Wednesday, June 9, 2010

Phase 3 Clinical Study Of A New Cancer Immunotherapy Extends Survival In Patients With Refractory Melanoma..JimBreitfeller

The Cancer Research Institute, a nonprofit organization dedicated to the development of immune system-based treatments for cancer, announced its celebration of a significant new breakthrough in the treatment of melanoma, the deadliest form of skin cancer. The new treatment, a cancer immunotherapy created by Cancer Research Institute Scientific Advisory Council Associate Director James P. Allison, Ph.D., is designed to "take the brakes off the immune system," and is the first treatment ever proven to extend life for patients whose melanomas are unresponsive to existing cancer therapies.

Results from a large, randomized, multicenter phase 3 clinical study, published Saturday in the New England Journal of Medicine, confirm that the new treatment, a monoclonal antibody called ipilimumab, successfully boosts and sustains immune system responses against melanoma tumors in a large percentage of treated patients. The study also shows that the new treatment confers a survival advantage in a significant number of patients, resulting in durable protection against cancer.

According to the study report, 46 percent of patients on the trial who received ipilimumab were still alive at one year compared to 25 percent of patients on the trial who did not receive the new treatment. At two years, 22 to 24 percent of treated patients were still living compared to 14 percent in the study's control arm. The study tested ipilimumab alone, in combination with a vaccine targeting the melanoma tumor antigen peptide gp100, and vaccine alone.

"As an organization that for nearly 60 years has focused on advancing new immune system-based cancer treatments like the monoclonal antibody ipilimumab, the Cancer Research Institute considers this new breakthrough yet another significant success for the field of tumor immunotherapy and further validation that the immune system can be harnessed to treat, control, and prevent cancer," said CRI executive director Jill O'Donnell-Tormey, Ph.D.

In May this year the FDA approved the first therapeutic cancer vaccine, sipuleucel-T (Provenge®) for the treatment of prostate cancer. For the ipilimumab therapy, Bristol-Myers Squibb, the drug's manufacturer, says it expects to file for regulatory approval of its new treatment later this year. If successful, the drug could be the next cancer immunotherapy to receive FDA approval.

T cells (T lymphocytes) are immune cells the play a critical role in the body's attack against tumors. Ipilimumab represents the first in a new class of cancer immunotherapies called T-cell potentiators, which modulate the "stop/go" signals that control T-cell activation. By suppressing these "stop" signals, ipilimumab allows the T-cell response against cancer to proceed unimpeded.

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Ipilimumab specifically blocks CTLA-4, a molecule that inhibits the activity of T cells. Dr. Allison showed in 1995 that CTLA-4 was a negative regulator of T-cell responses, and hypothesized that blocking it could lead to strong tumor rejection. He went on to develop a monoclonal antibody that successfully blocks CTLA-4, and conducted the early mouse studies confirming his hypothesis of anti-CTLA-4-mediated tumor regression.

According to Dr. Allison, T-cell potentiation with ipilimumab may eventually help patients with many different types of cancer live longer. "Studies have shown that the immune system can recognize, target, and attack many different kinds of cancer," Allison said, "and ipilimumab may help to strengthen and sustain that immune response, no matter the type of cancer."

F. Stephen Hodi, M.D., a clinical researcher at the Dana-Farber Cancer Institute and principal investigator on the phase 3 study, said melanoma is just the beginning. "We can explore this new treatment in many other kinds of cancer, as well."

Smaller clinical studies of ipilimumab in other cancer types, including lung and prostate cancers, suggest the treatment has clinical activity, and further clinical research is ongoing to confirm these data.

According to Jedd D. Wolchok, M.D., Ph.D., also an associate director of the Cancer Research Institute Scientific Advisory Council, a CRI clinical investigator, and one of the clinicians involved in the large phase 3 study, there currently are no approved medicines indicated for patients whose melanomas return after primary treatment.

"The study is very significant," Wolchok stated, "as it is the first time ever that a randomized phase 3 study in melanoma has shown a new treatment to provide an overall survival benefit."

The landmark trial has other important implications for the field beyond establishing the effectiveness of this particular cancer immunotherapy. Axel Hoos, M.D., co-chairman of the executive committee of the CRI Cancer Immunotherapy Consortium, a program that seeks to optimize the development of the emerging field of immuno-oncology, and medical lead for ipilimumab at Bristol-Myers Squibb, said ipilimumab investigation represents a significant advance in how clinical studies of cancer immunotherapies are conducted and evaluated.

"The existing paradigm for evaluating the effectiveness of new cancer treatments is informed by experience with chemotherapy," Hoos said. "The chemotherapy paradigm does not entirely account for the biology and unique mechanisms of action of cancer immunotherapy."

To address this issue, the CRI Cancer Immunotherapy Consortium, in collaboration with international partner organizations, immunologists, and clinical oncologists around the world spearheaded the development of a new operating framework for immuno-oncology.

This new framework encompasses a clinical development paradigm that allows clinicians to more effectively investigate immunotherapies in clinical trials. According to Hoos, the ipilimumab trial results contribute to the validation of the new paradigm. "This offers a path forward for the field for more successful development of immunotherapies in the future," Hoos said.

The Cancer Research Institute is currently testing a variety of therapeutic cancer vaccines through its Cancer Vaccine Collaborative (CVC), a joint program with the Ludwig Institute for Cancer Research. Lloyd J. Old, M.D., director of the Cancer Vaccine Collaborative and director of the CRI Scientific Advisory Council, said the emergence of T-cell potentiators like ipilimumab as well as other modulators of immunosuppression has opened a new front for clinical discovery in cancer vaccine research.

"Over the past ten years, the Cancer Vaccine Collaborative has established an unprecedented understanding of the human immune system response to treatment with cancer vaccines," said Old. "There is now considerable evidence that the body recognizes cancer as foreign, but the full force of the immune system to combat cancer is blunted by inherent safeguards that have evolved over time to prevent the immune system from attacking healthy tissue, a condition called autoimmunity that can arise when these safeguard mechanisms fail. Blocking CTLA-4 with ipilimumab removes this constraint and permits more efficient immune control of the tumor."

According to Old, the introduction of ipilimumab and therapies that target other mechanisms involved in immune suppression launches a new era in the development of effective cancer vaccines, offering powerful new tools for overcoming the body's powerful restraints on generating protective cancer immunity.

"Ipilimumab represents a major step in the century old dream of incorporating the immune system in our battle against cancer," said Old, "and learning how to maximize the combined therapeutic effects of ipilimumab with other cancer therapies, including the new targeted therapies, is the immediate challenge."

"Our ultimate goal," said O'Donnell-Tormey, "is to establish highly effective immunotherapies as part of the standard of care in the treatment of cancer. The recent FDA approval of Provenge and the striking data on ipilimumab show that significant progress is being made toward achieving this goal."

"Given these recent advances," said Old, "we can predict that therapies based on immunological principles are poised to revolutionize our understanding and treatment of human cancer. Exploiting the power of the immune system to combat cancer is now clearly within our reach."

About the Cancer Research Institute

The Cancer Research Institute (CRI) is the world's only non-profit organization dedicated exclusively to the support and coordination of scientific and clinical efforts that will lead to the immunological treatment, control, and prevention of cancer. Guided by a world-renowned Scientific Advisory Council that includes four Nobel Prize winners and twenty-nine members of the National Academy of Sciences, CRI supports leading-edge cancer research at top medical centers and universities throughout the world. The Cancer Research Institute is ushering in a new era of scientific progress, hastening the discovery of effective cancer vaccines and other immune-based therapies that are providing new hope to cancer patients.

The Cancer Research Institute has one of the lowest overhead expense ratios among non-profit organizations, with more than 85 percent of its resources going directly to the support of its science, medical, and research programs. CRI meets or exceeds all 20 standards of the Better Business Bureau Wise Giving Alliance, the most comprehensive U.S. charity evaluation service, and according to Charity Navigator exceeds or meets industry standards and performs as well as or better than most cancer charities. CRI has also received an 'A' grade for fiscal disclosure and efficiency from the American Institute of Philanthropy as well as top accolades from other charity watchdog organizations.

Source: Cancer Research Institute

“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

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Greetings to One and All

This Blog is dedicated My Brother Kenny B. who passed away in the late 1970's with Cancer before the Internet.

It was he, who showed me How to live and give back. He was wise beyond his years.

Kenny B

Jimmy and Dee

Carepage: Jimmybreitfeller
Jimmy Breitfeller

My Profile as of 2009

My photo
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

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.


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..

Melanoma And The Magic Bullet (Monoclonal Antibodies)

Public Service Announcement

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.

Dr. Rosenberg's information

Dr. Rosenberg's Clinical Trials

For the Warriors

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.

Source Fastcures blog

Join the Relay for Life!!!


Dear Family and Friends,

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.

To donate on line now, click here to visit my personal page.
Jimmy B AKA Melanoma_Missionary

Relay For Life® is a life-changing event that brings together more than 3.5 million people worldwide to:

CELEBRATE the lives of those who have battled cancer. The strength of survivors inspires others to continue to fight.

REMEMBER loved ones lost to the disease. At Relay, people who have walked alongside people battling cancer can grieve and find healing.

FIGHT BACK. We Relay because we have been touched by cancer and desperately want to put an end to the disease.

Whatever you can give will help - it all adds up! I greatly appreciate your support and will keep you posted on my progress.

Keep the Fire Burning!!!



Jimmy Breitfeller
Turn off Music before you "Click to Play"
Signs of Melanoma Carcinoma Skin Cancer

How Skin Cancer Develops by " : 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.

Current Trial Centers

Phase I Study of Hepatic Arterial Melphalan Infusion and Hepatic Venous Hemofiltration Using
Percutaneously Placed Catheters in Patients With Unresectable Hepatic Malignancies

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)

Blog Archive

Call For Melanoma Patients!!!!

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?

Steve Rosenberg

Dr. Rosenberg's Clinical Trials

(For a copy of the research paper.. see My Shared files)

The news headlines shown above for Melanoma / Skin Cancer are provided courtesy of Medical News Today.