Friday, October 8, 2010

Activating the Danger Signal with Anti-CTLA-4 Blockade..Melanoma..Jim Breitfeller

Melanoma Stats
Initial Diagnosis: May 2003
Current Stage: Stage 4
Depth of Primary: Up to 1 mm
Treatment Stats
Doctor: Mario Sznol MD
Treatment Center: Yale New Haven
Clinical Trial(s): Ipilimumab
Treatment History
February, 2003 my wife noticed a dark spot on my balding head.

April 2003 Punch biopsy read asmelanoma, 0.76mm deep.

May 2003 Wide Local Excision

May-Sept - Multiple dysplastic nevi excised

Sept 2003 - Second primary, this time in situ, on my chest

PET scan, MRI and CT all negative

Oct 2003 - University of Pennsylvania Pigmented Lesion clinic in Philadelphia they reread my slides and reclassified it to a Breslow's depth of 0.86 and Clark's level 4 and told me I have Stage 1B with a specific note that there appeared to be no immunologic response by my body to the melanoma.

October 2003 - October 2006 Derm exam every 3 months. Many dysplastic nevi excised. Doing well, no more primaries, no problems.

October 2006 coughed up blood CT, PET showed a 5cm mass in my L lung. MRI negative for brain mets. No other lesions found.

October 30, 2006 - Thoracotomy at St. Peter's Hospital in Albany NY with removal of the lower lobe of my left lung. Did well after surgery.

November, 2006 - Local oncologist offers interferon but suggests I look into trials

December, 2006 - Accepted into University of Pennsylvania trial of Anti-CTLA4 if my scans remain clear

December 12, 2006 - Had MRI and CT for study and found I has a previously undiagnosed.
met to my brain
December 13, 2006 - Radiation oncologist suggests neurosurgery unless it is not safe to resect. Also heard I may have micro-mets in the lungs. Put on decadron. Seeing neurosurgeon on 12/14

December 14, 2006 - Neurosurgeon says "take it out"

December 20, 2006 - Craniotomy. Second major surgery in 7 weeks! Another stint in the ICU. Woke up unable to move my left leg

December 24, 2006 - One week in a rehabilitation hospital. Intense physical therapy and I walk out

January 2007 - Planned on SRS but more brain mets found. Underwent 15 sessions of WBR

March 2007 - More lung mets found - multiple, disseminated in both lungs, tiny

April 2, 2007 I start IL-2 at Deaconess Beth Isreal in Boston

June, 2007 Brain tumors bleed - emergency craniotomy

July, 2007 - Stereotactic radiation

Sept, Oct waititg for a trial...and waiting...and waiting



October 2007 Accepted in compassionate use trial WITH Ipilimumab (MDX-010 at Yale New Haven Hospital under the care of Dr. Sznol

October 31, 2007 First dose of Ipilimumab at Yale-New Haven Hospital.

November 20, 2007 Second Infusion of Ipilimumab

December 11, 2007 Third dose of Ipilimumab

December 18, 3007 Severe reaction to IPI
Admitted to YNHH with uncontrolled vomiting, dehydration, hyponatremia and weakness. Discharged December 23, 2007 to home. Began 4 mg oral steroids.

January 22, 2008 began to notice double vision, nausea and vomiting as steroids were tapered from 3mg to 2 mg. Steroids increased to 2.5 mg

January 23. , increased to 3mg
anuary 25, increased to 4 mg

January 28, 8 mg January 29 . Nausea and vomiting disappeared. Double vision improvement noted

February 4th…Have lost all peripheral vision.

March 2008 increased weakness noted in lower extremity resulting in confinement to
Wheelchair and walker. MRI noted area of increased swelling on right parietal lobe at site of June 2007 surgery. Not metastatic disease.

April 2008 prescribed high dose (40mg) oral steroids to reduce swelling and manage side effects until planned surgery May 2008.

May 8 2008 planned craniotomy (#3) to remove necrotic tissue iAfter 5 day inpatient stay, walked out of hospital without assistive device. Began taper of steroids.

May-June 2008 unable to tolerate steep taper, steroids increased and taper resequenced at much slower rate.

December 2009 Tumors still visible on scans in brain and lungs but no growth since 2008, Stable. No evidence of active disease.

UPDATE written October 7 2010

October 7, 2010. Four years after my diagnosis with Stage IV Melanoma I continue to show no evidence of active disease. I do have problems elated to treatmens: Simple Partial Seizures, Visual problems (Double and blurred) Short term memory loss, Episodes of fatigue. Symptoms that remind me about what I went through these past four years, but definitely things I CAN LIVE WITH. A hell of a lot better than I thought when I started to fighting the beast/
Mark, Catskill, NY




Activating the Danger Signal with Anti-CTLA-4 Blockade





Was it the combination Radiation, IL-2 plus the Anti-CTLA-4 blockage?




“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

Disclaimer

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..

https://app.box.com/shared/kjgr6dkztj

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.


http://www.melanomaresearchalliance.org/news/PSA/

Source Fastcures blog



Join the Relay for Life!!!

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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!!!

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Sincerely,

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

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.


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)
PingpankJF@UPMC.edu


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.