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Cancer: Prostate Message Board


Cancer: Prostate Board Index


Yesterday around 2 PM the Dendreon Corporation made history by announcing details of successful completion of the large, Phase III trial for Provenge at the annual meeting of the American Urological Association (AUA) in Chicago. Provenge became the first active immunotherapy to demonstrate improvement in overall survival for advanced prostate cancer. :jester: :D :cool:

This was the news we had been waiting for, and by now I have spent hours studying the slides for the talk presented by Dendreon and listening to a replay of a conference call after the presentation at the AUA about the trial. The bottom line: the details live up to the encouraging brief announcement of success by Dendreon two weeks ago. :D I've been around research results for prostate cancer for a number of years now and have become pretty good at seeing flaws in studies, but this study looks sound to me.

Personally, I'm impressed and delighted. This is a great time for prostate cancer survivors - especially for patients with very advanced disease, their families, and physicians treating the disease. It is gratifying to all of us who were rooting for this drug from the sidelines and sometimes the frontlines, such as at the FDA advisory committee hearing two years ago. :angel: :jester: :cool:

Here are some of the facts about the trial and its results, and I may be able to answer questions about other facts. Just to briefly repeat information from earlier on this thread, the trial involved
[LIST]512 patients whose prostate cancer was no longer being controlled by hormonal blockade (testosterone less than 50 and PSA rising or progression of the disease despite hormonal blockade),
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who had at least six months to live,[/LIST]
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who had adequate liver, kidney and blood function,[/LIST]
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and who were free of HIV, hepatitis B, and HTLV1 (had to check that one: human T-cell lymphotropic virus- I).[/LIST]

Scoring was based on length of "overall survival" from time from randomization to either the Provenge arm of the study or the placebo arm, and neither the patient nor the staff treating him knew whether he was getting Provenge or the placebo. (In research terminology, that made the study "double blind".) Twice as many of the 512 patients were assigned to the Provenge arm (341 patients) as to the placebo arm (171). Virtually all research studies lose some patients so that they can no longer be followed, and this study was no exception; however, only six patients were lost to followup, which strikes me as an exceptionally low number, especially for a large group of patients with such advanced disease, and is only 1.1% of the total. The rules for the trial were renegotiated with the FDA in 2002, and enrollment resumed at that time.

When the dust cleared at the end of the trial:

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Average (median) survival was 4.1 months greater in the Provenge group than in the placebo group. That's actually a pretty big hit for an oncology drug in a Phase III trial. Results should improve from that in practice, and remember that that is just the middle point, with half of the patients doing better, many a whole lot better. This result is better than the result with docetaxel (Taxotere) a few years ago that generated excitement, and the Provenge result is based on much longer follow-up, nearly three years on average.[/LIST]
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More encouragingly, 31.7% of the patients in the Provenge arm were alive at the three year point, compared to 23.0% of patients in the placebo group, a difference of 38%! Wow - that's striking! :angel: (52.1% for Provenge and 41.2% for placebo were alive at 24 months, and 20.5% for Provenge versus 16.0 for placebo were alive at the 48 month point.)[/LIST]
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The researchers pounded on the data to see if any other explanation or group of explanations could account for what seemed to be the treatment effect (including bisphosphonate use; primary Gleason grade of 4 or higher; more than 10 bone mets versus fewer; performance status; the locations of the mets; age; PSA, LDH, alkaline phosphatase, or hemoglobin above or below median; docetaxel use and timing; death from other causes; and two technical factors.) None of the other explanations had much influence on the results, strongly indicating that Provenge had made the difference.[/LIST]
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Reassuringly, side-effect results were very similar to the excellent results in the previous Provenge trials. The only side effects occuring in substantial percentages and substantially higher than in the placebo group were unpleasant but fairly mild and short-term (one or two days) chills (54.1%), fever (29.3%), headache (16%), flu-like illness (9.8%), hypertension (7.4%), and hyperhydrosis (meaning excessive sweating) (5.3%).[/LIST]
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Serious side-effects occuring in 4 or more patients in the Provenge group were rare, with the highest incidence at 1.8% for pyrexia (meaning fever) and for cerebrovascular accident (1.8%) - think that's a category for a stroke, but the incidence of the latter was just as high in the placebo group at 1.8%. We need to remember that many of these patients are elderly men, and they are subject to some of these diseases and incidents that would have occurred whether or not they were getting Provenge, the placebo, of even if they had not had prostate cancer. Of the 12 serious events listed, the placebo group was as high or higher in 8 of the 12 categories. Moreover, Dendreon said that most of these effects in most patients were mild and short. I read one news report filed yesterday by the AP in which the reporter did not understand the side effect issue well and thought that side-effect results might cause a problem in FDA approval. I'm thoroughly convinced that will not be the case - no problem on the side-effect front. It helps to remember that the FDA's advisory committee voted unanimously 17 to zip that drug safety was not a significant problem.
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Now, with the results in, doctors and researchers can start working on how to get even better results from more patients. For starters, all of such late-stage patients with bone mets should be on a bisphosphonate drug, probably the powerful drug Zometa, in my layman's opinion.

There's more to tell about these wonderful results, but this is enough for today from me. If you have learned more about the results, please pitch in.

These are exciting days! :D

Jim





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