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Redirecting and Modulating Rationalizations of Tumor-Immanent Normative Functions in Castration-Resistant Prostate Cancer

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Abstract

With a median survival period of approximately 19 months, therapeutic options for patients with castration-resistant prostate cancer (CRPC) remain limited. In a multicenter phase II trial, 65 patients with histologically confirmed CRPC continuously received a biomodulatory regimen during the 6-month core period for redirecting tumor-promoting normative notions, i.e. angiogenesis, inflammation, immune response and the osteoplastic process. Treatment comprised daily doses of imatinib mesylate, pioglitazone, etoricoxib, treosulfan, and dexamethasone. The primary endpoint was prostate-specific antigen (PSA) response, defined as a confirmed reduction in serum PSA of ≥  50  % in patients with a baseline value of ≥  5 ng/mL. Responders could enter an extension phase until disease progression or presence of intolerable toxicity. Mean PSA was 45.3 ng/mL at baseline, and 77  % of the patients had a PSA doubling time of <  3 months. Twenty three (37.7  %) out of the 61 evaluable patients were PSA responders, who showed a mean PSA decrease from 278.9 ± 784.1 ng/mL at baseline to 8.8 ± 11.6 ng/mL at the final visit (24 weeks or LOCF). The remaining 38 non-responders included 14 patients (23.0  %) with stable disease. In one center, 6 out of 16 patients showed nearly complete resolution of bone metastases. Out of the 947 adverse events observed, 57.6  % were suspected to be drug-related, 13.8  % led to dose adjustment or permanent discontinuation of the study medication, and 40.2  % required concomitant medication. Twenty seven patients experienced serious adverse events. This novel multi-targeted approach led to an impressive PSA response rate of 37.7  % in CRPC patients despite the fact that individual components had shown limited efficacy when applied on their own. The good PSA response rate and the manageable toxicity profile suggest that this combination may offer an alternative treatment option to present therapeutic regimens.

Clinical trial registration: NCT00427999 (http://clinicaltrials.gov/ct2/show/NCT00427999)

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Author information

Authors and Affiliations

  1. Department of Hematology and Oncology, University Hospital Regensburg, Regensburg, Germany

    M. Vogelhuber, R. Andreesen & A. Reichle

  2. Department of Urology, University Hospital Tuebingen, Tuebingen, Germany

    S. Feyerabend & A. Stenzl

  3. Department of Hematology and Oncology, Hospital Passau, Passau, Germany

    T. Suedhoff

  4. Outpatient Center for Urology and Oncology, Markkleeberg, Germany

    M. Schulze

  5. Department of Oncology, J. W. Goethe University, Frankfurt, Germany

    J. Huebner

  6. Department of Urology, Hospital Planegg, Planegg, Germany

    R. Oberneder

  7. Department of Urology, Hospital St. Josef, University Regensburg, Regensburg, Germany

    W. Wieland

  8. Department of Urology, University Hospital Bonn, Bonn, Germany

    S. Mueller

  9. Outpatient Center, Bad Reichenhall, Germany

    F. Eichhorn

  10. University Hospital Hamburg-Eppendorf, Hamburg, Germany

    H. Heinzer

  11. Novartis Pharma GmbH, Nuernberg, Germany

    K. Schmidt, M. Baier, A. Ruebel & K. Birkholz

  12. Outpatient Center for Medical Oncology, Hamburg, Germany

    A. Bakhshandeh-Bath

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  1. M. Vogelhuber
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  2. S. Feyerabend
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  9. S. Mueller
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  16. A. Bakhshandeh-Bath
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  17. R. Andreesen
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  18. A. Reichle
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Correspondence to A. Reichle .

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  1. , Department of Hematology and Oncology, University Hospital Regensburg, Franz-Josef-Strauss-Allee 11, Regensburg, 93042, Germany

    Albrecht Reichle

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Vogelhuber, M. et al. (2013). Redirecting and Modulating Rationalizations of Tumor-Immanent Normative Functions in Castration-Resistant Prostate Cancer. In: Reichle, A. (eds) Evolution-adjusted Tumor Pathophysiology:. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-6866-6_5

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