Drug’s delay mobilizes prostate patients to activism
He’d been fighting prostate cancer for 12 years, and his doctor told him the disease was spreading, but Ted Girgus still had hope.
In 2006, the retired college administrator had moved from Ventura County to Bellingham, Wash., to be closer to his three sons, his daughter and his wife’s family as his health worsened. While there, however, he learned of a Seattle-based company conducting studies on a new kind of cancer therapy, one that might extend the lives -- at least by a couple of months -- of men who had exhausted all other options.
“As an advanced-prostate cancer patient, I was elated,” Girgus says. “The company was sending all their data to the Food and Drug Administration, and the FDA had fast-tracked the drug.” Fast-tracking means the agency sees promise in a drug and agrees to evaluate it as soon as possible.
In March, an FDA advisory committee voted to recommend approval of the therapy, a cancer vaccine genetically engineered to prod the patient’s immune system to attack the disease with renewed vigor. But, in May, the FDA announced that it would require more data on the therapy -- called Provenge and made by Dendreon Corp. -- before reconsidering approval. The agency said there appeared to be no evidence that the vaccine was effective.
That turnaround has outraged many men with prostate cancer. They had been hoping for a promise of extra time, no matter how limited. It also has fueled a level of patient activism common among women with breast cancer but rarely seen among prostate cancer patients.
A coalition of prostate cancer patient advocacy groups, Raise a Voice, led a rally last June at the FDA and met with agency officials to push for more prostate cancer therapies. The coalition includes the Los Angeles-based Prostate Cancer Research Institute, Us Too International, Malecare, the Prostate Health Education Network and several state prostate cancer organizations.
The investor-led group Care to Live has held rallies in Washington, D.C., and Chicago and purchased bus and newspaper advertisements in Washington calling for a review of the FDA’s decision. That group, which is funded by private donations, also filed a lawsuit alleging that the FDA’s decision was influenced by conflicts of interest. The Abigail Alliance for Better Access to Developmental Drugs has backed the protests; that group has sued the FDA to allow dying patients greater access to unapproved products that have cleared preliminary safety tests.
Also, cancer doctors, patients and even one former FDA official have written editorials and letters to the FDA questioning the agency’s approval process and calling for more research and better treatments for prostate cancer. Earlier this month, three members of Congress called for a congressional hearing to investigate the FDA’s decision on the vaccine.
The reaction has been notable both for its tenor -- the two FDA advisory committee members who asked for more information on efficacy have received death threats -- and its focus on a specific drug. Other disease-specific activists generally support general research and development, not one medication.
Regardless of the emphasis, prostate cancer activists say, the response could herald a new era of patient advocacy. Often embarrassed by the disease and reticent to call attention to themselves, prostate cancer patients have been a relatively undemanding group considering the number of people afflicted.
About 230,000 American men are diagnosed with prostate cancer each year, and 27,000 die of the disease -- statistics that are roughly comparable to breast cancer. Yet federal funding for breast cancer research is more than double that of prostate cancer, according to the National Institutes of Health.
“This has really kick-started the prostate cancer community and given us some motivation and focus,” says Jan Manarite, a Raise a Voice volunteer and Florida educational facilitator with the Prostate Cancer Research Institute, or PCRI, a nonprofit education and research organization on prostate cancer. “I think we’re finally learning about advocacy. I hope this experience helps us learn how to work effectively with the FDA.”
Raise a Voice does not accept funding from Dendreon or other drug companies. PCRI accepts unrestricted educational grants from businesses, including pharmaceutical companies. It received two unrestricted grants from Dendreon in 2000 and 2003.
Some activists are dismayed by the occasional ugliness of the debate and say the movement needs to grow beyond this incident.
“While it was nice to see some people in the prostate cancer community mobilize, the way a few people handled it by making death threats was appalling,” says Jamie Bearse, executive vice president of the National Prostate Cancer Coalition, a nonprofit, education and advocacy group based in Washington, D.C. “All the protests in the world won’t get this drug approved if the science is not where it should be.”
It may not be. In Dendreon’s studies, patients taking Provenge experienced 4.5 months of survival time compared with 2.3 months of survival time for patients taking the only other drug approved for end-stage prostate cancer, a type of chemotherapy drug called taxotere. The Dendreon study failed to meet its primary objective of stopping the cancer’s spread.
But oncologists and prostate cancer activists say the vaccine represented not only hope for advanced prostate cancer therapies but also optimism that a new field of similar treatments, called active cellular immunotherapy, could change how some types of solid tumors are treated. Provenge would have been the first therapeutic cancer vaccine to receive FDA approval.
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Activating immune cells
To make the vaccine, white blood cells that activate other immune system cells are isolated from the patient’s blood. These cells, known as antigen-presenting cells, are mixed with a bioengineered molecule similar to one found on nearly all prostate cancer cells.
The vaccine is then administered to the patient in three infusions. The bolstered cells help the patient’s immune system identify the cancer cells in order to attack them.
The therapy is not a cure, but is intended to extend life in men with late-stage cancer that no longer responds to hormone therapy designed to halt tumor growth.
Although the FDA’s advisory committee voted 13 to 4 that the drug was effective and unanimously that it was safe, the FDA asked Dendreon to submit more data from a study designed specifically to show survival.
Furious patients and investors say the therapy’s safety and survival data warranted its approval. They can’t reconcile the advisory committee’s thumbs-up votes with the FDA’s ultimate decision.
“We were shocked,” says Mike Kearney, an Ohio investor in Dendreon who filed suit against the FDA last July accusing the agency of ignoring conflict-of-interest issues with some medical advisors who voted against the vaccine. “We firmly believe that politics and financial interests are the cause of this.”
One advisory panel member, Dr. Howard Scher, was a lead investigator for a competing cancer drug under development. The suit also contends that turf wars within the FDA may have derailed the approval.
In November, the 6th Circuit Court in Ohio dismissed most of the lawsuit. Kearney, a board member of Care to Live, said the group has filed an appeal. An FDA spokesperson said the agency would provide no further comment on Provenge because of the pending lawsuit.
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Concern in Congress
In a Dec. 12 letter to the House Committee on Energy and Commerce, three members of Congress also called for an exploration of whether conflicts of interest on the part of FDA advisory committee members had a role in the FDA’s decision. Representatives Mike Michaud (D-Maine), Tim Ryan (D-Ohio) and Dan Burton (R-Ind.) coauthored the letter.
The fact that Provenge appears to be safe and produces few side effects was a big plus in patients’ eyes, says Manarite, whose husband has advanced prostate cancer. The standard treatment, taxotere, can cause fatigue and other symptoms and increases the risk for infection.
“I will never take chemotherapy,” Girgus says. “It adds maybe two months to your life. And during those two months you lose your hair, have diarrhea, can’t eat. I can’t do that.”
But two doctors on the FDA advisory panel who voted against approval say the studies provided no proof of efficacy and that Provenge could not be approved without such proof.
One of the dissenting panel members, Dr. Maha Hussain, said in a statement provided to The Times that a larger trial is needed to provide definitive answers. A professor of genitourinary oncology at the University of Michigan, Hussain said doctors owe it to their patients to recommend therapies that are based on high scientific standards.
The other physician, Scher, chief of the genitourinary oncology service at Memorial Sloan-Kettering Cancer Center in New York City, said in a letter to the FDA that more research is needed to show the survival benefit was real and not based on chance.
In those comments, published in the Cancer Letter, a newsletter that covers federal cancer policy and funding, he noted that Provenge was not shown to stabilize the disease, improve quality of life or delay pain. He declined to be interviewed because of the pending lawsuit.
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FDA’s dilemma
The debate over Provenge highlights how difficult it is for scientists and the FDA to reach a decision about some drugs, says Dr. David Penson, an associate professor of urology and preventive medicine at the Keck School of Medicine at USC/Norris Cancer Center. He conducted some studies on Provenge and attended the FDA advisory committee meeting on the therapy last March.
Penson says he was struck by the committee’s essential dilemma: Approve too quickly and an ineffective drug might enter the marketplace. Approve too slowly and patients might be denied a potentially useful therapy.
“Provenge prolongs life, but not tremendously,” Penson says. “There is a three- to four-month survival advantage. That may not seem like a lot to you or me, but these men are really desperate.”
Because therapeutic cancer vaccines work differently than traditional cancer drugs, some experts say the FDA needs to evaluate them differently. Other measures of benefit may need to be used for immunotherapies prescribed for advanced disease instead of the traditional measures, such as tumor growth, used for chemotherapy, they say.
A former consultant for Dendreon, Penson says he no longer has a role or financial interest in the company. Many men still call his office to ask when they can get the drug, Penson says, adding that he supports approval of the vaccine.
An interim analysis of the FDA-requested 500-patient survival study will be completed next year, with the final study completed in 2010. The company, however, may seek FDA approval next year if interim data show a distinct survival benefit.
“I think the patient reaction underscores the need for new treatments and that patients are quite desperate,” Penson says. “It reminds me of the response that HIV patients had in the 1980s with the need for new HIV therapies. Prostate cancer is an extremely common tumor. Patients want the FDA to be responsive.”
Manarite says her organization’s response to Provenge represented its first advocacy efforts, and that she and others want a productive relationship with the FDA to increase treatment options.
“This is about men with prostate cancer; it’s not about Provenge,” she says. “But men with prostate cancer want Provenge.”
The prostate cancer community should rally around the issue of more research and new treatments -- not simply the issue of Provenge, says Bearse of the National Prostate Cancer Coalition.
“For most men, any excuse is a good excuse not to take care of your health, let alone be an advocate for it. That mentality has to change in a big way,” he says. “Only when we have a grass-roots swell even greater than what has transpired with Provenge will we achieve parity with breast cancer on the path to a cure.”
Girgus, who bought stock in Dendreon, says he hopes he can one day benefit from the drug. But he says his fight now is for others, including his adult sons.
“This has made an activist out of me,” he says, noting that in October he asked his local grocer why the store commemorated breast cancer awareness month each October by using pink grocery bags but did not recognize prostate cancer awareness month in September.
“I said, ‘Where are the blue bags?’ ” Girgus recalls. “The store manager is a lovely lady. She said, ‘I didn’t know about that. But I promise you we will have blue bags and blue ribbons in September.’ ”
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