In a small study, the median survival of men treated with Provenge was 26 months, just 4.5 months more than patients receiving a placebo. A survival edge in a second small study could have been by chance. And Provenge did not achieve one of its primary goals of delaying disease progression.But the controversy is even more pointed than that, this week, Diedtra Henderson wrote in the Boston Globe,
Yet the 4.5-month survival benefit was almost double that of Taxotere, a treatment with tough side effects that is the only other option for advanced, progressing cancer.
The FDA's expert advisory panel voted unanimously that Provenge is safe but voted only 13-4 that it was effective.
Prostate cancer activists have raised questions about two of the negative voters - academic medical oncologists Maha Hussain and Howard Scher. Both were granted conflict-of-interest waivers and have been members of an FDA advisory committee that evaluates conventional cancer drugs.
In an unusual move, both wrote letters to top FDA officials complaining about the advisory committee that recommended approval of Provenge.
Yesterday about 100 activists from 19 organizations rallied in Washington. The activists are petitioning Congress - and pressuring the FDA - to approve marketing of the promising prostate cancer "vaccine," while its manufacturer, Dendreon Corp., completes a 500-patient study.
Afterward, six of them met with FDA Commissioner Andrew von Eschenbach - who himself has been treated for prostate cancer.
The FDA's delay, the activists believe, could add years more to Provenge's long development odyssey.
'You're talking a minimum of two more years,' declared rally leader Thomas Farrington, founder of the Prostate Health Education Network, aimed at African American and other men at high risk of the disease. 'Since prostate cancer kills 27,000 men a year, you're talking 54,000 deaths.'
It actually gets worse than that. According to the New York Times,
When federal regulators delayed approving a promising new prostate cancer therapy, patients and the drug’s advocates reacted with more than disappointment.
They took a page from the playbook of AIDS activists and took to the streets and to the Internet, mounting an unusually intense lobbying campaign to pressure the Food and Drug Administration to reverse its stance on Provenge, the experimental cancer drug.
Blogs and websites are uniting disappointed cancer patients and disillusioned investors who put money on Seattle-based Dendreon Corp.’s Provenge, believing it could rally the body’s immune system to combat cancer.
Some, however, question whether some Provenge advocates are too aggressive. Some patient advocates say the FDA should be guided only by science.
'Do people in this country really want drugs to be approved by riot?'’ asked Abx bey Meyers, president of the National Organization for Rare Disorders. 'Every other patient organization is going to go down there and have a March on Washington and use political pressure to get their drug approved. That’s not what the American people want.'
Dr. Howard I. Scher, a Memorial Sloan-Kettering Cancer Center researcher whose image is featured on Vestal’s MySpace page and who was pilloried on the InvestorVillage website, received additional security during a recent cancer conference after receiving e-mails from Provenge supporters that he considered threatening.
Paul Goldberg, editor of The Cancer Letter, a weekly newsletter that reprinted letters from Scher and other Provenge skeptics, received a spate of irate e-mail messages, including one that said: 'I hope the entire male staff at the Cancer Letter is diagnosed with Prostate Cancer.'
Another Provenge supporter told him about her idea to create 'it squads,' people assigned to chat up FDA advisers during meeting breaks, Goldberg said.
‘‘The idea of a ‘hit squad’ is really unpleasant,’’ he said. ‘‘The idea of a committee member getting threats, being approached on the way to the restroom, at coffee breaks — this is about science.
‘‘Or it should be about science. That’s how patient interests are protected.’’
And Adam Feuerstein, a senior writer for TheStreet.com, received at least 100 e-mails, some of them anti-Semitic, after writing about Provenge and suggesting that investors ‘‘ditch Dendreon’’ stock.
Two prominent prostate cancer experts have been threatened for opposing approval of a controversial new drug and are being protected by bodyguards as they attend the nation’s largest cancer conference here.A quick internet search did reveal that both Dr Hussain and Dr Scher did have conflicts of interest.
The experts, Dr. Howard Scher of Memorial Sloan-Kettering Cancer Center and Dr. Maha Hussain of the University of Michigan, received e-mail and other threats, according to spokeswomen for Sloan-Kettering and for the cancer conference.
When he gave a talk at the conference on Sunday, Dr. Scher was accompanied by three men wearing suits and earphones, but not conference name badges, which attendees must wear.
A spokeswoman for the oncology association said it had been working with the two doctors and was increasing security at the conference.
Christine Hickey, a spokeswoman for Sloan-Kettering, said Dr. Scher had received e-mail messages and phone calls, including one e-mail entitled 'our murder.' A copy of his biographical page on the Sloan-Kettering website was vandalized.
It is not known who sent the threats. However, it is clear that the doctors’ public stance against the drug, Provenge, has inflamed the passions of some men with prostate cancer and patient advocates, who say the drug would offer hope to desperate patients with few or no alternatives.
'ntimidation or harassment is going to make qualified people think twice about serving in national positions,' Dr. Hussain said....
Dr Hussain acknowledged receiving consulting and lecture fees and holding stock in Sanofi (the forerunner of Sanofi-Aventis) in 2004 [Petrylak DP, Tangen CM, Hussain MHA et al. Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N Engl J Med 2004; 351: 1513-1520]; receiving research funding from Bristol-Myers-Squibb in 2005 [Hussain M, Bhandari MS. Epothilones and the next generation of phase III trials for prostate cancer. Brit J Urol 2005; 96: 296-302.]; owning stock in AstraZeneca in 2006 [Hussain M, Tangen CM, Higano C et al. Absolute prostate-specific antigen value after androgen deprivation is a strong independent predictor of survival in new metatstatic prostate cancer: data from Southwest Oncology Group Trial 9346 (INT-0162). J Clin Oncol 2006; 24: 3984-3990.]; and receiving research funding from Genentech in 2007 [Hussain MHA, MacVicar CR, Petrylak DP et al. Trastuzumab, paclitaxel, carboplatin, and gemcitabine in advanced human epidermal growth factor receptor-2/neu-positive urothelial carcinoma: results of a multicenter phase II National Cancer Institute Trial. J Clin Oncol 2007; 24: 2218-2224.]
Dr Scher acknowledged research funding from AstaZeneca, Bristol-Myers-Squibb, Novartis Pharmaceuticals, and Millenium Pharmaceuticals; consulting fees from Bristol-Myers-Squibb, Conforma Therapeutics, Genentech, Novartis, ProQuest Investments, and Wyeth-Ayerst Pharmaceuticals; membership in the speaker's bureau for AstraZeneca; and stock holdings or option holdings in Cell Therapeutics, Vidamed, ProQuest, Conforma, and Genta [Shaffer DR, Scher HI. Prostate cancer: a dynamic illness with shifting targets. Lancet Oncology 2003; 4: 407-413.]
But while we're on the topic of conflicts of interest, the Boston Globe article also noted,
Dendreon is among the drug industry sponsors that have provided funding for a patient advocacy group that [Thomas] Farrington founded.
What a mess.
On one hand, this appears to be yet another in our series of stories about FDA advisory panels that include members with conflicts of interests (see recent post here). The presence of such conflicts naturally raise questions about whether the actions of the panels are influenced by their members financial entanglements, thus challenging the validity of the whole process. In my humble opinion, I think that to restore integrity in its advisory panels and its operations in general, the FDA should not allow people with conflicts of interest to serve on these panels.
On the other hand, the advisory panel's decision unleashed far more than scientific or clinical criticism, or concerns about how its members' conflicts may have affected its decision. It unleashed not just political pressure, but apparently threats of intimidation by "hit squads" and ominous emails, to the extent that the conflicted panel members felt they needed bodyguards. Intimidation of this nature is plain wrong, and surely will not lead to a climate in which policy makers will make the best decisions for patients and the public at large. Such threats deserve investigation, and anyone who was waving the bloody shirt in a way that might have inspired people to make such threats ought to be ashamed. Two wrongs here surely do not make a right.