Holiday Wishes to you All !! Melanoma..Jim Breitfeller

I would like to wish each and every one of my carepage friends the warmest and deepest greetings this Holiday Season. We been through a lot and with the comfort of family and friends we can beat the Beast Melanoma.

It has been truely a renewed emergence in Melanoma therapy this past year with TWO therapies being FDA approved that extends survival for us Melanoma patients. At this time of the Season, please relect on the Worriors that are no longer with us, but made this all possible by offering their life to the progress of science.

They truely have shown us the gift of giving.

They truely are my/our HEROS!!!

We will miss them dearly.

Happy Holidays




“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

FDA approval of Roche melanoma drug (Vemurafenib) may come early

Reuters) - Regulators are moving quickly with Roche's application for targeted melanoma drug vemurafenib, which could receive approval as early as this week, according to a source familiar with the situation.

Vemurafenib, whose brand name is Zelboraf

Source: FDA approval of Roche melanoma drug may come early



Your tumors must be BRAFV600E positive




“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

ASCO Review with Dr. John Kirkwood on Melanoma Therapies..jim Breitfeller

The full Audio of the Dr. Kirkwood interview at ASCO 2011


Please if you get a chance, listen to the full interview of Dr. John Kirkwood on the lastest therapies for Melanoma. It might help save your life or loveone's life.

Get a cup of coffee and a pad and pencil.

Enjoy




“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

2011 ASCO Annual Meeting Highlights on Melanoma and Neuroblastoma, with Lynn Schuchter, MD ..jim breitfeller

2011 ASCO Annual Meeting Highlights on Melanoma and Neuroblastoma, with Lynn Schuchter, MD
June 5, 2011

2011 ASCO Annual Meeting Highlights on Melanoma and Neuroblastoma, with Lynn Schuchter, MD



“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

Bristol, Roche team up on melanoma study..Jim Breitfeller

By Bill Berkrot and Lewis Krauskopf

NEW YORK | Thu Jun 2, 2011 1:30pm EDT

NEW YORK (Reuters) - Bristol-Myers Squibb and Roche Holding AG said on Thursday they would evaluate their respective cancer drugs as a potential combination therapy for metastatic melanoma.

The collaboration involves a Phase I/II study with Bristol's recently approved Yervoy and Roche's experimental drug, vemurafenib, to determine the safety and efficacy of the combination in treating the deadliest form of skin cancer.

The announcement comes as the American Society of Clinical Oncology meeting begins this weekend in Chicago, where emerging treatments for melanoma will be in the spotlight.

Among the most eagerly anticipated studies being presented at the ASCO meeting will be a Phase III trial intended to show that vemurafenib extended the lives of patients with advanced melanoma, and another study comparing Yervoy to chemotherapy in patients with the fatal disease.

Yervoy won U.S. approval in March for patients with inoperable or metastatic melanoma, making it the first new treatment option in many years for patients for whom there was little hope and virtually no effective medicines.

Roche and Japanese drugmaker Daiichi Sankyo Co recently submitted U.S. and European applications seeking approval for vemurafenib. The drug was developed by Roche's Genentech unit and Plexxikon, which was recently acquired by Daiichi.

Vemurafenib, a so-called BRAF inhibitor, is designed to selectively target and inhibit a mutated form of the BRAF protein found in about half of all cases of melanoma. The combination study with Yervoy will be in patients with BRAF-mutated metastatic melanoma, Roche said.

Roche is also developing a combination diagnostic to help identify those patients with the BRAF mutation who are likely to benefit from vemurafenib.

"We are entering a new era for melanoma, and are committed to studying exciting combinations with investigational medicines in our own pipeline," Roche Chief Medical Officer Hal Barron said in a statement.

If proven effective and approved the Yervoy-vemurafenib combination would be an extremely expensive treatment option that could meet with reimbursement resistance from government programs and health insurers.

Bristol priced a four-infusion course of Yervoy at about $120,000. Vemurafenib will likely also command premium pricing if it too demonstrates an ability to help patients live longer.

More than 70,000 people in the United States and 160,000 worldwide are diagnosed with melanoma each year, according to the American Cancer Society. The five-year survival rate for the aggressive cancer is just 15 percent.

Source:http://www.reuters.com/article/2011/06/02/us-bristol-roche-melanoma-idUSTRE75151W20110602


All I can say.... It is about Time!!!! Lets all work together for the common good.


“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 call for patients that failed PLX-4032 Melanoma Jim Breitfeller

Genentech has just opened a study for people who have taken the Plexxikon/Roche/Genentech BRAF inhibitor, also known as PLX 4032. This study is a combination trial using PLX plus a MEK inhibitor. Some folks from this board have been in the BRAF/MEK trial being run by GSK, and this new trial is similar. One criteria, though, is that you must have taken the Plexxikon drug and have developed resistance to that drug. Currently three sites are open: Dr. Gajewski in Chicago, Dr. Ribas in UCLA, and Dr. Gonzalez in Denver. Four more sites will open soon. You can go to this link to find out information about melanoma relevant clinical trials, including this one: http://www.emergingmed.com/networks/MRF



Source: Tim--MRF



“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

Expanded access With RO5185426 in Patients With Metastatic Melanoma..Jim Breitfeller

Expanded access With RO5185426 in Patients With Metastatic Melanoma.
The locations are limited.

The drug is called RO5185426, which is interchangeable with PLX4032 and RG7204. Also, you must be Braf positive and failed a prior therapy.

Expanded access With RO5185426 in Patients With Metastatic Melanoma




“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

New Drugs Stir Debate on Rules of Clinical Trials..Melanoma - Jim Breitfeller

New Drugs Stir Debate on Rules of Clinical Trials..Melanoma -

New Drugs Stir Debate on Rules of Clinical Trials..Melanoma PLX4032


We should let the FDA ,Congress and Plexikkon know how us, the Patients feel about the clinical trial protocol process.
It doesn't smell right.


Stop monkeying round with Our Life. We are just trying to survive.



Peter Hirth CEO Plexxikon


Try These. I am not sure of the CEO’s email. Just try and see if they bounce back.

kphirth@plexxikon.com CEO

phirth@plexxikon.com CEO


kglaub@plexxikon.com President








Richard Pazdur
Richard Padzur to run its new Office of Oncology Drug Products (OODP)
pazdurr@cder.fda.gov

Plexikkon should open a compassionate care use to the patients that have no other trial available.Peter Hirth, show some compassion to your customers/patients.

Please Make the right choice!!!






Please write about your disgust to the above email addresses

Thanks in advance



“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

Promising new Melanoma Drug, PLX4032: Questions and Answers

Promising new melanoma drug: Questions and answers


By Liz Szabo, USA TODAY

A new drug for the treatment of advanced melanoma is generating rare excitement and optimism among cancer doctors. USA TODAYasked experts to explain the drug's benefits and limitations.
Q: Why is the drug promising?

A: The drug, PLX4032, shrank tumors in 26 of 32 melanoma patients who had a key mutation in their tumors, according to a study in today's New England Journal of Medicine.

That's "remarkable," because patients in small, early trials such as this often get no benefit at all. Typically, experimental drugs shrink tumors in only 5% to 10% of patients, says Keiran Smalley of the Moffitt Cancer Center and Research Institute in Tampa, who wasn't involved in the study.

Some patients began showing improvement within only a few days, says Lynn Schuchter of the University of Pennsylvania, who also worked on the study.

Q: Were those patients cured?

A: In two patients, tumors disappeared, and some patients' disease remains in check. It's too early to know whether patients will stay in remission, however. The median remission was more than seven months, the study says.

But even shrinking tumors is relatively rare in advanced melanoma that has spread to other organs. The two approved drugs for melanoma — a chemotherapy called dacarbazine and an immune therapy called interleukin-2 — shrink tumors for only about 10% to 20% of patients, the study says.

Q: Does the drug help all patients?

A: No, it helps only the roughly 50% of patients whose tumors have the mutations in a gene called BRAF, the study says. Patients who don't have the mutation get no benefit.

If the drug is approved, doctors probably will begin testing all patients with advanced melanoma for the mutations. A test such as this probably would cost a few hundred dollars, says the study's lead author, Keith Flaherty of Massachusetts General Hospital in Boston.

Q: How is the drug different from other treatments?

A: Unlike conventional chemo, which kills all fast-growing cells, the new drug — also known as RG7204 — is considered a "targeted therapy" because it aims to block a specific mutation found only in certain melanoma cells.

Q: What about side effects?

A: Because PLX4032 leaves most healthy cells alone, it causes far fewer side effects than chemo, Flaherty says. High-dose IL-2, for example, can cause life-threatening side effects and is given only in the hospital, so patients can be closely monitored. Patients can take PLX4032, a pill, at home.

But even relatively mild side effects can become bothersome over time, says Vernon Sondak of the Moffitt Cancer Center and Research Institute in Tampa, who wasn't involved in the study.

If PLX4032 helps keep patients alive a long time — either by itself or when combined with other experimental drugs — patients may be more troubled by fatigue, rash and joint pain, Sondak says.

Q: Who financed the study?

A: The study was paid for by the drug's co-developers, Plexxikon and Roche Pharmaceuticals.

Q: What will it cost?

A: The companies haven't announced a price, because the drug is still in early trials. Flaherty notes, however, that many new cancer therapies cost $5,000 to $7,000 a month.

Q: Is it possible to get the new drug?

A: Yes. Doctors are still enrolling patients with advanced melanoma in a large trial of 680 patients who haven't gotten other treatment. Additional studies are expected to be launched next year, Flaherty says. More information about PLX4032 is available by calling 888-662-6728.

Other experimental drugs for melanoma — including ones very similar to PLX4032 — also are being developed. More information can be found at clinicaltrials.gov

Q: When might the drug be approved?

A: If additional studies are positive, Roche Pharmaceuticals plans to apply for FDA approval in 2011, spokeswoman Amy Berry says. In June, PLX4032 was given "fast-track" status by the Food and Drug Administration — a process that helps speed up development of drugs that fill unmet needs.

Source:http://www.usatoday.com/news/health/2010-08-26-melanomaQA_ST_N.htm


Since it helps only the roughly 50% of patients whose tumors have the mutations in a gene called BRAF, Ipilimumab,PD-1 and Interluekin-2 would be other therapies to try.

My gut feeling is that we can beat Melanoma with combinatorial Therapy.

We just need to get the Drug companies and the Oncologists on board




“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

PLX4032 May Clear Path for Individualized Treatment of Metastatic Melanoma..Jim Breitfeller

PLX4032 May Clear Path for Individualized Treatment of Metastatic Melanoma

Elsevier Global Medical News. 2010 Aug 20, MG Sullivan

Chicago -- A drug that targets metastatic melanoma with mutations in the BRAF oncogene may be the first step on a path to individualized chemotherapy for patients with these formerly untreatable cancers.

"We are rapidly unraveling the molecular underpinnings of these tumors, and discovering the mechanisms by which they drive melanoma growth. These insights allow us to develop and select drugs on the basis of every patient's individual genome," Dr. Hensin Tsao said at the American Academy of Dermatology's Academy 2010 meeting.

PLX4032 is the first drug to successfully shrink both cutaneous and internal metastases of BRAF-mutated melanomas, said Dr. Tsao, a dermatologist who is director of the Massachusetts General Hospital Melanoma Genetics Program in Boston. His colleague, Dr. Keith Flaherty, is about to publish data from the drug's phase II trial of 87 patients; 81 percent of those with the BRAF-mutated melanoma responded with a 30 percent or more shrinkage of the targeted lesions.

After a phase I safety and dose-finding trial, investigators settled on an oral dose of 960 mg twice daily for the phase II study. The effect was little short of remarkable, Dr. Flaherty, director of developmental therapeutics at the Massachusetts General Hospital Cancer Center, said in an interview.

"My first responding patient had cutaneous and internal metastases, and the cutaneous metastases were clearly getting better right in front of our eyes," he said. "We have seen this in some other areas of cancer, but never in melanoma, which before this was a clinical scenario with an unmet need for therapy."

PLX4032, first engineered by the Berkeley, Calif., company Plexxikon Inc. and being developed in partnership with Roche, is not a foolproof cure, Dr. Tsao said in an interview. "It's clearly a huge leap forward for the patients who responded so rapidly, yet most are still progressing despite being on the drug. It's the best stun we've ever seen for melanoma, but it's not a permanent kill."

Sustained response in the phase I and II trials has varied from only two months to up to two years, Dr. Flaherty said. He could find no significant predictors of progression or response among the group except for initial tumor number and size. Typically, he said, the patients with the greatest mass of metastatic disease had the shortest duration of response, while those with a smaller tumor burden had a longer duration of response.

"When you have metastatic melanoma, your days are numbered--and numbered in a way we can't predict when metastatic disease is diagnosed," Dr. Flaherty said. "What this therapy does is push out the time until the disease worsens. We are not yet smart enough to understand what it is that allows a tumor to work its way around the drug's activity."

Chemotherapy-resistant cancers are nothing new, Dr. Tsao noted. What will be new is the full investigation of melanoma's genetic pathways, and the development of drugs to block them in multiple ways. "The next frontier will be to understand all the ways that melanoma can outsmart treatment. We may have to use multiple therapies to corner it. So a full discovery of all melanoma's potential vulnerabilities is very important."

Source:http://www.oncologystat.com/news/PLX4032_May_Clear_Path_for_Individualized_Treatment_of_Metastatic_Melanoma.html

The quote of the day

"The next frontier will be to understand all the ways that melanoma can outsmart treatment. We may have to use multiple therapies to corner it. So a full discovery of all melanoma's potential vulnerabilities is very important."

~Dr. Flaherty~




“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

Faltering Cancer Trials Melanoma.. Jim Breitfeller

Faltering Cancer Trials
Editorial
Published: April 24, 2010


The government’s system for judging the clinical effectiveness of cancer treatments, recently found to be in “a state of crisis,” must be repaired.

Here is a recent article from the New York Times. Thanks to Ed a carepage friend and colleage for bringing this to my attention.


Source:http://www.nytimes.com/2010/04/25/opinion/25sun1.html

Faltering Cancer Trials



We need the Patients to unite and get the best therapy for their condition. This is not rocket science, it is biochemistry at it's best. We need Big Pharma(Bristol Myer Sqiubb, Novartis,Pfizer, Plexikkon, Hoffman La Roche and others) to step up to the plate and do what is ethical. Not just looking at their bottom line. Without patients/consumers, these drug companies would not exist.

Our future survival is in our hands. The cure is out there. We need the medical community to take notice.




Take Care,
Jimmy B

Future Directions in Targeted Therapy for Melanoma..Jim Breitfeller

Future Directions in Targeted Therapy for Melanoma

“Our improved understanding of the molecular pathways that underlie the progression of melanoma has revealed numerous potential therapeutic approaches. We now face the challenge of developing targeted therapies directed at signaling pathways that are activated through mutations. Single-agent therapy is unlikely to be markedly successful,so there is also a pressing need to evaluate combination therapies, both with multiple targeted therapies and with targeted therapies plus conventional chemotherapeutic agents. It is hoped that these approaches will result in effective treatment options for patients with metastatic melanoma.”

~Dr. Keith T. Flaherty~


The Complexity of the T cell

In the midst of many promising discoveries, it became apparent to Dr. Allison and other researchers working in the field that stimulation of T cell response was more complicated than originally thought. As Dr. Allison and others discovered, first the T cell uses a structure called the antigen receptor to recognize a foreign antigen in the system (created by infecting viruses or bacteria, or new antigens found in tumor cells). Using an automobile as an analogy, Dr. Allison likens this step to turning the key in the car's ignition. "The car is running, but it's not going anywhere."

Recognition is not enough. Dr. Allison explains: "A second signal is also required, which, in the car analogy, would be the foot on the gas pedal." This second signal occurs when a particular family of molecules called the B7 molecule engages a molecule known as CD28 found on the surface of the T cell. Only these molecules are capable of initiating T cell response.

The final part of the car analogy is the immune system's brake -- an immune-regulating molecule, whose function was discovered by Dr. Allison's lab, known as cytotoxic T lymphocyte-associated antigen-4 (CTLA-4). CTLA-4 inhibits activated T cells in the immune system, preventing them from attacking the body's own tissues

It is now well accepted that recognition of specific antigen by the TCR is not sufficient for activation but that a second antigen nonspecific "co-stimulatory" signal is required. We have demonstrated that this second signal is provided the co-stimulatory receptor CD28 upon recognition of its counter-receptors, members of the B7 family, on the antigen-presenting cell. CD28 engagement is required under most situations for IL-2 production and proliferation. The lack of a CD28-mediated co-stimulatory signal upon TCR engagement can result in the induction of a long-lived state of nonresponsiveness.

We have recently found that co-stimulation is more complex than previously thought. CTLA-4, a homolog of CD28, also binds members of the B7 family, and binds them with affinities much higher than CD28. A wealth of data accumulated in the past few years show that CTLA-4 is an important downregulator of T cell responses. We have proposed that CTLA-4 plays a critical role in both the initiation and termination of T cell responses. According to this view, T cell activation is a dynamic process that is determined by the strength of the TCR signal; the strength of co-stimulation provided by CD28; and the magnitude of inhibitory signals generated by CTLA-4.

We have also demonstrated that CTLA-4 blockade can be used in combination with other methods of immunopotentiation or even conventional chemotherapy to obtain rejection of resistant tumors. We are currently examining the cellular and molecular mechanisms of the anti-tumor effect. The strategies we have developed in the mouse are currently in clinical trials for evaluation of effectiveness in treatment of prostate cancer and melanoma

Source: Sloan-Kettering Institute

"I believe that we are on the verge of bringing the manipulation of immune responses into the mainstream of cancer therapy," Dr. Allison said. "Recent work in cancer biology has shown that the genetic instability that is inherent in cancer results in a large number of mutations in proteins that create new antigens that the body has never seen before and ought to be readily recognized as foreign by the immune system. If we can kill some tumor cells, either as a result of a vaccine or treatment with more-conventional therapies, using agents such as anti-CTLA-4 ought to result in induction of potent immunity to these new targets. Thus, I believe that it is not unreasonable to think of many of the new targeted therapies as immunosupportive, and to use them in conjunction with the new approaches to enhancing immune responses."

~Dr. James Allison~

We are on the Verge of Harnessing the Immune System to recognize Melanoma cells as foreign. How this plays out will depend on if the Pharmaceutical companies like Bristol-Myer Squibb, Novartis, Pfizer, Hoffman La Roche, Plexikkon and other come together as one, to fight this Monster of a disease. Time will only tell. We owe it to the Patients.






Take care

Jimmy B

Melanoma_Missionary


"Today might be the worst day of your life...but tomorrow could be the best. You just have to get there."
~Unknown~

http://www.box.net/shared/kjgr6dkztj

Melanoma and The Magic Bullet (Monoclonal Antibodies)

There is No Magic Bullet to Cure Melanoma, And We Must Develop Multimodality Strategies..Melanoma..Jim Breitfeller

Expert opinion
“The research efforts directed towards the development of novel therapies for patients with metastatic melanoma have been intense despite disappointing clinical outcomes. It is clear that monotherapy for metastatic melanoma will not be successful, with every study to date yielding minimal clinical outcomes
data. Therefore, we must realize that there is no magic bullet to cure melanoma, and we must develop multimodality strategies to enhance the immune response to melanoma from different angles. This will require an unprecedented collaborative effort by many in order to overcome the historical competition between large pharmaceutical companies striving for ‘total cure’ with their drug.”

~ Dr.Adam I Riker~

We should realize that the future of drug development and design will depend heavily on the recent trend towards molecular medicine, and in particular, gene profiling efforts using gene microarray analysis. We are entering an entire new field of research dedicated to the molecular basis of cancer. Such research has the greatest potential to impact the way we treat patients with melanoma, focusing results on the prognostic significance of particular genes from a melanoma patient and basing clinical decisions as to whether such patients will (or will not) respond to a particular agent. The development of molecular signatures using gene microarray analysis has come to the forefront of existing research efforts identifying patients who may have an aggressive (versus indolent) form of melanoma and those patients with particular prognostic gene
signatures that may predict the response to forms of immunotherapy. The identification of such gene signatures has had important implications in the development of targeted immunotherapies for patients with metastatic disease. Thus, we must focus our efforts towards an improved understanding of the molecular and immunologic events involved in melanoma development and progression. We should also re-evaluate our present approach to immunotherapy and trial design, with many past trials failing to show clinical efficacy because of a lack of appropriate preclinical data that provide the essential rationale to perform such studies.

Source: http://www.southalabama.edu/mci/spf90/riker2.pdf

Immunotherapy of melanoma: a critical review of current concepts and future strategies








Take Care,

Jimmy B

Combinatorial Therapy, Will the Big Pharmaceutical Companies do what Is Ethically Right?Melanoma..Jim Breitfeller

Combinatorial Therapy, Will the Big Pharmaceutical Companies do what Is Ethically Right?




They include Plexikkon,Bristol-Myer Squibb, Pfizer, La Roche and Novartis.


I and other researchers have come to the conclusion that Combinatorial Therapy may be the only way to beat The BEAST, Melanoma



“A very obvious combination that we are trying to move forward now is PLX4032 with ipilimumab. There is unanimity among the academic researchers that this must be investigated. Both companies see the logic, but are reluctant with neither of their drugs yet being FDA approved. As you know ipilimumab (and tremelimumab) have not overwhelmed the FDA yet as they were told to show a response rate greater than 10% and neither drug could do so. Most melanoma researchers believe that there are additional patients who get real and long-term benefit without having their tumors shrink significantly in size, but the randomized trials are needed to show that. The worrying sign is the outcome of the tremelimumab randomized trial. So, now we are down to waiting for the results of the dacarbazine vs. dacarbazine plus ipilimumab phase III trial. If this is negative, we are in trouble as ipilimumab will have no clear path forward with the FDA. If it’s positive, then the idea of moving ahead with combinations becomes much, much easier. But, even it that trial is negative, we know that CTLA-4 blockade can induce phenomenal responses in some. So, in that case, we have to figure out (1) who those patients are and, (2) how to make those responses happen in more patients. The other way of thinking of #2 is that PLX4032 doesn’t work for as long as we would like and that making those responses more durable would be desirable.”


~ Dr. Keith Flaherty ~


“ Mike Weber was kind to forward your paper and email. It appears that you have a very good sense of, and interest in, the immune response to melanoma and to cancer in general. I believe you are right that timing of the various components of the immune response, especially with combination therapies, is important, just as it is in the orchestration of a beautiful symphony.”


~ Dr. Craig Slingluff ~



Dr Markovic,. I thought you might be interested in this combinatorial therapy

“We actually just submitted a paper to this affect in a small clinical trial where we used a conventional chemotherapeutic agent to induce a systemic anti-tumor immune response by simply timing drug delivery. And, it worked! It was a small study, so the data is only descriptive. I'm gearing up to move to a large trial right now.”


~Dr. Svetomir Markovic~



“To answer your last question first: Mutations in B-Raf and N-Ras have been shown to cluster at specific nucleotides. This strongly suggests that there is a cellular mechanism which targets these sites in each gene. However, you are probably right, that anti-CTLA4 and IL2 are working by enhancing immune surveillance of your melanoma.”


~Dr. Natalie Ahn~



“In conclusion, the combination of MART-1/DC with concomitant tremelimumab is feasible in patients with metastatic melanoma, especially when tremelimumab is administered every 3 months, and results in durable objective clinical responses at the higher range of the expected objective tumor response rates with either therapy alone. Therefore, this combination warrants further study in patients with advanced malignant melanoma.”

~Dr. Antoni Ribas~


The rationale for the CTLA-4 and IL-2 combination is once you activated the CD4+ Tcell and it crossprime the CD8+ Tcell , the IL-2 needed for the maintenance and functionality of the CD8+ T-cell.
If lymphocytes are cultured in the presence of Interleukin 2, it results in the development of effector cells which are cytotoxic to tumor cells.

“Fine theory but just theory that has never been tested in relevant clinical setting…”

~Dr. John M. Kirkwood~

"Glad to see your post on this series. From our perspective, the melanoma community isn’t waiting for a “miracle” to fall out of the sky to help patients. It’s clear that no single drug will likely effectively treat the disease; instead, a combination of drugs may be the answer. The Melanoma Research Foundation (MRF) is coordinating the Melanoma Breakthrough Consortium to accelerate research by bringing together leaders in drug development, laboratory and clinical research to find effective treatments. This collaboration will take years off the process. Patients with advanced melanoma have few or no treatment options and there’s no doubt in the urgency of moving forward to test new therapies today. More information is available at http://www.melanoma.org."

~Tim Turnham~
Executive Director
Melanoma Research Foundation




This is why we the patients need the Pharmaceutical companies to work together. Each therapy will not work alone as a single agent. The response rate is between 10 and 22 percent for each therapy. If you do a sequential treatment with the proper dosage and timing, you will see a synergistic outcome.

“There are three parts of the equation in a clinical trial. There’s who has control, who gets the reward, and who takes the risk. Patients take all the risk, they have no control, and they get no reward. Patients ought to be the ones driving the process and get the reward out of it and have the control, since they are the ones that take the risk.”


~Greg Simons~


If we are taking all the risk, shouldn’t we have a say in our Destiny?
“We need to all work together for the common good of the Melanoma Patients”
“We need to take greed out of the equation and just do what is ethically for humanity”

~Jimmy B~

Which elevator will you, The Pharmaceuticals Companies will Take?



Take Care,

Jimmy B

A Roller Coaster Chase for a Cure, Dr. Keith Flaherty Story..Melanoma..Jim Breitfeller

A Roller Coaster Chase for a Cure, Dr. Keith Flaherty Story

Published: February 21, 2010

PHILADELPHIA — His patient, a spunky Italian-American woman in her 60s, was waiting in an exam room down the hall for the answer: Was the experimental drug stopping her deadly skin cancer?


THE INVESTIGATOR Dr. Keith Flaherty oversees the testing of a drug known as PLX4032 calling it the best hope against melanoma “because it is based on what makes cancer tick.”


But as Dr. Keith Flaherty read out the measurements of her tumors from the latest CT scan, he could not keep the distress from his voice.

“She’s worse,” he said to the clinical trial nurse at the University of Pennsylvania’s melanoma clinic.

Source:http://www.nytimes.com/2010/02/22/health/research/22trial.html?pagewanted=1

A Roller Coaster Chase for a Cure, Dr. Keith Flaherty Story


As you can read, The research doesn't happen over night. You need a clinical Researcher that believes in the science.

I myself believe in our approach in how to get the host's immune system to see the Melanoma Cancer tumor cells. I have pages of Universities, Hospitals and Drugs companies following my blog at one time or another.

I even got this note from a world renowned Clinical Researher:

Dear Mr. Breitfeller,

Mike Weber was kind to forward your paper and email. It appears that you have a very good sense of, and interest in, the immune response to melanoma and to cancer in general. I believe you are right that timing of the various components of the immune response, especially with combination therapies, is important, just as it is in the orchestration of a beautiful symphony. I wish you success in your treatments and in your work to understand and to explain the immune response to cancer.

Craig Slingluff

Craig L. Slingluff, Jr. M.D.
Joseph Helms Farrow Professor of Surgery
Division of Surgical Oncology
Vice-Chair for Research
Director, Human Immune Therapy Center
University of Virginia

I have seen this treatment work. Until we have a Clinical trial in place, we won't know what the response rate would be.

We need more Clinical Researchers and Oncologists willing to step and think outside the box. Follow their passion and gut feelings to pursue a CURE. I tip my Hat to Dr. Keith Flaherty. Thanks for thinking outside the box!!!



Melanoma and The Magic Bullet (Monoclonal Antibodies)



Take care

Jimmy B

Melanoma_Missionary


"Today might be the worst day of your life...but tomorrow could be the best. You just have to get there."
~Unknown~

Braf PLX 4032 drug stopped working for first patient!!!Melanoma..Jim Breitfeller

This really crushes me. I was hoping this would be the beginning of the end for melanoma. Maybe it will with time and more research though.

I am not saying this will apply to anyone or everyone, but I think it is important that everyone needs to read this.

From MIF: Anyone currently on clincial trial of PLX 4032 or RO5185426 (jenniferslatton)

Posted: 3:20:38 pm on 1/27/2010 Modified: 4:12:04 pm on 1/27/2010

My 39-year-old husband is (as far as I know) the first U.S. patient to be in the Phase II BRAF-inhibitor trial funded by Roche Labs (partnering with Plexxikon). This trial uses the drug alone, without an arm that might include chemotherapy drugs (like the Phase III). He is on 960 mg twice aday of the drug, the highest tolerated dose. We are being treated at Moffitt in Tampa.

Clint began the trial the first week of October, about 15 weeks ago. We were astounded with the positive results and almost non-existent side effects (loss of body hair and mild muscle fatigue). That is, until last week, when the drug (PLX 4032/RO5185426) seems to have abruptly stopped working.

After much research we are learning that this is perhaps not an unexpected response. From my most recent reading it seems that for patients who are positive for the BRAF mutation (70% of melanoma patients), the BRAF-inhibitor may be necessary but not sufficient to create long-term effects. In my husband's case, we had genetic testing that determined the only mutation of note that could cause melanoma is the BRAF V600E mutation. But once he began the BRAF-inhibitor, the cancer seems to have created a new pathway around the drug. We will know shortly whether my husband's body has created new mutations and if so, which ones.

We are therefore, scrambling to find a new study that uses a combinatorial therapy of BRAF-inhibitor and MEK/RAS inhibitor (depending on what, if any, new mutations Clint has). I believe this combo therapy is likely to be the new frontier, and is already being studied in many places, including Australia and England. There is a combinatorial trial preparing to open in Nashville, TN, and I've got a call into their office to find out when. Now that the BRAF-inhibitor seems to have stopped working for my husband, we are in a race against the clock to once again stop his extremely aggressive, fast-moving disease.

In no way do I wish to "pull the rug out from under" any of you who are fortunate enough to be a patient on a BRAF-inhibitor trial. It has been an amazing drug! But I want to make sure we get our experience out there because we were very frustrated to not be given full disclosure about the likelihood of the disease finding new pathways. We had specifically asked our oncologist about a Plan B if the drug stopped working and he was dismissive of our question.

Now that we are in this scary place of seeing the disease quickly progress again, we have learned that the melanoma is now in his brain. This precludes Clint from most other clinical trials. If we had not let our guard down and had been looking ahead to combinatorial therapies, it would have made a big difference.


http://forum.melanomaintl.org/toastforums/toast.asp?sub=show&action=posts&fid=4&tid=9190

This is an indication that over time, Melanoma can mutate and change pathways to escape the immune system. As doctor's search for a cure, the BRAF therapy may end up as a "bridge therapy". Bascially something to fill in why they continue to look for more treatments.

I myself believe that the best way to overcome Melanoma is to use your own immune system.It can be done using a combination approach. Interferon,DTIC,Patrin-2,radiation,Anti-CTLA-4 and Interluekin-2. It is like a bicyle lock, you have to know the combination and proceed in the right order. The number of turns to the right or left corresponds to the doses and concentration.

Here is the combination, Good Luck!!!!!




Take Care,

Jimmy B

Man stands up for an ideal, or acts to improve the lots of others..Melanoma..Jim Breitfeller

Robert Kennedy said, "Few will have the greatness to bend history; but each of us can work to change a small portion of events, and in the total of all those acts will be written the history of a generation...it is from numberless diverse acts of courage and belief that human history is thus shaped. Each time a man stands up for an ideal, or acts to improve the lots of others, or strikes out against injustice, he sends forth a tiny ripple of hope, and crossing each other from a million different centers of energy and daring, those ripples build a current which can sweep down the mightiest wall of oppression and resistance."

This is a excerpt from a close friend from the Melanoma Community.

"Some of you have inquired about contacting administrators and clinical researchers both at Roche=BRAF and Bristol Myers Squib= Iplilmumab in order to have Bob get access to the clinical trials currently being done on Metastatic Melanoma. You are RIGHT ON! Indeed we must gather together and on behalf of Bob and so many more people we must contact these drug makers. Jimmy Breitfeller is a Carepage friend of ours who has beaten back his own beast of Metastatic Melanoma and has become a national advocate for those of us who are struggling with this disease. He is known as “The Melanoma Missionary” because of his daily dedication to cure of Melanoma. He has a petition that we can all sign entitled BMS COMPASSSIONATE INVESTIGATIONAL DRUG ACCESS. The electronic petition is located on his Blog

http://melanomamissionary.blogspot.com/ When you go to Jimmy's Blog you will read all his research and advocacy. This petition has taken his advocacy to a new level and it has been very effective in getting attention from the key decision makers at drug companies treating melanoma patients. It is critical for people like us to speak out and sign a petition to our government, whether it be the FDA or Congress and the Senate about the laws of Compassionate Care. Our officials need to be educated, especially when Healthcare is being debated RIGHT NOW in the Senate, and make the understand exactly what BIG PHARMA is doing correctly or NOT doing to help people who need access to medicine that might bring a cure to their diseases.

Day in and day out I read Carepages and talk to people who are at the end of their life. What I have learned from them and many of you who take the time to be updated on Bob's Journey is that we are all part of a much larger chain of life than we realize. Speaking only for myself, I have found internal happiness and joy when I have joined in the larger story, focusing less on myself and small issues and joining something wider. As you sign petitions and advocate for our loved one I think you will get a sense of what I feel on a daily basis working "the systems" to try gain access in order to find a cure for Bob's cancer. It is a kind of focus on our core purpose as a collective, which is to hand off a better world to the next generation, I find a deep sense of purpose. This is basically to say that some of the greatest joys and happiness these last 7 3/4 months has come from feeling in some small way together with Jimmy Breitfeller and many many many others we have contributed to making things better - especially for melanoma patients. What really does matter is how we treat each other.

Robert Kennedy said, "Few will have the greatness to bend history; but each of us can work to change a small portion of events, and in the total of all those acts will be written the history of a generation...it is from numberless diverse acts of courage and belief that human history is thus shaped. Each time a man stands up for an ideal, or acts to improve the lots of others, or strikes out against injustice, he sends forth a tiny ripple of hope, and crossing each other from a million different centers of energy and daring, those ripples build a current which can sweep down the mightiest wall of oppression and resistance."

Shabbat Shalom

I am proud to be a nanoparticle in this movement. See as particles get heated up, they move faster and faster. We start to collide with other things, this inturn starts everything into motion. Energy released from this motion may be in the form of heat. Heat can be good or bad. It just depends on which side you are on.

Please Join the movement. We owe it to all Cancer Patients around the world.

Take Care,

Jimmy B

Lifesaver... PLX-4032 Therapy for BRAF Mutations..Melanoma ..Jim Breitfeller

"Now, an incredible breakthrough. A tiny capsule that can stop even advanced Melanoma in its tracks.

It's called PLX 4032 — and the results are so swift and dramatic that it's got even the usually conservative medical community excited. Even better, this drug could mark the beginning of a cure for other forms of cancer. Already, it's giving some patients back their lives and, for people like 24-year-old Brendan Robbins, offering hope — just in time."

Reporter: Liz Hayes
Producer: Phil Goyen

Lifesaver... PLX-4032 Therapy for BRAF Mutations



Source:http://sixtyminutes.ninemsn.com.au/stories/927744/lifesaver-cancer

You may want to be checked for the BRAF Mutation.

Take Care,

Jimmy B