Wednesday, May 15, 2013

Bristol melanoma drug combo marks new advance in immunotherapy..melanoma..Jim Breitfeller

6:01 pm, May 15, 2013

(For more stories on new cancer data, see )

By Julie Steenhuysen

CHICAGO, May 15 (Reuters) - Melanoma patients treated with
two Bristol-Myers Squibb drugs fared much better than
those who received either of the medications individually, a new
advance for treatments that harness the body's immune system to
fight cancer.

Bristol released preliminary data from the early-stage trial
on Wednesday, with more detailed results expected to highlight
the American Society of Clinical Oncology's annual meeting in
Chicago that starts at the end of the month.

Patients in the study received Bristol's immunotherapy
Yervoy, which is already on the market, and an experimental
treatment called Nivolumab that attacks an
immune-system-inhibiting protein called PD-1. The combined
treatment shrank tumors in a majority of patients.

"We have never seen this with immunotherapy before," said Dr
Jedd Wolchok of New York's Memorial Sloan-Kettering Cancer
Center. "The vast majority of patients have a decrease in tumor
burden. In melanoma, we're used to seeing the opposite," he said
of the notoriously difficult-to-treat form of skin cancer.

Investors have been eager to see results of the study, with
Bristol shares reaching a 10-year high on Wednesday in advance
of the data release.

Both drugs are designed to target different parts of the
immune system that act as brakes even when cancer is present,
preventing immune cells from attacking tumors. By gumming up
these brakes, the drugs free the immune system to attack and
kill tumor cells.

Approved in 2011, Yervoy, or ipilimumab, was the first drug
to significantly extend survival in patients with advanced
melanoma, the most deadly form of skin cancer. It boosts the
immune system by blocking the action of a protein called CTLA-4.

Nivolumab, which is in late-stage testing, targets a protein
called PD-1, or Programmed Death receptor, a new class of
immune-system drugs that shows promise not only in melanoma but
also in lung and kidney cancer.

Typically, only about 11 percent of patients respond to
Yervoy, and recent studies in melanoma suggest Nivolumab
produces a response rate of about 41 percent, Wolchok told a
news briefing.

The current study looked at the combination of the two drugs
based on animal studies suggesting that together they might
work better than either drug alone.

Wolchok reported results for 86 patients in the trial as of
February 2013, including 52 patients who were on both drugs at
the same time. In one of the treatment groups, which will likely
advance to late-stage trials, 53 percent of patients treated
with both Yervoy and Nivolumab simultaneously had an objective
response - defined as at least a 50 percent reduction in tumor


Dr Sandra Swain, president of ASCO, called the findings
remarkable. "This combination treatment led to a very rapid and
profound lasting tumor shrinkage. Ninety percent of patients are
still responding," she said.

Three out of four patients who responded to the dual
treatment had tumor shrinkage in the first three months.

Among the most advanced melanoma patients, Wolchok said the
combination of the two drugs produced "rapid and deep
regressions, with many showing more than 80 percent tumor
regression by the time of the first scan."

Overall, most patients had some decrease in tumor size. In
31 percent of all patients taking the dual therapy, tumors
shrank by greater than 80 percent, Wolchok said.

In 18 percent of patients, the drug combination produced a
complete response, meaning tumors were no longer detectable,
Wolchok said in an interview. He said they do not yet have any
data on relapse because 90 percent of patients who responded to
the treatment are continuing to benefit.

The combination also appeared to be safe. About half of
patients who got both treatments had a drug-related side effect,
but in most cases it was linked to elevations in enzymes related
to the pancreas and liver.

"These are reversible, sometimes without treatment," Wolchok
said, although some patients did need a short course of the
steroid prednisone. There were no drug-related deaths.

"We really didn't see anything new with the combination"
related to safety, he said.

Bristol-Myers plans a late-stage clinical trial that looks
at both drugs in combination, as well as each separately, in
patients with melanoma. It has also begun testing the same
combination in lung cancer and renal-cell cancer.

"We view the combination of immunotherapy as a significant
one that we'll be pursuing," Michael Giordano, Bristol-Myers'
senior vice president of global development for oncology and 
immunology, said in an interview.

So far, Bristol-Myers is furthest ahead in its development
of a PD-1 inhibitor, but Merck & Co Inc last month won
designation from the U.S. Food and Drug Administration as a
"breakthrough therapy," which could speed development and
regulatory review of the product.

In a recent note, Bernstein Research analyst Tim Anderson
said Bristol's anti-cancer drug PD-1 "is the major driver of
investor interest at the moment," but said awareness is building
that competitors "may not be very far behind."

Last November, Merck reported results from a trial of its
drug in patients with advanced melanoma and saw a 47 percent
response rate. In that trial, the drug benefited patients who
had previously been treated with ipilimumab but had not
responded, said Dr. Gary Gilliland, a Merck senior vice
president for oncology.

Merck plans to present an update of this study on June 2 at
the ASCO meeting. Gilliland said the company also is studying
its treatment in so-called triple-negative breast cancer, a
hard-to-treat form of the disease, as well as head and neck
cancer and bladder cancer.

Other companies pursuing the PD-1 or related pathways
include Roche, GlaxoSmithKline and Teva

"PD-1 is arguably the most exciting breakthrough in cancer
therapy in a decade," said ISI Group analyst Mark Schoenebaum.
"There is speculation that it might offer a cure for some
patients with solid tumors. This is unprecedented."

(Additional reporting by Bill Berkrot in New York; Editing by
Michele Gershberg and Prudence Crowther)

“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


  1. Take a look at Scancell Holdings, melanoma in phase 1/11 trial targeting an immune respose via the dendritic cells using Vaccinces that produce a NON toxic immune response, so far very good results.Its called Immunobody.
    They have also patented Moditope that generates a cd4 + t cell response this is really the big boys of the immune system as they can direct attacks and switch to being cytotoxic Killer Cells .. which will destroy any cancer.

  2. Hello,
    My name is Flynn Post. I am not looking for a donation but want to share my story and talk with you about options for my situation!
    Thank you for your time!

  3. Hello,
    My name is Flynn Post. I am not looking for a donation but want to share my story and talk with you about options for my situation!
    Thank you for your time!


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.