Difference between revisions of "Prostate cancer"
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|[http://jco.ascopubs.org/content/15/3/1013.long Pilepich et al. 2005 (RTOG 85-31)] | |[http://jco.ascopubs.org/content/15/3/1013.long Pilepich et al. 2005 (RTOG 85-31)] | ||
− | |style="background-color:# | + | |style="background-color:#1a9851"|Phase III |
|[[Prostate_cancer_-_obsolete#Radiation_therapy|RT]] | |[[Prostate_cancer_-_obsolete#Radiation_therapy|RT]] | ||
|style="background-color:#1a9850"|Superior DFS | |style="background-color:#1a9850"|Superior DFS | ||
|- | |- | ||
|[http://www.nejm.org/doi/full/10.1056/NEJM199707313370502 Bolla et al. 1997] | |[http://www.nejm.org/doi/full/10.1056/NEJM199707313370502 Bolla et al. 1997] | ||
− | |style="background-color:# | + | |style="background-color:#1a9851"|Phase III |
|[[Prostate_cancer_-_obsolete#Radiation_therapy|RT]] | |[[Prostate_cancer_-_obsolete#Radiation_therapy|RT]] | ||
|style="background-color:#1a9850"|Superior OS | |style="background-color:#1a9850"|Superior OS | ||
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|[http://www.redjournal.org/article/S0360-3016(01)01579-6/abstract Pilepich et al. 2001 (RTOG 86-10)] | |[http://www.redjournal.org/article/S0360-3016(01)01579-6/abstract Pilepich et al. 2001 (RTOG 86-10)] | ||
− | |style="background-color:# | + | |style="background-color:#1a9851"|Phase III |
|[[Prostate_cancer_-_obsolete#Radiation_therapy|RT]] | |[[Prostate_cancer_-_obsolete#Radiation_therapy|RT]] | ||
|style="background-color:#91cf60"|Seems to have superior cause-specific mortality | |style="background-color:#91cf60"|Seems to have superior cause-specific mortality | ||
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|rowspan=2|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(05)70348-X/abstract Denham et al. 2005 (TTROG 96.01)] | |rowspan=2|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(05)70348-X/abstract Denham et al. 2005 (TTROG 96.01)] | ||
− | |rowspan=2 style="background-color:# | + | |rowspan=2 style="background-color:#1a9851"|Phase III |
|Goserelin & Flutatmide x 6m, RT | |Goserelin & Flutatmide x 6m, RT | ||
|style="background-color:#d3d3d3"|Not reported | |style="background-color:#d3d3d3"|Not reported | ||
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|- | |- | ||
|[http://jama.ama-assn.org/content/299/3/289.long D'Amico et al. 2008] | |[http://jama.ama-assn.org/content/299/3/289.long D'Amico et al. 2008] | ||
− | |style="background-color:# | + | |style="background-color:#1a9851"|Phase III |
|[[Prostate_cancer_-_obsolete#Radiation_therapy|RT]] | |[[Prostate_cancer_-_obsolete#Radiation_therapy|RT]] | ||
|style="background-color:#1a9850"|Superior OS | |style="background-color:#1a9850"|Superior OS | ||
|- | |- | ||
|[http://www.nejm.org/doi/full/10.1056/NEJMoa1012348 Jones et al. 2011] | |[http://www.nejm.org/doi/full/10.1056/NEJMoa1012348 Jones et al. 2011] | ||
− | |style="background-color:# | + | |style="background-color:#1a9851"|Phase III |
|[[Prostate_cancer_-_obsolete#Radiation_therapy|RT]] | |[[Prostate_cancer_-_obsolete#Radiation_therapy|RT]] | ||
|style="background-color:#91cf60"|Seems to have superior OS | |style="background-color:#91cf60"|Seems to have superior OS | ||
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|[http://www.nejm.org/doi/full/10.1056/NEJMoa1012348 Jones et al. 2011] | |[http://www.nejm.org/doi/full/10.1056/NEJMoa1012348 Jones et al. 2011] | ||
− | |style="background-color:# | + | |style="background-color:#1a9851"|Phase III |
|[[Prostate_cancer_-_obsolete#Radiation_therapy|RT]] | |[[Prostate_cancer_-_obsolete#Radiation_therapy|RT]] | ||
|style="background-color:#91cf60"|Seems to have superior OS | |style="background-color:#91cf60"|Seems to have superior OS | ||
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|[http://jco.ascopubs.org/content/21/21/3972.long Hanks et al. 2003 (RTOG 92-02)] | |[http://jco.ascopubs.org/content/21/21/3972.long Hanks et al. 2003 (RTOG 92-02)] | ||
− | |style="background-color:# | + | |style="background-color:#1a9851"|Phase III |
|[[#Observation|No further treatment]] | |[[#Observation|No further treatment]] | ||
|style="background-color:#91cf60"|Seems to have superior OS (*) | |style="background-color:#91cf60"|Seems to have superior OS (*) | ||
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|[http://jco.ascopubs.org/content/21/21/3972.long Hanks et al. 2003 (RTOG 92-02)] | |[http://jco.ascopubs.org/content/21/21/3972.long Hanks et al. 2003 (RTOG 92-02)] | ||
− | |style="background-color:# | + | |style="background-color:#1a9851"|Phase III |
|[[#Goserelin_monotherapy|Goserelin]] | |[[#Goserelin_monotherapy|Goserelin]] | ||
|style="background-color:#fc8d59"|Seems to have inferior OS (*) | |style="background-color:#fc8d59"|Seems to have inferior OS (*) | ||
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|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5533216 James et al. 2017 (STAMPEDE)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5533216 James et al. 2017 (STAMPEDE)] | ||
− | |style="background-color:# | + | |style="background-color:#1a9851"|Phase III |
|ADT | |ADT | ||
|style="background-color:#1a9850"|Superior OS | |style="background-color:#1a9850"|Superior OS | ||
|- | |- | ||
|[http://www.nejm.org/doi/full/10.1056/NEJMoa1704174 Fizazi et al. 2017 (LATITUDE)] | |[http://www.nejm.org/doi/full/10.1056/NEJMoa1704174 Fizazi et al. 2017 (LATITUDE)] | ||
− | |style="background-color:# | + | |style="background-color:#1a9851"|Phase III |
|ADT | |ADT | ||
|style="background-color:#1a9850"|Superior OS | |style="background-color:#1a9850"|Superior OS | ||
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|[http://www.nejm.org/doi/full/10.1056/NEJMoa1503747 Sweeney et al. 2015 (ECOG E3805)] | |[http://www.nejm.org/doi/full/10.1056/NEJMoa1503747 Sweeney et al. 2015 (ECOG E3805)] | ||
− | |style="background-color:# | + | |style="background-color:#1a9851"|Phase III |
|[[#Leuprolide_monotherapy|Leuprolide]] | |[[#Leuprolide_monotherapy|Leuprolide]] | ||
|style="background-color:#1a9850"|Superior OS | |style="background-color:#1a9850"|Superior OS | ||
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|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pubmed/9643663 Tyrrell et al. 1998] | |[https://www.ncbi.nlm.nih.gov/pubmed/9643663 Tyrrell et al. 1998] | ||
− | |style="background-color:# | + | |style="background-color:#1a9851"|Phase III |
|[[Prostate_cancer_-_obsolete#Castration|Castration]] | |[[Prostate_cancer_-_obsolete#Castration|Castration]] | ||
|style="background-color:#d3d3d3"|Not reported | |style="background-color:#d3d3d3"|Not reported | ||
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|- | |- | ||
|[http://jjco.oxfordjournals.org/content/34/1/20.full Akaza et al. 2004] | |[http://jjco.oxfordjournals.org/content/34/1/20.full Akaza et al. 2004] | ||
− | |style="background-color:# | + | |style="background-color:#1a9851"|Phase III |
|[[#Leuprolide_monotherapy|Leuprolide]] | |[[#Leuprolide_monotherapy|Leuprolide]] | ||
|style="background-color:#91cf60"|Seems to have superior TTP | |style="background-color:#91cf60"|Seems to have superior TTP | ||
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|- | |- | ||
|rowspan=2|[http://www.goldjournal.net/article/S0090-4295(99)80077-6/abstract Schellhammer et al. 1995 (CASODEX Combination Study Group)] | |rowspan=2|[http://www.goldjournal.net/article/S0090-4295(99)80077-6/abstract Schellhammer et al. 1995 (CASODEX Combination Study Group)] | ||
− | |rowspan=2 style="background-color:# | + | |rowspan=2 style="background-color:#1a9851"|Phase III |
|[[#Bicalutamide_.26_Leuprolide|Bicalutamide & Leuprolide]] | |[[#Bicalutamide_.26_Leuprolide|Bicalutamide & Leuprolide]] | ||
|style="background-color:#d3d3d3"|Not reported | |style="background-color:#d3d3d3"|Not reported | ||
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|- | |- | ||
|[http://jjco.oxfordjournals.org/content/34/1/20.full Akaza et al. 2004] | |[http://jjco.oxfordjournals.org/content/34/1/20.full Akaza et al. 2004] | ||
− | |style="background-color:# | + | |style="background-color:#1a9851"|Phase III |
|[[#Leuprolide_monotherapy|Leuprolide]] | |[[#Leuprolide_monotherapy|Leuprolide]] | ||
|style="background-color:#91cf60"|Seems to have superior TTP | |style="background-color:#91cf60"|Seems to have superior TTP | ||
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|- | |- | ||
|rowspan=2|[http://www.goldjournal.net/article/S0090-4295(99)80077-6/abstract Schellhammer et al. 1995 (CASODEX Combination Study Group)] | |rowspan=2|[http://www.goldjournal.net/article/S0090-4295(99)80077-6/abstract Schellhammer et al. 1995 (CASODEX Combination Study Group)] | ||
− | |rowspan=2 style="background-color:# | + | |rowspan=2 style="background-color:#1a9851"|Phase III |
|[[#Bicalutamide_.26_Goserelin|Bicalutamide & Goserelin]] | |[[#Bicalutamide_.26_Goserelin|Bicalutamide & Goserelin]] | ||
|style="background-color:#d3d3d3"|Not reported | |style="background-color:#d3d3d3"|Not reported | ||
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|- | |- | ||
|rowspan=2|[http://onlinelibrary.wiley.com/doi/10.1111/j.1464-410X.2008.08183.x/full Klotz et al. 2008 (CS21)] | |rowspan=2|[http://onlinelibrary.wiley.com/doi/10.1111/j.1464-410X.2008.08183.x/full Klotz et al. 2008 (CS21)] | ||
− | |rowspan=2 style="background-color:# | + | |rowspan=2 style="background-color:#1a9851"|Phase III |
|Degarelix 240/160 | |Degarelix 240/160 | ||
|style="background-color:#eeee00"|Non-inferior testosterone suppression | |style="background-color:#eeee00"|Non-inferior testosterone suppression | ||
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|- | |- | ||
|rowspan=2|[http://onlinelibrary.wiley.com/doi/10.1111/j.1464-410X.2008.08183.x/full Klotz et al. 2008 (CS21)] | |rowspan=2|[http://onlinelibrary.wiley.com/doi/10.1111/j.1464-410X.2008.08183.x/full Klotz et al. 2008 (CS21)] | ||
− | |rowspan=2 style="background-color:# | + | |rowspan=2 style="background-color:#1a9851"|Phase III |
|Degarelix 240/80 | |Degarelix 240/80 | ||
|style="background-color:#eeee00"|Non-inferior testosterone suppression | |style="background-color:#eeee00"|Non-inferior testosterone suppression | ||
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|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pubmed/9412794 Boccon-Gibod et al. 1997] | |[https://www.ncbi.nlm.nih.gov/pubmed/9412794 Boccon-Gibod et al. 1997] | ||
− | |style="background-color:# | + | |style="background-color:#1a9851"|Phase III |
|[[Prostate_cancer_-_obsolete#Castration|Orchiectomy]] | |[[Prostate_cancer_-_obsolete#Castration|Orchiectomy]] | ||
|style="background-color:#ffffbf"|Seems not superior | |style="background-color:#ffffbf"|Seems not superior | ||
|- | |- | ||
|[http://ascopubs.org/doi/full/10.1200/JCO.2001.19.1.62 Fosså et al. 2001 (EORTC)] | |[http://ascopubs.org/doi/full/10.1200/JCO.2001.19.1.62 Fosså et al. 2001 (EORTC)] | ||
− | |style="background-color:# | + | |style="background-color:#1a9851"|Phase III |
|[[#Prednisone_monotherapy|Prednisone]] | |[[#Prednisone_monotherapy|Prednisone]] | ||
|style="background-color:#ffffbf"|Seems not superior | |style="background-color:#ffffbf"|Seems not superior | ||
Line 538: | Line 538: | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pubmed/8367920 Denis et al. 1993 (EORTC 30853)] | |[https://www.ncbi.nlm.nih.gov/pubmed/8367920 Denis et al. 1993 (EORTC 30853)] | ||
− | |style="background-color:# | + | |style="background-color:#1a9851"|Phase III |
|[[Prostate_cancer_-_obsolete#Castration|Bilateral orchiectomy]] | |[[Prostate_cancer_-_obsolete#Castration|Bilateral orchiectomy]] | ||
|style="background-color:#91cf60"|Seems to have superior OS | |style="background-color:#91cf60"|Seems to have superior OS | ||
|- | |- | ||
|rowspan=2|[http://www.goldjournal.net/article/S0090-4295(99)80077-6/abstract Schellhammer et al. 1995 (CASODEX Combination Study Group)] | |rowspan=2|[http://www.goldjournal.net/article/S0090-4295(99)80077-6/abstract Schellhammer et al. 1995 (CASODEX Combination Study Group)] | ||
− | |rowspan=2 style="background-color:# | + | |rowspan=2 style="background-color:#1a9851"|Phase III |
|[[#Bicalutamide_.26_Goserelin|Bicalutamide & Goserelin]]<br> [[#Bicalutamide_.26_Leuprolide|Bicalutamide & Leuprolide]] | |[[#Bicalutamide_.26_Goserelin|Bicalutamide & Goserelin]]<br> [[#Bicalutamide_.26_Leuprolide|Bicalutamide & Leuprolide]] | ||
|style="background-color:#d73027"|Inferior TTTF | |style="background-color:#d73027"|Inferior TTTF | ||
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|- | |- | ||
|rowspan=2|[http://www.goldjournal.net/article/S0090-4295(99)80077-6/abstract Schellhammer et al. 1995 (CASODEX Combination Study Group)] | |rowspan=2|[http://www.goldjournal.net/article/S0090-4295(99)80077-6/abstract Schellhammer et al. 1995 (CASODEX Combination Study Group)] | ||
− | |rowspan=2 style="background-color:# | + | |rowspan=2 style="background-color:#1a9851"|Phase III |
|[[#Bicalutamide_.26_Goserelin|Bicalutamide & Goserelin]]<br> [[#Bicalutamide_.26_Leuprolide|Bicalutamide & Leuprolide]] | |[[#Bicalutamide_.26_Goserelin|Bicalutamide & Goserelin]]<br> [[#Bicalutamide_.26_Leuprolide|Bicalutamide & Leuprolide]] | ||
|style="background-color:#d73027"|Inferior TTTF | |style="background-color:#d73027"|Inferior TTTF | ||
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|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pubmed/1824732 Soloway et al. 1991 (Zoladex Prostate Study Group)] | |[https://www.ncbi.nlm.nih.gov/pubmed/1824732 Soloway et al. 1991 (Zoladex Prostate Study Group)] | ||
− | |style="background-color:# | + | |style="background-color:#1a9851"|Phase III |
|[[Prostate_cancer_-_obsolete#Castration|Bilateral orchiectomy]] | |[[Prostate_cancer_-_obsolete#Castration|Bilateral orchiectomy]] | ||
|style="background-color:#ffffbf"|Seems not superior | |style="background-color:#ffffbf"|Seems not superior | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pubmed/1828183 Kaisary et al. 1991] | |[https://www.ncbi.nlm.nih.gov/pubmed/1828183 Kaisary et al. 1991] | ||
− | |style="background-color:# | + | |style="background-color:#1a9851"|Phase III |
|[[Prostate_cancer_-_obsolete#Castration|Bilateral orchiectomy]] | |[[Prostate_cancer_-_obsolete#Castration|Bilateral orchiectomy]] | ||
|style="background-color:#ffffbf"|Seems not superior | |style="background-color:#ffffbf"|Seems not superior | ||
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|- | |- | ||
|[http://jjco.oxfordjournals.org/content/34/1/20.full Akaza et al. 2004] | |[http://jjco.oxfordjournals.org/content/34/1/20.full Akaza et al. 2004] | ||
− | |style="background-color:# | + | |style="background-color:#1a9851"|Phase III |
|[[#Bicalutamide_.26_Goserelin|Bicalutamide & Goserelin]]<br> [[#Bicalutamide_.26_Leuprolide|Bicalutamide & Leuprolide]] | |[[#Bicalutamide_.26_Goserelin|Bicalutamide & Goserelin]]<br> [[#Bicalutamide_.26_Leuprolide|Bicalutamide & Leuprolide]] | ||
|style="background-color:#fc8d59"|Seems to have inferior TTP | |style="background-color:#fc8d59"|Seems to have inferior TTP | ||
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|- | |- | ||
|rowspan=2|[http://onlinelibrary.wiley.com/doi/10.1111/j.1464-410X.2008.08183.x/full Klotz et al. 2008 (CS21)] | |rowspan=2|[http://onlinelibrary.wiley.com/doi/10.1111/j.1464-410X.2008.08183.x/full Klotz et al. 2008 (CS21)] | ||
− | |rowspan=2 style="background-color:# | + | |rowspan=2 style="background-color:#1a9851"|Phase III |
|[[#Degarelix_monotherapy|Degarelix 240/80]] | |[[#Degarelix_monotherapy|Degarelix 240/80]] | ||
|style="background-color:#eeee00"|Non-inferior testosterone suppression | |style="background-color:#eeee00"|Non-inferior testosterone suppression | ||
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|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pubmed/7678043 Janknegt et al. 1993 (International Anandron Study Group)] | |[https://www.ncbi.nlm.nih.gov/pubmed/7678043 Janknegt et al. 1993 (International Anandron Study Group)] | ||
− | |style="background-color:# | + | |style="background-color:#1a9851"|Phase III |
|[[Prostate_cancer_-_obsolete#Castration|Orchiectomy]] | |[[Prostate_cancer_-_obsolete#Castration|Orchiectomy]] | ||
|style="background-color:#1a9850"|Superior PFS | |style="background-color:#1a9850"|Superior PFS | ||
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|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3471149/ de Bono et al. 2011 (COU-AA-301)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3471149/ de Bono et al. 2011 (COU-AA-301)] | ||
− | |style="background-color:# | + | |style="background-color:#1a9851"|Phase III |
|14% (95% CI n/a), 29% | |14% (95% CI n/a), 29% | ||
|[[#Prednisone_monotherapy|Prednisone]] | |[[#Prednisone_monotherapy|Prednisone]] | ||
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|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3683570/ Ryan et al. 2013 (COU-AA-302)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3683570/ Ryan et al. 2013 (COU-AA-302)] | ||
− | |style="background-color:# | + | |style="background-color:#1a9851"|Phase III |
|36% (95% CI n/a), 62% | |36% (95% CI n/a), 62% | ||
|[[#Prednisone_monotherapy|Prednisone]] | |[[#Prednisone_monotherapy|Prednisone]] | ||
Line 802: | Line 802: | ||
|- | |- | ||
|[http://jco.ascopubs.org/content/22/6/1025.long Small et al. 2004 (CALGB 9583)] | |[http://jco.ascopubs.org/content/22/6/1025.long Small et al. 2004 (CALGB 9583)] | ||
− | |style="background-color:# | + | |style="background-color:#1a9851"|Phase III |
|[[#Ketoconazole_.26_Hydrocortisone|Ketoconazole & Hydrocortisone]] | |[[#Ketoconazole_.26_Hydrocortisone|Ketoconazole & Hydrocortisone]] | ||
|style="background-color:#d73027"|Inferior PSA response | |style="background-color:#d73027"|Inferior PSA response | ||
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|- | |- | ||
|[http://www.nejm.org/doi/full/10.1056/NEJMoa1207506 Scher et al. 2012 (AFFIRM)] | |[http://www.nejm.org/doi/full/10.1056/NEJMoa1207506 Scher et al. 2012 (AFFIRM)] | ||
− | |style="background-color:# | + | |style="background-color:#1a9851"|Phase III |
|29% (95% CI n/a), 54% | |29% (95% CI n/a), 54% | ||
|[[Prostate_cancer_-_obsolete#Placebo|Placebo]] | |[[Prostate_cancer_-_obsolete#Placebo|Placebo]] | ||
Line 871: | Line 871: | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4418931/ Beer et al. 2014 (PREVAIL)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4418931/ Beer et al. 2014 (PREVAIL)] | ||
− | |style="background-color:# | + | |style="background-color:#1a9851"|Phase III |
|59% (95% CI n/a), 78% | |59% (95% CI n/a), 78% | ||
|[[Prostate_cancer_-_obsolete#Placebo|Placebo]] | |[[Prostate_cancer_-_obsolete#Placebo|Placebo]] | ||
Line 879: | Line 879: | ||
|- | |- | ||
|[http://jco.ascopubs.org/content/34/18/2098.full Penson et al. 2016 (STRIVE)] | |[http://jco.ascopubs.org/content/34/18/2098.full Penson et al. 2016 (STRIVE)] | ||
− | |style="background-color:# | + | |style="background-color:#1a9851"|Randomized Phase II |
|60% (95% CI n/a), 81% | |60% (95% CI n/a), 81% | ||
|[[#Bicalutamide_monotherapy_2|Bicalutamide]] | |[[#Bicalutamide_monotherapy_2|Bicalutamide]] | ||
Line 916: | Line 916: | ||
|- | |- | ||
|[http://jco.ascopubs.org/content/22/6/1025.long Small et al. 2004 (CALGB 9583)] | |[http://jco.ascopubs.org/content/22/6/1025.long Small et al. 2004 (CALGB 9583)] | ||
− | |style="background-color:# | + | |style="background-color:#1a9851"|Phase III |
|pts w/ measurable disease: '''20%''' (95% CI 11 - 32), '''27%''' (95% CI 20 - 35) | |pts w/ measurable disease: '''20%''' (95% CI 11 - 32), '''27%''' (95% CI 20 - 35) | ||
|[[#Antiandrogen_withdrawal|Antiandrogen withdrawal]] | |[[#Antiandrogen_withdrawal|Antiandrogen withdrawal]] | ||
Line 966: | Line 966: | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3471149/ de Bono et al. 2011 (COU-AA-301)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3471149/ de Bono et al. 2011 (COU-AA-301)] | ||
− | |style="background-color:# | + | |style="background-color:#1a9851"|Phase III |
|[[#Abiraterone_.26_Prednisone|Abiraterone & Prednisone]] | |[[#Abiraterone_.26_Prednisone|Abiraterone & Prednisone]] | ||
|style="background-color:#d73027"|Inferior OS | |style="background-color:#d73027"|Inferior OS | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3683570/ Ryan et al. 2013 (COU-AA-302)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3683570/ Ryan et al. 2013 (COU-AA-302)] | ||
− | |style="background-color:# | + | |style="background-color:#1a9851"|Phase III |
|[[#Abiraterone_.26_Prednisone|Abiraterone & Prednisone]] | |[[#Abiraterone_.26_Prednisone|Abiraterone & Prednisone]] | ||
|style="background-color:#fc8d59"|Seems to have inferior OS | |style="background-color:#fc8d59"|Seems to have inferior OS | ||
|- | |- | ||
|[http://ascopubs.org/doi/full/10.1200/JCO.2015.65.5597 Smith et al. 2016 (COMET-1)] | |[http://ascopubs.org/doi/full/10.1200/JCO.2015.65.5597 Smith et al. 2016 (COMET-1)] | ||
− | |style="background-color:# | + | |style="background-color:#1a9851"|Phase III |
|[[#Cabozantinib_monotherapy|Cabozantinib]] | |[[#Cabozantinib_monotherapy|Cabozantinib]] | ||
|style="background-color:#ffffbf"|Seems not superior | |style="background-color:#ffffbf"|Seems not superior | ||
Line 994: | Line 994: | ||
|- | |- | ||
|[http://ascopubs.org/doi/full/10.1200/JCO.2001.19.1.62 Fosså et al. 2001 (EORTC)] | |[http://ascopubs.org/doi/full/10.1200/JCO.2001.19.1.62 Fosså et al. 2001 (EORTC)] | ||
− | |style="background-color:# | + | |style="background-color:#1a9851"|Phase III |
|[[#Flutamide_monotherapy|Flutamide]] | |[[#Flutamide_monotherapy|Flutamide]] | ||
|style="background-color:#ffffbf"|Seems not superior | |style="background-color:#ffffbf"|Seems not superior | ||
Line 1,032: | Line 1,032: | ||
|- | |- | ||
|rowspan = "2"|[http://ascopubs.org/doi/full/10.1200/JCO.2016.72.1068 Oudard et al. 2017 (FIRSTANA)] | |rowspan = "2"|[http://ascopubs.org/doi/full/10.1200/JCO.2016.72.1068 Oudard et al. 2017 (FIRSTANA)] | ||
− | |rowspan = "2" style="background-color:# | + | |rowspan = "2" style="background-color:#1a9851"|Phase III |
|Cabazitaxel 25 mg/m<sup>2</sup> & Prednisone | |Cabazitaxel 25 mg/m<sup>2</sup> & Prednisone | ||
|style="background-color:#ffffbf"|Seems not superior | |style="background-color:#ffffbf"|Seems not superior | ||
Line 1,040: | Line 1,040: | ||
|- | |- | ||
|[http://ascopubs.org/doi/full/10.1200/JCO.2016.72.1076 Eisenberger et al. 2017 (PROSELICA)] | |[http://ascopubs.org/doi/full/10.1200/JCO.2016.72.1076 Eisenberger et al. 2017 (PROSELICA)] | ||
− | |style="background-color:# | + | |style="background-color:#1a9851"|Phase III |
|Cabazitaxel 25 mg/m<sup>2</sup> & Prednisone | |Cabazitaxel 25 mg/m<sup>2</sup> & Prednisone | ||
|style="background-color:#eeee00"|Non-inferior OS | |style="background-color:#eeee00"|Non-inferior OS | ||
Line 1,062: | Line 1,062: | ||
|- | |- | ||
|[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2810%2961389-X/fulltext de Bono et al. 2010 (TROPIC)] | |[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2810%2961389-X/fulltext de Bono et al. 2010 (TROPIC)] | ||
− | |style="background-color:# | + | |style="background-color:#1a9851"|Phase III |
|14% (95% CI 10-19)<br> 39% (95% CI 34-44) (*) | |14% (95% CI 10-19)<br> 39% (95% CI 34-44) (*) | ||
|[[#Mitoxantrone_.26_Prednisone|Mitoxantrone & Prednisone]] | |[[#Mitoxantrone_.26_Prednisone|Mitoxantrone & Prednisone]] | ||
Line 1,070: | Line 1,070: | ||
|- | |- | ||
|rowspan = "2"|[http://ascopubs.org/doi/full/10.1200/JCO.2016.72.1068 Oudard et al. 2017 (FIRSTANA)] | |rowspan = "2"|[http://ascopubs.org/doi/full/10.1200/JCO.2016.72.1068 Oudard et al. 2017 (FIRSTANA)] | ||
− | |rowspan = "2" style="background-color:# | + | |rowspan = "2" style="background-color:#1a9851"|Phase III |
| | | | ||
|Cabazitaxel 20 mg/m<sup>2</sup> & Prednisone | |Cabazitaxel 20 mg/m<sup>2</sup> & Prednisone | ||
Line 1,084: | Line 1,084: | ||
|- | |- | ||
|[http://ascopubs.org/doi/full/10.1200/JCO.2016.72.1076 Eisenberger et al. 2017 (PROSELICA)] | |[http://ascopubs.org/doi/full/10.1200/JCO.2016.72.1076 Eisenberger et al. 2017 (PROSELICA)] | ||
− | |style="background-color:# | + | |style="background-color:#1a9851"|Phase III |
| | | | ||
|Cabazitaxel 20 mg/m<sup>2</sup> & Prednisone | |Cabazitaxel 20 mg/m<sup>2</sup> & Prednisone | ||
Line 1,092: | Line 1,092: | ||
|- | |- | ||
|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30605-8/fulltext Beer et al. 2017 (AFFINITY)] | |[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30605-8/fulltext Beer et al. 2017 (AFFINITY)] | ||
− | |style="background-color:# | + | |style="background-color:#1a9851"|Phase III |
| | | | ||
|Cabazitaxel, Prednisone, Custirsen | |Cabazitaxel, Prednisone, Custirsen | ||
Line 1,131: | Line 1,131: | ||
|- | |- | ||
|[http://ascopubs.org/doi/full/10.1200/JCO.2015.65.5597 Smith et al. 2016 (COMET-1)] | |[http://ascopubs.org/doi/full/10.1200/JCO.2015.65.5597 Smith et al. 2016 (COMET-1)] | ||
− | |style="background-color:# | + | |style="background-color:#1a9851"|Phase III |
|[[#Prednisone_monotherapy|Prednisone]] | |[[#Prednisone_monotherapy|Prednisone]] | ||
|style="background-color:#ffffbf"|Seems not superior | |style="background-color:#ffffbf"|Seems not superior | ||
Line 1,332: | Line 1,332: | ||
|- | |- | ||
|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70184-0/abstract Tannock et al. 2013 (VENICE)] | |[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70184-0/abstract Tannock et al. 2013 (VENICE)] | ||
− | |style="background-color:# | + | |style="background-color:#1a9851"|Phase III |
|Docetaxel, Prednisone, Dasatinib | |Docetaxel, Prednisone, Dasatinib | ||
|style="background-color:#ffffbf"|Seems not superior | |style="background-color:#ffffbf"|Seems not superior | ||
|- | |- | ||
|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70479-0/abstract Araujo et al. 2013 (READY)] | |[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70479-0/abstract Araujo et al. 2013 (READY)] | ||
− | |style="background-color:# | + | |style="background-color:#1a9851"|Phase III |
|Docetaxel, Prednisone, Dasatinib | |Docetaxel, Prednisone, Dasatinib | ||
|style="background-color:#ffffbf"|Seems not superior | |style="background-color:#ffffbf"|Seems not superior | ||
|- | |- | ||
|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)70025-2/abstract Petrylak et al. 2015 (MAINSAIL)] | |[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)70025-2/abstract Petrylak et al. 2015 (MAINSAIL)] | ||
− | |style="background-color:# | + | |style="background-color:#1a9851"|Phase III |
|Docetaxel, Prednisone, Lenalidomide | |Docetaxel, Prednisone, Lenalidomide | ||
|style="background-color:#1a9850"|Superior OS | |style="background-color:#1a9850"|Superior OS | ||
|- | |- | ||
|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30168-7/fulltext Chi et al. 2017 (SYNERGY)] | |[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30168-7/fulltext Chi et al. 2017 (SYNERGY)] | ||
− | |style="background-color:# | + | |style="background-color:#1a9851"|Phase III |
|Docetaxel, Prednisone, Custirsen | |Docetaxel, Prednisone, Custirsen | ||
|style="background-color:#ffffbf"|Seems not superior | |style="background-color:#ffffbf"|Seems not superior | ||
|- | |- | ||
|rowspan = "2"|[http://ascopubs.org/doi/full/10.1200/JCO.2016.72.1068 Oudard et al. 2017 (FIRSTANA)] | |rowspan = "2"|[http://ascopubs.org/doi/full/10.1200/JCO.2016.72.1068 Oudard et al. 2017 (FIRSTANA)] | ||
− | |rowspan = "2" style="background-color:# | + | |rowspan = "2" style="background-color:#1a9851"|Phase III |
|[[#Cabazitaxel_.26_Prednisone|Cabazitaxel 20 mg/m<sup>2</sup> & Prednisone]] | |[[#Cabazitaxel_.26_Prednisone|Cabazitaxel 20 mg/m<sup>2</sup> & Prednisone]] | ||
|style="background-color:#ffffbf"|Seems not superior | |style="background-color:#ffffbf"|Seems not superior | ||
Line 1,375: | Line 1,375: | ||
|- | |- | ||
|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2812%2970537-5/abstract Kellokumpu-Lehtinen et al. 2013 (PROSTY)] | |[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2812%2970537-5/abstract Kellokumpu-Lehtinen et al. 2013 (PROSTY)] | ||
− | |style="background-color:# | + | |style="background-color:#1a9851"|Phase III |
|Every 2-weeks Docetaxel & Prednisone | |Every 2-weeks Docetaxel & Prednisone | ||
|style="background-color:#fc8d59"|Seems to have inferior TTTF | |style="background-color:#fc8d59"|Seems to have inferior TTTF | ||
Line 1,402: | Line 1,402: | ||
|- | |- | ||
|rowspan=2|[http://www.nejm.org/doi/full/10.1056/NEJMoa040720 Tannock et al. 2004 (TAX 327)] | |rowspan=2|[http://www.nejm.org/doi/full/10.1056/NEJMoa040720 Tannock et al. 2004 (TAX 327)] | ||
− | |rowspan=2 style="background-color:# | + | |rowspan=2 style="background-color:#1a9851"|Phase III |
|rowspan=2|pts w/ measurable disease:'''12%''' (95% CI 7-19), '''45%''' (95% CI 40-51) | |rowspan=2|pts w/ measurable disease:'''12%''' (95% CI 7-19), '''45%''' (95% CI 40-51) | ||
|Weekly Docetaxel & Prednisone | |Weekly Docetaxel & Prednisone | ||
Line 1,433: | Line 1,433: | ||
|- | |- | ||
|rowspan=2|[http://www.nejm.org/doi/full/10.1056/NEJMoa040720 Tannock et al. 2004 (TAX 327)] | |rowspan=2|[http://www.nejm.org/doi/full/10.1056/NEJMoa040720 Tannock et al. 2004 (TAX 327)] | ||
− | |rowspan=2 style="background-color:# | + | |rowspan=2 style="background-color:#1a9851"|Phase III |
|Every 3-week Docetaxel & Prednisone | |Every 3-week Docetaxel & Prednisone | ||
|style="background-color:#d3d3d3"|Not reported | |style="background-color:#d3d3d3"|Not reported | ||
Line 1,459: | Line 1,459: | ||
|- | |- | ||
|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2812%2970537-5/abstract Kellokumpu-Lehtinen et al. 2013 (PROSTY] | |[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2812%2970537-5/abstract Kellokumpu-Lehtinen et al. 2013 (PROSTY] | ||
− | |style="background-color:# | + | |style="background-color:#1a9851"|Phase III |
|Every 3-weeks Docetaxel & Prednisone | |Every 3-weeks Docetaxel & Prednisone | ||
|style="background-color:#91cf60"|Seems to have superior TTTF | |style="background-color:#91cf60"|Seems to have superior TTTF | ||
Line 1,504: | Line 1,504: | ||
|- | |- | ||
|rowspan=2|[http://www.nejm.org/doi/full/10.1056/NEJMoa040720 Tannock et al. 2004 (TAX 327)] | |rowspan=2|[http://www.nejm.org/doi/full/10.1056/NEJMoa040720 Tannock et al. 2004 (TAX 327)] | ||
− | |rowspan=2 style="background-color:# | + | |rowspan=2 style="background-color:#1a9851"|Phase III |
|rowspan=2|pts w/ measurable disease: '''7%''' (95% CI 3-12), '''32%''' (95% CI 26-37) | |rowspan=2|pts w/ measurable disease: '''7%''' (95% CI 3-12), '''32%''' (95% CI 26-37) | ||
|[[#Docetaxel_.26_Prednisone|Weekly Docetaxel & Prednisone]] | |[[#Docetaxel_.26_Prednisone|Weekly Docetaxel & Prednisone]] | ||
Line 1,517: | Line 1,517: | ||
|- | |- | ||
|[http://www.nejm.org/doi/full/10.1056/NEJMoa041318 Petrylak et al. 2004 (SWOG 99-16)] | |[http://www.nejm.org/doi/full/10.1056/NEJMoa041318 Petrylak et al. 2004 (SWOG 99-16)] | ||
− | |style="background-color:# | + | |style="background-color:#1a9851"|Phase III |
| | | | ||
|Docetaxel & Estramustine | |Docetaxel & Estramustine | ||
Line 1,525: | Line 1,525: | ||
|- | |- | ||
|[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2810%2961389-X/fulltext de Bono et al. 2010 (TROPIC)] | |[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2810%2961389-X/fulltext de Bono et al. 2010 (TROPIC)] | ||
− | |style="background-color:# | + | |style="background-color:#1a9851"|Phase III |
|pts w/ measurable disease:<br>'''4.4%''' (95% CI 1.6 - 7.2), '''17.8%''' (95% CI 13.7 - 22.0) | |pts w/ measurable disease:<br>'''4.4%''' (95% CI 1.6 - 7.2), '''17.8%''' (95% CI 13.7 - 22.0) | ||
|[[#Cabazitaxel_.26_Prednisone|Cabazitaxel & Prednisone]] | |[[#Cabazitaxel_.26_Prednisone|Cabazitaxel & Prednisone]] | ||
Line 1,625: | Line 1,625: | ||
|- | |- | ||
|[http://www.nejm.org/doi/full/10.1056/NEJMoa1001294 Kantoff et al. 2010 (IMPACT)] | |[http://www.nejm.org/doi/full/10.1056/NEJMoa1001294 Kantoff et al. 2010 (IMPACT)] | ||
− | |style="background-color:# | + | |style="background-color:#1a9851"|Phase III |
|[[Prostate_cancer_-_obsolete#Placebo|Placebo]] | |[[Prostate_cancer_-_obsolete#Placebo|Placebo]] | ||
|style="background-color:#91cf60"|Seems to have superior OS | |style="background-color:#91cf60"|Seems to have superior OS | ||
Line 1,657: | Line 1,657: | ||
|- | |- | ||
|[http://www.nejm.org/doi/full/10.1056/NEJMoa1213755 Parker et al. 2013 (ALSYMPCA)] | |[http://www.nejm.org/doi/full/10.1056/NEJMoa1213755 Parker et al. 2013 (ALSYMPCA)] | ||
− | |style="background-color:# | + | |style="background-color:#1a9851"|Phase III |
|[[Prostate_cancer_-_obsolete#Placebo|Placebo]] | |[[Prostate_cancer_-_obsolete#Placebo|Placebo]] | ||
|style="background-color:#1a9850"|Superior OS | |style="background-color:#1a9850"|Superior OS | ||
Line 1,676: | Line 1,676: | ||
|- | |- | ||
|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(07)70147-X/abstract Nilsson et al. 2007] | |[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(07)70147-X/abstract Nilsson et al. 2007] | ||
− | |style="background-color:# | + | |style="background-color:#1a9851"|Randomized Phase II |
|[[Prostate_cancer_-_obsolete#Placebo|Placebo]] | |[[Prostate_cancer_-_obsolete#Placebo|Placebo]] | ||
|style="background-color:#d9ef8b"|Might have superior OS | |style="background-color:#d9ef8b"|Might have superior OS | ||
Line 1,714: | Line 1,714: | ||
|- | |- | ||
|[http://www.ejcancer.com/article/S0959-8049(97)00155-X/pdf Resche et al. 1997] | |[http://www.ejcancer.com/article/S0959-8049(97)00155-X/pdf Resche et al. 1997] | ||
− | |style="background-color:# | + | |style="background-color:#1a9851"|Phase III |
|Samarium-153 0.5 mCi/kg | |Samarium-153 0.5 mCi/kg | ||
|style="background-color:#91cf60"|Seems to have superior pain control at week 4 | |style="background-color:#91cf60"|Seems to have superior pain control at week 4 | ||
|- | |- | ||
|[http://www.goldjournal.net/article/S0090-4295%2804%2900143-8/abstract Sartor et al. 2004 (Quadramet 424Sm10/11 Study Group)] | |[http://www.goldjournal.net/article/S0090-4295%2804%2900143-8/abstract Sartor et al. 2004 (Quadramet 424Sm10/11 Study Group)] | ||
− | |style="background-color:# | + | |style="background-color:#1a9851"|Phase III |
|Samarium-152 (non-radioactive) | |Samarium-152 (non-radioactive) | ||
|style="background-color:#91cf60"|Seems to have superior pain control at week 4 | |style="background-color:#91cf60"|Seems to have superior pain control at week 4 |
Revision as of 18:39, 26 December 2017
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Is there a regimen missing from this list? Would you like to share a different dosage/schedule or an additional reference for a regimen? Have you noticed an error? Do you have an idea that will help the site grow to better meet your needs and the needs of many others? You are invited to contribute to the site. Are you looking for a regimen, but can't find it here? It is possible that we've moved it to the obsolete regimens page. If you still can't find it, please let us know so we can add it!
80 regimens on this page
112 variants on this page
|
Guidelines
ASCO
- 2017: Second-Line Hormonal Therapy for Men With Chemotherapy-Naïve, Castration-Resistant Prostate Cancer: American Society of Clinical Oncology Provisional Clinical Opinion PubMed
- 2016: Active Surveillance for the Management of Localized Prostate Cancer Endorsement
- 2015: Prostate Cancer Survivorship Care Guideline Endorsement
- 2014: Adjuvant and Salvage Radiotherapy After Prostatectomy Endorsement
- 2014: Systemic Therapy in Men with Metastatic Castration-Resistant Prostate Cancer (CRPC)
- 2012: Screening for Prostate Cancer with Prostate-Specific Antigen (PSA) Testing PCO
Older
- 2009: Use of 5-alpha Reductase Inhibitors for Prostate Cancer Chemoprevention
- 2007: Non-Hormonal Therapy for Men With Metastatic Hormone-Refractory (castration-resistant) Prostate Cancer Endorsement
ASCO & CCO
AUA
- Castration-Resistant Prostate Cancer: AUA Guideline @ AUAnet
- Castration-Resistant Prostate Cancer: AUA Guideline Amendment 2015 PubMed
EAU/ESTRO/SIOG
- 2017: EAU-ESTRO-SIOG Guidelines on Prostate Cancer. Part II: Treatment of Relapsing, Metastatic, and Castration-Resistant Prostate Cancer PubMed
ESMO
Older
- 2013: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
- 2012: ESMO Consensus Conference Guidelines PubMed
NCCN
St Gallen
Definitive ADT & radiotherapy
Goserelin & RT
back to top |
RT: Radiation Therapy
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Pilepich et al. 2005 (RTOG 85-31) | Phase III | RT | Superior DFS |
Bolla et al. 1997 | Phase III | RT | Superior OS |
Endocrine & Radiotherapy
- Goserelin (Zoladex) 3.6 mg SC once every 4 weeks, to start during the last week of radiation therapy and to continue indefinitely or until progression
- Radiation therapy, 1.8 to 2 Gy per fraction, with an initial 44 to 46 Gy to the pelvis, then an additional boost to the prostate that resulted in a total dose of 65 to 70 Gy in definitive radiation patients; 60 to 65 Gy total dose for post-prostatectomy patients
References
- Pilepich MV, Caplan R, Byhardt RW, Lawton CA, Gallagher MJ, Mesic JB, Hanks GE, Coughlin CT, Porter A, Shipley WU, Grignon D. Phase III trial of androgen suppression using goserelin in unfavorable-prognosis carcinoma of the prostate treated with definitive radiotherapy: report of Radiation Therapy Oncology Group Protocol 85-31. J Clin Oncol. 1997 Mar;15(3):1013-21. link to original article contains protocol PubMed
- Update: Lawton CA, Winter K, Murray K, Machtay M, Mesic JB, Hanks GE, Coughlin CT, Pilepich MV. Updated results of the phase III Radiation Therapy Oncology Group (RTOG) trial 85-31 evaluating the potential benefit of androgen suppression following standard radiation therapy for unfavorable prognosis carcinoma of the prostate. Int J Radiat Oncol Biol Phys. 2001 Mar 15;49(4):937-46. link to original article contains protocol PubMed
- Update: Pilepich MV, Winter K, Lawton CA, Krisch RE, Wolkov HB, Movsas B, Hug EB, Asbell SO, Grignon D. Androgen suppression adjuvant to definitive radiotherapy in prostate carcinoma--long-term results of phase III RTOG 85-31. Int J Radiat Oncol Biol Phys. 2005 Apr 1;61(5):1285-90. link to original article contains verified protocol PubMed
- Bolla M, Gonzalez D, Warde P, Dubois JB, Mirimanoff RO, Storme G, Bernier J, Kuten A, Sternberg C, Gil T, Collette L, Pierart M. Improved survival in patients with locally advanced prostate cancer treated with radiotherapy and goserelin. N Engl J Med. 1997 Jul 31;337(5):295-300. link to original article PubMed
Goserelin, Flutamide, RT
back to top |
RT: Radiation Therapy
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Pilepich et al. 2001 (RTOG 86-10) | Phase III | RT | Seems to have superior cause-specific mortality |
Hanks et al. 2003 (RTOG 92-02) | Non-randomized portion of RCT | ||
Denham et al. 2005 (TTROG 96.01) | Phase III | Goserelin & Flutatmide x 6m, RT | Not reported |
RT | Superior DFS | ||
D'Amico et al. 2008 | Phase III | RT | Superior OS |
Jones et al. 2011 | Phase III | RT | Seems to have superior OS |
Endocrine & Radiotherapy
- Goserelin (Zoladex) 3.6 mg SC once every 4 weeks, to start 2 months prior to radiation therapy and to continue at least through the end of radiation therapy
- Flutamide (Eulexin) 250 mg PO three times per day, to start 2 months prior to radiation therapy and to continue at least through the end of radiation therapy
- Radiation therapy is started 2 months after start of androgen deprivation therapy (ADT), 1.8 to 2 Gy per fraction, with an initial 44 to 46 Gy to the pelvis, then an additional conedown to the prostate that resulted in a total dose of 65 to 70 Gy
Patients in RTOG 92-02 were subsequently randomized to adjuvant goserelin x 2 years versus no further treatment.
References
- Pilepich MV, Winter K, John MJ, Mesic JB, Sause W, Rubin P, Lawton C, Machtay M, Grignon D. Phase III radiation therapy oncology group (RTOG) trial 86-10 of androgen deprivation adjuvant to definitive radiotherapy in locally advanced carcinoma of the prostate. Int J Radiat Oncol Biol Phys. 2001 Aug 1;50(5):1243-52. link to original article contains verified protocol PubMed
- Update: Roach M 3rd, Bae K, Speight J, Wolkov HB, Rubin P, Lee RJ, Lawton C, Valicenti R, Grignon D, Pilepich MV. Short-term neoadjuvant androgen deprivation therapy and external-beam radiotherapy for locally advanced prostate cancer: long-term results of RTOG 8610. J Clin Oncol. 2008 Feb 1;26(4):585-91. Epub 2008 Jan 2. link to original article contains verified protocol PubMed
- Hanks GE, Pajak TF, Porter A, Grignon D, Brereton H, Venkatesan V, Horwitz EM, Lawton C, Rosenthal SA, Sandler HM, Shipley WU; Radiation Therapy Oncology Group. Phase III trial of long-term adjuvant androgen deprivation after neoadjuvant hormonal cytoreduction and radiotherapy in locally advanced carcinoma of the prostate: the Radiation Therapy Oncology Group Protocol 92-02. J Clin Oncol. 2003 Nov 1;21(21):3972-8. Erratum in: J Clin Oncol. 2004 Jan 15;22(2):386. link to original article contains protocol PubMed
- Update: Horwitz EM, Bae K, Hanks GE, Porter A, Grignon DJ, Brereton HD, Venkatesan V, Lawton CA, Rosenthal SA, Sandler HM, Shipley WU. Ten-year follow-up of radiation therapy oncology group protocol 92-02: a phase III trial of the duration of elective androgen deprivation in locally advanced prostate cancer. J Clin Oncol. 2008 May 20;26(15):2497-504. Epub 2008 Apr 14. link to original article contains verified protocol PubMed
- Update: Lawton CAF, Lin X, Hanks GE, Lepor H, Grignon DJ, Brereton HD, Bedi M, Rosenthal SA, Zeitzer KL, Venkatesan VM, Horwitz EM, Pisansky TM, Kim H, Parliament MB, Rabinovitch R, Roach M 3rd, Kwok Y, Dignam JJ, Sandler HM. Duration of androgen deprivation in locally advanced prostate cancer: Long-term update of NRG Oncology RTOG 9202. Int J Radiat Oncol Biol Phys. 2017 Jun 1;98(2):296-303. Epub 2017 Feb 12. PubMed
- Denham JW, Steigler A, Lamb DS, Joseph D, Mameghan H, Turner S, Matthews J, Franklin I, Atkinson C, North J, Poulsen M, Christie D, Spry NA, Tai KH, Wynne C, Duchesne G, Kovacev O, D'Este C; Trans-Tasman Radiation Oncology Group. Short-term androgen deprivation and radiotherapy for locally advanced prostate cancer: results from the Trans-Tasman Radiation Oncology Group 96.01 randomised controlled trial. Lancet Oncol. 2005 Nov;6(11):841-50. link to original article contains protocol PubMed
- D'Amico AV, Chen MH, Renshaw AA, Loffredo M, Kantoff PW. Androgen suppression and radiation vs radiation alone for prostate cancer: a randomized trial. JAMA. 2008 Jan 23;299(3):289-95. link to original article PubMed content property of HemOnc.org
- Jones CU, Hunt D, McGowan DG, Amin MB, Chetner MP, Bruner DW, Leibenhaut MH, Husain SM, Rotman M, Souhami L, Sandler HM, Shipley WU. Radiotherapy and short-term androgen deprivation for localized prostate cancer. N Engl J Med. 2011 Jul 14;365(2):107-18. link to original article contains verified protocol PubMed
Leuprolide, Flutamide, RT
back to top |
RT: Radiation Therapy
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Jones et al. 2011 | Phase III | RT | Seems to have superior OS |
Endocrine & Radiotherapy
- Leuprolide (Lupron) 7.5 mg SC once every 4 weeks x 4 months, to start 2 months prior to radiation therapy
- Flutamide (Eulexin) 250 mg PO three times per day x 4 months, to start 2 months prior to radiation therapy
- Radiation therapy is started 2 months after start of androgen deprivation therapy (ADT), 1.8 to 2 Gy per fraction, with an initial 44 to 46 Gy to the pelvis, then an additional conedown to the prostate that resulted in a total dose of 65 to 70 Gy
References
- Jones CU, Hunt D, McGowan DG, Amin MB, Chetner MP, Bruner DW, Leibenhaut MH, Husain SM, Rotman M, Souhami L, Sandler HM, Shipley WU. Radiotherapy and short-term androgen deprivation for localized prostate cancer. N Engl J Med. 2011 Jul 14;365(2):107-18. link to original article contains verified protocol PubMed
Adjuvant hormonal therapy
Goserelin monotherapy
back to top |
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Hanks et al. 2003 (RTOG 92-02) | Phase III | No further treatment | Seems to have superior OS (*) |
Efficacy based on the 2017 update.
Preceding treatment
Endocrine therapy
- Goserelin (Zoladex) 3.6 mg SC once per month
2-year course
References
- Hanks GE, Pajak TF, Porter A, Grignon D, Brereton H, Venkatesan V, Horwitz EM, Lawton C, Rosenthal SA, Sandler HM, Shipley WU; Radiation Therapy Oncology Group. Phase III trial of long-term adjuvant androgen deprivation after neoadjuvant hormonal cytoreduction and radiotherapy in locally advanced carcinoma of the prostate: the Radiation Therapy Oncology Group Protocol 92-02. J Clin Oncol. 2003 Nov 1;21(21):3972-8. Erratum in: J Clin Oncol. 2004 Jan 15;22(2):386. link to original article contains protocol PubMed
- Update: Horwitz EM, Bae K, Hanks GE, Porter A, Grignon DJ, Brereton HD, Venkatesan V, Lawton CA, Rosenthal SA, Sandler HM, Shipley WU. Ten-year follow-up of radiation therapy oncology group protocol 92-02: a phase III trial of the duration of elective androgen deprivation in locally advanced prostate cancer. J Clin Oncol. 2008 May 20;26(15):2497-504. Epub 2008 Apr 14. link to original article contains verified protocol PubMed
- Update: Lawton CAF, Lin X, Hanks GE, Lepor H, Grignon DJ, Brereton HD, Bedi M, Rosenthal SA, Zeitzer KL, Venkatesan VM, Horwitz EM, Pisansky TM, Kim H, Parliament MB, Rabinovitch R, Roach M 3rd, Kwok Y, Dignam JJ, Sandler HM. Duration of androgen deprivation in locally advanced prostate cancer: Long-term update of NRG Oncology RTOG 9202. Int J Radiat Oncol Biol Phys. 2017 Jun 1;98(2):296-303. Epub 2017 Feb 12. PubMed
Observation
back to top |
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Hanks et al. 2003 (RTOG 92-02) | Phase III | Goserelin | Seems to have inferior OS (*) |
Efficacy based on the 2017 update.
Preceding treatment
References
- Hanks GE, Pajak TF, Porter A, Grignon D, Brereton H, Venkatesan V, Horwitz EM, Lawton C, Rosenthal SA, Sandler HM, Shipley WU; Radiation Therapy Oncology Group. Phase III trial of long-term adjuvant androgen deprivation after neoadjuvant hormonal cytoreduction and radiotherapy in locally advanced carcinoma of the prostate: the Radiation Therapy Oncology Group Protocol 92-02. J Clin Oncol. 2003 Nov 1;21(21):3972-8. Erratum in: J Clin Oncol. 2004 Jan 15;22(2):386. link to original article contains protocol PubMed
- Update: Horwitz EM, Bae K, Hanks GE, Porter A, Grignon DJ, Brereton HD, Venkatesan V, Lawton CA, Rosenthal SA, Sandler HM, Shipley WU. Ten-year follow-up of radiation therapy oncology group protocol 92-02: a phase III trial of the duration of elective androgen deprivation in locally advanced prostate cancer. J Clin Oncol. 2008 May 20;26(15):2497-504. Epub 2008 Apr 14. link to original article contains verified protocol PubMed
- Update: Lawton CAF, Lin X, Hanks GE, Lepor H, Grignon DJ, Brereton HD, Bedi M, Rosenthal SA, Zeitzer KL, Venkatesan VM, Horwitz EM, Pisansky TM, Kim H, Parliament MB, Rabinovitch R, Roach M 3rd, Kwok Y, Dignam JJ, Sandler HM. Duration of androgen deprivation in locally advanced prostate cancer: Long-term update of NRG Oncology RTOG 9202. Int J Radiat Oncol Biol Phys. 2017 Jun 1;98(2):296-303. Epub 2017 Feb 12. PubMed
Hormonal therapy for metastatic or locally advanced disease
ADT & Abiraterone
back to top |
ADT: Androgen Deprivation Therapy
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
James et al. 2017 (STAMPEDE) | Phase III | ADT | Superior OS |
Fizazi et al. 2017 (LATITUDE) | Phase III | ADT | Superior OS |
Endocrine therapy
- Abiraterone (Zytiga) 1000 mg PO once per day
- ADT with ONE of the following:
- LHRH agonist/analogue
- STAMPEDE only: LHRH antagonist
- Bilateral orchiectomy
Supportive medications
- Prevention of mineralocorticoid excess with ONE of the following:
- STAMPEDE except Switzerland: Prednisolone (Millipred) 5 mg PO once per day
- LATITUDE and STAMPEDE in Switzerland: Prednisone (Sterapred) 5 mg PO once per day
- LATITUDE: "dose increase of up to 10 mg/day is permitted to manage refractory mineralocorticoid related toxicities"
Continued until progression unless radiotherapy planned, in which case continued for up to 2 years
References
- James ND, de Bono JS, Spears MR, Clarke NW, Mason MD, Dearnaley DP, Ritchie AWS, Amos CL, Gilson C, Jones RJ, Matheson D, Millman R, Attard G, Chowdhury S, Cross WR, Gillessen S, Parker CC, Russell JM, Berthold DR, Brawley C, Adab F, Aung S, Birtle AJ, Bowen J, Brock S, Chakraborti P, Ferguson C, Gale J, Gray E, Hingorani M, Hoskin PJ, Lester JF, Malik ZI, McKinna F, McPhail N, Money-Kyrle J, O'Sullivan J, Parikh O, Protheroe A, Robinson A, Srihari NN, Thomas C, Wagstaff J, Wylie J, Zarkar A, Parmar MKB, Sydes MR; STAMPEDE Investigators. Abiraterone for prostate cancer not previously treated with hormone therapy. N Engl J Med. 2017 Jul 27;377(4):338-351. Epub 2017 Jun 3. link to original article link to PMC article supplementary protocol contains verified protocol in supplement PubMed
- Fizazi K, Tran N, Fein L, Matsubara N, Rodriguez-Antolin A, Alekseev BY, Özgüroğlu M, Ye D, Feyerabend S, Protheroe A, De Porre P, Kheoh T, Park YC, Todd MB, Chi KN; LATITUDE Investigators. Abiraterone plus prednisone in metastatic, castration-sensitive prostate cancer. N Engl J Med. 2017 Jul 27;377(4):352-360. Epub 2017 Jun 4. link to original article supplementary protocol contains verified protocol in supplement PubMed
ADT & Docetaxel
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ADT: Androgen Deprivation Therapy
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Sweeney et al. 2015 (ECOG E3805) | Phase III | Leuprolide | Superior OS |
Patients already on androgen deprivation therapy were eligible to participate in ECOG E3805 if there was no evidence of disease progression and if they had started ADT no more than 120 days before randomization.
Chemohormonal therapy
- Docetaxel (Taxotere) 75 mg/m2 IV over 1 hour once on day 1
- ADT with one of the following:
- LHRH agonist/analogue
- LHRH antagonist
- Bilateral orchiectomy
- Intermittent hormonal therapy was not allowed. Antiandrogens e.g. bicalutamide were allowed at the start of therapy "at the discretion of the investigator."
Supportive medications
- Dexamethasone (Decadron) 8 mg PO given three times; 12 hours, 3 hours, and 1 hour before Docetaxel (Taxotere)
- Daily prednisone was not required
- At least calcium 500 mg and vitamin D 400 IU PO once per day
21-day cycle for up to 6 cycles
References
- Gravis G, Fizazi K, Joly F, Oudard S, Priou F, Esterni B, Latorzeff I, Delva R, Krakowski I, Laguerre B, Rolland F, Théodore C, Deplanque G, Ferrero JM, Pouessel D, Mourey L, Beuzeboc P, Zanetta S, Habibian M, Berdah JF, Dauba J, Baciuchka M, Platini C, Linassier C, Labourey JL, Machiels JP, El Kouri C, Ravaud A, Suc E, Eymard JC, Hasbini A, Bousquet G, Soulie M. Androgen-deprivation therapy alone or with docetaxel in non-castrate metastatic prostate cancer (GETUG-AFU 15): a randomised, open-label, phase 3 trial. Lancet Oncol. 2013 Feb;14(2):149-58. Epub 2013 Jan 8. link to original article PubMed
- Update: Gravis G, Boher JM, Joly F, Soulié M, Albiges L, Priou F, Latorzeff I, Delva R, Krakowski I, Laguerre B, Rolland F, Théodore C, Deplanque G, Ferrero JM, Culine S, Mourey L, Beuzeboc P, Habibian M, Oudard S, Fizazi K; GETUG. Androgen deprivation therapy (ADT) plus docetaxel versus ADT alone in metastatic non castrate prostate cancer: Impact of metastatic burden and long-term survival analysis of the randomized phase 3 GETUG-AFU15 trial. Eur Urol. 2016 Aug;70(2):256-62. Epub 2015 Nov 21. link to original article PubMed
- Sweeney CJ, Chen YH, Carducci M, Liu G, Jarrard DF, Eisenberger M, Wong YN, Hahn N, Kohli M, Cooney MM, Dreicer R, Vogelzang NJ, Picus J, Shevrin D, Hussain M, Garcia JA, DiPaola RS. Chemohormonal therapy in metastatic hormone-sensitive prostate cancer. N Engl J Med. 2015 Aug 20;373(8):737-46. Epub 2015 Aug 5. link to original article contains verified protocol Pubmed
- James ND, Sydes MR, Clarke NW, Mason MD, Dearnaley DP, Spears MR, Ritchie AW, Parker CC, Russell JM, Attard G, de Bono J, Cross W, Jones RJ, Thalmann G, Amos C, Matheson D, Millman R, Alzouebi M, Beesley S, Birtle AJ, Brock S, Cathomas R, Chakraborti P, Chowdhury S, Cook A, Elliott T, Gale J, Gibbs S, Graham JD, Hetherington J, Hughes R, Laing R, McKinna F, McLaren DB, O'Sullivan JM, Parikh O, Peedell C, Protheroe A, Robinson AJ, Srihari N, Srinivasan R, Staffurth J, Sundar S, Tolan S, Tsang D, Wagstaff J, Parmar MK; STAMPEDE investigators. Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial. Lancet. 2016 Mar 19;387(10024):1163-77. Epub 2015 Dec 21. link to original article link to PMC article PubMed
Bicalutamide monotherapy
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Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Tyrrell et al. 1998 | Phase III | Castration | Not reported |
Not approved for monotherapy in the United States. See combination regimens with Goserelin & Leuprolide.
Endocrine therapy
- Bicalutamide (Casodex) 150 mg PO once per day
References
- Tyrrell CJ, Kaisary AV, Iversen P, Anderson JB, Baert L, Tammela T, Chamberlain M, Webster A, Blackledge G. A randomised comparison of 'Casodex' (bicalutamide) 150 mg monotherapy versus castration in the treatment of metastatic and locally advanced prostate cancer. Eur Urol. 1998;33(5):447-56. contains protocol PubMed
- Update: Iversen P, Tyrrell CJ, Kaisary AV, Anderson JB, Van Poppel H, Tammela TL, Chamberlain M, Carroll K, Melezinek I. Bicalutamide monotherapy compared with castration in patients with nonmetastatic locally advanced prostate cancer: 6.3 years of followup. J Urol. 2000 Nov;164(5):1579-82. link to original article contains verified protocol PubMed
Bicalutamide & Goserelin
back to top |
Regimen #1
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Akaza et al. 2004 | Phase III | Leuprolide | Seems to have superior TTP |
Endocrine therapy
- Bicalutamide (Casodex) 80 mg PO once per day
- Goserelin (Zoladex) 3.6 mg SC once every 4 weeks
Regimen #2
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Schellhammer et al. 1995 (CASODEX Combination Study Group) | Phase III | Bicalutamide & Leuprolide | Not reported |
Flutamide & Goserelin Flutamide & Leuprolide |
Superior TTTF |
Endocrine therapy
- Bicalutamide (Casodex) 50 mg PO once per day
- Goserelin (Zoladex) 3.6 mg SC once every 4 weeks
References
- Schellhammer P, Sharifi R, Block N, Soloway M, Venner P, Patterson AL, Sarosdy M, Vogelzang N, Jones J, Kolvenbag G. A controlled trial of bicalutamide versus flutamide, each in combination with luteinizing hormone-releasing hormone analogue therapy, in patients with advanced prostate cancer. Casodex Combination Study Group. Urology. 1995 May;45(5):745-52. link to original article PubMed
- Update: Schellhammer PF, Sharifi R, Block NL, Soloway MS, Venner PM, Patterson AL, Sarosdy MF, Vogelzang NJ, Chen Y, Kolvenbag GJ. A controlled trial of bicalutamide versus flutamide, each in combination with luteinizing hormone-releasing hormone analogue therapy, in patients with advanced prostate carcinoma. Analysis of time to progression. CASODEX Combination Study Group. Cancer. 1996 Nov 15;78(10):2164-9. link to original article contains protocol PubMed
- Update: Soloway MS, Schellhammer P, Sharifi R, Venner P, Patterson AL, Sarosdy M, Vogelzang N, Jones J, Kolvenbag G. A controlled trial of Casodex (bicalutamide) vs. flutamide, each in combination with luteinising hormone-releasing hormone analogue therapy in patients with advanced prostate cancer. Casodex Combination Study Group. Eur Urol. 1996;29 Suppl 2:105-9. contains protocol PubMed
- Akaza H, Yamaguchi A, Matsuda T, Igawa M, Kumon H, Soeda A, Arai Y, Usami M, Naito S, Kanetake H, Ohashi Y. Superior anti-tumor efficacy of bicalutamide 80 mg in combination with a luteinizing hormone-releasing hormone (LHRH) agonist versus LHRH agonist monotherapy as first-line treatment for advanced prostate cancer: interim results of a randomized study in Japanese patients. Jpn J Clin Oncol. 2004 Jan;34(1):20-8. link to original article contains verified protocol PubMed
Bicalutamide & Leuprolide
back to top |
Regimen #1
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Akaza et al. 2004 | Phase III | Leuprolide | Seems to have superior TTP |
Endocrine therapy
- Bicalutamide (Casodex) 80 mg PO once per day
- Leuprolide (Lupron) 1-month depot 3.75 mg SC once every 4 weeks
Regimen #2
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Schellhammer et al. 1995 (CASODEX Combination Study Group) | Phase III | Bicalutamide & Goserelin | Not reported |
Flutamide & Goserelin Flutamide & Leuprolide |
Superior TTTF |
Endocrine therapy
- Bicalutamide (Casodex) 50 mg PO once per day
- Leuprolide (Lupron) 1-month depot 7.5 mg IM once every 4 weeks
References
- Schellhammer P, Sharifi R, Block N, Soloway M, Venner P, Patterson AL, Sarosdy M, Vogelzang N, Jones J, Kolvenbag G. A controlled trial of bicalutamide versus flutamide, each in combination with luteinizing hormone-releasing hormone analogue therapy, in patients with advanced prostate cancer. Casodex Combination Study Group. Urology. 1995 May;45(5):745-52. link to original article PubMed
- Update: Schellhammer PF, Sharifi R, Block NL, Soloway MS, Venner PM, Patterson AL, Sarosdy MF, Vogelzang NJ, Chen Y, Kolvenbag GJ. A controlled trial of bicalutamide versus flutamide, each in combination with luteinizing hormone-releasing hormone analogue therapy, in patients with advanced prostate carcinoma. Analysis of time to progression. CASODEX Combination Study Group. Cancer. 1996 Nov 15;78(10):2164-9. link to original article contains protocol PubMed
- Update: Soloway MS, Schellhammer P, Sharifi R, Venner P, Patterson AL, Sarosdy M, Vogelzang N, Jones J, Kolvenbag G. A controlled trial of Casodex (bicalutamide) vs. flutamide, each in combination with luteinising hormone-releasing hormone analogue therapy in patients with advanced prostate cancer. Casodex Combination Study Group. Eur Urol. 1996;29 Suppl 2:105-9. contains protocol PubMed
- Akaza H, Yamaguchi A, Matsuda T, Igawa M, Kumon H, Soeda A, Arai Y, Usami M, Naito S, Kanetake H, Ohashi Y. Superior anti-tumor efficacy of bicalutamide 80 mg in combination with a luteinizing hormone-releasing hormone (LHRH) agonist versus LHRH agonist monotherapy as first-line treatment for advanced prostate cancer: interim results of a randomized study in Japanese patients. Jpn J Clin Oncol. 2004 Jan;34(1):20-8. link to original article contains verified protocol PubMed
Degarelix monotherapy
Example orders
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Regimen #1, 240/80
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Klotz et al. 2008 (CS21) | Phase III | Degarelix 240/160 | Non-inferior testosterone suppression |
Leuprolide | Non-inferior testosterone suppression |
This is the recommended dose in package insert.
Endocrine therapy
- Degarelix (Firmagon) 240 mg (given as 2 x 120 mg injections) SC once, then 80 mg SC once every 28 days
Regimen #2, 240/160
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Klotz et al. 2008 (CS21) | Phase III | Degarelix 240/80 | Non-inferior testosterone suppression |
Leuprolide | Non-inferior testosterone suppression |
Endocrine therapy
- Degarelix (Firmagon) 240 mg (given as 2 x 120 mg injections) SC once, then 160 mg SC once every 28 days
References
- Klotz L, Boccon-Gibod L, Shore ND, Andreou C, Persson BE, Cantor P, Jensen JK, Olesen TK, Schröder FH. The efficacy and safety of degarelix: a 12-month, comparative, randomized, open-label, parallel-group phase III study in patients with prostate cancer. BJU Int. 2008 Dec;102(11):1531-8. link to original article contains verified protocol PubMed
- Update: Tombal B, Miller K, Boccon-Gibod L, Schröder F, Shore N, Crawford ED, Moul J, Jensen JK, Kold Olesen T, Persson BE. Additional analysis of the secondary end point of biochemical recurrence rate in a phase 3 trial (CS21) comparing degarelix 80 mg versus leuprolide in prostate cancer patients segmented by baseline characteristics. Eur Urol. 2010 May;57(5):836-42. Epub 2009 Nov 20. link to original article contains verified protocol PubMed
Flutamide monotherapy
back to top |
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Boccon-Gibod et al. 1997 | Phase III | Orchiectomy | Seems not superior |
Fosså et al. 2001 (EORTC) | Phase III | Prednisone | Seems not superior |
Not approved for monotherapy in the United States. See combination regimens with Goserelin & Leuprolide.
Endocrine therapy
- Flutamide (Eulexin) 250 mg PO three times per day
References
- Boccon-Gibod L, Fournier G, Bottet P, Marechal JM, Guiter J, Rischman P, Hubert J, Soret JY, Mangin P, Mallo C, Fraysse CE. Flutamide versus orchidectomy in the treatment of metastatic prostate carcinoma. Eur Urol. 1997;32(4):391-5. contains protocol PubMed
- Eisenberger MA, Blumenstein BA, Crawford ED, Miller G, McLeod DG, Loehrer PJ, Wilding G, Sears K, Culkin DJ, Thompson IM Jr, Bueschen AJ, Lowe BA. Bilateral orchiectomy with or without flutamide for metastatic prostate cancer. N Engl J Med. 1998 Oct 8;339(15):1036-42. link to original article PubMed
- Fosså SD, Slee PH, Brausi M, Horenblas S, Hall RR, Hetherington JW, Aaronson N, de Prijck L, Collette L. Flutamide versus prednisone in patients with prostate cancer symptomatically progressing after androgen-ablative therapy: a phase III study of the European organization for research and treatment of cancer genitourinary group. J Clin Oncol. 2001 Jan 1;19(1):62-71. link to original article contains protocol PubMed
Flutamide & Goserelin
back to top |
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Denis et al. 1993 (EORTC 30853) | Phase III | Bilateral orchiectomy | Seems to have superior OS |
Schellhammer et al. 1995 (CASODEX Combination Study Group) | Phase III | Bicalutamide & Goserelin Bicalutamide & Leuprolide |
Inferior TTTF |
Flutamide & Leuprolide | Not reported |
Endocrine therapy
- Flutamide (Eulexin) 250 mg PO three times per day
- Goserelin (Zoladex) 3.6 mg SC once every 4 weeks
References
- Denis LJ, Carnelro de Moura JL, Bono A, Sylvester R, Whelan P, Newling D, Depauw M. Goserelin acetate and flutamide versus bilateral orchiectomy: a phase III EORTC trial (30853). EORTC GU Group and EORTC Data Center. Urology. 1993 Aug;42(2):119-29; discussion 129-30. contains protocol PubMed
- Update: Denis LJ, Keuppens F, Smith PH, Whelan P, de Moura JL, Newling D, Bono A, Sylvester R. Maximal androgen blockade: final analysis of EORTC phase III trial 30853. EORTC Genito-Urinary Tract Cancer Cooperative Group and the EORTC Data Center. Eur Urol. 1998;33(2):144-51. PubMed
- Schellhammer P, Sharifi R, Block N, Soloway M, Venner P, Patterson AL, Sarosdy M, Vogelzang N, Jones J, Kolvenbag G. A controlled trial of bicalutamide versus flutamide, each in combination with luteinizing hormone-releasing hormone analogue therapy, in patients with advanced prostate cancer. Casodex Combination Study Group. Urology. 1995 May;45(5):745-52. link to original article PubMed
- Update: Schellhammer PF, Sharifi R, Block NL, Soloway MS, Venner PM, Patterson AL, Sarosdy MF, Vogelzang NJ, Chen Y, Kolvenbag GJ. A controlled trial of bicalutamide versus flutamide, each in combination with luteinizing hormone-releasing hormone analogue therapy, in patients with advanced prostate carcinoma. Analysis of time to progression. CASODEX Combination Study Group. Cancer. 1996 Nov 15;78(10):2164-9. link to original article contains protocol PubMed
- Update: Soloway MS, Schellhammer P, Sharifi R, Venner P, Patterson AL, Sarosdy M, Vogelzang N, Jones J, Kolvenbag G. A controlled trial of Casodex (bicalutamide) vs. flutamide, each in combination with luteinising hormone-releasing hormone analogue therapy in patients with advanced prostate cancer. Casodex Combination Study Group. Eur Urol. 1996;29 Suppl 2:105-9. contains protocol PubMed
- Hussain M, Tangen CM, Berry DL, Higano CS, Crawford ED, Liu G, Wilding G, Prescott S, Kanaga Sundaram S, Small EJ, Dawson NA, Donnelly BJ, Venner PM, Vaishampayan UN, Schellhammer PF, Quinn DI, Raghavan D, Ely B, Moinpour CM, Vogelzang NJ, Thompson IM Jr. Intermittent versus continuous androgen deprivation in prostate cancer. N Engl J Med. 2013 Apr 4;368(14):1314-25. link to original article link to PMC article supplementary protocol contains verified protocol in supplementary protocol PubMed
Flutamide & Leuprolide
back to top |
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Schellhammer et al. 1995 (CASODEX Combination Study Group) | Phase III | Bicalutamide & Goserelin Bicalutamide & Leuprolide |
Inferior TTTF |
Flutamide & Goserelin | Not reported |
Endocrine therapy
- Flutamide (Eulexin) 250 mg PO three times per day
- Leuprolide (Lupron) 1-month depot 7.5 mg IM once every 4 weeks
References
- Schellhammer P, Sharifi R, Block N, Soloway M, Venner P, Patterson AL, Sarosdy M, Vogelzang N, Jones J, Kolvenbag G. A controlled trial of bicalutamide versus flutamide, each in combination with luteinizing hormone-releasing hormone analogue therapy, in patients with advanced prostate cancer. Casodex Combination Study Group. Urology. 1995 May;45(5):745-52. link to original article PubMed
- Update: Schellhammer PF, Sharifi R, Block NL, Soloway MS, Venner PM, Patterson AL, Sarosdy MF, Vogelzang NJ, Chen Y, Kolvenbag GJ. A controlled trial of bicalutamide versus flutamide, each in combination with luteinizing hormone-releasing hormone analogue therapy, in patients with advanced prostate carcinoma. Analysis of time to progression. CASODEX Combination Study Group. Cancer. 1996 Nov 15;78(10):2164-9. link to original article contains protocol PubMed
- Update: Soloway MS, Schellhammer P, Sharifi R, Venner P, Patterson AL, Sarosdy M, Vogelzang N, Jones J, Kolvenbag G. A controlled trial of Casodex (bicalutamide) vs. flutamide, each in combination with luteinising hormone-releasing hormone analogue therapy in patients with advanced prostate cancer. Casodex Combination Study Group. Eur Urol. 1996;29 Suppl 2:105-9. contains protocol PubMed
- Hussain M, Tangen CM, Berry DL, Higano CS, Crawford ED, Liu G, Wilding G, Prescott S, Kanaga Sundaram S, Small EJ, Dawson NA, Donnelly BJ, Venner PM, Vaishampayan UN, Schellhammer PF, Quinn DI, Raghavan D, Ely B, Moinpour CM, Vogelzang NJ, Thompson IM Jr. Intermittent versus continuous androgen deprivation in prostate cancer. N Engl J Med. 2013 Apr 4;368(14):1314-25. link to original article link to PMC article supplementary protocol contains verified protocol in supplementary protocol PubMed
Goserelin monotherapy
Example orders
back to top |
Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Soloway et al. 1991 (Zoladex Prostate Study Group) | Phase III | Bilateral orchiectomy | Seems not superior |
Kaisary et al. 1991 | Phase III | Bilateral orchiectomy | Seems not superior |
Endocrine therapy
- Goserelin (Zoladex) 3.6 mg SC once every 4 weeks
References
- Soloway MS, Chodak G, Vogelzang NJ, Block NL, Schellhammer PF, Smith JA Jr, Scott M, Kennealey G, Gau TC. Zoladex versus orchiectomy in treatment of advanced prostate cancer: a randomized trial. Zoladex Prostate Study Group. Urology. 1991 Jan;37(1):46-51. PubMed
- Update: Vogelzang NJ, Chodak GW, Soloway MS, Block NL, Schellhammer PF, Smith JA Jr, Caplan RJ, Kennealey GT. Goserelin versus orchiectomy in the treatment of advanced prostate cancer: final results of a randomized trial. Zoladex Prostate Study Group. Urology. 1995 Aug;46(2):220-6. link to original article contains verified protocol PubMed
- Kaisary AV, Tyrrell CJ, Peeling WB, Griffiths K. Comparison of LHRH analogue (Zoladex) with orchiectomy in patients with metastatic prostatic carcinoma. Br J Urol. 1991 May;67(5):502-8. PubMed
Leuprolide monotherapy
Example orders
back to top |
Regimen #1, 1-month depot, 3.75 mg
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Akaza et al. 2004 | Phase III | Bicalutamide & Goserelin Bicalutamide & Leuprolide |
Seems to have inferior TTP |
Endocrine therapy
- Leuprolide (Lupron) 1-month depot 3.75 mg SC once every 4 weeks
Regimen #2, 1-month depot, 7.5 mg
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Klotz et al. 2008 (CS21) | Phase III | Degarelix 240/80 | Non-inferior testosterone suppression |
Degarelix 240/160 | Non-inferior testosterone suppression |
Endocrine therapy
- Leuprolide (Lupron) 1-month depot 7.5 mg IM once every 4 weeks
Regimen #3, 3-month depot
Study | Evidence |
Sharifi et al. 1996 | Phase II |
Endocrine therapy
- Leuprolide (Lupron) 3-month depot 22.5 mg IM once every 12 weeks
Regimen #4, 4-month depot
Study | Evidence |
Sharifi et al. 1998 | Phase II |
Endocrine therapy
- Leuprolide (Lupron) 4-month depot 30 mg IM once every 16 weeks
Other
- One of the following:
- Leuprolide (Lupron) 6-month depot 45 mg IM once every 24 weeks
- Leuprolide (Lupron) 4-month depot 30 mg IM once every 16 weeks
- Leuprolide (Lupron) 3-month depot 22.5 mg IM once every 12 weeks
- Leuprolide (Lupron) 1-month depot 7.5 mg IM once every 4 weeks
Supportive medications
- (varies depending on reference):
- Bicalutamide (Casodex) 50 mg PO once per day for protection from testosterone flare
References
- Sharifi R, Bruskewitz RC, Gittleman MC, Graham SD Jr, Hudson PB, Stein B. Leuprolide acetate 22.5 mg 12-week depot formulation in the treatment of patients with advanced prostate cancer. Clin Ther. 1996 Jul-Aug;18(4):647-57. link to original article contains verified protocol PubMed
- Sharifi R, Knoll LD, Smith J, Kramolowsky E. Leuprolide acetate (30-mg depot every four months) in the treatment of advanced prostate cancer. Urology. 1998 Feb;51(2):271-6. link to original article PubMed
- Akaza H, Yamaguchi A, Matsuda T, Igawa M, Kumon H, Soeda A, Arai Y, Usami M, Naito S, Kanetake H, Ohashi Y. Superior anti-tumor efficacy of bicalutamide 80 mg in combination with a luteinizing hormone-releasing hormone (LHRH) agonist versus LHRH agonist monotherapy as first-line treatment for advanced prostate cancer: interim results of a randomized study in Japanese patients. Jpn J Clin Oncol. 2004 Jan;34(1):20-8. link to original article contains verified protocol PubMed
- Loblaw DA, Virgo KS, Nam R, Somerfield MR, Ben-Josef E, Mendelson DS, Middleton R, Sharp SA, Smith TJ, Talcott J, Taplin M, Vogelzang NJ, Wade JL 3rd, Bennett CL, Scher HI; American Society of Clinical Oncology. Initial hormonal management of androgen-sensitive metastatic, recurrent, or progressive prostate cancer: 2006 update of an American Society of Clinical Oncology practice guideline. J Clin Oncol. 2007 Apr 20;25(12):1596-605. Epub 2007 Apr 2. link to original article PubMed
- Klotz L, Boccon-Gibod L, Shore ND, Andreou C, Persson BE, Cantor P, Jensen JK, Olesen TK, Schröder FH. The efficacy and safety of degarelix: a 12-month, comparative, randomized, open-label, parallel-group phase III study in patients with prostate cancer. BJU Int. 2008 Dec;102(11):1531-8. link to original article contains verified protocol PubMed
- Update: Tombal B, Miller K, Boccon-Gibod L, Schröder F, Shore N, Crawford ED, Moul J, Jensen JK, Kold Olesen T, Persson BE. Additional analysis of the secondary end point of biochemical recurrence rate in a phase 3 trial (CS21) comparing degarelix 80 mg versus leuprolide in prostate cancer patients segmented by baseline characteristics. Eur Urol. 2010 May;57(5):836-42. Epub 2009 Nov 20. link to original article contains verified protocol PubMed
- Sweeney CJ, Chen YH, Carducci M, Liu G, Jarrard DF, Eisenberger M, Wong YN, Hahn N, Kohli M, Cooney MM, Dreicer R, Vogelzang NJ, Picus J, Shevrin D, Hussain M, Garcia JA, DiPaola RS. Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer. N Engl J Med. 2015 Aug 20;373(8):737-46. Epub 2015 Aug 5. link to original article contains verified protocol Pubmed
Nilutamide & Orchiectomy
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Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Janknegt et al. 1993 (International Anandron Study Group) | Phase III | Orchiectomy | Superior PFS |
Nilutamide to start the day of, or day after surgical castration/orchiectomy.
Endocrine therapy
- Nilutamide (Nilandron) 300 mg PO once per day x 1 month, then 150 mg PO once per day
References
- Janknegt RA, Abbou CC, Bartoletti R, Bernstein-Hahn L, Bracken B, Brisset JM, Da Silva FC, Chisholm G, Crawford ED, Debruyne FM et al. Orchiectomy and nilutamide or placebo as treatment of metastatic prostatic cancer in a multinational double-blind randomized trial. J Urol. 1993 Jan;149(1):77-82; discussion 83. PubMed
- Update: Janknegt RA. Total androgen blockade with the use of orchiectomy and nilutamide (Anandron) or placebo as treatment of metastatic prostate cancer. Anandron International Study Group. Cancer. 1993 Dec 15;72(12 Suppl):3874-7. PubMed
- Update: Dijkman GA, Janknegt RA, De Reijke TM, Debruyne FM. Long-term efficacy and safety of nilutamide plus castration in advanced prostate cancer, and the significance of early prostate specific antigen normalization. International Anandron Study Group. J Urol. 1997 Jul;158(1):160-3. PubMed
- Update: de Reijke T, Derobert E; Anandron /Nilutamide Study Group. Prognostic factor analysis in patients with advanced prostate cancer treated by castration plus anandron or placebo: a final update. Eur Urol. 2002 Aug;42(2):139-46. link to original article contains verified protocol PubMed
- Nilutamide (Nilandron) package insert
Metastatic disease, second-line hormonal therapy
Abiraterone & Prednisone
back to top |
Regimen
Study | Evidence | ORR, PSA RR | Comparator | Comparator ORR, PSA RR | Efficacy | Pt Population |
---|---|---|---|---|---|---|
de Bono et al. 2011 (COU-AA-301) | Phase III | 14% (95% CI n/a), 29% | Prednisone | 3% (95% CI n/a), 6% | Superior OS | Chemo-exposed |
Ryan et al. 2013 (COU-AA-302) | Phase III | 36% (95% CI n/a), 62% | Prednisone | 16% (95% CI n/a), 24% | Seems to have superior OS | Chemo-naive |
Endocrine therapy
- Abiraterone (Zytiga) 1000 mg PO once per day, 1 hour before or 2 hours after meals
- Prednisone (Sterapred) 5 mg PO BID
References
- de Bono JS, Logothetis CJ, Molina A, Fizazi K, North S, Chu L, Chi KN, Jones RJ, Goodman OB Jr, Saad F, Staffurth JN, Mainwaring P, Harland S, Flaig TW, Hutson TE, Cheng T, Patterson H, Hainsworth JD, Ryan CJ, Sternberg CN, Ellard SL, Fléchon A, Saleh M, Scholz M, Efstathiou E, Zivi A, Bianchini D, Loriot Y, Chieffo N, Kheoh T, Haqq CM, Scher HI; COU-AA-301 Investigators. Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med. 2011 May 26;364(21):1995-2005. link to original article contains verified protocol link to PMC article PubMed
- Update: Fizazi K, Scher HI, Molina A, Logothetis CJ, Chi KN, Jones RJ, Staffurth JN, North S, Vogelzang NJ, Saad F, Mainwaring P, Harland S, Goodman OB Jr, Sternberg CN, Li JH, Kheoh T, Haqq CM, de Bono JS; COU-AA-301 Investigators. Abiraterone acetate for treatment of metastatic castration-resistant prostate cancer: final overall survival analysis of the COU-AA-301 randomised, double-blind, placebo-controlled phase 3 study. Lancet Oncol. 2012 Oct;13(10):983-92. Epub 2012 Sep 18. link to original article contains verified protocol PubMed
- Update: Logothetis CJ, Basch E, Molina A, Fizazi K, North SA, Chi KN, Jones RJ, Goodman OB, Mainwaring PN, Sternberg CN, Efstathiou E, Gagnon DD, Rothman M, Hao Y, Liu CS, Kheoh TS, Haqq CM, Scher HI, de Bono JS. Effect of abiraterone acetate and prednisone compared with placebo and prednisone on pain control and skeletal-related events in patients with metastatic castration-resistant prostate cancer: exploratory analysis of data from the COU-AA-301 randomised trial. Lancet Oncol. 2012 Dec;13(12):1210-7. Epub 2012 Nov 9. link to original article contains verified protocol PubMed
- Ryan CJ, Smith MR, de Bono JS, Molina A, Logothetis CJ, de Souza P, Fizazi K, Mainwaring P, Piulats JM, Ng S, Carles J, Mulders PF, Basch E, Small EJ, Saad F, Schrijvers D, Van Poppel H, Mukherjee SD, Suttmann H, Gerritsen WR, Flaig TW, George DJ, Yu EY, Efstathiou E, Pantuck A, Winquist E, Higano CS, Taplin ME, Park Y, Kheoh T, Griffin T, Scher HI, Rathkopf DE; COU-AA-302 Investigators. Abiraterone in metastatic prostate cancer without previous chemotherapy. N Engl J Med. 2013 Jan 10;368(2):138-48. Epub 2012 Dec 10. link to original article contains verified protocol link to PMC article PubMed
- Update: Ryan CJ, Smith MR, Fizazi K, Saad F, Mulders PF, Sternberg CN, Miller K, Logothetis CJ, Shore ND, Small EJ, Carles J, Flaig TW, Taplin ME, Higano CS, de Souza P, de Bono JS, Griffin TW, De Porre P, Yu MK, Park YC, Li J, Kheoh T, Naini V, Molina A, Rathkopf DE; COU-AA-302 Investigators. Abiraterone acetate plus prednisone versus placebo plus prednisone in chemotherapy-naive men with metastatic castration-resistant prostate cancer (COU-AA-302): final overall survival analysis of a randomised, double-blind, placebo-controlled phase 3 study. Lancet Oncol. 2015 Feb;16(2):152-60. Epub 2015 Jan 16. link to original article PubMed
Antiandrogen withdrawal
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Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Small et al. 2004 (CALGB 9583) | Phase III | Ketoconazole & Hydrocortisone | Inferior PSA response |
Refers to cessation of antiandrogen therapy.
References
- Small EJ, Halabi S, Dawson NA, Stadler WM, Rini BI, Picus J, Gable P, Torti FM, Kaplan E, Vogelzang NJ. Antiandrogen withdrawal alone or in combination with ketoconazole in androgen-independent prostate cancer patients: a phase III trial (CALGB 9583). J Clin Oncol. 2004 Mar 15;22(6):1025-33. link to original article contains verified protocol PubMed
Bicalutamide monotherapy
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Regimen
Study | Evidence | ORR, PSA RR | Comparator | Comparator ORR, PSA RR | Efficacy | Pt Population |
---|---|---|---|---|---|---|
Penson et al. 2016 (STRIVE) | Phase II | pts w/ measurable disease: 14% (95% CI n/a), 31% (95% CI n/a) | Enzalutamide | pts w/ measurable disease: 60% (95% CI n/a), 81% (95% CI n/a) | Inferior PFS | Chemo-naive, abi and keto-naive |
Patients continued ADT while on study; details not provided.
Endocrine therapy
- Bicalutamide (Casodex) 50 mg PO once per day
Continued until progression
References
- Penson DF, Armstrong AJ, Concepcion R, Agarwal N, Olsson C, Karsh L, Dunshee C, Wang F, Wu K, Krivoshik A, Phung D, Higano CS. Enzalutamide Versus Bicalutamide in Castration-Resistant Prostate Cancer: The STRIVE Trial. J Clin Oncol. 2016 Jun 20;34(18):2098-106. Epub 2016 Jan 25. link to original article contains protocol PubMed
Enzalutamide monotherapy
back to top |
Regimen
Study | Evidence | ORR, PSA RR | Comparator | Comparator ORR, PSA RR | Efficacy | Pt Population |
---|---|---|---|---|---|---|
Scher et al. 2012 (AFFIRM) | Phase III | 29% (95% CI n/a), 54% | Placebo | 4% (95% CI n/a), 2% | Superior OS | Chemo-exposed (docetaxel) |
Beer et al. 2014 (PREVAIL) | Phase III | 59% (95% CI n/a), 78% | Placebo | 5% (95% CI n/a), 3% | Superior OS | Chemo and abiraterone naive |
Penson et al. 2016 (STRIVE) | Randomized Phase II | 60% (95% CI n/a), 81% | Bicalutamide | 14% (95% CI n/a), 31% | Superior PFS | Chemo and bicalutamide naive |
Patients in STRIVE continued ADT while on study; details not provided.
Endocrine therapy
- Enzalutamide (Xtandi) 160 mg PO once per day
Continued until progression
References
- Scher HI, Fizazi K, Saad F, Taplin ME, Sternberg CN, Miller K, de Wit R, Mulders P, Chi KN, Shore ND, Armstrong AJ, Flaig TW, Fléchon A, Mainwaring P, Fleming M, Hainsworth JD, Hirmand M, Selby B, Seely L, de Bono JS; AFFIRM Investigators. Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med. 2012 Sep 27;367(13):1187-97. Epub 2012 Aug 15. link to original article contains verified protocol PubMed
- Beer TM, Armstrong AJ, Rathkopf DE, Loriot Y, Sternberg CN, Higano CS, Iversen P, Bhattacharya S, Carles J, Chowdhury S, Davis ID, de Bono JS, Evans CP, Fizazi K, Joshua AM, Kim CS, Kimura G, Mainwaring P, Mansbach H, Miller K, Noonberg SB, Perabo F, Phung D, Saad F, Scher HI, Taplin ME, Venner PM, Tombal B; PREVAIL Investigators. Enzalutamide in metastatic prostate cancer before chemotherapy. N Engl J Med. 2014 Jul 31;371(5):424-33. Epub 2014 Jun 1. link to original article link to PMC article PubMed
- Penson DF, Armstrong AJ, Concepcion R, Agarwal N, Olsson C, Karsh L, Dunshee C, Wang F, Wu K, Krivoshik A, Phung D, Higano CS. Enzalutamide versus bicalutamide in castration-resistant prostate cancer: The STRIVE trial. J Clin Oncol. 2016 Jun 20;34(18):2098-106. Epub 2016 Jan 25. link to original article contains protocol PubMed
Ketoconazole & Hydrocortisone
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Regimen
Study | Evidence | ORR, PSA RR | Comparator | Comparator ORR, PSA RR | Efficacy | Pt Population |
---|---|---|---|---|---|---|
Small et al. 2004 (CALGB 9583) | Phase III | pts w/ measurable disease: 20% (95% CI 11 - 32), 27% (95% CI 20 - 35) | Antiandrogen withdrawal | pts w/ measurable disease: 2% (95% CI 0 - 11), 11% (95% CI 7 - 17) | Superior PSA response | Progression at ADT, i.e. CRPC |
Endocrine therapy
- Ketoconazole (Nizoral) 400 mg PO three times per day
- Hydrocortisone (Cortef) 30 mg PO QAM and 10 mg PO QPM
References
- Small EJ, Halabi S, Dawson NA, Stadler WM, Rini BI, Picus J, Gable P, Torti FM, Kaplan E, Vogelzang NJ. Antiandrogen withdrawal alone or in combination with ketoconazole in androgen-independent prostate cancer patients: a phase III trial (CALGB 9583). J Clin Oncol. 2004 Mar 15;22(6):1025-33. link to original article contains verified protocol PubMed
Ketoconazole, Hydrocortisone, Dutasteride
back to top |
Regimen
Study | Evidence |
Taplin et al. 2009 | Phase II |
Endocrine therapy
- Ketoconazole (Nizoral) 400 mg PO three times per day
- Hydrocortisone (Cortef) 30 mg PO QAM and 10 mg PO QPM
- Dutasteride (Avodart) 0.5 mg PO once per day
References
- Taplin ME, Regan MM, Ko YJ, Bubley GJ, Duggan SE, Werner L, Beer TM, Ryan CW, Mathew P, Tu SM, Denmeade SR, Oh WK, Sartor O, Mantzoros CS, Rittmaster R, Kantoff PW, Balk SP. Phase II study of androgen synthesis inhibition with ketoconazole, hydrocortisone, and dutasteride in asymptomatic castration-resistant prostate cancer. Clin Cancer Res. 2009 Nov 15;15(22):7099-105. Epub 2009 Nov 3. link to original article contains verified protocol link to PMC article PubMed
Prednisone monotherapy
back to top |
Regimen #1, 5 mg BID
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
de Bono et al. 2011 (COU-AA-301) | Phase III | Abiraterone & Prednisone | Inferior OS |
Ryan et al. 2013 (COU-AA-302) | Phase III | Abiraterone & Prednisone | Seems to have inferior OS |
Smith et al. 2016 (COMET-1) | Phase III | Cabozantinib | Seems not superior |
Endocrine therapy
- Prednisone (Sterapred) 5 mg PO BID
Continuously
Regimen #2, 5 mg QID
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Fosså et al. 2001 (EORTC) | Phase III | Flutamide | Seems not superior |
Endocrine therapy
- Prednisone (Sterapred) 5 mg PO QID (4 times per day)
Continuously
References
- Tannock IF, Osoba D, Stockler MR, Ernst DS, Neville AJ, Moore MJ, Armitage GR, Wilson JJ, Venner PM, Coppin CM, Murphy KC. Chemotherapy with mitoxantrone plus prednisone or prednisone alone for symptomatic hormone-resistant prostate cancer: a Canadian randomized trial with palliative end points. J Clin Oncol. 1996 Jun;14(6):1756-64. link to original article PubMed
- HRQoL analysis: Osoba D, Tannock IF, Ernst DS, Neville AJ. Health-related quality of life in men with metastatic prostate cancer treated with prednisone alone or mitoxantrone and prednisone. J Clin Oncol. 1999 Jun;17(6):1654-63. link to original article PubMed
- Fosså SD, Slee PH, Brausi M, Horenblas S, Hall RR, Hetherington JW, Aaronson N, de Prijck L, Collette L. Flutamide versus prednisone in patients with prostate cancer symptomatically progressing after androgen-ablative therapy: a phase III study of the European organization for research and treatment of cancer genitourinary group. J Clin Oncol. 2001 Jan 1;19(1):62-71. link to original article contains protocol PubMed
- de Bono JS, Logothetis CJ, Molina A, Fizazi K, North S, Chu L, Chi KN, Jones RJ, Goodman OB Jr, Saad F, Staffurth JN, Mainwaring P, Harland S, Flaig TW, Hutson TE, Cheng T, Patterson H, Hainsworth JD, Ryan CJ, Sternberg CN, Ellard SL, Fléchon A, Saleh M, Scholz M, Efstathiou E, Zivi A, Bianchini D, Loriot Y, Chieffo N, Kheoh T, Haqq CM, Scher HI; COU-AA-301 Investigators. Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med. 2011 May 26;364(21):1995-2005. link to original article contains verified protocol link to PMC article PubMed
- Update: Fizazi K, Scher HI, Molina A, Logothetis CJ, Chi KN, Jones RJ, Staffurth JN, North S, Vogelzang NJ, Saad F, Mainwaring P, Harland S, Goodman OB Jr, Sternberg CN, Li JH, Kheoh T, Haqq CM, de Bono JS; COU-AA-301 Investigators. Abiraterone acetate for treatment of metastatic castration-resistant prostate cancer: final overall survival analysis of the COU-AA-301 randomised, double-blind, placebo-controlled phase 3 study. Lancet Oncol. 2012 Oct;13(10):983-92. Epub 2012 Sep 18. link to original article contains verified protocol PubMed
- Update: Logothetis CJ, Basch E, Molina A, Fizazi K, North SA, Chi KN, Jones RJ, Goodman OB, Mainwaring PN, Sternberg CN, Efstathiou E, Gagnon DD, Rothman M, Hao Y, Liu CS, Kheoh TS, Haqq CM, Scher HI, de Bono JS. Effect of abiraterone acetate and prednisone compared with placebo and prednisone on pain control and skeletal-related events in patients with metastatic castration-resistant prostate cancer: exploratory analysis of data from the COU-AA-301 randomised trial. Lancet Oncol. 2012 Dec;13(12):1210-7. Epub 2012 Nov 9. link to original article contains verified protocol PubMed
- Ryan CJ, Smith MR, de Bono JS, Molina A, Logothetis CJ, de Souza P, Fizazi K, Mainwaring P, Piulats JM, Ng S, Carles J, Mulders PF, Basch E, Small EJ, Saad F, Schrijvers D, Van Poppel H, Mukherjee SD, Suttmann H, Gerritsen WR, Flaig TW, George DJ, Yu EY, Efstathiou E, Pantuck A, Winquist E, Higano CS, Taplin ME, Park Y, Kheoh T, Griffin T, Scher HI, Rathkopf DE; COU-AA-302 Investigators. Abiraterone in metastatic prostate cancer without previous chemotherapy. N Engl J Med. 2013 Jan 10;368(2):138-48. Epub 2012 Dec 10. link to original article contains verified protocol link to PMC article PubMed
- Update: Ryan CJ, Smith MR, Fizazi K, Saad F, Mulders PF, Sternberg CN, Miller K, Logothetis CJ, Shore ND, Small EJ, Carles J, Flaig TW, Taplin ME, Higano CS, de Souza P, de Bono JS, Griffin TW, De Porre P, Yu MK, Park YC, Li J, Kheoh T, Naini V, Molina A, Rathkopf DE; COU-AA-302 Investigators. Abiraterone acetate plus prednisone versus placebo plus prednisone in chemotherapy-naive men with metastatic castration-resistant prostate cancer (COU-AA-302): final overall survival analysis of a randomised, double-blind, placebo-controlled phase 3 study. Lancet Oncol. 2015 Feb;16(2):152-60. Epub 2015 Jan 16. link to SD article PubMed
- Smith M, De Bono J, Sternberg C, Le Moulec S, Oudard S, De Giorgi U, Krainer M, Bergman A, Hoelzer W, De Wit R, Bögemann M, Saad F, Cruciani G, Thiery-Vuillemin A, Feyerabend S, Miller K, Houédé N, Hussain S, Lam E, Polikoff J, Stenzl A, Mainwaring P, Ramies D, Hessel C, Weitzman A, Fizazi K. Phase III study of cabozantinib in previously treated metastatic castration-resistant prostate cancer: COMET-1. J Clin Oncol. 2016 Sep 1;34(25):3005-13. Epub 2016 Jul 11. link to original article contains verified protocol PubMed
Chemotherapy for metastatic castrate-resistant disease
Cabazitaxel & Prednisone
back to top |
Example orders
Regimen #1, 20 mg/m2
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Oudard et al. 2017 (FIRSTANA) | Phase III | Cabazitaxel 25 mg/m2 & Prednisone | Seems not superior |
Docetaxel & Prednisone | Seems not superior | ||
Eisenberger et al. 2017 (PROSELICA) | Phase III | Cabazitaxel 25 mg/m2 & Prednisone | Non-inferior OS |
Chemotherapy
- Cabazitaxel (Jevtana) 20 mg/m2 IV once on day 1
- Prednisone (Sterapred) 10 mg PO once per day
21-day cycles
Regimen #2, 25 mg/m2
Study | Evidence | ORR, PSA RR | Comparator | Comparator ORR, PSA RR | Efficacy | Pt Population |
---|---|---|---|---|---|---|
de Bono et al. 2010 (TROPIC) | Phase III | 14% (95% CI 10-19) 39% (95% CI 34-44) (*) |
Mitoxantrone & Prednisone | 4% (95% CI 2-7) 18% (95% CI 14-22) (*) |
Superior OS | Progressed on docetaxel |
Oudard et al. 2017 (FIRSTANA) | Phase III | Cabazitaxel 20 mg/m2 & Prednisone | Seems not superior | |||
Docetaxel & Prednisone | Seems not superior | |||||
Eisenberger et al. 2017 (PROSELICA) | Phase III | Cabazitaxel 20 mg/m2 & Prednisone | Non-inferior OS | |||
Beer et al. 2017 (AFFINITY) | Phase III | Cabazitaxel, Prednisone, Custirsen | Seems not superior | Progressed on docetaxel |
Note: ORRs in TROPIC were only reported for patients with measurable disease.
Chemotherapy
- Cabazitaxel (Jevtana) 25 mg/m2 IV over 1 hour once on day 1
- Prednisone (Sterapred) 10 mg PO once per day
Supportive medications
- Antihistamine given at least 30 minutes before Cabazitaxel (Jevtana)
- Corticosteroid (dexamethasone 8 mg or equivalent) given at least 30 minutes before Cabazitaxel (Jevtana)
- Histamine H2-antagonist (except cimetidine) given at least 30 minutes before Cabazitaxel (Jevtana)
21-day cycle for up to 10 cycles (TROPIC) or until progression (PROSELICA)
References
- de Bono JS, Oudard S, Ozguroglu M, Hansen S, Machiels JP, Kocak I, Gravis G, Bodrogi I, Mackenzie MJ, Shen L, Roessner M, Gupta S, Sartor AO; TROPIC Investigators. Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial. Lancet. 2010 Oct 2;376(9747):1147-54. link to original article contains verified protocol PubMed
- Oudard S, Fizazi K, Sengeløv L, Daugaard G, Saad F, Hansen S, Hjälm-Eriksson M, Jassem J, Thiery-Vuillemin A, Caffo O, Castellano D, Mainwaring PN, Bernard J, Shen L, Chadjaa M, Sartor O. Cabazitaxel versus docetaxel as first-line therapy for patients with metastatic castration-resistant prostate cancer: A randomized phase III Trial-FIRSTANA. J Clin Oncol. 2017 Oct 1;35(28):3189-3197. Epub 2017 Jul 28. link to original article contains verified protocol PubMed
- Eisenberger M, Hardy-Bessard AC, Kim CS, Géczi L, Ford D, Mourey L, Carles J, Parente P, Font A, Kacso G, Chadjaa M, Zhang W, Bernard J, de Bono J. Phase III study comparing a reduced dose of cabazitaxel (20 mg/m(2)) and the currently approved dose (25 mg/m(2)) in postdocetaxel patients with metastatic castration-resistant prostate cancer-PROSELICA. J Clin Oncol. 2017 Oct 1;35(28):3198-3206. Epub 2017 Aug 15 link to original article contains verified protocol in supplement PubMed
- Beer TM, Hotte SJ, Saad F, Alekseev B, Matveev V, Fléchon A, Gravis G, Joly F, Chi KN, Malik Z, Blumenstein B, Stewart PS, Jacobs CA, Fizazi K. Custirsen (OGX-011) combined with cabazitaxel and prednisone versus cabazitaxel and prednisone alone in patients with metastatic castration-resistant prostate cancer previously treated with docetaxel (AFFINITY): a randomised, open-label, international, phase 3 trial. Lancet Oncol. 2017 Nov;18(11):1532-1542. Epub 2017 Oct 9. link to original article PubMed
Cabozantinib monotherapy
back to top |
Regimen #1
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Smith et al. 2016 (COMET-1) | Phase III | Prednisone | Seems not superior |
Chemotherapy
- Cabozantinib (Cometriq) 60 mg PO once per day
Regimen #2
Study | Evidence |
Smith et al. 2012 | Phase II |
Chemotherapy
- Cabozantinib (Cometriq) 100 mg PO once per day
References
- Smith DC, Smith MR, Sweeney C, Elfiky AA, Logothetis C, Corn PG, Vogelzang NJ, Small EJ, Harzstark AL, Gordon MS, Vaishampayan UN, Haas NB, Spira AI, Lara PN Jr, Lin CC, Srinivas S, Sella A, Schöffski P, Scheffold C, Weitzman AL, Hussain M. Cabozantinib in patients with advanced prostate cancer: results of a phase II randomized discontinuation trial. J Clin Oncol. 2013 Feb 1;31(4):412-9. Epub 2012 Nov 19. link to original article contains verified protocol link to PMC article PubMed
- Smith M, De Bono J, Sternberg C, Le Moulec S, Oudard S, De Giorgi U, Krainer M, Bergman A, Hoelzer W, De Wit R, Bögemann M, Saad F, Cruciani G, Thiery-Vuillemin A, Feyerabend S, Miller K, Houédé N, Hussain S, Lam E, Polikoff J, Stenzl A, Mainwaring P, Ramies D, Hessel C, Weitzman A, Fizazi K. Phase III study of cabozantinib in previously treated metastatic castration-resistant prostate cancer: COMET-1. J Clin Oncol. 2016 Sep 1;34(25):3005-13. Epub 2016 Jul 11. link to original article contains verified protocol PubMed
Carboplatin & Docetaxel
back to top |
Example orders
Regimen #1
Study | Evidence |
Ross et al. 2008 | Phase II |
Patients enrolled in the trial had hormone-refractory prostate cancer and progression of disease during docetaxel treatment or within 45 days of stopping docetaxel treatment.
Chemotherapy
- Carboplatin (Paraplatin) AUC 4 (Calvert formula) IV over 1 hour once on day 1, given second
- Docetaxel (Taxotere) 60 mg/m2 IV over 1 hour once on day 1, given first
Supportive medications
- "Standard dexamethasone premedication was used"
- Patients continued to receive androgen deprivation therapy
21-day cycles, given until progression of disease or unacceptable toxicity
Regimen #2, weekly docetaxel
Study | Evidence |
Reuter et al. 2010 | Phase II |
Patients enrolled in the trial had progression of disease on docetaxel chemotherapy and castration-resistant disease.
Chemotherapy
- Carboplatin (Paraplatin) AUC 5 IV over 30 minutes once on day 1
- Docetaxel (Taxotere) 35 mg/m2 IV over 1 hour once per day on days 1, 8, 15
- Note: In contrast to its abstract, Reuter et al. 2010 sometimes used "days 1, 8, (15)" to describe when docetaxel was given. The paper did not specifically say what "(15)" meant, such as whether this meant that the day 15 dose was optional.
- Prednisone (Sterapred) 5 mg PO BID on days 1 to 28
Supportive medications
- "Standard dexamethasone premedication was used"
- Patients continued to receive LHRH (luteinizing hormone releasing hormone) agonists
- No routine use of granulocyte colony-stimulating factor (G-CSF)
28-day cycles, given until progression of disease or unacceptable toxicity
References
- Ross RW, Beer TM, Jacobus S, Bubley GJ, Taplin ME, Ryan CW, Huang J, Oh WK; Prostate Cancer Clinical Trials Consortium. A phase 2 study of carboplatin plus docetaxel in men with metastatic hormone-refractory prostate cancer who are refractory to docetaxel. Cancer. 2008 Feb 1;112(3):521-6. link to original article contains verified protocol PubMed
- Nakabayashi M, Sartor O, Jacobus S, Regan MM, McKearn D, Ross RW, Kantoff PW, Taplin ME, Oh WK. Response to docetaxel/carboplatin-based chemotherapy as first- and second-line therapy in patients with metastatic hormone-refractory prostate cancer. BJU Int. 2008 Feb;101(3):308-12. link to original article PubMed
- Reuter CW, Morgan MA, Ivanyi P, Fenner M, Ganser A, Grünwald V. Carboplatin plus weekly docetaxel as salvage chemotherapy in docetaxel-resistant and castration-resistant prostate cancer. World J Urol. 2010 Jun;28(3):391-8. Epub 2010 Mar 14. link to original article contains verified protocol PubMed
Carboplatin & Paclitaxel
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Regimen #1
Study | Evidence |
Kentepozidis et al. 2012 | Phase II |
Chemotherapy
- Carboplatin (Paraplatin) AUC 3 (Calvert formula) IV once per day on days 1 & 15, given second
- Paclitaxel (Taxol) 135 mg/m2 IV over 1 hour once per day on days 1 & 15, given first
Supportive medications
- "All patients received a concomitant anti-emetic prophylaxis"
- Dexamethasone (Decadron) 20 mg PO given twice, 12 and 6 hours prior to Paclitaxel (Taxol)
- Diphenhydramine (Benadryl) 50 mg IV once "prior to each dose" (there was nothing else after this in Kentepozidis et al. 2012, and it is assumed to mean prior to each dose of Paclitaxel (Taxol))
- Cimetidine (Tagamet) 300 mg IV once "prior to each dose" (there was nothing else after this in Kentepozidis et al. 2012, and it is assumed to mean prior to each dose of Paclitaxel (Taxol))
- No prophylactic G-CSF
28-day cycles, given until progression of disease or unacceptable toxicity
Regimen #2
Study | Evidence |
Jeske et al. 2010 | Retrospective |
Chemotherapy
- Carboplatin (Paraplatin) AUC 4 to 6 IV once on day 1
- Paclitaxel (Taxol) 60 to 80 mg/m2 IV once per day on days 1, 8, 15
28-day cycles, given until progression of disease or unacceptable toxicity
References
- Jeske S, Tagawa ST, Olowokure O, Selzer J, Giannakakou P, Nanus DM. Carboplatin plus paclitaxel therapy after docetaxel in men with metastatic castrate resistant prostate cancer. Urol Oncol. 2011 Nov-Dec;29(6):676-81. Epub 2010 May 7. link to original article contains verified protocol PubMed
- Kentepozidis N, Soultati A, Giassas S, Vardakis N, Kalykaki A, Kotsakis A, Papadimitraki E, Pantazopoulos N, Bozionellou V, Georgoulias V. Paclitaxel in combination with carboplatin as salvage treatment in patients with castration-resistant prostate cancer: a Hellenic oncology research group multicenter phase II study. Cancer Chemother Pharmacol. 2012 Jul;70(1):161-8. Epub 2012 Jun 3. link to original article contains verified protocol PubMed
CMF
CMF: Cyclophosphamide, Methotrexate, Five-FU
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Regimen
Study | Evidence |
Wozniak et al. 1993 | Phase II |
This regimen is "minimally active in hormone-refractory metastatic prostate cancer" per Wozniak et al. 1993 and is included for historical reference only.
Chemotherapy
- Cyclophosphamide (Cytoxan) 100 mg/m2 PO once per day on days 1 to 7
- Methotrexate (MTX) 15 mg/m2 IV once on day 1
- Fluorouracil (5-FU) 300 mg/m2 IV once on day 1
7-day cycles, given until progression of disease or unacceptable toxicity
References
- Wozniak AJ, Blumenstein BA, Crawford ED, Boileau M, Rivkin SE, Fletcher WS. Cyclophosphamide, methotrexate, and 5-fluorouracil in the treatment of metastatic prostate cancer. A Southwest Oncology Group study. Cancer. 1993 Jun 15;71(12):3975-8. link to original article contains verified protocol PubMed
Cyclophosphamide, Prednisone, Diethylstilbestrol
CPD: Cyclophosphamide, Prednisone, Diethylstilbestrol
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Regimen
Study | Evidence | Efficacy |
---|---|---|
Hellerstedt et al. 2003 | Phase II | 50% or greater decline in PSA: 42% |
Chemotherapy
- Cyclophosphamide (Cytoxan) 100 mg PO once per day on days 1 to 20
- Prednisone (Sterapred) 10 mg PO once per day on days 1 to 30
- Diethylstilbestrol (DES) 1 mg PO once per day on days 1 to 30
Supportive medications
- Warfarin (Coumadin) 1 mg PO once per day to decrease risk of DVT
30-day cycles, given until progression of disease or unacceptable toxicity
References
- Hellerstedt B, Pienta KJ, Redman BG, Esper P, Dunn R, Fardig J, Olson K, Smith DC. Phase II trial of oral cyclophosphamide, prednisone, and diethylstilbestrol for androgen-independent prostate carcinoma. Cancer. 2003 Oct 15;98(8):1603-10. link to original article contains verified protocol PubMed
Docetaxel & Prednisone
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Example orders
Regimen #1, every 3-weeks schedule, indefinite, with prednisone
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Tannock et al. 2013 (VENICE) | Phase III | Docetaxel, Prednisone, Dasatinib | Seems not superior |
Araujo et al. 2013 (READY) | Phase III | Docetaxel, Prednisone, Dasatinib | Seems not superior |
Petrylak et al. 2015 (MAINSAIL) | Phase III | Docetaxel, Prednisone, Lenalidomide | Superior OS |
Chi et al. 2017 (SYNERGY) | Phase III | Docetaxel, Prednisone, Custirsen | Seems not superior |
Oudard et al. 2017 (FIRSTANA) | Phase III | Cabazitaxel 20 mg/m2 & Prednisone | Seems not superior |
Cabazitaxel 25 mg/m2 & Prednisone | Seems not superior |
Chemotherapy
- Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
- Prednisone (Sterapred) 10 mg/day PO
- Some regimens give as 5 mg PO BID, some as 10 mg PO once per day
21-day cycles, given until progression of disease or unacceptable toxicity
Regimen #2, every 3-weeks schedule, indefinite, with prednisolone
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Kellokumpu-Lehtinen et al. 2013 (PROSTY) | Phase III | Every 2-weeks Docetaxel & Prednisone | Seems to have inferior TTTF |
Chemotherapy
- Docetaxel (Taxotere) 75 mg/m2 IV over 60 minutes once on day 1
- Prednisolone (Millipred) 10 mg PO once per day
Supportive medications
- Dexamethasone (Decadron) 7.5 to 8 mg daily, started 1 day before Docetaxel (Taxotere) and stopped 1 to 2 days after docetaxel infusion (in other words, from day -1 to day 2 or 3); reference did not specify route of administration
- G-CSF not recommended unless patients developed febrile neutropenia or severe infection
- "Treatment with bisphosphonates, erythropoietin, and palliative radiation therapy was allowed"
21-day cycles, given until progression of disease or unacceptable toxicity
Regimen #3, every 3-weeks schedule, limited duration
Study | Evidence | ORR, PSA RR | Comparator | Comparator ORR, PSA RR | Efficacy | Pt Population |
---|---|---|---|---|---|---|
Tannock et al. 2004 (TAX 327) | Phase III | pts w/ measurable disease:12% (95% CI 7-19), 45% (95% CI 40-51) | Weekly Docetaxel & Prednisone | pts w/ measurable disease:8% (95% CI 4-14), 48% (95% CI 42-54) | Not reported | Chemo-naive |
Mitoxantrone & Prednisone | pts w/ measurable disease:7% (95% CI 3-12), 32% (95% CI 26-37) | Superior OS | Chemo-naive |
Chemotherapy
- Docetaxel (Taxotere) 75 mg/m2 IV over 1 hour once on day 1
- Prednisone (Sterapred) 5 mg PO BID
Supportive medications
- Dexamethasone (Decadron) 8 mg (route not specified) given three times; 12 hours, 3 hours, and 1 hour before Docetaxel (Taxotere)
- Antiemetics "according to local practice"
21-day cycle for up to 10 cycles
Regimen #4, weekly schedule
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Tannock et al. 2004 (TAX 327) | Phase III | Every 3-week Docetaxel & Prednisone | Not reported |
Mitoxantrone & Prednisone | Seems not superior |
Chemotherapy
- Docetaxel (Taxotere) 30 mg/m2 IV over 30 minutes once per day on days 1, 8, 15, 22, 29
- Prednisone (Sterapred) 5 mg PO BID
Supportive medications
- Dexamethasone (Decadron) 8 mg (route not specified) once 1 hour before Docetaxel (Taxotere)
- Antiemetics "according to local practice"
42-day cycle for up to 5 cycles
Regimen #5, bi-weekly
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Kellokumpu-Lehtinen et al. 2013 (PROSTY | Phase III | Every 3-weeks Docetaxel & Prednisone | Seems to have superior TTTF |
Chemotherapy
- Docetaxel (Taxotere) 50 mg/m2 IV over 60 minutes once per day on days 1 & 15
- Prednisolone (Millipred) 10 mg PO once per day
Supportive medications
- Dexamethasone (Decadron) 7.5 to 8 mg once per day, started 1 day before Docetaxel (Taxotere) and stopped 1 to 2 days after docetaxel infusion (in other words, from day -1 to day 2 or 3); reference did not specify route of administration
- G-CSF not recommended unless patients developed febrile neutropenia or severe infection
- "Treatment with bisphosphonates, erythropoietin, and palliative radiation therapy was allowed"
28-day cycles, given until progression of disease or unacceptable toxicity
References
- Tannock IF, de Wit R, Berry WR, Horti J, Pluzanska A, Chi KN, Oudard S, Théodore C, James ND, Turesson I, Rosenthal MA, Eisenberger MA; TAX 327 Investigators. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med. 2004 Oct 7;351(15):1502-12. link to original article contains verified protocol PubMed
- Update: Berthold DR, Pond GR, Soban F, de Wit R, Eisenberger M, Tannock IF. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer: updated survival in the TAX 327 study. J Clin Oncol. 2008 Jan 10;26(2):242-5. link to original article contains verified protocol PubMed
- Kellokumpu-Lehtinen PL, Harmenberg U, Joensuu T, McDermott R, Hervonen P, Ginman C, Luukkaa M, Nyandoto P, Hemminki A, Nilsson S, McCaffrey J, Asola R, Turpeenniemi-Hujanen T, Laestadius F, Tasmuth T, Sandberg K, Keane M, Lehtinen I, Luukkaala T, Joensuu H; for the PROSTY study group. 2-weekly versus 3-weekly docetaxel to treat castration-resistant advanced prostate cancer: a randomised, phase 3 trial. Lancet Oncol. 2013 Feb;14(2):117-24. Epub 2013 Jan 4. link to original article contains verified protocol PubMed
- Tannock IF, Fizazi K, Ivanov S, Karlsson CT, Fléchon A, Skoneczna I, Orlandi F, Gravis G, Matveev V, Bavbek S, Gil T, Viana L, Arén O, Karyakin O, Elliott T, Birtle A, Magherini E, Hatteville L, Petrylak D, Tombal B, Rosenthal M; VENICE investigators. Aflibercept versus placebo in combination with docetaxel and prednisone for treatment of men with metastatic castration-resistant prostate cancer (VENICE): a phase 3, double-blind randomised trial. Lancet Oncol. 2013 Jul;14(8):760-8. Epub 2013 Jun 4.link to original article contains protocol PubMed
- Araujo JC, Trudel GC, Saad F, Armstrong AJ, Yu EY, Bellmunt J, Wilding G, McCaffrey J, Serrano SV, Matveev VB, Efstathiou E, Oudard S, Morris MJ, Sizer B, Goebell PJ, Heidenreich A, de Bono JS, Begbie S, Hong JH, Richardet E, Gallardo E, Paliwal P, Durham S, Cheng S, Logothetis CJ. Docetaxel and dasatinib or placebo in men with metastatic castration-resistant prostate cancer (READY): a randomised, double-blind phase 3 trial. Lancet Oncol. 2013 Dec;14(13):1307-16. Epub 2013 Nov 8. link to original article contains protocol link to PMC article PubMed
- Petrylak DP, Vogelzang NJ, Budnik N, Wiechno PJ, Sternberg CN, Doner K, Bellmunt J, Burke JM, de Olza MO, Choudhury A, Gschwend JE, Kopyltsov E, Flechon A, Van As N, Houede N, Barton D, Fandi A, Jungnelius U, Li S, de Wit R, Fizazi K. Docetaxel and prednisone with or without lenalidomide in chemotherapy-naive patients with metastatic castration-resistant prostate cancer (MAINSAIL): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet Oncol. 2015 Apr;16(4):417-25. Epub 2015 Mar 3.link to original article contains protocol PubMed
- Chi KN, Higano CS, Blumenstein B, Ferrero JM, Reeves J, Feyerabend S, Gravis G, Merseburger AS, Stenzl A, Bergman AM, Mukherjee SD, Zalewski P, Saad F, Jacobs C, Gleave M, de Bono JS. Custirsen in combination with docetaxel and prednisone for patients with metastatic castration-resistant prostate cancer (SYNERGY trial): a phase 3, multicentre, open-label, randomised trial. Lancet Oncol. 2017 Apr;18(4):473-485. Epub 2017 Mar 8. link to original article contains protocol PubMed
- Oudard S, Fizazi K, Sengeløv L, Daugaard G, Saad F, Hansen S, Hjälm-Eriksson M, Jassem J, Thiery-Vuillemin A, Caffo O, Castellano D, Mainwaring PN, Bernard J, Shen L, Chadjaa M, Sartor O. Cabazitaxel versus docetaxel as first-line therapy for patients with metastatic castration-resistant prostate cancer: A randomized phase III Trial-FIRSTANA. J Clin Oncol. 2017 Oct 1;35(28):3189-3197. Epub 2017 Jul 28. link to original article contains verified protocol PubMed
Mitoxantrone & Prednisone
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Example orders
Regimen
Study | Evidence | ORR, PSA RR | Comparator | Comparator ORR, PSA RR | Efficacy | Pt Population |
---|---|---|---|---|---|---|
Tannock et al. 2004 (TAX 327) | Phase III | pts w/ measurable disease: 7% (95% CI 3-12), 32% (95% CI 26-37) | Weekly Docetaxel & Prednisone | pts w/ measurable disease: 8% (95% CI 4-14), 48% (95% CI 42-54) | Seems not superior | Chemo naive |
Every 3-week Docetaxel & Prednisone | pts w/ measurable disease: 12% (95% CI 7-19), 45% (95% CI 40-51) | Inferior OS | Chemo naive | |||
Petrylak et al. 2004 (SWOG 99-16) | Phase III | Docetaxel & Estramustine | Seems to have inferior OS | |||
de Bono et al. 2010 (TROPIC) | Phase III | pts w/ measurable disease: 4.4% (95% CI 1.6 - 7.2), 17.8% (95% CI 13.7 - 22.0) |
Cabazitaxel & Prednisone | pts w/ measurable disease: 14.4% (95% CI 9.6 - 19.3), 39.2% (95% CI 33.9 - 44.5) |
Inferior OS | Progressed on docetaxel |
Chemotherapy
- Mitoxantrone (Novantrone) 12 mg/m2 IV over 15 to 30 minutes once on day 1
- Prednisone (Sterapred) 10 mg PO once per day (or 5 mg PO BID) on days 1 to 21
21-day cycle for up to 10 cycles
References
- Tannock IF, Osoba D, Stockler MR, Ernst DS, Neville AJ, Moore MJ, Armitage GR, Wilson JJ, Venner PM, Coppin CM, Murphy KC. Chemotherapy with mitoxantrone plus prednisone or prednisone alone for symptomatic hormone-resistant prostate cancer: a Canadian randomized trial with palliative end points. J Clin Oncol. 1996 Jun;14(6):1756-64. link to original article PubMed
- HRQoL analysis: Osoba D, Tannock IF, Ernst DS, Neville AJ. Health-related quality of life in men with metastatic prostate cancer treated with prednisone alone or mitoxantrone and prednisone. J Clin Oncol. 1999 Jun;17(6):1654-63. link to original article PubMed
- Tannock IF, de Wit R, Berry WR, Horti J, Pluzanska A, Chi KN, Oudard S, Théodore C, James ND, Turesson I, Rosenthal MA, Eisenberger MA; TAX 327 Investigators. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med. 2004 Oct 7;351(15):1502-12. link to original article contains verified protocol PubMed
- Update: Berthold DR, Pond GR, Soban F, de Wit R, Eisenberger M, Tannock IF. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer: updated survival in the TAX 327 study. J Clin Oncol. 2008 Jan 10;26(2):242-5. link to original article contains verified protocol PubMed
- Petrylak DP, Tangen CM, Hussain MH, Lara PN Jr, Jones JA, Taplin ME, Burch PA, Berry D, Moinpour C, Kohli M, Benson MC, Small EJ, Raghavan D, Crawford ED. Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N Engl J Med. 2004 Oct 7;351(15):1513-20. link to original article PubMed
- de Bono JS, Oudard S, Ozguroglu M, Hansen S, Machiels JP, Kocak I, Gravis G, Bodrogi I, Mackenzie MJ, Shen L, Roessner M, Gupta S, Sartor AO; TROPIC Investigators. Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial. Lancet. 2010 Oct 2;376(9747):1147-54. link to original article contains verified protocol PubMed
Olaparib monotherapy
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Regimen
Study | Evidence |
Kaufman et al. 2014 | Phase II, <20 pts in subgroup |
Mateo et al. 2015 (TOPARP-A) | Phase II |
- Patients in Kaufman et al. 2014 had germline BRCA1/2 mutations and had progression on hormonal and one systemic therapy.
- Patients in Mateo et al. 2015 (TOPARP-A) who were found to have homozygous deletions, deleterious mutations, or both in DNA-repair genes were much more likely to respond to olaparib.
Chemotherapy
- Olaparib (Lynparza) 400 mg PO BID
Given until progression of disease or unacceptable toxicity
References
- Kaufman B, Shapira-Frommer R, Schmutzler RK, Audeh MW, Friedlander M, Balmaña J, Mitchell G, Fried G, Stemmer SM, Hubert A, Rosengarten O, Steiner M, Loman N, Bowen K, Fielding A, Domchek SM. Olaparib monotherapy in patients with advanced cancer and a germline BRCA1/2 mutation. J Clin Oncol. 2015 Jan 20;33(3):244-50. Epub 2014 Nov 3. link to original article contains verified protocol PubMed
- Mateo J, Carreira S, Sandhu S, Miranda S, Mossop H, Perez-Lopez R, Nava Rodrigues D, Robinson D, Omlin A, Tunariu N, Boysen G, Porta N, Flohr P, Gillman A, Figueiredo I, Paulding C, Seed G, Jain S, Ralph C, Protheroe A, Hussain S, Jones R, Elliott T, McGovern U, Bianchini D, Goodall J, Zafeiriou Z, Williamson CT, Ferraldeschi R, Riisnaes R, Ebbs B, Fowler G, Roda D, Yuan W, Wu YM, Cao X, Brough R, Pemberton H, A'Hern R, Swain A, Kunju LP, Eeles R, Attard G, Lord CJ, Ashworth A, Rubin MA, Knudsen KE, Feng FY, Chinnaiyan AM, Hall E, de Bono JS. DNA-Repair Defects and Olaparib in Metastatic Prostate Cancer. N Engl J Med. 2015 Oct 29;373(18):1697-708. link to original article contains verified protocol link to PMC article PubMed
Immunotherapy for metastatic castrate-resistant disease
Ipilimumab & RT
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RT: Radiation Therapy
Regimen
Study | Evidence | ORR | Patient population |
Slovin et al. 2013 | Phase I/II | 4% (95% CI n/a), PSA RR: 16%; | Most had ADT, some had docetaxel use. 10 mg/kg cohort reported here. |
Immunoradiotherapy
- Ipilimumab (Yervoy) 10 mg/kg IV over 90 minutes once on day 1
- Lower doses including 3 mg/kg (the FDA approved dose) were investigated, but the 10 mg/kg dose was recommended in this study
- Concurrent radiotherapy given focally at a single dose of 8 Gy per target bone lesion for up to three bone lesions per patient at 24 to 48 h before the first ipilimumab dose.
21-day cycle for 4 cycles
References
- Slovin SF, Higano CS, Hamid O, Tejwani S, Harzstark A, Alumkal JJ, Scher HI, Chin K, Gagnier P, McHenry MB, Beer TM. Ipilimumab alone or in combination with radiotherapy in metastatic castration-resistant prostate cancer: results from an open-label, multicenter phase I/II study. Ann Oncol. 2013 Jul;24(7):1813-21. link to original article contains verified protocol link to PMC article PubMed
Sipuleucel-T monotherapy
Example orders
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Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Kantoff et al. 2010 (IMPACT) | Phase III | Placebo | Seems to have superior OS |
Immunotherapy
- Sipuleucel-T (Provenge): leukapheresis followed 3 days later with at least 50 million autologous CD54+ cells activated with PAP-GM-CSF, to be done on weeks 0, 2, and 4
Supportive medications
- Acetaminophen (Tylenol) PO once 30 minutes before each dose
- Antihistamine PO once 30 minutes before each dose
References
- Kantoff PW, Higano CS, Shore ND, Berger ER, Small EJ, Penson DF, Redfern CH, Ferrari AC, Dreicer R, Sims RB, Xu Y, Frohlich MW, Schellhammer PF; IMPACT Study Investigators. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med. 2010 Jul 29;363(5):411-22. link to original article contains verified protocol PubMed
- Safety analysis: Hall SJ, Klotz L, Pantuck AJ, George DJ, Whitmore JB, Frohlich MW, Sims RB. Integrated safety data from 4 randomized, double-blind, controlled trials of autologous cellular immunotherapy with sipuleucel-T in patients with prostate cancer. J Urol. 2011 Sep;186(3):877-81. Epub 2011 Jul 23. link to original article contains verified protocol PubMed
Radioactive agents for bony metastatic disease
Radium-223 monotherapy
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Regimen #1
Study | Evidence | Comparator | Efficacy | Toxicity |
---|---|---|---|---|
Parker et al. 2013 (ALSYMPCA) | Phase III | Placebo | Superior OS | Superior EQ-5D score |
Radiotherapy
- Radium-223 (Xofigo) 50 kBq/kg IV once on day 1
28-day cycle for 6 cycles
Regimen #2
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Nilsson et al. 2007 | Randomized Phase II | Placebo | Might have superior OS |
Patients in the study had "bone pain needing EBRT" (external beam radiation therapy). Treatment with radium 223 began within 7 days after EBRT.
Radiotherapy
- Radium-223 (Xofigo) 50 kBq/kg IV once on day 1
28-day cycle for 4 cycles
References
- Nilsson S, Franzén L, Parker C, Tyrrell C, Blom R, Tennvall J, Lennernäs B, Petersson U, Johannessen DC, Sokal M, Pigott K, Yachnin J, Garkavij M, Strang P, Harmenberg J, Bolstad B, Bruland OS. Bone-targeted radium-223 in symptomatic, hormone-refractory prostate cancer: a randomised, multicentre, placebo-controlled phase II study. Lancet Oncol. 2007 Jul;8(7):587-94. link to original article contains verified protocol PubMed
- Update: Nilsson S, Franzén L, Parker C, Tyrrell C, Blom R, Tennvall J, Lennernäs B, Petersson U, Johannessen DC, Sokal M, Pigott K, O'Bryan-Tear CG, Thuresson M, Bolstad B, Bruland ØS. Two-year survival follow-up of the randomized, double-blind, placebo-controlled phase II study of radium-223 chloride in patients with castration-resistant prostate cancer and bone metastases. Clin Genitourin Cancer. 2013 Mar;11(1):20-6. Epub 2012 Sep 26. link to original article contains verified protocol PubMed
- Parker C, Nilsson S, Heinrich D, Helle SI, O'Sullivan JM, Fosså SD, Chodacki A, Wiechno P, Logue J, Seke M, Widmark A, Johannessen DC, Hoskin P, Bottomley D, James ND, Solberg A, Syndikus I, Kliment J, Wedel S, Boehmer S, Dall'Oglio M, Franzén L, Coleman R, Vogelzang NJ, O'Bryan-Tear CG, Staudacher K, Garcia-Vargas J, Shan M, Bruland ØS, Sartor O; ALSYMPCA Investigators. Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med. 2013 Jul 18;369(3):213-23. link to original article contains verified protocol PubMed
- Subgroup analysis: Prof Peter Hoskin MD, Prof Oliver Sartor MD, Prof Joe M O'Sullivan MD, Dag Clement Johannessen MD, Svein I Helle MD, John Logue FRCR, David Bottomley FRCR, Prof Sten Nilsson MD, Prof Nicholas J Vogelzang MD, Fang Fang PhD, Mona Wahba MD, Anne-Kirsti Aksnes PhD, Christopher Parker MD. Efficacy and safety of radium-223 dichloride in patients with castration-resistant prostate cancer and symptomatic bone metastases, with or without previous docetaxel use: a prespecified subgroup analysis from the randomised, double-blind, phase 3 ALSYMPCA trial. The Lancet Oncology, Volume 15, Issue 12, Pages 1397 - 1406, November 2014. link to original article
- HRQoL analysis: Nilsson S, Cislo P, Sartor O, Vogelzang NJ, Coleman RE, O'Sullivan JM, Reuning-Scherer J, Shan M, Zhan L, Parker C. Patient-reported quality-of-life analysis of radium-223 dichloride from the phase III ALSYMPCA study. Ann Oncol. 2016 May;27(5):868-74. Epub 2016 Feb 23. link to original article link to PMC article PubMed
Samarium-153 monotherapy
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Regimen
Study | Evidence | Comparator | Efficacy |
---|---|---|---|
Resche et al. 1997 | Phase III | Samarium-153 0.5 mCi/kg | Seems to have superior pain control at week 4 |
Sartor et al. 2004 (Quadramet 424Sm10/11 Study Group) | Phase III | Samarium-152 (non-radioactive) | Seems to have superior pain control at week 4 |
Radiotherapy
- Samarium-153 (Quadramet) 1 mCi/kg IV over 1 minute once on day 1
Supportive medications
- 1000 mL of fluid PO/IV given twice, 4 hours before and 6 hours after treatment
1 dose
References
- Resche I, Chatal JF, Pecking A, Ell P, Duchesne G, Rubens R, Fogelman I, Houston S, Fauser A, Fischer M, Wilkins D. A dose-controlled study of 153Sm-ethylenediaminetetramethylenephosphonate (EDTMP) in the treatment of patients with painful bone metastases. Eur J Cancer. 1997 Sep;33(10):1583-91. link to original article contains verified protocol PubMed
- Sartor O, Reid RH, Hoskin PJ, Quick DP, Ell PJ, Coleman RE, Kotler JA, Freeman LM, Olivier P; Quadramet 424Sm10/11 Study Group. Samarium-153-Lexidronam complex for treatment of painful bone metastases in hormone-refractory prostate cancer. Urology. 2004 May;63(5):940-5. link to original article contains verified protocol PubMed
Measuring disease progression
- Criteria used for disease progression in prostate cancer clinical trials, Prostate Cancer Clinical Trials Working Group 2 (PCWG2):[1]
- Castrate level of serum testosterone is less than 50 ng/dL (less than 1.7 nmol/L)
- However, there is controversy/disagreement in other references about whether a lower level should be used, such as less than 20 ng/dL (0.7 nmol/L)[2]
- PSA rise
- Starting PSA of at least 2.0 ng/mL
- Rising PSA values which are measured at least 1-week apart
- Pretherapy PSA doubling times (PSA-DT) can be estimated if there are at least 3 PSA values measured at least 4 weeks apart
- Bony metastases
- At least 2 new lesions indicates progressive disease
- It is recommended to assess ambiguous results with other imaging modalities such as CT or MRI
- Measurable lesions (RECIST) - this is a lower priority criteria by the PCWG2 because fewer patients have measurable lesions as compared to, for example, bony metastases
- Baseline imaging involves chest imaging with x-ray or CT, CT or MRI of the abdomen/pelvis, and radionuclide bone scan
- It is recommended that local disease is assessed by endorectal MRI or prostatic ultrasound
- Neurologic symptoms should be assessed with MRI of the spine and base of the skull
- Positron emission tomography (PET) is not recommended and is considered investigational
- Measurable lesions should be followed with RECIST criteria
- "Up to 10 visceral and nodal lesions in total should be recorded (with a maximum of five in any one organ)"
- It is suggested that a lymph node must be at least 2 cm in maximal dimension on spiral CT to count as a target lesion.
- Castrate level of serum testosterone is less than 50 ng/dL (less than 1.7 nmol/L)
Statistics
- Four-Year Actuarial Progression-Free Probability (PFP) After Salvage Radiotherapy based on Gleason score, PSA, positive margins, etc.[3] (flowchart is in Figure 2)
- SEER Stat Fact Sheets: Prostate Cancer
- CDC Prostate Cancer Statistics
- Cancer.Net Prostate Cancer Statistics
Links
- Decipher, GenomeDx's genomic prognostic prostate cancer assay
- "the Decipher Test uses the expression of these biomarkers to calculate the probability of clinical metastasis within 5 years of radical prostatectomy surgery, and within 3 years of successive PSA rise (biochemical recurrence)."
- MSKCC prostate cancer nomograms
- MSKCC PSA doubling time calculator
- MSKCC Prostate volume calculator
- Oncotype DX Prostate Genomic Health's Genomic Prostate Score (GPS) & prognostic prostate cancer assay
- Partin tables to predict pathologic stage based on clinical TNM stage, PSA, and Gleason score
- PCA3 RNA urine test
- Prolaris, Myriad's biomarker prognostic prostate cancer assay
- Roswell Park's Calculator for Estimating Overall Life Expectancy and Lifetime Risk for Prostate Cancer Death in Newly Diagnosed Men Managed without Definitive Local Therapy
- UCSF-CAPRA score
Quality of life assessment tools
- EPIC-CP: Expanded Prostate Cancer Index Composite for Clinical Practice (BIDMC)
- AUA Symptom Score (OR) (local backup); AUA Symptom Score (UCF) (local backup). Also known as International Prostate Symptom Score (I-PSS/IPSS) or AUASS
References
- ↑ Scher HI, Halabi S, Tannock I, Morris M, Sternberg CN, Carducci MA, Eisenberger MA, Higano C, Bubley GJ, Dreicer R, Petrylak D, Kantoff P, Basch E, Kelly WK, Figg WD, Small EJ, Beer TM, Wilding G, Martin A, Hussain M; Prostate Cancer Clinical Trials Working Group. Design and end points of clinical trials for patients with progressive prostate cancer and castrate levels of testosterone: recommendations of the Prostate Cancer Clinical Trials Working Group. J Clin Oncol. 2008 Mar 1;26(7):1148-59. link to original article link to PMC article PubMed
- ↑ Oefelein MG, Feng A, Scolieri MJ, Ricchiutti D, Resnick MI. Reassessment of the definition of castrate levels of testosterone: implications for clinical decision making. Urology. 2000 Dec 20;56(6):1021-4. link to original article PubMed
- ↑ Stephenson AJ, Shariat SF, Zelefsky MJ, Kattan MW, Butler EB, Teh BS, Klein EA, Kupelian PA, Roehrborn CG, Pistenmaa DA, Pacholke HD, Liauw SL, Katz MS, Leibel SA, Scardino PT, Slawin KM. Salvage Radiotherapy for Recurrent Prostate Cancer After Radical Prostatectomy. JAMA. 2004 Mar 17;291(11):1325-32. link to original article PubMed