Authors

      Chen M, Osman I, Orlow SJ 

      Institution

      Departments of Medicine and Cell Biology, and the New York University Cancer Institute Clinical Cancer Center, New York, New York.

      Source

      Mol Cancer Res 2009 May 12.

      Abstract

      Most metastatic melanoma patients fail to respond to available therapy, underscoring the need to develop more effective treatments. We screened 2,000 compounds from the Spectrum Library in human melanoma cell lines to identify compounds that enhanced the cytotoxic effect of temozolomide, a drug used to treat metastatic melanoma. Screening was done with the temozolomide-resistant melanoma cell line SK-MEL-19, and six compounds were identified that had little or no inherent cytotoxicity but significantly enhanced growth-inhibition by temozolomide. These compounds were tested in five additional melanoma cell lines. Cell proliferation and death assays were used to compare the efficacy of single agent temozolomide versus combination treatments. Effects of combination treatment on levels of DNA double-strand breaks, the DNA repair protein O(6)-methylguanine-DNA-methyltransferase, apoptosis [measured by cleaved caspase-3 and poly(ADP-ribose) polymerase], and cell cycle were examined. Pyrimethamine, an antiparasitic, sensitized melanoma cells to temozolomide. Temozolomide combined with Pyrimethamine synergistically inhibited cell proliferation in melanoma cells with combination index values of 0.7 or less. In addition, combination treatment induced cell cycle arrest and increased both DNA damage and apoptosis. The increase in cell death due to combination treatment was rescued by leucovorin. Other folate antagonists were also effective enhancers of temozolomide-induced cytotoxicity, and the effects of antifolates were also evident in gliomas. Our screening approach led to the identification of Pyrimethamine, an orally available drug that efficiently crosses the blood-brain barrier, as a potent enhancer of the efficacy of temozolomide as an antineoplastic agent via inhibition of folate metabolism.(Mol Cancer Res 2009;7(5):703-12).

       

      Dying Tumor Cells Attracts Dendritic Cells That Activates T cells

      More interestingly, the researchers discovered that tumors cells dying from the viral attack secreted a protein called HMGB1. This protein is specifically recognized by the receptor TLR2 present at the surface of another particular class of white blood cells called myeloid dendritic cells. The presence of HMGB1 attracts and activates the dendritic cells into the brain which, in turn, activate the T lymphocyte cells essential in killing other tumors growing in the brain.

      New Treatment for Brain Tumors ?

      While the effectiveness of such an immunotherapy approach still needs to be proven in humans as a potential treatment against cancer, this study presents a very elegant demonstration of using the specialized mechanisms of the immune system in conjunction with chemotherapy to deliver effective treatment against cancer. It would be interesting to know if such approach could ultimately be considered for the eradication of other types of cancer.

      Read more at Suite101: Anti-Tumor Immunotherapy for Brain Cancer: HMGB1 from Tumor Cells Activates TLR2 Signaling in Dendritic Cells http://www.suite101.com/content/antitumor-immunotherapy-for-brain-cancer-a90636#ixzz1946SNsts

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