PSA Rising Prostate Cancer Blog

The Unreachable Availability of Provenge

2008-11-08T18:48:06Z

By Dan Abshear

Terminal patients are those who are not expected to live, usually due to an illness such as advanced cancer. Typically, a cancer patient is considered terminally ill if it appears he or she has 6 months or less to live. Cancer patients who are terminally ill, without cure or tolerable treatment, with the expectation that they will die soon, may seek and desire even unproven treatment options.

Understandably, for patients at a severe stage of illness, such as advanced prostate cancer, possible extension of life with comfort is worthwhile regardless of lack of evidence of proof that the treatment will indeed provide those benefits.

The FDA claims authority over the treatment options of such patients. Yet in recent years the FDA, with its frequent drug recalls and black box warnings –usually imposed only under pressure from the public — has proven itself to be rather inadequate. The FDA may not be an ideal judge of treatment options for very sick patients.

Individuals should be the deciding factor in selecting their treatment course along with their health care provider, and not an unreliable FDA.

Prostate cancer is the second most common cause of cancer death in men, with between 10 to 20 percent of men predicted to acquire the disease during their lifespan, resulting in the USA in about 30,000 deaths a year from this disease. The more aggressive and advanced prostate cancer becomes, as determined by measures such as Gleason score and methods such as bone scan, the harder it is to treat the patient.

Yet innovation still exists in medicine. A few years ago, a small biotechnology company called Dendreon was working on a conceptually new treatment for prostate cancer. They called it Provenge.

The immunotherapy method developed by Dendreon requires the removal from each diseased patient of some white blood cells (part of the immune system). These are reinjected into the donor patient after being processed by a method designed to make the cells attack a target found only on tumors — in this case a chemical called PAP, which is over-produced by prostate cancer tumors.

As developed in the race to make Provenge the first immunotherapy biologic treatment for progressed prostate cancer patients, Dendreon commenced clinical trials on patients who, no longer responding to standard available treatments, had no approved option remaining except for a chemotherapy called Taxotere. At such a traumatic stage of prostate cancer, many patients, foreseeing brutal side effects from Taxotere, refuse treatment entirely. As tested in clinical trials, Provenge requires just three injections in a period of six weeks.

Provenge received Fast Track status from the FDA because initial evidence indicated potential benefit for terminal patients. Dendreon proceeded to gathered evidence of the safety and efficacy of Provenge as a therapy of benefit for severe prostate cancer patients. Clinical trial results indicated that men with advanced prostate cancer who were treated with Provenge obtained life extension twice that of patients receiving chemotherapy, and without the concerning side effects of chemotherapy.

The medical community and survivors of prostate cancer were elated and waited with great anticipation for access to this treatment method. Patients and their families expressed great joy. Caregivers and specialists such as urologists and oncologists who treat such patients were no less elated. In March 2007, an FDA panel recommended with clarity the approval of Provenge based on its proven and substantial efficacy and safety, as demonstrated in its trials.

Now for the bad news: to great shock and surprise, the FDA agency rejected the approval of this great treatment for very sick patients. They announced this rejection, due to, they said, ‘lack of data, ’ in May of 2007. This decision contradicted their own experts’ favorable opinion of Provenge weeks before delivering this terrible news. Especially on considering that the FDA Commissioner is a prostate cancer survivor himself, many found this ruling completely unbelievable.

Soon after the FDA passed this judgment, others discovered conflicts of interest. In particular, one of the oncologist’s specializing in prostate cancer who helped evaluate Provenge on behalf of the FDA agency, Dr. Howard Scher, was found to have a financial commitment to a future competitor of Provenge that was being produced by another biotech company called Novacea. This company had signed a co-promotion agreement with a major pharmaceutical company, Schering, to provide support for development of this competing therapy for advanced prostate cancer.

Dr. Scher never disclosed this conflict during the approval process of Provenge. As it turned out, eventually, Novacea’s drug was discovered to have serious flaws, and Schering pulled out of their agreement with Novacea.

In addition, in an incident between March and May of 2007, baseless letters were anonymously delivered to the FDA stating negative qualities about Provenge, claims which critics believe were without merit, speculative and even fabricated.

Overall, the FDA’s refusal to approve Provenge angered many, and a newly formed advocacy group called Care to Live last year filed a lawsuit against the FDA charging clear lack of protocol or knowledge about such complex treatment agents as Provenge.

Terminal patients, I surmise, desire comfort during the progressive disease that has placed them in the last chapter of their lives. They certainly should have a right to choose any treatment that possibly could benefit them. Most are willing to assume any risks of unapproved, yet potentially beneficial treatments such as Provenge. Because they have a terminal illness, for these patients possible benefits clearly take priority over safety issues of unapproved treatments.

The controversy could be concluded by a terminal patient’s signing a waiver of some sort, perhaps, stating that they are responsible for the consequences of an unapproved treatment regimen such as Provenge. Yet the FDA, with reckless disregard and overt harshness, denied what likely was a great treatment method for these very ill patients. Considering the available data on Provenge, granting approval, especially for terminal patients, would seem completely rational.

The FDA does in fact presently have the ability to grant what is called conditional approval for such treatment methods as Provenge at this time, and why they have not remains completely unknown. What is known is that they are harming those they pledged to protect so long ago. The FDA ultimately harmed others more by not approving Provenge nor offering any exceptions for cancer patients in this extreme situation.

I would go as far as to say that the FDA appears to be a bought, corrupt, and incompetent administration without loyalty and dedication to the public and its health. In view of the FDA’s past failures with regard to drugs belatedly taken off the market and the increasing need to label other approved drugs with black box warnings, individuals should be the deciding factor in selecting their treatment course along with their health care provider, and not an unreliable Administration.

“Facts do not cease to exist because they are ignored.” — Aldous Huxley

Dan Abshear is a freelance medical writer and healthcare journalist. After serving with the Navy and Marine corps. and receiving training as a medic, Abshear worked in pharmaceutical sales for 10 years. He has worked Tenet Healthcare promoting prostate screening and as a representative for Merck, Pharmacia, and Novartis.

Androgen Deprivation May Spur Prostate Cancer Spread

2008-11-17T01:59:23Z

Androgen deprivation therapy, heavily-prescribed for men with prostate cancer, may have an unforeseen downside. According to a new study, lack of androgen may make any surviving cancer cells more invasive.

Generally, when prostate tumors are deprived of androgens (male sex hormones, notably testosterone and its precursors), they shrink for extended periods of time. But androgen deprivation therapy, Johns Hopkins researchers have found, may produce a protein called nestin, which makes prostate cancer cells more likely to spread throughout the body.

The Johns Hopkins researchers caution that their discovery is far too preliminary for prostate cancer patients or physicians to stop using it, but they believe that the finding could eventually lead to changes in this standard treatment for a sometimes deadly disease. The therapy is effective at slowing tumor growth, they emphasize

A team led by David Berman, an assistant professor of pathology, urology and oncology at The Johns Hopkins University School of Medicine identified this unsuspected potential problem with treatments that suppress testosterone after discovering that the gene that codes for the protein, called nestin, was active in lab-grown human prostate cancer cells.

Curious about whether prostate cancer cells in humans also produce nestin, the team looked for nestin in cells taken from men who had surgery to remove locally confined cancers of their prostates and found none.

But when they looked for nestin in prostate cancer cells isolated from patients who had died of metastatic prostate cancer - in which cancer cells spread out from the prostate tumor - they found substantial evidence that the nestin gene was active.

What was different, Berman speculated, is that androgen deprivation therapy, a treatment that reduces testosterone in the body, is generally given only when prostate cancers become aggressive and likely to metastasize.

Because prostate cancer growth is typically stimulated by testosterone, the treatment is thought to slow tumor growth and weaken the disease. Patients who eventually die because their disease metastasizes are almost certain to have received this type of therapy, he says.

Speculating that depriving cells of androgens might also affect nestin expression, the researchers experimented on a prostate cancer cell line that depends on androgens to grow. When they removed androgens from the chemical mixture that the cells live in, their production of nestin increased.

Aware that the nestin gene has long been suggested to play some role in cell growth and development, Berman and his colleagues used what they describe as a bit of “laboratory sabotage” called RNA interference to decrease the genetic expression of nestin.

They found that these nestin-void cells weren’t able to move around and through other cells nearly as efficiently as could cells with normal nestin levels.

Prostate cancer cells with hampered nestin expression were also less likely than normal prostate cancer cells to migrate to other parts of the body when transplanted into mice. However, while nestin expression seemed pivotal for metastasis in these experiments, it didn’t seem to make a difference in tumor growth.

“What all this suggests is that nestin levels increased when prostate cancer cells are deprived of androgens and may encourage the cells to metastasize,” says Berman.

In men, androgen deprivation may occur either naturally, rhough aging or by means of anti-prostate cancer drugs, Berman’s articl;e notes:

“These results specify a function for nestin in cell motility and identify a novel pathway for prostate cancer metastasis. Activity of this pathway may be selected by the extraprostatic environment or, as supported by our data, may originate within the prostate after androgen deprivation. Further dissection of this novel Nestin migration pathway may lead to strategies to prevent and neutralize metastatic spread.”

Besides Berman, other Johns Hopkins researchers involved in this study were Wolfram Kleeberger, M.D., G. Steven Bova, M.D., Matthew E. Nielsen, M.D., Mehsati Herawi, M.D., Ph.D., Ai-Ying Chuang, M.D., and Jonathan I. Epstein, M.D.

The research, published in the Oct. 1, 2007 issue of Cancer Research, was funded by grants from the National Institutes of Health, National Cancer Institute, Evensen Family Foundation, and German Cancer Aid Foundation.

androgen blockade

Prostate Cancer Symposium, Bethesda, Sept 24

2008-10-18T21:03:38Z

Dr. Snuffy Myers will be the principal speaker at the “Prostate Cancer Symposium” held on Monday September 24th at the Suburban Hospital at 8600 Old Georgetown Road in Bethesda, Maryland. Registration is required. Reception is at 6:30 PM followed by the presentation at 7PM. The Symposium is free as are the snacks that are served during the reception. Get more info from ProstateSymp9-2007.pdf.

African American Prostate Cancer Disparity Summit

2008-10-22T05:22:10Z

The Third Annual African American Prostate Cancer Disparity Summit will be held:
September 27 & 28, 2007 at Rayburn House Office Building, Washington, DC

MAJOR SESSION TITLES

1. RECOGNIZING THE AFRICAN AMERICAN PROSTATE CANCER EPIDEMIC THROUGH LEGISLATION
This session will analyze and present how and where key legislation can be used as a catalyst to gather resources to fight this epidemic.

2. THE GLOBAL BLACK PROSTATE CANCER CRISIS
Presentations on global prostate cancer research findings targeting Black men of African ancestry, concluding with a discussion of a global consortium to address the Black prostate cancer crisis.

3. PROSTATE CANCER IMMUNOTHERAPY VACCINES - A PROGRESS REPORT
The first ever prostate cancer immunotherapy vaccine went before the FDA for approval in 2007. What are the prospects for an immunotherapy vaccine approval within the next one to three years? Why is patient advocacy vital for approval? Who are the companies involved in developing immunotherapy treatments? What efforts need to take place now to insure accessibility of these new treatments for African American patients.

4. PARTICIPATION IN RESEARCH ACTIVITIES
African American participation in clinical trials in support of prostate cancer research activities is problematic. This session will explore strategies for increasing African American participation in prostate cancer clinical trials and other research activities.

PRESENTATION

THE CASE FOR WATCHFUL WAITING THROUGH ACTIVE SURVEILLANCE AS AN IMPORTANT TREATMENT OPTION
With a higher incidence rate and more later-stage diagnoses, are African American men at a greater risk to receive more radical treatments for non life threatening prostate cancers? This presentation will examine research and data supporting active surveillance as a treatment approach. It will also analyze imaging technologies as a means of active surveillance.

http://www.prostatehealthed.org/

Merv Griffin Fought Recurrent Prostate Cancer for Years

2008-10-22T05:23:21Z

When Merv Griffin died on August 12, his family said on his website :

Griffin, who turned 82 on July 6th, was recently diagnosed during a routine examination with a recurrence of the prostate cancer that he had overcome more than a decade ago. Its aggressive progression to other organs was unexpected and immediate, according to his doctors at Cedars-Sinai Medical Center in Los Angeles.

The notion of a sudden fatal resurgence may mislead other men who are fighting prostate cancer.This description of Griffin as “recently diagnosed” during a “routine examination” with a recurrence of a cancer “overcome” a decade ago surprised some prostate cancer patients and alarmed others. It really doesn’t fit with the typical pattern of prostate cancer recurrence and progression. It’s not how most patients who suffer recurrence learn about it.

The statement by the Cedars-Sinai doctors may have been intended to preserve Griffin’s privacy and to assure family members that nothing more could have been done. More detail came from The National Enquirer, which reported that Griffin’s prostate cancer had spread to his bones, bladder, back and lungs. A catheter was put into his bladder to ease urination; blood was drained from his lungs.

A spokeswoman for The Griffin Group replied to a patient’s query: “1996. treated by radiation. brief episode in 1999. Reappeared as small spots on bone 2 months ago, and spread rapidly and aggressively, and there was some chemo. . . . Merv had frequent check-ups and always came away with a clean bill of health until the day he didn’t.”

Why bury the fact that he knew years ago that his cancer had come back? “Always a clean bill of health” does not fit with what Merv’s son Tony Griffin told Larry King Live on August 23.

Griffin was treated with radiation in 1996. According to Tony, he knew his prostate cancer had come back 4 or 5 years before he died. He received follow up treatment for recurrent prostate cancer from a specialist at Cedars-Sinai. Merv Griffin made none of this public at the time. In fact, he did not tell his son what was really happening until entering hospital about 6 weeks before he died.

In early July this year, Merv’s assistant called in Merv’s son for what they both perceived as a breathing problem related to smoking. Merv was very ill and needed day and night assistance to get from couch to bed to bathroom. Merv was in pain, which grew worse. He entered Cedars- Sinai Medical Center. There he told his son that the prostate cancer had progressed to his bones. He died 33 days later after 5 days in the ICU.

Here’s what Tony Griffin told Larry King, August 13:

The end seems to be a little bit more longer than most people know. He got sick six to seven weeks prior to him dying…. And sick I mean he — his assistant, Ronnie Ward, called me and said, “Come on over here. You need to see your dad. He’s really wheezing.”

I go, “What is he smoking?”

He goes, “Oh, yes, he’s smoking.”

I said, “Oh, Ronnie, get those cigarettes from him.”

He goes, “I can’t, I can’t.”

So I come over and he was having trouble moving from the couch to the bathroom to the bedroom. And we knew something was wrong and he didn’t want any of us to stay. He wanted someone staying there at night.

So Ronnie and I started switching off nights and taking care of him and switching off days. We didn’t leave him.

And then he was having pain here. And so we said, well, jeez, dad, you’ve got to go to the hospital. And I was at home and my cousin Mike called me and said, hey, he just went to the hospital because he went in to see about the pain. It was right before July 4th.

So it was on July 3rd. So he went in the hospital. So I said, “Dad, what are you doing here? What’s going on?”

And he finally told me he — his prostate cancer had metastasized to his bones.

KING: Now, he told everyone he had beaten prostate cancer.

T. GRIFFIN: Yes, I know.

KING: He hadn’t?

T. GRIFFIN: No.

KING: He didn’t at the time?

T. GRIFFIN: How do you — you know, how do you quantify it? I don’t know. He — I guess about three or four years ago, he had not told any of us and went to this specialist, Dr. David Agus and who is the chief guy at Cedars, runs the cancer lab. And I guess they were treating it. I’m not sure. I’m not clear.

KING: Did he know he was dying?

T. GRIFFIN: The last 33 days in the hospital he kept asking me every day if he was dying. So he — he kind of knew. I mean it was getting worse and worse so…. “

(from CNN transcript, August 13)

About one third of men who are treated for prostate cancer do experience recurrence. And close to 30 thousand of these men a year die of metastatic prostate cancer, i.e. of prostate cancer progressed to other organs, typically to bone and commonly also to liver, lungs, and/or brain.

Usually, men whose prostate can comes back, either immediately or years after initial therapy with surgery and/or radiation and or/androgen blockade, are likely to know about this, from regular follow-up tests, months or years before the disease reaches final, exponentially metastatic stages. Recurrent prostate cancer is usually treated with various types and levels of hormonal manipulation and with chemotherapy. Newer treatments, some already approved and some in clinical trials, include monoclonal antibodies and immunotherapies.

Free Prostate Cancer Symposium, Houston Tx, October 07

2008-10-22T05:27:33Z

Free Prostate Cancer Symposium on October 20, 2007 — The Methodist Hospital, Houston, Texas. Speakers are physician-scientists from The Methodist Hospital, Baylor College of Medicine and UT. Focus is on the roles of XRT, Robotic and Laparoscopic Surgeries; Hormone Management and Alternatives to Hormone Therapy and treatments in the pipeline such as Vaccines and Gene Therapy. Save the Date!

Evidence-based Complementary and Alternative Cancer Therapies for Cancer Advocates

2008-10-22T05:28:15Z

The Annie Appleseed Project invites you to its conference on “Evidence-based Complementary and Alternative Cancer Therapies for Cancer Advocates” aka CAM for Cancer Advocates.
January 10-11, 2008 in West Palm Beach, FL

Registration is open, hotel link is up! We’ll have tables for exhibitors, show some DVDs and network. Organic food served.

Check out our speakers bios and website links. All the details can be found at:
http://annieappleseedproject.org/evcamforadc.html

We want to help educate advocates, people with cancer, and interested others about the evidence behind CAM. We’ll also be talking about evidence gaps, funding, choices, patients’ stories, opportunities, and much more. Since studies show so many are interested, so few talk to their healthcare practitioners and there is so much evidence, come find out. Bring this information back to your communities, and help answer the questions.

Neuvenge Breast Cancer Vaccine Phase 1 Results

2008-10-18T20:51:51Z

Results from a Phase 1 study of NEUVENGE, Dendreon’s candidate vaccine for breast cancer, appeared today in Journal of Clinical Oncology. Testing of Neuvenge in clinical trials runs several years behind Provenge, which is in an ongoing Phase 3 trial. Out of 18 patients with advanced breast cancer who received Neuvenge, 1 patient showed partial response for 6 months and 3 patients had stable disease lasting more than a year.

Neuvenge antigen is made from “sequences from intracellular and extracellular domains of human epidermal growth factor receptor 2 (HER-2) linked to granulocyte-macrophage colony-stimulating factor.”

Results: Nineteen patients were enrolled; 18 patients received treatment. Therapy was well tolerated, with no grade 3 or 4 adverse events associated with the treatment. Significant cellular immune responses specific for the immunizing antigen and HER-2 sequences were induced after treatment, as measured by lymphocyte proliferation and interferon gamma enzyme-linked immunospot assay. One patient experienced a PR [partial response] lasting 6 months. Three additional patients had SD [stable disease] lasting more than 1 year.

Treatment With Autologous Antigen-Presenting Cells Activated With the HER-2 Ã¢â‚¬â€œBased….

Dendreon Corp released a statement today:

“In addition to demonstrating that NEUVENGE was safe and well tolerated, the T-cell responses seen in these patients and the prolonged disease stabilization in the absence of other anti-cancer therapies in many patients is promising,” said John W. Park, M.D., associate clinical professor of medicine and neurosurgery at the University of California, San Francisco and lead author of the publication. “These observations are encouraging and are suggestive of the clinical benefit of NEUVENGE, particularly in light of the aggressive cancer seen in these patients who had progressed while on standard therapy. The findings warrant additional studies of NEUVENGE for the many women with advanced breast cancer who have exhausted many of their treatment options.”

“We are pleased that the results from this Phase I study of NEUVENGE demonstrate its potential as a treatment for advanced breast cancer patients,” said Mark Frohlich, M.D., vice president of clinical affairs at Dendreon. “These data, together with the data we have published on the use of Provenge (sipuleucel-T) in prostate cancer, further substantiate the promise of active cellular immunotherapies as new treatments for different types of cancer.”

Full release at Dendreon.com

HIFU and Chemotherapy Trial in France for Prostate Cancer

2008-10-18T21:07:47Z

Edap TMS SA (EDAP) said it is currently conducting clinical investigations in France under an approved clinical trial combining the company’s Ablatherm-HIFU device with chemotherapy using docetaxel.

The study is a primary treatment therapy program for men suffering from clinically localized but aggressive high risk prostate cancer typically classified as stage T2c. The study began in late 2006 and the company expects to enroll up to 30 men, of which more than 10 have already been treated. More details — press release.

Merv Griffin dies of prostate cancer at age 82

2008-10-22T05:46:22Z

Merv Griffin (July 6, 1925- August 12, 2007), a pioneer in the TV entertainment industry, has died at age 82 of prostate cancer. Merv Griffin, a singer and talk show host, created the TV games Wheel of Fortune and Jeopardy. Diagnosed with prostate cancer in 1996, he was treated initially with brachytherapy therapy [see correction below]. Although the exact time of his cancer’s recurrence and what treatments he then received have not been announced, his family say on his website

Griffin, who turned 82 on July 6th, was recently diagnosed during a routine examination with a recurrence of the prostate cancer that he had overcome more than a decade ago. Its aggressive progression to other organs was unexpected and immediate, according to his doctors at Cedars-Sinai Medical Center in Los Angeles.merv.com:

Griffin spoke on TV about receiving fitness tips from his friend Arnold Schwarzenegger but said that he continued smoke. In July he told Larry King on TV that that his prostate cancer had come back and was advanced. Last week, gravely ill, he entered Cedars Sinai Hospital in Los Angeles and, according to his son interviewed on Entertainment Tonight, was sedated for 5 days, intubated and treated for extreme pain. He died on Sunday August 12.

Merv Griffin’s warmth, charm and talent are on display at You Tube in fuzzy videos such as his performance with friends of WHAT IS THIS THING CALLED LOVE”.

Merv Griffin’s career is outlined at CNN. Entertainer, businessman Merv Griffin dies at 82.