What Can You Do?

  • I believe that most men considering Provenge treatment have the motivation and intelligence to understand the two explanations for the trial data, and have the right to decide with full information which explanation the balance of the data best supports. Sharing this website is the best way to help reach as many of these men as possible.
  • The JNCI publication has demonstrated the legitimacy of the alternative explanation, which the FDA appears not to have considered in its approval, and this website is my best shot at equipping as many people as possible with the necessary information to reach their own conclusions.
  • If you would like to help stimulate this long-overdue public debate, I have made some suggestions below. However, nobody knows how best to use your skills, resources and connections but you. Please let me know if I can help (contact).

Checklist: 4 questions that need legitimate answers to support Provenge efficacy:

  1. What evidence is there to support the major assumption that the very large, repeated cell losses from the placebo group are not harmful to people over 65? And to people over 65 with metastatic castration-resistant prostate cancer?
  2. Why are the placebo patients >65 in the trials living 11 months shorter than placebo patients <65? (no difference is expected given evidence from thousands of placebo patients from other recent trials)
  3. Why does Provenge not appear to work in patients <65? And derive all its "efficacy data" from patients >65? Everything we know about the immune system and other immunotherapies suggests this is the OPPOSITE of what would be expected.
  4. For a disease where age is not normally related to survival, how does the following make any sense?: The age group in whom Provenge DOESN’T work lives LONGER than the age group in whom Provenge DOES work.

Common rebuttals that dodge the issues (show/hide)

  1. What evidence is there to support the ASSUMPTION that the very large, repeated cell losses from the placebo group are not harmful to people over 65? And people over 65 with metastatic prostate cancer? Without this evidence, Provenge is not proven safe or effective.

Common rebuttals that dodge the issue:

  • The lymphocyte losses might be 95% of the lymphocytes in the blood, but they are only about 2% of the lymphocytes in the body.
    • THIS IS NOT EVIDENCE, nor an answer to the question. 
    • This is a misleading oversimplification (see video and/or FAQ)
    • This neglects the known harmful effects of repeated cell divisions in older people as their lymphocytes replicate to fill the space left by the removed cells. 
    • Such a significant shock to a fragile system (whether via cells, cytokines, or other mediators) could have consequences related to the acute disruption which are unrelated to the long-term repopulation of the blood with lymphocytes from elsewhere.
  • It is implausible that this would be harmful
    • THIS IS NOT EVIDENCE. 
    • There is evidence in humans that lymphocyte loss is particularly harmful in the elserly. See video "What else we know".
    • It would be hypocritical to claim that we know so much about the immune system that we know that this immunodepletion is safe while simultaneously claiming we know so little about the immune system that we cannot provide any good evidence for the mechanism of Provenge.
  • People over 65 can donate blood.
    • The number of lymphocytes in a standard 450ml donation of whole blood is less than 10% the number which are removed from placebo patients (with <12% returned 3 days later) THREE times in 4 weeks. There is no comparison. Losing 10% is very different to losing 90% if the best way to replace them is by replicating the lymphocytes remaining in the blood.
    • Healthy people donate blood, not people with metastatic cancer. We know that the immune systems of cancer patients are compromised in many ways that are not yet well understood.

  1. Why are the placebo patients >65 in the trials living 11 months shorter than patients <65? (no difference is expected given evidence from thousands of placebo patients from other recent trials)

Common rebuttals that dodge the issue:

  • This is retrospective and therefore unimportant
    • See FAQ page for why this is an insufficient reason to ignore the data.
  • Patients under 65 were a small proportion of those in the trials
    • 27% of placebo patients were under 65. More than enough for robust statistics showing this did not arise by chance.
  • This was just the result of chance
    • It would be less than a 1/50,000 chance. The relationship of age and survival in the placebo group is the most statistically significant result in the trial. 
  • Younger patients were treated more aggressively by their physicians in the post-progression period than older patients.
    • Invalid speculation. If this were true, younger patients in placebo groups from other trials would also be treated more aggressively and be living longer. This is not seen. Also, variations in standard-of-care are not capable of producing an 11 month survival difference (docetaxel achieved a 2.9 month survival benefit). 

  1. Why does Provenge not work in patients <65? Everything we know about the immune system indicates these are the only patients we have a good reason to believe it SHOULD work in.

Common rebuttals that dodge the issue:

  • This is retrospective and therefore unimportant
    • See FAQ page for why this is an insufficient reason to ignore the data.
  • Patients under 65 were a small proportion of those in the trials
    • Untrue. Almost one quarter of all patients in the trials were under 65.
  • This was just the result of chance
    • Untrue. The medians and 95% confidence intervals overlap almost perfectly.
  • Provenge works in mysterious ways.
    • When these mysterious ways fly in the face of established science, that is exactly when alternative explanations deserve the most serious consideration.

  1. For a disease where age is not normally related to survival, how you make sense of the following?: The age group in whom Provenge DOESN’T work lives LONGER than the age group in whom Provenge DOES work.

  2. I have never heard any suggestions to unravel this conundrum. I cannot think of any drug where patients it doesn’t benefit do better than patients it does benefit. Examples welcome.


For Everyone
  • If you have, or discover, good answers for any questions from the checklist above, please send them to me and I will share them on website (and to the email distribution list) so that others can benefit from including these in the debate.
  • Share this website with anyone you think might be interested in it, should be aware of it, or could bring wide attention to the debate (this may include health & science journalists, bloggers, hospital administrators, doctors, immunology researchers, trial design experts, officials, etc).
  • Contact Information:


For Investigators in the Provenge Trials (show/hide)
  • Were you informed of the problematic age data from the trials prior to the approval of Provenge? (none of the investigators I spoke with had seen it previously)
    • You may wish to understand why (if you were not)
  • Are you comfortable that placebo patients you enrolled into these trials were given an intervention which removed over 90% of their PBMCs and returned less than 12% of these on each of their 3 treatments? Were trial participants informed of this? Were reassurances given that this cell loss was known to be safe? Do you believe that trial participants should have been informed that this is what the placebo intervention involved?
    • If the answer to any of these questions is no, you will do as you feel appropriate. 
    • If not, please share any evidence you may have been provided to justify assuming it was safe.
  • Are you comfortable that a median of 65% of harvested lymphocytes are lost during the manufacture of Provenge? The same questions as above for placebo patients apply here.


For Doctors Currently Prescribing Provenge (show/hide)
  • The JNCI paper suggests that the FDA overlooked an important consideration when approving this therapy. To believe in the safety and efficacy of Provenge requires either: complete faith that the FDA does not make mistakes and has not overlooked an important alternative explanation for the Provenge trial data, or, good answers to the questions in the checklist.
  • Are you comfortable that you have answers to the checklist of questions above (blue box)?
  • If so, please send them to me and I will share them on the front page of this website so that everyone can include them in the debate.
  • If not, i'm sure you will respond as you find appropriate.
  • Share your opinions with peers. Encourage the debate. Do not accept dismissals or obfuscation as part of this debate.


For Doctors and Scientists from any Discipline
(show/hide)
  • Share your opinions with peers. Encourage the debate. Do not accept dismissals or obfuscation as part of this debate.
  • Share your opinions and expertise with people that could influence or bring attention or action to these issues.


For People in Europe (show/hide)
  • Provenge has filed for approval with the EMA based upon the same trials as discussed in this website. If you believe the concerns raised here should be included in these approval discussions, you could share this website and your opinions with the European Medicines Agency.