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Data from clinical trials of Provenge appears to have been analyzed differently by researchers...

Data from clinical trials of Provenge appears to have been analyzed differently by researchers than how Dendreon (DNDN +0.2%) told the FDA it would be. DNDN had originally said the data would be analyzed by age, using a cut-point of 65, but when the report was published its stated age was 71. The company says the discrepancy is immaterial and that Provenge is safe and effective. The FDA also stands by its decision to approve the treatment.
Comments (13)
  • doncl316
    , contributor
    Comments (7) | Send Message
     
    ***YAWN***
    11 Oct 2012, 01:59 PM Reply Like
  • John2468
    , contributor
    Comments (39) | Send Message
     
    Of course the FDA would say that- they screwed up and have just as much incentive to cover their as.s as Dendreon has to cover their lies.

     

    Dendreon has still never explained why their results show all sorts of unprecedented weirdness. The truth will emerge in time.
    11 Oct 2012, 02:22 PM Reply Like
  • Theodore Cohen
    , contributor
    Comments (1903) | Send Message
     
    Are we going to have to go through this all again...Huber et al. and their specious 'immunodepletion theory' as it pertains to Provenge?

     

    First, it should be noted the Journal of the National Cancer Institute (JNCI) has no relationship whatsoever--NONE--with the US National Cancer Institute. The JNCI is a publication of Oxford University, Cambridge, England.

     

    Second, Huber, et al.'s so-called 'theory' was previously introduced at the CMS MEDCAP review of Provenge held on November 17, 2010 by Dr. Bart Clausen (sp). (This earlier work never was referenced by Huber, et al.) Almost immediately, Dr. James L. Gulley, M.D., Ph.D., F.A.C.P., who is the director of the Clinical Trials Group, Laboratory of Tumor, Immunology and Biology, and a principal investigator of the medical oncology branch at the Center for Cancer Research at NCI, the National Cancer Institute, asked for the floor:

     

    25 DR. GOODMAN: Doctor, we got your point, thank
    00266
    1 you very much. Yes, Dr. Gulley.
    2 DR. GULLEY: I would just like to respond to
    3 that one comment.
    4 DR. GOODMAN: Please keep it brief.
    5 DR. GULLEY: I will. The number of white blood
    6 cells that were, the proportion of white blood cells that
    7 are removed in terms of the total body white blood cell
    8 count is around two percent, so it is not a clinically
    9 meaningful amount.
    10 DR. GOODMAN: Thank you, Dr. Gulley.

     

    The JNCI paper was also reviewed by Dr. Carl A. Olsson in the March 2012 issue of AUA Today. Here, he made the following statement: 'The authors missed the report by Hall et al that “there was no evidence that leukapheresis led to immunodepletion,” citing literature proving that each apheresis removed less than 1% of the total body pool of 10 to the 12th power lymphocytes and reporting a normal measured cell count after the third apheresis in all men.' (Hall SJ, Klotz L, Pantuck AJ et al: Integrated safety data from 4 randomized, double-blind, controlled trials of autologous cellular immunotherapy with sipuleucel-T in patients with prostate cancer. J Urol 2011; 186: 877.)

     

    In closing his review, Olsson had this to say about Ms. Huber: "Finally, we are all used to the values of interdisciplinary conferences, which usually combine the experiential qualities of urology, clinical oncology, immunology and other disciplines. However, “healthcare analyst” and “investment management” are talents that appear unseemly in major publications."

     

    I'm not sure why Reuters in general and Sharon Bagley in particular continue to push this dead horse up the hill, but one only can conclude (1) it's a slow news day, or (2) party or parties unknown won't rest until they have put Dendreon out of business. If the latter is the case, they should be very (very!) careful, given the broadening investigation by the government into biotechnology and pharmaceutical stocks.
    11 Oct 2012, 02:43 PM Reply Like
  • John2468
    , contributor
    Comments (39) | Send Message
     
    Just because Gulley said something, doesn't make it true.

     

    His point is irrelevant because lymphocytes aren't free to move around the body, and it wouldn't prove anything even if they were. DNDN has never given any evidence that massive lymphocyte depletion is safe- and there's a reason for that.
    15 Oct 2012, 09:35 AM Reply Like
  • Theodore Cohen
    , contributor
    Comments (1903) | Send Message
     
    John, how nice to see you. By the way, I still don't see your bio. Would you please post one so my readers can judge better the veracity of your comments?

     

    You're certainly welcome to your own opinion, by the way, but you're not welcome to your own facts. From what background are you challenging the statements made by Dr. James L. Gulley, M.D., Ph.D., F.A.C.P., who is the director of the Clinical Trials Group, Laboratory of Tumor, Immunology and Biology, and a principal investigator of the medical oncology branch at the Center for Cancer Research at NCI, the National Cancer Institute.

     

    Further, would you please take a moment and comment on this paper, which Huber et al. complerely overlooked and which is directly applicable to what they incorrectly claim to be THEIR so-called 'immunotherapy' theory:

     

    Hall SJ, Klotz L, Pantuck AJ et al: Integrated safety data from 4 randomized, double-blind, controlled trials of autologous cellular immunotherapy with sipuleucel-T in patients with prostate cancer. J Urol 2011; 186: 877.

     

    According to Hall et al, “there was no evidence that leukapheresis led to immunodepletion,”citing literature proving that each apheresis removed less than 1% of the total body pool of 10**12 lymphocytes and reporting a normal measured cell count after the third apheresis in all men.

     

    Thanks.

     

    Ted
    15 Oct 2012, 09:53 AM Reply Like
  • John2468
    , contributor
    Comments (39) | Send Message
     
    You just exemplified the problem in this debate very neatly-
    you cannot "judge the veracity" of what someone says by who they are. All that matters is what they say. What I said above, is true. It would be true whether I was a Nobel laureate or a slum-child from Mumbai.

     

    Equally true is the fact that 4 or 5 analyses have shown that age was a significant predictor of survival in the Provenge trials (see below), a result that was not seen in any of the last 9 large, phIII trials in mCRPC: Chemotherapy-naïve: docetaxel , abiraterone , calcitriol , bevacizumab , atrasentan . Post-chemotherapy: satraplatin , cabazitaxel , abiraterone , MDV3100 .

     

    **********************...
    It is therefore incumbent upon the study investigators to explain why their results from all 3 Provenge trials show a feature that has never before been seen in this population. Fact.
    **********************...

     

    In a univariate analysis, hazard of death increased by 2.6% per year of age (p<0.001)
    <Source> Higano CS, Small EJ, Schellhammer PF, et al. Poster presented as ASCO, June, 2010. Survival consistency persists across subgroups in the Integrated Analysis of Provenge Trials. Also in podium presentation by Celestia Higano titled “Survival consistency in study subpopulations and predictors of outcome from the integrated analysis of sipuleucel-T trials in metastatic castration resistant prostate cancer”.

     

    Analyzing the sipuleucel-T and ‘placebo’ arms separately, hazard of death increased by 2.8% and 3.1% per year of age, respectively
    <Source> Kantoff PF, et al. Correspondence Re: Interdisciplinary critique of sipuleucel-T. J Natl Cancer Inst 2012; 104(14):1107-1109. “In a pooled analysis of these studies, age (in 10-year increments) was a statistically significant predictor of OS in both sipuleucel-T (hazard ratio [HR] of death = 1.28, 95% confidence interval [CI] = 1.12 to 1.47) and control (HR of death = 1.31, 95% CI = 1.10 to 1.56) arms (Dendreon data on file)”

     

    Pooling just the first two trials (n=225), hazard of death increased by 3% per year of age (p<0.05)
    <Source> 2007 Statistical Review p28 http://1.usa.gov/Xk9Lqy

     

    Prespecified subgroup analysis of overall survival by age (in JNCI article)
    <Source> Zhen B, Gupta G. FDA Statistical Review and Evaluation Sipuleucel-T. Completed 04/30/2010. p34 http://1.usa.gov/SYJXj8
    16 Oct 2012, 04:57 PM Reply Like
  • Theodore Cohen
    , contributor
    Comments (1903) | Send Message
     
    Please stay on topic, which is specifically focused on the data used in the trial and their analysis:

     

    http://go.cms.gov/P5tdYr

     

    pp. 22-23

     

    http://1.usa.gov/zTnQhC

     

    pp. 37-38

     

    Thanks.

     

    Ted
    16 Oct 2012, 05:25 PM Reply Like
  • John2468
    , contributor
    Comments (39) | Send Message
     
    Please stay with the facts. This is on topic..... these are all analyses of data produced by the trials (there is no such thing as "data used in the trial").

     

    All of these analyses were produced and presented by Dendreon and/or their principal investigators. I have provided all of the sources proving this.

     

    Obfuscation helps no one.

     

    Thanks,

     

    Truthseeker John
    17 Oct 2012, 01:36 AM Reply Like
  • Theodore Cohen
    , contributor
    Comments (1903) | Send Message
     
    I misspoke...the evaluation of the data produced by the trials.

     

    The simple fact is, 'John' (or whoever you are (Huber?)), the government's review of the data and the resulting approval of Dendreon, stand. There is nothing you can say or publish that is going to change that.
    17 Oct 2012, 08:31 AM Reply Like
  • John2468
    , contributor
    Comments (39) | Send Message
     
    I cannot change the past, that is true.

     

    But the truth will prevail and I predict that Provenge will be shown for the harmful sham that it is and either the FDA, the Red Cross or the insurers will kill it.
    17 Oct 2012, 09:08 AM Reply Like
  • Theodore Cohen
    , contributor
    Comments (1903) | Send Message
     
    You sound very angry. What's bothering you? Did you lose a lot of money on Dendreon? Did you or a family member used to work for the company and you or they lost their job?
    17 Oct 2012, 09:35 AM Reply Like
  • Lawrence Marc-Aurele
    , contributor
    Comments (106) | Send Message
     
    The best thing that could happen for prostate cancer research is to ban requiring clinical trial participants from having to undergo and fail ADT. It needs to be found out if Provenge, or any other treatment, is a cure, not just a treatment. Give that treatment--at the patient's option-INSTEAD of ADT or anything else. That way it can be learned whether or not it is a cure. It makes no sense to create a sicker patient, and then try to get him well. The search for a cure has to be more than words. Try Provenge on its own merits. That still has not been done.
    11 Oct 2012, 11:16 PM Reply Like
  • Theodore Cohen
    , contributor
    Comments (1903) | Send Message
     
    Lawrence, I could not agree with you more.

     

    Ted
    15 Oct 2012, 09:54 AM Reply Like
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