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Improved efficacy of mitoxantrone in patients with castration-resistant prostate cancer after vaccination with GM-CSF-transduced allogeneic prostate cancer cells
Previous vaccination studies in patients with castration-resistant prostate cancer (CRPC) showed improved survival without prolongation of progression-free survival (PFS). This might be explained by enhanced efficacy of subsequent therapies because of heightened immune status. We therefore evaluated...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4839338/ https://www.ncbi.nlm.nih.gov/pubmed/27141390 http://dx.doi.org/10.1080/2162402X.2015.1105431 |
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author | van Dodewaard-de Jong, Joyce M. Santegoets, Saskia JAM van de Ven, Peter M. Versluis, Jurjen Verheul, Henk M. W. de Gruijl, Tanja D. Gerritsen, Winald R. van den Eertwegh, Alfons J. M. |
author_facet | van Dodewaard-de Jong, Joyce M. Santegoets, Saskia JAM van de Ven, Peter M. Versluis, Jurjen Verheul, Henk M. W. de Gruijl, Tanja D. Gerritsen, Winald R. van den Eertwegh, Alfons J. M. |
author_sort | van Dodewaard-de Jong, Joyce M. |
collection | PubMed |
description | Previous vaccination studies in patients with castration-resistant prostate cancer (CRPC) showed improved survival without prolongation of progression-free survival (PFS). This might be explained by enhanced efficacy of subsequent therapies because of heightened immune status. We therefore evaluated the efficacy of chemotherapy in CRPC patients after immunotherapy. We retrospectively analyzed 28 patients who were treated with ipilimumab and GVAX, an allogeneic vaccine, and 21 patients who were randomized to GVAX or no vaccination. To study whether immune status was related to the efficacy of chemotherapy, frequencies of myeloid and lymphocyte subsets were determined. Of 28 patients treated with GVAX and ipilimumab, 23 patients received docetaxel and 13 patients mitoxantrone. Median PFS after docetaxel was 6.4 mo (range 0.8–11.2), while median PFS after mitoxantrone was markedly longer than expected (4.8 mo; range 1.4–13.7). High CD8(+)ICOS(+) Tcell/Treg and pDC/mMDSC ratios were associated with relatively long PFS after mitoxantrone, suggesting a correlation between activated immune status and benefit of mitoxantrone. Analysis of 21 patients, randomized to GVAX or not, revealed a median PFS after docetaxel of 9.9 mo for vaccinated patients and 7.1 mo for unvaccinated patients. Interestingly, PFS after mitoxantrone (n = 14) was significantly longer in vaccinated patients as compared to controls (5.9 vs. 1.6 mo, p = 0.0048). In conclusion, mitoxantrone seems more effective in CRPC patients after immunotherapy, which may be related to the immune-stimulating effect of mitoxantrone in patients with heightened antitumor immunity. As this was a retrospective study with limited sample size, prospective studies are warranted to definitively show proof of principle. |
format | Online Article Text |
id | pubmed-4839338 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-48393382016-12-21 Improved efficacy of mitoxantrone in patients with castration-resistant prostate cancer after vaccination with GM-CSF-transduced allogeneic prostate cancer cells van Dodewaard-de Jong, Joyce M. Santegoets, Saskia JAM van de Ven, Peter M. Versluis, Jurjen Verheul, Henk M. W. de Gruijl, Tanja D. Gerritsen, Winald R. van den Eertwegh, Alfons J. M. Oncoimmunology Original Research Previous vaccination studies in patients with castration-resistant prostate cancer (CRPC) showed improved survival without prolongation of progression-free survival (PFS). This might be explained by enhanced efficacy of subsequent therapies because of heightened immune status. We therefore evaluated the efficacy of chemotherapy in CRPC patients after immunotherapy. We retrospectively analyzed 28 patients who were treated with ipilimumab and GVAX, an allogeneic vaccine, and 21 patients who were randomized to GVAX or no vaccination. To study whether immune status was related to the efficacy of chemotherapy, frequencies of myeloid and lymphocyte subsets were determined. Of 28 patients treated with GVAX and ipilimumab, 23 patients received docetaxel and 13 patients mitoxantrone. Median PFS after docetaxel was 6.4 mo (range 0.8–11.2), while median PFS after mitoxantrone was markedly longer than expected (4.8 mo; range 1.4–13.7). High CD8(+)ICOS(+) Tcell/Treg and pDC/mMDSC ratios were associated with relatively long PFS after mitoxantrone, suggesting a correlation between activated immune status and benefit of mitoxantrone. Analysis of 21 patients, randomized to GVAX or not, revealed a median PFS after docetaxel of 9.9 mo for vaccinated patients and 7.1 mo for unvaccinated patients. Interestingly, PFS after mitoxantrone (n = 14) was significantly longer in vaccinated patients as compared to controls (5.9 vs. 1.6 mo, p = 0.0048). In conclusion, mitoxantrone seems more effective in CRPC patients after immunotherapy, which may be related to the immune-stimulating effect of mitoxantrone in patients with heightened antitumor immunity. As this was a retrospective study with limited sample size, prospective studies are warranted to definitively show proof of principle. Taylor & Francis 2015-12-21 /pmc/articles/PMC4839338/ /pubmed/27141390 http://dx.doi.org/10.1080/2162402X.2015.1105431 Text en © 2016 The Author(s). Published with license by Taylor & Francis Group, LLC. http://creativecommons.org/licenses/by/3.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The moral rights of the named author(s) have been asserted. |
spellingShingle | Original Research van Dodewaard-de Jong, Joyce M. Santegoets, Saskia JAM van de Ven, Peter M. Versluis, Jurjen Verheul, Henk M. W. de Gruijl, Tanja D. Gerritsen, Winald R. van den Eertwegh, Alfons J. M. Improved efficacy of mitoxantrone in patients with castration-resistant prostate cancer after vaccination with GM-CSF-transduced allogeneic prostate cancer cells |
title | Improved efficacy of mitoxantrone in patients with castration-resistant prostate cancer after vaccination with GM-CSF-transduced allogeneic prostate cancer cells |
title_full | Improved efficacy of mitoxantrone in patients with castration-resistant prostate cancer after vaccination with GM-CSF-transduced allogeneic prostate cancer cells |
title_fullStr | Improved efficacy of mitoxantrone in patients with castration-resistant prostate cancer after vaccination with GM-CSF-transduced allogeneic prostate cancer cells |
title_full_unstemmed | Improved efficacy of mitoxantrone in patients with castration-resistant prostate cancer after vaccination with GM-CSF-transduced allogeneic prostate cancer cells |
title_short | Improved efficacy of mitoxantrone in patients with castration-resistant prostate cancer after vaccination with GM-CSF-transduced allogeneic prostate cancer cells |
title_sort | improved efficacy of mitoxantrone in patients with castration-resistant prostate cancer after vaccination with gm-csf-transduced allogeneic prostate cancer cells |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4839338/ https://www.ncbi.nlm.nih.gov/pubmed/27141390 http://dx.doi.org/10.1080/2162402X.2015.1105431 |
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