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Biomodulatory Treatment of Patients with Castration-Resistant Prostate Cancer: A Phase II Study of Imatinib with Pioglitazone, Etoricoxib, Dexamethasone and Low-Dose Treosulfan

Therapeutic options for patients with castration-resistant prostate cancer (CRPC) remain limited. In a multicenter, Phase II study, 65 patients with histologically confirmed CRPC received a biomodulatory regimen during the six-month core study. Treatment comprised daily doses of imatinib mesylate, p...

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Autores principales: Vogelhuber, M., Feyerabend, S., Stenzl, A., Suedhoff, T., Schulze, M., Huebner, J., Oberneder, R., Wieland, W., Mueller, S., Eichhorn, F., Heinzer, H., Schmidt, K., Baier, M., Ruebel, A., Birkholz, K., Bakhshandeh-Bath, A., Andreesen, R., Herr, W., Reichle, A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Netherlands 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4449347/
https://www.ncbi.nlm.nih.gov/pubmed/25503648
http://dx.doi.org/10.1007/s12307-014-0161-7
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author Vogelhuber, M.
Feyerabend, S.
Stenzl, A.
Suedhoff, T.
Schulze, M.
Huebner, J.
Oberneder, R.
Wieland, W.
Mueller, S.
Eichhorn, F.
Heinzer, H.
Schmidt, K.
Baier, M.
Ruebel, A.
Birkholz, K.
Bakhshandeh-Bath, A.
Andreesen, R.
Herr, W.
Reichle, A.
author_facet Vogelhuber, M.
Feyerabend, S.
Stenzl, A.
Suedhoff, T.
Schulze, M.
Huebner, J.
Oberneder, R.
Wieland, W.
Mueller, S.
Eichhorn, F.
Heinzer, H.
Schmidt, K.
Baier, M.
Ruebel, A.
Birkholz, K.
Bakhshandeh-Bath, A.
Andreesen, R.
Herr, W.
Reichle, A.
author_sort Vogelhuber, M.
collection PubMed
description Therapeutic options for patients with castration-resistant prostate cancer (CRPC) remain limited. In a multicenter, Phase II study, 65 patients with histologically confirmed CRPC received a biomodulatory regimen during the six-month core study. Treatment comprised daily doses of imatinib mesylate, pioglitazone, etoricoxib, treosulfan and dexamethasone. The primary endpoint was prostate-specific antigen (PSA) response. Responders could enter an extension phase until disease progression or intolerable toxicity occurred. Mean PSA was 45.3 ng/mL at baseline, and 77 % of patients had a PSA doubling time <3 months. Of the 61 evaluable patients, 37 patients (60.6 %) responded or had stable disease and 23 of them (37.7 % of 61 patients) were PSA responders. Among the 23 responders mean PSA decreased from 278.9 ± 784.1 ng/mL at baseline to 8.8 ± 11.6 ng/mL at the final visit (week 24). The progression-free survival (PFS) was 467 days in the ITT population. Of the 947 adverse events, 57.6 % were suspected to be drug-related, 13.8 % led to dose adjustment or permanent discontinuation and 40.2 % required concomitant medication. This novel combination approach led to an impressive PSA response rate of 37.7 % in CRPC patients. The good PSA response and PFS rate combined with the manageable toxicity profile suggest an alternative treatment option.
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spelling pubmed-44493472015-06-04 Biomodulatory Treatment of Patients with Castration-Resistant Prostate Cancer: A Phase II Study of Imatinib with Pioglitazone, Etoricoxib, Dexamethasone and Low-Dose Treosulfan Vogelhuber, M. Feyerabend, S. Stenzl, A. Suedhoff, T. Schulze, M. Huebner, J. Oberneder, R. Wieland, W. Mueller, S. Eichhorn, F. Heinzer, H. Schmidt, K. Baier, M. Ruebel, A. Birkholz, K. Bakhshandeh-Bath, A. Andreesen, R. Herr, W. Reichle, A. Cancer Microenviron Original Article Therapeutic options for patients with castration-resistant prostate cancer (CRPC) remain limited. In a multicenter, Phase II study, 65 patients with histologically confirmed CRPC received a biomodulatory regimen during the six-month core study. Treatment comprised daily doses of imatinib mesylate, pioglitazone, etoricoxib, treosulfan and dexamethasone. The primary endpoint was prostate-specific antigen (PSA) response. Responders could enter an extension phase until disease progression or intolerable toxicity occurred. Mean PSA was 45.3 ng/mL at baseline, and 77 % of patients had a PSA doubling time <3 months. Of the 61 evaluable patients, 37 patients (60.6 %) responded or had stable disease and 23 of them (37.7 % of 61 patients) were PSA responders. Among the 23 responders mean PSA decreased from 278.9 ± 784.1 ng/mL at baseline to 8.8 ± 11.6 ng/mL at the final visit (week 24). The progression-free survival (PFS) was 467 days in the ITT population. Of the 947 adverse events, 57.6 % were suspected to be drug-related, 13.8 % led to dose adjustment or permanent discontinuation and 40.2 % required concomitant medication. This novel combination approach led to an impressive PSA response rate of 37.7 % in CRPC patients. The good PSA response and PFS rate combined with the manageable toxicity profile suggest an alternative treatment option. Springer Netherlands 2014-12-11 /pmc/articles/PMC4449347/ /pubmed/25503648 http://dx.doi.org/10.1007/s12307-014-0161-7 Text en © The Author(s) 2014 https://creativecommons.org/licenses/by/4.0/ Open Access This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.
spellingShingle Original Article
Vogelhuber, M.
Feyerabend, S.
Stenzl, A.
Suedhoff, T.
Schulze, M.
Huebner, J.
Oberneder, R.
Wieland, W.
Mueller, S.
Eichhorn, F.
Heinzer, H.
Schmidt, K.
Baier, M.
Ruebel, A.
Birkholz, K.
Bakhshandeh-Bath, A.
Andreesen, R.
Herr, W.
Reichle, A.
Biomodulatory Treatment of Patients with Castration-Resistant Prostate Cancer: A Phase II Study of Imatinib with Pioglitazone, Etoricoxib, Dexamethasone and Low-Dose Treosulfan
title Biomodulatory Treatment of Patients with Castration-Resistant Prostate Cancer: A Phase II Study of Imatinib with Pioglitazone, Etoricoxib, Dexamethasone and Low-Dose Treosulfan
title_full Biomodulatory Treatment of Patients with Castration-Resistant Prostate Cancer: A Phase II Study of Imatinib with Pioglitazone, Etoricoxib, Dexamethasone and Low-Dose Treosulfan
title_fullStr Biomodulatory Treatment of Patients with Castration-Resistant Prostate Cancer: A Phase II Study of Imatinib with Pioglitazone, Etoricoxib, Dexamethasone and Low-Dose Treosulfan
title_full_unstemmed Biomodulatory Treatment of Patients with Castration-Resistant Prostate Cancer: A Phase II Study of Imatinib with Pioglitazone, Etoricoxib, Dexamethasone and Low-Dose Treosulfan
title_short Biomodulatory Treatment of Patients with Castration-Resistant Prostate Cancer: A Phase II Study of Imatinib with Pioglitazone, Etoricoxib, Dexamethasone and Low-Dose Treosulfan
title_sort biomodulatory treatment of patients with castration-resistant prostate cancer: a phase ii study of imatinib with pioglitazone, etoricoxib, dexamethasone and low-dose treosulfan
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4449347/
https://www.ncbi.nlm.nih.gov/pubmed/25503648
http://dx.doi.org/10.1007/s12307-014-0161-7
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