This is Jim Breitfeller's journey into the Maze of Melanoma. Jim Breitfeller has gathered medical information for the patient and the caregiver.
As Lance Armstrong would say "Lets stand Up to Cancer"
Jim's Battle with the Beast July 2005 to present.
Dr. Sigal is the Director of Research at BMS.
Please send a note to Dr. Sigal requesting that BMS open compassionate use for Mr. Doherty. I know it is a long shot/ Hail Mary Pass but, base on my research, this drug with the combination of IL-2 may be able to beat the odds.
Bristol Myer Squibb says "At Bristol-Myers Squibb, we are firmly focused on our Mission to discover, develop and deliver innovative medicines that help patients prevail over serious diseases."
Is this all lip service? Let see if BMS puts their money where their mouth is and grant this compassionate care use for this derserving family. Doherty with his clinal trial of Yervoy (Anti-CTLA-4 therapy) helped get the drug FDA approved through his survival data. The least Bristol could do is to grant the dying man compassionate use of the next generation drug called Anti-PD-1, (BMS-936558)
Bristol-Myer Squibb needs to show some compassion.
It is their ETHICAL Responsibility.
“It is not the strongest of the species that survives, nor the most intelligent, but the one most responsive to change.”
~Charles Darwin~
Take Care,
Jimmy B
I want to thank all the people that has made this day a very special Day.
As a stage IV Melanoma Survivor, I never dreamed that I would be here today to witness my children spread their wings and learn to fly. My daughter was just entering college when I was first diagnosed and my son, Chris was a sophmore in High School. Today, I am preparing to help my son relocate to Connecticut. He just landed an engineering job at an areospace company. My daughter, Jessica is globe-trotting around the world working on her dual Masters in "International Affairs" and "Natural Resources & Sustainable Development". This day, marks Dee and I as offically "Empty Nesters".
This all was made possible by entering a journey that entailed four clinical trials along with the best and internationally renowned medical team that makes climbing Mt. Everst apiece a cake. And you , My carepage friends that kept me on the "Yellow Brick Road". I have won the "lottery of life."
Many Thanks
“It is not the strongest of the species that survives, nor the most intelligent, but the one most responsive to change.”
~Charles Darwin~
Emily Jackson Staff Reporter Darcy Doherty’s last chance at life lies in an experimental drug. The yet-to-be-approved treatment is the only option left for the 48-year-old father of three with metastatic melanoma, believes his oncologist Dr. David Hogg, an attending physician at Princess Margaret Hospital. But maker Bristol-Myers Squibb (BMS) refuses to give Doherty the drug, saying it’s not yet safe for use outside the clinical trial, which Doherty was excluded from because of new cancer growth in his brain. That reason is simply not good enough for Doherty’s family and friends. If he will certainly die without the drug, why not let him try it? “They have an ethical responsibility to try to save a life,” his wife Rebecca Cumming said as she handed out “Help Save Darcy” stickers at the Ride to Conquer Cancer Sunday. “I think they’re afraid it will be harder to get the drug to market if the drug brings harm to patients like Darcy.” About 30 family friends were at the fundraiser to promote a change.org petition pressuring BMS to give Doherty access to the drug by Father’s Day. Wait much longer, Cumming said, and it will be too late. More than 171,000 have signed the plea. “We love our dad very much and we want a lot more time with him,” Doherty’s emotional 13-year-old son Ganden said in a video. A cancerous mole was first removed from Doherty’s back in 2003. By 2007 the cancer spread to his brain. He survived because of a then-experimental drug. His doctor said immune system off-switch blocker BMS-936558, which has had success in phase one of testing, could have similar benefits. BMS is aware of the petition, but did not budge on its decision. The company empathizes with patients who have limited treatment options, said spokeswoman Sonia Choi in a statement Sunday. Compassionate use requests are carefully reviewed using information from a patient’s physician, she said. To get access, the benefits must outweigh the risks. “At this time, there are not enough data on BMS-936558 to allow its use outside of a clinical trial.” Choi could not provide a timeframe on when more data might become available. The trial’s final stages are set for later this year or early 2013. “In the long term, the best way to ensure the broadest access for patients is to successfully register a medicine with health authorities through the conduct of well-controlled clinical trials.” “There’s no obligation on the drug companies to provide compassionate relief,” said Bernard Dickens, professor emeritus of health law and policy at the University of Toronto. BMS “can’t invest money in handing out unproven products if they’re not going to get data for study purposes.” But if the drug wasn’t safe enough to test on humans, it would not go to stage-two testing, argued advocate Frank Burroughs, founder of American organization the Abigail Alliance for Better Access to Developmental Drugs. For now, Doherty tires quickly. Sitting in his wheelchair at the fundraiser, the former big-bank financial services managing director called the petition an “amazing show of the human spirit.” He thinks it’s “kind of crazy” that he can’t get the drug. “It doesn’t hurt to give a guy a chance.” Source:http://www.thestar.com/news/article/1209218--dying-man-fights-to-get-experimental-drug-bristol-myers-squibb-won-t-give-him We have seen this type of action numerous times with BMS.They did this with Yervoy in the early days, closing compationate use. They appear to have no compassion or ethics, Just Greed!!!! to make a buck. I believe Bristol Myer Squibb is doing a disservice to the Cancer Community especially the Melanoma Patients.
"What sets us apart? We believe it's our commitment to patients with serious diseases, our focus on finding innovative medicines that combat those diseases, and our dedication to extending and enhancing human life."
There is no commitment to patients with stage IV Melanoma.
They have dollars Signs in the eyes and don't give a cr%& about the patients.
This is what Big Pharma has become. (Greed)
Take Care,
“It is not the strongest of the species that survives, nor the most intelligent, but the one most responsive to change.”
I have been following this new treatment for a number of years and am trying to get my arms around the science.
When a T-cell is activated, the PD-1 , CTLA-4, ICOS, and others molecule are expressed and upregulated to the surface of the T-cell. Both PD-1 and CTLA-4 are checkpoint molecules that regulate the immune response. They are inhibitory to the point that they can shut down T-cell activation. ICOS on the other hand is a costimulatory molecule that is needed, along with IL-2 to keep the T-cell activated and help proliferate the T-cells.Elevated levels of ICOS mRNA can be detected already one hour after TCR engagement, followed by surface expression within 12 hours. Protein expression reaches a maximum after 48 hours and declines then slightly.
It has been shown that ICOS is inducible within 48 hours of T cell activation on both CD4+ and CD8+ cells after CD28 signaling whereas cytotoxic T lymphocyte antigen-4 (CTLA-4) ligation prevents its upregulation.
First, CTLA-4 engagement on resting T-cells was found to indirectly block ICOS costimulation by interferring with the signals needed to induce ICOS cell surface expression. Second, on preactivated cells that had high levels of ICOS expression, CTLA-4 ligation blocked the ICOS-mediated induction of IL-4, IL-10, and IL-13, suggesting an interference with downstream signaling pathways. The addition of IL-2 not only overcame both mechanisms, but also greatly augmented the level of cellular activation suggesting synergy between ICOS and IL-2 signaling.
So after T-cell Activation, IFN gamma is secreted (30 minutes), then IL-2 is secreted (45 minutes in) and so on,
The surface expression of ICOS is within 12 hours of activation. Since CTLA-4 blocks ICOS costimulation, Yervoy (anti-CTLA-4) must be used to counter the surpressive signalling. PD-1 also upregulates to the surface in the early activation process. PD-1 is upregulated within 24h after T cell activation.PD-1-Mediated Suppression of IL-2 Production Induces CD8+ T Cell ...anergy was associated with a marked down-regulation of IL-2.
Blockade of PD-1 by monoclonal antibodies specific to its ligands (PD-L1 and PD-L2) results in significant enhancement of proliferation and cytokine (gamma interferon [IFN-gamma] and interleukin-2 [IL-2] secretion by tumor-specific CTLs. PD-1 blockade also resulted in down-regulation of intracellular FoxP3 expression by Tregs.
PD-1 blockade seem to augment the proliferation of the CD4+ helper cells.
Now you know why just using Anti-PD1 and or Yervoy as a monotherapy will not have a large response rate. Combinational Therapy is a must if we are to see synergistic responses. IL-2 also plays a major roll in the immune response. IL-2 is added to help maintain fuctionality and survival of the Cytotoxic T Lymphocytes (CTLs) that is despartly needed to eradicate the Melanoma tumors. Our immune system can cure cancer, I am living proof of it.
Jimmy B
“It is not the strongest of the species that survives, nor the most intelligent, but the one most responsive to change.”
~Charles Darwin~
Take Care,
Jimmy B
A while back , in 2011 I wrote about combinatorial therapy as the way to form a curative therapy for melanoma.See blog entry "“Schedule and Dose for Combination Therapy,”
It is now just starting to gain acceptance in the oncology world ASCO 2012. You need to block multiple pathways to shutdown the tumor's ability to side-step the immune system.If you search on my blog using the search field, you will be able to follow the science.
“It is not the strongest of the species that survives, nor the most intelligent, but the one most responsive to change.”
Last July (2005)I was riding my bicycle to work at the Eastman Kodak Research Labs about 3 miles from home. I was wearing a knapsack to carry my things to and from the labs. I started noticing an ache on my back. So I decide to go to the dermatologist. To make the long story short, it was cancer. I knew from my research that I would be needing adjuvant therapy. So I started communicating with Sloan Kettering, University of Pittsburgh Cancer Center, and a couple of others including the Wilmot Cancer Center at Strong.
I realized that by telling my story, I might help someone else out there in a similar situation. So to all who are linked by diagnosis or by relation to someone with melanoma, I wish you well. Stay positive, read as much as you can
(information helps to eliminate the fear associated with the unknown), and live for today, as no one can predict what tomorrow may bring.
Jimmy B.
posted 12/15/08
The information contained within this Blog is not meant to replace the examination or advice of your Oncologist or Medical Team. The educational material that is covered here or Linked to, does not cover every detail of each disorder discussed. Only your physician/Oncologist can make medical decisions and treatment plans that are appropriate for you. But, An Educated Consumer is a Smart consumer. As Dr. Casey Culberson Said: "The BEST melanoma patient is an ACTIVE PARTICIPANT in his or her treatment (not a PASSIVE RECIPIENT)"
Melanoma and the “Magic Bullet” (Monoclonal Antibodies)
Just to let you know I posted the first draft of the Melanoma and the “Magic Bullet” (Monoclonal Antibodies). on Melanoma Missionary In the Shared File Section. you can download it for 19.95 (Only kidding) it is Free for the taking.
It is 33 pages long and may help you in your quest for the Yellow Brick Broad. Just to let you know it is only the first draft. Revisions are sure to come. I wanted to get it to the people that need it the most, the Melanoma Patients.
Preview:
So, where does Interluekin-2 (IL-2) come into play? According to Byung-Scok et al and recent reports, IL-2 is not needed for developmental CD4+ CD25+ Treg cells in the thymus but does play an important role in the maintenance and function in the peripheral.18 Peripheral is defines as secondary system outside the bone marrow and thymus. It entails the site of antigen, immune system interaction. IL-2 is required for the peripheral generation of Tregs based Abbas’s and colleagues research.19
IL-2 prevents the spontaneous apoptosis of the CD4+ CD25+ Treg cells. It has been reported that patients with multiple advance-stage tumors have elevated levels of Tregs within the tumor microenviroment.20 Interluekin-2 is the survival factor for CD4+ CD25+ Treg cells.21 If the addition of IL-2 is on or before the maximum propagation of the CD4+ T cells, the Tregs population can increase 5-fold in a 96 hour period based on certain growth mediums.
By controlling the addition of the endogenous IL-2, one has a knob to turn and can lead to the control of the expansion of the Tregs. When you combined this control with the anti-CTLA-4 blockage, you can shift the balance of the immune response.
Now here is the catch. The maintenance and function of the CD8+ T-cells require CD4+ cells which secrete IL-2. So we don’t want to deplete the CD4+ cells, we want to control the expansion of the Tregs which are a subset of the CD4+ cells. It has been postulated by some researchers that the Anti-CTLA-4 blockage also suppresses the Treg function in a different mechanism. By using IL-2 as the rate limiting factor, we can suppress the CD4+ CD25+ Treg cell expansion by controlling the concentration and timing of the Inerluekin-2 at the tumor microenvironment.
The Interluekin-2 plays another role in this Melanoma Maze. In a study by Janas et al, Il-2 increases the expressions of the perforin and granzyme A, B and C genes in the CD8+ T-cells. This increase expression causes the CD8+ T-cells to mature into Cytoxic T Lymphocytes (CTLs). The exogenous IL-2 is required for the granzyme proteins. As stated previously, CTLs have cytoplasmic granules that contain the proteins perforin and granzymes. A dozen or more perforin molecules insert themselves into the plasma membrane of target cells forming a pore that enables granzymes to enter the cell. Once in the tumor cell, these enzymes are able to breakup (lyse) the cell and destroy it. This is the beginning of the end for the cancer cells. The tumors begin to shrink and the rest is history,
“
On the other hand, prolong therapy with Il-2 can result in causing apoptotic death of the tumor- specific CD8+ T-cells.23
Clearly in a clinical setting, timing, dose, and exposure to these drugs play a major roll in the immunotherapy, and can have dramatic effects on the outcome.
All it takes is that one magic bullet to start the immune reaction..
A call for Melanoma Patients by Dr. Steven A Rosenberg
"We continue to see a high rate of clinical responses in our cell transfer immunotherapy treatments for patients with metastatic melanoma", Dr. Rosenberg said.
"We are actively seeking patients for these trials and any note of that on a patient-directed web site would be appreciated."
If you would like to apply for his trials, here is the website and information.
The Melanoma Research Alliance has partnered with Bruce Springsteen, the E Street Band, and the Federici family to alleviate suffering and death from melanoma. Please view Bruce Springsteen’s public service announcement inspired by Danny Federici. Danny was the E Street Band’s organist and keyboard player. He died on April 17, 2008 at Memorial Sloan-Kettering Cancer Center in New York City after a three year battle with melanoma.
I’ve decided to take a stand and fight back against cancer by participating in the American Cancer Society Relay For Life® event right here in my community! Please support me in this important cause by making a secure, tax-deductible donation online using the link below.
How Skin Cancer Develops by "About.com : Dermatology"
Call for Patients with Unresectable Liver Metastases Due to Melanoma Delcath Systems Granted Orphan-Drug Designations for Cutaneous and Ocular Melanoma
Delcath is actively enrolling patients in a Phase III clinical trial testing its proprietary drug delivery system, known as Percutaneous Hepatic Perfusion (“PHP”), with melphalan for the treatment of ocular and cutaneous melanoma metastatic to the liver.
This NCI-led trial is enrolling patients at leading cancer centers throughout the United States. Commenting on these orphan-drug designations, Richard L. Taney, President and CEO of Delcath, stated, “These favorable designations are important steps in our efforts to secure Delcath’s commercial position upon conclusion of our pivotal Phase III trial for metastatic melanoma. We remain steadfast in our commitment to become the leader in the regional treatment of liver cancers and we continue to enroll patients in this study, and advance our technology and the promise that it offers to patients with these deadly forms of melanoma and other cancers of the liver, all with limited treatment options.”
Orphan drug designation, when granted by the FDA’s Office of Orphan Products Development, allows for up to seven years of market exclusivity upon FDA approval, as well as clinical study incentives, study design assistance, waivers of certain FDA user fees, and potential tax credits.
James F. Pingpank, Jr., MD, FACS Associate Professor of Surgery Division of Surgical Oncology Suite 406, UPMC Cancer Pavillion 5150 Centre Avenue Pittsburgh, PA 15232 412-692-2852 (Office) 412-692-2520 (Fax) PingpankJF@UPMC.edu
Call For Melanoma Patients!!!! Dr. Rosenberg Has a New Clinical Trial. Our latest treatment has a 72% objective response rate with 36% complete responses.
We are currently recruiting patients for our latest trial.
Is there some way to post this “Call for Patients” on the web site?
