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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| Veröffentlicht in: | Cancer microenvironment 2015-04, Vol.8 (1), p.33-41 |
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| creator | 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. |
| 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 |
| doi_str_mv | 10.1007/s12307-014-0161-7 |
| format | Article |
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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.</description><identifier>ISSN: 1875-2292</identifier><identifier>EISSN: 1875-2284</identifier><identifier>DOI: 10.1007/s12307-014-0161-7</identifier><identifier>PMID: 25503648</identifier><language>eng</language><publisher>Dordrecht: Springer Netherlands</publisher><subject>Biochemistry ; Biomedical and Life Sciences ; Biomedicine ; Cancer Research ; Cell Biology ; Immunology ; Oncology ; Original ; Original Article</subject><ispartof>Cancer microenvironment, 2015-04, Vol.8 (1), p.33-41</ispartof><rights>The Author(s) 2014</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c479t-aa92a7875a8da601aa877c6177919c365d8cab38bf2f6a5b4b3210190eeb6d833</citedby><cites>FETCH-LOGICAL-c479t-aa92a7875a8da601aa877c6177919c365d8cab38bf2f6a5b4b3210190eeb6d833</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4449347/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4449347/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25503648$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Vogelhuber, M.</creatorcontrib><creatorcontrib>Feyerabend, S.</creatorcontrib><creatorcontrib>Stenzl, A.</creatorcontrib><creatorcontrib>Suedhoff, T.</creatorcontrib><creatorcontrib>Schulze, M.</creatorcontrib><creatorcontrib>Huebner, J.</creatorcontrib><creatorcontrib>Oberneder, R.</creatorcontrib><creatorcontrib>Wieland, W.</creatorcontrib><creatorcontrib>Mueller, S.</creatorcontrib><creatorcontrib>Eichhorn, F.</creatorcontrib><creatorcontrib>Heinzer, H.</creatorcontrib><creatorcontrib>Schmidt, K.</creatorcontrib><creatorcontrib>Baier, M.</creatorcontrib><creatorcontrib>Ruebel, A.</creatorcontrib><creatorcontrib>Birkholz, K.</creatorcontrib><creatorcontrib>Bakhshandeh-Bath, A.</creatorcontrib><creatorcontrib>Andreesen, R.</creatorcontrib><creatorcontrib>Herr, W.</creatorcontrib><creatorcontrib>Reichle, A.</creatorcontrib><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><title>Cancer microenvironment</title><addtitle>Cancer Microenvironment</addtitle><addtitle>Cancer Microenviron</addtitle><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.</description><subject>Biochemistry</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cancer Research</subject><subject>Cell Biology</subject><subject>Immunology</subject><subject>Oncology</subject><subject>Original</subject><subject>Original Article</subject><issn>1875-2292</issn><issn>1875-2284</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><recordid>eNp9kd1u1DAQhS1ERX_gAbhBfoAG7NiJEy6QyrbASiuxgnJtTRJn11ViV7ZDuzxVH5FZha7oTS8sj3zmfLbnEPKWs_ecMfUh8lwwlTEucZU8Uy_ICa9UkeV5JV8e6jo_Jqcx3jBWSsHEK3KcFwUTpaxOyMNn60ffTQMkH3b0OhhIo3GJ-p6uIVksI72zaUsXEFPAE--yHybamAC71sFjkQyqrjXhI72g6y1EQ5dL-jNN3W7PWY5oc7aZOWvrN4NN8Mc7c06v8Frb-nvbnNNLcw-jSehHiYLr6MrfZZcecfguH6ehB_eaHPUwRPPm335Gfn25ul58y1bfvy4XF6uslapOGUCdg8L_Q9VByThApVRbcqVqXreiLLqqhUZUTZ_3JRSNbETOGa-ZMU3ZVUKckU8z93ZqRtO1OIgAg74NdoSw0x6sfqo4u9Ub_1tLKWshFQL4DGhxRjGY_uDlTO_j03N8GuPT-_j03vPu_0sPjse8sCGfGyJKbmOCvvFTcDiIZ6h_AVUIqqI</recordid><startdate>20150401</startdate><enddate>20150401</enddate><creator>Vogelhuber, M.</creator><creator>Feyerabend, S.</creator><creator>Stenzl, A.</creator><creator>Suedhoff, T.</creator><creator>Schulze, M.</creator><creator>Huebner, J.</creator><creator>Oberneder, R.</creator><creator>Wieland, W.</creator><creator>Mueller, S.</creator><creator>Eichhorn, F.</creator><creator>Heinzer, H.</creator><creator>Schmidt, K.</creator><creator>Baier, M.</creator><creator>Ruebel, A.</creator><creator>Birkholz, K.</creator><creator>Bakhshandeh-Bath, A.</creator><creator>Andreesen, R.</creator><creator>Herr, W.</creator><creator>Reichle, A.</creator><general>Springer Netherlands</general><scope>C6C</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>5PM</scope></search><sort><creationdate>20150401</creationdate><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><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></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c479t-aa92a7875a8da601aa877c6177919c365d8cab38bf2f6a5b4b3210190eeb6d833</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Biochemistry</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cancer Research</topic><topic>Cell Biology</topic><topic>Immunology</topic><topic>Oncology</topic><topic>Original</topic><topic>Original Article</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Vogelhuber, M.</creatorcontrib><creatorcontrib>Feyerabend, S.</creatorcontrib><creatorcontrib>Stenzl, A.</creatorcontrib><creatorcontrib>Suedhoff, T.</creatorcontrib><creatorcontrib>Schulze, M.</creatorcontrib><creatorcontrib>Huebner, J.</creatorcontrib><creatorcontrib>Oberneder, R.</creatorcontrib><creatorcontrib>Wieland, W.</creatorcontrib><creatorcontrib>Mueller, S.</creatorcontrib><creatorcontrib>Eichhorn, F.</creatorcontrib><creatorcontrib>Heinzer, H.</creatorcontrib><creatorcontrib>Schmidt, K.</creatorcontrib><creatorcontrib>Baier, M.</creatorcontrib><creatorcontrib>Ruebel, A.</creatorcontrib><creatorcontrib>Birkholz, K.</creatorcontrib><creatorcontrib>Bakhshandeh-Bath, A.</creatorcontrib><creatorcontrib>Andreesen, R.</creatorcontrib><creatorcontrib>Herr, W.</creatorcontrib><creatorcontrib>Reichle, A.</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cancer microenvironment</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Vogelhuber, M.</au><au>Feyerabend, S.</au><au>Stenzl, A.</au><au>Suedhoff, T.</au><au>Schulze, M.</au><au>Huebner, J.</au><au>Oberneder, R.</au><au>Wieland, W.</au><au>Mueller, S.</au><au>Eichhorn, F.</au><au>Heinzer, H.</au><au>Schmidt, K.</au><au>Baier, M.</au><au>Ruebel, A.</au><au>Birkholz, K.</au><au>Bakhshandeh-Bath, A.</au><au>Andreesen, R.</au><au>Herr, W.</au><au>Reichle, A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Biomodulatory Treatment of Patients with Castration-Resistant Prostate Cancer: A Phase II Study of Imatinib with Pioglitazone, Etoricoxib, Dexamethasone and Low-Dose Treosulfan</atitle><jtitle>Cancer microenvironment</jtitle><stitle>Cancer Microenvironment</stitle><addtitle>Cancer Microenviron</addtitle><date>2015-04-01</date><risdate>2015</risdate><volume>8</volume><issue>1</issue><spage>33</spage><epage>41</epage><pages>33-41</pages><issn>1875-2292</issn><eissn>1875-2284</eissn><abstract>Therapeutic options for patients with castration-resistant prostate cancer (CRPC) remain limited. 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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.</abstract><cop>Dordrecht</cop><pub>Springer Netherlands</pub><pmid>25503648</pmid><doi>10.1007/s12307-014-0161-7</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| source | Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | Biochemistry Biomedical and Life Sciences Biomedicine Cancer Research Cell Biology Immunology Oncology Original Original Article |
| title | Biomodulatory Treatment of Patients with Castration-Resistant Prostate Cancer: A Phase II Study of Imatinib with Pioglitazone, Etoricoxib, Dexamethasone and Low-Dose Treosulfan |
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