What’s being presented at the AUA in May: Part I

This is the first of several summary posts commenting briefly on new data to be presented at the annual meeting of the American Urological Association (AUA) this year. Individual presentations of important new data will be separately addressed (but the only one of these we have seen so far is the one giving data about the new 4Kscore Test, and the true value of that test is still to be fully evaluated).

In the session entitled Prostate Cancer: Advanced I, on Tuesday, May 20, there are 12 papers being orally presented. Among the more interesting of these papers are the following:

  • A paper by da Silva et al. (abstract no. PD27-02) providing additional data supportive of the appropriate use of intermittent androgen deprivation therapy (IADT) in the management of men with advanced forms of prostate cancer, and most particularly in those men who have a good initial response to treatment.
  • A paper by O’Shaughnessy et al. (abstract no. PD27-03) that addresses the potential role of multimodal therapy  — including surgery, radiation therapy, and androgen deprivation therapy (ADT) — in men with limited stage M1 metastatic prostate cancer, and  most specifically in those who have a complete response to initial treatment. Data are provided on just 20 patients, but the paper does suggest the potential value of surgical debulking of the primary tumor along with radiation and ADT in carefully selected men.
  • A paper by Hall et al (abstract no. PD27-04) giving us a little more insight into the way sipuleucel-T may actually work in extending the survival of some patients with advanced prostate cancer.
  • A paper by Crawford et al. (abstract no. PD27-05) discussing data from the intermittent use of the LHRH antagonist degarelix. The authors conclude that intermittent use of degarelix is non-inferior to continuous use of degarelix and to continuous use of the LHRH agonist leuprolide acetate when degarelix was administered in a 7-month on-treatment/7-month off-treatment regimen with treatment restarted for men with PSA levels that rose to > 2 ng/ml. Patient age of < 65 years was apparently predictive of good recovery of serum testosterone levels.
  • A paper by Babcook et al. (abstract no. PD27-06) that suggests, on the basis of laboratory data only, that the combination of simvastatin and metformin may have value in the management of metastatic castration-resistant prostate cancer (mCRPC).
  • Another paper by da Silva et al. (abstract no. PD27-10), based on a retrospective analysis of data from a Phase III clinical trial, suggesting that prior simvastatin therapy may improve survival among men receiving continuous or intermittent ADT for locally advanced or metastatic prostate cancer. (However, these data are based on only a small subset of all patients originally enrolled in the Phase II trial.)
  • A paper by Patrick et al. (abstract no. PD27-11) that reports results from a very small, Phase II, randomized trial of methylphenidate vs. a placebo in the management of LHRH agonist-induced fatigue among men with prostate cancer. The authors are enthusiastic about the apparent benefits associated with methylphenidate therapy, but The “New” Prostate Cancer InfoLink thinks that we are going to need data from a larger and better-conducted study to confirm the data reported by Patrick et al. There were clearly significant problems with the implementation of the study reported here since so few of the eligible patients were willing to participate.

4 Responses

  1. The PROVENGE (sipuleucel-T study)

    Thanks for highlighting this study: “A paper by Hall et al (abstract no. PD27-04) giving us a little more insight into the way sipuleucel-T may actually work in extending the survival of some patients with advanced prostate cancer.”

    As I understand the abstract, the authors looked at “broadening of the immune response (antigen spread)” as an indicator of the effectiveness of treatment with Provenge. Provenge treatment involves the prostatic acid phosphatase (PAP), but they looked at spread of the immune response to PSA and two other “prostate antigens”, and they got an interesting, potentially quite useful result involving PSA:

    “… In the sipuleucel-T arm of IMPACT, IgG response against PSA was positively correlated with improved OS (HR = 0.41; 95% CI, 0.22–0.78; p33 months) in pts with IgG response to PSA (n = 35), compared to 22 months in pts with no IgG response to PSA (n = 105), and 21.4 months for the control group. IgG responses to PSMA and hK2 were not correlated with OS….”

    Those are pretty impressive figures, and I’m especially impressed that they were based on blood work comparing baseline with approximately just 2-4 weeks after treatment! Such an early indicator of success or failure could help with managing follow-up treatment, but it’s reasonable to anticipate that Dendreon will work on improving this approach now that they have proof of this principle that relies on analyzing “antigen spread”.

    I’m wondering if they are working on analysis of antigen spread involving pre-treatment blood samples subjected to some kind of proxy mini-treatment, if that is even possible. If that worked out, at some point patients and their doctors might have an advance idea whether Provenge were likely to work.


    Thanks for mentioning this attention grabbing study: PD27-06: Simvastatin and Metformin: A Deadly Combination for Metastatic Castration-Resistant Prostate Cancer

    I did a double take as I read the title, quickly checking the text to confirm the authors meant deadly for the cancer, which they did, and not for the patient. I was stunned by the following lines from the result and conclusion sections, trying to keep perspective in that this was still a lab study and not a clinical trial.

    “… Treatment with either low- or high-dose SIM/MET combination completely inhibited tumor growth, cachexia, and metastasis to bone; prevented PSA failure more effectively than Dtx [docetaxel], SIM, or MET alone. Dtx treatment caused tumor growth inhibition, but resulted in severe toxicity and mortality. SIM/MET combination did not demonstrate any apparent toxicity. SIM and MET were bioavailable in plasma and prostate tissue.

    “Combination SIM and MET significantly and synergistically inhibited metastatic CRPC survival both in vitro and in vivo, and may be a promising chemotherapeutic alternative for metastatic CRPC.”

    Say again? Did I read that right about the simvastatin/metformin combo completely inhibited tumor growth … and metastasis to bone, more effective against PSA failure, and no apparent toxicity?
    My reaction is WOW!!!, and I’ll bet that’s how the results struck the researchers. This is a cell and animal study, so it’s a real leap to replication in men, but if this combo were to have the same result in humans as in mice, we could have a highly effective, highly tolerable, and extremely cheap alternative to chemo! I’ll bet they already have a Phase I or Phase II trial underway. I hope so.

  3. Jim:

    While these laboratory data are certainly “eye-opening”, this is a very long way from being the first time that people have had lab results like this that never came anywhere close to being replicable in man. I tend to be extremely cautious about data like these.

    The other thing one has to recognize is that metformin and simvastatin are both genetric drugs, so the sources of financing to conduct clinical trials will be restricted to the federal government and places like the Prostate Cancer Foundation. The federal government isn’t exactly flush with money these days!

  4. Regarding funding for trials of simvastatin and metformin, it strikes me that a Phase II or III trial would be attractive under the Prostate Cancer Research Program (PCRP) of the Congressionally Directed Medical Research Program. The PCRP will probably have about $80 million this year, as in past years, which includes administrative expenses, to cover many accepted proposals. The goal of one of the main award mechanisms is to fund “high risk/high reward” innovative research, and this would certainly qualify for consideration under the risk/reward philosophy. It’s possible the lab success would move the approach out of the mandatory “innovative” zone, but I suspect the lab/animal evidence would be regarded as acceptable and desired proof of principle data that does not compromise innovativeness.

    I’m mentioning this as just one potential source of funding.

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