URO ONCO

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  • The impact of a BRCA2 mutation on mortality from screen-detected prostate cancer.

    Akbari MR, Wallis CJ, Toi A, Trachtenberg J, Sun P, Narod SA, Nam RK.

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    Comment from Henk van der Poel:
    BRCA2 carriers not only have an increased risk of prostate cancer but also worse prognosis when detected in a screening program.
  • A randomized phase II efficacy and safety study of vandetanib (ZD6474) in combination with bicalutamide versus bicalutamide alone in patients with chemotherapy naïve castration-resistant prostate cancer

    Azad AA, Beardsley EK, Hotte SJ, Ellard SL, Klotz L, Chin J, Kollmannsberger C, Mukherjee SD, Chi KN.

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    Comment from Henk van der Poel:
    After VEGF inhibition by suninitib, bevacizumab, and aflibercept also vandetanib failed as tyrosine kinase inhibitor in men with castration resistant prostate cancer.
  • Real-time immune monitoring to guide plasmid DNA vaccination schedule targeting prostatic acid phosphatase in patients with castration-resistant prostate cancer.

    McNeel DG, Becker JT, Eickhoff JC, Johnson LE, Bradley E, Pohlkamp I, Staab MJ, Liu G, Wilding G, Olson BM.

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    Comment from Henk van der Poel:
    Vaccinations for prostate cancer with both ProstVac and Sipuleucel-T have shown a benefit for survival without apparent delays in progression-free survival in clinical trials. Since clinical progression was not associated with survival in these studies and prolonged vaccination may improve immunization monitoring of vaccination efficacy. McNeel et al. showed PAP-specific T-cells in the majority of men treated with DNA vaccines but failed to associate these with clinical outcome and vaccination scheme.
  • Impact of the Site of Metastases on Survival in Patients with Metastatic Prostate Cancer

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    Comment from Henk van der Poel:
    In a large SEER registry population covering more than one-quarter of the US population, 3857 men over 65 years of age were identified with metastasized prostate cancer. More than 90% had bone metastases. Excluding men with prior local treatment, it became apparent that the presence of visceral metastases resulted in a drop in median overall survival of 10 months. Interestingly, men with visceral metastases were less likely to receive docetaxel chemotherapy. When correcting for this imbalance of chemotherapy use, men with visceral metastases did still worse compared to men with only bone or lymph node metastases.
    The fact that men with both bone and visceral metastases did worse than men with visceral metastases-only with respect to survival clearly shows that the presence of bone metastases does not confer a more favorable course of disease. Rather metastases volume may be needed to be estimated in order to clearly show that location of metastases impacts upon survival and the worse outcome is not an effect of a larger tumor burden. Median overall survival of men with nodal metastases was almost double that of men with bone metastases.  Nodal metastasized disease is generally of low volume supporting the notion that metastases volume rather than location impacts upon prognosis.
  • Ipilimumab versus placebo after radiotherapy in patients with metastatic castration-resistant prostate cancer that had progressed after docetaxel chemotherapy (CA184-043): a multicentre, randomised, double-blind, phase 3 trial.

    Kwon ED, Drake CG, Scher HI, Fizazi K, Bossi A, van den Eertwegh AJ, Krainer M, Houede N, Santos R, Mahammedi H, Ng S, Maio M, Franke FA, Sundar S, Agarwal N, Bergman AM, Ciuleanu TE, Korbenfeld E, Sengeløv L, Hansen S, Logothetis C, Beer TM, McHenry MB,

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    Comment from Henk van der Poel:
    Being breakthrough of the year in 2013 as announced by the journal Science certainly holds some promise for immunotherapy and cancer. Earlier studies on immunomodulators in prostate cancer management revealed improved overall survival despite absence of clear benefits for progression-free survival. Ipilimumab, an inhibitor of CTLA4, combined with 1x8Gy radiotherapy to bone metastases, however, failed to improve overall survival in this trial. Subgroup analysis, however, clearly showed benefit and unlike earlier immunotherapy trials in prostate cancer, ipilimumab and radiotherapy significantly delayed clinical progression by almost a month. What can we learn from this trial? Patients with visceral metastases were unlikely to response favorably to ipilimumab. Even worse, death was 46% more likely after 5 months in the ipilimumab group compared to placebo. Then again, in men with low alkaline phosphatase levels, no anemia and no visceral metastases at entry, median overall survival gain in the ipilimumab was an impressive 6.9 months and comparable to figures from the sipuleucel-T trial (IMPACT trial). Interestingly, in the sipuleucel-T trial where CRPC patients were treated with sipuleucel-T vaccination therapy, median overall survival in the control population was 21.7months that is more than twice the median survival in the ipilimumab trial. Likewise, whereas prior docetaxel was given in only 15% of men in the sipuleucel-T trial all men in the ipilimumab trial had prior docetaxel treatment at entry. These observations suggest that if used in CRPC, immunotherapy seems most effective when given early. With a mild toxicity profile (5% diarrhea as most frequent toxicity) ipilimumab may certainly have a role in prostate cancer management despite this negative trial. Men with castration resistant prostate cancer, no prior docetaxel, no visceral metastases and good performance status are currently studied in the CA184-095 trial comparing ipilimumab to placebo. The trial completed accrual. In this trial no radiotherapy is applied but the inclusion criteria remarkably resemble those of the men that were most likely to benefit in the CA184-043.
  • Effect of radium-223 dichloride on symptomatic skeletal events in patients with castration-resistant prostate cancer and bone metastases: results from a phase 3, double-blind, randomised trial.

    Sartor O, Coleman R, Nilsson S, Heinrich D, Helle SI, O'Sullivan JM, Fosså SD, Chodacki A, Wiechno P, Logue J, Widmark A, Johannessen DC, Hoskin P, James ND, Solberg A, Syndikus I, Vogelzang NJ, O'Bryan-Tear CG, Shan M, Bruland ØS, Parker C.

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    Comment from Henk van der Poel: The ALSYMPCA trial showed an median overall survival benefit of 3.6 months in men with castration resistant prostate cancer. In the publication by Sartor et al., the skeletal related events were studied as an endpoint. Six times Rad223 infusion was shown to reduce the need of external beam radiotherapy for painful bone metastases, and the presence of spinal cord compression, but not symptomatic pathological fractures and tumor-related orthotopic surgery. Median overall time to first SRE was delayed by 6.6 months in the Rad223 group compared to placebo. This is longer than shown in studies comparing placebo and denosumab of zoledronic acid. Interestingly, the benefit of Rad223 for preventing SRE is most marked in patients with earlier docetaxel use or bisphosphonate use at study entry. The relatively mild toxicity profile and limited interval of use (6 months) render Rad223 an interesting agent not only to improve survival but also decrease the burden of skeletal related events, in particular spinal cord compression, in men with CRPC.
  • Abiraterone acetate plus prednisone versus prednisone alone in chemotherapy-naive men with metastatic castration-resistant prostate cancer: patient-reported outcome results of a randomised phase 3 trial

    Ethan Basch, Karen Autio, Charles J Ryan, Peter Mulders, Neal Shore, Thian Kheoh, Karim Fizazi, Christopher J Logothetis, Dana Rathkopf, Matthew R Smith, Paul N Mainwaring, Yanni Hao, Thomas Griffin, Susan Li, Michael L Meyers, Arturo Molina, Charles Clee

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    Comment by Henk van der Poel:
    Abiraterone preserves QOL better than docetaxel. Abiraterone and prednisone delays QOL deterioration by more than 6 months. That is at least comparable to changes in QOL with docetaxel in the TAX327 at a lower toxicity rate for abiraterone.

     

     

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