Sunday, May 31, 2009

Two-Year Survival Rate Ranging from 30 to 42 Percent in Metastatic Melanoma Patients Treated with Ipilimumab Melanoma..Jim Breitfeller

Results from Three Phase 2 Studies Reported a Two-Year Survival Rate Ranging from 30 to 42 Percent in Metastatic Melanoma Patients Treated with Ipilimumab (10 mg/kg)

PRINCETON, N.J.--(BUSINESS WIRE)--May. 31, 2009--Bristol-Myers
Squibb Company (NYSE: BMY) and Medarex,
Inc. (NASDAQ: MEDX) today announced updated survival results from
follow-up extensions of three Phase 2 ipilimumab studies of patients
with advanced metastatic melanoma (Stage III or IV). The two-year
survival rate ranged from 29.8 to 41.8 percent in patients who received
ipilimumab (10 mg/kg). Results of the survival data were presented at
the 45th Annual Meeting of the American Society of Clinical
Oncology in Orlando, FL., May 29 -- June 2, 2009.

The results are based on follow-up of up to 37.5 months (median
follow-up ranging from 10.1 to 16.3 months) of the patient population
from studies 008, 022 and 007 treated with 10 mg/kg of ipilimumab
(induction and maintenance) and, specifically, showed:

Two-year survival rate of 32.8 percent (95% CI: 25.37%- 40.49%) in
patients who had progressed while on or after receiving standard
treatment (Study 008, Abstract #9033);

Two-year survival rate of 29.8 percent (95% CI: 19.13%- 41.14%) in
patients who were previously treated, relapsed or failed to respond to
experimental treatment or were unable to tolerate currently approved
therapies (Study 022, Abstract #9033);

Two-year survival rate of 40.6 percent (95% CI: 27.12%- 54.37%) and
41.8 percent (95% CI: 28.30%- 55.46%) in patients receiving ipilimumab
plus budesonide or ipilimumab plus placebo, respectively, which
included treatment-naïve patients and patients previously treated with
therapy other than ipilimumab (Study 007, Abstract #9033).

Historical melanoma survival rates from previous clinical trials have
been estimated by a recent meta-analysis of 42 Phase 2 trials of over
2,100 patients with Stage III or IV metastatic melanoma indicating that,
at one year, approximately 25 percent of patients were alive. Results
from three separately published randomized Phase 3 studies using
dacarbazine as the control arm reported that, at two years,
approximately 8 to 12 percent of metastatic melanoma patients were alive.

The updated survival analyses did not include additional safety data. As
previously reported, safety results include follow-up of up to 16.3
months with a median follow-up ranging from 4.7 to 5.65 months. The most
common immune-related adverse events were rash, diarrhea and hepatitis.
Grade 3 and 4 immune-related adverse event rates were approximately 20
to 29 percent and zero to 12 percent, respectively, in patients who
received 10 mg/kg of ipilimumab. Adverse events were managed with the
use of supportive care and systemic steroids using established treatment
guidelines in the majority of patients. Additionally, the use of
systemic steroids to manage adverse events does not appear to diminish
or impact the clinical effect of ipilimumab (Abstract #9037).

"The ongoing survival data observed with ipilimumab are encouraging,
particularly because the advanced melanoma patient population currently
has limited treatment options," said Steven J. O'Day, M.D., Chief of
Research and Director of the Melanoma Program at The Angeles Clinic and
Research Institute, California. "The potential of ipilimumab is also
underscored by the fact that we can report two-year survival results
from these studies involving a significant number of metastatic melanoma

Candidate Biomarkers of Ipilimumab

Researchers also presented an exploratory analysis from four Phase 2
ipilimumab studies (008, 022, 007 and 004) that looked at the
association between clinical activity and multiple potential biomarkers,
including the change in absolute lymphocyte count (ALC) in melanoma
patients after they received ipilimumab (Abstracts #9008 and #3020). ALC
is a measure of the number of immune cells in circulation.

In a combined analysis of studies 007, 008 and 022, clinical activity
was associated with an increase in the rate of change in ALC. Patients
with clinical activity had a higher average increase in ALC over time
than did patients without clinical activity (P=0.0013) and no patient
with a decrease in ALC over time had clinical activity. This association
was separately confirmed in Study 004. Increases in ALC following
administration of ipilimumab were also significantly associated with
dose (studies 007, 008, 022: P<0.0001; study 004: P=0.0015), favoring
the 10 mg/kg regimen. Based on these early biomarker findings, further
research to explore the implication of ALC and other potential
biomarkers of clinical activity of ipilimumab continues.

About Studies 008, 022 and 007

The three studies enrolled a total of 487

patients across North
America, Europe, South America, Africa and Australia with Stage III or
Stage IV metastatic melanoma treated with ipilimumab therapy (0.3 mg/kg,
3.0 mg/kg or 10 mg/kg every three weeks for up to four doses, followed
by maintenance dosing every 12 weeks). Specifically, the three Phase 2
monotherapy trials include:

A Phase 2 open-label, single-arm trial (008) evaluating overall
response rate in 155 patients who progressed while on or after
receiving standard treatment;

A Phase 2 randomized, double-blind trial (022) evaluating the efficacy
of three dose levels of ipilimumab in 217 patients who were previously
treated, relapsed or failed to respond to experimental treatment or
were unable to tolerate currently approved therapies; and

A Phase 2 randomized, double-blind trial (007) evaluating the rate of
Grade 2+ diarrhea in 115 patients receiving ipilimumab with or without
prophylactic oral budesonide.

The primary endpoint of studies 008 and 022 was best overall response
rate and the primary endpoint of study 007 was to compare the rate of
Grade 2+ diarrhea in patients receiving ipilimumab with or without
prophylactic oral budesonide. Overall survival, one-year survival rates,
disease control rate, stable disease, and other measurements of
anti-tumor activity and patterns of responses were secondary endpoints
in studies 008, 022 and 007. The two-year survival data reported are
current (through March, 2009) for all subjects followed: 93.6% from
study 008, 91.7% from study 022 and 84.2% and 82.8% from the two
subgroups of study 007 (placebo and budesonide, respectively).

About Study 004

Study 004 is a Phase 2 randomized, double-blind biomarker trial. The
study enrolled 82 patients with advanced melanoma who were previously
treated with therapy other than ipilimumab or who received no prior
therapy. All patients received ipilimumab therapy (3.0 mg/kg or 10
mg/kg). Pre- and post-treatment (week four) tumor biopsies were
performed to assess associations between tumor biomarkers and clinical
activity of ipilimumab. Clinical activity was defined as complete or
partial response or stable disease at ≥24 weeks using modified World
Health Organization criteria.

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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.