Met with Ocular Melanoma Oncologist

[ammebarb]

Lani, I can stand any little piece of good news that I can get! No one ever mentioned gender difference when it came to mets, so this was a boost to read. I am trying not to be insensitive to the men who are also dealing with this horrible disease. Thanks, Lani!

[Lani]

this may not be good news--but it may turn out to be very useful information advising caution with avastin shots in the eye in those with ocular melanoma:

this was done in mice and in petri dishes, but points out the theoretical risk if any melanoma cells are left

I also listed articles on both intracameral/intraocular and systemic avastin's effects on radiation induced injury to the eye--several done on those receiving proton therapy, one even on micromets to the liver.

SO it should be possible for you to use entrez pub med to research based on intraocular vs systemic avastin and perhaps ask if they think they got every cell and if the avastin is preventative to protect your vision from the longterm effects of the radiation or to prevent recurrence/mets.

I have not yet looked up clinical trials but can give you the names my friend listed as knowing who might be best to consult. You are not so far from the NIH-- I have not yet identified who the NIH's ocular melanoma expert(s) is/are.

names: I think Sapna Patel or Scott Woodman at MDAnderson might know, also Rich Carvajal at MSKCC

MEK inibitors are being tried and there is a theoretical reason to try gamma secretase inhibitors. Now to look up trials...


Mol Vis. 2012;18:2454-67. Epub 2012 Oct 5.
Bevacizumab and intraocular tumors: an intriguing paradox.
el Filali M, Ly LV, Luyten GP, Versluis M, Grossniklaus HE, van der Velden PA, Jager MJ.
Source
Department of Ophthalmology, LUMC, Leiden, the Netherlands. m.el_filali@lumc.nl
Abstract
PURPOSE:
Bevacizumab, a humanized monoclonal antibody to vascular endothelial growth factor-A (VEGF-A), was originally developed as an anti-tumor treatment. In ocular oncology, it is being used to treat macular edema due to radiation retinopathy, but it may also be useful for the treatment of primary uveal melanoma (UM) or its metastases. We determined the effect of bevacizumab on the growth of B16F10 cells inside the eye and on B16F10 and UM cells cultured in vitro.
METHODS:
B16F10 melanoma cells were placed into the anterior chamber of the eye of C57Bl/6 mice and tumor growth was monitored after injection of different doses of bevacizumab or mock injection. In addition, the effect of bevacizumab on in vitro growth of B16F10 and human UM cells and on the expression of VEGF-A, GLUT-1, and HIF-1α was evaluated.
RESULTS:
Following intraocular injection of bevacizumab into murine B16 tumor-containing eyes, an acceleration of tumor growth was observed, with the occurrence of anterior chamber hemorrhages. Bevacizumab did not affect proliferation of B16F10 cells in vitro, while it inhibited UM cell proliferation. Expression analysis demonstrated that addition of bevacizumab under hypoxic conditions induced VEGF-A, GLUT-1 and HIF-1α in B16F10 cells as well as in UM cell lines and two of four primary UM tumor cultures.
CONCLUSIONS:
In contrast with expectations, intraocular injection of bevacizumab stimulated B16F10 melanoma growth in murine eyes. In vitro exposure of B16 and human UM cells to bevacizumab led to paradoxical VEGF-A upregulation. The use of VEGF inhibitors for treatment of macular edema (due to radiation retinopathy) after irradiation of UM should be considered carefully, because of the possible adverse effects on residual UM cells.
PMID: 23077404 [PubMed - indexed for MEDLINE] PMCID: PMC3472924 Free PMC Article

entrez pubmed---
Bevacizumab and intraocular tumors: an intriguing paradox.
el Filali M, Ly LV, Luyten GP, Versluis M, Grossniklaus HE, van der Velden PA, Jager MJ.
Mol Vis. 2012;18:2454-67. Epub 2012 Oct 5.
PMID: 23077404 [PubMed - indexed for MEDLINE] Free PMC Article
Related citations
Select item 22753717
2.
New therapeutic agents in uveal melanoma.
Velho TR, Kapiteijn E, Jager MJ.
Anticancer Res. 2012 Jul;32(7):2591-8. Review.
PMID: 22753717 [PubMed - indexed for MEDLINE]
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Select item 22270078
3.
Uveal melanoma.
Spagnolo F, Caltabiano G, Queirolo P.
Cancer Treat Rev. 2012 Aug;38(5):549-53. doi: 10.1016/j.ctrv.2012.01.002. Epub 2012 Jan 24. Review.
PMID: 22270078 [PubMed - indexed for MEDLINE]
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Select item 21445839
4.
Systemic bevacizumab (Avastin) for exudative retinal detachment secondary to choroidal melanoma.
Newman H, Finger PT, Chin KJ, Pavlick AC.
Eur J Ophthalmol. 2011 Nov-Dec;21(6):796-801. doi: 10.5301/EJO.2011.6477.
PMID: 21445839 [PubMed - indexed for MEDLINE]
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5.
Antivascular endothelial growth factor bevacizumab for radiation optic neuropathy: secondary to plaque radiotherapy.
Finger PT, Chin KJ.
Int J Radiat Oncol Biol Phys. 2012 Feb 1;82(2):789-98. doi: 10.1016/j.ijrobp.2010.11.075. Epub 2011 Jan 27.
PMID: 21277107 [PubMed - indexed for MEDLINE]
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6.
Current treatments for radiation retinopathy.
Giuliari GP, Sadaka A, Hinkle DM, Simpson ER.
Acta Oncol. 2011 Jan;50(1):6-13. doi: 10.3109/0284186X.2010.500299. Epub 2010 Aug 20. Review.
PMID: 20722590 [PubMed - indexed for MEDLINE]
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7.
Angiogenesis and vascular endothelial growth factors in intraocular tumors.
Missotten GS, Schlingemann RO, Jager MJ.
Dev Ophthalmol. 2010;46:123-32. doi: 10.1159/000320015. Epub 2010 Aug 10.
PMID: 20703038 [PubMed - indexed for MEDLINE]
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8.
Intravitreal bevacizumab for macular edema due to proton beam radiotherapy: Favorable results shown after eighteen months follow-up.
Loukianou E, Brouzas D, Georgopoulou E, Koutsandrea C, Apostolopoulos M.
Ther Clin Risk Manag. 2010 May 25;6:249-52.
PMID: 20526443 [PubMed] Free PMC Article
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9.
Intravitreal bevacizumab for iris neovascularization following proton beam irradiation for choroidal melanoma.
Yeung SN, Paton KE, Waite C, Maberley DA.
Can J Ophthalmol. 2010 Jun;45(3):269-73. doi: 10.3129/i09-259.
PMID: 20379286 [PubMed - indexed for MEDLINE]
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10.
Bevacizumab suppression of establishment of micrometastases in experimental ocular melanoma.
Yang H, Jager MJ, Grossniklaus HE.
Invest Ophthalmol Vis Sci. 2010 Jun;51(6):2835-42. doi: 10.1167/iovs.09-4755. Epub 2010 Jan 20.
PMID: 20089875 [PubMed - indexed for MEDLINE] Free PMC Article
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11.
[Intraocular bevacizumab as palliative therapy in melanoma-metastasis-associated rubeotic secondary glaucoma].
Jaissle GB, Ulmer A, Henke-Fahle S, Aisenbrey S, Fierlbeck G, Bartz-Schmidt KU, Szurman P.
Klin Monbl Augenheilkd. 2009 Jan;226(1):70-2. doi: 10.1055/s-2008-1027782. Epub 2009 Jan 27. German. No abstract available.
PMID: 19173168 [PubMed - indexed for MEDLINE]
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12.
Intracameral bevacizumab in the treatment of neovascular glaucoma and exudative retinal detachment after brachytherapy in choroidal melanoma.
Vásquez LM, Somani S, Altomare F, Simpson ER.
Can J Ophthalmol. 2009 Feb;44(1):106-7. doi: 10.3129/i08-171. No abstract available.
PMID: 19169330 [PubMed - indexed for MEDLINE]
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13.
Suppression of melanoma-associated neoangiogenesis by bevacizumab.
Jaissle GB, Ulmer A, Henke-Fahle S, Fierlbeck G, Bartz-Schmidt KU, Szurman P.
Arch Dermatol. 2008 Apr;144(4):525-7. doi: 10.1001/archdermatol.2007.38.
PMID: 18427047 [PubMed - indexed for MEDLINE]
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14.
Treatment of iris melanoma and secondary neovascular glaucoma using bevacizumab and plaque radiotherapy.
Bianciotto C, Shields CL, Kang B, Shields JA.
Arch Ophthalmol. 2008 Apr;126(4):578-9. doi: 10.1001/archopht.126.4.578. No abstract available.
PMID: 18413538 [PubMed - indexed for MEDLINE]
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[Lani]

I hope you never need this but Dr Rosenberg is the man I spoke of at the NIH who is curing widely metastatic melanoma patients who have had multiple multiple previous treatments with adoptive T cell therapy

From the NCI website:


Trial and Protocol Number
Melanoma
Phase II
Phase II Study in Patients With Metastatic Melanoma Using a Non-Myeloablative Lymphocyte Depleting Regimen of Chemotherapy Followed by Infusion of MART-1 Reactive Peripheral Blood Lymphocytes (PBL) With or Without High Dose Aldesleukin
NCI-12-C-0045, NCT01495572

Principal Investigator: Referral Contact:
Udai Kammula June A. Kryk
301-435-8606 1-866-820-4505
(Toll Free)
ncisbirc@mail.nih.gov
A Pilot Study of the Administration of Young Tumor Infiltrating Lymphocytes Following a Non-Myeloablative Lymphocyte Depleting Chemotherapy Regimen in Metastatic Melanoma
NCI-11-C-0260, NCT01468818

Principal Investigator: Referral Contact:
Steven A. Rosenberg June A. Kryk
1-866-820-4505 (Toll Free) 1-866-820-4505
(Toll Free)
ncisbirc@mail.nih.gov
Phase II Study of Tumor Infiltrating Lymphocytes Generated With Engineered Cells for Costimulation Enhancement in Patients With Metastatic Melanoma Following Lymphodepletion
NCI-11-C-0163, NCT01369875

Principal Investigator: Referral Contact:
Steven A. Rosenberg June A. Kryk
1-866-820-4505 (Toll Free) 1-866-820-4505
(Toll Free)
ncisbirc@mail.nih.gov
Phase I/II
A Phase I/II Study of IL-15 Administration Following a Non-Myeloablative Lymphocyte Depleting Chemotherapy Regimen and Autologous Lymphocyte Transfer in Metastatic Melanoma
NCI-11-C-0170, NCT01369888

Principal Investigator: Referral Contact:
Steven A. Rosenberg June A. Kryk
1-866-820-4505 (Toll Free) 1-866-820-4505
(Toll Free)
ncisbirc@mail.nih.gov
Phase I/II Study of Metastatic Melanoma Using Lymphodepleting Conditioning Followed by Infusion of CD8 Enriched Tumor Infiltrating Lymphocytes Genetically Engineered to Express IL-12
NCI-11-C-0011, NCT01236573

Principal Investigator: Referral Contact:
Steven A. Rosenberg June A. Kryk
1-866-820-4505 (Toll Free) 1-866-820-4505
(Toll Free)
ncisbirc@mail.nih.gov
Phase I
An Open-label, Multicenter, Single-arm, Phase I Dose-escalation With Efficacy Tail Extension Study of RO5185426 in Pediatric Patients With Surgically Incurable and Unresectable Stage IIIC or Stage IV Melanoma Harboring BRAF V600 Mutations
NCI-13-C-0064, NCT01519323

Principal Investigator: Referral Contact:
Melinda Merchant Pediatric Oncology
301-443-7955 301-496-4256
1-877-624-4878 (Toll free)

A Pilot Trial of the Combination of Vemurafenib With Adoptive Cell Therapy in Patients With Metastatic Melanoma
NCI-12-C-0114, NCT01585415

Principal Investigator: Referral Contact:
Steven A. Rosenberg June A. Kryk
1-866-820-4505 (Toll Free) 1-866-820-4505
(Toll Free)
ncisbirc@mail.nih.gov
No Phase
Prospective Randomized Study of Cell Transfer Therapy for Metastatic Melanoma Using Tumor Infiltrating Lymphocytes Plus IL-2 Following Non-Myeloablative Lymphocyte Depleting Chemo Regimen Alone or in Conjunction With 12Gy Total Body Irradiation (TBI)
NCI-11-C-0123, NCT01319565

Principal Investigator: Referral Contact:
Steven A. Rosenberg June A. Kryk
1-866-820-4505 (Toll Free) 1-866-820-4505
(Toll Free)
ncisbirc@mail.nih.gov



Trial and Protocol Number
Melanoma, Ocular (uveal)
Phase II
Phase II Study in Patients With Metastatic Ocular Melanoma Using a Non-myeloablative Lymphocyte Depleting Regimen of Chemotherapy Followed by Infusion of Autologous Tumor-Infiltrating Lymphocytes With or Without High Dose Aldesleukin
NCI-13-C-0093, NCT01814046

Principal Investigator: Referral Contact:
Udai Kammula June A. Kryk
301-435-8606 1-866-820-4505
(Toll Free)
ncisbirc@mail.nih.gov

[Lani]

WAS AT ASCO AND heard the second talk but not the first

THE good news is that you are not metastatic...the other good news is that they are finding more effective drugs (although immunotherapy sounds more promising in the long run)

The problem is your tumor is rare and they are finding it hard to recruit enough patients for their trials. Let's hope you don't need to be on them.



News and Insights from Memorial Sloan-Kettering
IN THE CLINIC
Memorial Sloan-Kettering Researchers Report on Major Advances in the Treatment of Metastatic Eye and Skin Melanoma
1 commentBy Media Staff | Monday, June 3, 2013

Medical oncologists Jedd Wolchok and Richard Carvajal
Memorial Sloan-Kettering clinician-researchers presented new research on treatments for two different types of melanoma this weekend as part of the 49th annual meeting of the American Society of Clinical Oncology (ASCO). The studies are shedding light on new therapies for advanced uveal melanoma, a rare cancer of the eye, and advanced skin melanoma – two cancers that have always been difficult to treat.

The first study showed that the experimental drug selumetinib is the first therapy able to improve progression-free survival and shrink tumors in patients with advanced uveal melanoma. If confirmed in another clinical trial, the findings might change the way this cancer has been treated for decades.

The second study, which was also published on June 2 in The New England Journal of Medicine, found that more than half of patients with advanced skin melanoma experienced tumor shrinkage of more than 80 percent when given the combination of the immunotherapy drug ipilimumab (YervoyTM) and the investigational antibody drug nivolumab, suggesting that these two drugs may work better together than on their own.

Targeted Drug for Uveal Melanoma
On Saturday, June 1, medical oncologist Richard Carvajal presented findings from a study testing the experimental drug selumetinib as a treatment for patients with metastatic uveal melanoma. This treatment more than doubled the time to progression when compared with chemotherapy. Many patients receiving selumetinib experienced tumor shrinkage, making selumetinib the first systemic therapy ever to benefit patients with this cancer. The findings are potentially practice changing for a disease that has previously had no known effective therapy.

In the Phase II trial, researchers randomly assigned 47 patients with metastatic uveal melanoma to receive selumetinib and 49 patients to receive the current standard therapy, temozolomide. In the selumetinib group, 50 percent of patients experienced tumor shrinkage, with 15 percent achieving major shrinkage.

In comparison, no patients in the temozolomide group achieved significant tumor shrinkage. However, patients whose disease worsened while on temozolomide were able to begin taking selumetinib.

In addition, selumetinib was shown to control tumor growth more than twice as long as temozolomide – for nearly 16 weeks versus seven weeks. Side effects caused by selumetinib were managed by modifying the dosage if needed.

“This is the first randomized study to show that a systemic therapy can provide significant benefit to advanced uveal melanoma patients, who have always had extremely limited treatment options,” says Dr. Carvajal, who is currently planning a confirmatory international, randomized trial for selumetinib led by Memorial Sloan-Kettering.

“Confirming these results could form a foundation for new drug combinations that would maximize selumetinib’s effect, offering a whole new way to treat this historically untreatable disease,” he adds.

Although uveal melanoma is rare – there are only 2,500 cases diagnosed in the United States each year – about half of patients diagnosed eventually develop metastatic disease. The survival time for patients with advanced disease has held steady at nine months to a year for decades. There is currently no drug approved specifically for treatment of this cancer, which does not respond to the drugs given to patients with skin melanoma.

Dr. Carvajal and his team decided to test selumetinib because it blocks the activity of the MEK protein, a key component of a cellular process called the MAPK pathway. This pathway is activated by mutations in the genes Gnaq and Gna11 that occur in more than 85 percent of patients with uveal melanoma, inducing the growth and progression of tumors. Nearly 85 percent of the patients in the trial had such mutations.

Read more about the trial in this story from Reuters.(don't know how to perpetuate link)

for you to appreciate how important this may be, the NCI had the following on their website, which is how I found the article:



News
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Posted: 06/04/2013
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NCI Cancer Center News
Targeted drug for uveal melanoma
Researchers from Memorial Sloan-Kettering Cancer Center presented findings at the annual meeting of the American Society for Clinical Oncology from a study testing the experimental drug selumetinib as a treatment for patients with metastatic uveal melanoma. This treatment more than doubled the time to progression when compared with chemotherapy. Many patients receiving selumetinib experienced tumor shrinkage, making selumetinib the first systemic therapy ever to benefit patients with this cancer. The findings are potentially practice changing for a disease that has previously had no known effective therapy.