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Page editor		Section editor
	Laura S. Graham, MD University of Colorado Anschutz Medical Campus Aurora, CO, USA LinkedIn		Ali Raza Khaki, MD Stanford University Palo Alto, CA, USA LinkedIn

Are you looking for a regimen, but can't find it here? It is possible that we've moved it to the historical regimens page. For placebo or observational studies in this condition, please visit this page. If you still can't find it, please let us know so we can add it!
Note: many regimens on this page contain androgen deprivation therapy (ADT), which is not further defined by the cited clinical trials. Specific approaches to ADT include pharmacologic and surgical interventions; see individual papers for details.
Note: this page contains regimens for prostate cancer which were not tested in biomarker-specific populations. The following links will take you to biomarker-specific subpages:

Regimens for BRCA-mutated prostate cancer are here.

80 regimens on this page 111 variants on this page

Living Interactive Systematic Reviews

First-line treatment options in metastatic castration-sensitive prostate cancer (mCSPC)

Guidelines

Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.

ASCO

2023: Virgo et al. Initial Management of Noncastrate Advanced, Recurrent, or Metastatic Prostate Cancer: ASCO Guideline Update PubMed
- 2021: Virgo et al. Initial Management of Noncastrate Advanced, Recurrent, or Metastatic Prostate Cancer: ASCO Guideline Update PubMed
- 2018: Morris et al. Optimizing Anticancer Therapy in Metastatic Non-Castrate Prostate Cancer: American Society of Clinical Oncology Clinical Practice Guideline PubMed
2023: Garje et al. Systemic Therapy Update on 177Lutetium-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer: ASCO Guideline Rapid Recommendation Update PubMed
- 2022: Garje et al. Systemic Therapy Update on 177Lutetium-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer: ASCO Rapid Recommendation PubMed
2020: Trabulsi et al. Optimum Imaging Strategies for Advanced Prostate Cancer: ASCO Guideline PubMed
2019: Eggener et al. Molecular Biomarkers in Localized Prostate Cancer: ASCO Guideline PubMed
2017: Virgo et al. Second-Line Hormonal Therapy for Men With Chemotherapy-Naïve, Castration-Resistant Prostate Cancer: American Society of Clinical Oncology Provisional Clinical Opinion PubMed

ASCO & CCO

2014: Basch et al. Systemic Therapy in Men With Metastatic Castration-Resistant Prostate Cancer: American Society of Clinical Oncology and Cancer Care Ontario Clinical Practice Guideline PubMed

AUA

2023: Lowrance et al. Updates to Advanced Prostate Cancer: AUA/SUO Guideline (2023) PubMed
- 2020: Lowrance et al. Advanced Prostate Cancer: AUA/ASTRO/SUO Guideline PART I PubMed

2018: Cookson et al. Castration-Resistant Prostate Cancer: AUA Guideline Amendment 2018 PubMed
- 2015: Lowrance et al. Castration-Resistant Prostate Cancer: AUA Guideline Amendment 2015 PubMed
- 2014: Cookson et al. Castration-resistant prostate cancer: AUA guideline amendment PubMed
- 2013: Cookson et al. Castration-resistant prostate cancer: AUA Guideline PubMed

AUA/ASCO/SUO

2024: Holzbeierlein et al. Treatment of Non-Metastatic Muscle-Invasive Bladder Cancer: AUA/ASCO/SUO GUIDELINE (2017; Amended 2020, 2024) PubMed

ASTRO/ASCO/AUA

2018: Morgan et al. Hypofractionated Radiation Therapy for Localized Prostate Cancer: An ASTRO, ASCO, and AUA Evidence-Based Guideline PubMed

EAU/ESTRO/SIOG

2017: Cornford et al. EAU-ESTRO-SIOG Guidelines on Prostate Cancer. Part II: Treatment of Relapsing, Metastatic, and Castration-Resistant Prostate Cancer PubMed

ESMO

2023: Fizazi et al. Updated treatment recommendations for prostate cancer from the ESMO Clinical Practice Guideline considering treatment intensification and use of novel systemic agents PubMed
- 2020: Parker et al. Prostate cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
- 2015: Parker et al. Cancer of the prostate: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
- 2013: Horwich et al. ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
- 2012: Horwich et al. Prostate cancer: ESMO Consensus Conference Guidelines PubMed
- 2010: Horwich et al. Prostate cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
- 2009: Horwich et al. Prostate cancer: ESMO clinical recommendations for diagnosis, treatment and follow-up PubMed
- 2008: Horwich et al. Prostate cancer: ESMO clinical recommendations for diagnosis, treatment and follow-up PubMed
- 2007: Horwich & Parker. Prostate cancer: ESMO clinical recommendations for diagnosis, treatment and follow-up PubMed
- 2003: Kataja. ESMO Minimum Clinical Recommendations for diagnosis, treatment and follow-up of prostate cancer PubMed
2022: Kanesvaran et al. Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with prostate cancer PubMed

NCCN

NCCN Guidelines - Prostate Cancer
- 2023: Schaeffer et al. Prostate Cancer, Version 4.2023, NCCN Clinical Practice Guidelines in Oncology. PubMed
- 2019: Mohler et al. Prostate Cancer, Version 2.2019, NCCN Clinical Practice Guidelines in Oncology. PubMed
- 2018: Carroll et al. NCCN Guidelines Updates: Prostate Cancer and Prostate Cancer Early Detection. PubMed
- 2016: Mohler et al. Prostate Cancer, Version 1.2016. PubMed
- 2015: Carroll et al. NCCN Clinical Practice Guidelines Prostate Cancer Early Detection, Version 2.2015. PubMed
- 2014: Carroll et al. Prostate cancer early detection, version 1.2014. Featured updates to the NCCN Guidelines. PubMed
- 2014: Mohler et al. Prostate cancer, version 2.2014. PubMed
- 2013: Mohler et al. Prostate cancer, version 1.2014. PubMed
- 2012: Mohler et al. Prostate cancer, Version 3.2012: featured updates to the NCCN guidelines. PubMed
- 2010: Kawachi et al. NCCN clinical practice guidelines in oncology: prostate cancer early detection. PubMed
- 2010: Mohler et al. NCCN clinical practice guidelines in oncology: prostate cancer. PubMed
- 2007: Kawachi et al. [ Prostate cancer early detection. Clinical practice guidelines in oncology.] PubMed
- 2007: Mohler et al. [ Prostate cancer. Clinical practice guidelines in oncology.] PubMed
- 2004: Authors not listed. Prostate cancer early detection. Clinical practice guidelines in oncology. PubMed
- 2004: Authors not listed. Prostate cancer. NCCN clinical practice guidelines in oncology. PubMed
- 2003: Babaian et al. [ Prostate cancer early detection clinical practice guidelines in oncology.] PubMed

SIOG

2019: Boyle et al. Updated recommendations of the International Society of Geriatric Oncology on prostate cancer management in older patients PubMed

SITC

2016: McNeel et al. The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of prostate carcinoma PubMed

St Gallen

2022: Gillessen et al. Management of Patients with Advanced Prostate Cancer. Part I: Intermediate-/High-risk and Locally Advanced Disease, Biochemical Relapse, and Side Effects of Hormonal Treatment: Report of the Advanced Prostate Cancer Consensus Conference 2022 PubMed
- 2022: Gillessen et al. Management of Patients with Advanced Prostate Cancer: Report from the Advanced Prostate Cancer Consensus Conference 2021 PubMed
- 2019: Gillessen et al. Management of Patients with Advanced Prostate Cancer: Report of the Advanced Prostate Cancer Consensus Conference 2019 PubMed
- 2017: Gillessen et al. Management of Patients with Advanced Prostate Cancer: The Report of the Advanced Prostate Cancer Consensus Conference APCCC 2017 PubMed
- 2015: Gillessen et al. Management of patients with advanced prostate cancer: recommendations of the St Gallen Advanced Prostate Cancer Consensus Conference (APCCC) PubMed

Induction ADT

ADT

ADT: Androgen Deprivation Therapy

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Roach et al. 2003 (RTOG 94-13)	1995-1999	Phase 3 (E-switch-ic)	ADT; adjuvant	Did not meet primary endpoint of PFS
Pisansky et al. 2014 (RTOG 9910)	2000-2004	Phase 3 (C)	ADT x 28 weeks	Did not meet primary endpoint of disease-specific mortality

Note: these are clinical trials that did not specify a particular approach to androgen deprivation. See papers for details.

Endocrine therapy

ADT

8-week course

Subsequent treatment

Definitive ADT & RT

References

RTOG 94-13: Roach M 3rd, DeSilvio M, Lawton C, Uhl V, Machtay M, Seider MJ, Rotman M, Jones C, Asbell SO, Valicenti RK, Hahn S, Thomas CR Jr, Shipley WS; Radiation Therapy Oncology Group. Phase III trial comparing whole-pelvic versus prostate-only radiotherapy and neoadjuvant versus adjuvant combined androgen suppression: Radiation Therapy Oncology Group 9413. J Clin Oncol. 2003 May 15;21(10):1904-11. link to original article PubMed NCT00769548
1. Update: Lawton CA, DeSilvio M, Roach M 3rd, Uhl V, Kirsch R, Seider M, Rotman M, Jones C, Asbell S, Valicenti R, Hahn S, Thomas CR Jr. An update of the phase III trial comparing whole pelvic to prostate only radiotherapy and neoadjuvant to adjuvant total androgen suppression: updated analysis of RTOG 94-13, with emphasis on unexpected hormone/radiation interactions. Int J Radiat Oncol Biol Phys. 2007 Nov 1;69(3):646-55. Epub 2007 May 24. link to original article link to PMC article PubMed
RTOG 9910: Pisansky TM, Hunt D, Gomella LG, Amin MB, Balogh AG, Chinn DM, Seider MJ, Duclos M, Rosenthal SA, Bauman GS, Gore EM, Rotman MZ, Lukka HR, Shipley WU, Dignam JJ, Sandler HM. Duration of androgen suppression before radiotherapy for localized prostate cancer: Radiation Therapy Oncology Group randomized clinical trial 9910. J Clin Oncol. 2015 Feb 1;33(4):332-9. Epub 2014 Dec 22. link to original article link to PMC article PubMed NCT00005044

Bicalutamide & Goserelin

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Mason et al. 2012 (FE200486 CS30)	2009-NR	Phase 3 (C)	Degarelix	Non-inferior total prostate volume reduction at week 12

Endocrine therapy

Bicalutamide (Casodex) 50 mg PO once per day on days 0 to 16
Goserelin (Zoladex) 3.6 mg SC once per day on days 3, 31, 59

12-week course

Subsequent treatment

Definitive RT

References

FE200486 CS30: Mason M, Maldonado Pijoan X, Steidle C, Guerif S, Wiegel T, van der Meulen E, Bergqvist PB, Khoo V. Neoadjuvant androgen deprivation therapy for prostate volume reduction, lower urinary tract symptom relief and quality of life improvement in men with intermediate- to high-risk prostate cancer: a randomised non-inferiority trial of degarelix versus goserelin plus bicalutamide. Clin Oncol (R Coll Radiol). 2013 Mar;25(3):190-6. Epub 2012 Dec 17. link to original article contains dosing details in manuscript PubMed NCT00833248

Degarelix monotherapy

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Mason et al. 2012 (FE200486 CS30)	2009-NR	Phase 3 (E-switch-ic)	Bicalutamide & Goserelin	Non-inferior total prostate volume reduction at week 12 (primary endpoint)

Endocrine therapy

Degarelix (Firmagon) 240 mg SC once on day 0, then 80 mg SC once per day on days 28 & 56

12-week course

Subsequent treatment

Definitive RT

References

FE200486 CS30: Mason M, Maldonado Pijoan X, Steidle C, Guerif S, Wiegel T, van der Meulen E, Bergqvist PB, Khoo V. Neoadjuvant androgen deprivation therapy for prostate volume reduction, lower urinary tract symptom relief and quality of life improvement in men with intermediate- to high-risk prostate cancer: a randomised non-inferiority trial of degarelix versus goserelin plus bicalutamide. Clin Oncol (R Coll Radiol). 2013 Mar;25(3):190-6. Epub 2012 Dec 17. link to original article contains dosing details in manuscript PubMed NCT00833248

Flutamide & Goserelin

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Crook et al. 2004	1995-2001	Phase 3 (C)	Flutamide & Goserelin x 8 mo	Did not meet primary endpoint of PSA-PFS

Note: the goserelin dose is not explicitly defined in the manuscript.

Endocrine therapy

Flutamide (Eulexin) 250 mg PO three times per day, started 2 weeks before first dose of goserelin
Goserelin (Zoladex) 3.6 mg SC once on day 1

28-day cycle for 3 cycles

Subsequent treatment

Definitive RT

References

Crook J, Ludgate C, Malone S, Lim J, Perry G, Eapen L, Bowen J, Robertson S, Lockwood G. Report of a multicenter Canadian phase III randomized trial of 3 months vs 8 months neoadjuvant androgen deprivation before standard-dose radiotherapy for clinically localized prostate cancer. Int J Radiat Oncol Biol Phys. 2004 Sep 1;60(1):15-23. link to original article contains partial dosing details in manuscript PubMed
1. Update: Crook J, Ludgate C, Malone S, Perry G, Eapen L, Bowen J, Robertson S, Lockwood G. Final report of multicenter Canadian Phase III randomized trial of 3 versus 8 months of neoadjuvant androgen deprivation therapy before conventional-dose radiotherapy for clinically localized prostate cancer. Int J Radiat Oncol Biol Phys. 2009 Feb 1;73(2):327-33. Epub 2008 Aug 15. link to original article PubMed

Leuprolide monotherapy

Regimen

Study	Dates of enrollment	Evidence
Denham et al. 2014 (RADAR)	2003-2007	Non-randomized part of phase 3 RCT

Note: this trial had 4 arms including a randomization to zoledronic acid; see paper for details.

Endocrine therapy

Leuprolide (Lupron) 3-month depot 22.5 mg IM once on day 1

3-month cycle for 2 cycles

Subsequent treatment

Definitive RT, then adjuvant Leuprolide x 12 mo versus Observation

References

RADAR: Denham JW, Joseph D, Lamb DS, Spry NA, Duchesne G, Matthews J, Atkinson C, Tai KH, Christie D, Kenny L, Turner S, Gogna NK, Diamond T, Delahunt B, Oldmeadow C, Attia J, Steigler A. Short-term androgen suppression and radiotherapy versus intermediate-term androgen suppression and radiotherapy, with or without zoledronic acid, in men with locally advanced prostate cancer (TROG 03.04 RADAR): an open-label, randomised, phase 3 factorial trial. Lancet Oncol. 2014 Sep;15(10):1076-89. Epub 2014 Aug 14. link to original article PubMed NCT00193856
1. Update: Denham JW, Joseph D, Lamb DS, Spry NA, Duchesne G, Matthews J, Atkinson C, Tai KH, Christie D, Kenny L, Turner S, Gogna NK, Diamond T, Delahunt B, Oldmeadow C, Attia J, Steigler A. Short-term androgen suppression and radiotherapy versus intermediate-term androgen suppression and radiotherapy, with or without zoledronic acid, in men with locally advanced prostate cancer (TROG 03.04 RADAR): 10-year results from a randomised, phase 3, factorial trial. Lancet Oncol. 2019 Feb;20(2):267-281. Epub 2018 Dec 19. link to original article PubMed

Definitive therapy, including active surveillance

Active surveillance

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Holmberg et al. 2002 (SPCG-4)	1989-1999	Phase 3 (C)	Radical prostatectomy	Inferior OS¹
Wilt et al. 2012 (PIVOT)	1994-2002	Phase 3 (C)	Radical prostatectomy	Did not meet primary endpoint of OS
Hamdy et al. 2016 (ProtecT)	1999-2009	Phase 3 (C)	1. Prostatectomy 2. RT	Did not meet primary endpoint of OS
Fleshner et al. 2012 (REDEEM)	2006-08-10 to 2007-03-26	Phase 3 (C)	Dutasteride	Inferior TTP
Azzouzi et al. 2016 (CLIN1001 PCM301)	2011-2013	Phase 3 (C)	Padeliporfin	Inferior TTP

¹Reported efficacy for SPCG-4 is based on the 2018 update.
No antineoplastic therapy; consists of various strategies of close monitoring and re-biopsy.

References

SPCG-4: Holmberg L, Bill-Axelson A, Helgesen F, Salo JO, Folmerz P, Häggman M, Andersson SO, Spångberg A, Busch C, Nordling S, Palmgren J, Adami HO, Johansson JE, Norlén BJ; Scandinavian Prostatic Cancer Group. A randomized trial comparing radical prostatectomy with watchful waiting in early prostate cancer. N Engl J Med. 2002 Sep 12;347(11):781-9. link to original article PubMed
1. Update: Bill-Axelson A, Holmberg L, Ruutu M, Häggman M, Andersson SO, Bratell S, Spångberg A, Busch C, Nordling S, Garmo H, Palmgren J, Adami HO, Norlén BJ, Johansson JE; Scandinavian Prostate Cancer Group. Radical prostatectomy versus watchful waiting in early prostate cancer. N Engl J Med. 2005 May 12;352(19):1977-84. link to original article PubMed
2. Update: Bill-Axelson A, Holmberg L, Filén F, Ruutu M, Garmo H, Busch C, Nordling S, Häggman M, Andersson SO, Bratell S, Spångberg A, Palmgren J, Adami HO, Johansson JE; Scandinavian Prostate Cancer Group. Radical prostatectomy versus watchful waiting in localized prostate cancer: the Scandinavian prostate cancer group-4 randomized trial. J Natl Cancer Inst. 2008 Aug 20;100(16):1144-54. Epub 2008 Aug 11. link to original article link to PMC article PubMed
3. Update: Bill-Axelson A, Holmberg L, Ruutu M, Garmo H, Stark JR, Busch C, Nordling S, Häggman M, Andersson SO, Bratell S, Spångberg A, Palmgren J, Steineck G, Adami HO, Johansson JE; SPCG-4 Investigators. Radical prostatectomy versus watchful waiting in early prostate cancer. N Engl J Med. 2011 May 5;364(18):1708-17. link to original article PubMed
4. Update: Bill-Axelson A, Holmberg L, Garmo H, Rider JR, Taari K, Busch C, Nordling S, Häggman M, Andersson SO, Spångberg A, Andrén O, Palmgren J, Steineck G, Adami HO, Johansson JE. Radical prostatectomy or watchful waiting in early prostate cancer. N Engl J Med. 2014 Mar 6;370(10):932-42. link to original article link to PMC article PubMed
5. Update: Bill-Axelson A, Holmberg L, Garmo H, Taari K, Busch C, Nordling S, Häggman M, Andersson SO, Andrén O, Steineck G, Adami HO, Johansson JE. Radical Prostatectomy or Watchful Waiting in Prostate Cancer - 29-Year Follow-up. N Engl J Med. 2018 Dec 13;379(24):2319-2329. link to original article PubMed
REDEEM: Fleshner NE, Lucia MS, Egerdie B, Aaron L, Eure G, Nandy I, Black L, Rittmaster RS. Dutasteride in localised prostate cancer management: the REDEEM randomised, double-blind, placebo-controlled trial. Lancet. 2012 Mar 24;379(9821):1103-11. Epub 2012 Jan 24. link to original article PubMed NCT00363311
PIVOT: Wilt TJ, Brawer MK, Jones KM, Barry MJ, Aronson WJ, Fox S, Gingrich JR, Wei JT, Gilhooly P, Grob BM, Nsouli I, Iyer P, Cartagena R, Snider G, Roehrborn C, Sharifi R, Blank W, Pandya P, Andriole GL, Culkin D, Wheeler T; Prostate Cancer Intervention versus Observation Trial (PIVOT) Study Group. Radical prostatectomy versus observation for localized prostate cancer. N Engl J Med. 2012 Jul 19;367(3):203-13. Erratum in: N Engl J Med. 2012 Aug 9;367(6):582. link to original article link to PMC article PubMed NCT00007644
1. Update: Wilt TJ, Jones KM, Barry MJ, Andriole GL, Culkin D, Wheeler T, Aronson WJ, Brawer MK. Follow-up of prostatectomy versus observation for early prostate cancer. N Engl J Med. 2017 Jul 13;377(2):132-142. link to original article PubMed
ProtecT: Hamdy FC, Donovan JL, Lane JA, Mason M, Metcalfe C, Holding P, Davis M, Peters TJ, Turner EL, Martin RM, Oxley J, Robinson M, Staffurth J, Walsh E, Bollina P, Catto J, Doble A, Doherty A, Gillatt D, Kockelbergh R, Kynaston H, Paul A, Powell P, Prescott S, Rosario DJ, Rowe E, Neal DE; ProtecT Study Group. 10-Year Outcomes after Monitoring, Surgery, or Radiotherapy for Localized Prostate Cancer. N Engl J Med. 2016 Oct 13;375(15):1415-1424. Epub 2016 Sep 14. link to original article PubMed NCT02044172
1. Update: Hamdy FC, Donovan JL, Lane JA, Metcalfe C, Davis M, Turner EL, Martin RM, Young GJ, Walsh EI, Bryant RJ, Bollina P, Doble A, Doherty A, Gillatt D, Gnanapragasam V, Hughes O, Kockelbergh R, Kynaston H, Paul A, Paez E, Powell P, Rosario DJ, Rowe E, Mason M, Catto JWF, Peters TJ, Oxley J, Williams NJ, Staffurth J, Neal DE; ProtecT Study Group. Fifteen-Year Outcomes after Monitoring, Surgery, or Radiotherapy for Prostate Cancer. N Engl J Med. 2023 Apr 27;388(17):1547-1558. Epub 2023 Mar 11. link to original article PubMed
CLIN1001 PCM301: Azzouzi AR, Vincendeau S, Barret E, Cicco A, Kleinclauss F, van der Poel HG, Stief CG, Rassweiler J, Salomon G, Solsona E, Alcaraz A, Tammela TT, Rosario DJ, Gomez-Veiga F, Ahlgren G, Benzaghou F, Gaillac B, Amzal B, Debruyne FM, Fromont G, Gratzke C, Emberton M; PCM301 Study Group. Padeliporfin vascular-targeted photodynamic therapy versus active surveillance in men with low-risk prostate cancer (CLIN1001 PCM301): an open-label, phase 3, randomised controlled trial. Lancet Oncol. 2017 Feb;18(2):181-191. Epub 2016 Dec 20. link to original article PubMed NCT01310894

ADT

ADT: Androgen Deprivation Therapy

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Warde et al. 2011 (NCIC-CTG PR.3/UK MRC PR07)	1995-2005	Phase 3 (C)	ADT & RT	Seems to have inferior OS

Note: these are clinical trials that did not specify a particular approach to androgen deprivation. See papers for details.

Endocrine therapy

ADT

References

NCIC-CTG PR.3/UK MRC PR07: Warde P, Mason M, Ding K, Kirkbride P, Brundage M, Cowan R, Gospodarowicz M, Sanders K, Kostashuk E, Swanson G, Barber J, Hiltz A, Parmar MK, Sathya J, Anderson J, Hayter C, Hetherington J, Sydes MR, Parulekar W; NCIC-CTG; MRC. Combined androgen deprivation therapy and radiation therapy for locally advanced prostate cancer: a randomised, phase 3 trial. Lancet. 2011 Dec 17;378(9809):2104-11. Epub 2011 Nov 2. link to original article link to PMC article PubMed NCT00002633

ADT & RT

ADT & RT: Androgen Deprivation Therapy & Radiation Therapy

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
d'Amico et al. 2004	1995-2001	Phase 3 (E-esc)	RT	Seems to have superior OS (co-primary endpoint) OS60: 88% vs 78% (HR 0.48, 95% CI 0.24-0.98)
Warde et al. 2011 (NCIC-CTG PR.3/UK MRC PR07)	1995-2005	Phase 3 (E-esc)	ADT	Seems to have superior OS (primary endpoint) OS84: 74% vs 66% (HR 0.77, 95% CI 0.61-0.98)
Bolla et al. 2009 (EORTC 22961)	1997-2001	Non-randomized part of phase 3 RCT
Rosenthal et al. 2008 (RTOG 9902)	2000-2004	Non-randomized part of phase 3 RCT
Pisansky et al. 2014 (RTOG 9910)	2000-2004	Non-randomized part of phase 3 RCT
Nabid et al. 2018 (PCS IV)	2000-2008	Non-randomized part of phase 3 RCT
Nabid et al. 2020 (PCS III)	2000-2010	Phase 3 (E-esc)	1. RT	Superior biochemical failure (primary endpoint)
Nabid et al. 2020 (PCS III)	2000-2010	Phase 3 (E-esc)	2. ADT & RT; dose-escalated RT	Did not meet primary endpoint of biochemical failure
Ito et al. 2020	2001-2006	Non-randomized part of phase 3 RCT
Bolla et al. 2016 (EORTC 22991)	2001-2008	Phase 3 (E-esc)	RT	Superior PFS (secondary endpoint) DFS60: 88.7% vs 80.8% (HR 0.63, 95% CI 0.48-0.84)
Malone et al. 2019	2002-2012	Non-randomized part of phase 3 RCT
Zapatero et al. 2015 (DART01/05 GICOR)	2005-2010	Non-randomized part of phase 3 RCT
D'Amico et al. 2021 (DFCI 05-043)	2005-2015	Phase 3 (C)	ADT, Docetaxel, RT	Did not meet primary endpoint of OS
Yorozu et al. 2023 (TRIP)	2010-10 to 2013-03	Non-randomized part of phase 3 RCT

Note: these were clinical trials that did not specify a particular approach for androgen deprivation. See papers for details.

Preceding treatment

RTOG 9902 & DART01/05 GICOR: Induction ADT x 8 weeks
RTOG 9910: Induction ADT x 8 weeks versus ADT x 28 weeks

Endocrine therapy

ADT

Radiotherapy

External beam radiotherapy

8-week course

Subsequent treatment

RTOG 9902: Adjuvant ADT x 2 y versus TEE x 4 followed by ADT x 2 y
EORTC 22961: Adjuvant ADT x 6 months versus ADT x 36 months
DART01/05 GICOR: Adjuvant ADT x 24 months versus no further treatment
PCS IV: Adjuvant ADT x 18 months versus ADT x 36 months

References

D'Amico AV, Manola J, Loffredo M, Renshaw AA, DellaCroce A, Kantoff PW. 6-month androgen suppression plus radiation therapy vs radiation therapy alone for patients with clinically localized prostate cancer: a randomized controlled trial. JAMA. 2004 Aug 18;292(7):821-7. link to original article PubMed
RTOG 9902: Rosenthal SA, Bae K, Pienta KJ, Sobczak ML, Asbell SO, Rajan R, Kerlin KJ, Michalski JM, Sandler HM; Radiation Therapy Oncology Group. Phase III multi-institutional trial of adjuvant chemotherapy with paclitaxel, estramustine, and oral etoposide combined with long-term androgen suppression therapy and radiotherapy versus long-term androgen suppression plus radiotherapy alone for high-risk prostate cancer: preliminary toxicity analysis of RTOG 99-02. Int J Radiat Oncol Biol Phys. 2009 Mar 1;73(3):672-8. Epub 2008 Nov 5. link to original article PubMed NCT00004054
1. Update: Rosenthal SA, Hunt D, Sartor AO, Pienta KJ, Gomella L, Grignon D, Rajan R, Kerlin KJ, Jones CU, Dobelbower M, Shipley WU, Zeitzer K, Hamstra DA, Donavanik V, Rotman M, Hartford AC, Michalski J, Seider M, Kim H, Kuban DA, Moughan J, Sandler H. A phase 3 trial of 2 years of androgen suppression and radiation therapy with or without adjuvant chemotherapy for high-risk prostate cancer: final results of radiation therapy oncology group phase 3 randomized trial NRG Oncology RTOG 9902. Int J Radiat Oncol Biol Phys. 2015 Oct 1;93(2):294-302. Epub 2015 Jul 21. link to original article link to PMC article PubMed
EORTC 22961: Bolla M, de Reijke TM, Van Tienhoven G, Van den Bergh AC, Oddens J, Poortmans PM, Gez E, Kil P, Akdas A, Soete G, Kariakine O, van der Steen-Banasik EM, Musat E, Piérart M, Mauer ME, Collette L; EORTC Radiation Oncology Group; EORTC Genito-Urinary Tract Cancer Group. Duration of androgen suppression in the treatment of prostate cancer. N Engl J Med. 2009 Jun 11;360(24):2516-27. link to original article PubMed NCT00003026
NCIC-CTG PR.3/UK MRC PR07: Warde P, Mason M, Ding K, Kirkbride P, Brundage M, Cowan R, Gospodarowicz M, Sanders K, Kostashuk E, Swanson G, Barber J, Hiltz A, Parmar MK, Sathya J, Anderson J, Hayter C, Hetherington J, Sydes MR, Parulekar W; NCIC; MRC. Combined androgen deprivation therapy and radiation therapy for locally advanced prostate cancer: a randomised, phase 3 trial. Lancet. 2011 Dec 17;378(9809):2104-11. Epub 2011 Nov 2. link to original article link to PMC article PubMed NCT00002633
RTOG 9910: Pisansky TM, Hunt D, Gomella LG, Amin MB, Balogh AG, Chinn DM, Seider MJ, Duclos M, Rosenthal SA, Bauman GS, Gore EM, Rotman MZ, Lukka HR, Shipley WU, Dignam JJ, Sandler HM. Duration of androgen suppression before radiotherapy for localized prostate cancer: Radiation Therapy Oncology Group randomized clinical trial 9910. J Clin Oncol. 2015 Feb 1;33(4):332-9. Epub 2014 Dec 22. link to original article link to PMC article PubMed NCT00005044
DART01/05 GICOR: Zapatero A, Guerrero A, Maldonado X, Alvarez A, Gonzalez San Segundo C, Cabeza Rodríguez MA, Macias V, Pedro Olive A, Casas F, Boladeras A, de Vidales CM, Vazquez de la Torre ML, Villà S, Perez de la Haza A, Calvo FA. High-dose radiotherapy with short-term or long-term androgen deprivation in localised prostate cancer (DART01/05 GICOR): a randomised, controlled, phase 3 trial. Lancet Oncol. 2015 Mar;16(3):320-7. Epub 2015 Feb 19. Erratum in: Lancet Oncol. 2015 Jun;16(6):e262. link to original article PubMed NCT02175212
EORTC 22991: Bolla M, Maingon P, Carrie C, Villa S, Kitsios P, Poortmans PM, Sundar S, van der Steen-Banasik EM, Armstrong J, Bosset JF, Herrera FG, Pieters B, Slot A, Bahl A, Ben-Yosef R, Boehmer D, Scrase C, Renard L, Shash E, Coens C, van den Bergh AC, Collette L. Short androgen suppression and radiation dose escalation for intermediate- and high-risk localized prostate cancer: results of EORTC trial 22991. J Clin Oncol. 2016 May 20;34(15):1748-56. Epub 2016 Mar 14. link to original article PubMed NCT00021450
1. Subgroup analysis: Bolla M, Neven A, Maingon P, Carrie C, Boladeras A, Andreopoulos D, Engelen A, Sundar S, van der Steen-Banasik EM, Armstrong J, Peignaux-Casasnovas K, Boustani J, Herrera FG, Pieters BR, Slot A, Bahl A, Scrase CD, Azria D, Jansa J, O'Sullivan JM, Van Den Bergh ACM, Collette L; EORTC Radiation Oncology Group. Short Androgen Suppression and Radiation Dose Escalation in Prostate Cancer: 12-Year Results of EORTC Trial 22991 in Patients With Localized Intermediate-Risk Disease. J Clin Oncol. 2021 Sep 20;39(27):3022-3033. Epub 2021 Jul 26. link to original article PubMed
PCS IV: Nabid A, Carrier N, Martin AG, Bahary JP, Lemaire C, Vass S, Bahoric B, Archambault R, Vincent F, Bettahar R, Duclos M, Garant MP, Souhami L. Duration of Androgen Deprivation Therapy in High-risk Prostate Cancer: A Randomized Phase III Trial. Eur Urol. 2018 Oct;74(4):432-441. Epub 2018 Jul 3. link to original article PubMed NCT00223171
Malone S, Roy S, Eapen L, E C, MacRae R, Perry G, Bowen J, Samant R, Morgan S, Craig J, Malone K, Grimes S. Sequencing of Androgen-Deprivation Therapy With External-Beam Radiotherapy in Localized Prostate Cancer: A Phase III Randomized Controlled Trial. J Clin Oncol. 2020 Feb 20;38(6):593-601. Epub 2019 Dec 12. Erratum in: J Clin Oncol. 2020 Jun 10;38(17):2005. link to original article link to PMC article PubMed
Ito K, Kobayashi M, Komiyama M, Naito S, Nishimura K, Yonese J, Hashine K, Saito S, Arai G, Shinohara M, Masumori N, Shimizu N, Satoh T, Yamauchi A, Tochigi T, Takezawa Y, Fujimoto H, Yokomizo A, Kakimoto KI, Fukui I, Karasawa K, Tsukamoto T, Nozaki M, Hasumi M, Ishiyama H, Ohtani M, Kuwahara M, Harada M, Ohashi Y, Kotake T, Kakizoe T, Suzuki K, Yamanaka H; National Research Project on Endocrine-Radiation Combination Therapy for Locally Advanced Prostate Cancer Investigators. Oncological outcomes for patients with locally advanced prostate cancer treated with neoadjuvant endocrine and external-beam radiation therapy followed by adjuvant continuous/intermittent endocrine therapy in an open-label, randomized, phase 3 trial. Cancer. 2020 Sep 1;126(17):3961-3971. Epub 2020 Jun 23. link to original article PubMed
PCS III: Nabid A, Carrier N, Vigneault E, Van Nguyen T, Vavassis P, Brassard MA, Bahoric B, Archambault R, Vincent F, Bettahar R, Wilke D, Souhami L. Androgen deprivation therapy and radiotherapy in intermediate-risk prostate cancer: A randomised phase III trial. Eur J Cancer. 2021 Jan;143:64-74. Epub 2020 Dec 3. link to original article PubMed NCT00223145
DFCI 05-043: D'Amico AV, Xie W, McMahon E, Loffredo M, Medeiros S, Joseph D, Denham J, Kumar P, Bubley G, Sullivan M, Hellwig R, Carlos Vera J, Freter R, Jeffrey Baker W, Wong JY, Renshaw AA, Kantoff PW. Radiation and Androgen Deprivation Therapy With or Without Docetaxel in the Management of Nonmetastatic Unfavorable-Risk Prostate Cancer: A Prospective Randomized Trial. J Clin Oncol. 2021 Sep 10;39(26):2938-2947. Epub 2021 Jul 1. link to original article link to PMC article PubMed NCT00116142
TRIP: Yorozu A, Namiki M, Saito S, Egawa S, Yaegashi H, Konaka H, Momma T, Fukagai T, Tanaka N, Ohashi T, Takahashi H, Nakagawa Y, Kikuchi T, Mizokami A, Stone NN. Trimodality Therapy With Iodine-125 Brachytherapy, External Beam Radiation Therapy, and Short- or Long-Term Androgen Deprivation Therapy for High-Risk Localized Prostate Cancer: Results of a Multicenter, Randomized Phase 3 Trial (TRIP/TRIGU0907). Int J Radiat Oncol Biol Phys. 2024 Feb 1;118(2):390-401. Epub 2023 Oct 4. link to original article PubMed UMIN000003992

Flutamide, Goserelin, RT

Flutamide, Goserelin, RT: Flutamide, Goserelin, Radiation Therapy

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Pilepich et al. 1995	1987-1991	Phase 3 (E-RT-esc)	RT	Superior DFS
Pilepich et al. 2001 (RTOG 86-10)	1987-1991	Phase 3 (E-esc)	RT	Seems to have superior cause-specific mortality
Hanks et al. 2003 (RTOG 92-02)	1992-1995	Non-randomized part of phase 3 RCT
Jones et al. 2011 (RTOG 94-08)	1994-2001	Phase 3 (E-esc)	RT	Seems to have superior OS (primary endpoint) OS120: 62% vs 57% (HR 0.85, 95% CI 0.74-0.99)
D'Amico et al. 2008 (DFCI 95-096)	1995-2001	Randomized (E-esc)	RT	Superior OS (primary endpoint) OS96: 74% vs 61% (HR 0.56, 95% CI 0.34-0.91)
Denham et al. 2005 (TROG 96.01)	1996-2000	Phase 3 (E-esc)	1. Flutamide, Goserelin, RT; 6 months of ADT	Not reported
Denham et al. 2005 (TROG 96.01)	1996-2000	Phase 3 (E-esc)	2. RT	Superior EFS (secondary endpoint)

Endocrine therapy

Flutamide (Eulexin) 250 mg PO three times per day on days 1 to 28
Goserelin (Zoladex) 3.6 mg SC once on day 1

28-day cycles, starting 2 months prior to radiation therapy and continuing at least through the end of radiation therapy

Radiotherapy

External beam radiotherapy is started 2 months after start of androgen deprivation therapy (ADT), 1.8 to 200 cGy per fraction, with an initial 44 to 4600 cGy to the pelvis, then an additional conedown to the prostate that resulted in a total dose of 65 to 7000 cGy

7-week course

Subsequent treatment

RTOG 92-02: Adjuvant goserelin x 2 y versus no further treatment

References

Pilepich MV, Krall JM, al-Sarraf M, John MJ, Doggett RL, Sause WT, Lawton CA, Abrams RA, Rotman M, Rubin P, Shipley WU, Grignon D, Caplan R, Cox JD; Radiation Therapy Oncology Group. Androgen deprivation with radiation therapy compared with radiation therapy alone for locally advanced prostatic carcinoma: a randomized comparative trial of the Radiation Therapy Oncology Group. Urology. 1995 Apr;45(4):616-23. link to original article PubMed
RTOG 86-10: 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 dosing details in manuscript PubMed
1. 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 dosing details in manuscript PubMed
RTOG 92-02: 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 dosing details in abstract PubMed
1. 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 dosing details in manuscript PubMed
2. 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. link to original article link to PMC article PubMed
TROG 96.01: 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 dosing details in abstract PubMed ACTRN12607000237482
1. Update: Denham JW, Steigler A, Lamb DS, Joseph D, Turner S, Matthews J, Atkinson C, North J, Christie D, Spry NA, Tai KH, Wynne C, D'Este C. Short-term neoadjuvant androgen deprivation and radiotherapy for locally advanced prostate cancer: 10-year data from the TROG 96.01 randomised trial. Lancet Oncol. 2011 May;12(5):451-9. link to original article PubMed
DFCI 95-096: 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 NCT00116220
1. Update: D'Amico AV, Chen MH, Renshaw A, Loffredo M, Kantoff PW. Long-term Follow-up of a Randomized Trial of Radiation With or Without Androgen Deprivation Therapy for Localized Prostate Cancer. JAMA. 2015 Sep 22-29;314(12):1291-3. link to original article PubMed
RTOG 94-08: 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 dosing details in manuscript PubMed NCT00002597

Flutamide, Leuprolide, RT

Flutamide, Leuprolide, RT: Flutamide, Leuprolide, Radiation Therapy

Regimen variant #1, 4 months of ADT

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Jones et al. 2011 (RTOG 94-08)	1994-2001	Phase 3 (E-esc)	RT	Seems to have superior OS (primary endpoint) OS120: 62% vs 57% (HR 0.85, 95% CI 0.74-0.99)

Endocrine therapy

Flutamide (Eulexin) 250 mg PO three times per day, to start 2 months prior to radiation therapy
Leuprolide (Lupron) 7.5 mg SC once on day 1, to start 2 months prior to radiation therapy

28-day cycle for 4 cycles

Radiotherapy

External beam radiotherapy is started 2 months after start of androgen deprivation therapy (ADT), 1.8 to 200 cGy per fraction, with an initial 44 to 4600 cGy to the pelvis, then an additional conedown to the prostate that resulted in a total dose of 65 to 7000 cGy

Regimen variant #2, 3 years of ADT

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Mottet et al. 2012 (TAP 32)	2000-2003	Phase 3 (E-esc)	Flutamide & Leuprolide	Superior PFS60 (primary endpoint)

Endocrine therapy

Flutamide (Eulexin) 750 mg/day PO for one month
Leuprolide (Lupron) 11.25 mg SC once on day 1

3-month cycle for 12 cycles (3 years)

Radiotherapy

External beam radiotherapy to the pelvis, started within 90 days of initiation of ADT: 44 to 4800 cGy given in 25 fractions over 5 weeks
External beam radiotherapy to the prostate: 20 to 2800 cGy boost given in 10 to 12 fractions over 15 to 20 days

One course

Regimen variant #3, indefinite ADT, monthly leuprolide

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Widmark et al. 2008 (SPCG-7/SFUO-3)	1996-2002	Phase 3 (C)	Flutamide & Leuprolide	Superior OS

Endocrine therapy

Flutamide (Eulexin) 250 mg PO three times per day on days 1 to 28, starting 3 months prior to radiation therapy
Leuprolide (Lupron) as follows, starting 3 months prior to radiation therapy:
- Cycles 1 to 3: 3.75 mg SC once on day 1

28-day cycles

Radiotherapy

External beam radiotherapy 5000 cGy + 2000 cGy boost (total dose minimum of 7000 cGy)

Regimen variant #4, indefinite ADT, 3-monthly leuprolide

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Widmark et al. 2008 (SPCG-7/SFUO-3)	1996-2002	Phase 3 (C)	Flutamide & Leuprolide	Superior OS

Endocrine therapy

Flutamide (Eulexin) 250 mg PO three times per day on days 1 to 28, starting 3 months prior to radiation therapy
Leuprolide (Lupron) as follows, starting 3 months prior to radiation therapy:
- Cycle 1: 11.25 mg SC once on day 1

28-day cycles

Radiotherapy

External beam radiotherapy 5000 cGy + 2000 cGy boost (total dose minimum of 7000 cGy)

References

SPCG-7/SFUO-3: Widmark A, Klepp O, Solberg A, Damber JE, Angelsen A, Fransson P, Lund JA, Tasdemir I, Hoyer M, Wiklund F, Fosså SD; Scandinavian Prostate Cancer Group; Swedish Association for Urological Oncology. Endocrine treatment, with or without radiotherapy, in locally advanced prostate cancer (SPCG-7/SFUO-3): an open randomised phase III trial. Lancet. 2009 Jan 24;373(9660):301-8. Epub 2008 Dec 16. Erratum in: Lancet. 2009 Apr 4;373(9670):1174. link to original article contains dosing details in manuscript PubMed ISRCTN01534787
RTOG 94-08: 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 dosing details in manuscript PubMed NCT00002597
TAP 32: Mottet N, Peneau M, Mazeron JJ, Molinie V, Richaud P. Addition of radiotherapy to long-term androgen deprivation in locally advanced prostate cancer: an open randomised phase 3 trial. Eur Urol. 2012 Aug;62(2):213-9. Epub 2012 Apr 3. link to original article PubMed NCT01122121
1. Update: Sargos P, Mottet N, Bellera C, Richaud P. Long-term androgen deprivation, with or without radiotherapy, in locally advanced prostate cancer: updated results from a phase III randomised trial. BJU Int. 2020 Jun;125(6):810-816. Epub 2020 Mar 2. link to original article contains dosing details in manuscript PubMed

Goserelin & RT

Goserelin & RT: Goserelin & Radiation Therapy

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Pilepich et al. 2005 (RTOG 85-31)	1987-1992	Phase 3 (E-esc)	RT	Superior DFS
Bolla et al. 1997 (EORTC 22863)	1987-1995	Phase 3 (E-esc)	RT	Superior OS

Endocrine therapy

Goserelin (Zoladex) 3.6 mg SC once on day 1, started during the last week of radiation therapy

28-day cycles

Radiotherapy

External beam radiotherapy, 1.8 to 200 cGy per fraction, with an initial 44 to 4600 cGy to the pelvis, then an additional boost to the prostate that resulted in a total dose of 65 to 7000 cGy in definitive radiation patients; 60 to 6500 cGy total dose for post-prostatectomy patients

One course

References

RTOG 85-31: 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 dosing details in abstract PubMed
1. 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 dosing details in abstract PubMed
2. 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 dosing details in manuscript PubMed
EORTC 22863: 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 NCT00849082
1. Update: Bolla M, Collette L, Blank L, Warde P, Dubois JB, Mirimanoff RO, Storme G, Bernier J, Kuten A, Sternberg C, Mattelaer J, Lopez Torecilla J, Pfeffer JR, Lino Cutajar C, Zurlo A, Pierart M. Long-term results with immediate androgen suppression and external irradiation in patients with locally advanced prostate cancer (an EORTC study): a phase III randomised trial. Lancet. 2002 Jul 13;360(9327):103-6. link to original article PubMed
2. Update: Bolla M, Van Tienhoven G, Warde P, Dubois JB, Mirimanoff RO, Storme G, Bernier J, Kuten A, Sternberg C, Billiet I, Torecilla JL, Pfeffer R, Cutajar CL, Van der Kwast T, Collette L. External irradiation with or without long-term androgen suppression for prostate cancer with high metastatic risk: 10-year results of an EORTC randomised study. Lancet Oncol. 2010 Nov;11(11):1066-73. Epub 2010 Oct 7. link to original article PubMed

Adjuvant therapy

Bicalutamide & Goserelin

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Dorff et al. 2011 (SWOG S9921)	2000-2007	Phase 3 (C)	ADT & Mitoxantrone	Did not meet primary endpoint of OS¹

¹Reported efficacy is based on the 2018 update.
Dosing details are not available in the manuscript; this is the common dosing used.

Preceding treatment

Radical prostatectomy

Endocrine therapy

Bicalutamide (Casodex) 50 mg PO once per day
Goserelin (Zoladex) 10.8 mg SC once on day 1

12-week cycle for 9 cycles (2 years)

References

SWOG S9921: Dorff TB, Flaig TW, Tangen CM, Hussain MH, Swanson GP, Wood DP Jr, Sakr WA, Dawson NA, Haas NB, Crawford ED, Vogelzang NJ, Thompson IM, Glode LM. Adjuvant androgen deprivation for high-risk prostate cancer after radical prostatectomy: SWOG S9921 study. J Clin Oncol. 2011 May 20;29(15):2040-5. Epub 2011 Apr 18. link to original article does not contain dosing details link to PMC article PubMed NCT00004124
1. Update: Hussain M, Tangen CM, Thompson IM Jr, Swanson GP, Wood DP, Sakr W, Dawson NA, Haas NB, Flaig TW, Dorff TB, Lin DW, Crawford ED, Quinn DI, Vogelzang NJ, Glode LM. Phase III Intergroup Trial of Adjuvant Androgen Deprivation With or Without Mitoxantrone Plus Prednisone in Patients With High-Risk Prostate Cancer After Radical Prostatectomy: SWOG S9921. J Clin Oncol. 2018 May 20;36(15):1498-1504. Epub 2018 Apr 6. Erratum in: J Clin Oncol. 2018 Jul 10;36(20):2131. link to original article link to PMC article PubMed

Goserelin monotherapy

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Messing et al. 1999 (ECOG E3886)	1988-1993	Phase 3 (E-esc)	No further treatment	Seems to have superior OS
Hanks et al. 2003 (RTOG 92-02)	1992-1995	Phase 3 (E-esc)	No further treatment	Seems to have superior OS¹

¹Reported efficacy of RTOG 92-02 based on the 2017 update.

Preceding treatment

ECOG E3886: Radical prostatectomy
RTOG 92-02: Definitive Flutamide, Goserelin, RT

Endocrine therapy

Goserelin (Zoladex) 3.6 mg SC once per month

2-year course (RTOG 92-02) or until rising PSA detected (ECOG E3886)

References

ECOG E3886: Messing EM, Manola J, Sarosdy M, Wilding G, Crawford ED, Trump D; ECOG. Immediate hormonal therapy compared with observation after radical prostatectomy and pelvic lymphadenectomy in men with node-positive prostate cancer. N Engl J Med. 1999 Dec 9;341(24):1781-8. link to original article contains dosing details in manuscript PubMed
1. Update: Messing EM, Manola J, Yao J, Kiernan M, Crawford D, Wilding G, di'SantAgnese PA, Trump D; ECOG. Immediate versus deferred androgen deprivation treatment in patients with node-positive prostate cancer after radical prostatectomy and pelvic lymphadenectomy. Lancet Oncol. 2006 Jun;7(6):472-9. link to original article PubMed
RTOG 92-02: 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 dosing details in abstract PubMed
1. 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 dosing details in manuscript PubMed
2. 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. link to original article link to PMC article PubMed
ERADICATE: NCT04484818

Triptorelin & RT

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Sargos et al. 2020 (GETUG-AFU 17)	2008-2016	Phase 3 (C)	Triptorelin & RT; salvage	Did not meet primary endpoint of EFS

Statistical power was compromised due to unexpectedly low event rate. GETUG-AFU 17 was published concurrently along with two other Phase 3 trials looking at timing of radiotherapy following radical prostatectomy: RADICALS-RT and ANZUP RAVES. All three trials were also analyzed as part of a pre-planned meta-analysis ARTISTIC which failed to show an EFS benefit with adjuvant radiotherapy vs. salvage radiotherapy.

Preceding treatment

Radical prostatectomy

Endocrine therapy

Triptorelin (Trelstar LA) 11.25 mg IM once on day 1

12-week cycle for 2 cycles (6 months)

Radiotherapy

External beam radiotherapy

References

GETUG-AFU 17: Sargos P, Chabaud S, Latorzeff I, Magne N, Benyoucef A, Supiot S, Pasquier D, Abdiche MS, Gilliot O, Graff-Cailleaud P, Silva M, Bergerot P, Baumann P, Belkacemi Y, Azria D, Brihoum M, Soulie M, Richaud P. Adjuvant radiotherapy versus early salvage radiotherapy plus short-term androgen deprivation therapy in men with localized prostate cancer after radical prostatectomy (GETUG-AFU 17): a randomised, phase 3 trial. Lancet Oncol. 2020 Oct; 21(10):1341-1352. link to original article does not contain dosing details PubMed NCT00667069

Salvage ADT & radiotherapy

ADT & RT

ADT & RT: Androgen Deprivation Therapy & Radiation Therapy

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Pollack et al. 2022 (SPPORT)	2008-2015	Phase 3 (E-esc)	RT	Superior FFP (primary endpoint)

Endocrine therapy

Antiandrogen (ONE of the following):
- Bicalutamide (Casodex) 50 mg PO once per day
- Flutamide (Eulexin) 250 mg PO three times per day
LHRH agonist (ONE of the following):

Radiotherapy

External beam radiotherapy

References

SPPORT: Pollack A, Karrison TG, Balogh AG, Gomella LG, Low DA, Bruner DW, Wefel JS, Martin AG, Michalski JM, Angyalfi SJ, Lukka H, Faria SL, Rodrigues GB, Beauchemin MC, Lee RJ, Seaward SA, Allen AM, Monitto DC, Seiferheld W, Sartor O, Feng F, Sandler HM. The addition of androgen deprivation therapy and pelvic lymph node treatment to prostate bed salvage radiotherapy (NRG Oncology/RTOG 0534 SPPORT): an international, multicentre, randomised phase 3 trial. Lancet. 2022 May 14;399(10338):1886-1901. link to original article link to PMC article PubMed NCT00567580

Bicalutamide & RT

Bicalutamide & RT: Bicalutamide & Radiation Therapy

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Shipley et al. 2017 (RTOG 9601)	1998-2003	Phase 3 (E-esc)	RT	Seems to have superior OS (primary endpoint) OS144: 76.3% vs 71.3% (HR 0.77, 95% CI 0.59-0.99)

Preceding treatment

Prostatectomy with lymphadenectomy, with a postoperative detectable PSA level of 0.2 to 4.0 ng/mL

Endocrine therapy

Bicalutamide (Casodex) 150 mg PO once per day

2-year course

Radiotherapy

External beam radiotherapy, 6480 cGy in 36 daily fractions of 180 cGy

7-week course

References

RTOG 9601: Shipley WU, Seiferheld W, Lukka HR, Major PP, Heney NM, Grignon DJ, Sartor O, Patel MP, Bahary JP, Zietman AL, Pisansky TM, Zeitzer KL, Lawton CA, Feng FY, Lovett RD, Balogh AG, Souhami L, Rosenthal SA, Kerlin KJ, Dignam JJ, Pugh SL, Sandler HM; NRG Oncology RTOG. Radiation with or without antiandrogen therapy in recurrent prostate cancer. N Engl J Med. 2017 Feb 2;376(5):417-428. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00002874

Goserelin & RT

Goserelin & RT: Goserelin & Radiation Therapy

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Carrie et al. 2016 (GETUG-AFU 16)	2006-2010	Phase 3 (E-esc)	RT	Superior PFS (primary endpoint) PFS60: 80% vs 62% (HR 0.50, 95% CI 0.38-0.66)

Preceding treatment

Prostatectomy, with rising PSA

Endocrine therapy

Goserelin (Zoladex) 0.8 mg SC once on day 1

3-month cycle for 2 cycles

Radiotherapy

External beam radiotherapy, 6600 cGy in 33 daily fractions of 200 cGy

7-week course

References

GETUG-AFU 16: Carrie C, Hasbini A, de Laroche G, Richaud P, Guerif S, Latorzeff I, Supiot S, Bosset M, Lagrange JL, Beckendorf V, Lesaunier F, Dubray B, Wagner JP, N'Guyen TD, Suchaud JP, Créhange G, Barbier N, Habibian M, Ferlay C, Fourneret P, Ruffion A, Dussart S. Salvage radiotherapy with or without short-term hormone therapy for rising prostate-specific antigen concentration after radical prostatectomy (GETUG-AFU 16): a randomised, multicentre, open-label phase 3 trial. Lancet Oncol. 2016 Jun;17(6):747-756. Epub 2016 May 6. Erratum in: Lancet Oncol. 2016 Jun;17 (6):e223. link to original article contains dosing details in abstract PubMed NCT00423475
1. Update: Carrie C, Magné N, Burban-Provost P, Sargos P, Latorzeff I, Lagrange JL, Supiot S, Belkacemi Y, Peiffert D, Allouache N, Dubray BM, Servagi-Vernat S, Suchaud JP, Crehange G, Guerif S, Brihoum M, Barbier N, Graff-Cailleaud P, Ruffion A, Dussart S, Ferlay C, Chabaud S. Short-term androgen deprivation therapy combined with radiotherapy as salvage treatment after radical prostatectomy for prostate cancer (GETUG-AFU 16): a 112-month follow-up of a phase 3, randomised trial. Lancet Oncol. 2019 Dec;20(12):1740-1749. Epub 2019 Oct 16. link to original article PubMed
ECOG-ACRIN EA8191: NCT04423211

Hormonal therapy for non-metastatic castrate sensitive disease

ADT

ADT: Androgen Deprivation Therapy

Regimen variant #1, 6 months

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Figg et al. 2009	2000-03 to 2005-01	Phase 3 (C)	ADT & Thalidomide	Did not meet primary endpoint of PFS

Note: these are clinical trials that did not specify a particular approach to be used for androgen deprivation. See papers for details.

Endocrine therapy

ADT

6-month course

Regimen variant #2, 12 months

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Oudard et al. 2019 (RisingPSA)	2003-2007	Phase 3 (C)	ADT & Docetaxel	Did not meet primary endpoint of PSA-PFS

Note: these are clinical trials that did not specify a particular approach to be used for androgen deprivation. See papers for details.

Endocrine therapy

ADT

12-month course

Regimen variant #3, indefinite

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Duchesne et al. 2016 (TOAD)	2004-2012	Phase 3 (E-switch-ic)	ADT; delayed	Seems to have superior OS (primary endpoint) OS60: 91.2% vs 86.4% (HR 0.55, 95% CI 0.30-1.00)
Schulman et al. 2015 (ICELAND)	2006-NR	Phase 3 (C)	Intermittent ADT	Did not meet primary endpoint of TTP
Aggarwal et al. 2024 (PRESTO)	2017-03 to 2022-04	Phase 3 (C)	1. ADT & Apalutamide 2. ADT, Abiraterone, Apalutamide	Inferior PSA-PFS (primary endpoint)

Note: these are clinical trials that did not specify a particular approach to be used for androgen deprivation. See papers for details.

Endocrine therapy

ADT

Continued indefinitely

References

Figg WD, Hussain MH, Gulley JL, Arlen PM, Aragon-Ching JB, Petrylak DP, Higano CS, Steinberg SM, Chatta GS, Parnes H, Wright JJ, Sartor O, Dahut WL. A double-blind randomized crossover study of oral thalidomide versus placebo for androgen dependent prostate cancer treated with intermittent androgen ablation. J Urol. 2009 Mar;181(3):1104-13. Epub 2009 Jan 23. link to original article link to PMC article PubMed NCT00004635
EORTC 30891: Studer UE, Whelan P, Wimpissinger F, Casselman J, de Reijke TM, Knönagel H, Loidl W, Isorna S, Sundaram SK, Collette L; EORTC Genitourinary Cancer Group. Differences in time to disease progression do not predict for cancer-specific survival in patients receiving immediate or deferred androgen-deprivation therapy for prostate cancer: final results of EORTC randomized trial 30891 with 12 years of follow-up. Eur Urol. 2014 Nov;66(5):829-38. Epub 2013 Jul 24. link to original article PubMed NCT01819285
ICELAND: Schulman C, Cornel E, Matveev V, Tammela TL, Schraml J, Bensadoun H, Warnack W, Persad R, Salagierski M, Gómez Veiga F, Baskin-Bey E, López B, Tombal B. Intermittent versus continuous androgen deprivation therapy in patients with relapsing or locally advanced prostate cancer: a phase 3b randomised study (ICELAND). Eur Urol. 2016 Apr;69(4):720-727. Epub 2015 Oct 29. link to original article PubMed NCT00378690
TOAD: Duchesne GM, Woo HH, Bassett JK, Bowe SJ, D'Este C, Frydenberg M, King M, Ledwich L, Loblaw A, Malone S, Millar J, Milne R, Smith RG, Spry N, Stockler M, Syme RA, Tai KH, Turner S. Timing of androgen-deprivation therapy in patients with prostate cancer with a rising PSA (TROG 03.06 and VCOG PR 01-03 [TOAD]): a randomised, multicentre, non-blinded, phase 3 trial. Lancet Oncol. 2016 Jun;17(6):727-737. Epub 2016 May 4. Erratum in: Lancet Oncol. 2016 Jun;17 (6):e223. Lancet Oncol. 2017 Sep;18(9):e510. link to original article PubMed NCT00110162
RisingPSA: Oudard S, Latorzeff I, Caty A, Miglianico L, Sevin E, Hardy-Bessard AC, Delva R, Rolland F, Mourey L, Priou F, Beuzeboc P, Gravis G, Linassier C, Gomez P, Voog E, Muracciole X, Abraham C, Banu E, Ferrero JM, Ravaud A, Krakowski I, Lagrange JL, Deplanque G, Zylberait D, Bozec L, Houede N, Culine S, Elaidi R. Effect of adding docetaxel to androgen-deprivation therapy in patients with high-risk prostate cancer with rising prostate-specific antigen levels after primary local therapy: a randomized clinical trial. JAMA Oncol. 2019 May 1;5(5):623-632. Epub 2019 Jan 31. link to original article link to PMC article PubMed NCT00764166
PRESTO: Aggarwal R, Heller G, Hillman DW, Xiao H, Picus J, Taplin ME, Dorff T, Appleman L, Weckstein D, Patnaik A, Bryce A, Shevrin D, Mohler J, Anderson D, Rao A, Tagawa S, Tan A, Halabi S, Dooley K, O'Brien P, Chen R, Ryan CJ, Eggener SE, Morris MJ; EORTC-55994 Study Group. PRESTO: A Phase III, Open-Label Study of Intensification of Androgen Blockade in Patients With High-Risk Biochemically Relapsed Castration-Sensitive Prostate Cancer (AFT-19). J Clin Oncol. 2024 Apr 1;42(10):1114-1123. Epub 2024 Jan 23. link to original article contains dosing details in manuscript PubMed NCT03009981

ADT, Abiraterone, Apalutamide

ADT, Abiraterone, Apalutamide: Androgen Deprivation Therapy, Abiraterone, Apalutamide

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Aggarwal et al. 2024 (PRESTO)	2017-03 to 2022-04	Phase 3 (E-esc)	1. ADT	Superior PSA-PFS (primary endpoint) Median PSA-PFS: 26 vs 20 mo (HR 0.48, 95% CI 0.32-0.71)
Aggarwal et al. 2024 (PRESTO)	2017-03 to 2022-04	Phase 3 (E-esc)	2. ADT & Apalutamide	Not reported

Eligibility criteria

Prior radical prostatectomy, castrate-sensitive biochemical recurrence with PSA at least 0.5 ng/mL, non-metastatic, PSA doubling time less than 9 months

Endocrine therapy

ADT
Abiraterone (Zytiga) 1000 mg PO once per day
Apalutamide (Erleada) 240 mg PO once per day

Supportive therapy

Prednisone (Sterapred) 5 mg PO once per day

1-year course

References

PRESTO: Aggarwal R, Heller G, Hillman DW, Xiao H, Picus J, Taplin ME, Dorff T, Appleman L, Weckstein D, Patnaik A, Bryce A, Shevrin D, Mohler J, Anderson D, Rao A, Tagawa S, Tan A, Halabi S, Dooley K, O'Brien P, Chen R, Ryan CJ, Eggener SE, Morris MJ; EORTC-55994 Study Group. PRESTO: A Phase III, Open-Label Study of Intensification of Androgen Blockade in Patients With High-Risk Biochemically Relapsed Castration-Sensitive Prostate Cancer (AFT-19). J Clin Oncol. 2024 Apr 1;42(10):1114-1123. Epub 2024 Jan 23. link to original article contains dosing details in manuscript PubMed NCT03009981

ADT & Apalutamide

ADT & Apalutamide: Androgen Deprivation Therapy & Apalutamide

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Aggarwal et al. 2024 (PRESTO)	2017-03 to 2022-04	Phase 3 (E-esc)	1. ADT	Superior PSA-PFS (primary endpoint) Median PSA-PFS: 24.9 vs 20.3 mo (HR 0.52, 95% CI 0.35-0.77)
Aggarwal et al. 2024 (PRESTO)	2017-03 to 2022-04	Phase 3 (E-esc)	2. ADT, Abiraterone, Apalutamide	Not reported

Eligibility criteria

Prior radical prostatectomy, castrate-sensitive biochemical recurrence with PSA at least 0.5 ng/mL, non-metastatic, PSA doubling time less than 9 months

Endocrine therapy

ADT
Apalutamide (Erleada) 240 mg PO once per day

1-year course

References

PRESTO: Aggarwal R, Heller G, Hillman DW, Xiao H, Picus J, Taplin ME, Dorff T, Appleman L, Weckstein D, Patnaik A, Bryce A, Shevrin D, Mohler J, Anderson D, Rao A, Tagawa S, Tan A, Halabi S, Dooley K, O'Brien P, Chen R, Ryan CJ, Eggener SE, Morris MJ; EORTC-55994 Study Group. PRESTO: A Phase III, Open-Label Study of Intensification of Androgen Blockade in Patients With High-Risk Biochemically Relapsed Castration-Sensitive Prostate Cancer (AFT-19). J Clin Oncol. 2024 Apr 1;42(10):1114-1123. Epub 2024 Jan 23. link to original article contains dosing details in manuscript PubMed NCT03009981

Enzalutamide monotherapy

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Freedland et al. 2023 (EMBARK)	2015-01 to 2018-08	Phase 3 (E-RT-switch-ooc)	1. Leuprolide	Superior MFS (secondary endpoint) MFS60: 80% vs 71.4% (HR 0.63, 95% CI 0.43-0.87)
Freedland et al. 2023 (EMBARK)	2015-01 to 2018-08	Phase 3 (E-RT-switch-ooc)	2. Enzalutamide & Leuprolide	Not reported

Endocrine therapy

Enzalutamide (Xtandi) 160 mg PO once per day

Continued indefinitely

References

EMBARK: Freedland SJ, de Almeida Luz M, De Giorgi U, Gleave M, Gotto GT, Pieczonka CM, Haas GP, Kim CS, Ramirez-Backhaus M, Rannikko A, Tarazi J, Sridharan S, Sugg J, Tang Y, Tutrone RF Jr, Venugopal B, Villers A, Woo HH, Zohren F, Shore ND. Improved Outcomes with Enzalutamide in Biochemically Recurrent Prostate Cancer. N Engl J Med. 2023 Oct 19;389(16):1453-1465. link to original article contains dosing details in abstract PubMed NCT02319837
1. HRQoL analysis: Freedland SJ, Gleave M, De Giorgi U, Rannikko A, Pieczonka CM, Tutrone RF, Venugopal B, Woo HH, Ramirez-Backhaus M, Supiot S, Lantz A, Ganguli A, Ivanova J, Kral P, Huang SP, Saad F, Shore ND. Enzalutamide and Quality of Life in Biochemically Recurrent Prostate Cancer. NEJM Evidence. 2023 Dec;2(12):EVIDoa2300251. Epub 2023 Oct 22. link to original article PubMed

Enzalutamide & Leuprolide

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Freedland et al. 2023 (EMBARK)	2015-01 to 2018-08	Phase 3 (E-RT-esc)	1. Leuprolide	Superior MFS (primary endpoint) MFS60: 87.3% vs 71.4% (HR 0.42, 95% CI 0.30-0.61)
Freedland et al. 2023 (EMBARK)	2015-01 to 2018-08	Phase 3 (E-RT-esc)	2. Enzalutamide	Not reported

Endocrine therapy

Enzalutamide (Xtandi) 160 mg PO once per day on days 1 to 84
Leuprolide (Lupron) 3-month depot 22.5 mg IM once on day 1

84-day cycles

References

EMBARK: Freedland SJ, de Almeida Luz M, De Giorgi U, Gleave M, Gotto GT, Pieczonka CM, Haas GP, Kim CS, Ramirez-Backhaus M, Rannikko A, Tarazi J, Sridharan S, Sugg J, Tang Y, Tutrone RF Jr, Venugopal B, Villers A, Woo HH, Zohren F, Shore ND. Improved Outcomes with Enzalutamide in Biochemically Recurrent Prostate Cancer. N Engl J Med. 2023 Oct 19;389(16):1453-1465. link to original article contains dosing details in abstract PubMed NCT02319837
1. HRQoL analysis: Freedland SJ, Gleave M, De Giorgi U, Rannikko A, Pieczonka CM, Tutrone RF, Venugopal B, Woo HH, Ramirez-Backhaus M, Supiot S, Lantz A, Ganguli A, Ivanova J, Kral P, Huang SP, Saad F, Shore ND. Enzalutamide and Quality of Life in Biochemically Recurrent Prostate Cancer. NEJM Evidence. 2023 Dec;2(12):EVIDoa2300251. Epub 2023 Oct 22. link to original article PubMed

Leuprolide monotherapy

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Freedland et al. 2023 (EMBARK)	2015-01 to 2018-08	Phase 3 (C)	1. Enzalutamide & Leuprolide 2. Enzalutamide	Inferior MFS

Endocrine therapy

Leuprolide (Lupron) 3-month depot 22.5 mg IM once on day 1

84-day cycles

References

EMBARK: Freedland SJ, de Almeida Luz M, De Giorgi U, Gleave M, Gotto GT, Pieczonka CM, Haas GP, Kim CS, Ramirez-Backhaus M, Rannikko A, Tarazi J, Sridharan S, Sugg J, Tang Y, Tutrone RF Jr, Venugopal B, Villers A, Woo HH, Zohren F, Shore ND. Improved Outcomes with Enzalutamide in Biochemically Recurrent Prostate Cancer. N Engl J Med. 2023 Oct 19;389(16):1453-1465. link to original article contains dosing details in abstract PubMed NCT02319837
1. HRQoL analysis: Freedland SJ, Gleave M, De Giorgi U, Rannikko A, Pieczonka CM, Tutrone RF, Venugopal B, Woo HH, Ramirez-Backhaus M, Supiot S, Lantz A, Ganguli A, Ivanova J, Kral P, Huang SP, Saad F, Shore ND. Enzalutamide and Quality of Life in Biochemically Recurrent Prostate Cancer. NEJM Evidence. 2023 Dec;2(12):EVIDoa2300251. Epub 2023 Oct 22. link to original article PubMed

Hormonal therapy for non-metastatic castrate resistant disease

ADT

ADT: Androgen Deprivation Therapy

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Smith et al. 2017 (SPARTAN)	2013-2016	Phase 3 (C)	ADT & Apalutamide	Seems to have inferior OS¹
Hussain et al. 2018 (PROSPER_PrCA)	2013-2017	Phase 3 (C)	ADT & Enzalutamide	Inferior OS²
Fizazi et al. 2019 (ARAMIS)	2014-2018	Phase 3 (C)	ADT & Darolutamide	Inferior OS³

¹Reported efficacy for SPARTAN is based on the 2020 update.
²Reported efficacy for PROSPER is based on the 2020 update.
³Reported efficacy for ARAMIS is based on the 2020 update.
Note: these are clinical trials that did not specify a particular approach for androgen deprivation. See papers for details.

Endocrine therapy

ADT

Continued indefinitely

References

SPARTAN: Smith MR, Saad F, Chowdhury S, Oudard S, Hadaschik BA, Graff JN, Olmos D, Mainwaring PN, Lee JY, Uemura H, Lopez-Gitlitz A, Trudel GC, Espina BM, Shu Y, Park YC, Rackoff WR, Yu MK, Small EJ; SPARTAN Investigators. Apalutamide treatment and metastasis-free survival in prostate cancer. N Engl J Med. 2018 Apr 12;378(15):1408-1418. Epub 2018 Feb 8. link to original article link to supplementary appendix contains dosing details in manuscript PubMed NCT01946204
1. HRQoL analysis: Saad F, Cella D, Basch E, Hadaschik BA, Mainwaring PN, Oudard S, Graff JN, McQuarrie K, Li S, Hudgens S, Lawson J, Lopez-Gitlitz A, Yu MK, Smith MR, Small EJ. Effect of apalutamide on health-related quality of life in patients with non-metastatic castration-resistant prostate cancer: an analysis of the SPARTAN randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2018 Oct;19(10):1404-1416. Epub 2018 Sep 10. link to original article PubMed
2. Update: Small EJ, Saad F, Chowdhury S, Oudard S, Hadaschik BA, Graff JN, Olmos D, Mainwaring PN, Lee JY, Uemura H, De Porre P, Smith AA, Zhang K, Lopez-Gitlitz A, Smith MR. Apalutamide and overall survival in non-metastatic castration-resistant prostate cancer. Ann Oncol. 2019 Nov 1;30(11):1813-1820. link to original article link to PMC article PubMed
3. Update: Smith MR, Saad F, Chowdhury S, Oudard S, Hadaschik BA, Graff JN, Olmos D, Mainwaring PN, Lee JY, Uemura H, De Porre P, Smith AA, Brookman-May SD, Li S, Zhang K, Rooney B, Lopez-Gitlitz A, Small EJ. Apalutamide and Overall Survival in Prostate Cancer. Eur Urol. 2021 Jan;79(1):150-158. Epub 2020 Sep 6. link to original article PubMed
PROSPER_PrCA: Hussain M, Fizazi K, Saad F, Rathenborg P, Shore N, Ferreira U, Ivashchenko P, Demirhan E, Modelska K, Phung D, Krivoshik A, Sternberg CN. Enzalutamide in men with nonmetastatic, castration-resistant prostate cancer. N Engl J Med. 2018 Jun 28;378(26):2465-2474. link to original article contains dosing details in abstract link to PMC article PubMed NCT02003924
1. Update: Sternberg CN, Fizazi K, Saad F, Shore ND, De Giorgi U, Penson DF, Ferreira U, Efstathiou E, Madziarska K, Kolinsky MP, Cubero DIG, Noerby B, Zohren F, Lin X, Modelska K, Sugg J, Steinberg J, Hussain M; PROSPER Investigators. Enzalutamide and Survival in Nonmetastatic, Castration-Resistant Prostate Cancer. N Engl J Med. 2020 Jun 4;382(23):2197-2206. Epub 2020 May 29. link to original article PubMed
ARAMIS: Fizazi K, Shore N, Tammela TL, Ulys A, Vjaters E, Polyakov S, Jievaltas M, Luz M, Alekseev B, Kuss I, Kappeler C, Snapir A, Sarapohja T, Smith MR; ARAMIS Investigators. Darolutamide in nonmetastatic, castration-resistant prostate cancer. N Engl J Med. 2019 Mar 28;380(13):1235-1246. Epub 2019 Feb 14. link to original article PubMed NCT02200614
1. Update: Fizazi K, Shore N, Tammela TL, Ulys A, Vjaters E, Polyakov S, Jievaltas M, Luz M, Alekseev B, Kuss I, Le Berre MA, Petrenciuc O, Snapir A, Sarapohja T, Smith MR; ARAMIS Investigators. Nonmetastatic, Castration-Resistant Prostate Cancer and Survival with Darolutamide. N Engl J Med. 2020 Sep 10;383(11):1040-1049. link to original article PubMed

ADT & Apalutamide

ADT & Apalutamide: Androgen Deprivation Therapy & Apalutamide

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Smith et al. 2017 (SPARTAN)	2013-2016	Phase 3 (E-RT-esc)	ADT	Superior MFS (primary endpoint) Median MFS: 40.5 vs 16.2 mo (HR 0.28, 95% CI 0.23-0.35) Seems to have superior OS¹ (secondary endpoint) Median OS: 73.9 vs 59.9 mo (HR 0.78, 95% CI 0.64-0.96)

¹Reported efficacy is based on the 2020 update.

Eligibility criteria

Castrate-resistant, non-metastatic, PSA doubling time less than 10 months

Endocrine therapy

Apalutamide (Erleada) 240 mg PO once per day
Patients should concurrently be receiving GnRH analog or have had bilateral orchiectomy

Continued indefinitely

References

SPARTAN: Smith MR, Saad F, Chowdhury S, Oudard S, Hadaschik BA, Graff JN, Olmos D, Mainwaring PN, Lee JY, Uemura H, Lopez-Gitlitz A, Trudel GC, Espina BM, Shu Y, Park YC, Rackoff WR, Yu MK, Small EJ; SPARTAN Investigators. Apalutamide treatment and metastasis-free survival in prostate cancer. N Engl J Med. 2018 Apr 12;378(15):1408-1418. Epub 2018 Feb 8. link to original article link to supplementary appendix contains dosing details in manuscript PubMed NCT01946204
1. HRQoL analysis: Saad F, Cella D, Basch E, Hadaschik BA, Mainwaring PN, Oudard S, Graff JN, McQuarrie K, Li S, Hudgens S, Lawson J, Lopez-Gitlitz A, Yu MK, Smith MR, Small EJ. Effect of apalutamide on health-related quality of life in patients with non-metastatic castration-resistant prostate cancer: an analysis of the SPARTAN randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2018 Oct;19(10):1404-1416. Epub 2018 Sep 10. link to original article PubMed
2. Update: Small EJ, Saad F, Chowdhury S, Oudard S, Hadaschik BA, Graff JN, Olmos D, Mainwaring PN, Lee JY, Uemura H, De Porre P, Smith AA, Zhang K, Lopez-Gitlitz A, Smith MR. Apalutamide and overall survival in non-metastatic castration-resistant prostate cancer. Ann Oncol. 2019 Nov 1;30(11):1813-1820. link to original article link to PMC article PubMed
3. Update: Smith MR, Saad F, Chowdhury S, Oudard S, Hadaschik BA, Graff JN, Olmos D, Mainwaring PN, Lee JY, Uemura H, De Porre P, Smith AA, Brookman-May SD, Li S, Zhang K, Rooney B, Lopez-Gitlitz A, Small EJ. Apalutamide and Overall Survival in Prostate Cancer. Eur Urol. 2021 Jan;79(1):150-158. Epub 2020 Sep 6. link to original article PubMed

ADT & Darolutamide

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Fizazi et al. 2019 (ARAMIS)	2014-2018	Phase 3 (E-RT-esc)	ADT	Superior OS¹ (secondary endpoint) OS36: 83% vs 77% (HR 0.69, 95% CI 0.53-0.88) Superior MFS (primary endpoint) Median MFS: 40.4 vs 18.4 mo (HR 0.41, 95% CI 0.34-0.50)

¹Reported efficacy is based on the 2020 update.

Endocrine therapy

GnRH agonist or GnRH antagonist
Darolutamide (Nubeqa) 600 mg PO twice per day

Continued indefinitely

References

ARAMIS: Fizazi K, Shore N, Tammela TL, Ulys A, Vjaters E, Polyakov S, Jievaltas M, Luz M, Alekseev B, Kuss I, Kappeler C, Snapir A, Sarapohja T, Smith MR; ARAMIS Investigators. Darolutamide in nonmetastatic, castration-resistant prostate cancer. N Engl J Med. 2019 Mar 28;380(13):1235-1246. Epub 2019 Feb 14. link to original article PubMed NCT02200614
1. Update: Fizazi K, Shore N, Tammela TL, Ulys A, Vjaters E, Polyakov S, Jievaltas M, Luz M, Alekseev B, Kuss I, Le Berre MA, Petrenciuc O, Snapir A, Sarapohja T, Smith MR; ARAMIS Investigators. Nonmetastatic, Castration-Resistant Prostate Cancer and Survival with Darolutamide. N Engl J Med. 2020 Sep 10;383(11):1040-1049. link to original article PubMed

ADT & Enzalutamide

ADT & Enzalutamide: Androgen Deprivation Therapy & Enzalutamide

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Hussain et al. 2018 (PROSPER_PrCA)	2013-2017	Phase 3 (E-RT-esc)	ADT	Superior OS¹ (secondary endpoint) Median OS: 67 vs 56.3 mo (HR 0.73, 95% CI 0.61-0.89) Superior MFS (primary endpoint) Median MFS: 36.6 vs 14.7 mo (HR 0.29, 95% CI 0.24-0.35)

¹Reported efficacy is based on the 2020 update.

Eligibility criteria

Castrate-resistant, non-metastatic, prostate cancer with PSA doubling time less than 10 months

Endocrine therapy

ADT
Enzalutamide (Xtandi) 160 mg PO once per day

Continued indefinitely

References

PROSPER_PrCA: Hussain M, Fizazi K, Saad F, Rathenborg P, Shore N, Ferreira U, Ivashchenko P, Demirhan E, Modelska K, Phung D, Krivoshik A, Sternberg CN. Enzalutamide in men with nonmetastatic, castration-resistant prostate cancer. N Engl J Med. 2018 Jun 28;378(26):2465-2474. link to original article contains dosing details in abstract link to PMC article PubMed NCT02003924
1. Update: Sternberg CN, Fizazi K, Saad F, Shore ND, De Giorgi U, Penson DF, Ferreira U, Efstathiou E, Madziarska K, Kolinsky MP, Cubero DIG, Noerby B, Zohren F, Lin X, Modelska K, Sugg J, Steinberg J, Hussain M; PROSPER Investigators. Enzalutamide and Survival in Nonmetastatic, Castration-Resistant Prostate Cancer. N Engl J Med. 2020 Jun 4;382(23):2197-2206. Epub 2020 May 29. link to original article PubMed

Hormonal therapy for metastatic or locally advanced disease

Abarelix monotherapy

Regimen

Study	Dates of enrollment	Evidence
Koch et al. 2003	NR	Non-randomized (RT)

Endocrine therapy

Abarelix (Plenaxis) 100 mg IM once on day 1

Monthly cycles

References

Koch M, Steidle C, Brosman S, Centeno A, Gaylis F, Campion M, Garnick MB; Abarelix Study Group. An open-label study of abarelix in men with symptomatic prostate cancer at risk of treatment with LHRH agonists. Urology. 2003 Nov;62(5):877-82. link to original article PubMed

ADT

ADT: Androgen Deprivation Therapy

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Schröder et al. 2004 (EORTC 30846)	1986-1998	Phase 3 (C)	ADT; delayed	Did not meet primary endpoint of OS
Fizazi et al. 2015 (GETUG 12)	2002-2006	Phase 3 (C)	ADT, Docetaxel, Estramustine	Seems to have inferior RFS
Gravis et al. 2013 (GETUG-AFU 15)	2004-2008	Phase 3 (C)	ADT & Docetaxel	Did not meet primary endpoint of OS
Boevé et al. 2018 (HORRAD)	2004-2014	Phase 3 (C)	ADT & RT	Did not meet primary endpoint of OS
James et al. 2012 (STAMPEDE_celecoxib)	2005-2011	Phase 3 (C)	ADT & Celecoxib	Did not meet intermediate primary endpoint of FFS
James et al. 2015 (STAMPEDE_docetaxel)	2005-2011	Phase 3 (C)	ADT & Docetaxel	Inferior OS
James et al. 2017 (STAMPEDE_abiraterone)	2005-2011	Phase 3 (C)	ADT & Abiraterone	Inferior OS
Sweeney et al. 2015 (CHAARTED)	2006-2012	Phase 3 (C)	ADT & Docetaxel	Inferior OS¹
Kamba et al. 2016 (ZAPCA)	2008-2010	Phase 3 (C)	ADT & Zoledronic acid	Might have inferior TTTF
Fizazi et al. 2017 (LATITUDE)	2013-02-12 to 2014-12-11	Phase 3 (C)	ADT & Abiraterone	Inferior OS
Chi et al. 2019 (TITAN_prostate)	2015-2017	Phase 3 (C)	ADT & Apalutamide	Inferior OS
Armstrong et al. 2019 (ARCHES)	2016-2018	Phase 3 (C)	ADT & Enzalutamide	Inferior OS²

¹In the 2018 update of CHAARTED, only patients with high-volume disease had inferior survival in the control arm.
²Reported efficacy is based on the 2022 update.
Note: STAMPEDE is a platform RCT; each subtrial is denoted by the therapy used in the experimental arm. These are clinical trials that did not specify a particular approach to androgen deprivation. See papers for details.

Endocrine therapy

ADT

Continued indefinitely

References

EORTC 30846: Schröder FH, Kurth KH, Fosså SD, Hoekstra W, Karthaus PP, Debois M, Collette L; European Organisation for the Research and Treatment of Cancer Genito-urinary Group. Early versus delayed endocrine treatment of pN1-3 M0 prostate cancer without local treatment of the primary tumor: results of European Organisation for the Research and Treatment of Cancer 30846--a phase III study. J Urol. 2004 Sep;172(3):923-7. link to original article PubMed
STAMPEDE_celecoxib: James ND, Sydes MR, Mason MD, Clarke NW, Anderson J, Dearnaley DP, Dwyer J, Jovic G, Ritchie AW, Russell JM, Sanders K, Thalmann GN, Bertelli G, Birtle AJ, O'Sullivan JM, Protheroe A, Sheehan D, Srihari N, Parmar MK; STAMPEDE Investigators. Celecoxib plus hormone therapy versus hormone therapy alone for hormone-sensitive prostate cancer: first results from the STAMPEDE multiarm, multistage, randomised controlled trial. Lancet Oncol. 2012 May;13(5):549-58. Epub 2012 Mar 26. Erratum in: Lancet Oncol. 2013 Jan;14(1):e5. link to original article link to PMC article PubMed NCT00268476
GETUG-AFU 15: 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 NCT00104715
1. 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
GETUG 12: Fizazi K, Faivre L, Lesaunier F, Delva R, Gravis G, Rolland F, Priou F, Ferrero JM, Houede N, Mourey L, Theodore C, Krakowski I, Berdah JF, Baciuchka M, Laguerre B, Fléchon A, Ravaud A, Cojean-Zelek I, Oudard S, Labourey JL, Chinet-Charrot P, Legouffe E, Lagrange JL, Linassier C, Deplanque G, Beuzeboc P, Davin JL, Martin AL, Habibian M, Laplanche A, Culine S. Androgen deprivation therapy plus docetaxel and estramustine versus androgen deprivation therapy alone for high-risk localised prostate cancer (GETUG 12): a phase 3 randomised controlled trial. Lancet Oncol. 2015 Jul;16(7):787-94. Epub 2015 May 28. link to original article PubMed NCT00055731
CHAARTED: 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 dosing details in manuscript link to PMC article PubMed NCT00309985
1. Update: Kyriakopoulos CE, Chen YH, Carducci MA, Liu G, Jarrard DF, Hahn NM, Shevrin DH, Dreicer R, Hussain M, Eisenberger M, Kohli M, Plimack ER, Vogelzang NJ, Picus J, Cooney MM, Garcia JA, DiPaola RS, Sweeney CJ. Chemohormonal therapy in metastatic hormone-sensitive prostate cancer: long-term survival analysis of the randomized phase III E3805 CHAARTED trial. J Clin Oncol. 2018 Apr 10;36(11):1080-1087. Epub 2018 Jan 31. link to original article link to PMC article PubMed
2. HRQoL analysis: Morgans AK, Chen YH, Sweeney CJ, Jarrard DF, Plimack ER, Gartrell BA, Carducci MA, Hussain M, Garcia JA, Cella D, DiPaola RS, Patrick-Miller LJ. Quality of life during treatment with chemohormonal therapy: analysis of E3805 chemohormonal androgen ablation randomized trial in prostate cancer. J Clin Oncol. 2018 Apr 10;36(11):1088-1095. Epub 2018 Mar 9. link to original article link to PMC article PubMed
STAMPEDE_docetaxel: 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 contains dosing details in manuscript PubMed NCT00268476
1. Update: Clarke NW, Ali A, Ingleby FC, Hoyle A, Amos CL, Attard G, Brawley CD, Calvert J, Chowdhury S, Cook A, Cross W, Dearnaley DP, Douis H, Gilbert D, Gillessen S, Jones RJ, Langley RE, MacNair A, Malik Z, Mason MD, Matheson D, Millman R, Parker CC, Ritchie AWS, Rush H, Russell JM, Brown J, Beesley S, Birtle A, Capaldi L, Gale J, Gibbs S, Lydon A, Nikapota A, Omlin A, O'Sullivan JM, Parikh O, Protheroe A, Rudman S, Srihari NN, Simms M, Tanguay JS, Tolan S, Wagstaff J, Wallace J, Wylie J, Zarkar A, Sydes MR, Parmar MKB, James ND. Addition of docetaxel to hormonal therapy in low- and high-burden metastatic hormone sensitive prostate cancer: long-term survival results from the STAMPEDE trial. Ann Oncol. 2019 Dec 1;30(12):1992-2003. link to original article link to PMC article PubMed
ZAPCA: Kamba T, Kamoto T, Maruo S, Kikuchi T, Shimizu Y, Namiki S, Fujimoto K, Kawanishi H, Sato F, Narita S, Satoh T, Saito H, Sugimoto M, Teishima J, Masumori N, Egawa S, Sakai H, Okada Y, Terachi T, Ogawa O; ZAPCA Study Group. A phase III multicenter, randomized, controlled study of combined androgen blockade with versus without zoledronic acid in prostate cancer patients with metastatic bone disease: results of the ZAPCA trial. Int J Clin Oncol. 2017 Feb;22(1):166-173. Epub 2016 Sep 10. link to original article PubMed NCT00685646
STAMPEDE_abiraterone: 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 dosing details in supplement PubMed NCT00268476
1. Meta-analysis: Attard G, Murphy L, Clarke NW, Cross W, Jones RJ, Parker CC, Gillessen S, Cook A, Brawley C, Amos CL, Atako N, Pugh C, Buckner M, Chowdhury S, Malik Z, Russell JM, Gilson C, Rush H, Bowen J, Lydon A, Pedley I, O'Sullivan JM, Birtle A, Gale J, Srihari N, Thomas C, Tanguay J, Wagstaff J, Das P, Gray E, Alzoueb M, Parikh O, Robinson A, Syndikus I, Wylie J, Zarkar A, Thalmann G, de Bono JS, Dearnaley DP, Mason MD, Gilbert D, Langley RE, Millman R, Matheson D, Sydes MR, Brown LC, Parmar MKB, James ND; Systemic Therapy in Advancing or Metastatic Prostate cancer: Evaluation of Drug Efficacy (STAMPEDE) investigators. Abiraterone acetate and prednisolone with or without enzalutamide for high-risk non-metastatic prostate cancer: a meta-analysis of primary results from two randomised controlled phase 3 trials of the STAMPEDE platform protocol. Lancet. 2022 Jan 29;399(10323):447-460. Epub 2021 Dec 23. link to original article PubMed
2. Update: Attard G, Murphy L, Clarke NW, Sachdeva A, Jones C, Hoyle A, Cross W, Jones RJ, Parker CC, Gillessen S, Cook A, Brawley C, Gilson C, Rush H, Abdel-Aty H, Amos CL, Murphy C, Chowdhury S, Malik Z, Russell JM, Parkar N, Pugh C, Diaz-Montana C, Pezaro C, Grant W, Saxby H, Pedley I, O'Sullivan JM, Birtle A, Gale J, Srihari N, Thomas C, Tanguay J, Wagstaff J, Das P, Gray E, Alzouebi M, Parikh O, Robinson A, Montazeri AH, Wylie J, Zarkar A, Cathomas R, Brown MD, Jain Y, Dearnaley DP, Mason MD, Gilbert D, Langley RE, Millman R, Matheson D, Sydes MR, Brown LC, Parmar MKB, James ND; STAMPEDE investigators. Abiraterone acetate plus prednisolone with or without enzalutamide for patients with metastatic prostate cancer starting androgen deprivation therapy: final results from two randomised phase 3 trials of the STAMPEDE platform protocol. Lancet Oncol. 2023 May;24(5):443-456. link to original article PubMed
LATITUDE: 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 dosing details in supplement PubMed NCT01715285
1. HRQoL analysis: Chi KN, Protheroe A, Rodríguez-Antolín A, Facchini G, Suttman H, Matsubara N, Ye Z, Keam B, Damião R, Li T, McQuarrie K, Jia B, De Porre P, Martin J, Todd MB, Fizazi K. Patient-reported outcomes following abiraterone acetate plus prednisone added to androgen deprivation therapy in patients with newly diagnosed metastatic castration-naive prostate cancer (LATITUDE): an international, randomised phase 3 trial. Lancet Oncol. 2018 Feb;19(2):194-206. Epub 2018 Jan 8. link to original article PubMed
2. Update: Fizazi K, Tran N, Fein L, Matsubara N, Rodriguez-Antolin A, Alekseev BY, Özgüroğlu M, Ye D, Feyerabend S, Protheroe A, Sulur G, Luna Y, Li S, Mundle S, Chi KN. Abiraterone acetate plus prednisone in patients with newly diagnosed high-risk metastatic castration-sensitive prostate cancer (LATITUDE): final overall survival analysis of a randomised, double-blind, phase 3 trial. Lancet Oncol. 2019 May;20(5):686-700. Epub 2019 Apr 12. link to original article PubMed
HORRAD: Boevé LMS, Hulshof MCCM, Vis AN, Zwinderman AH, Twisk JWR, Witjes WPJ, Delaere KPJ, Moorselaar RJAV, Verhagen PCMS, van Andel G. Effect on Survival of Androgen Deprivation Therapy Alone Compared to Androgen Deprivation Therapy Combined with Concurrent Radiation Therapy to the Prostate in Patients with Primary Bone Metastatic Prostate Cancer in a Prospective Randomised Clinical Trial: Data from the HORRAD Trial. Eur Urol. 2019 Mar;75(3):410-418. Epub 2018 Sep 25. link to original article PubMed
TITAN_prostate: Chi KN, Agarwal N, Bjartell A, Chung BH, Pereira de Santana Gomes AJ, Given R, Juárez Soto Á, Merseburger AS, Özgüroğlu M, Uemura H, Ye D, Deprince K, Naini V, Li J, Cheng S, Yu MK, Zhang K, Larsen JS, McCarthy S, Chowdhury S; TITAN Investigators. Apalutamide for metastatic, castration-sensitive prostate cancer. N Engl J Med. 2019 Jul 4;381(1):13-24. Epub 2019 May 31. link to original article contains dosing details in abstract PubMed NCT02489318
1. Update: Chi KN, Chowdhury S, Bjartell A, Chung BH, Pereira de Santana Gomes AJ, Given R, Juárez A, Merseburger AS, Özgüroğlu M, Uemura H, Ye D, Brookman-May S, Mundle SD, McCarthy SA, Larsen JS, Sun W, Bevans KB, Zhang K, Bandyopadhyay N, Agarwal N. Apalutamide in Patients With Metastatic Castration-Sensitive Prostate Cancer: Final Survival Analysis of the Randomized, Double-Blind, Phase III TITAN Study. J Clin Oncol. 2021 Jul 10;39(20):2294-2303. Epub 2021 Apr 29. link to original article PubMed
ARCHES: Armstrong AJ, Szmulewitz RZ, Petrylak DP, Holzbeierlein J, Villers A, Azad A, Alcaraz A, Alekseev B, Iguchi T, Shore ND, Rosbrook B, Sugg J, Baron B, Chen L, Stenzl A. ARCHES: a randomized, phase III study of androgen deprivation therapy with enzalutamide or placebo in men with metastatic hormone-sensitive prostate cancer. J Clin Oncol. 2019 Nov 10;37(32):2974-2986. Epub 2019 Jul 22. link to original article contains dosing details in abstract link to PMC article PubMed NCT02677896

ADT & Abiraterone

ADT & Abiraterone: Androgen Deprivation Therapy & Abiraterone

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
James et al. 2017 (STAMPEDE_abiraterone)	2005-2011	Phase 3 (E-esc)	ADT	Superior OS (primary endpoint) OS36: 83% vs 76% (HR 0.63, 95% CI 0.52-0.76)
Fizazi et al. 2017 (LATITUDE)	2013-02-12 to 2014-12-11	Phase 3 (E-RT-esc)	ADT	Superior OS (co-primary endpoint) Median OS: NYR vs 34.7 mo (HR 0.62, 95% CI 0.51-0.76)

Note: STAMPEDE is a platform RCT; this subtrial is labeled by the experimental arm additive therapy. While LATITUDE allowed for a dose increase in prednisone, the FDA recommended dose is 5 mg PO once per day.

Endocrine therapy

Abiraterone (Zytiga) 1000 mg PO once per day
ADT with ONE of the following:
- LHRH agonist/analog
- STAMPEDE_abiraterone only: LHRH antagonist
- Bilateral orchiectomy

Supportive therapy

Prevention of mineralocorticoid excess with ONE of the following:
- STAMPEDE_abiraterone except Switzerland: Prednisolone (Millipred) 5 mg PO once per day
- LATITUDE and STAMPEDE_abiraterone 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 indefinitely unless radiotherapy planned, in which case continued for up to 2 years

References

STAMPEDE_abiraterone: 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 dosing details in supplement PubMed NCT00268476
1. Meta-analysis: Attard G, Murphy L, Clarke NW, Cross W, Jones RJ, Parker CC, Gillessen S, Cook A, Brawley C, Amos CL, Atako N, Pugh C, Buckner M, Chowdhury S, Malik Z, Russell JM, Gilson C, Rush H, Bowen J, Lydon A, Pedley I, O'Sullivan JM, Birtle A, Gale J, Srihari N, Thomas C, Tanguay J, Wagstaff J, Das P, Gray E, Alzoueb M, Parikh O, Robinson A, Syndikus I, Wylie J, Zarkar A, Thalmann G, de Bono JS, Dearnaley DP, Mason MD, Gilbert D, Langley RE, Millman R, Matheson D, Sydes MR, Brown LC, Parmar MKB, James ND; Systemic Therapy in Advancing or Metastatic Prostate cancer: Evaluation of Drug Efficacy (STAMPEDE) investigators. Abiraterone acetate and prednisolone with or without enzalutamide for high-risk non-metastatic prostate cancer: a meta-analysis of primary results from two randomised controlled phase 3 trials of the STAMPEDE platform protocol. Lancet. 2022 Jan 29;399(10323):447-460. Epub 2021 Dec 23. link to original article PubMed
2. Update: Attard G, Murphy L, Clarke NW, Sachdeva A, Jones C, Hoyle A, Cross W, Jones RJ, Parker CC, Gillessen S, Cook A, Brawley C, Gilson C, Rush H, Abdel-Aty H, Amos CL, Murphy C, Chowdhury S, Malik Z, Russell JM, Parkar N, Pugh C, Diaz-Montana C, Pezaro C, Grant W, Saxby H, Pedley I, O'Sullivan JM, Birtle A, Gale J, Srihari N, Thomas C, Tanguay J, Wagstaff J, Das P, Gray E, Alzouebi M, Parikh O, Robinson A, Montazeri AH, Wylie J, Zarkar A, Cathomas R, Brown MD, Jain Y, Dearnaley DP, Mason MD, Gilbert D, Langley RE, Millman R, Matheson D, Sydes MR, Brown LC, Parmar MKB, James ND; STAMPEDE investigators. Abiraterone acetate plus prednisolone with or without enzalutamide for patients with metastatic prostate cancer starting androgen deprivation therapy: final results from two randomised phase 3 trials of the STAMPEDE platform protocol. Lancet Oncol. 2023 May;24(5):443-456. link to original article PubMed
LATITUDE: 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 dosing details in supplement PubMed NCT01715285
1. HRQoL analysis: Chi KN, Protheroe A, Rodríguez-Antolín A, Facchini G, Suttman H, Matsubara N, Ye Z, Keam B, Damião R, Li T, McQuarrie K, Jia B, De Porre P, Martin J, Todd MB, Fizazi K. Patient-reported outcomes following abiraterone acetate plus prednisone added to androgen deprivation therapy in patients with newly diagnosed metastatic castration-naive prostate cancer (LATITUDE): an international, randomised phase 3 trial. Lancet Oncol. 2018 Feb;19(2):194-206. Epub 2018 Jan 8. link to original article PubMed
2. Update: Fizazi K, Tran N, Fein L, Matsubara N, Rodriguez-Antolin A, Alekseev BY, Özgüroğlu M, Ye D, Feyerabend S, Protheroe A, Sulur G, Luna Y, Li S, Mundle S, Chi KN. Abiraterone acetate plus prednisone in patients with newly diagnosed high-risk metastatic castration-sensitive prostate cancer (LATITUDE): final overall survival analysis of a randomised, double-blind, phase 3 trial. Lancet Oncol. 2019 May;20(5):686-700. Epub 2019 Apr 12. link to original article PubMed

ADT & Apalutamide

ADT & Apalutamide: Androgen Deprivation Therapy & Apalutamide

Regimen

FDA-recommended dose

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Chi et al. 2019 (TITAN_prostate)	2015-2017	Phase 3 (E-RT-esc)	ADT	Superior OS¹ (co-primary endpoint) Median OS: NYR vs 52.2 mo (HR 0.65, 95% CI 0.53-0.79)

¹Reported efficacy is based on the 2021 update.
Note: there are several other trials in other cancer subtypes named TITAN.

Endocrine therapy

Apalutamide (Erleada) 240 mg PO once per day
LHRH agonist/analog

Continued indefinitely

References

TITAN_prostate: Chi KN, Agarwal N, Bjartell A, Chung BH, Pereira de Santana Gomes AJ, Given R, Juárez Soto Á, Merseburger AS, Özgüroğlu M, Uemura H, Ye D, Deprince K, Naini V, Li J, Cheng S, Yu MK, Zhang K, Larsen JS, McCarthy S, Chowdhury S; TITAN Investigators. Apalutamide for metastatic, castration-sensitive prostate cancer. N Engl J Med. 2019 Jul 4;381(1):13-24. Epub 2019 May 31. link to original article contains dosing details in abstract PubMed NCT02489318
1. Update: Chi KN, Chowdhury S, Bjartell A, Chung BH, Pereira de Santana Gomes AJ, Given R, Juárez A, Merseburger AS, Özgüroğlu M, Uemura H, Ye D, Brookman-May S, Mundle SD, McCarthy SA, Larsen JS, Sun W, Bevans KB, Zhang K, Bandyopadhyay N, Agarwal N. Apalutamide in Patients With Metastatic Castration-Sensitive Prostate Cancer: Final Survival Analysis of the Randomized, Double-Blind, Phase III TITAN Study. J Clin Oncol. 2021 Jul 10;39(20):2294-2303. Epub 2021 Apr 29. link to original article PubMed

ADT & Bicalutamide

ADT & Bicalutamide: Androgen Deprivation Therapy & Bicalutamide

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Davis et al. 2019 (ENZAMET)	2014-2017	Phase 3 (C)	ADT & Enzalutamide	Inferior OS¹
Gu et al. 2022 (CHART)	2018-2020	Phase 3 (C)	ADT & Rezvilutamide	Inferior OS

¹Reported efficacy for ENZAMET is based on the 2023 update.

Endocrine therapy

LHRH agonist/analog
- ENZAMET also allowed Bilateral orchiectomy
Bicalutamide (Casodex) 50 mg PO once per day

Continued indefinitely

References

ENZAMET: Davis ID, Martin AJ, Stockler MR, Begbie S, Chi KN, Chowdhury S, Coskinas X, Frydenberg M, Hague WE, Horvath LG, Joshua AM, Lawrence NJ, Marx G, McCaffrey J, McDermott R, McJannett M, North SA, Parnis F, Parulekar W, Pook DW, Reaume MN, Sandhu SK, Tan A, Tan TH, Thomson A, Tu E, Vera-Badillo F, Williams SG, Yip S, Zhang AY, Zielinski RR, Sweeney CJ; ENZAMET Trial Investigators and the Australian and New Zealand Urogenital and Prostate Cancer Trials Group. Enzalutamide with standard first-line therapy in metastatic prostate cancer. N Engl J Med. 2019 Jul 11;381(2):121-131. Epub 2019 Jun 2. link to original article contains dosing details in supplement PubMed NCT02446405
1. Update: Sweeney CJ, Martin AJ, Stockler MR, Begbie S, Cheung L, Chi KN, Chowdhury S, Frydenberg M, Horvath LG, Joshua AM, Lawrence NJ, Marx G, McCaffrey J, McDermott R, McJannett M, North SA, Parnis F, Parulekar W, Pook DW, Reaume MN, Sandhu SK, Tan A, Tan TH, Thomson A, Vera-Badillo F, Williams SG, Winter D, Yip S, Zhang AY, Zielinski RR, Davis ID; ENZAMET trial investigators and Australian and New Zealand Urogenital and Prostate Cancer Trials Group. Testosterone suppression plus enzalutamide versus testosterone suppression plus standard antiandrogen therapy for metastatic hormone-sensitive prostate cancer (ENZAMET): an international, open-label, randomised, phase 3 trial. Lancet Oncol. 2023 Apr;24(4):323-334. link to original article PubMed
CHART: Gu W, Han W, Luo H, Zhou F, He D, Ma L, Guo H, Liang C, Chong T, Jiang J, Chen Z, Wang Y, Zou Q, Tian Y, Xiao J, Huang J, Zhu S, Dong Q, Zhang X, Li H, Yang X, Chen C, Li J, Jin C, Zhang X, Ye D; CHART Investigators. Rezvilutamide versus bicalutamide in combination with androgen-deprivation therapy in patients with high-volume, metastatic, hormone-sensitive prostate cancer (CHART): a randomised, open-label, phase 3 trial. Lancet Oncol. 2022 Oct;23(10):1249-1260. Epub 2022 Sep 5. link to original article contains dosing details in abstract PubMed NCT03520478

ADT, Darolutamide, Docetaxel

ADT, Darolutamide, Docetaxel: Androgen Deprivation Therapy, Darolutamide, Docetaxel

Regimen

FDA-recommended dose

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Smith et al. 2022 (ARASENS)	2016-2018	Phase 3 (E-RT-esc)	ADT & Docetaxel	Superior OS (primary endpoint) Median OS: NYR vs 48.9 mo (HR 0.68, 95% CI 0.57-0.80)

Chemotherapy

Docetaxel (Taxotere) as follows:
- Cycles 1 to 6: 75 mg/m² IV once on day 1

Endocrine therapy

Darolutamide (Nubeqa) 600 mg PO twice per day on days 1 to 21
ADT

21-day cycles

References

ARASENS: Smith MR, Hussain M, Saad F, Fizazi K, Sternberg CN, Crawford ED, Kopyltsov E, Park CH, Alekseev B, Montesa-Pino Á, Ye D, Parnis F, Cruz F, Tammela TLJ, Suzuki H, Utriainen T, Fu C, Uemura M, Méndez-Vidal MJ, Maughan BL, Joensuu H, Thiele S, Li R, Kuss I, Tombal B; ARASENS Trial Investigators. Darolutamide and Survival in Metastatic, Hormone-Sensitive Prostate Cancer. N Engl J Med. 2022 Mar 24;386(12):1132-1142. Epub 2022 Feb 17. link to original article PubMed NCT02799602

ADT & Docetaxel

ADT & Docetaxel: Androgen Deprivation Therapy & Docetaxel

Regimen variant #1, 6 cycles

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
James et al. 2015 (STAMPEDE_docetaxel)	2005-2011	Phase 3 (E-esc)	ADT	Superior OS (primary endpoint) Median OS: 81 vs 71 mo (HR 0.78, 95% CI 0.66-0.93)
Sweeney et al. 2015 (CHAARTED)	2006-2012	Phase 3 (E-esc)	ADT	Superior OS¹ (primary endpoint) Median OS: 57.6 vs 47.2 mo (HR 0.72, 95% CI 0.59-0.89)
Smith et al. 2022 (ARASENS)	2016-2018	Phase 3 (C)	ADT, Darolutamide, Docetaxel	Inferior OS

¹Reported efficacy for CHAARTED is for the overall population in the 2018 update; in subgroup analysis, only patients with high-volume disease had superior survival in the experimental arm.
Note: STAMPEDE is a platform RCT; this subtrial is labeled by the experimental arm additive therapy. Patients already on androgen deprivation therapy were eligible to participate in CHAARTED if there was no evidence of disease progression and if they had started ADT no more than 120 days before randomization.

Chemotherapy

Docetaxel (Taxotere) 75 mg/m² IV over 60 minutes once on day 1

Endocrine therapy

ADT
- Intermittent hormonal therapy was not allowed. Antiandrogens e.g. bicalutamide were allowed at the start of therapy "at the discretion of the investigator."

Supportive therapy

Dexamethasone (Decadron) 8 mg PO given three times; 12 hours, 3 hours, and 1 hour prior to docetaxel
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

Regimen variant #2, 9 cycles

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Gravis et al. 2013 (GETUG-AFU 15)	2004-2008	Phase 3 (E-esc)	ADT	Did not meet primary endpoint of OS Median OS: 58.9 vs 54.2 mo (HR 1.01, 95% CI 0.75-1.36)

Chemotherapy

Docetaxel (Taxotere) 75 mg/m² IV over 60 minutes once on day 1

Endocrine therapy

ADT with one of the following:
- LHRH agonist/analog with or without nonsteroidal androgen receptor inhibitors
- Bilateral orchiectomy with or without nonsteroidal androgen receptor inhibitors

21-day cycle for up to 9 cycles

References

GETUG-AFU 15: 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 NCT00104715
1. 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
CHAARTED: 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 dosing details in manuscript link to PMC article PubMed NCT00309985
1. Update: Kyriakopoulos CE, Chen YH, Carducci MA, Liu G, Jarrard DF, Hahn NM, Shevrin DH, Dreicer R, Hussain M, Eisenberger M, Kohli M, Plimack ER, Vogelzang NJ, Picus J, Cooney MM, Garcia JA, DiPaola RS, Sweeney CJ. Chemohormonal therapy in metastatic hormone-sensitive prostate cancer: long-term survival analysis of the randomized phase III E3805 CHAARTED trial. J Clin Oncol. 2018 Apr 10;36(11):1080-1087. Epub 2018 Jan 31. link to original article link to PMC article PubMed
2. HRQoL analysis: Morgans AK, Chen YH, Sweeney CJ, Jarrard DF, Plimack ER, Gartrell BA, Carducci MA, Hussain M, Garcia JA, Cella D, DiPaola RS, Patrick-Miller LJ. Quality of life during treatment with chemohormonal therapy: analysis of E3805 chemohormonal androgen ablation randomized trial in prostate cancer. J Clin Oncol. 2018 Apr 10;36(11):1088-1095. Epub 2018 Mar 9. link to original article link to PMC article PubMed
STAMPEDE_docetaxel: 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 contains dosing details in manuscript PubMed NCT00268476
1. Update: Clarke NW, Ali A, Ingleby FC, Hoyle A, Amos CL, Attard G, Brawley CD, Calvert J, Chowdhury S, Cook A, Cross W, Dearnaley DP, Douis H, Gilbert D, Gillessen S, Jones RJ, Langley RE, MacNair A, Malik Z, Mason MD, Matheson D, Millman R, Parker CC, Ritchie AWS, Rush H, Russell JM, Brown J, Beesley S, Birtle A, Capaldi L, Gale J, Gibbs S, Lydon A, Nikapota A, Omlin A, O'Sullivan JM, Parikh O, Protheroe A, Rudman S, Srihari NN, Simms M, Tanguay JS, Tolan S, Wagstaff J, Wallace J, Wylie J, Zarkar A, Sydes MR, Parmar MKB, James ND. Addition of docetaxel to hormonal therapy in low- and high-burden metastatic hormone sensitive prostate cancer: long-term survival results from the STAMPEDE trial. Ann Oncol. 2019 Dec 1;30(12):1992-2003. link to original article link to PMC article PubMed
ARASENS: Smith MR, Hussain M, Saad F, Fizazi K, Sternberg CN, Crawford ED, Kopyltsov E, Park CH, Alekseev B, Montesa-Pino Á, Ye D, Parnis F, Cruz F, Tammela TLJ, Suzuki H, Utriainen T, Fu C, Uemura M, Méndez-Vidal MJ, Maughan BL, Joensuu H, Thiele S, Li R, Kuss I, Tombal B; ARASENS Trial Investigators. Darolutamide and Survival in Metastatic, Hormone-Sensitive Prostate Cancer. N Engl J Med. 2022 Mar 24;386(12):1132-1142. Epub 2022 Feb 17. link to original article PubMed NCT02799602
PEACE-1: Fizazi K, Foulon S, Carles J, Roubaud G, McDermott R, Fléchon A, Tombal B, Supiot S, Berthold D, Ronchin P, Kacso G, Gravis G, Calabro F, Berdah JF, Hasbini A, Silva M, Thiery-Vuillemin A, Latorzeff I, Mourey L, Laguerre B, Abadie-Lacourtoisie S, Martin E, El Kouri C, Escande A, Rosello A, Magne N, Schlurmann F, Priou F, Chand-Fouche ME, Freixa SV, Jamaluddin M, Rieger I, Bossi A; PEACE-1 investigators. Abiraterone plus prednisone added to androgen deprivation therapy and docetaxel in de novo metastatic castration-sensitive prostate cancer (PEACE-1): a multicentre, open-label, randomised, phase 3 study with a 2 x 2 factorial design. Lancet. 2022 Apr 30;399(10336):1695-1707. Epub 2022 Apr 8. link to original article PubMed NCT01957436

ADT & Enzalutamide

ADT & Enzalutamide: Androgen Deprivation Therapy & Enzalutamide

Regimen

FDA-recommended dose

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Davis et al. 2019 (ENZAMET)	2014-2017	Phase 3 (E-switch-ic)	1a. ADT & Bicalutamide 1b. ADT & Flutamide 1c. ADT & Niluatmide	Superior OS¹ (primary endpoint) OS60: 67% vs 57% (HR 0.70, 95% CI 0.58-0.84)
Armstrong et al. 2019 (ARCHES)	2016-2018	Phase 3 (E-RT-esc)	ADT	Superior OS² (secondary endpoint) Median OS: NYR vs NYR (HR 0.66, 95% CI 0.53-0.81) Superior rPFS (primary endpoint) Median rPFS: NYR vs 19 mo (HR 0.39, 95% CI 0.30-0.50)
Agarwal et al. 2023 (TALAPRO-2)	2019-01-07 to 2020-09-17	Phase 3 (C)	ADT, Enzalutamide, Talazoparib	Inferior rPFS

¹Reported efficacy for ENZAMET is based on the 2023 update.
²Reported efficacy for ARCHES is based on the 2022 update.

Endocrine therapy

ADT
Enzalutamide (Xtandi) 160 mg PO once per day

Continued indefinitely

References

ENZAMET: Davis ID, Martin AJ, Stockler MR, Begbie S, Chi KN, Chowdhury S, Coskinas X, Frydenberg M, Hague WE, Horvath LG, Joshua AM, Lawrence NJ, Marx G, McCaffrey J, McDermott R, McJannett M, North SA, Parnis F, Parulekar W, Pook DW, Reaume MN, Sandhu SK, Tan A, Tan TH, Thomson A, Tu E, Vera-Badillo F, Williams SG, Yip S, Zhang AY, Zielinski RR, Sweeney CJ; ENZAMET Trial Investigators and the Australian and New Zealand Urogenital and Prostate Cancer Trials Group. Enzalutamide with standard first-line therapy in metastatic prostate cancer. N Engl J Med. 2019 Jul 11;381(2):121-131. Epub 2019 Jun 2. link to original article contains dosing details in abstract PubMed NCT02446405
1. Update: Sweeney CJ, Martin AJ, Stockler MR, Begbie S, Cheung L, Chi KN, Chowdhury S, Frydenberg M, Horvath LG, Joshua AM, Lawrence NJ, Marx G, McCaffrey J, McDermott R, McJannett M, North SA, Parnis F, Parulekar W, Pook DW, Reaume MN, Sandhu SK, Tan A, Tan TH, Thomson A, Vera-Badillo F, Williams SG, Winter D, Yip S, Zhang AY, Zielinski RR, Davis ID; ENZAMET trial investigators and Australian and New Zealand Urogenital and Prostate Cancer Trials Group. Testosterone suppression plus enzalutamide versus testosterone suppression plus standard antiandrogen therapy for metastatic hormone-sensitive prostate cancer (ENZAMET): an international, open-label, randomised, phase 3 trial. Lancet Oncol. 2023 Apr;24(4):323-334. link to original article PubMed
ARCHES: Armstrong AJ, Szmulewitz RZ, Petrylak DP, Holzbeierlein J, Villers A, Azad A, Alcaraz A, Alekseev B, Iguchi T, Shore ND, Rosbrook B, Sugg J, Baron B, Chen L, Stenzl A. ARCHES: a randomized, phase III study of androgen deprivation therapy with enzalutamide or placebo in men with metastatic hormone-sensitive prostate cancer. J Clin Oncol. 2019 Nov 10;37(32):2974-2986. Epub 2019 Jul 22. link to original article contains dosing details in abstract link to PMC article PubMed NCT02677896
1. HRQoL analysis: Stenzl A, Dunshee C, De Giorgi U, Alekseev B, Iguchi T, Szmulewitz RZ, Flaig TW, Tombal B, Morlock R, Ivanescu C, Ramaswamy K, Saad F, Armstrong AJ. Effect of Enzalutamide plus Androgen Deprivation Therapy on Health-related Quality of Life in Patients with Metastatic Hormone-sensitive Prostate Cancer: An Analysis of the ARCHES Randomised, Placebo-controlled, Phase 3 Study. Eur Urol. 2020 Oct;78(4):603-614. Epub 2020 Apr 23. link to original article PubMed
2. Update: Armstrong AJ, Azad AA, Iguchi T, Szmulewitz RZ, Petrylak DP, Holzbeierlein J, Villers A, Alcaraz A, Alekseev B, Shore ND, Gomez-Veiga F, Rosbrook B, Zohren F, Yamada S, Haas GP, Stenzl A. Improved Survival With Enzalutamide in Patients With Metastatic Hormone-Sensitive Prostate Cancer. J Clin Oncol. 2022 May 20;40(15):1616-1622. Epub 2022 Apr 14. link to original article link to PMC article PubMed
TALAPRO-2: Agarwal N, Azad AA, Carles J, Fay AP, Matsubara N, Heinrich D, Szczylik C, De Giorgi U, Young Joung J, Fong PCC, Voog E, Jones RJ, Shore ND, Dunshee C, Zschäbitz S, Oldenburg J, Lin X, Healy CG, Di Santo N, Zohren F, Fizazi K. Talazoparib plus enzalutamide in men with first-line metastatic castration-resistant prostate cancer (TALAPRO-2): a randomised, placebo-controlled, phase 3 trial. Lancet. 2023 Jul 22;402(10398):291-303. Epub 2023 Jun 4. Erratum in: Lancet. 2023 Jul 22;402(10398):290. link to original article contains dosing details in abstract PubMed NCT03395197

ADT, Enzalutamide, Talazoparib

ADT, Enzalutamide, Talazoparib: Androgen Deprivation Therapy, Enzalutamide, Talazoparib

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Agarwal et al. 2023 (TALAPRO-2)	2019-01-07 to 2020-09-17	Phase 3 (E-esc)	ADT & Enzalutamide	Superior rPFS (primary endpoint) Median rPFS: NYR vs 21.9 mo (HR 0.63, 95% CI 0.51-0.78)

Endocrine therapy

ADT
Enzalutamide (Xtandi) 160 mg PO once per day

Targeted therapy

Talazoparib (Talzenna) 0.5 mg PO once per day

Continued indefinitely

References

TALAPRO-2: Agarwal N, Azad AA, Carles J, Fay AP, Matsubara N, Heinrich D, Szczylik C, De Giorgi U, Young Joung J, Fong PCC, Voog E, Jones RJ, Shore ND, Dunshee C, Zschäbitz S, Oldenburg J, Lin X, Healy CG, Di Santo N, Zohren F, Fizazi K. Talazoparib plus enzalutamide in men with first-line metastatic castration-resistant prostate cancer (TALAPRO-2): a randomised, placebo-controlled, phase 3 trial. Lancet. 2023 Jul 22;402(10398):291-303. Epub 2023 Jun 4. Erratum in: Lancet. 2023 Jul 22;402(10398):290. link to original article contains dosing details in abstract PubMed NCT03395197

ADT & Flutamide

ADT & Flutamide: Androgen Deprivation Therapy & Flutamide

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Davis et al. 2019 (ENZAMET)	2014-2017	Phase 3 (C)	ADT & Enzalutamide	Inferior OS¹

¹Reported efficacy is based on the 2023 update.

Endocrine therapy

ADT
Flutamide (Eulexin) 250 mg PO three times per day

Continued indefinitely

References

ENZAMET: Davis ID, Martin AJ, Stockler MR, Begbie S, Chi KN, Chowdhury S, Coskinas X, Frydenberg M, Hague WE, Horvath LG, Joshua AM, Lawrence NJ, Marx G, McCaffrey J, McDermott R, McJannett M, North SA, Parnis F, Parulekar W, Pook DW, Reaume MN, Sandhu SK, Tan A, Tan TH, Thomson A, Tu E, Vera-Badillo F, Williams SG, Yip S, Zhang AY, Zielinski RR, Sweeney CJ; ENZAMET Trial Investigators and the Australian and New Zealand Urogenital and Prostate Cancer Trials Group. Enzalutamide with standard first-line therapy in metastatic prostate cancer. N Engl J Med. 2019 Jul 11;381(2):121-131. Epub 2019 Jun 2. link to original article contains dosing details in supplement PubMed NCT02446405
1. Update: Sweeney CJ, Martin AJ, Stockler MR, Begbie S, Cheung L, Chi KN, Chowdhury S, Frydenberg M, Horvath LG, Joshua AM, Lawrence NJ, Marx G, McCaffrey J, McDermott R, McJannett M, North SA, Parnis F, Parulekar W, Pook DW, Reaume MN, Sandhu SK, Tan A, Tan TH, Thomson A, Vera-Badillo F, Williams SG, Winter D, Yip S, Zhang AY, Zielinski RR, Davis ID; ENZAMET trial investigators and Australian and New Zealand Urogenital and Prostate Cancer Trials Group. Testosterone suppression plus enzalutamide versus testosterone suppression plus standard antiandrogen therapy for metastatic hormone-sensitive prostate cancer (ENZAMET): an international, open-label, randomised, phase 3 trial. Lancet Oncol. 2023 Apr;24(4):323-334. link to original article PubMed

ADT & Nilutamide

ADT & Nilutamide: Androgen Deprivation Therapy & Nilutamide

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Davis et al. 2019 (ENZAMET)	2014-2017	Phase 3 (C)	ADT & Enzalutamide	Inferior OS¹

¹Reported efficacy is based on the 2023 update.

Endocrine therapy

ADT
Nilutamide (Nilandron) 150 mg PO once per day

Continued indefinitely

References

ENZAMET: Davis ID, Martin AJ, Stockler MR, Begbie S, Chi KN, Chowdhury S, Coskinas X, Frydenberg M, Hague WE, Horvath LG, Joshua AM, Lawrence NJ, Marx G, McCaffrey J, McDermott R, McJannett M, North SA, Parnis F, Parulekar W, Pook DW, Reaume MN, Sandhu SK, Tan A, Tan TH, Thomson A, Tu E, Vera-Badillo F, Williams SG, Yip S, Zhang AY, Zielinski RR, Sweeney CJ; ENZAMET Trial Investigators and the Australian and New Zealand Urogenital and Prostate Cancer Trials Group. Enzalutamide with standard first-line therapy in metastatic prostate cancer. N Engl J Med. 2019 Jul 11;381(2):121-131. Epub 2019 Jun 2. link to original article contains dosing details in supplement PubMed NCT02446405
1. Update: Sweeney CJ, Martin AJ, Stockler MR, Begbie S, Cheung L, Chi KN, Chowdhury S, Frydenberg M, Horvath LG, Joshua AM, Lawrence NJ, Marx G, McCaffrey J, McDermott R, McJannett M, North SA, Parnis F, Parulekar W, Pook DW, Reaume MN, Sandhu SK, Tan A, Tan TH, Thomson A, Vera-Badillo F, Williams SG, Winter D, Yip S, Zhang AY, Zielinski RR, Davis ID; ENZAMET trial investigators and Australian and New Zealand Urogenital and Prostate Cancer Trials Group. Testosterone suppression plus enzalutamide versus testosterone suppression plus standard antiandrogen therapy for metastatic hormone-sensitive prostate cancer (ENZAMET): an international, open-label, randomised, phase 3 trial. Lancet Oncol. 2023 Apr;24(4):323-334. link to original article PubMed

Bicalutamide monotherapy

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Tyrrell et al. 1998	NR in abstract	Phase 3 (E-switch-ic)	Castration	Did not meet co-primary endpoints of PFS/OS¹
Iversen et al. 2002 (SPCG-6)	1995-1998	Phase 3 (E-esc)	Placebo	Superior OS² (HR 0.77, 95% CI 0.63-0.94)

¹Reported efficacy for Tyrrell et al. 1998 is based on the 2000 update.
²Reported efficacy for SPCG-6 is based on the 2015 update and is only for the locally advanced subgroup.
Note: Bicalutamide is not approved for monotherapy in the United States. See combination regimens with goserelin & leuprolide.

Endocrine therapy

Bicalutamide (Casodex) 150 mg PO once per day

Continued indefinitely

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. link to original article contains dosing details in abstract PubMed
1. 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 dosing details in manuscript PubMed
SPCG-6: Iversen P, Tammela TL, Vaage S, Lukkarinen O, Lodding P, Bull-Njaa T, Viitanen J, Hoisaeter P, Lundmo P, Rasmussen F, Johansson JE, Persson BE, Carroll K; Scandinavian Prostatic Cancer Group. A randomised comparison of bicalutamide ('Casodex') 150 mg versus placebo as immediate therapy either alone or as adjuvant to standard care for early non-metastatic prostate cancer: first report from the Scandinavian Prostatic Cancer Group Study No 6. Eur Urol. 2002 Sep;42(3):204-11. link to original article PubMed NCT00672282
1. Update: Iversen P, Johansson JE, Lodding P, Lukkarinen O, Lundmo P, Klarskov P, Tammela TL, Tasdemir I, Morris T, Carroll K; Scandinavian Prostatic Cancer Group. Bicalutamide (150 mg) versus placebo as immediate therapy alone or as adjuvant to therapy with curative intent for early nonmetastatic prostate cancer: 5.3-year median followup from the Scandinavian Prostate Cancer Group Study Number 6. J Urol. 2004 Nov;172(5 Pt 1):1871-6. link to original article PubMed
2. Update: Iversen P, Johansson JE, Lodding P, Kylmälä T, Lundmo P, Klarskov P, Tammela TL, Tasdemir I, Morris T, Armstrong J; Scandinavian Prostate Cancer Group. Bicalutamide 150 mg in addition to standard care for patients with early non-metastatic prostate cancer: updated results from the Scandinavian Prostate Cancer Period Group-6 Study after a median follow-up period of 7.1 years. Scand J Urol Nephrol. 2006;40(6):441-52. link to original article PubMed
3. Update: Thomsen FB, Brasso K, Christensen IJ, Johansson JE, Angelsen A, Tammela TL, Iversen P; Scandinavian Prostate Cancer Group. Survival benefit of early androgen receptor inhibitor therapy in locally advanced prostate cancer: long-term follow-up of the SPCG-6 study. Eur J Cancer. 2015 Jul;51(10):1283-92. Epub 2015 Apr 16. link to original article PubMed

Bicalutamide & Goserelin

Regimen variant #1, 50/3.6

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Schellhammer et al. 1995	1992-01 to 1993-09	Phase 3 (E-RT-switch-ic)	1. Bicalutamide & Leuprolide	Not reported
Schellhammer et al. 1995	1992-01 to 1993-09	Phase 3 (E-RT-switch-ic)	2. Flutamide & Goserelin 3. Flutamide & Leuprolide	Equivalent TTP¹

¹Reported efficacy for Schellhammer et al. 1995 is based on the 1997 final update.

Endocrine therapy

Bicalutamide (Casodex) 50 mg PO once per day on days 1 to 28
Goserelin (Zoladex) 3.6 mg SC once on day 1

28-day cycles

Regimen variant #2, 80/3.6

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Akaza et al. 2004	2000-02 to 2001-12	Phase 3 (E-esc)	1. Goserelin 2. Leuprolide	Seems to have superior OS¹ (secondary endpoint) Superior 12-week PSA normalization rate (primary endpoint)

¹Reported efficacy is based on the 2009 update.

Endocrine therapy

Bicalutamide (Casodex) 80 mg PO once per day on days 1 to 28
Goserelin (Zoladex) 3.6 mg SC once on day 1

28-day cycles

References

Schellhammer P, Sharifi R, Block N, Soloway M, Venner P, Patterson AL, Sarosdy M, Vogelzang N, Jones J, Kolvenbag G; Casodex Combination Study Group. A controlled trial of bicalutamide versus flutamide, each in combination with luteinizing hormone-releasing hormone analogue therapy, in patients with advanced prostate cancer. Urology. 1995 May;45(5):745-52. link to original article PubMed
1. Update: Schellhammer PF, Sharifi R, Block NL, Soloway MS, Venner PM, Patterson AL, Sarosdy MF, Vogelzang NJ, Chen Y, Kolvenbag GJ; CASODEX Combination Study Group. 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. Cancer. 1996 Nov 15;78(10):2164-9. link to original article contains dosing details in abstract PubMed
2. Update: Soloway MS, Schellhammer P, Sharifi R, Venner P, Patterson AL, Sarosdy M, Vogelzang N, Jones J, Kolvenbag G; Casodex Combination Study Group. A controlled trial of Casodex (bicalutamide) vs flutamide, each in combination with luteinising hormone-releasing hormone analogue therapy in patients with advanced prostate cancer. Eur Urol. 1996;29 Suppl 2:105-9. link to original article contains dosing details in abstract PubMed
3. Update: Schellhammer PF, Sharifi R, Block NL, Soloway MS, Venner PM, Patterson AL, Sarosdy MF, Vogelzang NJ, Schellenger JJ, Kolvenbag GJ; Casodex Combination Study Group. Clinical benefits of bicalutamide compared with flutamide in combined androgen blockade for patients with advanced prostatic carcinoma: final report of a double-blind, randomized, multicenter trial. Urology. 1997 Sep;50(3):330-6. 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 dosing details in manuscript PubMed
1. Update: Akaza H, Hinotsu S, Usami M, Arai Y, Kanetake H, Naito S, Hirao Y; Study Group for the Combined Androgen Blockade Therapy of Prostate Cancer. Combined androgen blockade with bicalutamide for advanced prostate cancer: long-term follow-up of a phase 3, double-blind, randomized study for survival. Cancer. 2009 Aug 1;115(15):3437-45. link to original article PubMed

Bicalutamide & Leuprolide

Regimen variant #1, 50 + 1 mo depot

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Schellhammer et al. 1995	1992-01 to 1993-09	Phase 3 (E-RT-switch-ic)	1. Bicalutamide & Goserelin	Not reported
Schellhammer et al. 1995	1992-01 to 1993-09	Phase 3 (E-RT-switch-ic)	2. Flutamide & Goserelin 3. Flutamide & Leuprolide	Equivalent TTP¹
Trachtenberg et al. 2002	NR	Phase 3 (C)	Abarelix	Inferior primary endpoint

¹Reported efficacy for Schellhammer et al. 1995 is based on the 1997 final update.

Endocrine therapy

Bicalutamide (Casodex) 50 mg PO once per day on days 1 to 28
Leuprolide (Lupron) 1-month depot 7.5 mg IM once on day 1

28-day cycles

Regimen variant #2, 50 + 3 mo depot

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Agarwal et al. 2022 (SWOG S1216)	2013-2017	Phase 3 (C)	ADT & Orteronel	Did not meet primary endpoint of OS

Endocrine therapy

Bicalutamide (Casodex) 50 mg PO once per day on days 1 to 90
Leuprolide (Lupron) 3-month depot 22.5 mg IM once on day 1

90-day cycles

Regimen variant #3, 80 + 1 mo depot

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Akaza et al. 2004	2000-02 to 2001-12	Phase 3 (E-esc)	1. Goserelin 2. Leuprolide	Seems to have superior OS¹ (secondary endpoint)

¹Reported efficacy is based on the 2009 update.

Endocrine therapy

Bicalutamide (Casodex) 80 mg PO once per day on days 1 to 28
Leuprolide (Lupron) 1-month depot 3.75 mg SC once on day 1

28-day cycles

References

Schellhammer P, Sharifi R, Block N, Soloway M, Venner P, Patterson AL, Sarosdy M, Vogelzang N, Jones J, Kolvenbag G; Casodex Combination Study Group. A controlled trial of bicalutamide versus flutamide, each in combination with luteinizing hormone-releasing hormone analogue therapy, in patients with advanced prostate cancer. Urology. 1995 May;45(5):745-52. link to original article PubMed
1. Update: Schellhammer PF, Sharifi R, Block NL, Soloway MS, Venner PM, Patterson AL, Sarosdy MF, Vogelzang NJ, Chen Y, Kolvenbag GJ; CASODEX Combination Study Group. 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. Cancer. 1996 Nov 15;78(10):2164-9. link to original article contains dosing details in abstract PubMed
2. Update: Soloway MS, Schellhammer P, Sharifi R, Venner P, Patterson AL, Sarosdy M, Vogelzang N, Jones J, Kolvenbag G; Casodex Combination Study Group. A controlled trial of Casodex (bicalutamide) vs flutamide, each in combination with luteinising hormone-releasing hormone analogue therapy in patients with advanced prostate cancer. Eur Urol. 1996;29 Suppl 2:105-9. link to original article contains dosing details in abstract PubMed
3. Update: Schellhammer PF, Sharifi R, Block NL, Soloway MS, Venner PM, Patterson AL, Sarosdy MF, Vogelzang NJ, Schellenger JJ, Kolvenbag GJ; Casodex Combination Study Group. Clinical benefits of bicalutamide compared with flutamide in combined androgen blockade for patients with advanced prostatic carcinoma: final report of a double-blind, randomized, multicenter trial. Urology. 1997 Sep;50(3):330-6. link to original article PubMed
Trachtenberg J, Gittleman M, Steidle C, Barzell W, Friedel W, Pessis D, Fotheringham N, Campion M, Garnick MB; Abarelix Study Group. A phase 3, multicenter, open label, randomized study of abarelix versus leuprolide plus daily antiandrogen in men with prostate cancer. J Urol. 2002 Apr;167(4):1670-4. link to original article contains dosing details in abstract 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 dosing details in manuscript PubMed
1. Update: Akaza H, Hinotsu S, Usami M, Arai Y, Kanetake H, Naito S, Hirao Y; Study Group for the Combined Androgen Blockade Therapy of Prostate Cancer. Combined androgen blockade with bicalutamide for advanced prostate cancer: long-term follow-up of a phase 3, double-blind, randomized study for survival. Cancer. 2009 Aug 1;115(15):3437-45. link to original article PubMed
SWOG S1216: Agarwal N, Tangen CM, Hussain MHA, Gupta S, Plets M, Lara PN, Harzstark AL, Twardowski PW, Paller CJ, Zylla D, Zibelman MR, Levine E, Roth BJ, Goldkorn A, Vaena DA, Kohli M, Crispino T, Vogelzang NJ, Thompson IM Jr, Quinn DI. Orteronel for Metastatic Hormone-Sensitive Prostate Cancer: A Multicenter, Randomized, Open-Label Phase III Trial (SWOG-1216). J Clin Oncol. 2022 Oct 1;40(28):3301-3309. Epub 2022 Apr 21. link to original article link to PMC article PubMed NCT01809691
1. Subgroup analysis: Sayegh N, Swami U, Jo Y, Gebrael G, Haaland B, Gupta S, Plets M, Hussain MHA, Quinn DI, Lara PN Jr, Thompson IM Jr, Agarwal N. Race and Treatment Outcomes in Patients With Metastatic Castration-Sensitive Prostate Cancer: A Secondary Analysis of the SWOG 1216 Phase 3 Trial. JAMA Netw Open. 2023 Aug 1;6(8):e2326546. link to original article link to PMC article PubMed

Degarelix monotherapy

Example orders

Example orders for Degarelix (Firmagon) in prostate cancer

Regimen variant #1, 240/80

FDA-recommended dose

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Klotz et al. 2008 (CS21)	2006-02 to 2007-10	Phase 3 (E-RT-switch-ic)	1. Degarelix; 240/160	Non-inferior testosterone suppression (primary endpoint)
Klotz et al. 2008 (CS21)	2006-02 to 2007-10	Phase 3 (E-RT-switch-ic)	2. Leuprolide	Non-inferior testosterone suppression (primary endpoint)

Endocrine therapy

Degarelix (Firmagon) as follows:
- Cycle 1: 240 mg SC once on day 1
- Cycle 2 onwards: 80 mg SC once on day 1

28-day cycles

Regimen variant #2, 240/160

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Klotz et al. 2008 (CS21)	2006-02 to 2007-10	Phase 3 (E-RT-switch-ic)	1. Degarelix; 240/80	Non-inferior testosterone suppression (primary endpoint)
Klotz et al. 2008 (CS21)	2006-02 to 2007-10	Phase 3 (E-RT-switch-ic)	2. Leuprolide	Non-inferior testosterone suppression (primary endpoint)

Endocrine therapy

Degarelix (Firmagon) as follows:
- Cycle 1: 240 mg SC once on day 1
- Cycle 2 onwards: 160 mg SC once on day 1

28-day cycles

Regimen variant #3, 240/480

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Ozono et al. 2018 (3550-CL-0010)	2013-NR	Phase 3 (E-switch-ic)	Goserelin	Non-inferior testosterone suppression (primary endpoint)

Endocrine therapy

Degarelix (Firmagon) as follows:
- Cycle 1: 240 mg SC once on day 1
- Cycle 2 onwards: 480 mg SC once on day 1

28-day course, then 12-week cycles

References

CS21: 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 dosing details in manuscript PubMed NCT00295750
1. 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 dosing details in manuscript PubMed
3550-CL-0010: Ozono S, Tsukamoto T, Naito S, Horie S, Ohashi Y, Uemura H, Yokomizo Y, Fukasawa S, Kusuoka H, Akazawa R, Saito M, Akaza H. Efficacy and safety of 3-month dosing regimen of degarelix in Japanese subjects with prostate cancer: a phase III study. Cancer Sci. 2018 Jun;109(6):1920-1929. Epub 2018 May 23. link to original article link to PMC article PubMed NCT01964170

Docetaxel, Estramustine, Goserelin

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Fizazi et al. 2015 (GETUG 12)	2002-2006	Phase 3 (E-esc)	ADT	Superior RFS (primary endpoint) RFS96: 62% vs 50% (HR 0.71, 95% CI 0.54-0.94)

Chemotherapy

Docetaxel (Taxotere) 70 mg/m² IV once on day 2
Estramustine (Emcyt) 10 mg/kg/day PO on days 1 to 5

21-day cycle for 4 cycles

Endocrine therapy

Goserelin (Zoladex) 10.8 mg SC once on day 1

3-month cycle for 12 cycles (3 years)

References

GETUG 12: Fizazi K, Faivre L, Lesaunier F, Delva R, Gravis G, Rolland F, Priou F, Ferrero JM, Houede N, Mourey L, Theodore C, Krakowski I, Berdah JF, Baciuchka M, Laguerre B, Fléchon A, Ravaud A, Cojean-Zelek I, Oudard S, Labourey JL, Chinet-Charrot P, Legouffe E, Lagrange JL, Linassier C, Deplanque G, Beuzeboc P, Davin JL, Martin AL, Habibian M, Laplanche A, Culine S. Androgen deprivation therapy plus docetaxel and estramustine versus androgen deprivation therapy alone for high-risk localised prostate cancer (GETUG 12): a phase 3 randomised controlled trial. Lancet Oncol. 2015 Jul;16(7):787-94. Epub 2015 May 28. link to original article contains dosing details in abstract PubMed NCT00055731

Flutamide monotherapy

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Boccon-Gibod et al. 1997	1989-1991	Phase 3 (E-switch-ic)	Bilateral orchiectomy	Did not meet primary endpoint of PFS
Fosså et al. 2001 (EORTC 30903)	1992-1998	Phase 3 (E-switch-ic)	Prednisone	Did not meet co-primary endpoints of TTP/OS

Note: Flutamide is 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

Continued indefinitely

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. link to original article contains dosing details in abstract PubMed
EORTC 30903: 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 dosing details in abstract PubMed

Flutamide & Goserelin

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Iversen et al. 1990	1986-06 to 1987-12	Phase 3 (E-switch-ic)	Bilateral orchiectomy	Did not meet co-primary endpoints of OS/PFS/TTP
Keuppens et al. 1990 (EORTC 30853)	1986-1988	Phase 3 (E-switch-ic)	Bilateral orchiectomy	Seems to have superior OS¹
Schellhammer et al. 1995	1992-01 to 1993-09	Phase 3 (C)	1. Bicalutamide & Goserelin 2. Bicalutamide & Leuprolide	Equivalent TTP²
Schellhammer et al. 1995	1992-01 to 1993-09	Phase 3 (C)	3. Flutamide & Leuprolide	Not reported
Hussain et al. 2013 (SWOG-9346)	1995-2008	Phase 3 (C)	Intermittent ADT	Inconclusive whether non-inferior OS

¹Reported efficacy for EORTC 30853 is based on the 1998 final update.
²Reported efficacy for Schellhammer et al. 1995 is based on the 1997 final update.

Endocrine therapy

Flutamide (Eulexin) 250 mg PO three times per day on days 1 to 28
Goserelin (Zoladex) 3.6 mg SC once on day 1

28-day cycles

References

EORTC 30853: Keuppens F, Denis L, Smith P, Carvalho AP, Newling D, Bond A, Sylvester R, De Pauw M, Vermeylen K, Ongena P; EORTC GU Group. Zoladex and flutamide versus bilateral orchiectomy: a randomized phase III EORTC 30853 study. Cancer. 1990 Sep 1;66(5 Suppl):1045-57. link to original article PubMed
1. Update: Denis LJ, Carnelro de Moura JL, Bono A, Sylvester R, Whelan P, Newling D, De Pauw M; EORTC GU Group. Goserelin acetate and flutamide versus bilateral orchiectomy: a phase III EORTC trial (30853). Urology. 1993 Aug;42(2):119-29. link to original article contains dosing details in abstract PubMed
2. Update: Denis LJ, Keuppens F, Smith PH, Whelan P, de Moura JL, Newling D, Bono A, Sylvester R; EORTC Genito-Urinary Tract Cancer Cooperative Group and the EORTC Data Center. Maximal androgen blockade: final analysis of EORTC phase III trial 30853. Eur Urol. 1998;33(2):144-51. link to original article PubMed
Iversen P, Christensen MG, Friis E, Hornbøl P, Hvidt V, Iversen HG, Klarskov P, Krarup T, Lund F, Mogensen P, Pedersen T, Rasmussen F, Rose C, Skaarup P, Wolf H. A phase III trial of zoladex and flutamide versus orchiectomy in the treatment of patients with advanced carcinoma of the prostate. Cancer. 1990 Sep 1;66(5 Suppl):1058-66. link to original article contains dosing details in manuscript PubMed
Schellhammer P, Sharifi R, Block N, Soloway M, Venner P, Patterson AL, Sarosdy M, Vogelzang N, Jones J, Kolvenbag G; Casodex Combination Study Group. A controlled trial of bicalutamide versus flutamide, each in combination with luteinizing hormone-releasing hormone analogue therapy, in patients with advanced prostate cancer. Urology. 1995 May;45(5):745-52. link to original article PubMed
1. Update: Schellhammer PF, Sharifi R, Block NL, Soloway MS, Venner PM, Patterson AL, Sarosdy MF, Vogelzang NJ, Chen Y, Kolvenbag GJ; CASODEX Combination Study Group. 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. Cancer. 1996 Nov 15;78(10):2164-9. link to original article contains dosing details in abstract PubMed
2. Update: Soloway MS, Schellhammer P, Sharifi R, Venner P, Patterson AL, Sarosdy M, Vogelzang N, Jones J, Kolvenbag G; Casodex Combination Study Group. A controlled trial of Casodex (bicalutamide) vs flutamide, each in combination with luteinising hormone-releasing hormone analogue therapy in patients with advanced prostate cancer. Eur Urol. 1996;29 Suppl 2:105-9. link to original article contains dosing details in abstract PubMed
3. Update: Schellhammer PF, Sharifi R, Block NL, Soloway MS, Venner PM, Patterson AL, Sarosdy MF, Vogelzang NJ, Schellenger JJ, Kolvenbag GJ; Casodex Combination Study Group. Clinical benefits of bicalutamide compared with flutamide in combined androgen blockade for patients with advanced prostatic carcinoma: final report of a double-blind, randomized, multicenter trial. Urology. 1997 Sep;50(3):330-6. link to original article PubMed
SWOG-9346: 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 dosing details in supplement PubMed NCT00002651

Flutamide & Leuprolide

Regimen variant #1, daily Lupron

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Crawford et al. 1989 (SWOG-8494)	1985-01 to 1986-04	Phase 3 (E-RT-esc)	Leuprolide	Seems to have superior OS

Note: this is likely of historic importance only, given the formulation of leuoprolide.

Endocrine therapy

Flutamide (Eulexin) 250 mg PO three times per day
Leuprolide (Lupron) 1 mg SC once per day

Continued indefinitely

Regimen variant #2, 1-month depot Lupron

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Schellhammer et al. 1995	1992-01 to 1993-09	Phase 3 (C)	1. Bicalutamide & Goserelin 2. Bicalutamide & Leuprolide	Equivalent TTP¹
Schellhammer et al. 1995	1992-01 to 1993-09	Phase 3 (C)	3. Flutamide & Goserelin	Not reported
Hussain et al. 2013 (SWOG-9346)	1995-2008	Phase 3 (C)	Intermittent ADT	Inconclusive whether non-inferior OS

¹Reported efficacy for Schellhammer et al. 1995 is based on the 1997 final update.

Endocrine therapy

Flutamide (Eulexin) 250 mg PO three times per day on days 1 to 28
Leuprolide (Lupron) 1-month depot 7.5 mg IM once on day 1

28-day cycles

References

SWOG-8494: Crawford ED, Eisenberger MA, McLeod DG, Spaulding JT, Benson R, Dorr FA, Blumenstein BA, Davis MA, Goodman PJ. A controlled trial of leuprolide with and without flutamide in prostatic carcinoma. N Engl J Med. 1989 Aug 17;321(7):419-24. Erratum in: N Engl J Med 1989 Nov 16;321(20):1420. link to original article contains dosing details in manuscript PubMed
Schellhammer P, Sharifi R, Block N, Soloway M, Venner P, Patterson AL, Sarosdy M, Vogelzang N, Jones J, Kolvenbag G; Casodex Combination Study Group. A controlled trial of bicalutamide versus flutamide, each in combination with luteinizing hormone-releasing hormone analogue therapy, in patients with advanced prostate cancer. Urology. 1995 May;45(5):745-52. link to original article PubMed
1. Update: Schellhammer PF, Sharifi R, Block NL, Soloway MS, Venner PM, Patterson AL, Sarosdy MF, Vogelzang NJ, Chen Y, Kolvenbag GJ; CASODEX Combination Study Group. 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. Cancer. 1996 Nov 15;78(10):2164-9. link to original article contains dosing details in abstract PubMed
2. Update: Soloway MS, Schellhammer P, Sharifi R, Venner P, Patterson AL, Sarosdy M, Vogelzang N, Jones J, Kolvenbag G; Casodex Combination Study Group. A controlled trial of Casodex (bicalutamide) vs flutamide, each in combination with luteinising hormone-releasing hormone analogue therapy in patients with advanced prostate cancer. Eur Urol. 1996;29 Suppl 2:105-9. link to original article contains dosing details in abstract PubMed
3. Update: Schellhammer PF, Sharifi R, Block NL, Soloway MS, Venner PM, Patterson AL, Sarosdy MF, Vogelzang NJ, Schellenger JJ, Kolvenbag GJ; Casodex Combination Study Group. Clinical benefits of bicalutamide compared with flutamide in combined androgen blockade for patients with advanced prostatic carcinoma: final report of a double-blind, randomized, multicenter trial. Urology. 1997 Sep;50(3):330-6. link to original article PubMed
SWOG-9346: 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 dosing details in supplement PubMed NCT00002651

Goserelin monotherapy

Example orders

Example orders for Goserelin (Zoladex) in prostate cancer

Regimen variant #1, 28-day cycles

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Soloway et al. 1991	NR	Phase 3 (E-switch-ic)	Bilateral orchiectomy	Did not meet efficacy endpoints
Kaisary et al. 1991	1983-1986	Phase 3 (E-switch-ic)	Bilateral orchiectomy	Did not meet efficacy endpoints
Waymont et al. 1992	1985-1987	Phase 3 (E-switch-ic)	DES	Seems to have superior time to first response
Tyrrell et al. 1991 (IPCSG)	1986-01 to 1987-07	Phase 3 (C)	Flutamide & Goserelin	Did not meet efficacy endpoints
Boccardo et al. 1993 (PONCAP)	1987-1990	Phase 3 (C)	Flutamide & Goserelin	Might have inferior PFS50%

Endocrine therapy

Goserelin (Zoladex) 3.6 mg SC once on day 1

28-day cycles

Regimen variant #2, 12-week cycles

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Ozono et al. 2018 (3550-CL-0010)	2013-NR	Phase 3 (C)	Degarelix	Non-inferior testosterone suppression

Endocrine therapy

Goserelin (Zoladex) as follows:
- Cycle 1: 3.6 mg SC once on day 1
- Cycle 2 onwards: 10.8 mg SC once on day 1

28-day course, then 12-week cycles

References

Soloway MS, Chodak G, Vogelzang NJ, Block NL, Schellhammer PF, Smith JA Jr, Scott M, Kennealey G, Gau TC; Zoladex Prostate Study Group. Zoladex versus orchiectomy in treatment of advanced prostate cancer: a randomized trial. Urology. 1991 Jan;37(1):46-51. link to original article PubMed
1. Update: Vogelzang NJ, Chodak GW, Soloway MS, Block NL, Schellhammer PF, Smith JA Jr, Caplan RJ, Kennealey GT; Zoladex Prostate Study Group. Goserelin versus orchiectomy in the treatment of advanced prostate cancer: final results of a randomized trial. Urology. 1995 Aug;46(2):220-6. link to original article contains dosing details in manuscript 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. link to original article PubMed
IPCSG: Tyrrell CJ, Altwein JE, Klippel F, Varenhorst E, Lunglmayr G, Boccardo F, Holdaway IM, Haefliger JM, Jordaan JP; International Prostate Cancer Study Group. A multicenter randomized trial comparing the luteinizing hormone-releasing hormone analogue goserelin acetate alone and with flutamide in the treatment of advanced prostate cancer. J Urol. 1991 Nov;146(5):1321-6. link to original article PubMed
Waymont B, Lynch TH, Dunn JA, Emtage LA, Arkell DG, Wallace DM, Blackledge GR. Phase III randomised study of zoladex versus stilboestrol in the treatment of advanced prostate cancer. Br J Urol. 1992 Jun;69(6):614-20. link to original article PubMed
PONCAP: Boccardo F, Pace M, Rubagotti A, Guarneri D, Decensi A, Oneto F, Martorana G, Giuliani L, Selvaggi F, Battaglia M, Delli Ponti U, Petracco S, Cortellini P, Ziveri M, Ferraris V, Bruttini GP, Epis R, Comeri G, Gallo G; Italian Prostatic Cancer Project (PONCAP) Study Group. Goserelin acetate with or without flutamide in the treatment of patients with locally advanced or metastatic prostate cancer. Eur J Cancer. 1993;29A(8):1088-93. link to original article PubMed
3550-CL-0010: Ozono S, Tsukamoto T, Naito S, Horie S, Ohashi Y, Uemura H, Yokomizo Y, Fukasawa S, Kusuoka H, Akazawa R, Saito M, Akaza H. Efficacy and safety of 3-month dosing regimen of degarelix in Japanese subjects with prostate cancer: a phase III study. Cancer Sci. 2018 Jun;109(6):1920-1929. Epub 2018 May 23. link to original article link to PMC article PubMed NCT01964170

Histrelin monotherapy

Regimen

Study	Dates of enrollment	Evidence
Schlegel 2006	NR	Non-randomized (RT)

Endocrine therapy

Histrelin (Vantas)

References

Schlegel PN; Histrelin Study Group. Efficacy and safety of histrelin subdermal implant in patients with advanced prostate cancer. J Urol. 2006 Apr;175(4):1353-8. link to original article PubMed

Intermittent ADT

IHT: Intermittent Hormone Therapy

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Calais da Silva et al. 2009 (SEUG 9401)	NR	Phase 3 (E-de-esc)	Continuous ADT	Did not meet primary endpoint of TTP
Hussain et al. 2013 (SWOG-9346)	1995-2008	Phase 3 (E-de-esc)	Continuous ADT	Inconclusive whether non-inferior OS (co-primary endpoint)
Crook et al. 2012 (NCIC-CTG PR.7)	1999-2005	Phase 3 (E-de-esc)	Continuous ADT	Non-inferior OS (primary endpoint) Median OS: 8.8 vs 9.1 y (HR 1.02, 95% CI 0.86-1.21)
Calais da Silva et al. 2013 (SEUG 9901)	2000-2007	Phase 3 (E-de-esc)	Continuous ADT	Non-inferior OS (primary endpoint)

Note: See papers for details about treatment holidays.

Endocrine therapy

LHRH agonist
Nonsteroidal antiandrogen for at least 4 weeks

8-month cycles

References

SEUG 9401: Calais da Silva FE, Bono AV, Whelan P, Brausi M, Marques Queimadelos A, Martin JA, Kirkali Z, Calais da Silva FM, Robertson C. Intermittent androgen deprivation for locally advanced and metastatic prostate cancer: results from a randomised phase 3 study of the South European Uroncological Group. Eur Urol. 2009 Jun;55(6):1269-77. Epub 2009 Feb 21. link to original article PubMed
NCIC-CTG PR.7: Crook JM, O'Callaghan CJ, Duncan G, Dearnaley DP, Higano CS, Horwitz EM, Frymire E, Malone S, Chin J, Nabid A, Warde P, Corbett T, Angyalfi S, Goldenberg SL, Gospodarowicz MK, Saad F, Logue JP, Hall E, Schellhammer PF, Ding K, Klotz L. Intermittent androgen suppression for rising PSA level after radiotherapy. N Engl J Med. 2012 Sep 6;367(10):895-903. Erratum in: N Engl J Med. 2012 Dec 6;367(23):2262. link to original article link to PMC article PubMed NCT00003653
SWOG-9346: 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 dosing details in supplement PubMed NCT00002651
SEUG 9901: Calais da Silva F, Calais da Silva FM, Gonçalves F, Santos A, Kliment J, Whelan P, Oliver T, Antoniou N, Pastidis S, Marques Queimadelos A, Robertson C. Locally advanced and metastatic prostate cancer treated with intermittent androgen monotherapy or maximal androgen blockade: results from a randomised phase 3 study by the South European Uroncological Group. Eur Urol. 2014 Aug;66(2):232-9. Epub 2013 Apr 4. link to original article PubMed NCT00363285

Leuprolide monotherapy

Example orders

Example orders for Leuprolide (Lupron) in prostate cancer

Regimen variant #1, daily

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy	Comparative Toxicity
Garnick et al. 1984	1981-NR	Phase 3 (E-switch-ic)	DES	Did not meet efficacy endpoints	Less toxic
Crawford et al. 1989 (SWOG-8494)	1985-01 to 1986-04	Phase 3 (C)	Flutamide & Leuprolide	Seems to have inferior OS

Note: this is of historic importance only, given the wide availability of depot formulations of leuoprolide.

Endocrine therapy

Leuprolide (Lupron) 1 mg SC once per day

Continued indefinitely

Regimen variant #2, 1-month depot, 3.75 mg

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Akaza et al. 2004	2000-02 to 2001-12	Phase 3 (C)	1. Bicalutamide & Goserelin 2. Bicalutamide & Leuprolide	Seems to have inferior OS¹

¹Reported efficacy is based on the 2009 update.

Endocrine therapy

Leuprolide (Lupron) 1-month depot 3.75 mg SC once on day 1

28-day cycles

Regimen variant #3, 1-month depot, 7.5 mg

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Sharifi & Soloway 1990	1986-NR	Non-randomized (RT)
Heyns et al. 2003	NR	Phase 3 (C)	Triptorelin	Seems to have inferior 9-month OS
Klotz et al. 2008 (CS21)	2006-02 to 2007-10	Phase 3 (C)	1. Degarelix; 240/80	Non-inferior testosterone suppression (primary endpoint)
Klotz et al. 2008 (CS21)	2006-02 to 2007-10	Phase 3 (C)	2. Degarelix; 240/160	Non-inferior testosterone suppression (primary endpoint)

Endocrine therapy

Leuprolide (Lupron) 1-month depot 7.5 mg IM once on day 1

28-day cycles

Regimen variant #4, 3-month depot

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Sharifi et al. 1996	NR	Phase 2 (RT)
Shore et al. 2020 (HERO)	2017-04 to 2018-10	Phase 3 (C)	Relugolix	Inferior testosterone suppression

Endocrine therapy

Leuprolide (Lupron) 3-month depot 22.5 mg IM once on day 1

84-day cycles

Regimen variant #5, 4-month depot

Study	Dates of enrollment	Evidence
Sharifi et al. 1998	NR	Phase 2 (RT)

Endocrine therapy

Leuprolide (Lupron) 4-month depot 30 mg IM once on day 1

16-week cycles

Regimen variant #6, 6-month depot

Study	Dates of enrollment	Evidence
Spitz et al. 2011 (L-PC07-169)	2008-2009	Non-randomized phase 3 (RT)

Endocrine therapy

Leuprolide (Lupron) 6-month depot 45 mg IM once on day 1

26-week cycles

References

Garnick MB, Glode LM; Leuprolide Study Group. Leuprolide versus diethylstilbestrol for metastatic prostate cancer. N Engl J Med. 1984 Nov 15;311(20):1281-6. link to original article contains dosing details in abstract PubMed
SWOG-8494: Crawford ED, Eisenberger MA, McLeod DG, Spaulding JT, Benson R, Dorr FA, Blumenstein BA, Davis MA, Goodman PJ. A controlled trial of leuprolide with and without flutamide in prostatic carcinoma. N Engl J Med. 1989 Aug 17;321(7):419-24. Erratum in: N Engl J Med 1989 Nov 16;321(20):1420. link to original article contains dosing details in manuscript PubMed
Sharifi R, Soloway M; Leuprolide Study Group. Clinical study of leuprolide depot formulation in the treatment of advanced prostate cancer. J Urol. 1990 Jan;143(1):68-71. link to original article PubMed
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 dosing details in manuscript 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
Heyns CF, Simonin MP, Grosgurin P, Schall R, Porchet HC; South African Triptorelin Study Group. Comparative efficacy of triptorelin pamoate and leuprolide acetate in men with advanced prostate cancer. BJU Int. 2003 Aug;92(3):226-31. link to original article contains dosing details in abstract 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 dosing details in manuscript PubMed
1. Update: Akaza H, Hinotsu S, Usami M, Arai Y, Kanetake H, Naito S, Hirao Y; Study Group for the Combined Androgen Blockade Therapy of Prostate Cancer. Combined androgen blockade with bicalutamide for advanced prostate cancer: long-term follow-up of a phase 3, double-blind, randomized study for survival. Cancer. 2009 Aug 1;115(15):3437-45. link to original article PubMed
CS21: 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 dosing details in manuscript PubMed NCT00295750
1. 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 dosing details in manuscript PubMed
L-PC07-169: Spitz A, Young JM, Larsen L, Mattia-Goldberg C, Donnelly J, Chwalisz K. Efficacy and safety of leuprolide acetate 6-month depot for suppression of testosterone in patients with prostate cancer. Prostate Cancer Prostatic Dis. 2012 Mar;15(1):93-9. Epub 2011 Oct 25. link to original article link to PMC article PubMed NCT00626431
HERO: Shore ND, Saad F, Cookson MS, George DJ, Saltzstein DR, Tutrone R, Akaza H, Bossi A, van Veenhuyzen DF, Selby B, Fan X, Kang V, Walling J, Tombal B; HERO Study Investigators. Oral Relugolix for Androgen-Deprivation Therapy in Advanced Prostate Cancer. N Engl J Med. 2020 Jun 4;382(23):2187-2196. Epub 2020 May 29. link to original article contains dosing details in manuscript PubMed NCT03085095
1. HRQoL analysis: Tombal B, Collins S, Morgans AK, Hunsche E, Brown B, Zhu E, Bossi A, Shore N. Impact of Relugolix Versus Leuprolide on the Quality of Life of Men with Advanced Prostate Cancer: Results from the Phase 3 HERO Study. Eur Urol. 2023 Dec;84(6):579-587. Epub 2023 Oct 11. link to original article PubMed

Nilutamide & Orchiectomy

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Janknegt et al. 1993 (International Anandron Study)	1986-NR	Phase 3 (E-RT-esc)	Bilateral orchiectomy	Superior PFS

Note: Nilutamide was to start the day of, or day after surgical castration/orchiectomy.

Endocrine therapy

Nilutamide (Nilandron) as follows:
- Cycle 1: 300 mg PO once per day
- Cycle 2 onwards: 150 mg PO once per day
Bilateral orchiectomy

One-month cycles

References

International Anandron Study: Janknegt RA, Abbou CC, Bartoletti R, Bernstein-Hahn L, Bracken B, Brisset JM, Da Silva FC, Chisholm G, Crawford ED, Debruyne FM, Dijkman GD, Frick J, Goedhals J, Knönagel H, Venner PM. 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. link to original article PubMed
1. Update: Janknegt RA; Anandron International Study Group. Total androgen blockade with the use of orchiectomy and nilutamide (Anandron) or placebo as treatment of metastatic prostate cancer. Cancer. 1993 Dec 15;72(12 Suppl):3874-7. link to original article PubMed
2. Update: Dijkman GA, Janknegt RA, De Reijke TM, Debruyne FM; International Anandron Study Group. Long-term efficacy and safety of nilutamide plus castration in advanced prostate cancer, and the significance of early prostate specific antigen normalization. J Urol. 1997 Jul;158(1):160-3. link to original article PubMed
3. 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 dosing details in manuscript PubMed

Relugolix monotherapy

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Shore et al. 2020 (HERO)	2017-04 to 2018-10	Phase 3 (E-RT-switch-ic)	Leuprolide	Superior testosterone suppression (primary endpoint)

Endocrine therapy

Relugolix (Orgovyx) 360 mg PO once on day 1, then 120 mg PO once per day

48-week course

References

HERO: Shore ND, Saad F, Cookson MS, George DJ, Saltzstein DR, Tutrone R, Akaza H, Bossi A, van Veenhuyzen DF, Selby B, Fan X, Kang V, Walling J, Tombal B; HERO Study Investigators. Oral Relugolix for Androgen-Deprivation Therapy in Advanced Prostate Cancer. N Engl J Med. 2020 Jun 4;382(23):2187-2196. Epub 2020 May 29. link to original article contains dosing details in manuscript PubMed NCT03085095
1. HRQoL analysis: Tombal B, Collins S, Morgans AK, Hunsche E, Brown B, Zhu E, Bossi A, Shore N. Impact of Relugolix Versus Leuprolide on the Quality of Life of Men with Advanced Prostate Cancer: Results from the Phase 3 HERO Study. Eur Urol. 2023 Dec;84(6):579-587. Epub 2023 Oct 11. link to original article PubMed

Triptorelin monotherapy

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Heyns et al. 2003	NR	Phase 3 (E-RT-switch-ic)	Leuprolide	Seems to have superior 9-month OS (secondary endpoint) Equivalent rates of castrate testosterone levels (primary endpoint)

Endocrine therapy

Triptorelin (Trelstar LA) 3.75 mg IM once on day 1

28-day cycle for 9 cycles

References

Heyns CF, Simonin MP, Grosgurin P, Schall R, Porchet HC; South African Triptorelin Study Group. Comparative efficacy of triptorelin pamoate and leuprolide acetate in men with advanced prostate cancer. BJU Int. 2003 Aug;92(3):226-31. link to original article contains dosing details in manuscript PubMed

Metastatic disease, second-line hormonal therapy

Abiraterone monotherapy

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
de Bono et al. 2011 (COU-AA-301)	2008-05 to 2009-07	Phase 3 (E-RT-esc)	Prednisone	Superior OS¹ (primary endpoint) Median OS: 15.8 vs 11.2 mo (HR 0.74, 95% CI 0.64-0.86)
Ryan et al. 2013 (COU-AA-302)	2009-04 to 2010-06	Phase 3 (E-RT-esc)	Prednisone	Superior OS² (co-primary endpoint) Median OS: 34.7 vs 30.3 mo (HR 0.81, 95% CI 0.70-0.93)
Ye et al. 2017 (ABI-PRO-3002)	2012-03-27 to 2013-02-14	Phase 3 (E-esc)	Prednisone	Superior TTPP (primary endpoint)
Attard et al. 2018 (PLATO)	2013-NR	Phase 3 (C)	Abiraterone, Enzalutamide, Prednisone	Did not meet primary endpoint of PFS
Smith et al. 2019 (ERA 223)	2014-2016	Phase 3 (C)	Abiraterone, Radium-223, Prednisone	Did not meet primary endpoint of symptomatic skeletal EFS
Saad et al. 2021 (ACIS)	2014-2016	Phase 3 (C)	Abiraterone & Apalutamide	Inferior rPFS
de Wit et al. 2019 (CARD)	2015-2018	Phase 3 (C)	Cabazitaxel & Prednisone	Inferior PFSi/OS
Sweeney et al. 2021 (IPATential150)	2017-2019	Phase 3 (C)	Abiraterone & Ipatasertib	Seems to have inferior rPFS
Clarke et al. 2022 (PROpel)	2018-2020	Phase 3 (C)	Abiraterone & Olaparib	Might have inferior OS³
Antonarakis et al. 2023 (KEYLYNK-010)	2019-05-30 to 2021-07-16	Phase 3 (C)	Olaparib & Pembrolizumab	Did not meet co-primary endpoints of rPFS/OS

¹Reported efficacy for COU-AA-301 is based on the 2012 update.
²Reported efficacy for COU-AA-302 is based on the 2015 update.
³Reported efficacy for PROpel is based on the 2023 update.

Prior treatment criteria

COU-AA-301: Chemotherapy exposure
COU-AA-302, ABI-PRO-3002, PLATO, ERA 223, ACIS, IPATential150: Chemotherapy naive
KEYLYNK-010: Enzalutamide exposure

Preceding treatment

PLATO: First-line enzalutamide, with rising PSA

Endocrine therapy

Abiraterone (Zytiga) 1000 mg PO once per day on days 1 to 28

Supportive therapy

One of the following:
- Prednisone (Sterapred) 5 mg PO twice per day on days 1 to 28
- Prednisolone (Millipred) 5 mg PO twice per day on days 1 to 28

28-day cycles

References

COU-AA-301: 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 dosing details in manuscript link to PMC article PubMed NCT00638690
1. 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 dosing details in manuscript PubMed
2. 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 dosing details in manuscript PubMed
COU-AA-302: 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 dosing details in manuscript link to PMC article PubMed NCT00887198
1. 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
ABI-PRO-3002: Ye D, Huang Y, Zhou F, Xie K, Matveev V, Li C, Alexeev B, Tian Y, Qiu M, Li H, Zhou T, De Porre P, Yu M, Naini V, Liang H, Wu Z, Sun Y. A phase 3, double-blind, randomized placebo-controlled efficacy and safety study of abiraterone acetate in chemotherapy-naïve patients with mCRPC in China, Malaysia, Thailand and Russia. Asian J Urol. 2017 Apr;4(2):75-85. Epub 2017 Jan 23. link to original article link to PMC article contains dosing details in manuscript PubMed NCT01591122
PLATO: Attard G, Borre M, Gurney H, Loriot Y, Andresen-Daniil C, Kalleda R, Pham T, Taplin ME; PLATO collaborators. Abiraterone alone or in combination with enzalutamide in metastatic castration-resistant prostate cancer with rising prostate-specific antigen during enzalutamide treatment. J Clin Oncol. 2018 Sep 1;36(25):2639-2646. Epub 2018 Jul 20. link to original article contains dosing details in manuscript link to PMC article PubMed NCT01995513
ERA 223: Smith M, Parker C, Saad F, Miller K, Tombal B, Ng QS, Boegemann M, Matveev V, Piulats JM, Zucca LE, Karyakin O, Kimura G, Matsubara N, Nahas WC, Nolè F, Rosenbaum E, Heidenreich A, Kakehi Y, Zhang A, Krissel H, Teufel M, Shen J, Wagner V, Higano C. Addition of radium-223 to abiraterone acetate and prednisone or prednisolone in patients with castration-resistant prostate cancer and bone metastases (ERA 223): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2019 Mar;20(3):408-419. Epub 2019 Feb 6. link to original article contains dosing details in abstract PubMed NCT02043678
CARD: de Wit R, de Bono J, Sternberg CN, Fizazi K, Tombal B, Wülfing C, Kramer G, Eymard JC, Bamias A, Carles J, Iacovelli R, Melichar B, Sverrisdóttir Á, Theodore C, Feyerabend S, Helissey C, Ozatilgan A, Geffriaud-Ricouard C, Castellano D; CARD Investigators. Cabazitaxel versus Abiraterone or Enzalutamide in Metastatic Prostate Cancer. N Engl J Med. 2019 Dec 26;381(26):2506-2518. Epub 2019 Sep 30. link to original article contains dosing details in manuscript PubMed NCT02485691
1. HRQoL analysis: Fizazi K, Kramer G, Eymard JC, Sternberg CN, de Bono J, Castellano D, Tombal B, Wülfing C, Liontos M, Carles J, Iacovelli R, Melichar B, Sverrisdóttir Á, Theodore C, Feyerabend S, Helissey C, Oudard S, Facchini G, Poole EM, Ozatilgan A, Geffriaud-Ricouard C, Bensfia S, de Wit R. Quality of life in patients with metastatic prostate cancer following treatment with cabazitaxel versus abiraterone or enzalutamide (CARD): an analysis of a randomised, multicentre, open-label, phase 4 study. Lancet Oncol. 2020 Nov;21(11):1513-1525. Epub 2020 Sep 11. link to original article PubMed
IPATential150: Sweeney C, Bracarda S, Sternberg CN, Chi KN, Olmos D, Sandhu S, Massard C, Matsubara N, Alekseev B, Parnis F, Atduev V, Buchschacher GL Jr, Gafanov R, Corrales L, Borre M, Stroyakovskiy D, Alves GV, Bournakis E, Puente J, Harle-Yge ML, Gallo J, Chen G, Hanover J, Wongchenko MJ, Garcia J, de Bono JS. Ipatasertib plus abiraterone and prednisolone in metastatic castration-resistant prostate cancer (IPATential150): a multicentre, randomised, double-blind, phase 3 trial. Lancet. 2021 Jul 10;398(10295):131-142. link to original article PubMed NCT03072238
ACIS: Saad F, Efstathiou E, Attard G, Flaig TW, Franke F, Goodman OB Jr, Oudard S, Steuber T, Suzuki H, Wu D, Yeruva K, De Porre P, Brookman-May S, Li S, Li J, Thomas S, Bevans KB, Mundle SD, McCarthy SA, Rathkopf DE; ACIS Investigators. Apalutamide plus abiraterone acetate and prednisone versus placebo plus abiraterone and prednisone in metastatic, castration-resistant prostate cancer (ACIS): a randomised, placebo-controlled, double-blind, multinational, phase 3 study. Lancet Oncol. 2021 Nov;22(11):1541-1559. Epub 2021 Sep 30. link to original article contains dosing details in abstract link to PMC article PubMed NCT02257736
PROpel: Clarke NW, Armstrong AJ, Thiery-Vuillemin A, Oya M, Shore N, Loredo E, Procopio G, de Menezes J, Girotto G, Arslan C, Mehra N, Parnis F, Brown E, Schlürmann F, Joung JY, Sugimoto M, Virizuela JA, Emmenegger U, Navratil J, Buchschacher GL, Poehlein C, Harrington EA, Desai C, Kang J, Saad F; PROpel Investigators. Abiraterone and Olaparib for Metastatic Castration-Resistant Prostate Cancer. NEJM Evidence. 2022 Sep;1(9):EVIDoa2200043. Epub 2022 Jun 3. link to original article contains dosing details in manuscript PubMed NCT03732820
1. Update: Saad F, Clarke NW, Oya M, Shore N, Procopio G, Guedes JD, Arslan C, Mehra N, Parnis F, Brown E, Schlürmann F, Joung JY, Sugimoto M, Sartor O, Liu YZ, Poehlein C, Barker L, Del Rosario PM, Armstrong AJ. Olaparib plus abiraterone versus placebo plus abiraterone in metastatic castration-resistant prostate cancer (PROpel): final prespecified overall survival results of a randomised, double-blind, phase 3 trial. Lancet Oncol. 2023 Oct;24(10):1094-1108. Epub 2023 Sep 12. link to original article PubMed
KEYLYNK-010: Antonarakis ES, Park SH, Goh JC, Shin SJ, Lee JL, Mehra N, McDermott R, Sala-Gonzalez N, Fong PC, Greil R, Retz M, Sade JP, Yanez P, Huang YH, Begbie SD, Gafanov RA, De Santis M, Rosenbaum E, Kolinsky MP, Rey F, Chiu KY, Roubaud G, Kramer G, Sumitomo M, Massari F, Suzuki H, Qiu P, Zhang J, Kim J, Poehlein CH, Yu EY. Pembrolizumab Plus Olaparib for Patients With Previously Treated and Biomarker-Unselected Metastatic Castration-Resistant Prostate Cancer: The Randomized, Open-Label, Phase III KEYLYNK-010 Trial. J Clin Oncol. 2023 Aug 1;41(22):3839-3850. Epub 2023 Jun 8. link to original article contains dosing details in manuscript PubMed NCT03834519
AMPLITUDE: NCT04497844

Abiraterone & Apalutamide

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Saad et al. 2021 (ACIS)	2014-2016	Phase 3 (E-esc)	Abiraterone	Superior rPFS (primary endpoint) Median rPFS: 24 vs 16.6 mo (HR 0.70, 95% CI 0.60-0.83)

Endocrine therapy

Abiraterone (Zytiga) 1000 mg PO once per day on days 1 to 28
Apalutamide (Erleada) 240 mg PO once per day on days 1 to 28

Supportive therapy

Prednisone (Sterapred) 5 mg PO twice per day on days 1 to 28

28-day cycles

References

ACIS: Saad F, Efstathiou E, Attard G, Flaig TW, Franke F, Goodman OB Jr, Oudard S, Steuber T, Suzuki H, Wu D, Yeruva K, De Porre P, Brookman-May S, Li S, Li J, Thomas S, Bevans KB, Mundle SD, McCarthy SA, Rathkopf DE; ACIS Investigators. Apalutamide plus abiraterone acetate and prednisone versus placebo plus abiraterone and prednisone in metastatic, castration-resistant prostate cancer (ACIS): a randomised, placebo-controlled, double-blind, multinational, phase 3 study. Lancet Oncol. 2021 Nov;22(11):1541-1559. Epub 2021 Sep 30. link to original article contains dosing details in abstract link to PMC article PubMed NCT02257736

Abiraterone & Olaparib

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Clarke et al. 2022 (PROpel)	2018-2020	Phase 3 (E-RT-esc)	Abiraterone	Might have superior OS (secondary endpoint) Median OS: 42.1 vs 34.7 mo (HR 0.81, 95% CI 0.67-1.00) Superior ibPFS (primary endpoint) Median ibPFS: 24.8 vs 16.6 mo (HR 0.66, 95% CI 0.54-0.81)

¹Reported efficacy is based on the 2023 update.

Endocrine therapy

Abiraterone (Zytiga) 1000 mg PO once per day

Targeted therapy

Olaparib (Lynparza) 300 mg PO twice per day

Supportive therapy

One of the following:
- Prednisone (Sterapred) 5 mg PO twice per day
- Prednisolone (Millipred) 5 mg PO twice per day

21-day cycle for up to 10 cycles

References

PROpel: Clarke NW, Armstrong AJ, Thiery-Vuillemin A, Oya M, Shore N, Loredo E, Procopio G, de Menezes J, Girotto G, Arslan C, Mehra N, Parnis F, Brown E, Schlürmann F, Joung JY, Sugimoto M, Virizuela JA, Emmenegger U, Navratil J, Buchschacher GL, Poehlein C, Harrington EA, Desai C, Kang J, Saad F; PROpel Investigators. Abiraterone and Olaparib for Metastatic Castration-Resistant Prostate Cancer. NEJM Evidence. 2022 Sep;1(9):EVIDoa2200043. Epub 2022 Jun 3. link to original article contains dosing details in manuscript PubMed NCT03732820
1. Update: Saad F, Clarke NW, Oya M, Shore N, Procopio G, Guedes JD, Arslan C, Mehra N, Parnis F, Brown E, Schlürmann F, Joung JY, Sugimoto M, Sartor O, Liu YZ, Poehlein C, Barker L, Del Rosario PM, Armstrong AJ. Olaparib plus abiraterone versus placebo plus abiraterone in metastatic castration-resistant prostate cancer (PROpel): final prespecified overall survival results of a randomised, double-blind, phase 3 trial. Lancet Oncol. 2023 Oct;24(10):1094-1108. Epub 2023 Sep 12. link to original article PubMed

Antiandrogen withdrawal

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Small et al. 2004 (CALGB 9583)	NR	Phase 3 (C)	Ketoconazole & Hydrocortisone	Inferior PSA response

Refers to cessation of antiandrogen therapy.

References

CALGB 9583: 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 dosing details in manuscript PubMed NCT00002760

Apalutamide monotherapy

Regimen

Study	Dates of enrollment	Evidence
Rathkopf et al. 2017 (ARN-509-001)	2011-2012	Non-randomized

Endocrine therapy

Apalutamide (Erleada) 240 mg PO once per day

Continued indefinitely

References

ARN-509-001: Rathkopf DE, Antonarakis ES, Shore ND, Tutrone RF, Alumkal JJ, Ryan CJ, Saleh M, Hauke RJ, Bandekar R, Maneval EC, de Boer CJ, Yu MK, Scher HI. Safety and Antitumor Activity of Apalutamide (ARN-509) in Metastatic Castration-Resistant Prostate Cancer with and without Prior Abiraterone Acetate and Prednisone. Clin Cancer Res. 2017 Jul 15;23(14):3544-3551. Epub 2017 Feb 17. link to original article link to PMC article contains dosing details in manuscript PubMed NCT01171898

BAT

BAT: Bipolar Androgen Therapy

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Denmeade et al. 2021 (TRANSFORMER)	2015-2018	Randomized Phase 2 (E-esc)	Enzalutamide	Did not meet primary endpoint of PFS¹ Median PFS: 5.7 vs 5.7 mo

¹Study not powered for equivalency. Secondary endpoint of PFS2 after crossover was superior in BAT to enzalutamide arm.

Eligibility criteria

Castrate-resistant, metastatic, asymptomatic

Prior treatment criteria

Abiraterone, with progression

Endocrine therapy

ADT: All patients maintained on continuous testosterone suppression via surgical castration or GnRH agonist or GnRH antagonist
Bipolar Androgen Therapy (BAT): Testosterone cypionate 400 mg IM once every 28 days
Enzalutamide: 160 mg by mouth daily

Subsequent treatment

At progression, asymptomatic patients were allowed to cross over to alternative therapy

References

TRANSFORMER: Denmeade SR, Wang H, Agarwal N, Smith D, Schweizer MT, Stein MN, Assikis V, Twardowski P, Flaig T, Szmulewitz R, Holzbeierlein J, Hauke R, Sonpavde G, Garcia J, Hussain A, Sartor O, Mao S, Cao H, Fu W, Wang T, Abdallah R, Lim SJ, Bolejack V, Paller C, Carducci M, Markowski MC, Eisenberger MA, Antonarakis ES; TRANSFORMER investigators. TRANSFORMER: A Randomized Phase II Study Comparing Bipolar Androgen Therapy Versus Enzalutamide in Asymptomatic Men With Castration-Resistant Prostate Cancer. J Clin Oncol. 2021 Apr 20;39(12):1371-1382. Epub 2021 Feb 22. link to original article link to protocol link to PMC article PubMed NCT02286921

Bicalutamide monotherapy

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Shore et al. 2016 (TERRAIN)	2011-2013	Randomized Phase 2 (C)	Enzalutamide	Inferior PFS
Penson et al. 2016 (STRIVE)	2012-2014	Randomized Phase 2 (C)	Enzalutamide	Inferior PFS

Note: Patients enrollend in STRIVE continued ADT while on study; details not provided.

Prior treatment criteria

No prior chemotherapy, abiraterone, or ketoconazole

Endocrine therapy

Bicalutamide (Casodex) 50 mg PO once per day

Continued indefinitely

References

TERRAIN: Shore ND, Chowdhury S, Villers A, Klotz L, Siemens DR, Phung D, van Os S, Hasabou N, Wang F, Bhattacharya S, Heidenreich A. Efficacy and safety of enzalutamide versus bicalutamide for patients with metastatic prostate cancer (TERRAIN): a randomised, double-blind, phase 2 study. Lancet Oncol. 2016 Feb;17(2):153-163. Epub 2016 Jan 14. link to original article PubMed NCT01288911
STRIVE: 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 dosing details in abstract PubMed NCT01664923

Enzalutamide monotherapy

Regimen variant #1, 160 mg/day

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Scher et al. 2012 (AFFIRM)	2009-09 to 2010-11	Phase 3 (E-RT-esc)	Placebo	Superior OS (primary endpoint) Median OS: 18.4 vs 13.6 mo (HR 0.63, 95% CI 0.53-0.75)
Beer et al. 2014 (PREVAIL)	2010-2012	Phase 3 (E-RT-esc)	Placebo	Superior rPFS¹ (co-primary endpoint) Median rPFS: 20 vs 5.4 mo (HR 0.32, 95% CI 0.28-0.37) Superior OS² (co-primary endpoint) Median OS: 36 vs 31 mo (HR 0.83, 95% CI 0.75-0.93)
Shore et al. 2016 (TERRAIN)	2011-2013	Randomized Phase 2 (E-RT-switch-ic)	Bicalutamide	Superior PFS (primary endpoint) Median PFS: 15.7 vs 5.8 mo (HR 0.44, 95% CI 0.34-0.57)
Penson et al. 2016 (STRIVE)	2012-2014	Randomized Phase 2 (E-switch-ic)	Bicalutamide	Superior PFS (primary endpoint) Median PFS: 19.4 vs 5.7 mo (HR 0.24, 95% CI 0.18-0.32)
Attard et al. 2018 (PLATO)	2013-NR	Non-randomized part of phase 3 RCT
Morris et al. 2023 (Alliance A031201)	2014-01-28 to 2016-08-31	Phase 3 (C)	Abiraterone & Enzalutamide	Might have inferior OS (primary endpoint) Median OS: 32.7 vs 34.2 mo (HR 1.12, 95% CI 0.99-1.28)
Pu et al. 2022 (9785-CL-0232)	2014-04-23 to 2015-09-20	Phase 3 (E-esc)	Placebo	Superior OS (secondary endpoint) Median OS: NYR vs NYR (HR 0.33, 95% CI 0.16-0.67) Superior time to PSA progression (primary endpoint) Median time to PSA progression: 8.31 vs 2.86 mo (HR 0.38, 95% CI 0.27-0.52)
de Wit et al. 2019 (CARD)	2015-2018	Phase 3 (C)	Cabazitaxel & Prednisone	Inferior PFSi/OS
Denmeade et al. 2021 (TRANSFORMER)	2015-2018	Randomized Phase 2 (C)	Bipolar androgen therapy	Did not meet primary endpoint of PFS
Powles et al. 2022 (IMbassador250)	2017-06 to 2018-05	Phase 3 (C)	Enzalutamide & Atezolizumab	Did not meet primary endpoint of OS
Antonarakis et al. 2023 (KEYLYNK-010)	2019-05-30 to 2021-07-16	Phase 3 (C)	Olaparib & Pembrolizumab	Did not meet co-primary endpoints of rPFS/OS

¹Reported efficacy for rPFS in PREVAIL is based on the 2016 update.
¹Reported efficacy for OS in PREVAIL is based on the 2020 update.
Note: Patients in STRIVE, PLATO, & TRANSFORMER continued ADT while on study or had a history of bilateral orchiectomy; details not provided.

Prior treatment criteria

AFFIRM: Exposure to docetaxel
PREVAIL: Chemotherapy and abiraterone naive
STRIVE: Chemotherapy and bicalutamide naive
PLATO & 9785-CL-0232: Chemotherapy naive
TRANSFORMER & KEYLYNK-010: Exposure to abiraterone

Endocrine therapy

Enzalutamide (Xtandi) 160 mg PO once per day

Continued indefinitely

Subsequent treatment

PLATO, with rising PSA: Abiraterone versus Abiraterone & Enzalutamide
TRANSFORMER, asymptomatic PSA or radiographic progression: crossover to alternative arm. Secondary endpoint of PFS2 was statistically longer with BAT to Enzalutamide compared to Enzalutamide to BAT

Regimen variant #2, 240 mg/day

Historic variant

Study	Dates of enrollment	Evidence
Scher et al. 2010 (S-3100-1-01)	2007-2008	Phase 1/2

Note: this is the reported MTD from the phase 1 portion of the trial; however, it is NOT the dose used in subsequent phase 3 studies.

Endocrine therapy

Enzalutamide (Xtandi) 240 mg PO once per day

Continued indefinitely

References

S-3100-1-01: Scher HI, Beer TM, Higano CS, Anand A, Taplin ME, Efstathiou E, Rathkopf D, Shelkey J, Yu EY, Alumkal J, Hung D, Hirmand M, Seely L, Morris MJ, Danila DC, Humm J, Larson S, Fleisher M, Sawyers CL; Prostate Cancer Foundation/Department of Defense Prostate Cancer Clinical Trials Consortium. Antitumour activity of MDV3100 in castration-resistant prostate cancer: a phase 1-2 study. Lancet. 2010 Apr 24;375(9724):1437-46. Epub 2010 Apr 14. link to original article link to PMC article contains dosing details in abstract PubMed NCT00510718
AFFIRM: 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 dosing details in manuscript PubMed NCT00974311
PREVAIL: 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 NCT01212991
1. HRQoL analysis: Loriot Y, Miller K, Sternberg CN, Fizazi K, De Bono JS, Chowdhury S, Higano CS, Noonberg S, Holmstrom S, Mansbach H, Perabo FG, Phung D, Ivanescu C, Skaltsa K, Beer TM, Tombal B. Effect of enzalutamide on health-related quality of life, pain, and skeletal-related events in asymptomatic and minimally symptomatic, chemotherapy-naive patients with metastatic castration-resistant prostate cancer (PREVAIL): results from a randomised, phase 3 trial. Lancet Oncol. 2015 May;16(5):509-21. Epub 2015 Apr 14. link to original article PubMed
2. Update: Beer TM, Armstrong AJ, Rathkopf D, Loriot Y, Sternberg CN, Higano CS, Iversen P, Evans CP, Kim CS, Kimura G, Miller K, Saad F, Bjartell AS, Borre M, Mulders P, Tammela TL, Parli T, Sari S, van Os S, Theeuwes A, Tombal B. Enzalutamide in men with chemotherapy-naïve metastatic castration-resistant prostate cancer: Extended analysis of the phase 3 PREVAIL study. Eur Urol. 2017 Feb;71(2):151-154. Epub 2016 Jul 28. link to original article link to PMC article PubMed
3. HRQoL analysis: Devlin N, Herdman M, Pavesi M, Phung D, Naidoo S, Beer TM, Tombal B, Loriot Y, Ivanescu C, Parli T, Balk M, Holmstrom S. Health-related quality of life effects of enzalutamide in patients with metastatic castration-resistant prostate cancer: an in-depth post hoc analysis of EQ-5D data from the PREVAIL trial. Health Qual Life Outcomes. 2017 Jun 23;15(1):130. link to original article link to PMC article PubMed
4. Update: Armstrong AJ, Lin P, Tombal B, Saad F, Higano CS, Joshua AM, Parli T, Rosbrook B, van Os S, Beer TM. Five-year Survival Prediction and Safety Outcomes with Enzalutamide in Men with Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer from the PREVAIL Trial. Eur Urol. 2020 Sep;78(3):347-357. Epub 2020 Jun 9. link to original article PubMed
TERRAIN: Shore ND, Chowdhury S, Villers A, Klotz L, Siemens DR, Phung D, van Os S, Hasabou N, Wang F, Bhattacharya S, Heidenreich A. Efficacy and safety of enzalutamide versus bicalutamide for patients with metastatic prostate cancer (TERRAIN): a randomised, double-blind, phase 2 study. Lancet Oncol. 2016 Feb;17(2):153-163. Epub 2016 Jan 14. link to original article PubMed NCT01288911
STRIVE: 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 dosing details in abstract PubMed NCT01664923
PLATO: Attard G, Borre M, Gurney H, Loriot Y, Andresen-Daniil C, Kalleda R, Pham T, Taplin ME; PLATO collaborators. Abiraterone alone or in combination with enzalutamide in metastatic castration-resistant prostate cancer with rising prostate-specific antigen during enzalutamide treatment. J Clin Oncol. 2018 Sep 1;36(25):2639-2646. Epub 2018 Jul 20. link to original article contains dosing details in manuscript link to PMC article PubMed NCT01995513
CARD: de Wit R, de Bono J, Sternberg CN, Fizazi K, Tombal B, Wülfing C, Kramer G, Eymard JC, Bamias A, Carles J, Iacovelli R, Melichar B, Sverrisdóttir Á, Theodore C, Feyerabend S, Helissey C, Ozatilgan A, Geffriaud-Ricouard C, Castellano D; CARD Investigators. Cabazitaxel versus Abiraterone or Enzalutamide in Metastatic Prostate Cancer. N Engl J Med. 2019 Dec 26;381(26):2506-2518. Epub 2019 Sep 30. link to original article contains dosing details in manuscript PubMed NCT02485691
1. HRQoL analysis: Fizazi K, Kramer G, Eymard JC, Sternberg CN, de Bono J, Castellano D, Tombal B, Wülfing C, Liontos M, Carles J, Iacovelli R, Melichar B, Sverrisdóttir Á, Theodore C, Feyerabend S, Helissey C, Oudard S, Facchini G, Poole EM, Ozatilgan A, Geffriaud-Ricouard C, Bensfia S, de Wit R. Quality of life in patients with metastatic prostate cancer following treatment with cabazitaxel versus abiraterone or enzalutamide (CARD): an analysis of a randomised, multicentre, open-label, phase 4 study. Lancet Oncol. 2020 Nov;21(11):1513-1525. Epub 2020 Sep 11. link to original article PubMed
TRANSFORMER: Denmeade SR, Wang H, Agarwal N, Smith D, Schweizer MT, Stein MN, Assikis V, Twardowski P, Flaig T, Szmulewitz R, Holzbeierlein J, Hauke R, Sonpavde G, Garcia J, Hussain A, Sartor O, Mao S, Cao H, Fu W, Wang T, Abdallah R, Lim SJ, Bolejack V, Paller C, Carducci M, Markowski MC, Eisenberger MA, Antonarakis ES; TRANSFORMER investigators. TRANSFORMER: A Randomized Phase II Study Comparing Bipolar Androgen Therapy Versus Enzalutamide in Asymptomatic Men With Castration-Resistant Prostate Cancer. J Clin Oncol. 2021 Apr 20;39(12):1371-1382. Epub 2021 Feb 22. link to original article link to protocol link to PMC article PubMed NCT02286921
IMbassador250: Powles T, Yuen KC, Gillessen S, Kadel EE 3rd, Rathkopf D, Matsubara N, Drake CG, Fizazi K, Piulats JM, Wysocki PJ, Buchschacher GL Jr, Alekseev B, Mellado B, Karaszewska B, Doss JF, Rasuo G, Datye A, Mariathasan S, Williams P, Sweeney CJ. Atezolizumab with enzalutamide versus enzalutamide alone in metastatic castration-resistant prostate cancer: a randomized phase 3 trial. Nat Med. 2022 Jan;28(1):144-153. Epub 2022 Jan 10. link to original article contains dosing details in manuscript link to PMC article PubMed NCT03016312
9785-CL-0232: Pu YS, Ahn H, Han W, Huang SP, Wu HC, Ma L, Yamada S, Suga K, Xie LP. Enzalutamide in Chemotherapy-Naïve Metastatic Castration-Resistant Prostate Cancer: An Asian Multiregional, Randomized Study. Adv Ther. 2022 Jun;39(6):2641-2656. Epub 2022 Apr 10. link to original article contains dosing details in abstract link to PMC article PubMed NCT02294461
KEYLYNK-010: Antonarakis ES, Park SH, Goh JC, Shin SJ, Lee JL, Mehra N, McDermott R, Sala-Gonzalez N, Fong PC, Greil R, Retz M, Sade JP, Yanez P, Huang YH, Begbie SD, Gafanov RA, De Santis M, Rosenbaum E, Kolinsky MP, Rey F, Chiu KY, Roubaud G, Kramer G, Sumitomo M, Massari F, Suzuki H, Qiu P, Zhang J, Kim J, Poehlein CH, Yu EY. Pembrolizumab Plus Olaparib for Patients With Previously Treated and Biomarker-Unselected Metastatic Castration-Resistant Prostate Cancer: The Randomized, Open-Label, Phase III KEYLYNK-010 Trial. J Clin Oncol. 2023 Aug 1;41(22):3839-3850. Epub 2023 Jun 8. link to original article contains dosing details in manuscript PubMed NCT03834519
Alliance A031201: Morris MJ, Heller G, Hillman DW, Bobek O, Ryan C, Antonarakis ES, Bryce AH, Hahn O, Beltran H, Armstrong AJ, Schwartz L, Lewis LD, Beumer JH, Langevin B, McGary EC, Mehan PT, Goldkorn A, Roth BJ, Xiao H, Watt C, Taplin ME, Halabi S, Small EJ. Randomized Phase III Study of Enzalutamide Compared With Enzalutamide Plus Abiraterone for Metastatic Castration-Resistant Prostate Cancer (Alliance A031201 Trial). J Clin Oncol. 2023 Jun 20;41(18):3352-3362. Epub 2023 Mar 30. link to original article contains dosing details in manuscript link to PMC article PubMed NCT01949337
CASPAR: NCT04455750
TALAPRO-2: NCT03395197

Hydrocortisone monotherapy

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Kantoff et al. 1999 (CALGB 9182)	1992-1995	Phase 3 (C)	Mitoxantrone & Hydrocortisone	Did not meet primary endpoint of OS
Small et al. 2000	1994-1996	Phase 3 (C)	Suramin & Hydrocortisone	Inferior TTP
Abratt et al. 2004	1997-2001	Phase 3 (C)	Vinorelbine & Hydrocortisone	Might have inferior PFS

Endocrine therapy

Hydrocortisone (Cortef) 30 mg PO once per day, taken in the morning
Hydrocortisone (Cortef) 10 mg PO once per day, taken in the evening

Continued indefinitely

References

CALGB 9182: Kantoff PW, Halabi S, Conaway M, Picus J, Kirshner J, Hars V, Trump D, Winer EP, Vogelzang NJ. Hydrocortisone with or without mitoxantrone in men with hormone-refractory prostate cancer: results of the Cancer and Leukemia Group B 9182 study. J Clin Oncol. 1999 Aug;17(8):2506-13. link to original article contains dosing details in manuscript PubMed
Small EJ, Meyer M, Marshall ME, Reyno LM, Meyers FJ, Natale RB, Lenehan PF, Chen L, Slichenmyer WJ, Eisenberger M. Suramin therapy for patients with symptomatic hormone-refractory prostate cancer: results of a randomized phase III trial comparing suramin plus hydrocortisone to placebo plus hydrocortisone. J Clin Oncol. 2000 Apr;18(7):1440-50. link to original article PubMed
Abratt RP, Brune D, Dimopoulos MA, Kliment J, Breza J, Selvaggi FP, Beuzeboc P, Demkow T, Oudard S. Randomised phase III study of intravenous vinorelbine plus hormone therapy versus hormone therapy alone in hormone-refractory prostate cancer. Ann Oncol. 2004 Nov;15(11):1613-21. link to original article PubMed

Ketoconazole & Hydrocortisone

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Trachtenberg & Pont 1984	NR	Pilot
Small et al. 2004 (CALGB 9583)	NR	Phase 3 (E-esc)	Antiandrogen withdrawal	Superior PSA response

Endocrine therapy

Ketoconazole (Nizoral) 400 mg PO three times per day
Hydrocortisone (Cortef) 30 mg PO QAM and 10 mg PO QPM

Continued indefinitely

References

Trachtenberg J, Pont A. Ketoconazole therapy for advanced prostate cancer. Lancet. 1984 Aug 25;2(8400):433-5. link to original article PubMed
CALGB 9583: 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 dosing details in manuscript PubMed NCT00002760

Ketoconazole, Hydrocortisone, Dutasteride

Regimen

Study	Dates of enrollment	Evidence
Taplin et al. 2009	2005-2007	Phase 2

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

Continued indefinitely

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 dosing details in manuscript link to PMC article PubMed

Prednisone monotherapy

Regimen variant #1, 5 mg twice per day

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Tannock et al. 1989	1976-1980	Retrospective
Tannock et al. 1996 (CCI-NOV22)	1990-1994	Phase 3 (C)	Mitoxantrone & Prednisone	Inferior palliation
Berry et al. 2002	1997-1999	Phase 3 (C)	Mitoxantrone & Prednisone	Seems to have inferior TTTF
Sternberg et al. 2009 (SPARC)	2003-2006	Phase 3 (C)	Satraplatin & Prednisone	Inferior PFS
de Bono et al. 2011 (COU-AA-301)	2008-05 to 2009-07	Phase 3 (C)	Abiraterone	Inferior OS
Michaelson et al. 2013 (SUN 1120)	2008-2010	Phase 3 (C)	Sunitinib & Prednisone	Did not meet primary endpoint of OS
Ryan et al. 2013 (COU-AA-302)	2009-04 to 2010-06	Phase 3 (C)	Abiraterone	Inferior OS
Saad et al. 2015 (ELM-PC 4)	2010-2012	Phase 3 (C)	Orteronel & Prednisone	Inferior PFS
Fizazi et al. 2015 (ELM-PC 5)	2010-NR	Phase 3 (C)	Orteronel & Prednisone	Did not meet primary endpoint of OS
Smith et al. 2016 (COMET-1)	2012-2014	Phase 3 (C)	Cabozantinib	Did not meet primary endpoint of OS

Endocrine therapy

Prednisone (Sterapred) 5 mg PO twice per day

Continued indefinitely

Regimen variant #2, 5 mg QID

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Fosså et al. 2001 (EORTC 30903)	1992-1998	Phase 3 (C)	Flutamide	Did not meet co-primary endpoints of TTP/OS

Endocrine therapy

Prednisone (Sterapred) 5 mg PO four times per day

Continued indefinitely

References

Tannock I, Gospodarowicz M, Meakin W, Panzarella T, Stewart L, Rider W. Treatment of metastatic prostatic cancer with low-dose prednisone: evaluation of pain and quality of life as pragmatic indices of response. J Clin Oncol. 1989 May;7(5):590-7. link to original article PubMed
CCI-NOV22: 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 contains dosing details in manuscript PubMed
1. 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
EORTC 30903: 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 dosing details in abstract PubMed
Berry W, Dakhil S, Modiano M, Gregurich M, Asmar L. Phase III study of mitoxantrone plus low dose prednisone versus low dose prednisone alone in patients with asymptomatic hormone refractory prostate cancer. J Urol. 2002 Dec;168(6):2439-43. link to original article contains dosing details in abstract PubMed
SPARC: Sternberg CN, Petrylak DP, Sartor O, Witjes JA, Demkow T, Ferrero JM, Eymard JC, Falcon S, Calabrò F, James N, Bodrogi I, Harper P, Wirth M, Berry W, Petrone ME, McKearn TJ, Noursalehi M, George M, Rozencweig M. Multinational, double-blind, phase III study of prednisone and either satraplatin or placebo in patients with castrate-refractory prostate cancer progressing after prior chemotherapy: the SPARC trial. J Clin Oncol. 2009 Nov 10;27(32):5431-8. Epub 2009 Oct 5. link to original article contains dosing details in abstract PubMed NCT00069745
COU-AA-301: 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 dosing details in manuscript link to PMC article PubMed NCT00638690
1. 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 dosing details in manuscript PubMed
2. 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 dosing details in manuscript PubMed
COU-AA-302: 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 dosing details in manuscript link to PMC article PubMed NCT00887198
1. 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
SUN 1120: Michaelson MD, Oudard S, Ou YC, Sengeløv L, Saad F, Houede N, Ostler P, Stenzl A, Daugaard G, Jones R, Laestadius F, Ullèn A, Bahl A, Castellano D, Gschwend J, Maurina T, Chow Maneval E, Wang SL, Lechuga MJ, Paolini J, Chen I. Randomized, placebo-controlled, phase III trial of sunitinib plus prednisone versus prednisone alone in progressive, metastatic, castration-resistant prostate cancer. J Clin Oncol. 2014 Jan 10;32(2):76-82. Epub 2013 Dec 9. link to original article contains dosing details in abstract PubMed NCT00676650
ELM-PC 5: Fizazi K, Jones R, Oudard S, Efstathiou E, Saad F, de Wit R, De Bono J, Cruz FM, Fountzilas G, Ulys A, Carcano F, Agarwal N, Agus D, Bellmunt J, Petrylak DP, Lee SY, Webb IJ, Tejura B, Borgstein N, Dreicer R. Phase III, randomized, double-blind, multicenter trial comparing orteronel (TAK-700) plus prednisone with placebo plus prednisone in patients with metastatic castration-resistant prostate cancer that has progressed during or after docetaxel-based therapy: ELM-PC 5. J Clin Oncol. 2015 Mar 1;33(7):723-31. Epub 2015 Jan 26. link to original article link to PMC article contains dosing details in abstract PubMed NCT01193257
ELM-PC 4: Saad F, Fizazi K, Jinga V, Efstathiou E, Fong PC, Hart LL, Jones R, McDermott R, Wirth M, Suzuki K, MacLean DB, Wang L, Akaza H, Nelson J, Scher HI, Dreicer R, Webb IJ, de Wit R; ELM-PC 4 investigators. Orteronel plus prednisone in patients with chemotherapy-naive metastatic castration-resistant prostate cancer (ELM-PC 4): a double-blind, multicentre, phase 3, randomised, placebo-controlled trial. Lancet Oncol. 2015 Mar;16(3):338-48. Epub 2015 Feb 18. link to original article contains dosing details in abstract PubMed NCT01193244
COMET-1: 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 dosing details in manuscript PubMed NCT01605227

Chemotherapy for metastatic castrate-sensitive disease

Cabazitaxel & Prednisone

Example orders

Example orders for Cabazitaxel (Jevtana) in prostate cancer

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
de Wit et al. 2019 (CARD)	2015-2018	Phase 3 (E-RT-switch-ooc)	1a. Abiraterone 1b. Enzalutamide	Superior PFSi (primary endpoint) Median PFSi: 8 vs 3.7 mo (HR 0.54, 95% CI 0.40-0.73) Superior OS (secondary endpoint) Median OS: 13.6 vs 11 mo (HR 0.64, 95% CI 0.46-0.89)

Note: patients in CARD had already received and progressed on the alternate androgen signaling targeted inhibitor.

Chemotherapy

Cabazitaxel (Jevtana) 25 mg/m² IV over 60 minutes once on day 1

Endocrine therapy

Prednisone (Sterapred) 10 mg PO once per day on days 1 to 21

Supportive therapy

Antihistamine once on day 1, at least 30 minutes prior to cabazitaxel
Corticosteroid (dexamethasone 8 mg or equivalent) once on day 1, at least 30 minutes prior to cabazitaxel
Histamine H2-antagonist (except cimetidine) once on day 1, at least 30 minutes prior to cabazitaxel

21-day cycles

References

CARD: de Wit R, de Bono J, Sternberg CN, Fizazi K, Tombal B, Wülfing C, Kramer G, Eymard JC, Bamias A, Carles J, Iacovelli R, Melichar B, Sverrisdóttir Á, Theodore C, Feyerabend S, Helissey C, Ozatilgan A, Geffriaud-Ricouard C, Castellano D; CARD Investigators. Cabazitaxel versus Abiraterone or Enzalutamide in Metastatic Prostate Cancer. N Engl J Med. 2019 Dec 26;381(26):2506-2518. Epub 2019 Sep 30. link to original article contains dosing details in manuscript PubMed NCT02485691
1. HRQoL analysis: Fizazi K, Kramer G, Eymard JC, Sternberg CN, de Bono J, Castellano D, Tombal B, Wülfing C, Liontos M, Carles J, Iacovelli R, Melichar B, Sverrisdóttir Á, Theodore C, Feyerabend S, Helissey C, Oudard S, Facchini G, Poole EM, Ozatilgan A, Geffriaud-Ricouard C, Bensfia S, de Wit R. Quality of life in patients with metastatic prostate cancer following treatment with cabazitaxel versus abiraterone or enzalutamide (CARD): an analysis of a randomised, multicentre, open-label, phase 4 study. Lancet Oncol. 2020 Nov;21(11):1513-1525. Epub 2020 Sep 11. link to original article PubMed

Chemotherapy for metastatic castrate-resistant disease

Cabazitaxel & Prednisolone

Example orders

Example orders for Cabazitaxel (Jevtana) in prostate cancer

Regimen variant #1, 16/10

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy	Comparative Toxicity
Oudard et al. 2023 (CABASTY)	NR	Phase 3 (E-de-esc)	Cabazitaxel & Prednisone; q3wk		Superior grade 3 or higher neutropenia and/or neutropenic complications (primary endpoint)

Chemotherapy

Cabazitaxel (Jevtana) 16 mg/m² IV over 60 minutes once on day 1

Endocrine therapy

Prednisolone (Millipred) 10 mg PO once per day

Supportive therapy

G-CSF (dose not specified) once per day on days 3 to 7

14-day cycle for up to 20 cycles

Regimen variant #2, 20/10

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Hofman et al. 2021 (TheraP)	2018-2019	Randomized Phase 2 (C)	Lu-177 Lu-PSMA-617	Inferior PSA response

Chemotherapy

Cabazitaxel (Jevtana) 20 mg/m² IV once on day 1

Endocrine therapy

Prednisolone (Millipred) 10 mg PO once per day

21-day cycle for up to 10 cycles

Regimen variant #3, 25/10

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy	Comparative Toxicity
Oudard et al. 2023 (CABASTY)	NR	Phase 3 (C)	Cabazitaxel & Prednisone; q2wk		Inferior grade 3 or higher neutropenia and/or neutropenic complications

Chemotherapy

Cabazitaxel (Jevtana) 25 mg/m² IV over 60 minutes once on day 1

Endocrine therapy

Prednisolone (Millipred) 10 mg PO once per day

Supportive therapy

G-CSF (dose not specified) once per day on days 3 to 7

21-day cycle for up to 10 cycles

References

TheraP: Hofman MS, Emmett L, Sandhu S, Iravani A, Joshua AM, Goh JC, Pattison DA, Tan TH, Kirkwood ID, Ng S, Francis RJ, Gedye C, Rutherford NK, Weickhardt A, Scott AM, Lee ST, Kwan EM, Azad AA, Ramdave S, Redfern AD, Macdonald W, Guminski A, Hsiao E, Chua W, Lin P, Zhang AY, McJannett MM, Stockler MR, Violet JA, Williams SG, Martin AJ, Davis ID; TheraP Trial Investigators and the Australian and New Zealand Urogenital and Prostate Cancer Trials Group. [177Lu]Lu-PSMA-617 versus cabazitaxel in patients with metastatic castration-resistant prostate cancer (TheraP): a randomised, open-label, phase 2 trial. Lancet. 2021 Feb 27;397(10276):797-804. Epub 2021 Feb 11. link to original article contains dosing details in abstract PubMed NCT03392428
1. Update: Hofman MS, Emmett L, Sandhu S, Iravani A, Buteau JP, Joshua AM, Goh JC, Pattison DA, Tan TH, Kirkwood ID, Ng S, Francis RJ, Gedye C, Rutherford NK, Weickhardt A, Scott AM, Lee ST, Kwan EM, Azad AA, Ramdave S, Redfern AD, Macdonald W, Guminski A, Hsiao E, Chua W, Lin P, Zhang AY, Stockler MR, Williams SG, Martin AJ, Davis ID; TheraP Trial Investigators and the Australian and New Zealand Urogenital and Prostate Cancer Trials Group. Overall survival with [177Lu]Lu-PSMA-617 versus cabazitaxel in metastatic castration-resistant prostate cancer (TheraP): secondary outcomes of a randomised, open-label, phase 2 trial. Lancet Oncol. 2024 Jan;25(1):99-107. Epub 2023 Nov 30. link to original article PubMed
CABASTY: Oudard S, Ratta R, Voog E, Barthelemy P, Thiery-Vuillemin A, Bennamoun M, Hasbini A, Aldabbagh K, Saldana C, Sevin E, Amela E, Von Amsberg G, Houede N, Besson D, Feyerabend S, Boegemann M, Pfister D, Schostak M, Huillard O, Di Fiore F, Quivy A, Lange C, Phan L, Belhouari H, Tran Y, Kotti S, Helissey C. Biweekly vs Triweekly Cabazitaxel in Older Patients With Metastatic Castration-Resistant Prostate Cancer: The CABASTY Phase 3 Randomized Clinical Trial. JAMA Oncol. 2023 Dec 1;9(12):1629-1638. Epub 2023 Oct 26. link to original article link to PMC article contains dosing details in manuscript PubMed NCT02961257

Cabazitaxel & Prednisone

Example orders

Example orders for Cabazitaxel (Jevtana) in prostate cancer

Regimen variant #1, 20/10, indefinite

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Oudard et al. 2017 (FIRSTANA)	2011-2013	Phase 3 (E-switch-ic)	1. Cabazitaxel & Prednisone; 25 mg/m²/10 mg	Did not meet primary endpoint of OS
Oudard et al. 2017 (FIRSTANA)	2011-2013	Phase 3 (E-switch-ic)	2. Docetaxel & Prednisone	Did not meet primary endpoint of OS
Eisenberger et al. 2017 (PROSELICA)	2011-2013	Phase 3 (E-RT-de-esc)	Cabazitaxel & Prednisone; 25 mg/m²/10 mg	Non-inferior OS (primary endpoint) Median OS: 13.4 vs 14.5 mo (HR 1.024, 98.89% CI 1.184)

Chemotherapy

Cabazitaxel (Jevtana) 20 mg/m² IV once on day 1

Endocrine therapy

Prednisone (Sterapred) 10 mg PO once per day on days 1 to 21

21-day cycles

Regimen variant #2, 25/10 x 10

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
de Bono et al. 2010 (TROPIC)	2007-01-02 to 2008-10-23	Phase 3 (E-RT-switch-ic)	Mitoxantrone & Prednisone	Superior OS (primary endpoint) Median OS: 15.1 vs 12.7 mo (HR 0.70, 95% CI 0.59-0.83)
Beer et al. 2017 (AFFINITY)	2012-2014	Phase 3 (C)	Cabazitaxel, Prednisone, Custirsen	Did not meet primary endpoint of OS

¹ORRs in TROPIC were only reported for patients with measurable disease.

Prior treatment criteria

TROPIC: Previous endocrine therapy, and failure of a docetaxel-containing regimen
AFFINITY: Castration-resistant prostate cancer and failure of a docetaxel-containing regimen

Chemotherapy

Cabazitaxel (Jevtana) 25 mg/m² IV over 60 minutes once on day 1

Endocrine therapy

Prednisone (Sterapred) 10 mg PO once per day

Supportive therapy

Antihistamine once on day 1, at least 30 minutes prior to cabazitaxel
Corticosteroid (dexamethasone 8 mg or equivalent) once on day 1, at least 30 minutes prior to cabazitaxel
Histamine H2-antagonist (except cimetidine) once on day 1, at least 30 minutes prior to cabazitaxel

21-day cycle for up to 10 cycles

Regimen variant #3, 25/10, indefinite

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Oudard et al. 2017 (FIRSTANA)	2011-2013	Phase 3 (E-switch-ic)	1. Cabazitaxel & Prednisone; 20 mg/m²/10 mg	Did not meet primary endpoint of OS
Oudard et al. 2017 (FIRSTANA)	2011-2013	Phase 3 (E-switch-ic)	2. Docetaxel & Prednisone	Did not meet primary endpoint of OS
Eisenberger et al. 2017 (PROSELICA)	2011-2013	Phase 3 (C)	Cabazitaxel & Prednisone; 20 mg/m²/10 mg	Non-inferior OS

Chemotherapy

Cabazitaxel (Jevtana) 25 mg/m² IV over 60 minutes once on day 1

Endocrine therapy

Prednisone (Sterapred) 10 mg PO once per day on days 1 to 21

Supportive therapy

Antihistamine once on day 1, at least 30 minutes prior to cabazitaxel
Corticosteroid (dexamethasone 8 mg or equivalent) once on day 1, at least 30 minutes prior to cabazitaxel
Histamine H2-antagonist (except cimetidine) once on day 1, at least 30 minutes prior to cabazitaxel

21-day cycles

References

TROPIC: 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 dosing details in manuscript PubMed NCT00417079
FIRSTANA: 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 dosing details in manuscript PubMed NCT01308567
PROSELICA: 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 dosing details in supplement PubMed NCT01308580
AFFINITY: 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 NCT01578655

Cabozantinib monotherapy

Regimen variant #1, 60 mg/day

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Smith et al. 2016 (COMET-1)	2012-2014	Phase 3 (E-switch-ooc)	Prednisone	Did not meet primary endpoint of OS

Targeted therapy

Cabozantinib (Cabometyx) 60 mg PO once per day on days 1 to 28

28-day cycles

Regimen variant #2, 100 mg/day

Study	Dates of enrollment	Evidence
Smith et al. 2012 (XL184-203)	2009-2011	Phase 2

Targeted therapy

Cabozantinib (Cabometyx) 100 mg PO once per day

Continued indefinitely

References

XL184-203: 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 dosing details in manuscript link to PMC article PubMed NCT00940225
COMET-1: 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 dosing details in manuscript PubMed NCT01605227

Carboplatin & Docetaxel

Example orders

Example orders for Docetaxel & Carboplatin in prostate cancer

Regimen

Study	Dates of enrollment	Evidence
Ross et al. 2008	2004-2006	Phase 2

Eligibility criteria

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 60 minutes once on day 1, given second
Docetaxel (Taxotere) 60 mg/m² IV over 60 minutes once on day 1, given first

Supportive therapy

"Standard dexamethasone premedication was used"
Patients continued to receive androgen deprivation therapy

21-day cycles

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 dosing details in manuscript PubMed
Retrospective: 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

Carboplatin, Docetaxel, Prednisone

Regimen

Study	Dates of enrollment	Evidence
Reuter et al. 2010	2005-NR	Phase 2

Prior treatment criteria

Docetaxel exposure with progression and castration-resistant disease

Chemotherapy

Carboplatin (Paraplatin) AUC 5 IV over 30 minutes once on day 1
Docetaxel (Taxotere) 35 mg/m² IV over 60 minutes 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.

Endocrine therapy

Prednisone (Sterapred) 5 mg PO twice per day on days 1 to 28

Supportive therapy

"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

References

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 dosing details in manuscript PubMed

Carboplatin & Paclitaxel (CP)

Regimen variant #1

Study	Dates of enrollment	Evidence
Kentepozidis et al. 2012	2006-2009	Phase 2

Chemotherapy

Carboplatin (Paraplatin) AUC 3 (Calvert formula) IV once per day on days 1 & 15, given second
Paclitaxel (Taxol) 135 mg/m² IV over 60 minutes once per day on days 1 & 15, given first

Supportive therapy

"All patients received a concomitant anti-emetic prophylaxis"
Dexamethasone (Decadron) 20 mg PO given twice, 12 and 6 hours prior to paclitaxel
Diphenhydramine (Benadryl) 50 mg IV once per day on days 1 & 15, "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)
Cimetidine (Tagamet) 300 mg IV once per day on days 1 & 15, "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)
No prophylactic G-CSF

28-day cycles

Regimen variant #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

References

Retrospective: 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 dosing details in manuscript PubMed
Kentepozidis N, Soultati A, Giassas S, Vardakis N, Kalykaki A, Kotsakis A, Papadimitraki E, Pantazopoulos N, Bozionellou V, Georgoulias V; Hellenic Oncology Research Group. 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 dosing details in manuscript PubMed

Docetaxel, Enzalutamide, Prednisolone

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Merseburger et al. 2022 (PRESIDE)	2014-2016	Phase 3 (E-esc)	Docetaxel & Prednisolone	Seems to have superior PFS (primary endpoint) Median PFS: 9.5 vs 8.3 mo (HR 0.72, 95% CI 0.53-0.96)

Chemotherapy

Docetaxel (Taxotere) 75 mg/m² IV once on day 1

Endocrine therapy

Enzalutamide (Xtandi) 160 mg PO once per day
Prednisolone (Millipred) 10 mg PO once per day

21-day cycle for up to 10 cycles

References

PRESIDE: Merseburger AS, Attard G, Åström L, Matveev VB, Bracarda S, Esen A, Feyerabend S, Senkus E, López-Brea Piqueras M, Boysen G, Gourgioti G, Martins K, Chowdhury S. Continuous enzalutamide after progression of metastatic castration-resistant prostate cancer treated with docetaxel (PRESIDE): an international, randomised, phase 3b study. Lancet Oncol. 2022 Nov;23(11):1398-1408. Epub 2022 Oct 18. link to original article contains dosing details in abstract PubMed NCT02288247

Docetaxel & Estramustine

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Petrylak et al. 2004 (SWOG S9916)	1999-2003	Phase 3 (E-switch-ic)	Mitoxantrone & Prednisone	Seems to have superior OS (primary endpoint) Median OS: 17.5 vs 15.6 mo (HR 0.80, 95% CI 0.67-0.97)

Prior treatment criteria

SWOG S9916: Hormone-independent prostate cancer

Chemotherapy

Docetaxel (Taxotere) 60 mg/m² IV once on day 2
Estramustine (Emcyt) 280 mg PO three times per day on days 1 to 5

21-day cycles

References

SWOG S9916: 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 contains dosing details in abstract PubMed NCT00004001
ECOG E1899: NCT00027859

Docetaxel & Prednisone

Example orders

Example orders for Docetaxel (Taxotere) in prostate cancer

Regimen variant #1, 30 mg/m² weekly

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Tannock et al. 2004 (TAX 327)	2000-2002	Phase 3 (E-RT-switch-ic)	1. Docetaxel & Prednisone; q3wk	Not reported
Tannock et al. 2004 (TAX 327)	2000-2002	Phase 3 (E-RT-switch-ic)	2. Mitoxantrone & Prednisone	Did not meet primary endpoint of OS Median OS: 17.4 vs 16.5 mo (HR 0.91, 95% CI 0.75-1.11)

Prior treatment criteria

TAX 327: Disease progression during hormonal therapy

Chemotherapy

Docetaxel (Taxotere) 30 mg/m² IV over 30 minutes once per day on days 1, 8, 15, 22, 29

Endocrine therapy

Prednisone (Sterapred) 5 mg PO twice per day

Supportive therapy

Dexamethasone (Decadron) 8 mg (route not specified) once 1 hour prior to docetaxel
Antiemetics "according to local practice"

42-day cycle for up to 5 cycles

Regimen variant #2, 75 mg/m² q3wk x 10

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Tannock et al. 2004 (TAX 327)	2000-2002	Phase 3 (E-RT-switch-ic)	1. Docetaxel & Prednisone; weekly	Not reported
Tannock et al. 2004 (TAX 327)	2000-2002	Phase 3 (E-RT-switch-ic)	2. Mitoxantrone & Prednisone	Superior OS (primary endpoint) Median OS: 18.9 vs 16.5 mo (HR 0.76, 95% CI 0.62-0.94)
Beer et al. 2011 (ASCENT_PRCA)	2002-2004	Phase 3 (C)	Calcitriol, Docetaxel, Prednisone	Superior OS¹
Meulenbeld et al. 2012 (NePro)	2004-2010	Phase 2/3 (C)	Docetaxel, Prednisone, Risedronate	Did not meet primary endpoint of TTP
Zhou et al. 2015 (DOCET_L_01833)	2007-2010	Phase 3 (E-switch-ic)	Mitoxantrone & Prednisone	Superior OS (primary endpoint) Median OS: 21.9 vs 13.7 mo (HR 0.63, 95% CI 0.46-0.86)
Vogelzang et al. 2022 (VIABLE)	2014-2017	Phase 3 (C)	Docetaxel, Prednisone, DCVAC/PCa	Did not meet primary endpoint of OS

¹Reported efficacy for ASCENT is based on the 2011 update.
Note: ASCENT is labeled ASCENT_PRCA to distinguish from the trial by the same name in TNBC.

Prior treatment criteria

TAX 327: Disease progression during hormonal therapy

Chemotherapy

Docetaxel (Taxotere) 75 mg/m² IV over 60 minutes once on day 1

Endocrine therapy

Prednisone (Sterapred) 5 mg PO twice per day or 10 mg PO once per day

Supportive therapy

Dexamethasone (Decadron) 8 mg PO given three times; 12 hours, 3 hours, and 1 hour prior to docetaxel
Antiemetics "according to local practice"

21-day cycle for up to 10 cycles

Regimen variant #3, 75 mg/m² q3wk x 12

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Quinn et al. 2013 (SWOG S0421)	2006-2010	Phase 3 (C)	Atrasentan, Docetaxel, Prednisone	Did not meet co-primary endpoints of PFS/OS

Chemotherapy

Docetaxel (Taxotere) 75 mg/m² IV over 60 minutes once on day 1

Endocrine therapy

Prednisone (Sterapred) 5 mg PO twice per day

Supportive therapy

Dexamethasone (Decadron) 8 mg PO given three times; 12 hours, 3 hours, and 1 hour prior to docetaxel
Antiemetics "according to local practice"

21-day cycle for up to 12 cycles

Regimen variant #4, 75 mg/m² q3wk, indefinite

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Kelly et al. 2012 (CALGB 90401)	2005-2007	Phase 3 (C)	Docetaxel, Prednisone, Bevacizumab	Did not meet primary endpoint of OS
Tannock et al. 2013 (VENICE)	2007-2010	Phase 3 (C)	Aflibercept, Docetaxel, Prednisone	Did not meet primary endpoint of OS
Araujo et al. 2013 (READY)	2008-2011	Phase 3 (C)	Dasatinib, Docetaxel, Prednisone	Did not meet primary endpoint of OS
Fizazi et al. 2013 (ENTHUSE)	2008-NR	Phase 3 (C)	1a. Docetaxel, Prednisolone, Zibotentan 1b. Docetaxel, Prednisone, Zibotentan	Did not meet primary endpoint of OS
Petrylak et al. 2015 (MAINSAIL)	2009-2011	Phase 3 (C)	Docetaxel, Lenalidomide, Prednisone	Superior OS
Chi et al. 2017 (SYNERGY)	2010-2012	Phase 3 (C)	Custirsen, Docetaxel, Prednisone	Did not meet primary endpoint of OS
Oudard et al. 2017 (FIRSTANA)	2011-2013	Phase 3 (C)	1. Cabazitaxel & Prednisone; 20 mg/m²/10 mg	Did not meet primary endpoint of OS
Oudard et al. 2017 (FIRSTANA)	2011-2013	Phase 3 (C)	2. Cabazitaxel & Prednisone; 25 mg/m²/10 mg	Did not meet primary endpoint of OS

Note: patients in CALGB 90401 discontinued treatment after a maximum of 2 years.

Chemotherapy

Docetaxel (Taxotere) 75 mg/m² IV once on day 1

Endocrine therapy

Prednisone (Sterapred) by the following study-specific criteria:
- CALGB 90401: 5 mg PO once per day on days 1 to 21
- Others: 10 mg/day; some regimens give as 5 mg PO twice per day, some as 10 mg PO once per day

21-day cycles

References

TAX 327: 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 dosing details in manuscript PubMed
1. 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 dosing details in manuscript PubMed
ASCENT_PRCA: Beer TM, Ryan CW, Venner PM, Petrylak DP, Chatta GS, Ruether JD, Redfern CH, Fehrenbacher L, Saleh MN, Waterhouse DM, Carducci MA, Vicario D, Dreicer R, Higano CS, Ahmann FR, Chi KN, Henner WD, Arroyo A, Clow FW; ASCENT Investigators. Double-blinded randomized study of high-dose calcitriol plus docetaxel compared with placebo plus docetaxel in androgen-independent prostate cancer: a report from the ASCENT Investigators. J Clin Oncol. 2007 Feb 20;25(6):669-74. link to original article PubMed NCT00273338
1. Update: Scher HI, Jia X, Chi K, de Wit R, Berry WR, Albers P, Henick B, Waterhouse D, Ruether DJ, Rosen PJ, Meluch AA, Nordquist LT, Venner PM, Heidenreich A, Chu L, Heller G. Randomized, open-label phase III trial of docetaxel plus high-dose calcitriol versus docetaxel plus prednisone for patients with castration-resistant prostate cancer. J Clin Oncol. 2011 Jun 1;29(16):2191-8. Epub 2011 Apr 11. link to original article PubMed
CALGB 90401: Kelly WK, Halabi S, Carducci M, George D, Mahoney JF, Stadler WM, Morris M, Kantoff P, Monk JP, Kaplan E, Vogelzang NJ, Small EJ. Randomized, double-blind, placebo-controlled phase III trial comparing docetaxel and prednisone with or without bevacizumab in men with metastatic castration-resistant prostate cancer: CALGB 90401. J Clin Oncol. 2012 May 1;30(13):1534-40. Epub 2012 Mar 26. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00110214
NePro: Meulenbeld HJ, van Werkhoven ED, Coenen JL, Creemers GJ, Loosveld OJ, de Jong PC, Ten Tije AJ, Fosså SD, Polee M, Gerritsen W, Dalesio O, de Wit R. Randomised phase II/III study of docetaxel with or without risedronate in patients with metastatic Castration Resistant Prostate Cancer (CRPC), the Netherlands Prostate Study (NePro). Eur J Cancer. 2012 Nov;48(16):2993-3000. Epub 2012 Jun 6. link to original article contains dosing details in manuscript PubMed
VENICE: 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 dosing details in abstract PubMed NCT00519285
SWOG S0421: Quinn DI, Tangen CM, Hussain M, Lara PN Jr, Goldkorn A, Moinpour CM, Garzotto MG, Mack PC, Carducci MA, Monk JP, Twardowski PW, Van Veldhuizen PJ, Agarwal N, Higano CS, Vogelzang NJ, Thompson IM Jr. Docetaxel and atrasentan versus docetaxel and placebo for men with advanced castration-resistant prostate cancer (SWOG S0421): a randomised phase 3 trial. Lancet Oncol. 2013 Aug;14(9):893-900. Epub 2013 Jul 17. link to original article link to PMC article contains dosing details in manuscript PubMed NCT00134056
READY: 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 dosing details in abstract link to PMC article PubMed NCT00744497
DOCET_L_01833: Zhou T, Zeng SX, Ye DW, Wei Q, Zhang X, Huang YR, Ye ZQ, Yang Y, Zhang W, Tian Y, Zhou FJ, Jie J, Chen SP, Sun Y, Xie LP, Yao X, Na YQ, Sun YH. A multicenter, randomized clinical trial comparing the three-weekly docetaxel regimen plus prednisone versus mitoxantone plus prednisone for Chinese patients with metastatic castration refractory prostate cancer. PLoS One. 2015 Jan 27;10(1):e0117002. link to original article link to PMC article contains dosing details in manuscript PubMed NCT00436839
MAINSAIL: 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 dosing details in abstract PubMed NCT00988208
SYNERGY: 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 dosing details in abstract PubMed NCT01188187
FIRSTANA: 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 dosing details in manuscript PubMed NCT01308567
Bianchi S, Mosca A, Dalla Volta A, Prati V, Ortega C, Buttigliero C, Fea E, Vanella P, Valcamonico F, Zamparini M, Sirotova Z, Chiappino I, Dal Canton O, Masini C, Sacco C, Amoroso D, Montagnani F, Comandone A, Bellissimo AR, Ciccone G, Baier S, Gennari A, Tucci M, Berruti A. Maintenance versus discontinuation of androgen deprivation therapy during continuous or intermittent docetaxel administration in castration-resistant prostate cancer patients: A multicentre, randomised Phase III study by the Piemonte Oncology Network. Eur J Cancer. 2021 Sep;155:127-135. Epub 2021 Aug 6. link to original article PubMed
VIABLE: Vogelzang NJ, Beer TM, Gerritsen W, Oudard S, Wiechno P, Kukielka-Budny B, Samal V, Hajek J, Feyerabend S, Khoo V, Stenzl A, Csöszi T, Filipovic Z, Goncalves F, Prokhorov A, Cheung E, Hussain A, Sousa N, Bahl A, Hussain S, Fricke H, Kadlecova P, Scheiner T, Korolkiewicz RP, Bartunkova J, Spisek R; VIABLE Investigators. Efficacy and Safety of Autologous Dendritic Cell-Based Immunotherapy, Docetaxel, and Prednisone vs Placebo in Patients With Metastatic Castration-Resistant Prostate Cancer: The VIABLE Phase 3 Randomized Clinical Trial. JAMA Oncol. 2022 Apr 1;8(4):546-552. link to original article contains dosing details in manuscript link to PMC article PubMed NCT02111577
DORA: NCT03574571

Docetaxel & Prednisolone

Example orders

Example orders for Docetaxel (Taxotere) in prostate cancer

Regimen variant #1, 50 mg/m² bi-weekly

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Kellokumpu-Lehtinen et al. 2013 (PROSTY)	2004-2009	Phase 3 (E-switch-ic)	Docetaxel & Prednisolone; q3wk	Superior TTTF (primary endpoint) Median TTTF: 5.6 vs 4.9 mo (HR 0.77, 95% CI 0.625-0.91)

Chemotherapy

Docetaxel (Taxotere) 50 mg/m² IV over 60 minutes once on day 1

Endocrine therapy

Prednisolone (Millipred) 10 mg PO once per day on days 1 to 14

Supportive therapy

Dexamethasone (Decadron) 7.5 to 8 mg (route not specified) once per day, started 1 day prior to docetaxel and stopped 1 to 2 days after docetaxel infusion (in other words, from day -1 to day 2 or 3)
G-CSF not recommended unless patients developed febrile neutropenia or severe infection
"Treatment with bisphosphonates, erythropoietin, and palliative radiation therapy was allowed"

14-day cycles

Regimen variant #2, 75 mg/m² q3wk, 10 cycles

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Merseburger et al. 2022 (PRESIDE)	2014-2016	Phase 3 (C)	Docetaxel, Enzalutamide, Prednisolone	Seems to have inferior PFS

Chemotherapy

Docetaxel (Taxotere) 75 mg/m² IV once on day 1

Endocrine therapy

Prednisolone (Millipred) 10 mg PO once per day on days 1 to 21

21-day cycle for up to 10 cycles

Regimen variant #3, 75 mg/m² q3wk, indefinite

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Kellokumpu-Lehtinen et al. 2013 (PROSTY)	2004-2009	Phase 3 (C)	Docetaxel & Prednisolone; q2wk	Inferior TTTF
Fizazi et al. 2013 (ENTHUSE)	2008-NR	Phase 3 (C)	1a. Docetaxel, Prednisolone, Zibotentan 1b. Docetaxel, Prednisone, Zibotentan	Did not meet primary endpoint of OS

Chemotherapy

Docetaxel (Taxotere) 75 mg/m² IV over 60 minutes once on day 1

Endocrine therapy

Prednisolone (Millipred) 10 mg PO once per day on days 1 to 21
- Alternative dosing in Fizazi et al. 2013: 5 mg PO twice per day

Supportive therapy

Dexamethasone (Decadron) 7.5 to 8 mg daily, started 1 day prior to docetaxel 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

References

PROSTY: 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; 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 dosing details in manuscript PubMed NCT00255606
ENTHUSE: Fizazi K, Higano CS, Nelson JB, Gleave M, Miller K, Morris T, Nathan FE, McIntosh S, Pemberton K, Moul JW. Phase III, randomized, placebo-controlled study of docetaxel in combination with zibotentan in patients with metastatic castration-resistant prostate cancer. J Clin Oncol. 2013 May 10;31(14):1740-7. Epub 2013 Apr 8. Erratum in: J Clin Oncol. 2014 Oct 20;32(30):3461. Fizazi, Karim S [Corrected to Fizazi, Karim]. link to original article contains dosing details in manuscript PubMed NCT00617669
PRESIDE: Merseburger AS, Attard G, Åström L, Matveev VB, Bracarda S, Esen A, Feyerabend S, Senkus E, López-Brea Piqueras M, Boysen G, Gourgioti G, Martins K, Chowdhury S. Continuous enzalutamide after progression of metastatic castration-resistant prostate cancer treated with docetaxel (PRESIDE): an international, randomised, phase 3b study. Lancet Oncol. 2022 Nov;23(11):1398-1408. Epub 2022 Oct 18. link to original article contains dosing details in abstract PubMed NCT02288247

Mitoxantrone & Hydrocortisone

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Kantoff et al. 1999 (CALGB 9182)	1992-1995	Phase 3 (E-RT-esc)	Hydrocortisone	Did not meet primary endpoint of OS

Chemotherapy

Mitoxantrone (Novantrone) 14 mg/m² IV once on day 1

Endocrine therapy

Hydrocortisone (Cortef) 30 mg PO once per day on days 1 to 21, taken in the morning
Hydrocortisone (Cortef) 10 mg PO once per day on days 1 to 21, taken in the evening

21-day cycles

References

CALGB 9182: Kantoff PW, Halabi S, Conaway M, Picus J, Kirshner J, Hars V, Trump D, Winer EP, Vogelzang NJ. Hydrocortisone with or without mitoxantrone in men with hormone-refractory prostate cancer: results of the Cancer and Leukemia Group B 9182 study. J Clin Oncol. 1999 Aug;17(8):2506-13. link to original article contains dosing details in manuscript PubMed

Mitoxantrone & Prednisone

Example orders

Example orders for Mitoxantrone (Novantrone) in prostate cancer

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Moore et al. 1994	NR	Phase 2 (RT)
Tannock et al. 1996 (CCI-NOV22)	1990-1994	Phase 3 (E-RT-esc)	Prednisone	Superior palliation
Berry et al. 2002	1997-1999	Phase 3 (E-esc)	Prednisone	Seems to have superior TTTF
Petrylak et al. 2004 (SWOG S9916)	1999-2003	Phase 3 (C)	Docetaxel & Estramustine	Seems to have inferior OS
Tannock et al. 2004 (TAX 327)	2000-2002	Phase 3 (C)	1. Weekly Docetaxel & Prednisone	Did not meet primary endpoint of OS
Tannock et al. 2004 (TAX 327)	2000-2002	Phase 3 (C)	2. Every 3-week Docetaxel & Prednisone	Inferior OS
de Bono et al. 2010 (TROPIC)	2007-01-02 to 2008-10-23	Phase 3 (C)	Cabazitaxel & Prednisone	Inferior OS

Prior treatment criteria

SWOG S9916: Hormone-independent prostate cancer
TAX 327: Disease progression during endocrine therapy, and no prior chemotherapy
TROPIC: Previous endocrine therapy, and failure of a docetaxel-containing regimen

Chemotherapy

Mitoxantrone (Novantrone) 12 mg/m² IV over 15 to 30 minutes once on day 1

Endocrine therapy

Prednisone (Sterapred) 10 mg PO once per day on days 1 to 21
- Some protocols give 5 mg PO twice per day

21-day cycle for up to 10 cycles

References

Moore MJ, Osoba D, Murphy K, Tannock IF, Armitage A, Findlay B, Coppin C, Neville A, Venner P, Wilson J. Use of palliative end points to evaluate the effects of mitoxantrone and low-dose prednisone in patients with hormonally resistant prostate cancer. J Clin Oncol. 1994 Apr;12(4):689-94. link to original article PubMed
CCI-NOV22: 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
1. 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
Berry W, Dakhil S, Modiano M, Gregurich M, Asmar L. Phase III study of mitoxantrone plus low dose prednisone versus low dose prednisone alone in patients with asymptomatic hormone refractory prostate cancer. J Urol. 2002 Dec;168(6):2439-43. link to original article contains dosing details in abstract PubMed
TAX 327: 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 dosing details in manuscript PubMed
1. 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 dosing details in manuscript PubMed
SWOG S9916: 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 NCT00004001
TROPIC: 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 dosing details in manuscript PubMed NCT00417079

Immunotherapy for metastatic castrate-resistant disease

Ipilimumab & RT

Ipilimumab & RT: Ipilimumab & Radiation Therapy

Regimen

Study	Evidence	Efficacy	Patient population
Slovin et al. 2013 (CA184-017)	Phase 1/2	ORR: 4% (95% CI n/a), PSA RR: 16%;	Most had ADT, some had docetaxel use. 10 mg/kg cohort reported here.

Note: Lower doses of ipilimumab including 3 mg/kg (the FDA approved dose) were investigated, but the 10 mg/kg dose was recommended in this study.

Immunotherapy

Ipilimumab (Yervoy) 10 mg/kg IV over 90 minutes once on day 1

Radiotherapy

Radiation therapy given focally at a single dose of 800 cGy per target bone lesion for up to three bone lesions per patient, given 24 to 48 h before the first ipilimumab dose

21-day cycle for 4 cycles

References

CA184-017: 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. Epub 2013 Mar 27. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00323882

Sipuleucel-T monotherapy

Example orders

Example orders for Sipuleucel-T (Provenge) in prostate cancer

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Small et al. 2006 (D9901)	2000-01 to 2001-10	Phase 3 (E-RT-esc)	Placebo	Might have superior TTP (primary endpoint)
Higano et al. 2009 (D9902A)	2000-2003	Phase 3 (E-esc)	Placebo	Might have superior TTP (primary endpoint)
Kantoff et al. 2010 (IMPACT_prostate)	2003-2007	Phase 3 (E-RT-esc)	Placebo	Seems to have superior OS (primary endpoint) Median OS: 25.8 vs 21.7 mo (HR 0.78, 95% CI 0.61-0.98)

Note: Higano et al. 2009 was a pooled update but also the first publication to describe results of D9902A. IMPACT should not be confused with the studies of the same name in breast cancer and colorectal cancer.

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 therapy

Acetaminophen (Tylenol) PO once per week on weeks 0, 2, 4; 30 minutes prior to sipuleucel-T
Antihistamine PO once per week on weeks 0, 2, 4; 30 minutes prior to sipuleucel-T

One course

References

D9901: Small EJ, Schellhammer PF, Higano CS, Redfern CH, Nemunaitis JJ, Valone FH, Verjee SS, Jones LA, Hershberg RM. Placebo-controlled phase III trial of immunologic therapy with sipuleucel-T (APC8015) in patients with metastatic, asymptomatic hormone refractory prostate cancer. J Clin Oncol. 2006 Jul 1;24(19):3089-94. link to original article PubMed NCT00005947
1. Pooled update: Higano CS, Schellhammer PF, Small EJ, Burch PA, Nemunaitis J, Yuh L, Provost N, Frohlich MW. Integrated data from 2 randomized, double-blind, placebo-controlled, phase 3 trials of active cellular immunotherapy with sipuleucel-T in advanced prostate cancer. Cancer. 2009 Aug 15;115(16):3670-9. link to original article PubMed
D9902A: Higano CS, Schellhammer PF, Small EJ, Burch PA, Nemunaitis J, Yuh L, Provost N, Frohlich MW. Integrated data from 2 randomized, double-blind, placebo-controlled, phase 3 trials of active cellular immunotherapy with sipuleucel-T in advanced prostate cancer. Cancer. 2009 Aug 15;115(16):3670-9. link to original article PubMed NCT01133704
IMPACT: 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 dosing details in manuscript PubMed NCT00065442
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 dosing details in manuscript PubMed

Radioactive agents for bony metastatic disease

Lutetium Lu 177 vipivotide tetraxetan monotherapy

Regimen

FDA-recommended dose

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Sartor et al. 2021 (VISION_PrCA)	2018-06 to 2019-10	Phase 3 (E-RT-switch-ooc)	Standard of care (excluding chemotherapy, immunotherapy, or Radium-223)	Superior OS (co-primary endpoint) Median OS: 15.3 vs 11.3 mo (HR 0.62, 95% CI 0.52-0.74)

Radiotherapy

Lutetium Lu 177 vipivotide tetraxetan (Pluvicto) 7.4 GBq IV once on day 1

6-week cycles for 6 cycles

References

TheraP: Hofman MS, Emmett L, Sandhu S, Iravani A, Joshua AM, Goh JC, Pattison DA, Tan TH, Kirkwood ID, Ng S, Francis RJ, Gedye C, Rutherford NK, Weickhardt A, Scott AM, Lee ST, Kwan EM, Azad AA, Ramdave S, Redfern AD, Macdonald W, Guminski A, Hsiao E, Chua W, Lin P, Zhang AY, McJannett MM, Stockler MR, Violet JA, Williams SG, Martin AJ, Davis ID; TheraP Trial Investigators and the Australian and New Zealand Urogenital and Prostate Cancer Trials Group. [177Lu]Lu-PSMA-617 versus cabazitaxel in patients with metastatic castration-resistant prostate cancer (TheraP): a randomised, open-label, phase 2 trial. Lancet. 2021 Feb 27;397(10276):797-804. Epub 2021 Feb 11. link to original article PubMed NCT03392428
1. Update: Hofman MS, Emmett L, Sandhu S, Iravani A, Buteau JP, Joshua AM, Goh JC, Pattison DA, Tan TH, Kirkwood ID, Ng S, Francis RJ, Gedye C, Rutherford NK, Weickhardt A, Scott AM, Lee ST, Kwan EM, Azad AA, Ramdave S, Redfern AD, Macdonald W, Guminski A, Hsiao E, Chua W, Lin P, Zhang AY, Stockler MR, Williams SG, Martin AJ, Davis ID; TheraP Trial Investigators and the Australian and New Zealand Urogenital and Prostate Cancer Trials Group. Overall survival with [177Lu]Lu-PSMA-617 versus cabazitaxel in metastatic castration-resistant prostate cancer (TheraP): secondary outcomes of a randomised, open-label, phase 2 trial. Lancet Oncol. 2024 Jan;25(1):99-107. Epub 2023 Nov 30. link to original article PubMed
VISION_PrCA: Sartor O, de Bono J, Chi KN, Fizazi K, Herrmann K, Rahbar K, Tagawa ST, Nordquist LT, Vaishampayan N, El-Haddad G, Park CH, Beer TM, Armour A, Pérez-Contreras WJ, DeSilvio M, Kpamegan E, Gericke G, Messmann RA, Morris MJ, Krause BJ; VISION Investigators. Lutetium-177-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer. N Engl J Med. 2021 Sep 16;385(12):1091-1103. Epub 2021 Jun 23. link to original article link to PMC article PubMed NCT03511664
1. HRQoL analysis: Fizazi K, Herrmann K, Krause BJ, Rahbar K, Chi KN, Morris MJ, Sartor O, Tagawa ST, Kendi AT, Vogelzang N, Calais J, Nagarajah J, Wei XX, Koshkin VS, Beauregard JM, Chang B, Ghouse R, DeSilvio M, Messmann RA, de Bono J. Health-related quality of life and pain outcomes with [177Lu]Lu-PSMA-617 plus standard of care versus standard of care in patients with metastatic castration-resistant prostate cancer (VISION): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2023 Jun;24(6):597-610. link to original article PubMed

Radium-223 monotherapy

Regimen variant #1

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy	Comparative Toxicity
Parker et al. 2013 (ALSYMPCA)	2008-2011	Phase 3 (E-RT-esc)	Placebo	Superior OS (primary endpoint) Median OS: 14 vs 11.2 mo (HR 0.70, 95% CI 0.55-0.88)	Superior EQ-5D score

Radiotherapy

Radium-223 (Xofigo) 50 kBq/kg IV once on day 1

28-day cycle for 6 cycles

Regimen variant #2

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Nilsson et al. 2007	2004-2005	Randomized Phase 2 (E-esc)	Placebo	Might have superior OS (secondary endpoint)

Note: 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 dosing details in manuscript PubMed
1. 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 dosing details in manuscript PubMed
ALSYMPCA: 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 dosing details in manuscript PubMed NCT00699751
1. Subgroup analysis: Sartor O, Coleman R, Nilsson S, Heinrich D, Helle SI, O'Sullivan JM, Fosså SD, Chodacki A, Wiechno P, Logue J, Widmark A, Johannessen DC, Hoskin P, James ND, Solberg A, Syndikus I, Vogelzang NJ, O'Bryan-Tear CG, Shan M, Bruland ØS, Parker C. Effect of radium-223 dichloride on symptomatic skeletal events in patients with castration-resistant prostate cancer and bone metastases: results from a phase 3, double-blind, randomised trial. Lancet Oncol. 2014 Jun;15(7):738-46. Epub 2014 May 13. link to original article PubMed
2. Subgroup analysis: Hoskin P, Sartor O, O'Sullivan JM, Johannessen DC, Helle SI, Logue J, Bottomley D, Nilsson S, Vogelzang NJ, Fang F, Wahba M, Aksnes AK, Parker C. 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. Lancet Oncol. 2014 Nov;15(12):1397-406. Epub 2014 Oct 17. link to original article PubMed
3. 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

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Resche et al. 1997	NR	Phase 3 (E-esc)	Samarium-153; 0.5 mCi/kg	Seems to have superior pain control at week 4
Sartor et al. 2004	NR	Phase 3 (E-esc)	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 therapy

1000 mL of fluid IV or PO 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 dosing details in manuscript 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 dosing details in manuscript 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 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.

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
- PCA3.org
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
Heme Onc Notes GU page

Quality of life assessment tools

EPIC-CP: Expanded Prostate Cancer Index Composite for Clinical Practice (twice per dayMC)
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

[1] 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

[2] 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

[3] 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

[1]

[2]

[3]

@@ Line 1: / Line 1: @@
-{| class="wikitable" style="text-align:center; width:100%;"
+<span id="BackToTop"></span>
-! colspan="2" style="color:white; font-size:125%; background-color:#08519c" align="center" |'''Page editor'''
+<div class="noprint" style="background-color:LightGray; position:fixed; bottom:2%; right:0.25%; padding-left:5px; padding-right:5px; margin: 15px; opacity:0.8; border-style: solid; border-color:DarkGray; border-width: 1px">
-! colspan="2" style="color:white; font-size:125%; background-color:#08519c" align="center" |'''Section editor'''
+[[#top|Back to Top]]
-|-
+</div>
-| style="background-color:#F0F0F0" |[[File:LauraGraham.jpg|frameless|upright=0.3|center]]
+{{#lst:Editorial board transclusions|prca}}
-|<big>Laura S. Graham, MD<br>University of Washington<br>Fred Hutchinson Cancer Research Center<br>Seattle, WA</big><br>[[File:Social-twitter-icon.png|frameless|upright=0.1]] [https://twitter.com/LauraGrahamMD LauraGrahamMD]
-| style="background-color:#F0F0F0" |[[File:Alikhaki.jpg|frameless|upright=0.3|center]]
-| style="width:35%" |<big>[[User:Alikhaki|Ali Raza Khaki, MD]]<br>Stanford University<br>Palo Alto, CA</big><br>[[File:Social-twitter-icon.png|frameless|upright=0.1]] [https://twitter.com/arkhaki arkhaki]
-|-
-|}
 ''Are you looking for a regimen, but can't find it here? It is possible that we've moved it to the [[Prostate_cancer_-_historical|historical regimens page]]. For placebo or observational studies in this condition, please visit [[Prostate cancer - null regimens|this page]]. If you still can't find it, please let us know so we can add it!'' <br>
+'''''Note: many regimens on this page contain androgen deprivation therapy (ADT), which is not further defined by the cited clinical trials. Specific approaches to ADT include pharmacologic and surgical interventions; see individual papers for details.'''''<br>
 '''Note: this page contains regimens for prostate cancer which were not tested in biomarker-specific populations. The following links will take you to biomarker-specific subpages:'''
 *Regimens for [[Prostate_cancer,_BRCA-mutated|'''BRCA-mutated prostate cancer are here''']].
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 |}
 {{TOC limit|limit=3}}
+=Living Interactive Systematic Reviews=
+*[https://mcspc.living-evidence.com/ First-line treatment options in metastatic castration-sensitive prostate cancer (mCSPC)]
 =Guidelines=
+'''Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.'''
 ==[https://www.asco.org/practice-guidelines/quality-guidelines/guidelines/genitourinary-cancer ASCO]==
+*'''2023:''' Virgo et al. [https://doi.org/10.1200/jco.23.00155 Initial Management of Noncastrate Advanced, Recurrent, or Metastatic Prostate Cancer: ASCO Guideline Update] [https://pubmed.ncbi.nlm.nih.gov/37011338/ PubMed]
+**'''2021:''' Virgo et al. [https://doi.org/10.1200/jco.20.03256 Initial Management of Noncastrate Advanced, Recurrent, or Metastatic Prostate Cancer: ASCO Guideline Update] [https://pubmed.ncbi.nlm.nih.gov/33497248/ PubMed]
+**'''2018:''' Morris et al. [https://doi.org/10.1200/JCO.2018.78.0619 Optimizing Anticancer Therapy in Metastatic Non-Castrate Prostate Cancer: American Society of Clinical Oncology Clinical Practice Guideline] [https://pubmed.ncbi.nlm.nih.gov/29608397/ PubMed]
+*'''2023:''' Garje et al. [https://doi.org/10.1200/jco.23.02128 Systemic Therapy Update on 177Lutetium-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer: ASCO Guideline Rapid Recommendation Update] [https://pubmed.ncbi.nlm.nih.gov/37931186/ PubMed]
+**'''2022:''' Garje et al. [https://doi.org/10.1200/jco.22.01865 Systemic Therapy Update on 177Lutetium-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer: ASCO Rapid Recommendation] [https://pubmed.ncbi.nlm.nih.gov/36112960/ PubMed]
+*'''2020:''' Trabulsi et al. [https://doi.org/10.1200/jco.19.02757 Optimum Imaging Strategies for Advanced Prostate Cancer: ASCO Guideline] [https://pubmed.ncbi.nlm.nih.gov/31940221/ PubMed]
+*'''2019:''' Eggener et al. [https://doi.org/10.1200/jco.19.02768 Molecular Biomarkers in Localized Prostate Cancer: ASCO Guideline] [https://pubmed.ncbi.nlm.nih.gov/31829902/ PubMed]
+*'''2017:''' Virgo et al. [https://doi.org/10.1200/JCO.2017.72.8030 Second-Line Hormonal Therapy for Men With Chemotherapy-Naïve, Castration-Resistant Prostate Cancer: American Society of Clinical Oncology Provisional Clinical Opinion] [https://pubmed.ncbi.nlm.nih.gov/28441112/ PubMed]
-*'''2018:''' Morris et al. [https://doi.org/10.1200/JCO.2018.78.0619 Optimizing Anticancer Therapy in Metastatic Non-Castrate Prostate Cancer: American Society of Clinical Oncology Clinical Practice Guideline]
+==ASCO & CCO==
-*'''2017:''' Virgo et al. [https://doi.org/10.1200/JCO.2017.72.8030 Second-Line Hormonal Therapy for Men With Chemotherapy-Naïve, Castration-Resistant Prostate Cancer: American Society of Clinical Oncology Provisional Clinical Opinion] [https://www.ncbi.nlm.nih.gov/pubmed/28441112 PubMed]
-*'''2016:''' [https://www.asco.org/practice-guidelines/quality-guidelines/guidelines/genitourinary-cancer#/9336 Active Surveillance for the Management of Localized Prostate Cancer Endorsement]
-*'''2015:''' [https://www.asco.org/practice-guidelines/quality-guidelines/guidelines/genitourinary-cancer#/9426 Prostate Cancer Survivorship Care Guideline Endorsement]
-===Older===
+*'''2014:''' Basch et al. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4876355/ Systemic Therapy in Men With Metastatic Castration-Resistant Prostate Cancer: American Society of Clinical Oncology and Cancer Care Ontario Clinical Practice Guideline] [https://pubmed.ncbi.nlm.nih.gov/25199761/ PubMed]
+==AUA==
+*'''2023:''' Lowrance et al. [https://doi.org/10.1097/ju.0000000000003452 Updates to Advanced Prostate Cancer: AUA/SUO Guideline (2023)] [https://pubmed.ncbi.nlm.nih.gov/37096583/ PubMed]
+**'''2020:''' Lowrance et al. [https://doi.org/10.1097/ju.0000000000001375 Advanced Prostate Cancer: AUA/ASTRO/SUO Guideline PART I] [https://pubmed.ncbi.nlm.nih.gov/32960679/ PubMed]
-*'''2014:''' [https://www.asco.org/practice-guidelines/quality-guidelines/guidelines/genitourinary-cancer#/9486 Adjuvant and Salvage Radiotherapy After Prostatectomy Endorsement]
+*'''2018:''' Cookson et al. [https://doi.org/10.1016/j.juro.2018.07.090 Castration-Resistant Prostate Cancer: AUA Guideline Amendment 2018] [https://pubmed.ncbi.nlm.nih.gov/30086276/ PubMed]
-*'''2012:''' [https://www.asco.org/practice-guidelines/quality-guidelines/guidelines/genitourinary-cancer#/9501 Screening for Prostate Cancer with Prostate-Specific Antigen (PSA) Testing PCO]
+**'''2015:''' Lowrance et al. [https://doi.org/10.1016/j.juro.2015.10.086 Castration-Resistant Prostate Cancer: AUA Guideline Amendment 2015] [https://pubmed.ncbi.nlm.nih.gov/26498056/ PubMed]
-*'''2009:''' [https://www.asco.org/practice-guidelines/quality-guidelines/guidelines/genitourinary-cancer#/9511 Use of 5-alpha Reductase Inhibitors for Prostate Cancer Chemoprevention]
+**'''2014:''' Cookson et al. [https://doi.org/10.1016/j.juro.2014.10.104 Castration-resistant prostate cancer: AUA guideline amendment] [https://pubmed.ncbi.nlm.nih.gov/25444753/ PubMed]
-*'''2007:''' [https://www.asco.org/practice-guidelines/quality-guidelines/guidelines/genitourinary-cancer#/9516 Non-Hormonal Therapy for Men With Metastatic Hormone-Refractory (castration-resistant) Prostate Cancer Endorsement]
+**'''2013:''' Cookson et al. [https://doi.org/10.1016/j.juro.2013.05.005 Castration-resistant prostate cancer: AUA Guideline] [https://pubmed.ncbi.nlm.nih.gov/23665272/ PubMed]
-==ASCO & CCO==
+==AUA/ASCO/SUO==
+*'''2024:''' Holzbeierlein et al. [https://doi.org/10.1097/ju.0000000000003981 Treatment of Non-Metastatic Muscle-Invasive Bladder Cancer: AUA/ASCO/SUO GUIDELINE (2017; Amended 2020, 2024)] [https://pubmed.ncbi.nlm.nih.gov/38661067/ PubMed]
-*'''2014:''' Basch et al. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4876355/ Systemic Therapy in Men With Metastatic Castration-Resistant Prostate Cancer: American Society of Clinical Oncology and Cancer Care Ontario Clinical Practice Guideline]
+==ASTRO/ASCO/AUA==
+*'''2018:''' Morgan et al. [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6269129/ Hypofractionated Radiation Therapy for Localized Prostate Cancer: An ASTRO, ASCO, and AUA Evidence-Based Guideline] [https://pubmed.ncbi.nlm.nih.gov/30307776/ PubMed]
-==AUA==
-*[https://www.auanet.org/education/guidelines/castration-resistant-prostate-cancer.cfm Castration-Resistant Prostate Cancer: AUA Guideline @ AUAnet]
-**[https://www.auanet.org/common/pdf/education/clinical-guidance/Castration-Resistant-Prostate-Cancer.pdf PDF (2015) @ AUAnet]
-*[https://www.auajournals.org/doi/full/10.1016/j.juro.2015.10.086 Castration-Resistant Prostate Cancer: AUA Guideline Amendment 2015] [https://www.ncbi.nlm.nih.gov/pubmed/26498056 PubMed]
 ==EAU/ESTRO/SIOG==
-*'''2017:''' [http://www.europeanurology.com/article/S0302-2838(16)30469-9/fulltext EAU-ESTRO-SIOG Guidelines on Prostate Cancer. Part II: Treatment of Relapsing, Metastatic, and Castration-Resistant Prostate Cancer] [https://www.ncbi.nlm.nih.gov/pubmed/27591931 PubMed]
+*'''2017:''' Cornford et al. [https://doi.org/10.1016/j.eururo.2016.08.002 EAU-ESTRO-SIOG Guidelines on Prostate Cancer. Part II: Treatment of Relapsing, Metastatic, and Castration-Resistant Prostate Cancer] [https://pubmed.ncbi.nlm.nih.gov/27591931/ PubMed]
+==[https://www.esmo.org/ ESMO]==
+*'''2023:''' Fizazi et al. [https://doi.org/10.1016/j.annonc.2023.02.015 Updated treatment recommendations for prostate cancer from the ESMO Clinical Practice Guideline considering treatment intensification and use of novel systemic agents] [https://pubmed.ncbi.nlm.nih.gov/36958590/ PubMed]
+**'''2020:''' Parker et al. [https://doi.org/10.1016/j.annonc.2020.06.011 Prostate cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/32593798/ PubMed]
+**'''2015:''' Parker et al. [https://doi.org/10.1093/annonc/mdv222 Cancer of the prostate: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/26205393/ PubMed]
+**'''2013:''' Horwich et al. [https://doi.org/10.1093/annonc/mdt208 ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/23813930/ PubMed]
+**'''2012:''' Horwich et al. [https://doi.org/10.1093/annonc/mds624 Prostate cancer: ESMO Consensus Conference Guidelines] [https://pubmed.ncbi.nlm.nih.gov/23303340/ PubMed]
+**'''2010:''' Horwich et al. [https://doi.org/10.1093/annonc/mdq174 Prostate cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/20555062/ PubMed]
+**'''2009:''' Horwich et al. [https://doi.org/10.1093/annonc/mdp135 Prostate cancer: ESMO clinical recommendations for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/19454471/ PubMed]
+**'''2008:''' Horwich et al. [https://doi.org/10.1093/annonc/mdn084 Prostate cancer: ESMO clinical recommendations for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/18456765/ PubMed]
+**'''2007:''' Horwich & Parker. [https://doi.org/10.1093/annonc/mdm028 Prostate cancer: ESMO clinical recommendations for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/17491038/ PubMed]
+**'''2003:''' Kataja. [https://doi.org/10.1093/annonc/mdg293 ESMO Minimum Clinical Recommendations for diagnosis, treatment and follow-up of prostate cancer] [https://pubmed.ncbi.nlm.nih.gov/12853339/ PubMed]
+*'''2022:''' Kanesvaran et al. [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9434138/ Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with prostate cancer] [https://pubmed.ncbi.nlm.nih.gov/35797737/ PubMed]
-==[http://www.esmo.org/ ESMO]==
+==NCCN==
-*'''2020:''' Parker et al. [https://doi.org/10.1016/j.annonc.2020.06.011 Prostate cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up]
+*[https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1459 NCCN Guidelines - Prostate Cancer]
-===Older===
+**'''2023:''' Schaeffer et al. [https://doi.org/10.6004/Jnccn.2023.0050 Prostate Cancer, Version 4.2023, NCCN Clinical Practice Guidelines in Oncology.] [https://pubmed.ncbi.nlm.nih.gov/37856213/ PubMed]
-*'''2015:''' Parker et al. [https://www.esmo.org/Guidelines/Genitourinary-Cancers/Cancer-of-the-Prostate ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up]
+**'''2019:''' Mohler et al. [https://doi.org/10.6004/Jnccn.2019.0023 Prostate Cancer, Version 2.2019, NCCN Clinical Practice Guidelines in Oncology.] [https://pubmed.ncbi.nlm.nih.gov/31085757/ PubMed]
-*'''2013:''' Horwich et al. [https://academic.oup.com/annonc/article-lookup/doi/10.1093/annonc/mdt208 ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up] [https://www.ncbi.nlm.nih.gov/pubmed/23813930 PubMed]
+**'''2018:''' Carroll et al. [https://doi.org/10.6004/Jnccn.2018.0036 NCCN Guidelines Updates: Prostate Cancer and Prostate Cancer Early Detection.] [https://pubmed.ncbi.nlm.nih.gov/29784740/ PubMed]
-*'''2012:''' Horwich et al. [https://annonc.oxfordjournals.org/content/24/5/1141.full.pdf+html ESMO Consensus Conference Guidelines] [https://www.ncbi.nlm.nih.gov/pubmed/23303340 PubMed]
+**'''2016:''' Mohler et al. [https://doi.org/10.6004/Jnccn.2016.0004 Prostate Cancer, Version 1.2016.] [https://pubmed.ncbi.nlm.nih.gov/26733552/ PubMed]
+**'''2015:''' Carroll et al. [https://doi.org/10.6004/Jnccn.2015.0181 NCCN Clinical Practice Guidelines Prostate Cancer Early Detection, Version 2.2015.] [https://pubmed.ncbi.nlm.nih.gov/26656522/ PubMed]
+**'''2014:''' Carroll et al. [https://doi.org/10.6004/Jnccn.2014.0120 Prostate cancer early detection, version 1.2014. Featured updates to the NCCN Guidelines.] [https://pubmed.ncbi.nlm.nih.gov/25190691/ PubMed]
+**'''2014:''' Mohler et al. [https://doi.org/10.6004/Jnccn.2014.0072 Prostate cancer, version 2.2014.] [https://pubmed.ncbi.nlm.nih.gov/24812137/ PubMed]
+**'''2013:''' Mohler et al. [https://doi.org/10.6004/Jnccn.2013.0174 Prostate cancer, version 1.2014.] [https://pubmed.ncbi.nlm.nih.gov/24335682/ PubMed]
+**'''2012:''' Mohler et al. [https://doi.org/10.6004/Jnccn.2012.0114 Prostate cancer, Version 3.2012: featured updates to the NCCN guidelines.] [https://pubmed.ncbi.nlm.nih.gov/22956807/ PubMed]
+**'''2010:''' Kawachi et al. [https://doi.org/10.6004/Jnccn.2010.0016 NCCN clinical practice guidelines in oncology: prostate cancer early detection.] [https://pubmed.ncbi.nlm.nih.gov/20141680/ PubMed]
+**'''2010:''' Mohler et al. [https://doi.org/10.6004/Jnccn.2010.0012 NCCN clinical practice guidelines in oncology: prostate cancer.] [https://pubmed.ncbi.nlm.nih.gov/20141676/ PubMed]
+**'''2007:''' Kawachi et al. [ Prostate cancer early detection. Clinical practice guidelines in oncology.] [https://pubmed.ncbi.nlm.nih.gov/17692177/ PubMed]
+**'''2007:''' Mohler et al. [ Prostate cancer. Clinical practice guidelines in oncology.] [https://pubmed.ncbi.nlm.nih.gov/17692170/ PubMed]
+**'''2004:''' Authors not listed. [https://doi.org/10.6004/Jnccn.2004.0018 Prostate cancer early detection. Clinical practice guidelines in oncology.] [https://pubmed.ncbi.nlm.nih.gov/19795604/ PubMed]
+**'''2004:''' Authors not listed. [https://doi.org/10.6004/Jnccn.2004.0021 Prostate cancer. NCCN clinical practice guidelines in oncology.] [https://pubmed.ncbi.nlm.nih.gov/19795607/ PubMed]
+**'''2003:''' Babaian et al. [ Prostate cancer early detection clinical practice guidelines in oncology.] [https://pubmed.ncbi.nlm.nih.gov/19795575/ PubMed]
-==[https://www.nccn.org/ NCCN]==
+==SIOG==
+*'''2019:''' Boyle et al. [https://doi.org/10.1016/j.ejca.2019.04.031 Updated recommendations of the International Society of Geriatric Oncology on prostate cancer management in older patients] [https://pubmed.ncbi.nlm.nih.gov/31195356/ PubMed]
+**'''2017:''' Droz et al. [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc3258484/ https://doi.org/10.1016/j.eururo.2016.12.025 Management of Prostate Cancer in Elderly Patients: Recommendations of a Task Force of the International Society of Geriatric Oncology] [https://pubmed.ncbi.nlm.nih.gov/28089304/ PubMed]
+**'''2014:''' Droz et al. [https://doi.org/10.1016/s1470-2045(14)70018-x Management of prostate cancer in older patients: updated recommendations of a working group of the International Society of Geriatric Oncology] [https://pubmed.ncbi.nlm.nih.gov/25079103/ PubMed]
+**'''2010:''' Droz et al. [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc3258484/ Management of prostate cancer in older men: recommendations of a working group of the International Society of Geriatric Oncology] [https://pubmed.ncbi.nlm.nih.gov/20346033/ PubMed]
-*[http://www.nccn.org/professionals/physician_gls/pdf/prostate.pdf NCCN Guidelines - Prostate Cancer]
+==SITC==
+*'''2016:''' McNeel et al. [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5170901/ The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of prostate carcinoma] [https://pubmed.ncbi.nlm.nih.gov/28031820/ PubMed]
 ==St Gallen==
+*'''2022:''' Gillessen et al. [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7614721/ Management of Patients with Advanced Prostate Cancer. Part I: Intermediate-/High-risk and Locally Advanced Disease, Biochemical Relapse, and Side Effects of Hormonal Treatment: Report of the Advanced Prostate Cancer Consensus Conference 2022] [https://pubmed.ncbi.nlm.nih.gov/36494221/ PubMed]
-*'''2015:''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4511225/ Management of patients with advanced prostate cancer: recommendations of the St Gallen Advanced Prostate Cancer Consensus Conference (APCCC)]
+**'''2022:''' Gillessen et al. [https://doi.org/10.1016/j.eururo.2022.04.002 Management of Patients with Advanced Prostate Cancer: Report from the Advanced Prostate Cancer Consensus Conference 2021] [https://pubmed.ncbi.nlm.nih.gov/35450732/ PubMed]
+**'''2019:''' Gillessen et al. [https://doi.org/10.1016/j.eururo.2020.01.012 Management of Patients with Advanced Prostate Cancer: Report of the Advanced Prostate Cancer Consensus Conference 2019] [https://pubmed.ncbi.nlm.nih.gov/32001144/ PubMed]
+**'''2017:''' Gillessen et al. [https://doi.org/10.1016/j.eururo.2017.06.002 Management of Patients with Advanced Prostate Cancer: The Report of the Advanced Prostate Cancer Consensus Conference APCCC 2017] [https://pubmed.ncbi.nlm.nih.gov/28655541/ PubMed]
+**'''2015:''' Gillessen et al. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4511225/ Management of patients with advanced prostate cancer: recommendations of the St Gallen Advanced Prostate Cancer Consensus Conference (APCCC)] [https://pubmed.ncbi.nlm.nih.gov/26041764/ PubMed]
 =Induction ADT=
 ==ADT {{#subobject:8ab01b|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
 ADT: '''<u>A</u>'''ndrogen '''<u>D</u>'''eprivation '''<u>T</u>'''herapy
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:25b39f|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 ! style="width: 20%" |Study
-! style="width: 20%" |Years of enrollment
+! style="width: 20%" |Dates of enrollment
 ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 ! style="width: 20%" |Comparator
@@ Line 82: / Line 111: @@
 |[https://doi.org/10.1200/JCO.2003.05.004 Roach et al. 2003 (RTOG 94-13)]
 |1995-1999
-| style="background-color:#1a9851" |Phase III (E-switch-ic)
+| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 |[[#ADT|ADT]]; adjuvant
 | style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
@@ Line 88: / Line 117: @@
 |[https://doi.org/10.1200/JCO.2014.58.0662 Pisansky et al. 2014 (RTOG 9910)]
 |2000-2004
-| style="background-color:#1a9851" |Phase III (C)
+| style="background-color:#1a9851" |Phase 3 (C)
 |[[#ADT|ADT]] x 28 weeks
 | style="background-color:#ffffbf" |Did not meet primary endpoint of disease-specific mortality
 |-
 |}
-''Note: these are clinical trials that did not specify a particular drug to be used for androgen deprivation. See papers for details.''
+''Note: these are clinical trials that did not specify a particular approach to androgen deprivation. See papers for details.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Endocrine therapy====
+*[[:Category:Androgen-deprivation therapy|ADT]]
-*[[:Category:GnRH agonists|LHRH agonist]]
-*[[Bicalutamide (Casodex)]] or [[Flutamide (Eulexin)]]
 '''8-week course'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
 ====Subsequent treatment====
+*Definitive [[#ADT_.26_RT|ADT & RT]]
-*[[#ADT_.26_RT|ADT & RT]]
+</div></div>
 ===References===
+#'''RTOG 94-13:''' Roach M 3rd, DeSilvio M, Lawton C, Uhl V, Machtay M, Seider MJ, Rotman M, Jones C, Asbell SO, Valicenti RK, Hahn S, Thomas CR Jr, Shipley WS; Radiation Therapy Oncology Group. Phase III trial comparing whole-pelvic versus prostate-only radiotherapy and neoadjuvant versus adjuvant combined androgen suppression: Radiation Therapy Oncology Group 9413. J Clin Oncol. 2003 May 15;21(10):1904-11. [https://doi.org/10.1200/JCO.2003.05.004 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12743142/ PubMed] [https://clinicaltrials.gov/study/NCT00769548 NCT00769548]
+##'''Update:''' Lawton CA, DeSilvio M, Roach M 3rd, Uhl V, Kirsch R, Seider M, Rotman M, Jones C, Asbell S, Valicenti R, Hahn S, Thomas CR Jr. An update of the phase III trial comparing whole pelvic to prostate only radiotherapy and neoadjuvant to adjuvant total androgen suppression: updated analysis of RTOG 94-13, with emphasis on unexpected hormone/radiation interactions. Int J Radiat Oncol Biol Phys. 2007 Nov 1;69(3):646-55. Epub 2007 May 24. [https://doi.org/10.1016/j.ijrobp.2007.04.003 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2917177/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/17531401/ PubMed]
+#'''RTOG 9910:''' Pisansky TM, Hunt D, Gomella LG, Amin MB, Balogh AG, Chinn DM, Seider MJ, Duclos M, Rosenthal SA, Bauman GS, Gore EM, Rotman MZ, Lukka HR, Shipley WU, Dignam JJ, Sandler HM. Duration of androgen suppression before radiotherapy for localized prostate cancer: Radiation Therapy Oncology Group randomized clinical trial 9910. J Clin Oncol. 2015 Feb 1;33(4):332-9. Epub 2014 Dec 22. [https://doi.org/10.1200/JCO.2014.58.0662 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4302214/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25534388/ PubMed] [https://clinicaltrials.gov/study/NCT00005044 NCT00005044]
-#'''RTOG 94-13:''' Roach M 3rd, DeSilvio M, Lawton C, Uhl V, Machtay M, Seider MJ, Rotman M, Jones C, Asbell SO, Valicenti RK, Han S, Thomas CR Jr, Shipley WS; Radiation Therapy Oncology Group. Phase III trial comparing whole-pelvic versus prostate-only radiotherapy and neoadjuvant versus adjuvant combined androgen suppression: Radiation Therapy Oncology Group 9413. J Clin Oncol. 2003 May 15;21(10):1904-11. [https://doi.org/10.1200/JCO.2003.05.004 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/12743142 PubMed]
+==Bicalutamide & Goserelin {{#subobject:bmbj66 |Regimen=1}}==
-##'''Update:''' Lawton CA, DeSilvio M, Roach M 3rd, Uhl V, Kirsch R, Seider M, Rotman M, Jones C, Asbell S, Valicenti R, Hahn S, Thomas CR Jr. An update of the phase III trial comparing whole pelvic to prostate only radiotherapy and neoadjuvant to adjuvant total androgen suppression: updated analysis of RTOG 94-13, with emphasis on unexpected hormone/radiation interactions. Int J Radiat Oncol Biol Phys. 2007 Nov 1;69(3):646-55. Epub 2007 May 24. [https://www.redjournal.org/article/S0360-3016(07)00641-4/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2917177/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/17531401 PubMed]
+<div class="toccolours" style="background-color:#eeeeee">
-#'''RTOG 9910:''' Pisansky TM, Hunt D, Gomella LG, Amin MB, Balogh AG, Chinn DM, Seider MJ, Duclos M, Rosenthal SA, Bauman GS, Gore EM, Rotman MZ, Lukka HR, Shipley WU, Dignam JJ, Sandler HM. Duration of androgen suppression before radiotherapy for localized prostate cancer: Radiation Therapy Oncology Group randomized clinical trial 9910. J Clin Oncol. 2015 Feb 1;33(4):332-9. Epub 2014 Dec 22. [https://doi.org/10.1200/JCO.2014.58.0662 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4302214/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/25534388 PubMed] NCT00005044
+===Regimen {{#subobject:afoogc |Variant=1}}===
-==Flutamide & Goserelin {{#subobject:b10d66 |Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
-===Regimen {{#subobject:afbb9c |Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 ! style="width: 20%" |Study
-! style="width: 20%" |Years of enrollment
+! style="width: 20%" |Dates of enrollment
 ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 ! style="width: 20%" |Comparator
 ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.redjournal.org/article/S0360-3016(04)00264-0/fulltext Crook et al. 2004]
+|[https://doi.org/10.1016/j.clon.2012.09.010 Mason et al. 2012 (FE200486 CS30)]
-|1995-2001
+|2009-NR
-| style="background-color:#1a9851" |Phase III (C)
+| style="background-color:#1a9851" |Phase 3 (C)
-|[[#Flutamide_.26_Goserelin|Flutamide & Goserelin]] x 8 mo
+|[[#Degarelix_monotherapy|Degarelix]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of PSA-PFS
+| style="background-color:#eeee01" |Non-inferior total prostate volume reduction at week 12
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Endocrine therapy====
+*[[Bicalutamide (Casodex)]] 50 mg PO once per day on days 0 to 16
-*[[Flutamide (Eulexin)]]
+*[[Goserelin (Zoladex)]] 3.6 mg SC once per day on days 3, 31, 59
-*[[Goserelin (Zoladex)]]
+'''12-week course'''
+</div>
-'''3-month course'''
+<div class="toccolours" style="background-color:#cbd5e7">
 ====Subsequent treatment====
+*Definitive [[Prostate_cancer_-_historical#Radiation_therapy|RT]]
-*[[Prostate_cancer_-_historical#Radiation_therapy|RT]]
+</div></div>
 ===References===
+#'''FE200486 CS30:''' Mason M, Maldonado Pijoan X, Steidle C, Guerif S, Wiegel T, van der Meulen E, Bergqvist PB, Khoo V. Neoadjuvant androgen deprivation therapy for prostate volume reduction, lower urinary tract symptom relief and quality of life improvement in men with intermediate- to high-risk prostate cancer: a randomised non-inferiority trial of degarelix versus goserelin plus bicalutamide. Clin Oncol (R Coll Radiol). 2013 Mar;25(3):190-6. Epub 2012 Dec 17. [https://doi.org/10.1016/j.clon.2012.09.010 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23257248/ PubMed] [https://clinicaltrials.gov/study/NCT00833248 NCT00833248]
-#Crook J, Ludgate C, Malone S, Lim J, Perry G, Eapen L, Bowen J, Robertson S, Lockwood G. Report of a multicenter Canadian phase III randomized trial of 3 months vs 8 months neoadjuvant androgen deprivation before standard-dose radiotherapy for clinically localized prostate cancer. Int J Radiat Oncol Biol Phys. 2004 Sep 1;60(1):15-23. [https://www.redjournal.org/article/S0360-3016(04)00264-0/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15337535 PubMed]
+==Degarelix monotherapy {{#subobject:uga516 |Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
-==Leuprolide monotherapy {{#subobject:1a6bc7 |Regimen=1}}==
+===Regimen {{#subobject:a0s9obj |Variant=1}}===
-{| class="wikitable" style="float:right; margin-left: 5px;"
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+! style="width: 20%" |Study
+! style="width: 20%" |Dates of enrollment
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |Comparator
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[[#top|back to top]]
+|[https://doi.org/10.1016/j.clon.2012.09.010 Mason et al. 2012 (FE200486 CS30)]
-|}
+|2009-NR
-===Regimen {{#subobject:53abfc |Variant=1}}===
+| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
-{| class="wikitable" style="width: 50%; text-align:center;"
+|[[#Bicalutamide_.26_Goserelin|Bicalutamide & Goserelin]]
-! style="width: 25%" |Study
+| style="background-color:#eeee01" |Non-inferior total prostate volume reduction at week 12 (primary endpoint)
-! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-|-
-|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70328-6/fulltext Denham et al. 2014 (RADAR)]
-| style="background-color:#91cf61" |Non-randomized portion of RCT
 |-
 |}
-''Note: this trial had 4 arms including a randomization to zoledronic acid; see paper for details.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Endocrine therapy====
+*[[Degarelix (Firmagon)]] 240 mg SC once on day 0, then 80 mg SC once per day on days 28 & 56
-*[[Leuprolide (Lupron)|Leuprolide (Lupron) 3-month depot]] 22.5 mg IM once on day 1
+'''12-week course'''
+</div>
-'''3-month cycle for 2 cycles'''
+<div class="toccolours" style="background-color:#cbd5e7">
 ====Subsequent treatment====
+*Definitive [[Prostate_cancer_-_historical#Radiation_therapy|RT]]
-*[[Prostate_cancer_-_historical#Radiation_therapy|RT]], then [[#Leuprolide_monotherapy|Leuprolide]] x 12 mo versus [[Prostate_cancer_-_null_regimens#Observation|Observation]]
+</div></div>
 ===References===
+#'''FE200486 CS30:''' Mason M, Maldonado Pijoan X, Steidle C, Guerif S, Wiegel T, van der Meulen E, Bergqvist PB, Khoo V. Neoadjuvant androgen deprivation therapy for prostate volume reduction, lower urinary tract symptom relief and quality of life improvement in men with intermediate- to high-risk prostate cancer: a randomised non-inferiority trial of degarelix versus goserelin plus bicalutamide. Clin Oncol (R Coll Radiol). 2013 Mar;25(3):190-6. Epub 2012 Dec 17. [https://doi.org/10.1016/j.clon.2012.09.010 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23257248/ PubMed] [https://clinicaltrials.gov/study/NCT00833248 NCT00833248]
-#'''RADAR:''' Denham JW, Joseph D, Lamb DS, Spry NA, Duchesne G, Matthews J, Atkinson C, Tai KH, Christie D, Kenny L, Turner S, Gogna NK, Diamond T, Delahunt B, Oldmeadow C, Attia J, Steigler A. Short-term androgen suppression and radiotherapy versus intermediate-term androgen suppression and radiotherapy, with or without zoledronic acid, in men with locally advanced prostate cancer (TROG 03.04 RADAR): an open-label, randomised, phase 3 factorial trial. Lancet Oncol. 2014 Sep;15(10):1076-89. Epub 2014 Aug 14. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70328-6/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/25130995 PubMed] NCT00193856
+==Flutamide & Goserelin {{#subobject:b10d66 |Regimen=1}}==
-##'''Update:''' Denham JW, Joseph D, Lamb DS, Spry NA, Duchesne G, Matthews J, Atkinson C, Tai KH, Christie D, Kenny L, Turner S, Gogna NK, Diamond T, Delahunt B, Oldmeadow C, Attia J, Steigler A. Short-term androgen suppression and radiotherapy versus intermediate-term androgen suppression and radiotherapy, with or without zoledronic acid, in men with locally advanced prostate cancer (TROG 03.04 RADAR): 10-year results from a randomised, phase 3, factorial trial. Lancet Oncol. 2019 Feb;20(2):267-281. Epub 2018 Dec 19. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(18)30757-5/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/30579763 PubMed]
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:afbb9c |Variant=1}}===
-=Definitive therapy, including active surveillance=
-==Active surveillance==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
-===Regimen===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 ! style="width: 20%" |Study
-! style="width: 20%" |Years of enrollment
+! style="width: 20%" |Dates of enrollment
 ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 ! style="width: 20%" |Comparator
 ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.nejm.org/doi/10.1056/NEJMoa012794 Holmberg et al. 2002 (SPCG-4)]
+|[https://doi.org/10.1016/j.ijrobp.2004.02.022 Crook et al. 2004]
-|1989-1999
+|1995-2001
-| style="background-color:#1a9851" |Phase III (C)
+| style="background-color:#1a9851" |Phase 3 (C)
-|[[Surgery#Radical_prostatectomy|Radical prostatectomy]]
+|[[#Flutamide_.26_Goserelin|Flutamide & Goserelin]] x 8 mo
-| style="background-color:#d73027" |Inferior OS<sup>1</sup>
+| style="background-color:#ffffbf" |Did not meet primary endpoint of PSA-PFS
+|-
+|}
+''Note: the goserelin dose is not explicitly defined in the manuscript.''
+<div class="toccolours" style="background-color:#b3e2cd">
+====Endocrine therapy====
+*[[Flutamide (Eulexin)]] 250 mg PO three times per day, started 2 weeks before first dose of goserelin
+*[[Goserelin (Zoladex)]] 3.6 mg SC once on day 1
+'''28-day cycle for 3 cycles'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
+====Subsequent treatment====
+*Definitive [[Prostate_cancer_-_historical#Radiation_therapy|RT]]
+</div></div>
+===References===
+#Crook J, Ludgate C, Malone S, Lim J, Perry G, Eapen L, Bowen J, Robertson S, Lockwood G. Report of a multicenter Canadian phase III randomized trial of 3 months vs 8 months neoadjuvant androgen deprivation before standard-dose radiotherapy for clinically localized prostate cancer. Int J Radiat Oncol Biol Phys. 2004 Sep 1;60(1):15-23. [https://doi.org/10.1016/j.ijrobp.2004.02.022 link to original article] '''contains partial dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15337535/ PubMed]
+##'''Update:''' Crook J, Ludgate C, Malone S, Perry G, Eapen L, Bowen J, Robertson S, Lockwood G. Final report of multicenter Canadian Phase III randomized trial of 3 versus 8 months of neoadjuvant androgen deprivation therapy before conventional-dose radiotherapy for clinically localized prostate cancer. Int J Radiat Oncol Biol Phys. 2009 Feb 1;73(2):327-33. Epub 2008 Aug 15. [https://doi.org/10.1016/j.ijrobp.2008.04.075 link to original article] [https://pubmed.ncbi.nlm.nih.gov/18707821/ PubMed]
+==Leuprolide monotherapy {{#subobject:1a6bc7 |Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:53abfc |Variant=1}}===
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
+!style="width: 33%"|Study
+!style="width: 33%"|Dates of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+|-
+|[https://doi.org/10.1016/S1470-2045(14)70328-6 Denham et al. 2014 (RADAR)]
+|2003-2007
+| style="background-color:#91cf61" |Non-randomized part of phase 3 RCT
+|-
+|}
+''Note: this trial had 4 arms including a randomization to zoledronic acid; see paper for details.''
+<div class="toccolours" style="background-color:#b3e2cd">
+====Endocrine therapy====
+*[[Leuprolide (Lupron)|Leuprolide (Lupron) 3-month depot]] 22.5 mg IM once on day 1
+'''3-month cycle for 2 cycles'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
+====Subsequent treatment====
+*Definitive [[Prostate_cancer_-_historical#Radiation_therapy|RT]], then adjuvant [[#Leuprolide_monotherapy|Leuprolide]] x 12 mo versus [[Prostate_cancer_-_null_regimens#Observation|Observation]]
+</div></div>
+===References===
+#'''RADAR:''' Denham JW, Joseph D, Lamb DS, Spry NA, Duchesne G, Matthews J, Atkinson C, Tai KH, Christie D, Kenny L, Turner S, Gogna NK, Diamond T, Delahunt B, Oldmeadow C, Attia J, Steigler A. Short-term androgen suppression and radiotherapy versus intermediate-term androgen suppression and radiotherapy, with or without zoledronic acid, in men with locally advanced prostate cancer (TROG 03.04 RADAR): an open-label, randomised, phase 3 factorial trial. Lancet Oncol. 2014 Sep;15(10):1076-89. Epub 2014 Aug 14. [https://doi.org/10.1016/S1470-2045(14)70328-6 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25130995/ PubMed] [https://clinicaltrials.gov/study/NCT00193856 NCT00193856]
+##'''Update:''' Denham JW, Joseph D, Lamb DS, Spry NA, Duchesne G, Matthews J, Atkinson C, Tai KH, Christie D, Kenny L, Turner S, Gogna NK, Diamond T, Delahunt B, Oldmeadow C, Attia J, Steigler A. Short-term androgen suppression and radiotherapy versus intermediate-term androgen suppression and radiotherapy, with or without zoledronic acid, in men with locally advanced prostate cancer (TROG 03.04 RADAR): 10-year results from a randomised, phase 3, factorial trial. Lancet Oncol. 2019 Feb;20(2):267-281. Epub 2018 Dec 19. [https://doi.org/10.1016/S1470-2045(18)30757-5 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30579763/ PubMed]
+=Definitive therapy, including active surveillance=
+==Active surveillance==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+! style="width: 20%" |Study
+! style="width: 20%" |Dates of enrollment
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |Comparator
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1056/NEJMoa012794 Holmberg et al. 2002 (SPCG-4)]
+|1989-1999
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[Surgery#Radical_prostatectomy|Radical prostatectomy]]
+| style="background-color:#d73027" |Inferior OS<sup>1</sup>
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3429335/ Wilt et al. 2012 (PIVOT)]
 |1994-2002
-| style="background-color:#1a9851" |Phase III (C)
+| style="background-color:#1a9851" |Phase 3 (C)
 |[[Surgery#Radical_prostatectomy|Radical prostatectomy]]
 | style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 |-
-|[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)61619-X/fulltext Fleshner et al. 2012 (REDEEM)]
+|[https://doi.org/10.1056/nejmoa1606220 Hamdy et al. 2016 (ProtecT)]
-|2006-2007
+|1999-2009
-| style="background-color:#1a9851" |Phase III (C)
+| style="background-color:#1a9851" |Phase 3 (C)
-|Dutasteride
+|1. [[Surgery#Radical_prostatectomy|Prostatectomy]]<br>2. [[Prostate_cancer_-_historical#Radiation_therapy|RT]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+|-
+|[https://doi.org/10.1016/S0140-6736(11)61619-X Fleshner et al. 2012 (REDEEM)]
+|2006-08-10 to 2007-03-26
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#Dutasteride_monotherapy_888|Dutasteride]]
 | style="background-color:#d73027" |Inferior TTP
 |-
-|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(16)30661-1/fulltext Azzouzi et al. 2016 (CLIN1001 PCM301)]
+|[https://doi.org/10.1016/S1470-2045(16)30661-1 Azzouzi et al. 2016 (CLIN1001 PCM301)]
 |2011-2013
-| style="background-color:#1a9851" |Phase III (C)
+| style="background-color:#1a9851" |Phase 3 (C)
-|Padeliporfin
+|[[#Padeliporfin_monotherapy_777|Padeliporfin]]
 | style="background-color:#d73027" |Inferior TTP
 |-
 |}
-''<sup>1</sup>Reported efficacy for SPCG-4 is based on the 2014 update.''<br>
+''<sup>1</sup>Reported efficacy for SPCG-4 is based on the 2018 update.''<br>
 ''No antineoplastic therapy; consists of various strategies of close monitoring and re-biopsy.''
+</div></div>
 ===References===
+#'''SPCG-4:''' Holmberg L, Bill-Axelson A, Helgesen F, Salo JO, Folmerz P, Häggman M, Andersson SO, Spångberg A, Busch C, Nordling S, Palmgren J, Adami HO, Johansson JE, Norlén BJ; Scandinavian Prostatic Cancer Group. A randomized trial comparing radical prostatectomy with watchful waiting in early prostate cancer. N Engl J Med. 2002 Sep 12;347(11):781-9. [https://doi.org/10.1056/NEJMoa012794 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12226148/ PubMed]
-#'''SPCG-4:''' Holmberg L, Bill-Axelson A, Helgesen F, Salo JO, Folmerz P, Häggman M, Andersson SO, Spångberg A, Busch C, Nordling S, Palmgren J, Adami HO, Johansson JE, Norlén BJ; Scandinavian Prostatic Cancer Group. A randomized trial comparing radical prostatectomy with watchful waiting in early prostate cancer. N Engl J Med. 2002 Sep 12;347(11):781-9. [https://www.nejm.org/doi/10.1056/NEJMoa012794 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/12226148 PubMed]
+##'''Update:''' Bill-Axelson A, Holmberg L, Ruutu M, Häggman M, Andersson SO, Bratell S, Spångberg A, Busch C, Nordling S, Garmo H, Palmgren J, Adami HO, Norlén BJ, Johansson JE; Scandinavian Prostate Cancer Group. Radical prostatectomy versus watchful waiting in early prostate cancer. N Engl J Med. 2005 May 12;352(19):1977-84. [https://doi.org/10.1056/NEJMoa043739 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15888698/ PubMed]
-##'''Update:''' Bill-Axelson A, Holmberg L, Ruutu M, Häggman M, Andersson SO, Bratell S, Spångberg A, Busch C, Nordling S, Garmo H, Palmgren J, Adami HO, Norlén BJ, Johansson JE; Scandinavian Prostate Cancer Group. Radical prostatectomy versus watchful waiting in early prostate cancer. N Engl J Med. 2005 May 12;352(19):1977-84. [https://www.nejm.org/doi/full/10.1056/NEJMoa043739 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15888698 PubMed]
+##'''Update:''' Bill-Axelson A, Holmberg L, Filén F, Ruutu M, Garmo H, Busch C, Nordling S, Häggman M, Andersson SO, Bratell S, Spångberg A, Palmgren J, Adami HO, Johansson JE; Scandinavian Prostate Cancer Group. Radical prostatectomy versus watchful waiting in localized prostate cancer: the Scandinavian prostate cancer group-4 randomized trial. J Natl Cancer Inst. 2008 Aug 20;100(16):1144-54. Epub 2008 Aug 11. [https://academic.oup.com/jnci/article/100/16/1144/916419 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2518167/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/18695132/ PubMed]
-##'''Update:''' Bill-Axelson A, Holmberg L, Filén F, Ruutu M, Garmo H, Busch C, Nordling S, Häggman M, Andersson SO, Bratell S, Spångberg A, Palmgren J, Adami HO, Johansson JE; Scandinavian Prostate Cancer Group. Radical prostatectomy versus watchful waiting in localized prostate cancer: the Scandinavian prostate cancer group-4 randomized trial. J Natl Cancer Inst. 2008 Aug 20;100(16):1144-54. Epub 2008 Aug 11. [https://academic.oup.com/jnci/article/100/16/1144/916419 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2518167/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/18695132 PubMed]
+##'''Update:''' Bill-Axelson A, Holmberg L, Ruutu M, Garmo H, Stark JR, Busch C, Nordling S, Häggman M, Andersson SO, Bratell S, Spångberg A, Palmgren J, Steineck G, Adami HO, Johansson JE; SPCG-4 Investigators. Radical prostatectomy versus watchful waiting in early prostate cancer. N Engl J Med. 2011 May 5;364(18):1708-17. [https://doi.org/10.1056/NEJMoa1011967 link to original article] [https://pubmed.ncbi.nlm.nih.gov/21542742/ PubMed]
-##'''Update:''' Bill-Axelson A, Holmberg L, Ruutu M, Garmo H, Stark JR, Busch C, Nordling S, Häggman M, Andersson SO, Bratell S, Spångberg A, Palmgren J, Steineck G, Adami HO, Johansson JE; SPCG-4 Investigators. Radical prostatectomy versus watchful waiting in early prostate cancer. N Engl J Med. 2011 May 5;364(18):1708-17. [https://www.nejm.org/doi/10.1056/NEJMoa1011967 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/21542742 PubMed]
+##'''Update:''' Bill-Axelson A, Holmberg L, Garmo H, Rider JR, Taari K, Busch C, Nordling S, Häggman M, Andersson SO, Spångberg A, Andrén O, Palmgren J, Steineck G, Adami HO, Johansson JE. Radical prostatectomy or watchful waiting in early prostate cancer. N Engl J Med. 2014 Mar 6;370(10):932-42. [https://doi.org/10.1056/NEJMoa1311593 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4118145/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24597866/ PubMed]
-##'''Update:''' Bill-Axelson A, Holmberg L, Garmo H, Rider JR, Taari K, Busch C, Nordling S, Häggman M, Andersson SO, Spångberg A, Andrén O, Palmgren J, Steineck G, Adami HO, Johansson JE. Radical prostatectomy or watchful waiting in early prostate cancer. N Engl J Med. 2014 Mar 6;370(10):932-42. [https://www.nejm.org/doi/10.1056/NEJMoa1311593 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4118145/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/24597866 PubMed]
+##'''Update:''' Bill-Axelson A, Holmberg L, Garmo H, Taari K, Busch C, Nordling S, Häggman M, Andersson SO, Andrén O, Steineck G, Adami HO, Johansson JE. Radical Prostatectomy or Watchful Waiting in Prostate Cancer - 29-Year Follow-up. N Engl J Med. 2018 Dec 13;379(24):2319-2329. [https://doi.org/10.1056/NEJMoa1807801 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30575473/ PubMed]
-##'''Update:''' Bill-Axelson A, Holmberg L, Garmo H, Taari K, Busch C, Nordling S, Häggman M, Andersson SO, Andrén O, Steineck G, Adami HO, Johansson JE. Radical Prostatectomy or Watchful Waiting in Prostate Cancer - 29-Year Follow-up. N Engl J Med. 2018 Dec 13;379(24):2319-2329. [https://www.nejm.org/doi/full/10.1056/NEJMoa1807801 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/30575473 PubMed]
+#'''REDEEM:''' Fleshner NE, Lucia MS, Egerdie B, Aaron L, Eure G, Nandy I, Black L, Rittmaster RS. Dutasteride in localised prostate cancer management: the REDEEM randomised, double-blind, placebo-controlled trial. Lancet. 2012 Mar 24;379(9821):1103-11. Epub 2012 Jan 24. [https://doi.org/10.1016/S0140-6736(11)61619-X link to original article] [https://pubmed.ncbi.nlm.nih.gov/22277570/ PubMed] [https://clinicaltrials.gov/study/NCT00363311 NCT00363311]
-#'''REDEEM:''' Fleshner NE, Lucia MS, Egerdie B, Aaron L, Eure G, Nandy I, Black L, Rittmaster RS. Dutasteride in localised prostate cancer management: the REDEEM randomised, double-blind, placebo-controlled trial. Lancet. 2012 Mar 24;379(9821):1103-11. Epub 2012 Jan 24. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)61619-X/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/22277570 PubMed] NCT00363311
+#'''PIVOT:''' Wilt TJ, Brawer MK, Jones KM, Barry MJ, Aronson WJ, Fox S, Gingrich JR, Wei JT, Gilhooly P, Grob BM, Nsouli I, Iyer P, Cartagena R, Snider G, Roehrborn C, Sharifi R, Blank W, Pandya P, Andriole GL, Culkin D, Wheeler T; Prostate Cancer Intervention versus Observation Trial (PIVOT) Study Group. Radical prostatectomy versus observation for localized prostate cancer. N Engl J Med. 2012 Jul 19;367(3):203-13. Erratum in: N Engl J Med. 2012 Aug 9;367(6):582. [https://doi.org/10.1056/NEJMoa1113162 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3429335/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22808955/ PubMed] [https://clinicaltrials.gov/study/NCT00007644 NCT00007644]
-#'''PIVOT:''' Wilt TJ, Brawer MK, Jones KM, Barry MJ, Aronson WJ, Fox S, Gingrich JR, Wei JT, Gilhooly P, Grob BM, Nsouli I, Iyer P, Cartagena R, Snider G, Roehrborn C, Sharifi R, Blank W, Pandya P, Andriole GL, Culkin D, Wheeler T; Prostate Cancer Intervention versus Observation Trial (PIVOT) Study Group. Radical prostatectomy versus observation for localized prostate cancer. N Engl J Med. 2012 Jul 19;367(3):203-13. Erratum in: N Engl J Med. 2012 Aug 9;367(6):582. [https://www.nejm.org/doi/10.1056/NEJMoa1113162 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3429335/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/22808955 PubMed] NCT00007644
+##'''Update:''' Wilt TJ, Jones KM, Barry MJ, Andriole GL, Culkin D, Wheeler T, Aronson WJ, Brawer MK. Follow-up of prostatectomy versus observation for early prostate cancer. N Engl J Med. 2017 Jul 13;377(2):132-142. [https://doi.org/10.1056/NEJMoa1615869 link to original article] [https://pubmed.ncbi.nlm.nih.gov/28700844/ PubMed]
-##'''Update:''' Wilt TJ, Jones KM, Barry MJ, Andriole GL, Culkin D, Wheeler T, Aronson WJ, Brawer MK. Follow-up of prostatectomy versus observation for early prostate cancer. N Engl J Med. 2017 Jul 13;377(2):132-142. [https://www.nejm.org/doi/10.1056/NEJMoa1615869 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/28700844 PubMed]
+#'''ProtecT:''' Hamdy FC, Donovan JL, Lane JA, Mason M, Metcalfe C, Holding P, Davis M, Peters TJ, Turner EL, Martin RM, Oxley J, Robinson M, Staffurth J, Walsh E, Bollina P, Catto J, Doble A, Doherty A, Gillatt D, Kockelbergh R, Kynaston H, Paul A, Powell P, Prescott S, Rosario DJ, Rowe E, Neal DE; ProtecT Study Group. 10-Year Outcomes after Monitoring, Surgery, or Radiotherapy for Localized Prostate Cancer. N Engl J Med. 2016 Oct 13;375(15):1415-1424. Epub 2016 Sep 14. [https://doi.org/10.1056/nejmoa1606220 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27626136/ PubMed] [https://clinicaltrials.gov/study/NCT02044172 NCT02044172]
-#'''CLIN1001 PCM301:''' Azzouzi AR, Vincendeau S, Barret E, Cicco A, Kleinclauss F, van der Poel HG, Stief CG, Rassweiler J, Salomon G, Solsona E, Alcaraz A, Tammela TT, Rosario DJ, Gomez-Veiga F, Ahlgren G, Benzaghou F, Gaillac B, Amzal B, Debruyne FM, Fromont G, Gratzke C, Emberton M; PCM301 Study Group. Padeliporfin vascular-targeted photodynamic therapy versus active surveillance in men with low-risk prostate cancer (CLIN1001 PCM301): an open-label, phase 3, randomised controlled trial. Lancet Oncol. 2017 Feb;18(2):181-191. Epub 2016 Dec 20. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(16)30661-1/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/28007457 PubMed] NCT01310894
+##'''Update:''' Hamdy FC, Donovan JL, Lane JA, Metcalfe C, Davis M, Turner EL, Martin RM, Young GJ, Walsh EI, Bryant RJ, Bollina P, Doble A, Doherty A, Gillatt D, Gnanapragasam V, Hughes O, Kockelbergh R, Kynaston H, Paul A, Paez E, Powell P, Rosario DJ, Rowe E, Mason M, Catto JWF, Peters TJ, Oxley J, Williams NJ, Staffurth J, Neal DE; ProtecT Study Group. Fifteen-Year Outcomes after Monitoring, Surgery, or Radiotherapy for Prostate Cancer. N Engl J Med. 2023 Apr 27;388(17):1547-1558. Epub 2023 Mar 11. [https://doi.org/10.1056/nejmoa2214122 link to original article] [https://pubmed.ncbi.nlm.nih.gov/36912538/ PubMed]
+#'''CLIN1001 PCM301:''' Azzouzi AR, Vincendeau S, Barret E, Cicco A, Kleinclauss F, van der Poel HG, Stief CG, Rassweiler J, Salomon G, Solsona E, Alcaraz A, Tammela TT, Rosario DJ, Gomez-Veiga F, Ahlgren G, Benzaghou F, Gaillac B, Amzal B, Debruyne FM, Fromont G, Gratzke C, Emberton M; PCM301 Study Group. Padeliporfin vascular-targeted photodynamic therapy versus active surveillance in men with low-risk prostate cancer (CLIN1001 PCM301): an open-label, phase 3, randomised controlled trial. Lancet Oncol. 2017 Feb;18(2):181-191. Epub 2016 Dec 20. [https://doi.org/10.1016/S1470-2045(16)30661-1 link to original article] [https://pubmed.ncbi.nlm.nih.gov/28007457/ PubMed] [https://clinicaltrials.gov/study/NCT01310894 NCT01310894]
 ==ADT {{#subobject:c3c2cb|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
 ADT: '''<u>A</u>'''ndrogen '''<u>D</u>'''eprivation '''<u>T</u>'''herapy
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:c615a3|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 ! style="width: 20%" |Study
-! style="width: 20%" |Years of enrollment
+! style="width: 20%" |Dates of enrollment
 ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 ! style="width: 20%" |Comparator
@@ Line 243: / Line 324: @@
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3243932/ Warde et al. 2011 (NCIC-CTG PR.3/UK MRC PR07)]
 |1995-2005
-| style="background-color:#1a9851" |Phase III (C)
+| style="background-color:#1a9851" |Phase 3 (C)
 |[[#ADT_.26_RT|ADT & RT]]
 | style="background-color:#fc8d59" |Seems to have inferior OS
 |-
 |}
-''Note: these are clinical trials that did not specify a particular therapy to be used for androgen deprivation. See papers for details; the below are examples.''
+''Note: these are clinical trials that did not specify a particular approach to androgen deprivation. See papers for details.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Endocrine therapy====
+*[[:Category:Androgen-deprivation therapy|ADT]]
-*ADT with ONE of the following:
+</div></div>
-**[[:Category:GnRH agonists|LHRH agonist/analogue]]
-**[[:Category:GnRH antagonists|LHRH antagonist]]
-**[[Endocrine_ablation_surgery#Bilateral_orchiectomy|Bilateral orchiectomy]]
 ===References===
+#'''NCIC-CTG PR.3/UK MRC PR07:''' Warde P, Mason M, Ding K, Kirkbride P, Brundage M, Cowan R, Gospodarowicz M, Sanders K, Kostashuk E, Swanson G, Barber J, Hiltz A, Parmar MK, Sathya J, Anderson J, Hayter C, Hetherington J, Sydes MR, Parulekar W; NCIC-CTG; MRC. Combined androgen deprivation therapy and radiation therapy for locally advanced prostate cancer: a randomised, phase 3 trial. Lancet. 2011 Dec 17;378(9809):2104-11. Epub 2011 Nov 2. [https://doi.org/10.1016/S0140-6736(11)61095-7 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3243932/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22056152/ PubMed] [https://clinicaltrials.gov/study/NCT00002633 NCT00002633]
-#'''NCIC-CTG PR.3/UK MRC PR07:''' Warde P, Mason M, Ding K, Kirkbride P, Brundage M, Cowan R, Gospodarowicz M, Sanders K, Kostashuk E, Swanson G, Barber J, Hiltz A, Parmar MK, Sathya J, Anderson J, Hayter C, Hetherington J, Sydes MR, Parulekar W; NCIC-CTG; MRC. Combined androgen deprivation therapy and radiation therapy for locally advanced prostate cancer: a randomised, phase 3 trial. Lancet. 2011 Dec 17;378(9809):2104-11. Epub 2011 Nov 2. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)61095-7/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3243932/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/22056152 PubMed] NCT00002633
 ==ADT & RT {{#subobject:514ac2|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
 ADT & RT: '''<u>A</u>'''ndrogen '''<u>D</u>'''eprivation '''<u>T</u>'''herapy & '''<u>R</u>'''adiation '''<u>T</u>'''herapy
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:4aac55|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 ! style="width: 20%" |Study
-! style="width: 20%" |Years of enrollment
+! style="width: 20%" |Dates of enrollment
 ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 ! style="width: 20%" |Comparator
@@ Line 276: / Line 349: @@
 |[https://jamanetwork.com/journals/jama/fullarticle/199273 d'Amico et al. 2004]
 |1995-2001
-| style="background-color:#1a9851" |Phase III (E-esc)
+| style="background-color:#1a9851" |Phase 3 (E-esc)
 |[[Prostate_cancer_-_historical#Radiation_therapy|RT]]
-| style="background-color:#91cf60" |Seems to have superior OS
+| style="background-color:#91cf60" |Seems to have superior OS (co-primary endpoint)<br>OS60: 88% vs 78%<br>(HR 0.48, 95% CI 0.24-0.98)
 |-
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3243932/ Warde et al. 2011 (NCIC-CTG PR.3/UK MRC PR07)]
 |1995-2005
-| style="background-color:#1a9851" |Phase III (E-esc)
+| style="background-color:#1a9851" |Phase 3 (E-esc)
 |[[#ADT_2|ADT]]
-| style="background-color:#91cf60" |Seems to have superior OS
+| style="background-color:#91cf60" |Seems to have superior OS (primary endpoint)<br>OS84: 74% vs 66%<br>(HR 0.77, 95% CI 0.61-0.98)
 |-
-|[https://www.nejm.org/doi/10.1056/NEJMoa0810095 Bolla et al. 2009 (EORTC 22961)]
+|[https://doi.org/10.1056/NEJMoa0810095 Bolla et al. 2009 (EORTC 22961)]
 |1997-2001
-| style="background-color:#91cf61" |Non-randomized portion of RCT
+| style="background-color:#91cf61" |Non-randomized part of phase 3 RCT
 | style="background-color:#d3d3d3" |
 | style="background-color:#d3d3d3" |
@@ Line 294: / Line 367: @@
 |[https://doi.org/10.1016/j.ijrobp.2008.05.020 Rosenthal et al. 2008 (RTOG 9902)]
 |2000-2004
-| style="background-color:#91cf61" |Non-randomized portion of RCT
+| style="background-color:#91cf61" |Non-randomized part of phase 3 RCT
 | style="background-color:#d3d3d3" |
 | style="background-color:#d3d3d3" |
@@ Line 300: / Line 373: @@
 |[https://doi.org/10.1200/JCO.2014.58.0662 Pisansky et al. 2014 (RTOG 9910)]
 |2000-2004
-| style="background-color:#91cf61" |Non-randomized portion of RCT
+| style="background-color:#91cf61" |Non-randomized part of phase 3 RCT
 | style="background-color:#d3d3d3" |
 | style="background-color:#d3d3d3" |
 |-
-|[https://www.europeanurology.com/article/S0302-2838(18)30443-3/fulltext Nabid et al. 2018 (PCS IV)]
+|[https://doi.org/10.1016/j.eururo.2018.06.018 Nabid et al. 2018 (PCS IV)]
 |2000-2008
-| style="background-color:#91cf61" |Non-randomized portion of RCT
+| style="background-color:#91cf61" |Non-randomized part of phase 3 RCT
 | style="background-color:#d3d3d3" |
 | style="background-color:#d3d3d3" |
@@ Line 312: / Line 385: @@
 |rowspan=2|[https://doi.org/10.1016/j.ejca.2020.10.023 Nabid et al. 2020 (PCS III)]
 |rowspan=2|2000-2010
-|rowspan=2 style="background-color:#1a9851" |Phase III (E-esc)
+|rowspan=2 style="background-color:#1a9851" |Phase 3 (E-esc)
 |1. [[Prostate_cancer_-_historical#Radiation_therapy|RT]]
-| style="background-color:#1a9850" |Superior biochemical failure
+| style="background-color:#1a9850" |Superior biochemical failure (primary endpoint)
 |-
 |2. [[#ADT_.26_RT|ADT & RT]]; dose-escalated RT
 | style="background-color:#ffffbf" |Did not meet primary endpoint of biochemical failure
+|-
+|[https://doi.org/10.1002/cncr.33034 Ito et al. 2020]
+|2001-2006
+| style="background-color:#91cf61" |Non-randomized part of phase 3 RCT
+| style="background-color:#d3d3d3" |
+| style="background-color:#d3d3d3" |
 |-
 |[https://doi.org/10.1200/JCO.2015.64.8055 Bolla et al. 2016 (EORTC 22991)]
 |2001-2008
-| style="background-color:#1a9851" |Phase III (E-esc)
+| style="background-color:#1a9851" |Phase 3 (E-esc)
 |[[Prostate_cancer_-_historical#Radiation_therapy|RT]]
-| style="background-color:#1a9850" |Superior PFS
+| style="background-color:#1a9850" |Superior PFS (secondary endpoint)<br>DFS60: 88.7% vs 80.8%<br>(HR 0.63, 95% CI 0.48-0.84)
 |-
-|[http://www.ncbi.nlm.nih.gov/pmc/articles/pmc7186584/ Malone et al. 2019]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7186584/ Malone et al. 2019]
 |2002-2012
-| style="background-color:#91cf61" |Non-randomized portion of RCT
+| style="background-color:#91cf61" |Non-randomized part of phase 3 RCT
 | style="background-color:#d3d3d3" |
 | style="background-color:#d3d3d3" |
 |
 |-
-|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)70045-8/fulltext Zapatero et al. 2015 (DART01/05 GICOR)]
+|[https://doi.org/10.1016/S1470-2045(15)70045-8 Zapatero et al. 2015 (DART01/05 GICOR)]
 |2005-2010
-| style="background-color:#91cf61" |Non-randomized portion of RCT
+| style="background-color:#91cf61" |Non-randomized part of phase 3 RCT
+| style="background-color:#d3d3d3" |
+| style="background-color:#d3d3d3" |
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8425842/ D'Amico et al. 2021 (DFCI 05-043)]
+|2005-2015
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#ADT.2C_Docetaxel.2C_RT_999|ADT, Docetaxel, RT]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+|-
+|[https://doi.org/10.1016/j.ijrobp.2023.08.046 Yorozu et al. 2023 (TRIP)]
+|2010-10 to 2013-03
+| style="background-color:#91cf61" |Non-randomized part of phase 3 RCT
 | style="background-color:#d3d3d3" |
 | style="background-color:#d3d3d3" |
 |-
 |}
-''Note: these are clinical trials that did not specify a particular drug to be used for androgen deprivation. See papers for details.''
+''Note: these were clinical trials that did not specify a particular approach for androgen deprivation. See papers for details.''
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
+*RTOG 9902 & DART01/05 GICOR: Induction [[#ADT|ADT]] x 8 weeks
-*RTOG 9902 & DART01/05 GICOR: [[#ADT|ADT]] x 8 weeks
+*RTOG 9910: Induction [[#ADT|ADT]] x 8 weeks versus [[#ADT|ADT]] x 28 weeks
-*RTOG 9910: [[#ADT|ADT]] x 8 weeks versus [[#ADT|ADT]] x 28 weeks
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Endocrine therapy====
+*[[:Category:Androgen-deprivation therapy|ADT]]
-*ADT with ONE of the following:
-**[[:Category:GnRH agonists|LHRH agonist]]
-**Some protocols: [[Endocrine_ablation_surgery#Bilateral_orchiectomy|Bilateral orchiectomy]]
-**Some protocols: [[Bicalutamide (Casodex)]] or [[Flutamide (Eulexin)]]
 ====Radiotherapy====
 *[[External beam radiotherapy]]
 '''8-week course'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
 ====Subsequent treatment====
+*RTOG 9902: Adjuvant [[#ADT_2|ADT]] x 2 y versus [[#TEE_999|TEE]] x 4 followed by [[#ADT_2|ADT]] x 2 y
-*RTOG 9902: ADT x 2 y versus TEE x 4, then ADT x 2 y
+*EORTC 22961: Adjuvant [[#ADT_2|ADT]] x 6 months versus [[#ADT_2|ADT]] x 36 months
-*EORTC 22961: ADT for 6 months versus ADT for 36 months
+*DART01/05 GICOR: Adjuvant [[#ADT_2|ADT]] x 24 months versus [[Prostate_cancer_-_null_regimens#Observation|no further treatment]]
-*DART01/05 GICOR: ADT for 24 months versus no further treatment
+*PCS IV: Adjuvant [[#ADT_2|ADT]] x 18 months versus [[#ADT_2|ADT]] x 36 months
-*PCS IV: ADT for 18 months versus ADT for 36 months
+</div></div>
 ===References===
+#D'Amico AV, Manola J, Loffredo M, Renshaw AA, DellaCroce A, Kantoff PW. 6-month androgen suppression plus radiation therapy vs radiation therapy alone for patients with clinically localized prostate cancer: a randomized controlled trial. JAMA. 2004 Aug 18;292(7):821-7. [https://jamanetwork.com/journals/jama/fullarticle/199273 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15315996/ PubMed]
-#D'Amico AV, Manola J, Loffredo M, Renshaw AA, DellaCroce A, Kantoff PW. 6-month androgen suppression plus radiation therapy vs radiation therapy alone for patients with clinically localized prostate cancer: a randomized controlled trial. JAMA. 2004 Aug 18;292(7):821-7. [https://jamanetwork.com/journals/jama/fullarticle/199273 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15315996 PubMed]
+#'''RTOG 9902:''' Rosenthal SA, Bae K, Pienta KJ, Sobczak ML, Asbell SO, Rajan R, Kerlin KJ, Michalski JM, Sandler HM; Radiation Therapy Oncology Group. Phase III multi-institutional trial of adjuvant chemotherapy with paclitaxel, estramustine, and oral etoposide combined with long-term androgen suppression therapy and radiotherapy versus long-term androgen suppression plus radiotherapy alone for high-risk prostate cancer: preliminary toxicity analysis of RTOG 99-02. Int J Radiat Oncol Biol Phys. 2009 Mar 1;73(3):672-8. Epub 2008 Nov 5. [https://doi.org/10.1016/j.ijrobp.2008.05.020 link to original article] [https://pubmed.ncbi.nlm.nih.gov/18990504/ PubMed] [https://clinicaltrials.gov/study/NCT00004054 NCT00004054]
-#'''RTOG 9902:''' Rosenthal SA, Bae K, Pienta KJ, Sobczak ML, Asbell SO, Rajan R, Kerlin KJ, Michalski JM, Sandler HM; Radiation Therapy Oncology Group. Phase III multi-institutional trial of adjuvant chemotherapy with paclitaxel, estramustine, and oral etoposide combined with long-term androgen suppression therapy and radiotherapy versus long-term androgen suppression plus radiotherapy alone for high-risk prostate cancer: preliminary toxicity analysis of RTOG 99-02. Int J Radiat Oncol Biol Phys. 2009 Mar 1;73(3):672-8. Epub 2008 Nov 5. [https://doi.org/10.1016/j.ijrobp.2008.05.020 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/18990504 PubMed]
+##'''Update:''' Rosenthal SA, Hunt D, Sartor AO, Pienta KJ, Gomella L, Grignon D, Rajan R, Kerlin KJ, Jones CU, Dobelbower M, Shipley WU, Zeitzer K, Hamstra DA, Donavanik V, Rotman M, Hartford AC, Michalski J, Seider M, Kim H, Kuban DA, Moughan J, Sandler H. A phase 3 trial of 2 years of androgen suppression and radiation therapy with or without adjuvant chemotherapy for high-risk prostate cancer: final results of radiation therapy oncology group phase 3 randomized trial NRG Oncology RTOG 9902. Int J Radiat Oncol Biol Phys. 2015 Oct 1;93(2):294-302. Epub 2015 Jul 21. [https://doi.org/10.1016/j.ijrobp.2015.05.024 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4719152/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26209502/ PubMed]
-##'''Update:''' Rosenthal SA, Hunt D, Sartor AO, Pienta KJ, Gomella L, Grignon D, Rajan R, Kerlin KJ, Jones CU, Dobelbower M, Shipley WU, Zeitzer K, Hamstra DA, Donavanik V, Rotman M, Hartford AC, Michalski J, Seider M, Kim H, Kuban DA, Moughan J, Sandler H. A phase 3 trial of 2 years of androgen suppression and radiation therapy with or without adjuvant chemotherapy for high-risk prostate cancer: final results of radiation therapy oncology group phase 3 randomized trial NRG Oncology RTOG 9902. Int J Radiat Oncol Biol Phys. 2015 Oct 1;93(2):294-302. Epub 2015 Jul 21. [https://www.redjournal.org/article/S0360-3016(15)00552-0/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4719152/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26209502 PubMed]
+#'''EORTC 22961:''' Bolla M, de Reijke TM, Van Tienhoven G, Van den Bergh AC, Oddens J, Poortmans PM, Gez E, Kil P, Akdas A, Soete G, Kariakine O, van der Steen-Banasik EM, Musat E, Piérart M, Mauer ME, Collette L; [[Study_Groups#EORTC|EORTC]] Radiation Oncology Group; [[Study_Groups#EORTC|EORTC]] Genito-Urinary Tract Cancer Group. Duration of androgen suppression in the treatment of prostate cancer. N Engl J Med. 2009 Jun 11;360(24):2516-27. [https://doi.org/10.1056/NEJMoa0810095 link to original article] [https://pubmed.ncbi.nlm.nih.gov/19516032/ PubMed] [https://clinicaltrials.gov/study/NCT00003026 NCT00003026]
-#'''EORTC 22961:''' Bolla M, de Reijke TM, Van Tienhoven G, Van den Bergh AC, Oddens J, Poortmans PM, Gez E, Kil P, Akdas A, Soete G, Kariakine O, van der Steen-Banasik EM, Musat E, Piérart M, Mauer ME, Collette L; [[Study_Groups#EORTC|EORTC]] Radiation Oncology Group; [[Study_Groups#EORTC|EORTC]] Genito-Urinary Tract Cancer Group. Duration of androgen suppression in the treatment of prostate cancer. N Engl J Med. 2009 Jun 11;360(24):2516-27. [https://www.nejm.org/doi/10.1056/NEJMoa0810095 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/19516032 PubMed] NCT00003026
+#'''NCIC-CTG PR.3/UK MRC PR07:''' Warde P, Mason M, Ding K, Kirkbride P, Brundage M, Cowan R, Gospodarowicz M, Sanders K, Kostashuk E, Swanson G, Barber J, Hiltz A, Parmar MK, Sathya J, Anderson J, Hayter C, Hetherington J, Sydes MR, Parulekar W; NCIC; MRC. Combined androgen deprivation therapy and radiation therapy for locally advanced prostate cancer: a randomised, phase 3 trial. Lancet. 2011 Dec 17;378(9809):2104-11. Epub 2011 Nov 2. [https://doi.org/10.1016/S0140-6736(11)61095-7 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3243932/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22056152/ PubMed] [https://clinicaltrials.gov/study/NCT00002633 NCT00002633]
-#'''NCIC-CTG PR.3/UK MRC PR07:''' Warde P, Mason M, Ding K, Kirkbride P, Brundage M, Cowan R, Gospodarowicz M, Sanders K, Kostashuk E, Swanson G, Barber J, Hiltz A, Parmar MK, Sathya J, Anderson J, Hayter C, Hetherington J, Sydes MR, Parulekar W; NCIC; MRC. Combined androgen deprivation therapy and radiation therapy for locally advanced prostate cancer: a randomised, phase 3 trial. Lancet. 2011 Dec 17;378(9809):2104-11. Epub 2011 Nov 2. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)61095-7/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3243932/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/22056152 PubMed] NCT00002633
+#'''RTOG 9910:''' Pisansky TM, Hunt D, Gomella LG, Amin MB, Balogh AG, Chinn DM, Seider MJ, Duclos M, Rosenthal SA, Bauman GS, Gore EM, Rotman MZ, Lukka HR, Shipley WU, Dignam JJ, Sandler HM. Duration of androgen suppression before radiotherapy for localized prostate cancer: Radiation Therapy Oncology Group randomized clinical trial 9910. J Clin Oncol. 2015 Feb 1;33(4):332-9. Epub 2014 Dec 22. [https://doi.org/10.1200/JCO.2014.58.0662 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4302214/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25534388/ PubMed] [https://clinicaltrials.gov/study/NCT00005044 NCT00005044]
-#'''RTOG 9910:''' Pisansky TM, Hunt D, Gomella LG, Amin MB, Balogh AG, Chinn DM, Seider MJ, Duclos M, Rosenthal SA, Bauman GS, Gore EM, Rotman MZ, Lukka HR, Shipley WU, Dignam JJ, Sandler HM. Duration of androgen suppression before radiotherapy for localized prostate cancer: Radiation Therapy Oncology Group randomized clinical trial 9910. J Clin Oncol. 2015 Feb 1;33(4):332-9. Epub 2014 Dec 22. [https://doi.org/10.1200/JCO.2014.58.0662 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4302214/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/25534388 PubMed] NCT00005044
+#'''DART01/05 GICOR:''' Zapatero A, Guerrero A, Maldonado X, Alvarez A, Gonzalez San Segundo C, Cabeza Rodríguez MA, Macias V, Pedro Olive A, Casas F, Boladeras A, de Vidales CM, Vazquez de la Torre ML, Villà S, Perez de la Haza A, Calvo FA. High-dose radiotherapy with short-term or long-term androgen deprivation in localised prostate cancer (DART01/05 GICOR): a randomised, controlled, phase 3 trial. Lancet Oncol. 2015 Mar;16(3):320-7. Epub 2015 Feb 19. Erratum in: Lancet Oncol. 2015 Jun;16(6):e262. [https://doi.org/10.1016/S1470-2045(15)70045-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25702876/ PubMed] [https://clinicaltrials.gov/study/NCT02175212 NCT02175212]
-#'''DART01/05 GICOR:''' Zapatero A, Guerrero A, Maldonado X, Alvarez A, Gonzalez San Segundo C, Cabeza Rodríguez MA, Macias V, Pedro Olive A, Casas F, Boladeras A, de Vidales CM, Vazquez de la Torre ML, Villà S, Perez de la Haza A, Calvo FA. High-dose radiotherapy with short-term or long-term androgen deprivation in localised prostate cancer (DART01/05 GICOR): a randomised, controlled, phase 3 trial. Lancet Oncol. 2015 Mar;16(3):320-7. Epub 2015 Feb 19. Erratum in: Lancet Oncol. 2015 Jun;16(6):e262. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)70045-8/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/25702876 PubMed] NCT02175212
+#'''EORTC 22991:''' Bolla M, Maingon P, Carrie C, Villa S, Kitsios P, Poortmans PM, Sundar S, van der Steen-Banasik EM, Armstrong J, Bosset JF, Herrera FG, Pieters B, Slot A, Bahl A, Ben-Yosef R, Boehmer D, Scrase C, Renard L, Shash E, Coens C, van den Bergh AC, Collette L. Short androgen suppression and radiation dose escalation for intermediate- and high-risk localized prostate cancer: results of EORTC trial 22991. J Clin Oncol. 2016 May 20;34(15):1748-56. Epub 2016 Mar 14. [https://doi.org/10.1200/JCO.2015.64.8055 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26976418/ PubMed] [https://clinicaltrials.gov/study/NCT00021450 NCT00021450]
-#'''EORTC 22991:''' Bolla M, Maingon P, Carrie C, Villa S, Kitsios P, Poortmans PM, Sundar S, van der Steen-Banasik EM, Armstrong J, Bosset JF, Herrera FG, Pieters B, Slot A, Bahl A, Ben-Yosef R, Boehmer D, Scrase C, Renard L, Shash E, Coens C, van den Bergh AC, Collette L. Short androgen suppression and radiation dose escalation for intermediate- and high-risk localized prostate cancer: results of EORTC trial 22991. J Clin Oncol. 2016 May 20;34(15):1748-56. Epub 2016 Mar 14. [https://doi.org/10.1200/JCO.2015.64.8055 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/26976418 PubMed] NCT00021450
+##'''Subgroup analysis:''' Bolla M, Neven A, Maingon P, Carrie C, Boladeras A, Andreopoulos D, Engelen A, Sundar S, van der Steen-Banasik EM, Armstrong J, Peignaux-Casasnovas K, Boustani J, Herrera FG, Pieters BR, Slot A, Bahl A, Scrase CD, Azria D, Jansa J, O'Sullivan JM, Van Den Bergh ACM, Collette L; EORTC Radiation Oncology Group. Short Androgen Suppression and Radiation Dose Escalation in Prostate Cancer: 12-Year Results of EORTC Trial 22991 in Patients With Localized Intermediate-Risk Disease. J Clin Oncol. 2021 Sep 20;39(27):3022-3033. Epub 2021 Jul 26. [https://doi.org/10.1200/jco.21.00855 link to original article] [https://pubmed.ncbi.nlm.nih.gov/34310202/ PubMed]
-#'''PCS IV:''' Nabid A, Carrier N, Martin AG, Bahary JP, Lemaire C, Vass S, Bahoric B, Archambault R, Vincent F, Bettahar R, Duclos M, Garant MP, Souhami L. Duration of Androgen Deprivation Therapy in High-risk Prostate Cancer: A Randomized Phase III Trial. Eur Urol. 2018 Oct;74(4):432-441. Epub 2018 Jul 3. [https://www.europeanurology.com/article/S0302-2838(18)30443-3/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/29980331 PubMed] NCT00223171
+#'''PCS IV:''' Nabid A, Carrier N, Martin AG, Bahary JP, Lemaire C, Vass S, Bahoric B, Archambault R, Vincent F, Bettahar R, Duclos M, Garant MP, Souhami L. Duration of Androgen Deprivation Therapy in High-risk Prostate Cancer: A Randomized Phase III Trial. Eur Urol. 2018 Oct;74(4):432-441. Epub 2018 Jul 3. [https://doi.org/10.1016/j.eururo.2018.06.018 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29980331/ PubMed] [https://clinicaltrials.gov/study/NCT00223171 NCT00223171]
-#Malone S, Roy S, Eapen L, E C, MacRae R, Perry G, Bowen J, Samant R, Morgan S, Craig J, Malone K, Grimes S. Sequencing of Androgen-Deprivation Therapy With External-Beam Radiotherapy in Localized Prostate Cancer: A Phase III Randomized Controlled Trial. J Clin Oncol. 2020 Feb 20;38(6):593-601. Epub 2019 Dec 12. Erratum in: J Clin Oncol. 2020 Jun 10;38(17):2005. [https://doi.org/10.1200/jco.19.01904 link to original article] [http://www.ncbi.nlm.nih.gov/pmc/articles/pmc7186584/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31829912/ PubMed]
+#Malone S, Roy S, Eapen L, E C, MacRae R, Perry G, Bowen J, Samant R, Morgan S, Craig J, Malone K, Grimes S. Sequencing of Androgen-Deprivation Therapy With External-Beam Radiotherapy in Localized Prostate Cancer: A Phase III Randomized Controlled Trial. J Clin Oncol. 2020 Feb 20;38(6):593-601. Epub 2019 Dec 12. Erratum in: J Clin Oncol. 2020 Jun 10;38(17):2005. [https://doi.org/10.1200/jco.19.01904 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7186584/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31829912/ PubMed]
-#'''PCS III:''' Nabid A, Carrier N, Vigneault E, Van Nguyen T, Vavassis P, Brassard MA, Bahoric B, Archambault R, Vincent F, Bettahar R, Wilke D, Souhami L. Androgen deprivation therapy and radiotherapy in intermediate-risk prostate cancer: A randomised phase III trial. Eur J Cancer. 2021 Jan;143:64-74. Epub 2020 Dec 3. [https://doi.org/10.1016/j.ejca.2020.10.023 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33279855/ PubMed] NCT00223145
+#Ito K, Kobayashi M, Komiyama M, Naito S, Nishimura K, Yonese J, Hashine K, Saito S, Arai G, Shinohara M, Masumori N, Shimizu N, Satoh T, Yamauchi A, Tochigi T, Takezawa Y, Fujimoto H, Yokomizo A, Kakimoto KI, Fukui I, Karasawa K, Tsukamoto T, Nozaki M, Hasumi M, Ishiyama H, Ohtani M, Kuwahara M, Harada M, Ohashi Y, Kotake T, Kakizoe T, Suzuki K, Yamanaka H; National Research Project on Endocrine-Radiation Combination Therapy for Locally Advanced Prostate Cancer Investigators. Oncological outcomes for patients with locally advanced prostate cancer treated with neoadjuvant endocrine and external-beam radiation therapy followed by adjuvant continuous/intermittent endocrine therapy in an open-label, randomized, phase 3 trial. Cancer. 2020 Sep 1;126(17):3961-3971. Epub 2020 Jun 23. [https://doi.org/10.1002/cncr.33034 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32573779/ PubMed]
+#'''PCS III:''' Nabid A, Carrier N, Vigneault E, Van Nguyen T, Vavassis P, Brassard MA, Bahoric B, Archambault R, Vincent F, Bettahar R, Wilke D, Souhami L. Androgen deprivation therapy and radiotherapy in intermediate-risk prostate cancer: A randomised phase III trial. Eur J Cancer. 2021 Jan;143:64-74. Epub 2020 Dec 3. [https://doi.org/10.1016/j.ejca.2020.10.023 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33279855/ PubMed] [https://clinicaltrials.gov/study/NCT00223145 NCT00223145]
+#'''DFCI 05-043:''' D'Amico AV, Xie W, McMahon E, Loffredo M, Medeiros S, Joseph D, Denham J, Kumar P, Bubley G, Sullivan M, Hellwig R, Carlos Vera J, Freter R, Jeffrey Baker W, Wong JY, Renshaw AA, Kantoff PW. Radiation and Androgen Deprivation Therapy With or Without Docetaxel in the Management of Nonmetastatic Unfavorable-Risk Prostate Cancer: A Prospective Randomized Trial. J Clin Oncol. 2021 Sep 10;39(26):2938-2947. Epub 2021 Jul 1. [https://doi.org/10.1200/jco.21.00596 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8425842/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34197181/ PubMed] [https://clinicaltrials.gov/study/NCT00116142 NCT00116142]
+#'''TRIP:''' Yorozu A, Namiki M, Saito S, Egawa S, Yaegashi H, Konaka H, Momma T, Fukagai T, Tanaka N, Ohashi T, Takahashi H, Nakagawa Y, Kikuchi T, Mizokami A, Stone NN. Trimodality Therapy With Iodine-125 Brachytherapy, External Beam Radiation Therapy, and Short- or Long-Term Androgen Deprivation Therapy for High-Risk Localized Prostate Cancer: Results of a Multicenter, Randomized Phase 3 Trial (TRIP/TRIGU0907). Int J Radiat Oncol Biol Phys. 2024 Feb 1;118(2):390-401. Epub 2023 Oct 4. [https://doi.org/10.1016/j.ijrobp.2023.08.046 link to original article] [https://pubmed.ncbi.nlm.nih.gov/37802225/ PubMed] UMIN000003992
 ==Flutamide, Goserelin, RT {{#subobject:2 |Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
 Flutamide, Goserelin, RT: Flutamide, Goserelin, '''<u>R</u>'''adiation '''<u>T</u>'''herapy
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:2 |Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 ! style="width: 20%" |Study
-! style="width: 20%" |Years of enrollment
+! style="width: 20%" |Dates of enrollment
 ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 ! style="width: 20%" |Comparator
 ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.goldjournal.net/article/S0090-4295(99)80053-3/pdf Pilepich et al. 1995]
+|[https://doi.org/10.1016/S0090-4295(99)80053-3 Pilepich et al. 1995]
 |1987-1991
-| style="background-color:#1a9851" |Phase III (E-RT-esc)
+| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
 |[[Prostate_cancer_-_historical#Radiation_therapy|RT]]
 | style="background-color:#1a9850" |Superior DFS
 |-
-|[http://www.redjournal.org/article/S0360-3016(01)01579-6/fulltext Pilepich et al. 2001 (RTOG 86-10)]
+|[https://doi.org/10.1016/s0360-3016(01)01579-6 Pilepich et al. 2001 (RTOG 86-10)]
 |1987-1991
-| style="background-color:#1a9851" |Phase III (E-esc)
+| style="background-color:#1a9851" |Phase 3 (E-esc)
 |[[Prostate_cancer_-_historical#Radiation_therapy|RT]]
 | style="background-color:#91cf60" |Seems to have superior cause-specific mortality
@@ Line 406: / Line 493: @@
 |[https://doi.org/10.1200/jco.2003.11.023 Hanks et al. 2003 (RTOG 92-02)]
 |1992-1995
-| style="background-color:#91cf61" |Non-randomized portion of RCT
+| style="background-color:#91cf61" |Non-randomized part of phase 3 RCT
 | style="background-color:#d3d3d3" |
 | style="background-color:#d3d3d3" |
 |-
-|[https://www.nejm.org/doi/full/10.1056/NEJMoa1012348 Jones et al. 2011 (RTOG 94-08)]
+|[https://doi.org/10.1056/NEJMoa1012348 Jones et al. 2011 (RTOG 94-08)]
 |1994-2001
-| style="background-color:#1a9851" |Phase III (E-esc)
+| style="background-color:#1a9851" |Phase 3 (E-esc)
 |[[Prostate_cancer_-_historical#Radiation_therapy|RT]]
-| style="background-color:#91cf60" |Seems to have superior OS
+| style="background-color:#91cf60" |Seems to have superior OS (primary endpoint)<br>OS120: 62% vs 57%<br>(HR 0.85, 95% CI 0.74-0.99)
 |-
 |[http://jama.ama-assn.org/content/299/3/289.long D'Amico et al. 2008 (DFCI 95-096)]
 |1995-2001
-| style="background-color:#1a9851" |Phase III (E-esc)
+| style="background-color:#1a9851" |Randomized (E-esc)
 |[[Prostate_cancer_-_historical#Radiation_therapy|RT]]
-| style="background-color:#1a9850" |Superior OS
+| style="background-color:#1a9850" |Superior OS (primary endpoint)<br>OS96: 74% vs 61%<br>(HR 0.56, 95% CI 0.34-0.91)
 |-
-| rowspan="2" |[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(05)70348-X/abstract Denham et al. 2005 (TTROG 96.01)]
+| rowspan="2" |[https://doi.org/10.1016/S1470-2045(05)70348-X Denham et al. 2005 (TROG 96.01)]
 | rowspan="2" |1996-2000
-| rowspan="2" style="background-color:#1a9851" |Phase III (E-esc)
+| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-esc)
-|1. Flutamide & Goserelin x 6 mo, RT
+|1. [[#Flutamide.2C_Goserelin.2C_RT|Flutamide, Goserelin, RT]]; 6 months of ADT
 | style="background-color:#d3d3d3" |Not reported
 |-
 |2. [[Prostate_cancer_-_historical#Radiation_therapy|RT]]
-| style="background-color:#1a9850" |Superior EFS
+| style="background-color:#1a9850" |Superior EFS (secondary endpoint)
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Endocrine therapy====
+*[[Flutamide (Eulexin)]] 250 mg PO three times per day on days 1 to 28
-*[[Flutamide (Eulexin)]] 250 mg PO three times per day
+*[[Goserelin (Zoladex)]] 3.6 mg SC once on day 1
-*[[Goserelin (Zoladex)]] 3.6 mg SC once on day 1
 '''28-day cycles, starting 2 months prior to radiation therapy and continuing at least through the end of radiation therapy'''
 ====Radiotherapy====
+*[[External beam radiotherapy]] is started 2 months after start of androgen deprivation therapy (ADT), 1.8 to 200 cGy per fraction, with an initial 44 to 4600 cGy to the pelvis, then an additional conedown to the prostate that resulted in a total dose of 65 to 7000 cGy
-*[[External beam radiotherapy]] 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
 '''7-week course'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
 ====Subsequent treatment====
+*RTOG 92-02: Adjuvant [[#Goserelin_monotherapy|goserelin]] x 2 y versus [[Prostate_cancer_-_null_regimens#Observation|no further treatment]]
-*RTOG 92-02: [[#Goserelin_monotherapy|adjuvant goserelin]] x 2 y versus [[Prostate_cancer_-_null_regimens#Observation|no further treatment]]
+</div></div>
 ===References===
+#Pilepich MV, Krall JM, al-Sarraf M, John MJ, Doggett RL, Sause WT, Lawton CA, Abrams RA, Rotman M, Rubin P, Shipley WU, Grignon D, Caplan R, Cox JD; Radiation Therapy Oncology Group. Androgen deprivation with radiation therapy compared with radiation therapy alone for locally advanced prostatic carcinoma: a randomized comparative trial of the Radiation Therapy Oncology Group. Urology. 1995 Apr;45(4):616-23. [https://doi.org/10.1016/S0090-4295(99)80053-3 link to original article] [https://pubmed.ncbi.nlm.nih.gov/7716842/ PubMed]
-#Pilepich MV, Krall JM, al-Sarraf M, John MJ, Doggett RL, Sause WT, Lawton CA, Abrams RA, Rotman M, Rubin P, Soloway MS; Radiation Therapy Oncology Group. Androgen deprivation with radiation therapy compared with radiation therapy alone for locally advanced prostatic carcinoma: a randomized comparative trial of the Radiation Therapy Oncology Group. Urology. 1995 Apr;45(4):616-23. [https://www.goldjournal.net/article/S0090-4295(99)80053-3/pdf link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/7716842 PubMed]
+#'''RTOG 86-10:''' 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. [https://doi.org/10.1016/s0360-3016(01)01579-6 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/11483335/ PubMed]
-#'''RTOG 86-10:''' 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. [http://www.redjournal.org/article/S0360-3016(01)01579-6/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/11483335 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. [https://doi.org/10.1200/jco.2007.13.9881 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18172188/ 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. [https://doi.org/10.1200/jco.2007.13.9881 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18172188 PubMed]
+#'''RTOG 92-02:''' 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. [https://doi.org/10.1200/jco.2003.11.023 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/14581419/ PubMed]
-#'''RTOG 92-02:''' 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. [https://doi.org/10.1200/jco.2003.11.023 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/14581419 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. [https://doi.org/10.1200/jco.2007.14.9021 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18413638/ 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. [https://doi.org/10.1200/jco.2007.14.9021 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18413638 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. [https://doi.org/10.1016/j.ijrobp.2017.02.004 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5603177/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28463149/ 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. [https://doi.org/10.1016/j.ijrobp.2017.02.004 link to original article] [http://www.ncbi.nlm.nih.gov/pmc/articles/pmc5603177/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/28463149 PubMed]
+#'''TROG 96.01:''' 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. [https://doi.org/10.1016/S1470-2045(05)70348-X link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/16257791/ PubMed] ACTRN12607000237482
-#'''TTROG 96.01:''' 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. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(05)70348-X/abstract link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16257791 PubMed]
+##'''Update:''' Denham JW, Steigler A, Lamb DS, Joseph D, Turner S, Matthews J, Atkinson C, North J, Christie D, Spry NA, Tai KH, Wynne C, D'Este C. Short-term neoadjuvant androgen deprivation and radiotherapy for locally advanced prostate cancer: 10-year data from the TROG 96.01 randomised trial. Lancet Oncol. 2011 May;12(5):451-9. [https://doi.org/10.1016/S1470-2045(11)70063-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/21440505/ PubMed]
-##'''Update:''' Denham JW, Steigler A, Lamb DS, Joseph D, Turner S, Matthews J, Atkinson C, North J, Christie D, Spry NA, Tai KH, Wynne C, D'Este C. Short-term neoadjuvant androgen deprivation and radiotherapy for locally advanced prostate cancer: 10-year data from the TROG 96.01 randomised trial. Lancet Oncol. 2011 May;12(5):451-9. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(11)70063-8/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/21440505 PubMed]
+#'''DFCI 95-096:''' 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. [http://jama.ama-assn.org/content/299/3/289.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/18212313/ PubMed] content property of [https://hemonc.org HemOnc.org] [https://clinicaltrials.gov/study/NCT00116220 NCT00116220]
-#'''DFCI 95-096:''' 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. [http://jama.ama-assn.org/content/299/3/289.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/18212313 PubMed] content property of [http://hemonc.org HemOnc.org]
+##'''Update:''' D'Amico AV, Chen MH, Renshaw A, Loffredo M, Kantoff PW. Long-term Follow-up of a Randomized Trial of Radiation With or Without Androgen Deprivation Therapy for Localized Prostate Cancer. JAMA. 2015 Sep 22-29;314(12):1291-3. [https://jamanetwork.com/journals/jama/fullarticle/2442924 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26393854/ PubMed]
-##'''Update:''' D'Amico AV, Chen MH, Renshaw A, Loffredo M, Kantoff PW. Long-term Follow-up of a Randomized Trial of Radiation With or Without Androgen Deprivation Therapy for Localized Prostate Cancer. JAMA. 2015 Sep 22-29;314(12):1291-3. [https://jamanetwork.com/journals/jama/fullarticle/2442924 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/26393854 PubMed]
+#'''RTOG 94-08:''' 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. [https://doi.org/10.1056/NEJMoa1012348 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21751904/ PubMed] [https://clinicaltrials.gov/study/NCT00002597 NCT00002597]
-#'''RTOG 94-08:''' 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. [https://www.nejm.org/doi/full/10.1056/NEJMoa1012348 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21751904 PubMed] NCT00002597
 ==Flutamide, Leuprolide, RT {{#subobject:3 |Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
 Flutamide, Leuprolide, RT: Flutamide, Leuprolide, '''<u>R</u>'''adiation '''<u>T</u>'''herapy
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #1, 4 months of ADT {{#subobject:3 |Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 ! style="width: 20%" |Study
-! style="width: 20%" |Years of enrollment
+! style="width: 20%" |Dates of enrollment
 ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 ! style="width: 20%" |Comparator
 ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.nejm.org/doi/full/10.1056/NEJMoa1012348 Jones et al. 2011 (RTOG 94-08)]
+|[https://doi.org/10.1056/NEJMoa1012348 Jones et al. 2011 (RTOG 94-08)]
 |1994-2001
-| style="background-color:#1a9851" |Phase III (E-esc)
+| style="background-color:#1a9851" |Phase 3 (E-esc)
 |[[Prostate_cancer_-_historical#Radiation_therapy|RT]]
-| style="background-color:#91cf60" |Seems to have superior OS
+| style="background-color:#91cf60" |Seems to have superior OS (primary endpoint)<br>OS120: 62% vs 57%<br>(HR 0.85, 95% CI 0.74-0.99)
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Endocrine therapy====
 *[[Flutamide (Eulexin)]] 250 mg PO three times per day, to start 2 months prior to radiation therapy
 *[[Leuprolide (Lupron)]] 7.5 mg SC once on day 1, to start 2 months prior to radiation therapy
 '''28-day cycle for 4 cycles'''
 ====Radiotherapy====
+*[[External beam radiotherapy]] is started 2 months after start of androgen deprivation therapy (ADT), 1.8 to 200 cGy per fraction, with an initial 44 to 4600 cGy to the pelvis, then an additional conedown to the prostate that resulted in a total dose of 65 to 7000 cGy
-*[[External beam radiotherapy]] 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
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #2, 3 years of ADT {{#subobject:38huac |Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 ! style="width: 20%" |Study
-! style="width: 20%" |Years of enrollment
+! style="width: 20%" |Dates of enrollment
 ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 ! style="width: 20%" |Comparator
@@ Line 504: / Line 581: @@
 |[https://doi.org/10.1016/j.eururo.2012.03.053 Mottet et al. 2012 (TAP 32)]
 |2000-2003
-| style="background-color:#1a9851" |Phase III (E-esc)
+| style="background-color:#1a9851" |Phase 3 (E-esc)
 |[[#Flutamide_.26_Leuprolide|Flutamide & Leuprolide]]
-| style="background-color:#1a9850" |Superior PFS
+| style="background-color:#1a9850" |Superior PFS60 (primary endpoint)
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Endocrine therapy====
 *[[Flutamide (Eulexin)]] 750 mg/day PO for one month
 *[[Leuprolide (Lupron)]] 11.25 mg SC once on day 1
 '''3-month cycle for 12 cycles (3 years)'''
 ====Radiotherapy====
+*[[External beam radiotherapy]] to the pelvis, started within 90 days of initiation of ADT: 44 to 4800 cGy given in 25 fractions over 5 weeks
-*[[External beam radiotherapy]] started within 90 days of initiation of ADT, as follows:
+*[[External beam radiotherapy]] to the prostate: 20 to 2800 cGy boost given in 10 to 12 fractions over 15 to 20 days
-**Pelvis: 44 to 48 Gy given in 25 fractions over 5 weeks
-**Prostate: 20 to 28 Gy boost given in 10 to 12 fractions over 15 to 20 days
 '''One course'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #3, indefinite ADT {{#subobject:5bddaf |Variant=1}}===
+===Regimen variant #3, indefinite ADT, monthly leuprolide {{#subobject:5bddaf |Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 ! style="width: 20%" |Study
-! style="width: 20%" |Years of enrollment
+! style="width: 20%" |Dates of enrollment
 ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 ! style="width: 20%" |Comparator
 ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(08)61815-2/fulltext Widmark et al. 2008 (SPCG-7/SFUO-3)]
+|[https://doi.org/10.1016/S0140-6736(08)61815-2 Widmark et al. 2008 (SPCG-7/SFUO-3)]
 |1996-2002
-| style="background-color:#1a9851" |Phase III (C)
+| style="background-color:#1a9851" |Phase 3 (C)
-|Flutamide & Leuprolide
+|[[#Flutamide_.26_Leuprolide|Flutamide & Leuprolide]]
 | style="background-color:#1a9850" |Superior OS
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Endocrine therapy====
+*[[Flutamide (Eulexin)]] 250 mg PO three times per day on days 1 to 28, '''starting 3 months prior to radiation therapy'''
-*[[Flutamide (Eulexin)]] 250 mg PO three times per day, to start 3 months prior to radiation therapy
+*[[Leuprolide (Lupron)]] as follows, '''starting 3 months prior to radiation therapy:'''
-*[[Leuprolide (Lupron)]] by one of the following, to start 3 months prior to radiation therapy:
+**Cycles 1 to 3: 3.75 mg SC once on day 1
-**3.75 mg SC once per month for 3 months
+'''28-day cycles'''
-**11.25 mg SC once
 ====Radiotherapy====
+*[[External beam radiotherapy]] 5000 cGy + 2000 cGy boost (total dose minimum of 7000 cGy)
-*[[External beam radiotherapy]] 50 Gy + 20 Gy boost (total dose minimum of 70 Gy)
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
-===References===
+===Regimen variant #4, indefinite ADT, 3-monthly leuprolide {{#subobject:5ihaaf |Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-#'''SPCG-7/SFUO-3:''' Widmark A, Klepp O, Solberg A, Damber JE, Angelsen A, Fransson P, Lund JA, Tasdemir I, Hoyer M, Wiklund F, Fosså SD; Scandinavian Prostate Cancer Group; Swedish Association for Urological Oncology. Endocrine treatment, with or without radiotherapy, in locally advanced prostate cancer (SPCG-7/SFUO-3): an open randomised phase III trial. Lancet. 2009 Jan 24;373(9660):301-8. Epub 2008 Dec 16. Erratum in: Lancet. 2009 Apr 4;373(9670):1174. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(08)61815-2/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19091394 PubMed] ISRCTN01534787
+! style="width: 20%" |Study
-#'''RTOG 94-08:''' 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. [https://www.nejm.org/doi/full/10.1056/NEJMoa1012348 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21751904 PubMed] NCT00002597
+! style="width: 20%" |Dates of enrollment
-#'''TAP 32:''' Mottet N, Peneau M, Mazeron JJ, Molinie V, Richaud P. Addition of radiotherapy to long-term androgen deprivation in locally advanced prostate cancer: an open randomised phase 3 trial. Eur Urol. 2012 Aug;62(2):213-9. Epub 2012 Apr 3. [https://doi.org/10.1016/j.eururo.2012.03.053 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/22502942 PubMed] NCT01122121
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
-##'''Update:''' Sargos P, Mottet N, Bellera C, Richaud P. Long-term androgen deprivation, with or without radiotherapy, in locally advanced prostate cancer: updated results from a phase III randomised trial. BJU Int. 2020 Jun;125(6):810-816. Epub 2020 Mar 2. [https://doi.org/10.1111/bju.14768 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/30946523 PubMed]
+! style="width: 20%" |Comparator
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-==Goserelin & RT {{#subobject:1 |Regimen=1}}==
+|-
-{| class="wikitable" style="float:right; margin-left: 5px;"
+|[https://doi.org/10.1016/S0140-6736(08)61815-2 Widmark et al. 2008 (SPCG-7/SFUO-3)]
+|1996-2002
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#Flutamide_.26_Leuprolide|Flutamide & Leuprolide]]
+| style="background-color:#1a9850" |Superior OS
 |-
-|[[#top|back to top]]
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Endocrine therapy====
+*[[Flutamide (Eulexin)]] 250 mg PO three times per day on days 1 to 28, '''starting 3 months prior to radiation therapy'''
+*[[Leuprolide (Lupron)]] as follows, '''starting 3 months prior to radiation therapy:'''
+**Cycle 1: 11.25 mg SC once on day 1
+'''28-day cycles'''
+====Radiotherapy====
+*[[External beam radiotherapy]] 5000 cGy + 2000 cGy boost (total dose minimum of 7000 cGy)
+</div></div>
+===References===
+#'''SPCG-7/SFUO-3:''' Widmark A, Klepp O, Solberg A, Damber JE, Angelsen A, Fransson P, Lund JA, Tasdemir I, Hoyer M, Wiklund F, Fosså SD; Scandinavian Prostate Cancer Group; Swedish Association for Urological Oncology. Endocrine treatment, with or without radiotherapy, in locally advanced prostate cancer (SPCG-7/SFUO-3): an open randomised phase III trial. Lancet. 2009 Jan 24;373(9660):301-8. Epub 2008 Dec 16. Erratum in: Lancet. 2009 Apr 4;373(9670):1174. [https://doi.org/10.1016/S0140-6736(08)61815-2 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19091394/ PubMed] ISRCTN01534787
+#'''RTOG 94-08:''' 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. [https://doi.org/10.1056/NEJMoa1012348 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21751904/ PubMed] [https://clinicaltrials.gov/study/NCT00002597 NCT00002597]
+#'''TAP 32:''' Mottet N, Peneau M, Mazeron JJ, Molinie V, Richaud P. Addition of radiotherapy to long-term androgen deprivation in locally advanced prostate cancer: an open randomised phase 3 trial. Eur Urol. 2012 Aug;62(2):213-9. Epub 2012 Apr 3. [https://doi.org/10.1016/j.eururo.2012.03.053 link to original article] [https://pubmed.ncbi.nlm.nih.gov/22502942/ PubMed] [https://clinicaltrials.gov/study/NCT01122121 NCT01122121]
+##'''Update:''' Sargos P, Mottet N, Bellera C, Richaud P. Long-term androgen deprivation, with or without radiotherapy, in locally advanced prostate cancer: updated results from a phase III randomised trial. BJU Int. 2020 Jun;125(6):810-816. Epub 2020 Mar 2. [https://doi.org/10.1111/bju.14768 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/30946523/ PubMed]
+==Goserelin & RT {{#subobject:1 |Regimen=1}}==
 Goserelin & RT: Goserelin & '''<u>R</u>'''adiation '''<u>T</u>'''herapy
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:1 |Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 ! style="width: 20%" |Study
-! style="width: 20%" |Years of enrollment
+! style="width: 20%" |Dates of enrollment
 ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 ! style="width: 20%" |Comparator
@@ Line 574: / Line 665: @@
 |[https://doi.org/10.1200/jco.1997.15.3.1013 Pilepich et al. 2005 (RTOG 85-31)]
 |1987-1992
-| style="background-color:#1a9851" |Phase III (E-esc)
+| style="background-color:#1a9851" |Phase 3 (E-esc)
 |[[Prostate_cancer_-_historical#Radiation_therapy|RT]]
 | style="background-color:#1a9850" |Superior DFS
 |-
-|[https://www.nejm.org/doi/full/10.1056/NEJM199707313370502 Bolla et al. 1997 (EORTC 22863)]
+|[https://doi.org/10.1056/NEJM199707313370502 Bolla et al. 1997 (EORTC 22863)]
 |1987-1995
-| style="background-color:#1a9851" |Phase III (E-esc)
+| style="background-color:#1a9851" |Phase 3 (E-esc)
 |[[Prostate_cancer_-_historical#Radiation_therapy|RT]]
 | style="background-color:#1a9850" |Superior OS
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Endocrine therapy====
 *[[Goserelin (Zoladex)]] 3.6 mg SC once on day 1, started during the last week of radiation therapy
 '''28-day cycles'''
 ====Radiotherapy====
+*[[External beam radiotherapy]], 1.8 to 200 cGy per fraction, with an initial 44 to 4600 cGy to the pelvis, then an additional boost to the prostate that resulted in a total dose of 65 to 7000 cGy in definitive radiation patients; 60 to 6500 cGy total dose for post-prostatectomy patients
-*[[External beam radiotherapy]], 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
 '''One course'''
+</div></div>
 ===References===
+#'''RTOG 85-31:''' 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. [https://doi.org/10.1200/jco.1997.15.3.1013 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/9060541/ PubMed]
-#'''RTOG 85-31:''' 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. [https://doi.org/10.1200/jco.1997.15.3.1013 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/9060541 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. [https://doi.org/10.1016/s0360-3016(00)01516-9 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/11240234/ 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. [http://www.redjournal.org/article/S0360-3016%2800%2901516-9/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/11240234 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. [https://doi.org/10.1016/j.ijrobp.2004.08.047 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15817329/ 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. [http://www.redjournal.org/article/S0360-3016(04)02468-X/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15817329 PubMed]
+#'''EORTC 22863:''' 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. [https://doi.org/10.1056/NEJM199707313370502 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9233866/ PubMed] [https://clinicaltrials.gov/study/NCT00849082 NCT00849082]
-#'''EORTC 22863:''' 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. [https://www.nejm.org/doi/full/10.1056/NEJM199707313370502 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/9233866 PubMed]
+##'''Update:''' Bolla M, Collette L, Blank L, Warde P, Dubois JB, Mirimanoff RO, Storme G, Bernier J, Kuten A, Sternberg C, Mattelaer J, Lopez Torecilla J, Pfeffer JR, Lino Cutajar C, Zurlo A, Pierart M. Long-term results with immediate androgen suppression and external irradiation in patients with locally advanced prostate cancer (an EORTC study): a phase III randomised trial. Lancet. 2002 Jul 13;360(9327):103-6. [https://doi.org/10.1016/S0140-6736(02)09408-4 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12126818/ PubMed]
-##'''Update:''' Bolla M, Collette L, Blank L, Warde P, Dubois JB, Mirimanoff RO, Storme G, Bernier J, Kuten A, Sternberg C, Mattelaer J, Lopez Torecilla J, Pfeffer JR, Lino Cutajar C, Zurlo A, Pierart M. Long-term results with immediate androgen suppression and external irradiation in patients with locally advanced prostate cancer (an EORTC study): a phase III randomised trial. Lancet. 2002 Jul 13;360(9327):103-6. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(02)09408-4/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/12126818 PubMed]
+##'''Update:''' Bolla M, Van Tienhoven G, Warde P, Dubois JB, Mirimanoff RO, Storme G, Bernier J, Kuten A, Sternberg C, Billiet I, Torecilla JL, Pfeffer R, Cutajar CL, Van der Kwast T, Collette L. External irradiation with or without long-term androgen suppression for prostate cancer with high metastatic risk: 10-year results of an EORTC randomised study. Lancet Oncol. 2010 Nov;11(11):1066-73. Epub 2010 Oct 7. [https://doi.org/10.1016/S1470-2045(10)70223-0 link to original article] [https://pubmed.ncbi.nlm.nih.gov/20933466/ PubMed]
-##'''Update:''' Bolla M, Van Tienhoven G, Warde P, Dubois JB, Mirimanoff RO, Storme G, Bernier J, Kuten A, Sternberg C, Billiet I, Torecilla JL, Pfeffer R, Cutajar CL, Van der Kwast T, Collette L. External irradiation with or without long-term androgen suppression for prostate cancer with high metastatic risk: 10-year results of an EORTC randomised study. Lancet Oncol. 2010 Nov;11(11):1066-73. Epub 2010 Oct 7. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(10)70223-0/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/20933466 PubMed]
 =Adjuvant therapy=
 ==Bicalutamide & Goserelin {{#subobject:611758|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
+<div class="toccolours" style="background-color:#eeeeee">
-|-
-|[[#top|back to top]]
-|}
 ===Regimen {{#subobject:bdfd60|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 ! style="width: 20%" |Study
-! style="width: 20%" |Years of enrollment
+! style="width: 20%" |Dates of enrollment
 ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 ! style="width: 20%" |Comparator
@@ Line 621: / Line 704: @@
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3107759/ Dorff et al. 2011 (SWOG S9921)]
 |2000-2007
-| style="background-color:#1a9851" |Phase III (C)
+| style="background-color:#1a9851" |Phase 3 (C)
-|ADT & Mitoxantrone
+|[[#ADT_.26_Mitoxantrone_999|ADT & Mitoxantrone]]
-| style="background-color:#d3d3d3" |Not reported
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS<sup>1</sup>
 |-
 |}
+''<sup>1</sup>Reported efficacy is based on the 2018 update.''<br>
 ''Dosing details are not available in the manuscript; this is the common dosing used.''
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
 *[[Surgery#Radical_prostatectomy|Radical prostatectomy]]
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Endocrine therapy====
 *[[Bicalutamide (Casodex)]] 50 mg PO once per day
 *[[Goserelin (Zoladex)]] 10.8 mg SC once on day 1
 '''12-week cycle for 9 cycles (2 years)'''
+</div></div>
 ===References===
+#'''SWOG S9921:''' Dorff TB, Flaig TW, Tangen CM, Hussain MH, Swanson GP, Wood DP Jr, Sakr WA, Dawson NA, Haas NB, Crawford ED, Vogelzang NJ, Thompson IM, Glode LM. Adjuvant androgen deprivation for high-risk prostate cancer after radical prostatectomy: SWOG S9921 study. J Clin Oncol. 2011 May 20;29(15):2040-5. Epub 2011 Apr 18. [https://doi.org/10.1200/JCO.2010.32.2776 link to original article] '''does not contain dosing details''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3107759/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21502546/ PubMed] [https://clinicaltrials.gov/study/NCT00004124 NCT00004124]
-#'''SWOG S9921:''' Dorff TB, Flaig TW, Tangen CM, Hussain MH, Swanson GP, Wood DP Jr, Sakr WA, Dawson NA, Haas NB, Crawford ED, Vogelzang NJ, Thompson IM, Glode LM. Adjuvant androgen deprivation for high-risk prostate cancer after radical prostatectomy: SWOG S9921 study. J Clin Oncol. 2011 May 20;29(15):2040-5. Epub 2011 Apr 18. [https://doi.org/10.1200/JCO.2010.32.2776 link to original article] '''does not contain protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3107759/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/21502546 PubMed] NCT00004124
+##'''Update:''' Hussain M, Tangen CM, Thompson IM Jr, Swanson GP, Wood DP, Sakr W, Dawson NA, Haas NB, Flaig TW, Dorff TB, Lin DW, Crawford ED, Quinn DI, Vogelzang NJ, Glode LM. Phase III Intergroup Trial of Adjuvant Androgen Deprivation With or Without Mitoxantrone Plus Prednisone in Patients With High-Risk Prostate Cancer After Radical Prostatectomy: SWOG S9921. J Clin Oncol. 2018 May 20;36(15):1498-1504. Epub 2018 Apr 6. Erratum in: J Clin Oncol. 2018 Jul 10;36(20):2131. [https://doi.org/10.1200/jco.2017.76.4126 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5959197/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29624463/ PubMed]
 ==Goserelin monotherapy {{#subobject:267ff5|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
+<div class="toccolours" style="background-color:#eeeeee">
-|-
+===Regimen {{#subobject:53d064|Variant=1}}===
-|[[#top|back to top]]
-|}
-===Regimen {{#subobject:53d064|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 ! style="width: 20%" |Study
-! style="width: 20%" |Years of enrollment
+! style="width: 20%" |Dates of enrollment
 ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 ! style="width: 20%" |Comparator
 ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.nejm.org/doi/full/10.1056/NEJM199912093412401 Messing et al. 1999 (ECOG E3886)]
+|[https://doi.org/10.1056/NEJM199912093412401 Messing et al. 1999 (ECOG E3886)]
 |1988-1993
-| style="background-color:#1a9851" |Phase III (E-esc)
+| style="background-color:#1a9851" |Phase 3 (E-esc)
 |[[Prostate_cancer_-_null_regimens#Observation|No further treatment]]
 | style="background-color:#91cf60" |Seems to have superior OS
@@ Line 664: / Line 743: @@
 |[https://doi.org/10.1200/jco.2003.11.023 Hanks et al. 2003 (RTOG 92-02)]
 |1992-1995
-| style="background-color:#1a9851" |Phase III (E-esc)
+| style="background-color:#1a9851" |Phase 3 (E-esc)
 |[[Prostate_cancer_-_null_regimens#Observation|No further treatment]]
 | style="background-color:#91cf60" |Seems to have superior OS<sup>1</sup>
@@ Line 670: / Line 749: @@
 |}
 ''<sup>1</sup>Reported efficacy of RTOG 92-02 based on the 2017 update.''
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
 *ECOG E3886: [[Surgery#Radical_prostatectomy|Radical prostatectomy]]
-*RTOG 92-02: [[#Flutamide.2C_Goserelin.2C_RT|Flutamide, Goserelin, RT]]
+*RTOG 92-02: Definitive [[#Flutamide.2C_Goserelin.2C_RT|Flutamide, Goserelin, RT]]
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Endocrine therapy====
 *[[Goserelin (Zoladex)]] 3.6 mg SC once per month
 '''2-year course (RTOG 92-02) or until rising PSA detected (ECOG E3886)'''
+</div></div>
 ===References===
+#'''ECOG E3886:''' Messing EM, Manola J, Sarosdy M, Wilding G, Crawford ED, Trump D; [[Study_Groups#ECOG|ECOG]]. Immediate hormonal therapy compared with observation after radical prostatectomy and pelvic lymphadenectomy in men with node-positive prostate cancer. N Engl J Med. 1999 Dec 9;341(24):1781-8. [https://doi.org/10.1056/NEJM199912093412401 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/10588962/ PubMed]
-#'''ECOG E3886:''' Messing EM, Manola J, Sarosdy M, Wilding G, Crawford ED, Trump D; [[Study_Groups#ECOG|ECOG]]. Immediate hormonal therapy compared with observation after radical prostatectomy and pelvic lymphadenectomy in men with node-positive prostate cancer. N Engl J Med. 1999 Dec 9;341(24):1781-8. [https://www.nejm.org/doi/full/10.1056/NEJM199912093412401 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/10588962 PubMed]
+##'''Update:''' Messing EM, Manola J, Yao J, Kiernan M, Crawford D, Wilding G, di'SantAgnese PA, Trump D; [[Study_Groups#ECOG|ECOG]]. Immediate versus deferred androgen deprivation treatment in patients with node-positive prostate cancer after radical prostatectomy and pelvic lymphadenectomy. Lancet Oncol. 2006 Jun;7(6):472-9. [https://doi.org/10.1016/S1470-2045(06)70700-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16750497/ PubMed]
-##'''Update:''' Messing EM, Manola J, Yao J, Kiernan M, Crawford D, Wilding G, di'SantAgnese PA, Trump D; [[Study_Groups#ECOG|ECOG]]. Immediate versus deferred androgen deprivation treatment in patients with node-positive prostate cancer after radical prostatectomy and pelvic lymphadenectomy. Lancet Oncol. 2006 Jun;7(6):472-9. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(06)70700-8/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/16750497 PubMed]
+#'''RTOG 92-02:''' 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. [https://doi.org/10.1200/jco.2003.11.023 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/14581419/ PubMed]
-#'''RTOG 92-02:''' 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. [https://doi.org/10.1200/jco.2003.11.023 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/14581419 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. [https://doi.org/10.1200/jco.2007.14.9021 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18413638/ 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. [https://doi.org/10.1200/jco.2007.14.9021 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18413638 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. [https://doi.org/10.1016/j.ijrobp.2017.02.004 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5603177/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28463149/ 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. [https://doi.org/10.1016/j.ijrobp.2017.02.004 link to original article] [http://www.ncbi.nlm.nih.gov/pmc/articles/pmc5603177/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/28463149 PubMed]
+#'''ERADICATE:''' [https://clinicaltrials.gov/study/NCT04484818 NCT04484818]
 ==Triptorelin & RT {{#subobject:611758|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
+<div class="toccolours" style="background-color:#eeeeee">
-|-
-|[[#top|back to top]]
-|}
 ===Regimen {{#subobject:bdfd60|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 ! style="width: 20%" |Study
-! style="width: 20%" |Years of enrollment
+! style="width: 20%" |Dates of enrollment
 ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 ! style="width: 20%" |Comparator
 ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(20)30454-X/fulltext/ Sargos et al. 2020 (GETUG-AFU 17)]
+|[https://doi.org/10.1016/S1470-2045(20)30454-X Sargos et al. 2020 (GETUG-AFU 17)]
 |2008-2016
-| style="background-color:#1a9851" |Phase III (C)
+| style="background-color:#1a9851" |Phase 3 (C)
-|Triptorelin & RT; salvage
+|[[#Triptorelin_.26_RT_999|Triptorelin & RT]]; salvage
 | style="background-color:#ffffbf" |Did not meet primary endpoint of EFS
 |-
 |}
-''Statistical power was compromised due to unexpectedly low event rate. GETUG-AFU 17 was published concurrently along with two other Phase III trials looking at timing of radiotherapy following radical prostatectomy: [https://pubmed.ncbi.nlm.nih.gov/33002429/ RADICALS-RT] and [https://pubmed.ncbi.nlm.nih.gov/33002437/ ANZUP RAVES]. All three trials were also analyzed as part of a pre-planned meta-analysis [https://pubmed.ncbi.nlm.nih.gov/33002431/ ARTISTIC] which failed to show an EFS benefit with adjuvant radiotherapy vs. salvage radiotherapy.''
+''Statistical power was compromised due to unexpectedly low event rate. GETUG-AFU 17 was published concurrently along with two other Phase 3 trials looking at timing of radiotherapy following radical prostatectomy: [https://pubmed.ncbi.nlm.nih.gov/33002429/ RADICALS-RT] and [https://pubmed.ncbi.nlm.nih.gov/33002437/ ANZUP RAVES]. All three trials were also analyzed as part of a pre-planned meta-analysis [https://pubmed.ncbi.nlm.nih.gov/33002431/ ARTISTIC] which failed to show an EFS benefit with adjuvant radiotherapy vs. salvage radiotherapy.''
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
 *[[Surgery#Radical_prostatectomy|Radical prostatectomy]]
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Endocrine therapy====
 *[[Triptorelin (Trelstar LA)]] 11.25 mg IM once on day 1
 '''12-week cycle for 2 cycles (6 months)'''
 ====Radiotherapy====
 *[[External beam radiotherapy]]
+</div></div>
 ===References===
+#'''GETUG-AFU 17:''' Sargos P, Chabaud S, Latorzeff I, Magne N, Benyoucef A, Supiot S, Pasquier D, Abdiche MS, Gilliot O, Graff-Cailleaud P, Silva M, Bergerot P, Baumann P, Belkacemi Y, Azria D, Brihoum M, Soulie M, Richaud P. Adjuvant radiotherapy versus early salvage radiotherapy plus short-term androgen deprivation therapy in men with localized prostate cancer after radical prostatectomy (GETUG-AFU 17): a randomised, phase 3 trial. Lancet Oncol. 2020 Oct; 21(10):1341-1352. [https://doi.org/10.1016/S1470-2045(20)30454-X link to original article] '''does not contain dosing details''' [https://pubmed.ncbi.nlm.nih.gov/33002438/ PubMed] [https://clinicaltrials.gov/study/NCT00667069 NCT00667069]
-#'''GETUG-AFU 17:''' Sargos P, Chabaud S, Latorzeff I, Magne N, Benyoucef A, Supiot S, Pasquier D, Abdiche MS, Gilliot O, Graff-Cailleaud P, Silva M, Bergerot P, Baumann P, Belkacemi Y, Azria D, Brihoum M, Soulie M, Richaud P. Adjuvant radiotherapy versus early salvage radiotherapy plus short-term androgen deprivation therapy in men with localized prostate cancer after radical prostatectomy (GETUG-AFU 17): a randomised, phase 3 trial. Lancet Oncol. 2020 Oct; 21(10):1341-1352. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(20)30454-X/fulltext link to original article] '''does not contain protocol''' [https://pubmed.ncbi.nlm.nih.gov/33002438/ PubMed] NCT00667069
 =Salvage ADT & radiotherapy=
-==Bicalutamide & RT {{#subobject:2c64f0 |Regimen=1}}==
+==ADT & RT {{#subobject:51ug72|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
+ADT & RT: '''<u>A</u>'''ndrogen '''<u>D</u>'''eprivation '''<u>T</u>'''herapy & '''<u>R</u>'''adiation '''<u>T</u>'''herapy
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:xi0c55|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+! style="width: 20%" |Study
+! style="width: 20%" |Dates of enrollment
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |Comparator
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9819649/ Pollack et al. 2022 (SPPORT)]
+|2008-2015
+| style="background-color:#1a9851" |Phase 3 (E-esc)
+|[[#Radiation_therapy_888|RT]]
+| style="background-color:#1a9850" |Superior FFP (primary endpoint)
 |-
-|[[#top|back to top]]
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Endocrine therapy====
+*Antiandrogen (ONE of the following):
+**[[Bicalutamide (Casodex)]] 50 mg PO once per day
+**[[Flutamide (Eulexin)]] 250 mg PO three times per day
+*[[:Category:GnRH agonists|LHRH agonist]] (ONE of the following):
+**[[Leuprolide (Lupron)]]
+**[[Goserelin (Zoladex)]]
+**[[Buserelin (Suprefact)]]
+**[[Triptorelin (Trelstar LA)]]
+====Radiotherapy====
+*[[External beam radiotherapy]]
+</div></div>
+===References===
+#'''SPPORT:''' Pollack A, Karrison TG, Balogh AG, Gomella LG, Low DA, Bruner DW, Wefel JS, Martin AG, Michalski JM, Angyalfi SJ, Lukka H, Faria SL, Rodrigues GB, Beauchemin MC, Lee RJ, Seaward SA, Allen AM, Monitto DC, Seiferheld W, Sartor O, Feng F, Sandler HM. The addition of androgen deprivation therapy and pelvic lymph node treatment to prostate bed salvage radiotherapy (NRG Oncology/RTOG 0534 SPPORT): an international, multicentre, randomised phase 3 trial. Lancet. 2022 May 14;399(10338):1886-1901. [https://doi.org/10.1016/S0140-6736(21)01790-6 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9819649/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/35569466/ PubMed] [https://clinicaltrials.gov/study/NCT00567580 NCT00567580]
+==Bicalutamide & RT {{#subobject:2c64f0 |Regimen=1}}==
 Bicalutamide & RT: Bicalutamide & '''<u>R</u>'''adiation '''<u>T</u>'''herapy
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:4f2e28 |Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 ! style="width: 20%" |Study
-! style="width: 20%" |Years of enrollment
+! style="width: 20%" |Dates of enrollment
 ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 ! style="width: 20%" |Comparator
@@ Line 744: / Line 844: @@
 |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5444881/ Shipley et al. 2017 (RTOG 9601)]
 |1998-2003
-| style="background-color:#1a9851" |Phase III (E-esc)
+| style="background-color:#1a9851" |Phase 3 (E-esc)
-|RT
+|[[#Radiation_therapy_888|RT]]
-| style="background-color:#91cf60" |Seems to have superior OS
+| style="background-color:#91cf60" |Seems to have superior OS (primary endpoint)<br>OS144: 76.3% vs 71.3%<br>(HR 0.77, 95% CI 0.59-0.99)
 |-
 |}
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
 *[[Surgery#Prostatectomy|Prostatectomy]] with [[Surgery#Lymphadenectomy|lymphadenectomy]], with a postoperative detectable PSA level of 0.2 to 4.0 ng/mL
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Endocrine therapy====
 *[[Bicalutamide (Casodex)]] 150 mg PO once per day
 '''2-year course'''
 ====Radiotherapy====
+*[[External beam radiotherapy]], 6480 cGy in 36 daily fractions of 180 cGy
-*[[External beam radiotherapy]], 64.8 Gy in 36 daily fractions of 1.8 Gy
 '''7-week course'''
+</div></div>
 ===References===
+#'''RTOG 9601:''' Shipley WU, Seiferheld W, Lukka HR, Major PP, Heney NM, Grignon DJ, Sartor O, Patel MP, Bahary JP, Zietman AL, Pisansky TM, Zeitzer KL, Lawton CA, Feng FY, Lovett RD, Balogh AG, Souhami L, Rosenthal SA, Kerlin KJ, Dignam JJ, Pugh SL, Sandler HM; NRG Oncology RTOG. Radiation with or without antiandrogen therapy in recurrent prostate cancer. N Engl J Med. 2017 Feb 2;376(5):417-428. [https://doi.org/10.1056/NEJMoa1607529 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5444881/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28146658/ PubMed] [https://clinicaltrials.gov/study/NCT00002874 NCT00002874]
-#'''RTOG 9601:''' Shipley WU, Seiferheld W, Lukka HR, Major PP, Heney NM, Grignon DJ, Sartor O, Patel MP, Bahary JP, Zietman AL, Pisansky TM, Zeitzer KL, Lawton CA, Feng FY, Lovett RD, Balogh AG, Souhami L, Rosenthal SA, Kerlin KJ, Dignam JJ, Pugh SL, Sandler HM; NRG Oncology RTOG. Radiation with or without antiandrogen therapy in recurrent prostate cancer. N Engl J Med. 2017 Feb 2;376(5):417-428. [https://www.nejm.org/doi/full/10.1056/NEJMoa1607529 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5444881/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/28146658 PubMed] NCT00002874
 ==Goserelin & RT {{#subobject:88575c |Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
 Goserelin & RT: Goserelin & '''<u>R</u>'''adiation '''<u>T</u>'''herapy
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen {{#subobject:fac0bd |Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 ! style="width: 20%" |Study
-! style="width: 20%" |Years of enrollment
+! style="width: 20%" |Dates of enrollment
 ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 ! style="width: 20%" |Comparator
 ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(16)00111-X/fulltext Carrie et al. 2016 (GETUG-AFU 16)]
+|[https://doi.org/10.1016/S1470-2045(16)00111-X Carrie et al. 2016 (GETUG-AFU 16)]
 |2006-2010
-| style="background-color:#1a9851" |Phase III (E-esc)
+| style="background-color:#1a9851" |Phase 3 (E-esc)
-|Salvage RT
+|[[#Radiation_therapy_888|RT]]
-| style="background-color:#1a9850" |Superior PFS
+| style="background-color:#1a9850" |Superior PFS (primary endpoint)<br>PFS60: 80% vs 62%<br>(HR 0.50, 95% CI 0.38-0.66)
 |-
 |}
+<div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
 *[[Surgery#Prostatectomy|Prostatectomy]], with rising PSA
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Endocrine therapy====
 *[[Goserelin (Zoladex)]] 0.8 mg SC once on day 1
 '''3-month cycle for 2 cycles'''
 ====Radiotherapy====
+*[[External beam radiotherapy]], 6600 cGy in 33 daily fractions of 200 cGy
-*[[External beam radiotherapy]], 66 Gy in 33 daily fractions of 2 Gy
 '''7-week course'''
+</div></div>
 ===References===
+#'''GETUG-AFU 16:''' Carrie C, Hasbini A, de Laroche G, Richaud P, Guerif S, Latorzeff I, Supiot S, Bosset M, Lagrange JL, Beckendorf V, Lesaunier F, Dubray B, Wagner JP, N'Guyen TD, Suchaud JP, Créhange G, Barbier N, Habibian M, Ferlay C, Fourneret P, Ruffion A, Dussart S. Salvage radiotherapy with or without short-term hormone therapy for rising prostate-specific antigen concentration after radical prostatectomy (GETUG-AFU 16): a randomised, multicentre, open-label phase 3 trial. Lancet Oncol. 2016 Jun;17(6):747-756. Epub 2016 May 6. Erratum in: Lancet Oncol. 2016 Jun;17 (6):e223. [https://doi.org/10.1016/S1470-2045(16)00111-X link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/27160475/ PubMed] [https://clinicaltrials.gov/study/NCT00423475 NCT00423475]
-#'''GETUG-AFU 16:''' Carrie C, Hasbini A, de Laroche G, Richaud P, Guerif S, Latorzeff I, Supiot S, Bosset M, Lagrange JL, Beckendorf V, Lesaunier F, Dubray B, Wagner JP, N'Guyen TD, Suchaud JP, Créhange G, Barbier N, Habibian M, Ferlay C, Fourneret P, Ruffion A, Dussart S. Salvage radiotherapy with or without short-term hormone therapy for rising prostate-specific antigen concentration after radical prostatectomy (GETUG-AFU 16): a randomised, multicentre, open-label phase 3 trial. Lancet Oncol. 2016 Jun;17(6):747-756. Epub 2016 May 6. Erratum in: Lancet Oncol. 2016 Jun;17 (6):e223. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(16)00111-X/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/27160475 PubMed] NCT00423475
+##'''Update:''' Carrie C, Magné N, Burban-Provost P, Sargos P, Latorzeff I, Lagrange JL, Supiot S, Belkacemi Y, Peiffert D, Allouache N, Dubray BM, Servagi-Vernat S, Suchaud JP, Crehange G, Guerif S, Brihoum M, Barbier N, Graff-Cailleaud P, Ruffion A, Dussart S, Ferlay C, Chabaud S. Short-term androgen deprivation therapy combined with radiotherapy as salvage treatment after radical prostatectomy for prostate cancer (GETUG-AFU 16): a 112-month follow-up of a phase 3, randomised trial. Lancet Oncol. 2019 Dec;20(12):1740-1749. Epub 2019 Oct 16.  [https://doi.org/10.1016/S1470-2045(19)30486-3 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31629656/ PubMed]
-##'''Update:''' Carrie C, Magné N, Burban-Provost P, Sargos P, Latorzeff I, Lagrange JL, Supiot S, Belkacemi Y, Peiffert D, Allouache N, Dubray BM, Servagi-Vernat S, Suchaud JP, Crehange G, Guerif S, Brihoum M, Barbier N, Graff-Cailleaud P, Ruffion A, Dussart S, Ferlay C, Chabaud S. Short-term androgen deprivation therapy combined with radiotherapy as salvage treatment after radical prostatectomy for prostate cancer (GETUG-AFU 16): a 112-month follow-up of a phase 3, randomised trial. Lancet Oncol. 2019 Dec;20(12):1740-1749. Epub 2019 Oct 16.  [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(19)30486-3/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/31629656 PubMed]
+#'''ECOG-ACRIN EA8191:''' [https://clinicaltrials.gov/study/NCT04423211 NCT04423211]
-<br />
 =Hormonal therapy for non-metastatic castrate sensitive disease=
 ==ADT {{#subobject:6e0da9|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
+ADT: '''<u>A</u>'''ndrogen '''<u>D</u>'''eprivation '''<u>T</u>'''herapy
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #1, 6 months {{#subobject:6625d3|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+! style="width: 20%" |Study
+! style="width: 20%" |Dates of enrollment
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |Comparator
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc2838198/ Figg et al. 2009]
+|2000-03 to 2005-01
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#ADT_.26_Thalidomide_999|ADT & Thalidomide]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 |-
-|[[#top|back to top]]
 |}
-ADT: '''<u>A</u>'''ndrogen '''<u>D</u>'''eprivation '''<u>T</u>'''herapy
+''Note: these are clinical trials that did not specify a particular approach to be used for androgen deprivation. See papers for details.''
-===Regimen {{#subobject:0415d3|Variant=1}}===
+<div class="toccolours" style="background-color:#b3e2cd">
+====Endocrine therapy====
+*[[:Category:Androgen-deprivation therapy|ADT]]
+'''6-month course'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #2, 12 months {{#subobject:0125d3|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 ! style="width: 20%" |Study
-! style="width: 20%" |Years of enrollment
+! style="width: 20%" |Dates of enrollment
 ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 ! style="width: 20%" |Comparator
@@ Line 827: / Line 933: @@
 |[https://jamanetwork.com/journals/jamaoncology/article-abstract/2723273 Oudard et al. 2019 (RisingPSA)]
 |2003-2007
-| style="background-color:#1a9851" |Phase III (C)
+| style="background-color:#1a9851" |Phase 3 (C)
-|ADT & Docetaxel
+|[[#ADT_.26_Docetaxel_999|ADT & Docetaxel]]
 | style="background-color:#ffffbf" |Did not meet primary endpoint of PSA-PFS
 |-
-|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(16)00107-8/fulltext Duchesne et al. 2016 (TOAD)]
+|}
-|2004-2012
+''Note: these are clinical trials that did not specify a particular approach to be used for androgen deprivation. See papers for details.''
-| style="background-color:#1a9851" |Phase III (E-switch-ic)
+<div class="toccolours" style="background-color:#b3e2cd">
-|Delayed ADT
+====Endocrine therapy====
-| style="background-color:#91cf60" |Seems to have superior OS
+*[[:Category:Androgen-deprivation therapy|ADT]]
+'''12-month course'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #3, indefinite {{#subobject:0415d3|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+! style="width: 20%" |Study
+! style="width: 20%" |Dates of enrollment
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |Comparator
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1016/S1470-2045(16)00107-8 Duchesne et al. 2016 (TOAD)]
+|2004-2012
+| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
+|[[#ADT_3|ADT]]; delayed
+| style="background-color:#91cf60" |Seems to have superior OS (primary endpoint)<br>OS60: 91.2% vs 86.4%<br>(HR 0.55, 95% CI 0.30-1.00)
 |-
-|[https://www.europeanurology.com/article/S0302-2838(15)00977-X/fulltext Schulman et al. 2015 (ICELAND)]
+|[https://doi.org/10.1016/j.eururo.2015.10.007 Schulman et al. 2015 (ICELAND)]
 |2006-NR
-| style="background-color:#1a9851" |Phase III (C)
+| style="background-color:#1a9851" |Phase 3 (C)
-|Intermittent ADT
+|[[#Intermittent_ADT_999|Intermittent ADT]]
 | style="background-color:#ffffbf" |Did not meet primary endpoint of TTP
+|-
+|[https://doi.org/10.1200/jco.23.01157 Aggarwal et al. 2024 (PRESTO)]
+|2017-03 to 2022-04
+|style="background-color:#1a9851" |Phase 3 (C)
+|1. [[#ADT_.26_Apalutamide|ADT & Apalutamide]]<br>2. [[#ADT.2C_Abiraterone.2C_Apalutamide|ADT, Abiraterone, Apalutamide]]
+| style="background-color:#d73027" |Inferior PSA-PFS (primary endpoint)
 |-
 |}
-''Note: these are clinical trials that did not specify a particular drug to be used for androgen deprivation. See papers for details.''
+''Note: these are clinical trials that did not specify a particular approach to be used for androgen deprivation. See papers for details.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Endocrine therapy====
+*[[:Category:Androgen-deprivation therapy|ADT]]
-*[[:Category:GnRH agonists|LHRH agonist]]
+'''Continued indefinitely'''
-*[[Bicalutamide (Casodex)]] or [[Flutamide (Eulexin)]]
+</div></div>
-'''12-month course (RisingPSA) or continued indefinitely'''
 ===References===
+#Figg WD, Hussain MH, Gulley JL, Arlen PM, Aragon-Ching JB, Petrylak DP, Higano CS, Steinberg SM, Chatta GS, Parnes H, Wright JJ, Sartor O, Dahut WL. A double-blind randomized crossover study of oral thalidomide versus placebo for androgen dependent prostate cancer treated with intermittent androgen ablation. J Urol. 2009 Mar;181(3):1104-13. Epub 2009 Jan 23. [https://doi.org/10.1016/j.juro.2008.11.026 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc2838198/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19167733/ PubMed] [https://clinicaltrials.gov/study/NCT00004635 NCT00004635]
+#'''EORTC 30891:''' Studer UE, Whelan P, Wimpissinger F, Casselman J, de Reijke TM, Knönagel H, Loidl W, Isorna S, Sundaram SK, Collette L; EORTC Genitourinary Cancer Group. Differences in time to disease progression do not predict for cancer-specific survival in patients receiving immediate or deferred androgen-deprivation therapy for prostate cancer: final results of EORTC randomized trial 30891 with 12 years of follow-up. Eur Urol. 2014 Nov;66(5):829-38. Epub 2013 Jul 24. [https://doi.org/10.1016/j.eururo.2013.07.024 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23932338/ PubMed] [https://clinicaltrials.gov/study/NCT01819285 NCT01819285]
+#'''ICELAND:''' Schulman C, Cornel E, Matveev V, Tammela TL, Schraml J, Bensadoun H, Warnack W, Persad R, Salagierski M, Gómez Veiga F, Baskin-Bey E, López B, Tombal B. Intermittent versus continuous androgen deprivation therapy in patients with relapsing or locally advanced prostate cancer: a phase 3b randomised study (ICELAND). Eur Urol. 2016 Apr;69(4):720-727. Epub 2015 Oct 29. [https://doi.org/10.1016/j.eururo.2015.10.007 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26520703/ PubMed] [https://clinicaltrials.gov/study/NCT00378690 NCT00378690]
+#'''TOAD:''' Duchesne GM, Woo HH, Bassett JK, Bowe SJ, D'Este C, Frydenberg M, King M, Ledwich L, Loblaw A, Malone S, Millar J, Milne R, Smith RG, Spry N, Stockler M, Syme RA, Tai KH, Turner S. Timing of androgen-deprivation therapy in patients with prostate cancer with a rising PSA (TROG 03.06 and VCOG PR 01-03 [TOAD]): a randomised, multicentre, non-blinded, phase 3 trial. Lancet Oncol. 2016 Jun;17(6):727-737. Epub 2016 May 4. Erratum in: Lancet Oncol. 2016 Jun;17 (6):e223. Lancet Oncol. 2017 Sep;18(9):e510. [https://doi.org/10.1016/S1470-2045(16)00107-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27155740/ PubMed] [https://clinicaltrials.gov/study/NCT00110162 NCT00110162]
+#'''RisingPSA:''' Oudard S, Latorzeff I, Caty A, Miglianico L, Sevin E, Hardy-Bessard AC, Delva R, Rolland F, Mourey L, Priou F, Beuzeboc P, Gravis G, Linassier C, Gomez P, Voog E, Muracciole X, Abraham C, Banu E, Ferrero JM, Ravaud A, Krakowski I, Lagrange JL, Deplanque G, Zylberait D, Bozec L, Houede N, Culine S, Elaidi R. Effect of adding docetaxel to androgen-deprivation therapy in patients with high-risk prostate cancer with rising prostate-specific antigen levels after primary local therapy: a randomized clinical trial. JAMA Oncol. 2019 May 1;5(5):623-632. Epub 2019 Jan 31. [https://jamanetwork.com/journals/jamaoncology/article-abstract/2723273 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6512307/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30703190/ PubMed] [https://clinicaltrials.gov/study/NCT00764166 NCT00764166]
+#'''PRESTO:''' Aggarwal R, Heller G, Hillman DW, Xiao H, Picus J, Taplin ME, Dorff T, Appleman L, Weckstein D, Patnaik A, Bryce A, Shevrin D, Mohler J, Anderson D, Rao A, Tagawa S, Tan A, Halabi S, Dooley K, O'Brien P, Chen R, Ryan CJ, Eggener SE, Morris MJ; EORTC-55994 Study Group. PRESTO: A Phase III, Open-Label Study of Intensification of Androgen Blockade in Patients With High-Risk Biochemically Relapsed Castration-Sensitive Prostate Cancer (AFT-19). J Clin Oncol. 2024 Apr 1;42(10):1114-1123. Epub 2024 Jan 23. [https://doi.org/10.1200/jco.23.01157 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/38261983/ PubMed] [https://clinicaltrials.gov/study/NCT03009981 NCT03009981]
-#'''ICELAND:''' Schulman C, Cornel E, Matveev V, Tammela TL, Schraml J, Bensadoun H, Warnack W, Persad R, Salagierski M, Gómez Veiga F, Baskin-Bey E, López B, Tombal B. Intermittent versus continuous androgen deprivation therapy in patients with relapsing or locally advanced prostate cancer: a phase 3b randomised study (ICELAND). Eur Urol. 2016 Apr;69(4):720-727. Epub 2015 Oct 29. [https://www.europeanurology.com/article/S0302-2838(15)00977-X/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/26520703 PubMed] NCT00378690
+==ADT, Abiraterone, Apalutamide {{#subobject:16agce |Regimen=1}}==
-#'''TOAD:''' Duchesne GM, Woo HH, Bassett JK, Bowe SJ, D'Este C, Frydenberg M, King M, Ledwich L, Loblaw A, Malone S, Millar J, Milne R, Smith RG, Spry N, Stockler M, Syme RA, Tai KH, Turner S. Timing of androgen-deprivation therapy in patients with prostate cancer with a rising PSA (TROG 03.06 and VCOG PR 01-03 [TOAD]): a randomised, multicentre, non-blinded, phase 3 trial. Lancet Oncol. 2016 Jun;17(6):727-737. Epub 2016 May 4. Erratum in: Lancet Oncol. 2016 Jun;17 (6):e223. Lancet Oncol. 2017 Sep;18(9):e510. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(16)00107-8/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/27155740 PubMed] NCT00110162
+ADT, Abiraterone, Apalutamide: '''<u>A</u>'''ndrogen '''<u>D</u>'''eprivation '''<u>T</u>'''herapy, Abiraterone, Apalutamide
-#'''RisingPSA:''' Oudard S, Latorzeff I, Caty A, Miglianico L, Sevin E, Hardy-Bessard AC, Delva R, Rolland F, Mouret L, Priou F, Beuzeboc P, Gravis G, Linassier C, Gomez P, Voog E, Muracciole X, Abraham C, Banu E, Ferrero JM, Ravaud A, Krakowski I, Lagrange JL, Deplanque G, Zylberait D, Bozec L, Houede N, Culine S, Elaidi R. Effect of adding docetaxel to androgen-deprivation therapy in patients with high-risk prostate cancer with rising prostate-specific antigen levels after primary local therapy: a randomized clinical trial. JAMA Oncol. 2019 May 1;5(5):623-632. Epub 2019 Jan 31. [https://jamanetwork.com/journals/jamaoncology/article-abstract/2723273 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6512307/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/30703190 PubMed] NCT00764166
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:#hmm5hv |Variant=1}}===
-=Hormonal therapy for non-metastatic castrate resistant disease=
-==ADT {{#subobject:68ajcbz|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
-ADT: '''<u>A</u>'''ndrogen '''<u>D</u>'''eprivation '''<u>T</u>'''herapy
-===Regimen {{#subobject:0a9b7x3|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 ! style="width: 20%" |Study
-! style="width: 20%" |Years of enrollment
+! style="width: 20%" |Dates of enrollment
 ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 ! style="width: 20%" |Comparator
 ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.nejm.org/doi/10.1056/NEJMoa1715546 Smith et al. 2017 (SPARTAN)]
+|rowspan=2|[https://doi.org/10.1200/jco.23.01157 Aggarwal et al. 2024 (PRESTO)]
-|2013-2016
+|rowspan=2|2017-03 to 2022-04
-| style="background-color:#1a9851" |Phase III (C)
+|rowspan=2 style="background-color:#1a9851" |Phase 3 (E-esc)
-|[[#ADT_.26_Apalutamide|ADT & Apalutamide]]
+|1. [[#ADT_3|ADT]]
-| style="background-color:#fc8d59" |Seems to have inferior OS<sup>1</sup>
+| style="background-color:#91cf60" |Superior PSA-PFS (primary endpoint)<br>Median PSA-PFS: 26 vs 20 mo<br>(HR 0.48, 95% CI 0.32-0.71)
 |-
-|[https://www.nejm.org/doi/full/10.1056/NEJMoa1800536 Hussain et al. 2018 (PROSPER)]
+|2. [[#ADT_.26_Apalutamide|ADT & Apalutamide]]
-|2013-2017
+| style="background-color:#d3d3d3" |Not reported
-| style="background-color:#1a9851" |Phase III (C)
-|[[#ADT_.26_Enzalutamide|ADT & Enzalutamide]]
-| style="background-color:#d73027" |Inferior MFS
-|-
-|[https://www.nejm.org/doi/full/10.1056/NEJMoa1815671 Fizazi et al. 2019 (ARAMIS)]
-|2014-2018
-| style="background-color:#1a9851" |Phase III (C)
-|[[#ADT_.26_Darolutamide|ADT & Darolutamide]]
-| style="background-color:#d73027" |Inferior OS<sup>2</sup>
 |-
 |}
-''<sup>1</sup>Reported efficacy for SPARTAN is based on the 2019 update.''<br>
+<div class="toccolours" style="background-color:#fdcdac">
-''<sup>2</sup>Reported efficacy for ARAMIS is based on the 2020 update.''<br>
+====Eligibility criteria====
-''Note: these are clinical trials that did not specify a particular drug to be used for androgen deprivation. See papers for details.''
+*Prior radical prostatectomy, castrate-sensitive biochemical recurrence with PSA at least 0.5 ng/mL, non-metastatic, PSA doubling time less than 9 months
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Endocrine therapy====
+*[[:Category:Androgen-deprivation therapy|ADT]]
+*[[Abiraterone (Zytiga)]] 1000 mg PO once per day
+*[[Apalutamide (Erleada)]] 240 mg PO once per day
+====Supportive therapy====
+*[[Prednisone (Sterapred)]] 5 mg PO once per day
+'''1-year course'''
+</div></div>
+===References===
+#'''PRESTO:''' Aggarwal R, Heller G, Hillman DW, Xiao H, Picus J, Taplin ME, Dorff T, Appleman L, Weckstein D, Patnaik A, Bryce A, Shevrin D, Mohler J, Anderson D, Rao A, Tagawa S, Tan A, Halabi S, Dooley K, O'Brien P, Chen R, Ryan CJ, Eggener SE, Morris MJ; EORTC-55994 Study Group. PRESTO: A Phase III, Open-Label Study of Intensification of Androgen Blockade in Patients With High-Risk Biochemically Relapsed Castration-Sensitive Prostate Cancer (AFT-19). J Clin Oncol. 2024 Apr 1;42(10):1114-1123. Epub 2024 Jan 23. [https://doi.org/10.1200/jco.23.01157 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/38261983/ PubMed] [https://clinicaltrials.gov/study/NCT03009981 NCT03009981]
-*[[:Category:GnRH_agonists|GnRH agonist]] or [[:Category:GnRH antagonists|GnRH antagonist]] or a history of [[Endocrine_ablation_surgery#Bilateral_orchiectomy|bilateral orchiectomy]]
+==ADT & Apalutamide {{#subobject:16fcae |Regimen=1}}==
+ADT & Apalutamide: '''<u>A</u>'''ndrogen '''<u>D</u>'''eprivation '''<u>T</u>'''herapy & Apalutamide
-'''Continued indefinitely'''
+<div class="toccolours" style="background-color:#eeeeee">
-===References===
+===Regimen {{#subobject:#e08yhv |Variant=1}}===
-#'''SPARTAN:''' Smith MR, Saad F, Chowdhury S, Oudard S, Hadaschik BA, Graff JN, Olmos D, Mainwaring PN, Lee JY, Uemura H, Lopez-Gitlitz A, Trudel GC, Espina BM, Shu Y, Park YC, Rackoff WR, Yu MK, Small EJ; SPARTAN Investigators. Apalutamide treatment and metastasis-free survival in prostate cancer. N Engl J Med. 2018 Apr 12;378(15):1408-1418. [https://www.nejm.org/doi/10.1056/NEJMoa1715546 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1715546/suppl_file/nejmoa1715546_appendix.pdf link to supplementary appendix] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/29420164 PubMed] NCT01946204
-##'''Update:''' Small EJ, Saad F, Chowdhury S, Oudard S, Hadaschik BA, Graff JN, Olmos D, Mainwaring PN, Lee JY, Uemura H, De Porre P, Smith AA, Zhang K, Lopez-Gitlitz A, Smith MR. Apalutamide and overall survival in non-metastatic castration-resistant prostate cancer. Ann Oncol. 2019 Nov 1;30(11):1813-1820. [https://doi.org/10.1093/annonc/mdz397 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6927320/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/31560066 PubMed]
-#'''PROSPER:''' Hussain M, Fizazi K, Saad F, Rathenborg P, Shore N, Ferreira U, Ivashchenko P, Demirhan E, Modelska K, Phung D, Krivoshik A, Sternberg CN. Enzalutamide in men with nonmetastatic, castration-resistant prostate cancer. N Engl J Med. 2018 Jun 28;378(26):2465-2474. [https://www.nejm.org/doi/full/10.1056/NEJMoa1800536 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/29949494 PubMed]
-#'''ARAMIS:''' Fizazi K, Shore N, Tammela TL, Ulys A, Vjaters E, Polyakov S, Jievaltas M, Luz M, Alekseev B, Kuss I, Kappeler C, Snapir A, Sarapohja T, Smith MR; ARAMIS Investigators. Darolutamide in nonmetastatic, castration-resistant prostate cancer. N Engl J Med. 2019 Mar 28;380(13):1235-1246. Epub 2019 Feb 14. [https://www.nejm.org/doi/full/10.1056/NEJMoa1815671 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/30763142 PubMed] NCT02200614
-##'''Update:''' Fizazi K, Shore N, Tammela TL, Ulys A, Vjaters E, Polyakov S, Jievaltas M, Luz M, Alekseev B, Kuss I, Le Berre MA, Petrenciuc O, Snapir A, Sarapohja T, Smith MR; ARAMIS Investigators. Nonmetastatic, Castration-Resistant Prostate Cancer and Survival with Darolutamide. N Engl J Med. 2020 Sep 10;383(11):1040-1049. [https://doi.org/10.1056/nejmoa2001342 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32905676 PubMed]
-==ADT & Apalutamide {{#subobject:a70eae |Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
-ADT & Apalutamide: '''<u>A</u>'''ndrogen '''<u>D</u>'''eprivation '''<u>T</u>'''herapy & Apalutamide
-===Regimen {{#subobject:#e085c7 |Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 ! style="width: 20%" |Study
-! style="width: 20%" |Years of enrollment
+! style="width: 20%" |Dates of enrollment
 ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 ! style="width: 20%" |Comparator
 ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.nejm.org/doi/10.1056/NEJMoa1715546 Smith et al. 2017 (SPARTAN)]
+|rowspan=2|[https://doi.org/10.1200/jco.23.01157 Aggarwal et al. 2024 (PRESTO)]
-|2013-2016
+|rowspan=2|2017-03 to 2022-04
-| style="background-color:#1a9851" |Phase III (E-RT-esc)
+|rowspan=2 style="background-color:#1a9851" |Phase 3 (E-esc)
-|[[#ADT_4|ADT]]
+|1. [[#ADT_3|ADT]]
-| style="background-color:#91cf60" |Seems to have superior OS<sup>1</sup> <br>(HR 0.75, 95% CI 0.59-0.96)
+| style="background-color:#91cf60" |Superior PSA-PFS (primary endpoint)<br>Median PSA-PFS: 24.9 vs 20.3 mo<br>(HR 0.52, 95% CI 0.35-0.77)
 |-
-|}
+|2. [[#ADT.2C_Abiraterone.2C_Apalutamide|ADT, Abiraterone, Apalutamide]]
-{| class="wikitable" style="width: 75%; text-align:center;"
+| style="background-color:#d3d3d3" |Not reported
-! style="width: 33%" |Metastasis-free survival
-! style="width: 33%" |Comparator metastasis-free survival
-! style="width: 33%" |Pt Population
-|-
-|40.5 months
-|16.2 months
-|Castrate-resistant, non-metastatic, PSA doubling time <10 months
 |-
 |}
-''<sup>1</sup>Reported efficacy is based on the 2019 update.''
+<div class="toccolours" style="background-color:#fdcdac">
+====Eligibility criteria====
+*Prior radical prostatectomy, castrate-sensitive biochemical recurrence with PSA at least 0.5 ng/mL, non-metastatic, PSA doubling time less than 9 months
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Endocrine therapy====
+*[[:Category:Androgen-deprivation therapy|ADT]]
 *[[Apalutamide (Erleada)]] 240 mg PO once per day
-*Patients should concurrently be receiving [[:Category:GnRH_agonists|GnRH analog]] or have had [[Endocrine_ablation_surgery#Bilateral_orchiectomy|bilateral orchiectomy]]
+'''1-year course'''
+</div></div>
-'''Continued indefinitely'''
 ===References===
+#'''PRESTO:''' Aggarwal R, Heller G, Hillman DW, Xiao H, Picus J, Taplin ME, Dorff T, Appleman L, Weckstein D, Patnaik A, Bryce A, Shevrin D, Mohler J, Anderson D, Rao A, Tagawa S, Tan A, Halabi S, Dooley K, O'Brien P, Chen R, Ryan CJ, Eggener SE, Morris MJ; EORTC-55994 Study Group. PRESTO: A Phase III, Open-Label Study of Intensification of Androgen Blockade in Patients With High-Risk Biochemically Relapsed Castration-Sensitive Prostate Cancer (AFT-19). J Clin Oncol. 2024 Apr 1;42(10):1114-1123. Epub 2024 Jan 23. [https://doi.org/10.1200/jco.23.01157 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/38261983/ PubMed] [https://clinicaltrials.gov/study/NCT03009981 NCT03009981]
-#'''SPARTAN:''' Smith MR, Saad F, Chowdhury S, Oudard S, Hadaschik BA, Graff JN, Olmos D, Mainwaring PN, Lee JY, Uemura H, Lopez-Gitlitz A, Trudel GC, Espina BM, Shu Y, Park YC, Rackoff WR, Yu MK, Small EJ; SPARTAN Investigators. Apalutamide treatment and metastasis-free survival in prostate cancer. N Engl J Med. 2018 Apr 12;378(15):1408-1418. [https://www.nejm.org/doi/10.1056/NEJMoa1715546 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1715546/suppl_file/nejmoa1715546_appendix.pdf link to supplementary appendix] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/29420164 PubMed] NCT01946204
+==Enzalutamide monotherapy {{#subobject:1ki2ec |Regimen=1}}==
-##'''Update:''' Small EJ, Saad F, Chowdhury S, Oudard S, Hadaschik BA, Graff JN, Olmos D, Mainwaring PN, Lee JY, Uemura H, De Porre P, Smith AA, Zhang K, Lopez-Gitlitz A, Smith MR. Apalutamide and overall survival in non-metastatic castration-resistant prostate cancer. Ann Oncol. 2019 Nov 1;30(11):1813-1820. [https://doi.org/10.1093/annonc/mdz397 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6927320/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/31560066 PubMed]
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:qnc5fc |Variant=1}}===
-==ADT & Darolutamide {{#subobject:d39ncb |Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
-===Regimen {{#subobject:#9276df |Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
-! style="width: 20%" |Study
+!style="width: 20%"|Study
-! style="width: 20%" |Years of enrollment
+!style="width: 20%"|Dates of enrollment
-! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
-! style="width: 20%" |Comparator
+!style="width: 20%"|Comparator
-! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.nejm.org/doi/full/10.1056/NEJMoa1815671 Fizazi et al. 2019 (ARAMIS)]
+|rowspan=2|[https://doi.org/10.1056/nejmoa2303974 Freedland et al. 2023 (EMBARK)]
-|2014-2018
+|rowspan=2|2015-01 to 2018-08
-| style="background-color:#1a9851" |Phase III (E-RT-esc)
+|rowspan=2 style="background-color:#1a9851" |Phase 3 (E-RT-switch-ooc)
-|[[#ADT_4|ADT]]
+|1. [[#Leuprolide_monotherapy_2|Leuprolide]]
-| style="background-color:#1a9850" |Superior OS<sup>1</sup> <br>(HR 0.69, 95% CI 0.53-0.88)
+| style="background-color:#1a9850" |Superior MFS (secondary endpoint)<br>MFS60: 80% vs 71.4%<br>(HR 0.63, 95% CI 0.43-0.87)
+|-
+|2. [[#Enzalutamide_.26_Leuprolide|Enzalutamide & Leuprolide]]
+| style="background-color:#d3d3d3" |Not reported
 |-
 |}
-''<sup>1</sup>Reported efficacy is based on the 2020 update.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Endocrine therapy====
+*[[Enzalutamide (Xtandi)]] 160 mg PO once per day
-*[[:Category:GnRH_agonists|GnRH agonist]] or [[:Category:GnRH antagonists|GnRH antagonist]]
-*[[Darolutamide (Nubeqa)]] 600 mg PO twice per day
 '''Continued indefinitely'''
+</div></div>
 ===References===
+#'''EMBARK:''' Freedland SJ, de Almeida Luz M, De Giorgi U, Gleave M, Gotto GT, Pieczonka CM, Haas GP, Kim CS, Ramirez-Backhaus M, Rannikko A, Tarazi J, Sridharan S, Sugg J, Tang Y, Tutrone RF Jr, Venugopal B, Villers A, Woo HH, Zohren F, Shore ND. Improved Outcomes with Enzalutamide in Biochemically Recurrent Prostate Cancer. N Engl J Med. 2023 Oct 19;389(16):1453-1465. [https://doi.org/10.1056/nejmoa2303974 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/37851874/ PubMed] [https://clinicaltrials.gov/study/NCT02319837 NCT02319837]
+##'''HRQoL analysis:''' Freedland SJ, Gleave M, De Giorgi U, Rannikko A, Pieczonka CM, Tutrone RF, Venugopal B, Woo HH, Ramirez-Backhaus M, Supiot S, Lantz A, Ganguli A, Ivanova J, Kral P, Huang SP, Saad F, Shore ND. Enzalutamide and Quality of Life in Biochemically Recurrent Prostate Cancer. NEJM Evidence. 2023 Dec;2(12):EVIDoa2300251. Epub 2023 Oct 22. [https://doi.org/10.1056/evidoa2300251 link to original article] [https://pubmed.ncbi.nlm.nih.gov/38320501/ PubMed]
-#'''ARAMIS:''' Fizazi K, Shore N, Tammela TL, Ulys A, Vjaters E, Polyakov S, Jievaltas M, Luz M, Alekseev B, Kuss I, Kappeler C, Snapir A, Sarapohja T, Smith MR; ARAMIS Investigators. Darolutamide in nonmetastatic, castration-resistant prostate cancer. N Engl J Med. 2019 Mar 28;380(13):1235-1246. Epub 2019 Feb 14. [https://www.nejm.org/doi/full/10.1056/NEJMoa1815671 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/30763142 PubMed] NCT02200614
+==Enzalutamide & Leuprolide {{#subobject:ut22ec |Regimen=1}}==
-##'''Update:''' Fizazi K, Shore N, Tammela TL, Ulys A, Vjaters E, Polyakov S, Jievaltas M, Luz M, Alekseev B, Kuss I, Le Berre MA, Petrenciuc O, Snapir A, Sarapohja T, Smith MR; ARAMIS Investigators. Nonmetastatic, Castration-Resistant Prostate Cancer and Survival with Darolutamide. N Engl J Med. 2020 Sep 10;383(11):1040-1049. [https://doi.org/10.1056/nejmoa2001342 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32905676 PubMed]
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:qni2cb |Variant=1}}===
-==ADT & Enzalutamide {{#subobject:d34e0b |Regimen=1}}==
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-{| class="wikitable" style="float:right; margin-left: 5px;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[[#top|back to top]]
+|rowspan=2|[https://doi.org/10.1056/nejmoa2303974 Freedland et al. 2023 (EMBARK)]
-|}
+|rowspan=2|2015-01 to 2018-08
-ADT & Enzalutamide: '''<u>A</u>'''ndrogen '''<u>D</u>'''eprivation '''<u>T</u>'''herapy & Enzalutamide
+|rowspan=2 style="background-color:#1a9851" |Phase 3 (E-RT-esc)
-===Regimen {{#subobject:#80614f |Variant=1}}===
+|1. [[#Leuprolide_monotherapy_2|Leuprolide]]
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
+| style="background-color:#1a9850" |Superior MFS (primary endpoint)<br>MFS60: 87.3% vs 71.4%<br>(HR 0.42, 95% CI 0.30-0.61)
-! style="width: 20%" |Study
-! style="width: 20%" |Years of enrollment
-! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
-! style="width: 20%" |Comparator
-! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.nejm.org/doi/full/10.1056/NEJMoa1800536 Hussain et al. 2018 (PROSPER)]
+|2. [[#Enzalutamide_monotherapy_2|Enzalutamide]]
-|2013-2017
+| style="background-color:#d3d3d3" |Not reported
-| style="background-color:#1a9851" |Phase III (E-RT-esc)
-|[[#ADT_4|ADT]]
-| style="background-color:#1a9850" |Superior MFS
 |-
 |}
-''Patients had castrate-resistant, non-metastatic, prostate cancer with PSA doubling time less than 10 months.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Endocrine therapy====
+*[[Enzalutamide (Xtandi)]] 160 mg PO once per day on days 1 to 84
-*[[Enzalutamide (Xtandi)]] 160 mg PO once per day
+*[[Leuprolide (Lupron)|Leuprolide (Lupron) 3-month depot]] 22.5 mg IM once on day 1
-*Patients should concurrently be receiving [[:Category:GnRH_agonists|GnRH agonist]] or [[:Category:GnRH antagonists|GnRH antagonist]] or have had [[Endocrine_ablation_surgery#Bilateral_orchiectomy|bilateral orchiectomy]]
+'''84-day cycles'''
+</div></div>
-'''Continued indefinitely'''
 ===References===
+#'''EMBARK:''' Freedland SJ, de Almeida Luz M, De Giorgi U, Gleave M, Gotto GT, Pieczonka CM, Haas GP, Kim CS, Ramirez-Backhaus M, Rannikko A, Tarazi J, Sridharan S, Sugg J, Tang Y, Tutrone RF Jr, Venugopal B, Villers A, Woo HH, Zohren F, Shore ND. Improved Outcomes with Enzalutamide in Biochemically Recurrent Prostate Cancer. N Engl J Med. 2023 Oct 19;389(16):1453-1465. [https://doi.org/10.1056/nejmoa2303974 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/37851874/ PubMed] [https://clinicaltrials.gov/study/NCT02319837 NCT02319837]
+##'''HRQoL analysis:''' Freedland SJ, Gleave M, De Giorgi U, Rannikko A, Pieczonka CM, Tutrone RF, Venugopal B, Woo HH, Ramirez-Backhaus M, Supiot S, Lantz A, Ganguli A, Ivanova J, Kral P, Huang SP, Saad F, Shore ND. Enzalutamide and Quality of Life in Biochemically Recurrent Prostate Cancer. NEJM Evidence. 2023 Dec;2(12):EVIDoa2300251. Epub 2023 Oct 22. [https://doi.org/10.1056/evidoa2300251 link to original article] [https://pubmed.ncbi.nlm.nih.gov/38320501/ PubMed]
-#'''PROSPER:''' Hussain M, Fizazi K, Saad F, Rathenborg P, Shore N, Ferreira U, Ivashchenko P, Demirhan E, Modelska K, Phung D, Krivoshik A, Sternberg CN. Enzalutamide in men with nonmetastatic, castration-resistant prostate cancer. N Engl J Med. 2018 Jun 28;378(26):2465-2474. [https://www.nejm.org/doi/full/10.1056/NEJMoa1800536 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/29949494 PubMed]
+==Leuprolide monotherapy {{#subobject:127yec |Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
-=Hormonal therapy for metastatic or locally advanced disease=
+===Regimen {{#subobject:5gq5fc |Variant=1}}===
-==ADT {{#subobject:45fc98|Regimen=1}}==
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-{| class="wikitable" style="float:right; margin-left: 5px;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1056/nejmoa2303974 Freedland et al. 2023 (EMBARK)]
+|2015-01 to 2018-08
+| style="background-color:#1a9851" |Phase 3 (C)
+|1. [[#Enzalutamide_.26_Leuprolide|Enzalutamide & Leuprolide]]<br>2. [[#Enzalutamide_monotherapy|Enzalutamide]]
+| style="background-color:#d73027" |Inferior MFS
 |-
-|[[#top|back to top]]
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Endocrine therapy====
+*[[Leuprolide (Lupron)|Leuprolide (Lupron) 3-month depot]] 22.5 mg IM once on day 1
+'''84-day cycles'''
+</div></div>
+===References===
+#'''EMBARK:''' Freedland SJ, de Almeida Luz M, De Giorgi U, Gleave M, Gotto GT, Pieczonka CM, Haas GP, Kim CS, Ramirez-Backhaus M, Rannikko A, Tarazi J, Sridharan S, Sugg J, Tang Y, Tutrone RF Jr, Venugopal B, Villers A, Woo HH, Zohren F, Shore ND. Improved Outcomes with Enzalutamide in Biochemically Recurrent Prostate Cancer. N Engl J Med. 2023 Oct 19;389(16):1453-1465. [https://doi.org/10.1056/nejmoa2303974 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/37851874/ PubMed] [https://clinicaltrials.gov/study/NCT02319837 NCT02319837]
+##'''HRQoL analysis:''' Freedland SJ, Gleave M, De Giorgi U, Rannikko A, Pieczonka CM, Tutrone RF, Venugopal B, Woo HH, Ramirez-Backhaus M, Supiot S, Lantz A, Ganguli A, Ivanova J, Kral P, Huang SP, Saad F, Shore ND. Enzalutamide and Quality of Life in Biochemically Recurrent Prostate Cancer. NEJM Evidence. 2023 Dec;2(12):EVIDoa2300251. Epub 2023 Oct 22. [https://doi.org/10.1056/evidoa2300251 link to original article] [https://pubmed.ncbi.nlm.nih.gov/38320501/ PubMed]
+=Hormonal therapy for non-metastatic castrate resistant disease=
+==ADT {{#subobject:68ajcbz|Regimen=1}}==
 ADT: '''<u>A</u>'''ndrogen '''<u>D</u>'''eprivation '''<u>T</u>'''herapy
-===Regimen {{#subobject:bd66bd|Variant=1}}===
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:0a9b7x3|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 ! style="width: 20%" |Study
-! style="width: 20%" |Years of enrollment
+! style="width: 20%" |Dates of enrollment
 ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 ! style="width: 20%" |Comparator
 ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.auajournals.org/doi/full/10.1097/01.ju.0000135742.13171.d2 Schröder et al. 2004 (EORTC 30846)]
+|[https://doi.org/10.1056/NEJMoa1715546 Smith et al. 2017 (SPARTAN)]
-|1986-1998
+|2013-2016
-| style="background-color:#1a9851" |Phase III (C)
+| style="background-color:#1a9851" |Phase 3 (C)
-|Delayed ADT
+|[[#ADT_.26_Apalutamide_2|ADT & Apalutamide]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+| style="background-color:#fc8d59" |Seems to have inferior OS<sup>1</sup>
 |-
-|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00011-X/fulltext Fizazi et al. 2015 (GETUG 12)]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8288034/ Hussain et al. 2018 (PROSPER<sub>PrCA</sub>)]
-|2002-2006
+|2013-2017
-| style="background-color:#1a9851" |Phase III (C)
+| style="background-color:#1a9851" |Phase 3 (C)
-|[[#ADT.2C_Docetaxel.2C_Estramustine|ADT, Docetaxel, Estramustine]]
+|[[#ADT_.26_Enzalutamide|ADT & Enzalutamide]]
-| style="background-color:#fc8d59" |Seems to have inferior RFS
+| style="background-color:#d73027" |Inferior OS<sup>2</sup>
 |-
-|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(12)70560-0/fulltext Gravis et al. 2013 (GETUG-AFU 15)]
+|[https://doi.org/10.1056/NEJMoa1815671 Fizazi et al. 2019 (ARAMIS)]
-|2004-2008
+|2014-2018
-| style="background-color:#1a9851" |Phase III (C)
+| style="background-color:#1a9851" |Phase 3 (C)
-|[[#ADT_.26_Docetaxel|ADT & Docetaxel]]
+|[[#ADT_.26_Darolutamide|ADT & Darolutamide]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+| style="background-color:#d73027" |Inferior OS<sup>3</sup>
-|-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3398767/ James et al. 2012 (STAMPEDE)]
-|2005-2011
-| style="background-color:#1a9851" |Phase III (C)
-|ADT & Celecoxib
-| style="background-color:#ffffbf" |Did not meet intermediate primary endpoint of FFS
-|-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4800035/ James et al. 2015 (STAMPEDE)]
-|2005-2011
-| style="background-color:#1a9851" |Phase III (C)
-|[[#ADT_.26_Docetaxel|ADT & Docetaxel]]
-| style="background-color:#d73027" |Inferior OS
-|-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5533216 James et al. 2017 (STAMPEDE)]
-|2005-2011
-| style="background-color:#1a9851" |Phase III (C)
-|[[#ADT_.26_Abiraterone|ADT & Abiraterone]]
-| style="background-color:#d73027" |Inferior OS
-|-
-|[http://www.ncbi.nlm.nih.gov/pmc/articles/pmc4562797/ Sweeney et al. 2015 (CHAARTED)]
-|2006-2012
-| style="background-color:#1a9851" |Phase III (C)
-|[[#ADT_.26_Docetaxel|ADT & Docetaxel]]
-| style="background-color:#d73027" |Inferior OS<sup>1</sup>
-|-
-|[https://link.springer.com/article/10.1007%2Fs10147-016-1037-2 Kamba et al. 2016 (ZAPCA)]
-|2008-2010
-| style="background-color:#1a9851" |Phase III (C)
-|ADT & Zoledronic acid
-| style="background-color:#fee08b" |Might have inferior TTTF
-|-
-|[https://www.nejm.org/doi/full/10.1056/NEJMoa1704174 Fizazi et al. 2017 (LATITUDE)]
-|2013-2014
-| style="background-color:#1a9851" |Phase III (C)
-|[[#ADT_.26_Abiraterone|ADT & Abiraterone]]
-| style="background-color:#d73027" |Inferior OS
 |-
 |}
-''<sup>1</sup>In the 2018 update of CHAARTED, only patients with high-volume disease had inferior survival in the control arm.''<br>
+''<sup>1</sup>Reported efficacy for SPARTAN is based on the 2020 update.''<br>
-''Note: these are clinical trials that did not specify a particular therapy to be used for androgen deprivation. See papers for details; the below are examples.''
+''<sup>2</sup>Reported efficacy for PROSPER is based on the 2020 update.''<br>
+''<sup>3</sup>Reported efficacy for ARAMIS is based on the 2020 update.''<br>
+''Note: these are clinical trials that did not specify a particular approach for androgen deprivation. See papers for details.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Endocrine therapy====
+*[[:Category:Androgen-deprivation therapy|ADT]]
-*ADT with ONE of the following:
-**[[:Category:GnRH agonists|LHRH agonist/analogue]]
-**[[:Category:GnRH antagonists|LHRH antagonist]]
-**[[Endocrine_ablation_surgery#Bilateral_orchiectomy|Bilateral orchiectomy]]
 '''Continued indefinitely'''
+</div></div>
 ===References===
+#'''SPARTAN:''' Smith MR, Saad F, Chowdhury S, Oudard S, Hadaschik BA, Graff JN, Olmos D, Mainwaring PN, Lee JY, Uemura H, Lopez-Gitlitz A, Trudel GC, Espina BM, Shu Y, Park YC, Rackoff WR, Yu MK, Small EJ; SPARTAN Investigators. Apalutamide treatment and metastasis-free survival in prostate cancer. N Engl J Med. 2018 Apr 12;378(15):1408-1418. Epub 2018 Feb 8. [https://doi.org/10.1056/NEJMoa1715546 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1715546/suppl_file/nejmoa1715546_appendix.pdf link to supplementary appendix] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/29420164/ PubMed] [https://clinicaltrials.gov/study/NCT01946204 NCT01946204]
+##'''HRQoL analysis:''' Saad F, Cella D, Basch E, Hadaschik BA, Mainwaring PN, Oudard S, Graff JN, McQuarrie K, Li S, Hudgens S, Lawson J, Lopez-Gitlitz A, Yu MK, Smith MR, Small EJ. Effect of apalutamide on health-related quality of life in patients with non-metastatic castration-resistant prostate cancer: an analysis of the SPARTAN randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2018 Oct;19(10):1404-1416. Epub 2018 Sep 10. [https://doi.org/10.1016/s1470-2045(18)30456-x link to original article] [https://pubmed.ncbi.nlm.nih.gov/30213449/ PubMed]
+##'''Update:''' Small EJ, Saad F, Chowdhury S, Oudard S, Hadaschik BA, Graff JN, Olmos D, Mainwaring PN, Lee JY, Uemura H, De Porre P, Smith AA, Zhang K, Lopez-Gitlitz A, Smith MR. Apalutamide and overall survival in non-metastatic castration-resistant prostate cancer. Ann Oncol. 2019 Nov 1;30(11):1813-1820. [https://doi.org/10.1093/annonc/mdz397 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6927320/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31560066/ PubMed]
+##'''Update:''' Smith MR, Saad F, Chowdhury S, Oudard S, Hadaschik BA, Graff JN, Olmos D, Mainwaring PN, Lee JY, Uemura H, De Porre P, Smith AA, Brookman-May SD, Li S, Zhang K, Rooney B, Lopez-Gitlitz A, Small EJ. Apalutamide and Overall Survival in Prostate Cancer. Eur Urol. 2021 Jan;79(1):150-158. Epub 2020 Sep 6. [https://doi.org/10.1016/j.eururo.2020.08.011 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32907777/ PubMed]
+#'''PROSPER<sub>PrCA</sub>:''' Hussain M, Fizazi K, Saad F, Rathenborg P, Shore N, Ferreira U, Ivashchenko P, Demirhan E, Modelska K, Phung D, Krivoshik A, Sternberg CN. Enzalutamide in men with nonmetastatic, castration-resistant prostate cancer. N Engl J Med. 2018 Jun 28;378(26):2465-2474. [https://doi.org/10.1056/NEJMoa1800536 link to original article] '''contains dosing details in abstract''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8288034/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29949494/ PubMed] [https://clinicaltrials.gov/study/NCT02003924 NCT02003924]
+##'''Update:''' Sternberg CN, Fizazi K, Saad F, Shore ND, De Giorgi U, Penson DF, Ferreira U, Efstathiou E, Madziarska K, Kolinsky MP, Cubero DIG, Noerby B, Zohren F, Lin X, Modelska K, Sugg J, Steinberg J, Hussain M; PROSPER Investigators. Enzalutamide and Survival in Nonmetastatic, Castration-Resistant Prostate Cancer. N Engl J Med. 2020 Jun 4;382(23):2197-2206. Epub 2020 May 29. [https://doi.org/10.1056/nejmoa2003892 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32469184/ PubMed]
+#'''ARAMIS:''' Fizazi K, Shore N, Tammela TL, Ulys A, Vjaters E, Polyakov S, Jievaltas M, Luz M, Alekseev B, Kuss I, Kappeler C, Snapir A, Sarapohja T, Smith MR; ARAMIS Investigators. Darolutamide in nonmetastatic, castration-resistant prostate cancer. N Engl J Med. 2019 Mar 28;380(13):1235-1246. Epub 2019 Feb 14. [https://doi.org/10.1056/NEJMoa1815671 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30763142/ PubMed] [https://clinicaltrials.gov/study/NCT02200614 NCT02200614]
+##'''Update:''' Fizazi K, Shore N, Tammela TL, Ulys A, Vjaters E, Polyakov S, Jievaltas M, Luz M, Alekseev B, Kuss I, Le Berre MA, Petrenciuc O, Snapir A, Sarapohja T, Smith MR; ARAMIS Investigators. Nonmetastatic, Castration-Resistant Prostate Cancer and Survival with Darolutamide. N Engl J Med. 2020 Sep 10;383(11):1040-1049. [https://doi.org/10.1056/nejmoa2001342 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32905676/ PubMed]
-#'''EORTC 30846:''' Schröder FH, Kurth KH, Fosså SD, Hoekstra W, Karthaus PP, Debois M, Collette L; European Organisation for the Research and Treatment of Cancer Genito-urinary Group. Early versus delayed endocrine treatment of pN1-3 M0 prostate cancer without local treatment of the primary tumor: results of European Organisation for the Research and Treatment of Cancer 30846--a phase III study. J Urol. 2004 Sep;172(3):923-7. [https://www.auajournals.org/doi/full/10.1097/01.ju.0000135742.13171.d2 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15310999 PubMed]
+==ADT & Apalutamide {{#subobject:a70eae |Regimen=1}}==
-#'''STAMPEDE:''' James ND, Sydes MR, Mason MD, Clarke NW, Anderson J, Dearnaley DP, Dwyer J, Jovic G, Ritchie AW, Russell JM, Sanders K, Thalmann GN, Bertelli G, Birtle AJ, O'Sullivan JM, Protheroe A, Sheehan D, Srihari N, Parmar MK; STAMPEDE Investigators. Celecoxib plus hormone therapy versus hormone therapy alone for hormone-sensitive prostate cancer: first results from the STAMPEDE multiarm, multistage, randomised controlled trial. Lancet Oncol. 2012 May;13(5):549-58. Epub 2012 Mar 26. Erratum in: Lancet Oncol. 2013 Jan;14(1):e5. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(12)70088-8/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3398767/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/22452894 PubMed] NCT00268476
+ADT & Apalutamide: '''<u>A</u>'''ndrogen '''<u>D</u>'''eprivation '''<u>T</u>'''herapy & Apalutamide
-#'''GETUG-AFU 15:''' 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. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(12)70560-0/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/23306100 PubMed] NCT00104715
+<div class="toccolours" style="background-color:#eeeeee">
-##'''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. [http://www.europeanurology.com/article/S0302-2838(15)01103-3/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/26610858 PubMed]
+===Regimen {{#subobject:#e085c7 |Variant=1}}===
-#'''GETUG 12:''' Fizazi K, Faivre L, Lesaunier F, Delva R, Gravis G, Rolland F, Priou F, Ferrero JM, Houede N, Mourey L, Theodore C, Krakowski I, Berdah JF, Baciuchka M, Laguerre B, Fléchon A, Ravaud A, Cojean-Zelek I, Oudard S, Labourey JL, Chinet-Charrot P, Legouffe E, Lagrange JL, Linassier C, Deplanque G, Beuzeboc P, Davin JL, Martin AL, Habibian M, Laplanche A, Culine S. Androgen deprivation therapy plus docetaxel and estramustine versus androgen deprivation therapy alone for high-risk localised prostate cancer (GETUG 12): a phase 3 randomised controlled trial. Lancet Oncol. 2015 Jul;16(7):787-94. Epub 2015 May 28. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00011-X/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/26028518 PubMed] NCT00055731
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-#'''CHAARTED:''' 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. [https://www.nejm.org/doi/full/10.1056/NEJMoa1503747 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pmc/articles/pmc4562797/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26244877 Pubmed] NCT00309985
-##'''Update:''' Kyriakopoulos CE, Chen YH, Carducci MA, Liu G, Jarrard DF, Hahn NM, Shevrin DH, Dreicer R, Hussain M, Eisenberger M, Kohli M, Plimack ER, Vogelzang NJ, Picus J, Cooney MM, Garcia JA, DiPaola RS, Sweeney CJ. Chemohormonal therapy in metastatic hormone-sensitive prostate cancer: long-term survival analysis of the randomized phase III E3805 CHAARTED trial. J Clin Oncol. 2018 Apr 10;36(11):1080-1087. Epub 2018 Jan 31. [https://doi.org/10.1200/JCO.2017.75.3657 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5891129/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/29384722 PubMed]
-##'''QoL analysis:''' Morgans AK, Chen YH, Sweeney CJ, Jarrard DF, Plimack ER, Gartrell BA, Carducci MA, Hussain M, Garcia JA, Cella D, DiPaola RS, Patrick-Miller LJ. Quality of life during treatment with chemohormonal therapy: analysis of E3805 chemohormonal androgen ablation randomized trial in prostate cancer. J Clin Oncol. 2018 Apr 10;36(11):1088-1095. Epub 2018 Mar 9. [https://doi.org/10.1200/JCO.2017.75.3335 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5891128/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/29522362 PubMed]
-#'''STAMPEDE:''' 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. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)01037-5/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4800035/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/26719232 PubMed] NCT00268476
-##'''Update:''' Clarke NW, Ali A, Ingleby FC, Hoyle A, Amos CL, Attard G, Brawley CD, Calvert J, Chowdhury S, Cook A, Cross W, Dearnaley DP, Douis H, Gilbert D, Gillessen S, Jones RJ, Langley RE, MacNair A, Malik Z, Mason MD, Matheson D, Millman R, Parker CC, Ritchie AWS, Rush H, Russell JM, Brown J, Beesley S, Birtle A, Capaldi L, Gale J, Gibbs S, Lydon A, Nikapota A, Omlin A, O'Sullivan JM, Parikh O, Protheroe A, Rudman S, Srihari NN, Simms M, Tanguay JS, Tolan S, Wagstaff J, Wallace J, Wylie J, Zarkar A, Sydes MR, Parmar MKB, James ND. Addition of docetaxel to hormonal therapy in low- and high-burden metastatic hormone sensitive prostate cancer: long-term survival results from the STAMPEDE trial. Ann Oncol. 2019 Dec 1;30(12):1992-2003. [https://doi.org/10.1093/annonc/mdz396 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6938598/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/31560068 PubMed]
-#'''ZAPCA:''' Kamba T, Kamoto T, Maruo S, Kikuchi T, Shimizu Y, Namiki S, Fujimoto K, Kawanishi H, Sato F, Narita S, Satoh T, Saito H, Sugimoto M, Teishima J, Masumori N, Egawa S, Sakai H, Okada Y, Terachi T, Ogawa O; ZAPCA Study Group. A phase III multicenter, randomized, controlled study of combined androgen blockade with versus without zoledronic acid in prostate cancer patients with metastatic bone disease: results of the ZAPCA trial. Int J Clin Oncol. 2017 Feb;22(1):166-173. Epub 2016 Sep 10. [https://link.springer.com/article/10.1007%2Fs10147-016-1037-2 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/27614621 PubMed] NCT00685646
-#'''STAMPEDE:''' 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. [https://www.nejm.org/doi/full/10.1056/NEJMoa1702900 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5533216 link to PMC article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1702900/suppl_file/nejmoa1702900_protocol.pdf supplementary protocol] '''contains verified protocol in supplement''' [https://www.ncbi.nlm.nih.gov/pubmed/28578639 PubMed] NCT00268476
-#'''LATITUDE:''' 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. [https://www.nejm.org/doi/full/10.1056/NEJMoa1704174 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1704174/suppl_file/nejmoa1704174_protocol.pdf supplementary protocol] '''contains verified protocol in supplement''' [https://www.ncbi.nlm.nih.gov/pubmed/28578607 PubMed]
-##'''HRQoL analysis:''' Chi KN, Protheroe A, Rodríguez-Antolín A, Facchini G, Suttman H, Matsubara N, Ye Z, Keam B, Damião R, Li T, McQuarrie K, Jia B, De Porre P, Martin J, Todd MB, Fizazi K. Patient-reported outcomes following abiraterone acetate plus prednisone added to androgen deprivation therapy in patients with newly diagnosed metastatic castration-naive prostate cancer (LATITUDE): an international, randomised phase 3 trial. Lancet Oncol. 2018 Feb;19(2):194-206. Epub 2018 Jan 8. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30911-7/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/29326030 PubMed]
-##'''Update:''' Fizazi K, Tran N, Fein L, Matsubara N, Rodriguez-Antolin A, Alekseev BY, Özgüroğlu M, Ye D, Feyerabend S, Protheroe A, Sulur G, Luna Y, Li S, Mundle S, Chi KN. Abiraterone acetate plus prednisone in patients with newly diagnosed high-risk metastatic castration-sensitive prostate cancer (LATITUDE): final overall survival analysis of a randomised, double-blind, phase 3 trial. Lancet Oncol. 2019 May;20(5):686-700. Epub 2019 Apr 12. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(19)30082-8/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/30987939 PubMed]
-==ADT & Abiraterone {{#subobject:02afb7|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
-ADT & Abiraterone: '''<u>A</u>'''ndrogen '''<u>D</u>'''eprivation '''<u>T</u>'''herapy & Abiraterone
-===Regimen {{#subobject:31ffca|Variant=1}}===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
 ! style="width: 20%" |Study
-! style="width: 20%" |Years of enrollment
+! style="width: 20%" |Dates of enrollment
 ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 ! style="width: 20%" |Comparator
 ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5533216 James et al. 2017 (STAMPEDE)]
+|[https://doi.org/10.1056/NEJMoa1715546 Smith et al. 2017 (SPARTAN)]
-|2005-2011
+<!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
-| style="background-color:#1a9851" |Phase III (E-esc)
+|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-176-1 <span style="color:white;">ESMO-MCBS (4)</span>]'''
-|[[#ADT_4|ADT]]
-| style="background-color:#1a9850" |Superior OS
 |-
-|[https://www.nejm.org/doi/full/10.1056/NEJMoa1704174 Fizazi et al. 2017 (LATITUDE)]
+|} -->
-|2013-2014
+|2013-2016
-| style="background-color:#1a9851" |Phase III (E-RT-esc)
+| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
 |[[#ADT_4|ADT]]
-| style="background-color:#1a9850" |Superior OS
+| style="background-color:#91cf60" |Superior MFS (primary endpoint)<br>Median MFS: 40.5 vs 16.2 mo<br>(HR 0.28, 95% CI 0.23-0.35)<br><br>Seems to have superior OS<sup>1</sup> (secondary endpoint)<br>Median OS: 73.9 vs 59.9 mo<br>(HR 0.78, 95% CI 0.64-0.96)
 |-
 |}
-''Note: while LATITUDE allowed for a dose increase in prednisone, the FDA recommended dose is 5 mg PO once per day.''
+''<sup>1</sup>Reported efficacy is based on the 2020 update.''
+<div class="toccolours" style="background-color:#fdcdac">
+====Eligibility criteria====
+*Castrate-resistant, non-metastatic, PSA doubling time less than 10 months
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Endocrine therapy====
+*[[Apalutamide (Erleada)]] 240 mg PO once per day
-*[[Abiraterone (Zytiga)]] 1000 mg PO once per day
+*Patients should concurrently be receiving [[:Category:GnRH_agonists|GnRH analog]] or have had [[Bilateral_orchiectomy|bilateral orchiectomy]]
-*ADT with ONE of the following:
+'''Continued indefinitely'''
-**[[:Category:GnRH agonists|LHRH agonist/analogue]]
+</div></div>
-**'''STAMPEDE only:''' [[:Category:GnRH antagonists|LHRH antagonist]]
-**[[Endocrine_ablation_surgery#Bilateral_orchiectomy|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 indefinitely unless radiotherapy planned, in which case continued for up to 2 years'''
 ===References===
+#'''SPARTAN:''' Smith MR, Saad F, Chowdhury S, Oudard S, Hadaschik BA, Graff JN, Olmos D, Mainwaring PN, Lee JY, Uemura H, Lopez-Gitlitz A, Trudel GC, Espina BM, Shu Y, Park YC, Rackoff WR, Yu MK, Small EJ; SPARTAN Investigators. Apalutamide treatment and metastasis-free survival in prostate cancer. N Engl J Med. 2018 Apr 12;378(15):1408-1418. Epub 2018 Feb 8. [https://doi.org/10.1056/NEJMoa1715546 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1715546/suppl_file/nejmoa1715546_appendix.pdf link to supplementary appendix] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/29420164/ PubMed] [https://clinicaltrials.gov/study/NCT01946204 NCT01946204]
+##'''HRQoL analysis:''' Saad F, Cella D, Basch E, Hadaschik BA, Mainwaring PN, Oudard S, Graff JN, McQuarrie K, Li S, Hudgens S, Lawson J, Lopez-Gitlitz A, Yu MK, Smith MR, Small EJ. Effect of apalutamide on health-related quality of life in patients with non-metastatic castration-resistant prostate cancer: an analysis of the SPARTAN randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2018 Oct;19(10):1404-1416. Epub 2018 Sep 10. [https://doi.org/10.1016/s1470-2045(18)30456-x link to original article] [https://pubmed.ncbi.nlm.nih.gov/30213449/ PubMed]
+##'''Update:''' Small EJ, Saad F, Chowdhury S, Oudard S, Hadaschik BA, Graff JN, Olmos D, Mainwaring PN, Lee JY, Uemura H, De Porre P, Smith AA, Zhang K, Lopez-Gitlitz A, Smith MR. Apalutamide and overall survival in non-metastatic castration-resistant prostate cancer. Ann Oncol. 2019 Nov 1;30(11):1813-1820. [https://doi.org/10.1093/annonc/mdz397 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6927320/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31560066/ PubMed]
+##'''Update:''' Smith MR, Saad F, Chowdhury S, Oudard S, Hadaschik BA, Graff JN, Olmos D, Mainwaring PN, Lee JY, Uemura H, De Porre P, Smith AA, Brookman-May SD, Li S, Zhang K, Rooney B, Lopez-Gitlitz A, Small EJ. Apalutamide and Overall Survival in Prostate Cancer. Eur Urol. 2021 Jan;79(1):150-158. Epub 2020 Sep 6. [https://doi.org/10.1016/j.eururo.2020.08.011 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32907777/ PubMed]
-#'''STAMPEDE:''' 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. [https://www.nejm.org/doi/full/10.1056/NEJMoa1702900 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5533216 link to PMC article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1702900/suppl_file/nejmoa1702900_protocol.pdf supplementary protocol] '''contains verified protocol in supplement''' [https://www.ncbi.nlm.nih.gov/pubmed/28578639 PubMed] NCT00268476
+==ADT & Darolutamide {{#subobject:d39ncb |Regimen=1}}==
-#'''LATITUDE:''' 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. [https://www.nejm.org/doi/full/10.1056/NEJMoa1704174 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1704174/suppl_file/nejmoa1704174_protocol.pdf supplementary protocol] '''contains verified protocol in supplement''' [https://www.ncbi.nlm.nih.gov/pubmed/28578607 PubMed]
+<div class="toccolours" style="background-color:#eeeeee">
-##'''HRQoL analysis:''' Chi KN, Protheroe A, Rodríguez-Antolín A, Facchini G, Suttman H, Matsubara N, Ye Z, Keam B, Damião R, Li T, McQuarrie K, Jia B, De Porre P, Martin J, Todd MB, Fizazi K. Patient-reported outcomes following abiraterone acetate plus prednisone added to androgen deprivation therapy in patients with newly diagnosed metastatic castration-naive prostate cancer (LATITUDE): an international, randomised phase 3 trial. Lancet Oncol. 2018 Feb;19(2):194-206. Epub 2018 Jan 8. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30911-7/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/29326030 PubMed]
+===Regimen {{#subobject:#9276df |Variant=1}}===
-##'''Update:''' Fizazi K, Tran N, Fein L, Matsubara N, Rodriguez-Antolin A, Alekseev BY, Özgüroğlu M, Ye D, Feyerabend S, Protheroe A, Sulur G, Luna Y, Li S, Mundle S, Chi KN. Abiraterone acetate plus prednisone in patients with newly diagnosed high-risk metastatic castration-sensitive prostate cancer (LATITUDE): final overall survival analysis of a randomised, double-blind, phase 3 trial. Lancet Oncol. 2019 May;20(5):686-700. Epub 2019 Apr 12. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(19)30082-8/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/30987939 PubMed]
-==ADT & Apalutamide {{#subobject:02eac3|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
-ADT & Apalutamide: '''<u>A</u>'''ndrogen '''<u>D</u>'''eprivation '''<u>T</u>'''herapy & Apalutamide
-===Regimen {{#subobject:31baz9|Variant=1}}===
-{| class="wikitable" style="color:white; background-color:#404040"
-|<small>'''FDA-recommended dose'''</small>
-|-
-|}
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 ! style="width: 20%" |Study
-! style="width: 20%" |Years of enrollment
+! style="width: 20%" |Dates of enrollment
 ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 ! style="width: 20%" |Comparator
 ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.nejm.org/doi/full/10.1056/NEJMoa1903307 Chi et al. 2019 (TITAN<sub>prostate</sub>)]
+|[https://doi.org/10.1056/NEJMoa1815671 Fizazi et al. 2019 (ARAMIS)]
-|2015-2017
+<!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
-| style="background-color:#1a9851" |Phase III (E-RT-esc)
+|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-183-1 <span style="color:white;">ESMO-MCBS (3)</span>]'''
+|-
+|} -->
+|2014-2018
+| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
 |[[#ADT_4|ADT]]
-| style="background-color:#1a9850" |Superior OS
+| style="background-color:#1a9850" |Superior OS<sup>1</sup> (secondary endpoint)<br>OS36: 83% vs 77%<br>(HR 0.69, 95% CI 0.53-0.88)<br><br>Superior MFS (primary endpoint)<br>Median MFS: 40.4 vs 18.4 mo<br>(HR 0.41, 95% CI 0.34-0.50)
 |-
 |}
-''Note: there are several other trials in other cancer subtypes named TITAN.''
+''<sup>1</sup>Reported efficacy is based on the 2020 update.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Endocrine therapy====
+*[[:Category:GnRH_agonists|GnRH agonist]] or [[:Category:GnRH antagonists|GnRH antagonist]]
-*[[Apalutamide (Erleada)]] 240 mg PO once per day
+*[[Darolutamide (Nubeqa)]] 600 mg PO twice per day
-*[[:Category:GnRH agonists|LHRH agonist/analogue]]
 '''Continued indefinitely'''
+</div></div>
 ===References===
+#'''ARAMIS:''' Fizazi K, Shore N, Tammela TL, Ulys A, Vjaters E, Polyakov S, Jievaltas M, Luz M, Alekseev B, Kuss I, Kappeler C, Snapir A, Sarapohja T, Smith MR; ARAMIS Investigators. Darolutamide in nonmetastatic, castration-resistant prostate cancer. N Engl J Med. 2019 Mar 28;380(13):1235-1246. Epub 2019 Feb 14. [https://doi.org/10.1056/NEJMoa1815671 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30763142/ PubMed] [https://clinicaltrials.gov/study/NCT02200614 NCT02200614]
+##'''Update:''' Fizazi K, Shore N, Tammela TL, Ulys A, Vjaters E, Polyakov S, Jievaltas M, Luz M, Alekseev B, Kuss I, Le Berre MA, Petrenciuc O, Snapir A, Sarapohja T, Smith MR; ARAMIS Investigators. Nonmetastatic, Castration-Resistant Prostate Cancer and Survival with Darolutamide. N Engl J Med. 2020 Sep 10;383(11):1040-1049. [https://doi.org/10.1056/nejmoa2001342 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32905676/ PubMed]
-#'''TITAN:''' Chi KN, Agarwal N, Bjartell A, Chung BH, Pereira de Santana Gomes AJ, Given R, Juárez Soto Á, Merseburger AS, Özgüroğlu M, Uemura H, Ye D, Deprince K, Naini V, Li J, Cheng S, Yu MK, Zhang K, Larsen JS, McCarthy S, Chowdhury S; TITAN Investigators. Apalutamide for metastatic, castration-sensitive prostate cancer. N Engl J Med. 2019 Jul 4;381(1):13-24. Epub 2019 May 31. [https://www.nejm.org/doi/full/10.1056/NEJMoa1903307 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/31150574 PubMed] NCT02489318
+==ADT & Enzalutamide {{#subobject:d34e0b |Regimen=1}}==
-##'''Update:''' Chi KN, Chowdhury S, Bjartell A, Chung BH, Pereira de Santana Gomes AJ, Given R, Juárez A, Merseburger AS, Özgüroğlu M, Uemura H, Ye D, Brookman-May S, Mundle SD, McCarthy SA, Larsen JS, Sun W, Bevans KB, Zhang K, Bandyopadhyay N, Agarwal N. Apalutamide in Patients With Metastatic Castration-Sensitive Prostate Cancer: Final Survival Analysis of the Randomized, Double-Blind, Phase III TITAN Study. J Clin Oncol. 2021 Apr 29.[https://ascopubs.org/doi/full/10.1200/JCO.20.03488 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33914595/ PubMed] NCT02489318
+ADT & Enzalutamide: '''<u>A</u>'''ndrogen '''<u>D</u>'''eprivation '''<u>T</u>'''herapy & Enzalutamide
+<div class="toccolours" style="background-color:#eeeeee">
-==ADT & Docetaxel {{#subobject:EJCADTdoceR|Regimen=1}}==
+===Regimen {{#subobject:#80614f |Variant=1}}===
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
-ADT & Docetaxel: '''<u>A</u>'''ndrogen '''<u>D</u>'''eprivation '''<u>T</u>'''herapy & Docetaxel
-===Regimen variant #1, 6 cycles {{#subobject:EJCADTdoceV|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 ! style="width: 20%" |Study
-! style="width: 20%" |Years of enrollment
+! style="width: 20%" |Dates of enrollment
 ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 ! style="width: 20%" |Comparator
 ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4800035/ James et al. 2015 (STAMPEDE)]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8288034/ Hussain et al. 2018 (PROSPER<sub>PrCA</sub>)]
-|2005-2011
+<!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
-| style="background-color:#1a9851" |Phase III (E-esc)
+|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-179-1 <span style="color:white;">ESMO-MCBS (3)</span>]'''
-|[[#ADT_4|ADT]]
-| style="background-color:#1a9850" |Superior OS
 |-
-|[http://www.ncbi.nlm.nih.gov/pmc/articles/pmc4562797/ Sweeney et al. 2015 (CHAARTED)]
+|} -->
-|2006-2012
+|2013-2017
-| style="background-color:#1a9851" |Phase III (E-esc)
+| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
 |[[#ADT_4|ADT]]
-| style="background-color:#1a9850" |Superior OS<sup>1</sup>
+| style="background-color:#1a9850" |Superior OS<sup>1</sup> (secondary endpoint)<br>Median OS: 67 vs 56.3 mo<br>(HR 0.73, 95% CI 0.61-0.89)<br><br>Superior MFS (primary endpoint)<br>Median MFS: 36.6 vs 14.7 mo<br>(HR 0.29, 95% CI 0.24-0.35)
 |-
 |}
-''<sup>1</sup>In the 2018 update of CHAARTED, only patients with high-volume disease had superior survival in the experimental arm.''<br>
+''<sup>1</sup>Reported efficacy is based on the 2020 update.''<br>
-''Patients already on androgen deprivation therapy were eligible to participate in CHAARTED if there was no evidence of disease progression and if they had started ADT no more than 120 days before randomization.''
+<div class="toccolours" style="background-color:#fdcdac">
-====Chemotherapy====
+====Eligibility criteria====
+*Castrate-resistant, non-metastatic, prostate cancer with PSA doubling time less than 10 months
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
+====Endocrine therapy====
+*[[:Category:Androgen-deprivation therapy|ADT]]
+*[[Enzalutamide (Xtandi)]] 160 mg PO once per day
+'''Continued indefinitely'''
+</div></div>
-*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV over 60 minutes once on day 1
+===References===
+#'''PROSPER<sub>PrCA</sub>:''' Hussain M, Fizazi K, Saad F, Rathenborg P, Shore N, Ferreira U, Ivashchenko P, Demirhan E, Modelska K, Phung D, Krivoshik A, Sternberg CN. Enzalutamide in men with nonmetastatic, castration-resistant prostate cancer. N Engl J Med. 2018 Jun 28;378(26):2465-2474. [https://doi.org/10.1056/NEJMoa1800536 link to original article] '''contains dosing details in abstract''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8288034/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29949494/ PubMed] [https://clinicaltrials.gov/study/NCT02003924 NCT02003924]
-====Endocrine therapy====
+##'''Update:''' Sternberg CN, Fizazi K, Saad F, Shore ND, De Giorgi U, Penson DF, Ferreira U, Efstathiou E, Madziarska K, Kolinsky MP, Cubero DIG, Noerby B, Zohren F, Lin X, Modelska K, Sugg J, Steinberg J, Hussain M; PROSPER Investigators. Enzalutamide and Survival in Nonmetastatic, Castration-Resistant Prostate Cancer. N Engl J Med. 2020 Jun 4;382(23):2197-2206. Epub 2020 May 29. [https://doi.org/10.1056/nejmoa2003892 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32469184/ PubMed]
-*ADT with ONE of the following:
+=Hormonal therapy for metastatic or locally advanced disease=
-**[[:Category:GnRH agonists|LHRH agonist/analogue]]
+==Abarelix monotherapy {{#subobject:accgjj |Regimen=1}}==
-**[[:Category:GnRH antagonists|LHRH antagonist]]
+<div class="toccolours" style="background-color:#eeeeee">
-**[[Endocrine_ablation_surgery#Bilateral_orchiectomy|Bilateral orchiectomy]]
+===Regimen {{#subobject:cf9gcc|Variant=1}}===
-**Intermittent hormonal therapy was not allowed. Antiandrogens e.g. [[Bicalutamide (Casodex)|bicalutamide]] were allowed at the start of therapy "at the discretion of the investigator."
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
+!style="width: 33%"|Study
-====Supportive medications====
+!style="width: 33%"|Dates of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
-*[[Dexamethasone (Decadron)]] 8 mg PO given three times; 12 hours, 3 hours, and 1 hour before [[Docetaxel (Taxotere)]]
+|-
-*Daily prednisone was not required
+|[https://doi.org/10.1016/s0090-4295(03)00656-3 Koch et al. 2003]
-*At least calcium 500 mg and vitamin D 400 IU PO once per day
+|NR
+| style="background-color:#91cf61" |Non-randomized (RT)
-'''21-day cycle for up to 6 cycles'''
+|-
+|}
-===Regimen variant #2, 9 cycles {{#subobject:257951|Variant=1}}===
+<div class="toccolours" style="background-color:#b3e2cd">
+====Endocrine therapy====
+*[[Abarelix (Plenaxis)]] 100 mg IM once on day 1
+'''Monthly cycles'''
+</div></div>
+===References===
+#Koch M, Steidle C, Brosman S, Centeno A, Gaylis F, Campion M, Garnick MB; Abarelix Study Group. An open-label study of abarelix in men with symptomatic prostate cancer at risk of treatment with LHRH agonists. Urology. 2003 Nov;62(5):877-82. [https://doi.org/10.1016/s0090-4295(03)00656-3 link to original article] [https://pubmed.ncbi.nlm.nih.gov/14624912/ PubMed]
+==ADT {{#subobject:45fc98|Regimen=1}}==
+ADT: '''<u>A</u>'''ndrogen '''<u>D</u>'''eprivation '''<u>T</u>'''herapy
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:bd66bd|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 ! style="width: 20%" |Study
-! style="width: 20%" |Years of enrollment
+! style="width: 20%" |Dates of enrollment
 ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 ! style="width: 20%" |Comparator
 ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(12)70560-0/fulltext Gravis et al. 2013 (GETUG-AFU 15)]
+|[https://www.auajournals.org/doi/full/10.1097/01.ju.0000135742.13171.d2 Schröder et al. 2004 (EORTC 30846)]
+|1986-1998
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#ADT_5|ADT]]; delayed
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+|-
+|[https://doi.org/10.1016/S1470-2045(15)00011-X Fizazi et al. 2015 (GETUG 12)]
+|2002-2006
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#ADT.2C_Docetaxel.2C_Estramustine|ADT, Docetaxel, Estramustine]]
+| style="background-color:#fc8d59" |Seems to have inferior RFS
+|-
+|[https://doi.org/10.1016/S1470-2045(12)70560-0 Gravis et al. 2013 (GETUG-AFU 15)]
 |2004-2008
-| style="background-color:#1a9851" |Phase III (E-esc)
+| style="background-color:#1a9851" |Phase 3 (C)
-|[[#ADT_4|ADT]]
+|[[#ADT_.26_Docetaxel|ADT & Docetaxel]]
 | style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 |-
-|}
+|[https://doi.org/10.1016/j.eururo.2018.09.008 Boevé et al. 2018 (HORRAD)]
-====Chemotherapy====
+|2004-2014
+| style="background-color:#1a9851" |Phase 3 (C)
-*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV over 60 minutes once on day 1
+|[[#ADT_.26_RT|ADT & RT]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
-====Endocrine therapy====
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3398767/ James et al. 2012 (STAMPEDE<sub>celecoxib</sub>)]
-*ADT with one of the following:
+|2005-2011
-**[[:Category:GnRH agonists|LHRH agonist/analogue]] with or without [[:Category:Nonsteroidal_androgen_receptor_inhibitors|nonsteroidal androgen receptor inhibitors]]
+| style="background-color:#1a9851" |Phase 3 (C)
-**[[Endocrine_ablation_surgery#Bilateral_orchiectomy|Bilateral orchiectomy]] with or without [[:Category:Nonsteroidal_androgen_receptor_inhibitors|nonsteroidal androgen receptor inhibitors]]
+|[[#ADT_.26_Celecoxib_999|ADT & Celecoxib]]
+| style="background-color:#ffffbf" |Did not meet intermediate primary endpoint of FFS
-'''21-day cycle for up to 9 cycles'''
-===References===
-#'''GETUG-AFU 15:''' 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. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(12)70560-0/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/23306100 PubMed] NCT00104715
-##'''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. [http://www.europeanurology.com/article/S0302-2838(15)01103-3/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/26610858 PubMed]
-#'''CHAARTED:''' 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. [https://www.nejm.org/doi/full/10.1056/NEJMoa1503747 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pmc/articles/pmc4562797/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26244877 Pubmed] NCT00309985
-##'''Update:''' Kyriakopoulos CE, Chen YH, Carducci MA, Liu G, Jarrard DF, Hahn NM, Shevrin DH, Dreicer R, Hussain M, Eisenberger M, Kohli M, Plimack ER, Vogelzang NJ, Picus J, Cooney MM, Garcia JA, DiPaola RS, Sweeney CJ. Chemohormonal therapy in metastatic hormone-sensitive prostate cancer: long-term survival analysis of the randomized phase III E3805 CHAARTED trial. J Clin Oncol. 2018 Apr 10;36(11):1080-1087. Epub 2018 Jan 31. [https://doi.org/10.1200/JCO.2017.75.3657 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5891129/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/29384722 PubMed]
-##'''QoL analysis:''' Morgans AK, Chen YH, Sweeney CJ, Jarrard DF, Plimack ER, Gartrell BA, Carducci MA, Hussain M, Garcia JA, Cella D, DiPaola RS, Patrick-Miller LJ. Quality of life during treatment with chemohormonal therapy: analysis of E3805 chemohormonal androgen ablation randomized trial in prostate cancer. J Clin Oncol. 2018 Apr 10;36(11):1088-1095. Epub 2018 Mar 9. [https://doi.org/10.1200/JCO.2017.75.3335 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5891128/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/29522362 PubMed]
-#'''STAMPEDE:''' 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. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)01037-5/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4800035/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/26719232 PubMed] NCT00268476
-##'''Update:''' Clarke NW, Ali A, Ingleby FC, Hoyle A, Amos CL, Attard G, Brawley CD, Calvert J, Chowdhury S, Cook A, Cross W, Dearnaley DP, Douis H, Gilbert D, Gillessen S, Jones RJ, Langley RE, MacNair A, Malik Z, Mason MD, Matheson D, Millman R, Parker CC, Ritchie AWS, Rush H, Russell JM, Brown J, Beesley S, Birtle A, Capaldi L, Gale J, Gibbs S, Lydon A, Nikapota A, Omlin A, O'Sullivan JM, Parikh O, Protheroe A, Rudman S, Srihari NN, Simms M, Tanguay JS, Tolan S, Wagstaff J, Wallace J, Wylie J, Zarkar A, Sydes MR, Parmar MKB, James ND. Addition of docetaxel to hormonal therapy in low- and high-burden metastatic hormone sensitive prostate cancer: long-term survival results from the STAMPEDE trial. Ann Oncol. 2019 Dec 1;30(12):1992-2003. [https://doi.org/10.1093/annonc/mdz396 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6938598/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/31560068 PubMed]
-==ADT, Docetaxel, Estramustine {{#subobject:7nc12c|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
 |-
-|[[#top|back to top]]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4800035/ James et al. 2015 (STAMPEDE<sub>docetaxel</sub>)]
-|}
+|2005-2011
-ADT, Docetaxel, Estramustine: '''<u>A</u>'''ndrogen '''<u>D</u>'''eprivation '''<u>T</u>'''herapy, Docetaxel, Estramustine
+| style="background-color:#1a9851" |Phase 3 (C)
-===Regimen {{#subobject:3ac6bc|Variant=1}}===
+|[[#ADT_.26_Docetaxel|ADT & Docetaxel]]
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
+| style="background-color:#d73027" |Inferior OS
-! style="width: 20%" |Study
-! style="width: 20%" |Years of enrollment
-! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
-! style="width: 20%" |Comparator
-! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00011-X/fulltext Fizazi et al. 2015 (GETUG 12)]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5533216 James et al. 2017 (STAMPEDE<sub>abiraterone</sub>)]
-|2002-2006
+|2005-2011
-| style="background-color:#1a9851" |Phase III (E-esc)
+| style="background-color:#1a9851" |Phase 3 (C)
-|[[#ADT_4|ADT]]
+|[[#ADT_.26_Abiraterone|ADT & Abiraterone]]
-| style="background-color:#91cf60" |Seems to have superior RFS
+| style="background-color:#d73027" |Inferior OS
 |-
-|}
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc4562797/ Sweeney et al. 2015 (CHAARTED)]
-====Chemotherapy====
+|2006-2012
+| style="background-color:#1a9851" |Phase 3 (C)
-*[[Docetaxel (Taxotere)]]
+|[[#ADT_.26_Docetaxel|ADT & Docetaxel]]
-*[[Estramustine (Emcyt)]]
+| style="background-color:#d73027" |Inferior OS<sup>1</sup>
-====Endocrine therapy====
-*ADT with one of the following:
-**[[:Category:GnRH agonists|LHRH agonist/analogue]] with or without [[:Category:Nonsteroidal_androgen_receptor_inhibitors|nonsteroidal androgen receptor inhibitors]]
-**[[Endocrine_ablation_surgery#Bilateral_orchiectomy|Bilateral orchiectomy]] with or without [[:Category:Nonsteroidal_androgen_receptor_inhibitors|nonsteroidal androgen receptor inhibitors]]
-===References===
-#'''GETUG 12:''' Fizazi K, Faivre L, Lesaunier F, Delva R, Gravis G, Rolland F, Priou F, Ferrero JM, Houede N, Mourey L, Theodore C, Krakowski I, Berdah JF, Baciuchka M, Laguerre B, Fléchon A, Ravaud A, Cojean-Zelek I, Oudard S, Labourey JL, Chinet-Charrot P, Legouffe E, Lagrange JL, Linassier C, Deplanque G, Beuzeboc P, Davin JL, Martin AL, Habibian M, Laplanche A, Culine S. Androgen deprivation therapy plus docetaxel and estramustine versus androgen deprivation therapy alone for high-risk localised prostate cancer (GETUG 12): a phase 3 randomised controlled trial. Lancet Oncol. 2015 Jul;16(7):787-94. Epub 2015 May 28. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00011-X/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/26028518 PubMed] NCT00055731
-==ADT & Enzalutamide {{#subobject:79lq3c|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
 |-
-|[[#top|back to top]]
+|[https://doi.org/10.1007/s10147-016-1037-2 Kamba et al. 2016 (ZAPCA)]
-|}
+|2008-2010
-ADT & Enzalutamide: '''<u>A</u>'''ndrogen '''<u>D</u>'''eprivation '''<u>T</u>'''herapy & Enzalutamide
+| style="background-color:#1a9851" |Phase 3 (C)
-===Regimen {{#subobject:29ncbc|Variant=1}}===
+|[[#ADT_.26_Zoledronic_acid_333|ADT & Zoledronic acid]]
-{| class="wikitable" style="color:white; background-color:#404040"
+| style="background-color:#fee08b" |Might have inferior TTTF
-|<small>'''FDA-recommended dose'''</small>
 |-
-|}
+|[https://doi.org/10.1056/NEJMoa1704174 Fizazi et al. 2017 (LATITUDE)]
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
+|2013-02-12 to 2014-12-11
-! style="width: 20%" |Study
+| style="background-color:#1a9851" |Phase 3 (C)
-! style="width: 20%" |Years of enrollment
+|[[#ADT_.26_Abiraterone|ADT & Abiraterone]]
-! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
+| style="background-color:#d73027" |Inferior OS
-! style="width: 20%" |Comparator
-! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.nejm.org/doi/full/10.1056/NEJMoa1903835 Davis et al. 2019 (ENZAMET)]
+|[https://doi.org/10.1056/NEJMoa1903307 Chi et al. 2019 (TITAN<sub>prostate</sub>)]
-|2014-2017
+|2015-2017
-| style="background-color:#1a9851" |Phase III (E-switch-ic)
+| style="background-color:#1a9851" |Phase 3 (C)
-|1. ADT & Bicalutamide<br> 2. ADT & Flutamide<br> 3. ADT & Niluatmide
+|[[#ADT_.26_Apalutamide_3|ADT & Apalutamide]]
-| style="background-color:#1a9850" |Superior OS
+| style="background-color:#d73027" |Inferior OS
 |-
-|[https://doi.org/10.1200/JCO.19.00799 Armstrong et al. 2019 (ARCHES)]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6839905/ Armstrong et al. 2019 (ARCHES)]
 |2016-2018
-| style="background-color:#1a9851" |Phase III (E-RT-esc)
+| style="background-color:#1a9851" |Phase 3 (C)
-|[[#ADT_5|ADT]]
+|[[#ADT_.26_Enzalutamide_2|ADT & Enzalutamide]]
-| style="background-color:#1a9850" |Superior rPFS
+| style="background-color:#d73027" |Inferior OS<sup>2</sup>
 |-
 |}
+''<sup>1</sup>In the 2018 update of CHAARTED, only patients with high-volume disease had inferior survival in the control arm.''<br>
+''<sup>2</sup>Reported efficacy is based on the 2022 update.''<br>
+''Note: STAMPEDE is a platform RCT; each subtrial is denoted by the therapy used in the experimental arm. These are clinical trials that did not specify a particular approach to androgen deprivation. See papers for details.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Endocrine therapy====
+*[[:Category:Androgen-deprivation therapy|ADT]]
-*[[Enzalutamide (Xtandi)]] 160 mg PO once per day
-*ADT with one of the following:
-**[[:Category:GnRH agonists|LHRH agonist/analogue]]
-**[[Endocrine_ablation_surgery#Bilateral_orchiectomy|Bilateral orchiectomy]]
 '''Continued indefinitely'''
+</div></div>
 ===References===
+#'''EORTC 30846:''' Schröder FH, Kurth KH, Fosså SD, Hoekstra W, Karthaus PP, Debois M, Collette L; European Organisation for the Research and Treatment of Cancer Genito-urinary Group. Early versus delayed endocrine treatment of pN1-3 M0 prostate cancer without local treatment of the primary tumor: results of European Organisation for the Research and Treatment of Cancer 30846--a phase III study. J Urol. 2004 Sep;172(3):923-7. [https://www.auajournals.org/doi/full/10.1097/01.ju.0000135742.13171.d2 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15310999/ PubMed]
-#'''ENZAMET:''' Davis ID, Martin AJ, Stockler MR, Begbie S, Chi KN, Chowdhury S, Coskinas X, Frydenberg M, Hague WE, Horvath LG, Joshua AM, Lawrence NJ, Marx G, McCaffrey J, McDermott R, McJannett M, North SA, Parnis F, Parulekar W, Pook DW, Reaume MN, Sandhu SK, Tan A, Tan TH, Thomson A, Tu E, Vera-Badillo F, Williams SG, Yip S, Zhang AY, Zielinski RR, Sweeney CJ; ENZAMET Trial Investigators and the Australian and New Zealand Urogenital and Prostate Cancer Trials Group. Enzalutamide with standard first-line therapy in metastatic prostate cancer. N Engl J Med. 2019 Jul 11;381(2):121-131. Epub 2019 Jun 2. [https://www.nejm.org/doi/full/10.1056/NEJMoa1903835 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/31157964 PubMed] NCT02446405
+#'''STAMPEDE<sub>celecoxib</sub>:''' James ND, Sydes MR, Mason MD, Clarke NW, Anderson J, Dearnaley DP, Dwyer J, Jovic G, Ritchie AW, Russell JM, Sanders K, Thalmann GN, Bertelli G, Birtle AJ, O'Sullivan JM, Protheroe A, Sheehan D, Srihari N, Parmar MK; STAMPEDE Investigators. Celecoxib plus hormone therapy versus hormone therapy alone for hormone-sensitive prostate cancer: first results from the STAMPEDE multiarm, multistage, randomised controlled trial. Lancet Oncol. 2012 May;13(5):549-58. Epub 2012 Mar 26. Erratum in: Lancet Oncol. 2013 Jan;14(1):e5. [https://doi.org/10.1016/S1470-2045(12)70088-8 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3398767/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22452894/ PubMed] [https://clinicaltrials.gov/study/NCT00268476 NCT00268476]
-#'''ARCHES:''' Armstrong AJ, Szmulewitz RZ, Petrylak DP, Holzbeierlein J, Villers A, Azad A, Alcaraz A, Alekseev B, Iguchi T, Shore ND, Rosbrook B, Sugg J, Baron B, Chen L, Stenzl A. ARCHES: a randomized, phase III study of androgen deprivation therapy with enzalutamide or placebo in men with metastatic hormone-sensitive prostate cancer. J Clin Oncol. 2019 Nov 10;37(32):2974-2986. Epub 2019 Jul 22. [https://doi.org/10.1200/JCO.19.00799 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/31329516 PubMed]
+#'''GETUG-AFU 15:''' 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. [https://doi.org/10.1016/S1470-2045(12)70560-0 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23306100/ PubMed] [https://clinicaltrials.gov/study/NCT00104715 NCT00104715]
+##'''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. [https://doi.org/10.1016/j.eururo.2015.11.005 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26610858/ PubMed]
-==Bicalutamide monotherapy {{#subobject:5 |Regimen=1}}==
+#'''GETUG 12:''' Fizazi K, Faivre L, Lesaunier F, Delva R, Gravis G, Rolland F, Priou F, Ferrero JM, Houede N, Mourey L, Theodore C, Krakowski I, Berdah JF, Baciuchka M, Laguerre B, Fléchon A, Ravaud A, Cojean-Zelek I, Oudard S, Labourey JL, Chinet-Charrot P, Legouffe E, Lagrange JL, Linassier C, Deplanque G, Beuzeboc P, Davin JL, Martin AL, Habibian M, Laplanche A, Culine S. Androgen deprivation therapy plus docetaxel and estramustine versus androgen deprivation therapy alone for high-risk localised prostate cancer (GETUG 12): a phase 3 randomised controlled trial. Lancet Oncol. 2015 Jul;16(7):787-94. Epub 2015 May 28. [https://doi.org/10.1016/S1470-2045(15)00011-X link to original article] [https://pubmed.ncbi.nlm.nih.gov/26028518/ PubMed] [https://clinicaltrials.gov/study/NCT00055731 NCT00055731]
-{| class="wikitable" style="float:right; margin-left: 5px;"
+#'''CHAARTED:''' 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. [https://doi.org/10.1056/NEJMoa1503747 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc4562797/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26244877/ PubMed] [https://clinicaltrials.gov/study/NCT00309985 NCT00309985]
-|-
+##'''Update:''' Kyriakopoulos CE, Chen YH, Carducci MA, Liu G, Jarrard DF, Hahn NM, Shevrin DH, Dreicer R, Hussain M, Eisenberger M, Kohli M, Plimack ER, Vogelzang NJ, Picus J, Cooney MM, Garcia JA, DiPaola RS, Sweeney CJ. Chemohormonal therapy in metastatic hormone-sensitive prostate cancer: long-term survival analysis of the randomized phase III E3805 CHAARTED trial. J Clin Oncol. 2018 Apr 10;36(11):1080-1087. Epub 2018 Jan 31. [https://doi.org/10.1200/JCO.2017.75.3657 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5891129/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29384722/ PubMed]
-|[[#top|back to top]]
+##'''HRQoL analysis:''' Morgans AK, Chen YH, Sweeney CJ, Jarrard DF, Plimack ER, Gartrell BA, Carducci MA, Hussain M, Garcia JA, Cella D, DiPaola RS, Patrick-Miller LJ. Quality of life during treatment with chemohormonal therapy: analysis of E3805 chemohormonal androgen ablation randomized trial in prostate cancer. J Clin Oncol. 2018 Apr 10;36(11):1088-1095. Epub 2018 Mar 9. [https://doi.org/10.1200/JCO.2017.75.3335 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5891128/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29522362/ PubMed]
-|}
+#'''STAMPEDE<sub>docetaxel</sub>:''' 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. [https://doi.org/10.1016/S0140-6736(15)01037-5 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4800035/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/26719232/ PubMed] [https://clinicaltrials.gov/study/NCT00268476 NCT00268476]
-===Regimen {{#subobject:5 |Variant=1}}===
+##'''Update:''' Clarke NW, Ali A, Ingleby FC, Hoyle A, Amos CL, Attard G, Brawley CD, Calvert J, Chowdhury S, Cook A, Cross W, Dearnaley DP, Douis H, Gilbert D, Gillessen S, Jones RJ, Langley RE, MacNair A, Malik Z, Mason MD, Matheson D, Millman R, Parker CC, Ritchie AWS, Rush H, Russell JM, Brown J, Beesley S, Birtle A, Capaldi L, Gale J, Gibbs S, Lydon A, Nikapota A, Omlin A, O'Sullivan JM, Parikh O, Protheroe A, Rudman S, Srihari NN, Simms M, Tanguay JS, Tolan S, Wagstaff J, Wallace J, Wylie J, Zarkar A, Sydes MR, Parmar MKB, James ND. Addition of docetaxel to hormonal therapy in low- and high-burden metastatic hormone sensitive prostate cancer: long-term survival results from the STAMPEDE trial. Ann Oncol. 2019 Dec 1;30(12):1992-2003. [https://doi.org/10.1093/annonc/mdz396 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6938598/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31560068/ PubMed]
+#'''ZAPCA:''' Kamba T, Kamoto T, Maruo S, Kikuchi T, Shimizu Y, Namiki S, Fujimoto K, Kawanishi H, Sato F, Narita S, Satoh T, Saito H, Sugimoto M, Teishima J, Masumori N, Egawa S, Sakai H, Okada Y, Terachi T, Ogawa O; ZAPCA Study Group. A phase III multicenter, randomized, controlled study of combined androgen blockade with versus without zoledronic acid in prostate cancer patients with metastatic bone disease: results of the ZAPCA trial. Int J Clin Oncol. 2017 Feb;22(1):166-173. Epub 2016 Sep 10. [https://doi.org/10.1007/s10147-016-1037-2 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27614621/ PubMed] [https://clinicaltrials.gov/study/NCT00685646 NCT00685646]
+#'''STAMPEDE<sub>abiraterone</sub>:''' 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. [https://doi.org/10.1056/NEJMoa1702900 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5533216 link to PMC article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1702900/suppl_file/nejmoa1702900_protocol.pdf supplementary protocol] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/28578639/ PubMed] [https://clinicaltrials.gov/study/NCT00268476 NCT00268476]
+##'''Meta-analysis:''' Attard G, Murphy L, Clarke NW, Cross W, Jones RJ, Parker CC, Gillessen S, Cook A, Brawley C, Amos CL, Atako N, Pugh C, Buckner M, Chowdhury S, Malik Z, Russell JM, Gilson C, Rush H, Bowen J, Lydon A, Pedley I, O'Sullivan JM, Birtle A, Gale J, Srihari N, Thomas C, Tanguay J, Wagstaff J, Das P, Gray E, Alzoueb M, Parikh O, Robinson A, Syndikus I, Wylie J, Zarkar A, Thalmann G, de Bono JS, Dearnaley DP, Mason MD, Gilbert D, Langley RE, Millman R, Matheson D, Sydes MR, Brown LC, Parmar MKB, James ND; Systemic Therapy in Advancing or Metastatic Prostate cancer: Evaluation of Drug Efficacy (STAMPEDE) investigators. Abiraterone acetate and prednisolone with or without enzalutamide for high-risk non-metastatic prostate cancer: a meta-analysis of primary results from two randomised controlled phase 3 trials of the STAMPEDE platform protocol. Lancet. 2022 Jan 29;399(10323):447-460. Epub 2021 Dec 23. [https://doi.org/10.1016/s0140-6736(21)02437-5 link to original article] [https://pubmed.ncbi.nlm.nih.gov/34953525/ PubMed]
+##'''Update:''' Attard G, Murphy L, Clarke NW, Sachdeva A, Jones C, Hoyle A, Cross W, Jones RJ, Parker CC, Gillessen S, Cook A, Brawley C, Gilson C, Rush H, Abdel-Aty H, Amos CL, Murphy C, Chowdhury S, Malik Z, Russell JM, Parkar N, Pugh C, Diaz-Montana C, Pezaro C, Grant W, Saxby H, Pedley I, O'Sullivan JM, Birtle A, Gale J, Srihari N, Thomas C, Tanguay J, Wagstaff J, Das P, Gray E, Alzouebi M, Parikh O, Robinson A, Montazeri AH, Wylie J, Zarkar A, Cathomas R, Brown MD, Jain Y, Dearnaley DP, Mason MD, Gilbert D, Langley RE, Millman R, Matheson D, Sydes MR, Brown LC, Parmar MKB, James ND; STAMPEDE investigators. Abiraterone acetate plus prednisolone with or without enzalutamide for patients with metastatic prostate cancer starting androgen deprivation therapy: final results from two randomised phase 3 trials of the STAMPEDE platform protocol. Lancet Oncol. 2023 May;24(5):443-456. [https://doi.org/10.1016/s1470-2045(23)00148-1 link to original article] [https://pubmed.ncbi.nlm.nih.gov/37142371/ PubMed]
+#'''LATITUDE:''' 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. [https://doi.org/10.1056/NEJMoa1704174 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1704174/suppl_file/nejmoa1704174_protocol.pdf supplementary protocol] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/28578607/ PubMed] [https://clinicaltrials.gov/study/NCT01715285 NCT01715285]
+##'''HRQoL analysis:''' Chi KN, Protheroe A, Rodríguez-Antolín A, Facchini G, Suttman H, Matsubara N, Ye Z, Keam B, Damião R, Li T, McQuarrie K, Jia B, De Porre P, Martin J, Todd MB, Fizazi K. Patient-reported outcomes following abiraterone acetate plus prednisone added to androgen deprivation therapy in patients with newly diagnosed metastatic castration-naive prostate cancer (LATITUDE): an international, randomised phase 3 trial. Lancet Oncol. 2018 Feb;19(2):194-206. Epub 2018 Jan 8. [https://doi.org/10.1016/S1470-2045(17)30911-7 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29326030/ PubMed]
+##'''Update:''' Fizazi K, Tran N, Fein L, Matsubara N, Rodriguez-Antolin A, Alekseev BY, Özgüroğlu M, Ye D, Feyerabend S, Protheroe A, Sulur G, Luna Y, Li S, Mundle S, Chi KN. Abiraterone acetate plus prednisone in patients with newly diagnosed high-risk metastatic castration-sensitive prostate cancer (LATITUDE): final overall survival analysis of a randomised, double-blind, phase 3 trial. Lancet Oncol. 2019 May;20(5):686-700. Epub 2019 Apr 12. [https://doi.org/10.1016/S1470-2045(19)30082-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30987939/ PubMed]
+#'''HORRAD:''' Boevé LMS, Hulshof MCCM, Vis AN, Zwinderman AH, Twisk JWR, Witjes WPJ, Delaere KPJ, Moorselaar RJAV, Verhagen PCMS, van Andel G. Effect on Survival of Androgen Deprivation Therapy Alone Compared to Androgen Deprivation Therapy Combined with Concurrent Radiation Therapy to the Prostate in Patients with Primary Bone Metastatic Prostate Cancer in a Prospective Randomised Clinical Trial: Data from the HORRAD Trial. Eur Urol. 2019 Mar;75(3):410-418. Epub 2018 Sep 25. [https://doi.org/10.1016/j.eururo.2018.09.008 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30266309/ PubMed]
+#'''TITAN<sub>prostate</sub>:''' Chi KN, Agarwal N, Bjartell A, Chung BH, Pereira de Santana Gomes AJ, Given R, Juárez Soto Á, Merseburger AS, Özgüroğlu M, Uemura H, Ye D, Deprince K, Naini V, Li J, Cheng S, Yu MK, Zhang K, Larsen JS, McCarthy S, Chowdhury S; TITAN Investigators. Apalutamide for metastatic, castration-sensitive prostate cancer. N Engl J Med. 2019 Jul 4;381(1):13-24. Epub 2019 May 31. [https://doi.org/10.1056/NEJMoa1903307 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/31150574/ PubMed] [https://clinicaltrials.gov/study/NCT02489318 NCT02489318]
+##'''Update:''' Chi KN, Chowdhury S, Bjartell A, Chung BH, Pereira de Santana Gomes AJ, Given R, Juárez A, Merseburger AS, Özgüroğlu M, Uemura H, Ye D, Brookman-May S, Mundle SD, McCarthy SA, Larsen JS, Sun W, Bevans KB, Zhang K, Bandyopadhyay N, Agarwal N. Apalutamide in Patients With Metastatic Castration-Sensitive Prostate Cancer: Final Survival Analysis of the Randomized, Double-Blind, Phase III TITAN Study. J Clin Oncol. 2021 Jul 10;39(20):2294-2303. Epub 2021 Apr 29. [https://doi.org/10.1200/jco.20.03488 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33914595/ PubMed]
+#'''ARCHES:''' Armstrong AJ, Szmulewitz RZ, Petrylak DP, Holzbeierlein J, Villers A, Azad A, Alcaraz A, Alekseev B, Iguchi T, Shore ND, Rosbrook B, Sugg J, Baron B, Chen L, Stenzl A. ARCHES: a randomized, phase III study of androgen deprivation therapy with enzalutamide or placebo in men with metastatic hormone-sensitive prostate cancer. J Clin Oncol. 2019 Nov 10;37(32):2974-2986. Epub 2019 Jul 22. [https://doi.org/10.1200/JCO.19.00799 link to original article] '''contains dosing details in abstract''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6839905/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31329516/ PubMed] [https://clinicaltrials.gov/study/NCT02677896 NCT02677896]
+==ADT & Abiraterone {{#subobject:02afb7|Regimen=1}}==
+ADT & Abiraterone: '''<u>A</u>'''ndrogen '''<u>D</u>'''eprivation '''<u>T</u>'''herapy & Abiraterone
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:31ffca|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 ! style="width: 20%" |Study
-! style="width: 20%" |Years of enrollment
+! style="width: 20%" |Dates of enrollment
 ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 ! style="width: 20%" |Comparator
 ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.karger.com/Article/Abstract/19634 Tyrrell et al. 1998]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5533216 James et al. 2017 (STAMPEDE<sub>abiraterone</sub>)]
-|NR in abstract
+<!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
-| style="background-color:#1a9851" |Phase III (E-switch-ic)
+|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-177-1 <span style="color:white;">ESMO-MCBS (4)</span>]'''
-|[[Prostate_cancer_-_historical#Castration|Castration]]
+|-
-| style="background-color:#ffffbf" |Did not meet primary endpoints of PFS/OS<sup>1</sup>
+|} -->
+|2005-2011
+| style="background-color:#1a9851" |Phase 3 (E-esc)
+|[[#ADT_5|ADT]]
+| style="background-color:#1a9850" |Superior OS (primary endpoint)<br>OS36: 83% vs 76%<br>(HR 0.63, 95% CI 0.52-0.76)
+|-
+|[https://doi.org/10.1056/NEJMoa1704174 Fizazi et al. 2017 (LATITUDE)]
+<!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
+|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-175-1 <span style="color:white;">ESMO-MCBS (4)</span>]'''
 |-
-|[https://www.europeanurology.com/article/S0302-2838(02)00311-1/fulltext Iversen et al. 2002 (SPCG-6)]
+|} -->
-|1995-1998
+|2013-02-12 to 2014-12-11
-| style="background-color:#1a9851" |Phase III (E-esc)
+| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
-|Placebo
+|[[#ADT_5|ADT]]
-| style="background-color:#1a9850" |Superior OS<sup>2</sup>
+| style="background-color:#1a9850" |Superior OS (co-primary endpoint)<br>Median OS: NYR vs 34.7 mo<br>(HR 0.62, 95% CI 0.51-0.76)
 |-
 |}
-''<sup>1</sup>Reported efficacy for Tyrrell et al. 1998 is based on the 2000 update.''<br>
+''Note: STAMPEDE is a platform RCT; this subtrial is labeled by the experimental arm additive therapy. While LATITUDE allowed for a dose increase in prednisone, the FDA recommended dose is 5 mg PO once per day.''
-''<sup>2</sup>Reported efficacy for SPCG-6 is based on the 2006 update and is only for the locally advanced subgroup.''<br>
+<div class="toccolours" style="background-color:#b3e2cd">
-''Not approved for monotherapy in the United States. See combination regimens with goserelin & leuprolide.''
 ====Endocrine therapy====
+*[[Abiraterone (Zytiga)]] 1000 mg PO once per day
-*[[Bicalutamide (Casodex)]] 150 mg PO once per day
+*ADT with ONE of the following:
+**[[:Category:GnRH agonists|LHRH agonist/analog]]
-'''Continued indefinitely'''
+**'''STAMPEDE<sub>abiraterone</sub> only:''' [[:Category:GnRH antagonists|LHRH antagonist]]
+**[[Bilateral_orchiectomy|Bilateral orchiectomy]]
+====Supportive therapy====
+*Prevention of mineralocorticoid excess with ONE of the following:
+**'''STAMPEDE<sub>abiraterone</sub> except Switzerland:''' [[Prednisolone (Millipred)]] 5 mg PO once per day
+**'''LATITUDE and STAMPEDE<sub>abiraterone</sub> 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 indefinitely unless radiotherapy planned, in which case continued for up to 2 years'''
+</div></div>
 ===References===
+#'''STAMPEDE<sub>abiraterone</sub>:''' 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. [https://doi.org/10.1056/NEJMoa1702900 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5533216 link to PMC article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1702900/suppl_file/nejmoa1702900_protocol.pdf supplementary protocol] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/28578639/ PubMed] [https://clinicaltrials.gov/study/NCT00268476 NCT00268476]
+##'''Meta-analysis:''' Attard G, Murphy L, Clarke NW, Cross W, Jones RJ, Parker CC, Gillessen S, Cook A, Brawley C, Amos CL, Atako N, Pugh C, Buckner M, Chowdhury S, Malik Z, Russell JM, Gilson C, Rush H, Bowen J, Lydon A, Pedley I, O'Sullivan JM, Birtle A, Gale J, Srihari N, Thomas C, Tanguay J, Wagstaff J, Das P, Gray E, Alzoueb M, Parikh O, Robinson A, Syndikus I, Wylie J, Zarkar A, Thalmann G, de Bono JS, Dearnaley DP, Mason MD, Gilbert D, Langley RE, Millman R, Matheson D, Sydes MR, Brown LC, Parmar MKB, James ND; Systemic Therapy in Advancing or Metastatic Prostate cancer: Evaluation of Drug Efficacy (STAMPEDE) investigators. Abiraterone acetate and prednisolone with or without enzalutamide for high-risk non-metastatic prostate cancer: a meta-analysis of primary results from two randomised controlled phase 3 trials of the STAMPEDE platform protocol. Lancet. 2022 Jan 29;399(10323):447-460. Epub 2021 Dec 23. [https://doi.org/10.1016/s0140-6736(21)02437-5 link to original article] [https://pubmed.ncbi.nlm.nih.gov/34953525/ PubMed]
+##'''Update:''' Attard G, Murphy L, Clarke NW, Sachdeva A, Jones C, Hoyle A, Cross W, Jones RJ, Parker CC, Gillessen S, Cook A, Brawley C, Gilson C, Rush H, Abdel-Aty H, Amos CL, Murphy C, Chowdhury S, Malik Z, Russell JM, Parkar N, Pugh C, Diaz-Montana C, Pezaro C, Grant W, Saxby H, Pedley I, O'Sullivan JM, Birtle A, Gale J, Srihari N, Thomas C, Tanguay J, Wagstaff J, Das P, Gray E, Alzouebi M, Parikh O, Robinson A, Montazeri AH, Wylie J, Zarkar A, Cathomas R, Brown MD, Jain Y, Dearnaley DP, Mason MD, Gilbert D, Langley RE, Millman R, Matheson D, Sydes MR, Brown LC, Parmar MKB, James ND; STAMPEDE investigators. Abiraterone acetate plus prednisolone with or without enzalutamide for patients with metastatic prostate cancer starting androgen deprivation therapy: final results from two randomised phase 3 trials of the STAMPEDE platform protocol. Lancet Oncol. 2023 May;24(5):443-456. [https://doi.org/10.1016/s1470-2045(23)00148-1 link to original article] [https://pubmed.ncbi.nlm.nih.gov/37142371/ PubMed]
+#'''LATITUDE:''' 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. [https://doi.org/10.1056/NEJMoa1704174 link to original article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1704174/suppl_file/nejmoa1704174_protocol.pdf supplementary protocol] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/28578607/ PubMed] [https://clinicaltrials.gov/study/NCT01715285 NCT01715285]
+##'''HRQoL analysis:''' Chi KN, Protheroe A, Rodríguez-Antolín A, Facchini G, Suttman H, Matsubara N, Ye Z, Keam B, Damião R, Li T, McQuarrie K, Jia B, De Porre P, Martin J, Todd MB, Fizazi K. Patient-reported outcomes following abiraterone acetate plus prednisone added to androgen deprivation therapy in patients with newly diagnosed metastatic castration-naive prostate cancer (LATITUDE): an international, randomised phase 3 trial. Lancet Oncol. 2018 Feb;19(2):194-206. Epub 2018 Jan 8. [https://doi.org/10.1016/S1470-2045(17)30911-7 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29326030/ PubMed]
+##'''Update:''' Fizazi K, Tran N, Fein L, Matsubara N, Rodriguez-Antolin A, Alekseev BY, Özgüroğlu M, Ye D, Feyerabend S, Protheroe A, Sulur G, Luna Y, Li S, Mundle S, Chi KN. Abiraterone acetate plus prednisone in patients with newly diagnosed high-risk metastatic castration-sensitive prostate cancer (LATITUDE): final overall survival analysis of a randomised, double-blind, phase 3 trial. Lancet Oncol. 2019 May;20(5):686-700. Epub 2019 Apr 12. [https://doi.org/10.1016/S1470-2045(19)30082-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30987939/ PubMed]
-#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. [https://www.karger.com/Article/Abstract/19634 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/9643663 PubMed]
+==ADT & Apalutamide {{#subobject:02eac3|Regimen=1}}==
-##'''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. [https://www.auajournals.org/article/S0022-5347(05)67032-2/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/11025708 PubMed]
+ADT & Apalutamide: '''<u>A</u>'''ndrogen '''<u>D</u>'''eprivation '''<u>T</u>'''herapy & Apalutamide
-#'''SPCG-6:''' Iversen P, Tammela TL, Vaage S, Lukkarinen O, Lodding P, Bull-Njaa T, Viitanen J, Hoisaeter P, Lundmo P, Rasmussen F, Johansson JE, Persson BE, Carroll K; Scandinavian Prostatic Cancer Group. A randomised comparison of bicalutamide ('Casodex') 150 mg versus placebo as immediate therapy either alone or as adjuvant to standard care for early non-metastatic prostate cancer: first report from the Scandinavian Prostatic Cancer Group Study No 6. Eur Urol. 2002 Sep;42(3):204-11. [https://www.europeanurology.com/article/S0302-2838(02)00311-1/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/12234503 PubMed]
+<div class="toccolours" style="background-color:#eeeeee">
-##'''Update:''' Iversen P, Johansson JE, Lodding P, Lukkarinen O, Lundmo P, Klarskov P, Tammela TL, Tasdemir I, Morris T, Carroll K; Scandinavian Prostatic Cancer Group. Bicalutamide (150 mg) versus placebo as immediate therapy alone or as adjuvant to therapy with curative intent for early nonmetastatic prostate cancer: 5.3-year median followup from the Scandinavian Prostate Cancer Group Study Number 6. J Urol. 2004 Nov;172(5 Pt 1):1871-6. [https://www.auajournals.org/article/S0022-5347(05)60880-4/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15540741 PubMed]
+===Regimen {{#subobject:31baz9|Variant=1}}===
-##'''Update:''' Iversen P, Johansson JE, Lodding P, Kylmälä T, Lundmo P, Klarskov P, Tammela TL, Tasdemir I, Morris T, Armstrong J; Scandinavian Prostate Cancer Group. Bicalutamide 150 mg in addition to standard care for patients with early non-metastatic prostate cancer: updated results from the Scandinavian Prostate Cancer Period Group-6 Study after a median follow-up period of 7.1 years. Scand J Urol Nephrol. 2006;40(6):441-52. [https://www.tandfonline.com/doi/abs/10.1080/00365590601017329 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/17130095 PubMed]
+{| class="wikitable" style="color:white; background-color:#404040"
+|<small>'''FDA-recommended dose'''</small>
-==Bicalutamide & Goserelin {{#subobject:10 |Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
 |-
-|[[#top|back to top]]
 |}
-===Regimen variant #1, 50/3.6 {{#subobject:10 |Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 ! style="width: 20%" |Study
-! style="width: 20%" |Years of enrollment
+! style="width: 20%" |Dates of enrollment
 ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 ! style="width: 20%" |Comparator
 ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-| rowspan="2" |[http://www.goldjournal.net/article/S0090-4295(99)80077-6/abstract Schellhammer et al. 1995]
+|[https://doi.org/10.1056/NEJMoa1903307 Chi et al. 2019 (TITAN<sub>prostate</sub>)]
-| rowspan="2" |1992-1993
+<!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
-| rowspan="2" style="background-color:#1a9851" |Phase III (E-RT-switch-ic)
+|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-184-1 <span style="color:white;">ESMO-MCBS (4)</span>]'''
-|1. [[#Bicalutamide_.26_Leuprolide|Bicalutamide & Leuprolide]]
-| style="background-color:#d3d3d3" |Not reported
 |-
-|2. [[#Flutamide_.26_Goserelin_2|Flutamide & Goserelin]]<br> 3. [[#Flutamide_.26_Leuprolide|Flutamide & Leuprolide]]
+|} -->
-| style="background-color:#eeee01" |Equivalent TTP<sup>1</sup>
+|2015-2017
+| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
+|[[#ADT_5|ADT]]
+| style="background-color:#1a9850" |Superior OS<sup>1</sup> (co-primary endpoint)<br>Median OS: NYR vs 52.2 mo<br>(HR 0.65, 95% CI 0.53-0.79)
 |-
 |}
-''<sup>1</sup>Reported efficacy for Schellhammer et al. 1995 is based on the 1997 final update.''
+''<sup>1</sup>Reported efficacy is based on the 2021 update.''<br>
+''Note: there are several other trials in other cancer subtypes named TITAN.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Endocrine therapy====
+*[[Apalutamide (Erleada)]] 240 mg PO once per day
+*[[:Category:GnRH agonists|LHRH agonist/analog]]
+'''Continued indefinitely'''
+</div></div>
+===References===
+#'''TITAN<sub>prostate</sub>:''' Chi KN, Agarwal N, Bjartell A, Chung BH, Pereira de Santana Gomes AJ, Given R, Juárez Soto Á, Merseburger AS, Özgüroğlu M, Uemura H, Ye D, Deprince K, Naini V, Li J, Cheng S, Yu MK, Zhang K, Larsen JS, McCarthy S, Chowdhury S; TITAN Investigators. Apalutamide for metastatic, castration-sensitive prostate cancer. N Engl J Med. 2019 Jul 4;381(1):13-24. Epub 2019 May 31. [https://doi.org/10.1056/NEJMoa1903307 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/31150574/ PubMed] [https://clinicaltrials.gov/study/NCT02489318 NCT02489318]
+##'''Update:''' Chi KN, Chowdhury S, Bjartell A, Chung BH, Pereira de Santana Gomes AJ, Given R, Juárez A, Merseburger AS, Özgüroğlu M, Uemura H, Ye D, Brookman-May S, Mundle SD, McCarthy SA, Larsen JS, Sun W, Bevans KB, Zhang K, Bandyopadhyay N, Agarwal N. Apalutamide in Patients With Metastatic Castration-Sensitive Prostate Cancer: Final Survival Analysis of the Randomized, Double-Blind, Phase III TITAN Study. J Clin Oncol. 2021 Jul 10;39(20):2294-2303. Epub 2021 Apr 29. [https://doi.org/10.1200/jco.20.03488 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33914595/ PubMed]
-*[[Bicalutamide (Casodex)]] 50 mg PO once per day
+==ADT & Bicalutamide {{#subobject:16eac3|Regimen=1}}==
-*[[Goserelin (Zoladex)]] 3.6 mg SC once on day 1
+ADT & Bicalutamide: '''<u>A</u>'''ndrogen '''<u>D</u>'''eprivation '''<u>T</u>'''herapy & Bicalutamide
+<div class="toccolours" style="background-color:#eeeeee">
-'''28-day cycles'''
+===Regimen {{#subobject:ug81c9|Variant=1}}===
-===Regimen variant #2, 80/3.6 {{#subobject:a8fe78|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 ! style="width: 20%" |Study
-! style="width: 20%" |Years of enrollment
+! style="width: 20%" |Dates of enrollment
 ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 ! style="width: 20%" |Comparator
 ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[http://jjco.oxfordjournals.org/content/34/1/20.full Akaza et al. 2004]
+|[https://doi.org/10.1056/NEJMoa1903835 Davis et al. 2019 (ENZAMET)]
-|2000-2001
+|2014-2017
-| style="background-color:#1a9851" |Phase III (E-esc)
+| style="background-color:#1a9851" |Phase 3 (C)
-|1. [[#Goserelin_monotherapy_2|Goserelin]]<br> 2. [[#Leuprolide_monotherapy_2|Leuprolide]]
+|[[#ADT_.26_Enzalutamide_2|ADT & Enzalutamide]]
-| style="background-color:#91cf60" |Seems to have superior OS<sup>1</sup>
+| style="background-color:#d73027" |Inferior OS<sup>1</sup>
+|-
+|[https://doi.org/10.1016/s1470-2045(22)00507-1 Gu et al. 2022 (CHART)]
+|2018-2020
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#ADT_.26_Rezvilutamide_777|ADT & Rezvilutamide]]
+| style="background-color:#d73027" |Inferior OS
 |-
 |}
-''<sup>1</sup>Reported efficacy is based on the 2009 update.''
+''<sup>1</sup>Reported efficacy for ENZAMET is based on the 2023 update.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Endocrine therapy====
+*[[:Category:GnRH agonists|LHRH agonist/analog]]
+**ENZAMET also allowed [[Bilateral_orchiectomy|Bilateral orchiectomy]]
+*[[Bicalutamide (Casodex)]] 50 mg PO once per day
+'''Continued indefinitely'''
+</div></div>
+===References===
+#'''ENZAMET:''' Davis ID, Martin AJ, Stockler MR, Begbie S, Chi KN, Chowdhury S, Coskinas X, Frydenberg M, Hague WE, Horvath LG, Joshua AM, Lawrence NJ, Marx G, McCaffrey J, McDermott R, McJannett M, North SA, Parnis F, Parulekar W, Pook DW, Reaume MN, Sandhu SK, Tan A, Tan TH, Thomson A, Tu E, Vera-Badillo F, Williams SG, Yip S, Zhang AY, Zielinski RR, Sweeney CJ; ENZAMET Trial Investigators and the Australian and New Zealand Urogenital and Prostate Cancer Trials Group. Enzalutamide with standard first-line therapy in metastatic prostate cancer. N Engl J Med. 2019 Jul 11;381(2):121-131. Epub 2019 Jun 2. [https://doi.org/10.1056/NEJMoa1903835 link to original article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/31157964/ PubMed] [https://clinicaltrials.gov/study/NCT02446405 NCT02446405]
+##'''Update:''' Sweeney CJ, Martin AJ, Stockler MR, Begbie S, Cheung L, Chi KN, Chowdhury S, Frydenberg M, Horvath LG, Joshua AM, Lawrence NJ, Marx G, McCaffrey J, McDermott R, McJannett M, North SA, Parnis F, Parulekar W, Pook DW, Reaume MN, Sandhu SK, Tan A, Tan TH, Thomson A, Vera-Badillo F, Williams SG, Winter D, Yip S, Zhang AY, Zielinski RR, Davis ID; ENZAMET trial investigators and Australian and New Zealand Urogenital and Prostate Cancer Trials Group. Testosterone suppression plus enzalutamide versus testosterone suppression plus standard antiandrogen therapy for metastatic hormone-sensitive prostate cancer (ENZAMET): an international, open-label, randomised, phase 3 trial. Lancet Oncol. 2023 Apr;24(4):323-334. [https://doi.org/10.1016/s1470-2045(23)00063-3 link to original article] [https://pubmed.ncbi.nlm.nih.gov/36990608/ PubMed]
+#'''CHART:''' Gu W, Han W, Luo H, Zhou F, He D, Ma L, Guo H, Liang C, Chong T, Jiang J, Chen Z, Wang Y, Zou Q, Tian Y, Xiao J, Huang J, Zhu S, Dong Q, Zhang X, Li H, Yang X, Chen C, Li J, Jin C, Zhang X, Ye D; CHART Investigators. Rezvilutamide versus bicalutamide in combination with androgen-deprivation therapy in patients with high-volume, metastatic, hormone-sensitive prostate cancer (CHART): a randomised, open-label, phase 3 trial. Lancet Oncol. 2022 Oct;23(10):1249-1260. Epub 2022 Sep 5. [https://doi.org/10.1016/s1470-2045(22)00507-1 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/36075260/ PubMed] [https://clinicaltrials.gov/study/NCT03520478 NCT03520478]
-*[[Bicalutamide (Casodex)]] 80 mg PO once per day
+==ADT, Darolutamide, Docetaxel {{#subobject:hga8cc|Regimen=1}}==
-*[[Goserelin (Zoladex)]] 3.6 mg SC once on day 1
+ADT, Darolutamide, Docetaxel: '''<u>A</u>'''ndrogen '''<u>D</u>'''eprivation '''<u>T</u>'''herapy, Darolutamide, Docetaxel
+<div class="toccolours" style="background-color:#eeeeee">
-'''28-day cycles'''
+===Regimen {{#subobject:yg7cxg|Variant=1}}===
-===References===
+{| class="wikitable" style="color:white; background-color:#404040"
+|<small>'''FDA-recommended dose'''</small>
-#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. [http://www.goldjournal.net/article/S0090-4295(99)80077-6/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/7538237 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. [https://onlinelibrary.wiley.com/doi/10.1002/(SICI)1097-0142(19961115)78:10%3C2164::AID-CNCR18%3E3.0.CO;2-X/abstract link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/8918410 PubMed]
-##'''Update:''' Soloway MS, Schellhammer P, Sharifi R, Venner P, Patterson AL, Sarosdy M, Vogelzang N, Jones J, Kolvenbag G; Casodex Combination Study Group. A controlled trial of Casodex (bicalutamide) vs flutamide, each in combination with luteinising hormone-releasing hormone analogue therapy in patients with advanced prostate cancer. Eur Urol. 1996;29 Suppl 2:105-9. [https://doi.org/10.1159/000473848 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/8717471 PubMed]
-##'''Update:''' Schellhammer PF, Sharifi R, Block NL, Soloway MS, Venner PM, Patterson AL, Sarosdy MF, Vogelzang NJ, Schellenger JJ, Kolvenbag GJ; Casodex Combination Study Group. Clinical benefits of bicalutamide compared with flutamide in combined androgen blockade for patients with advanced prostatic carcinoma: final report of a double-blind, randomized, multicenter trial. Urology. 1997 Sep;50(3):330-6. [https://www.goldjournal.net/article/S0090-4295(97)00279-3/pdf link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/9301693 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. [http://jjco.oxfordjournals.org/content/34/1/20.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15020659 PubMed]
-##'''Update:''' Akaza H, Hinotsu S, Usami M, Arai Y, Kanetake H, Naito S, Hirao Y; Study Group for the Combined Androgen Blockade Therapy of Prostate Cancer. Combined androgen blockade with bicalutamide for advanced prostate cancer: long-term follow-up of a phase 3, double-blind, randomized study for survival. Cancer. 2009 Aug 1;115(15):3437-45. [https://onlinelibrary.wiley.com/doi/full/10.1002/cncr.24395 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/19536889 PubMed]
-==Bicalutamide & Leuprolide {{#subobject:13 |Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
 |-
-|[[#top|back to top]]
 |}
-===Regimen variant #1, 50/7.5 {{#subobject:13 |Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 ! style="width: 20%" |Study
-! style="width: 20%" |Years of enrollment
+! style="width: 20%" |Dates of enrollment
 ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 ! style="width: 20%" |Comparator
 ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-| rowspan="2" |[http://www.goldjournal.net/article/S0090-4295(99)80077-6/abstract Schellhammer et al. 1995]
+|[https://doi.org/10.1056/nejmoa2119115 Smith et al. 2022 (ARASENS)]
-| rowspan="2" |1992-1993
+<!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
-| rowspan="2" style="background-color:#1a9851" |Phase III (E-RT-switch-ic)
+|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-352-1 <span style="color:white;">ESMO-MCBS (4)</span>]'''
-|1. [[#Bicalutamide_.26_Goserelin_2|Bicalutamide & Goserelin]]
-| style="background-color:#d3d3d3" |Not reported
 |-
-|2. [[#Flutamide_.26_Goserelin_2|Flutamide & Goserelin]]<br> 3. [[#Flutamide_.26_Leuprolide|Flutamide & Leuprolide]]
+|} -->
-| style="background-color:#eeee01" |Equivalent TTP<sup>1</sup>
+|2016-2018
-|-
+| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
-|[https://www.auajournals.org/doi/full/10.1016/S0022-5347%2805%2965175-0 Trachtenberg et al. 2002]
+|[[#ADT_.26_Docetaxel|ADT & Docetaxel]]
-|NR
+| style="background-color:#1a9850" |Superior OS (primary endpoint)<br>Median OS: NYR vs 48.9 mo<br>(HR 0.68, 95% CI 0.57-0.80)
-| style="background-color:#1a9851" |Phase III (C)
-|Abarelix
-| style="background-color:#d73027" |Inferior primary endpoint
 |-
 |}
-''<sup>1</sup>Reported efficacy for Schellhammer et al. 1995 is based on the 1997 final update.''
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Docetaxel (Taxotere)]] as follows:
+**Cycles 1 to 6: 75 mg/m<sup>2</sup> IV once on day 1
 ====Endocrine therapy====
+*[[Darolutamide (Nubeqa)]] 600 mg PO twice per day on days 1 to 21
+*[[:Category:Androgen-deprivation therapy|ADT]]
+'''21-day cycles'''
+</div></div>
+===References===
+#'''ARASENS:''' Smith MR, Hussain M, Saad F, Fizazi K, Sternberg CN, Crawford ED, Kopyltsov E, Park CH, Alekseev B, Montesa-Pino Á, Ye D, Parnis F, Cruz F, Tammela TLJ, Suzuki H, Utriainen T, Fu C, Uemura M, Méndez-Vidal MJ, Maughan BL, Joensuu H, Thiele S, Li R, Kuss I, Tombal B; ARASENS Trial Investigators. Darolutamide and Survival in Metastatic, Hormone-Sensitive Prostate Cancer. N Engl J Med. 2022 Mar 24;386(12):1132-1142. Epub 2022 Feb 17. [https://doi.org/10.1056/nejmoa2119115 link to original article] [https://pubmed.ncbi.nlm.nih.gov/35179323/ PubMed] [https://clinicaltrials.gov/study/NCT02799602 NCT02799602]
-*[[Bicalutamide (Casodex)]] 50 mg PO once per day
+==ADT & Docetaxel {{#subobject:EJCADTdoceR|Regimen=1}}==
-*[[Leuprolide (Lupron)|Leuprolide (Lupron) 1-month depot]] 7.5 mg IM once on day 1
+ADT & Docetaxel: '''<u>A</u>'''ndrogen '''<u>D</u>'''eprivation '''<u>T</u>'''herapy & Docetaxel
+<div class="toccolours" style="background-color:#eeeeee">
-'''28-day cycles'''
+===Regimen variant #1, 6 cycles {{#subobject:EJCADTdoceV|Variant=1}}===
-===Regimen variant #2, 80/3.75 {{#subobject:28699c|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 ! style="width: 20%" |Study
-! style="width: 20%" |Years of enrollment
+! style="width: 20%" |Dates of enrollment
 ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 ! style="width: 20%" |Comparator
 ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[http://jjco.oxfordjournals.org/content/34/1/20.full Akaza et al. 2004]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4800035/ James et al. 2015 (STAMPEDE<sub>docetaxel</sub>)]
-|2000-2001
+<!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
-| style="background-color:#1a9851" |Phase III (E-esc)
+|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-182-1 <span style="color:white;">ESMO-MCBS (4)</span>]'''
-|1. [[#Goserelin_monotherapy|Goserelin]]<br> 2. [[#Leuprolide_monotherapy_2|Leuprolide]]
-| style="background-color:#91cf60" |Seems to have superior OS<sup>1</sup>
 |-
-|}
+|} -->
-''<sup>1</sup>Reported efficacy is based on the 2009 update.''
+|2005-2011
-====Endocrine therapy====
+| style="background-color:#1a9851" |Phase 3 (E-esc)
+|[[#ADT_5|ADT]]
-*[[Bicalutamide (Casodex)]] 80 mg PO once per day
+| style="background-color:#1a9850" |Superior OS (primary endpoint)<br>Median OS: 81 vs 71 mo<br>(HR 0.78, 95% CI 0.66-0.93)
-*[[Leuprolide (Lupron)|Leuprolide (Lupron) 1-month depot]] 3.75 mg SC once on day 1
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc4562797/ Sweeney et al. 2015 (CHAARTED)]
-'''28-day cycles'''
+<!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
+|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-180-1 <span style="color:white;">ESMO-MCBS (4)</span>]'''
-===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. [http://www.goldjournal.net/article/S0090-4295(99)80077-6/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/7538237 PubMed]
+|2006-2012
-##'''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. [https://onlinelibrary.wiley.com/doi/10.1002/(SICI)1097-0142(19961115)78:10%3C2164::AID-CNCR18%3E3.0.CO;2-X/abstract link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/8918410 PubMed]
+| style="background-color:#1a9851" |Phase 3 (E-esc)
-##'''Update:''' Soloway MS, Schellhammer P, Sharifi R, Venner P, Patterson AL, Sarosdy M, Vogelzang N, Jones J, Kolvenbag G; Casodex Combination Study Group. A controlled trial of Casodex (bicalutamide) vs flutamide, each in combination with luteinising hormone-releasing hormone analogue therapy in patients with advanced prostate cancer. Eur Urol. 1996;29 Suppl 2:105-9. [https://doi.org/10.1159/000473848 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/8717471 PubMed]
+|[[#ADT_5|ADT]]
-##'''Update:''' Schellhammer PF, Sharifi R, Block NL, Soloway MS, Venner PM, Patterson AL, Sarosdy MF, Vogelzang NJ, Schellenger JJ, Kolvenbag GJ; Casodex Combination Study Group. Clinical benefits of bicalutamide compared with flutamide in combined androgen blockade for patients with advanced prostatic carcinoma: final report of a double-blind, randomized, multicenter trial. Urology. 1997 Sep;50(3):330-6. [https://www.goldjournal.net/article/S0090-4295(97)00279-3/pdf link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/9301693 PubMed]
+| style="background-color:#1a9850" |Superior OS<sup>1</sup> (primary endpoint)<br>Median OS: 57.6 vs 47.2 mo<br>(HR 0.72, 95% CI 0.59-0.89)
-#Trachtenberg J, Gittleman M, Steidle C, Barzell W, Friedel W, Pessis D, Fotheringham N, Campion M, Garnick MB; Abarelix Study Group. A phase 3, multicenter, open label, randomized study of abarelix versus leuprolide plus daily antiandrogen in men with prostate cancer. J Urol. 2002 Apr;167(4):1670-4. [https://www.auajournals.org/doi/full/10.1016/S0022-5347%2805%2965175-0 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/11912385 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. [http://jjco.oxfordjournals.org/content/34/1/20.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15020659 PubMed]
+|[https://doi.org/10.1056/nejmoa2119115 Smith et al. 2022 (ARASENS)]
-##'''Update:''' Akaza H, Hinotsu S, Usami M, Arai Y, Kanetake H, Naito S, Hirao Y; Study Group for the Combined Androgen Blockade Therapy of Prostate Cancer. Combined androgen blockade with bicalutamide for advanced prostate cancer: long-term follow-up of a phase 3, double-blind, randomized study for survival. Cancer. 2009 Aug 1;115(15):3437-45. [https://onlinelibrary.wiley.com/doi/full/10.1002/cncr.24395 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/19536889 PubMed]
+|2016-2018
+| style="background-color:#1a9851" |Phase 3 (C)
-==Degarelix monotherapy {{#subobject:7 |Regimen=1}}==
+|[[#ADT.2C_Darolutamide.2C_Docetaxel|ADT, Darolutamide, Docetaxel]]
-{| class="wikitable" style="float:right; margin-left: 5px;"
+| style="background-color:#d73027" |Inferior OS
 |-
-|[[#top|back to top]]
 |}
-===Example orders===
+''<sup>1</sup>Reported efficacy for CHAARTED is for the overall population in the 2018 update; in subgroup analysis, only patients with high-volume disease had superior survival in the experimental arm.''<br>
+''Note: STAMPEDE is a platform RCT; this subtrial is labeled by the experimental arm additive therapy. Patients already on androgen deprivation therapy were eligible to participate in CHAARTED if there was no evidence of disease progression and if they had started ADT no more than 120 days before randomization.''
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV over 60 minutes once on day 1
+====Endocrine therapy====
+*[[:Category:Androgen-deprivation therapy|ADT]]
+**Intermittent hormonal therapy was not allowed. Antiandrogens e.g. [[Bicalutamide (Casodex)|bicalutamide]] were allowed at the start of therapy "at the discretion of the investigator."
+====Supportive therapy====
+*[[Dexamethasone (Decadron)]] 8 mg PO given three times; 12 hours, 3 hours, and 1 hour prior to docetaxel
+*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'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
-*[[Example orders for Degarelix (Firmagon) in prostate cancer]]
+===Regimen variant #2, 9 cycles {{#subobject:257951|Variant=1}}===
-===Regimen variant #1, 240/80 {{#subobject:7 |Variant=1}}===
-{| class="wikitable" style="color:white; background-color:#404040"
-|<small>'''FDA-recommended dose'''</small>
-|-
-|}
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 ! style="width: 20%" |Study
-! style="width: 20%" |Years of enrollment
+! style="width: 20%" |Dates of enrollment
 ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 ! style="width: 20%" |Comparator
 ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-| rowspan="2" |[https://onlinelibrary.wiley.com/doi/10.1111/j.1464-410X.2008.08183.x/full Klotz et al. 2008 (CS21)]
+|[https://doi.org/10.1016/S1470-2045(12)70560-0 Gravis et al. 2013 (GETUG-AFU 15)]
-| rowspan="2" |2006-2007
+|2004-2008
-| rowspan="2" style="background-color:#1a9851" |Phase III (E-RT-switch-ic)
+| style="background-color:#1a9851" |Phase 3 (E-esc)
-|1. [[#Degarelix_monotherapy|Degarelix]]; 240/160
+|[[#ADT_5|ADT]]
-| style="background-color:#eeee01" |Non-inferior testosterone suppression
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS<br>Median OS: 58.9 vs 54.2 mo<br>(HR 1.01, 95% CI 0.75-1.36)
-|-
-|2. [[#Leuprolide_monotherapy_2|Leuprolide]]
-| style="background-color:#eeee01" |Non-inferior testosterone suppression
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV over 60 minutes once on day 1
 ====Endocrine therapy====
+*ADT with one of the following:
+**[[:Category:GnRH agonists|LHRH agonist/analog]] with or without [[:Category:Nonsteroidal_androgen_receptor_inhibitors|nonsteroidal androgen receptor inhibitors]]
+**[[Bilateral_orchiectomy|Bilateral orchiectomy]] with or without [[:Category:Nonsteroidal_androgen_receptor_inhibitors|nonsteroidal androgen receptor inhibitors]]
+'''21-day cycle for up to 9 cycles'''
+</div></div>
+===References===
+#'''GETUG-AFU 15:''' 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. [https://doi.org/10.1016/S1470-2045(12)70560-0 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23306100/ PubMed] [https://clinicaltrials.gov/study/NCT00104715 NCT00104715]
+##'''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. [https://doi.org/10.1016/j.eururo.2015.11.005 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26610858/ PubMed]
+#'''CHAARTED:''' 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. [https://doi.org/10.1056/NEJMoa1503747 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc4562797/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26244877/ PubMed] [https://clinicaltrials.gov/study/NCT00309985 NCT00309985]
+##'''Update:''' Kyriakopoulos CE, Chen YH, Carducci MA, Liu G, Jarrard DF, Hahn NM, Shevrin DH, Dreicer R, Hussain M, Eisenberger M, Kohli M, Plimack ER, Vogelzang NJ, Picus J, Cooney MM, Garcia JA, DiPaola RS, Sweeney CJ. Chemohormonal therapy in metastatic hormone-sensitive prostate cancer: long-term survival analysis of the randomized phase III E3805 CHAARTED trial. J Clin Oncol. 2018 Apr 10;36(11):1080-1087. Epub 2018 Jan 31. [https://doi.org/10.1200/JCO.2017.75.3657 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5891129/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29384722/ PubMed]
+##'''HRQoL analysis:''' Morgans AK, Chen YH, Sweeney CJ, Jarrard DF, Plimack ER, Gartrell BA, Carducci MA, Hussain M, Garcia JA, Cella D, DiPaola RS, Patrick-Miller LJ. Quality of life during treatment with chemohormonal therapy: analysis of E3805 chemohormonal androgen ablation randomized trial in prostate cancer. J Clin Oncol. 2018 Apr 10;36(11):1088-1095. Epub 2018 Mar 9. [https://doi.org/10.1200/JCO.2017.75.3335 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5891128/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29522362/ PubMed]
+#'''STAMPEDE<sub>docetaxel</sub>:''' 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. [https://doi.org/10.1016/S0140-6736(15)01037-5 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4800035/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/26719232/ PubMed] [https://clinicaltrials.gov/study/NCT00268476 NCT00268476]
+##'''Update:''' Clarke NW, Ali A, Ingleby FC, Hoyle A, Amos CL, Attard G, Brawley CD, Calvert J, Chowdhury S, Cook A, Cross W, Dearnaley DP, Douis H, Gilbert D, Gillessen S, Jones RJ, Langley RE, MacNair A, Malik Z, Mason MD, Matheson D, Millman R, Parker CC, Ritchie AWS, Rush H, Russell JM, Brown J, Beesley S, Birtle A, Capaldi L, Gale J, Gibbs S, Lydon A, Nikapota A, Omlin A, O'Sullivan JM, Parikh O, Protheroe A, Rudman S, Srihari NN, Simms M, Tanguay JS, Tolan S, Wagstaff J, Wallace J, Wylie J, Zarkar A, Sydes MR, Parmar MKB, James ND. Addition of docetaxel to hormonal therapy in low- and high-burden metastatic hormone sensitive prostate cancer: long-term survival results from the STAMPEDE trial. Ann Oncol. 2019 Dec 1;30(12):1992-2003. [https://doi.org/10.1093/annonc/mdz396 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6938598/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31560068/ PubMed]
+#'''ARASENS:''' Smith MR, Hussain M, Saad F, Fizazi K, Sternberg CN, Crawford ED, Kopyltsov E, Park CH, Alekseev B, Montesa-Pino Á, Ye D, Parnis F, Cruz F, Tammela TLJ, Suzuki H, Utriainen T, Fu C, Uemura M, Méndez-Vidal MJ, Maughan BL, Joensuu H, Thiele S, Li R, Kuss I, Tombal B; ARASENS Trial Investigators. Darolutamide and Survival in Metastatic, Hormone-Sensitive Prostate Cancer. N Engl J Med. 2022 Mar 24;386(12):1132-1142. Epub 2022 Feb 17. [https://doi.org/10.1056/nejmoa2119115 link to original article] [https://pubmed.ncbi.nlm.nih.gov/35179323/ PubMed] [https://clinicaltrials.gov/study/NCT02799602 NCT02799602]
+#'''PEACE-1:''' Fizazi K, Foulon S, Carles J, Roubaud G, McDermott R, Fléchon A, Tombal B, Supiot S, Berthold D, Ronchin P, Kacso G, Gravis G, Calabro F, Berdah JF, Hasbini A, Silva M, Thiery-Vuillemin A, Latorzeff I, Mourey L, Laguerre B, Abadie-Lacourtoisie S, Martin E, El Kouri C, Escande A, Rosello A, Magne N, Schlurmann F, Priou F, Chand-Fouche ME, Freixa SV, Jamaluddin M, Rieger I, Bossi A; PEACE-1 investigators. Abiraterone plus prednisone added to androgen deprivation therapy and docetaxel in de novo metastatic castration-sensitive prostate cancer (PEACE-1): a multicentre, open-label, randomised, phase 3 study with a 2 x 2 factorial design. Lancet. 2022 Apr 30;399(10336):1695-1707. Epub 2022 Apr 8. [https://doi.org/10.1016/s0140-6736(22)00367-1 link to original article] [https://pubmed.ncbi.nlm.nih.gov/35405085/ PubMed] [https://clinicaltrials.gov/study/NCT01957436 NCT01957436]
-*[[Degarelix (Firmagon)]] as follows:
+==ADT & Enzalutamide {{#subobject:79lq3c|Regimen=1}}==
-**Cycle 1: 240 mg SC once on day 1
+ADT & Enzalutamide: '''<u>A</u>'''ndrogen '''<u>D</u>'''eprivation '''<u>T</u>'''herapy & Enzalutamide
-**Cycle 2 onwards: 80 mg SC once on day 1
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:29ncbc|Variant=1}}===
-'''28-day cycles'''
+{| class="wikitable" style="color:white; background-color:#404040"
+|<small>'''FDA-recommended dose'''</small>
-===Regimen variant #2, 240/160 {{#subobject:7b |Variant=1}}===
+|-
+|}
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 ! style="width: 20%" |Study
-! style="width: 20%" |Years of enrollment
+! style="width: 20%" |Dates of enrollment
 ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 ! style="width: 20%" |Comparator
 ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-| rowspan="2" |[https://onlinelibrary.wiley.com/doi/10.1111/j.1464-410X.2008.08183.x/full Klotz et al. 2008 (CS21)]
+|[https://doi.org/10.1056/NEJMoa1903835 Davis et al. 2019 (ENZAMET)]
-| rowspan="2" |2006-2007
+<!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
-| rowspan="2" style="background-color:#1a9851" |Phase III (E-RT-switch-ic)
+|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-178-1 <span style="color:white;">ESMO-MCBS (4)</span>]'''
-|1. [[#Degarelix_monotherapy|Degarelix]]; 240/80
+|-
-| style="background-color:#eeee01" |Non-inferior testosterone suppression
+|} -->
+|2014-2017
+| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
+|1a. [[#ADT_.26_Bicalutamide|ADT & Bicalutamide]]<br>1b. [[#ADT_.26_Flutamide|ADT & Flutamide]]<br>1c. [[#ADT_.26_Nilutamide|ADT & Niluatmide]]
+| style="background-color:#1a9850" |Superior OS<sup>1</sup> (primary endpoint)<br>OS60: 67% vs 57%<br>(HR 0.70, 95% CI 0.58-0.84)
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6839905/ Armstrong et al. 2019 (ARCHES)]
+<!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
+|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-269-1 <span style="color:white;">ESMO-MCBS (3)</span>]'''
+|-
+|} -->
+|2016-2018
+| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
+|[[#ADT_5|ADT]]
+| style="background-color:#1a9850" |Superior OS<sup>2</sup> (secondary endpoint)<br>Median OS: NYR vs NYR<br>(HR 0.66, 95% CI 0.53-0.81)<br><br>Superior rPFS (primary endpoint)<br>Median rPFS: NYR vs 19 mo<br>(HR 0.39, 95% CI 0.30-0.50)
 |-
-|2. [[#Leuprolide_monotherapy_2|Leuprolide]]
+|[https://doi.org/10.1016/s0140-6736(23)01055-3 Agarwal et al. 2023 (TALAPRO-2)]
-| style="background-color:#eeee01" |Non-inferior testosterone suppression
+|2019-01-07 to 2020-09-17
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#ADT.2C_Enzalutamide.2C_Talazoparib|ADT, Enzalutamide, Talazoparib]]
+| style="background-color:#d73027" |Inferior rPFS
 |-
 |}
+''<sup>1</sup>Reported efficacy for ENZAMET is based on the 2023 update.''<br>
+''<sup>2</sup>Reported efficacy for ARCHES is based on the 2022 update.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Endocrine therapy====
+*[[:Category:Androgen-deprivation therapy|ADT]]
+*[[Enzalutamide (Xtandi)]] 160 mg PO once per day
+'''Continued indefinitely'''
+</div></div>
-*[[Degarelix (Firmagon)]] as follows:
+===References===
-**Cycle 1: 240 mg SC once on day 1
+#'''ENZAMET:''' Davis ID, Martin AJ, Stockler MR, Begbie S, Chi KN, Chowdhury S, Coskinas X, Frydenberg M, Hague WE, Horvath LG, Joshua AM, Lawrence NJ, Marx G, McCaffrey J, McDermott R, McJannett M, North SA, Parnis F, Parulekar W, Pook DW, Reaume MN, Sandhu SK, Tan A, Tan TH, Thomson A, Tu E, Vera-Badillo F, Williams SG, Yip S, Zhang AY, Zielinski RR, Sweeney CJ; ENZAMET Trial Investigators and the Australian and New Zealand Urogenital and Prostate Cancer Trials Group. Enzalutamide with standard first-line therapy in metastatic prostate cancer. N Engl J Med. 2019 Jul 11;381(2):121-131. Epub 2019 Jun 2. [https://doi.org/10.1056/NEJMoa1903835 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/31157964/ PubMed] [https://clinicaltrials.gov/study/NCT02446405 NCT02446405]
-**Cycle 2 onwards: 160 mg SC once on day 1
+##'''Update:''' Sweeney CJ, Martin AJ, Stockler MR, Begbie S, Cheung L, Chi KN, Chowdhury S, Frydenberg M, Horvath LG, Joshua AM, Lawrence NJ, Marx G, McCaffrey J, McDermott R, McJannett M, North SA, Parnis F, Parulekar W, Pook DW, Reaume MN, Sandhu SK, Tan A, Tan TH, Thomson A, Vera-Badillo F, Williams SG, Winter D, Yip S, Zhang AY, Zielinski RR, Davis ID; ENZAMET trial investigators and Australian and New Zealand Urogenital and Prostate Cancer Trials Group. Testosterone suppression plus enzalutamide versus testosterone suppression plus standard antiandrogen therapy for metastatic hormone-sensitive prostate cancer (ENZAMET): an international, open-label, randomised, phase 3 trial. Lancet Oncol. 2023 Apr;24(4):323-334. [https://doi.org/10.1016/s1470-2045(23)00063-3 link to original article] [https://pubmed.ncbi.nlm.nih.gov/36990608/ PubMed]
+#'''ARCHES:''' Armstrong AJ, Szmulewitz RZ, Petrylak DP, Holzbeierlein J, Villers A, Azad A, Alcaraz A, Alekseev B, Iguchi T, Shore ND, Rosbrook B, Sugg J, Baron B, Chen L, Stenzl A. ARCHES: a randomized, phase III study of androgen deprivation therapy with enzalutamide or placebo in men with metastatic hormone-sensitive prostate cancer. J Clin Oncol. 2019 Nov 10;37(32):2974-2986. Epub 2019 Jul 22. [https://doi.org/10.1200/JCO.19.00799 link to original article] '''contains dosing details in abstract''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6839905/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31329516/ PubMed] [https://clinicaltrials.gov/study/NCT02677896 NCT02677896]
+##'''HRQoL analysis:''' Stenzl A, Dunshee C, De Giorgi U, Alekseev B, Iguchi T, Szmulewitz RZ, Flaig TW, Tombal B, Morlock R, Ivanescu C, Ramaswamy K, Saad F, Armstrong AJ. Effect of Enzalutamide plus Androgen Deprivation Therapy on Health-related Quality of Life in Patients with Metastatic Hormone-sensitive Prostate Cancer: An Analysis of the ARCHES Randomised, Placebo-controlled, Phase 3 Study. Eur Urol. 2020 Oct;78(4):603-614. Epub 2020 Apr 23. [https://doi.org/10.1016/j.eururo.2020.03.019 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32336645/ PubMed]
+##'''Update:''' Armstrong AJ, Azad AA, Iguchi T, Szmulewitz RZ, Petrylak DP, Holzbeierlein J, Villers A, Alcaraz A, Alekseev B, Shore ND, Gomez-Veiga F, Rosbrook B, Zohren F, Yamada S, Haas GP, Stenzl A. Improved Survival With Enzalutamide in Patients With Metastatic Hormone-Sensitive Prostate Cancer. J Clin Oncol. 2022 May 20;40(15):1616-1622. Epub 2022 Apr 14. [https://doi.org/10.1200/jco.22.00193 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9113211/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/35420921/ PubMed]
+#'''TALAPRO-2:''' Agarwal N, Azad AA, Carles J, Fay AP, Matsubara N, Heinrich D, Szczylik C, De Giorgi U, Young Joung J, Fong PCC, Voog E, Jones RJ, Shore ND, Dunshee C, Zschäbitz S, Oldenburg J, Lin X, Healy CG, Di Santo N, Zohren F, Fizazi K. Talazoparib plus enzalutamide in men with first-line metastatic castration-resistant prostate cancer (TALAPRO-2): a randomised, placebo-controlled, phase 3 trial. Lancet. 2023 Jul 22;402(10398):291-303. Epub 2023 Jun 4. Erratum in: Lancet. 2023 Jul 22;402(10398):290. [https://doi.org/10.1016/s0140-6736(23)01055-3 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/37285865/ PubMed] [https://clinicaltrials.gov/study/NCT03395197 NCT03395197]
-'''28-day cycles'''
+==ADT, Enzalutamide, Talazoparib {{#subobject:79ltzc|Regimen=1}}==
+ADT, Enzalutamide, Talazoparib: '''<u>A</u>'''ndrogen '''<u>D</u>'''eprivation '''<u>T</u>'''herapy, Enzalutamide, Talazoparib
-===Regimen variant #3, 240/480 {{#subobject:01864f |Variant=1}}===
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:tlgcbc|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 ! style="width: 20%" |Study
-! style="width: 20%" |Years of enrollment
+! style="width: 20%" |Dates of enrollment
 ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 ! style="width: 20%" |Comparator
 ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5989846/ Ozono et al. 2018 (3550-CL-0010)]
+|[https://doi.org/10.1016/s0140-6736(23)01055-3 Agarwal et al. 2023 (TALAPRO-2)]
-|2013-NR
+|2019-01-07 to 2020-09-17
-| style="background-color:#1a9851" |Phase III (E-switch-ic)
+| style="background-color:#1a9851" |Phase 3 (E-esc)
-|[[#Goserelin_monotherapy_2|Goserelin]]
+|[[#ADT_.26_Enzalutamide_2|ADT & Enzalutamide]]
-| style="background-color:#eeee01" |Non-inferior testosterone suppression
+| style="background-color:#1a9850" |Superior rPFS (primary endpoint)<br>Median rPFS: NYR vs 21.9 mo<br>(HR 0.63, 95% CI 0.51-0.78)
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Endocrine therapy====
+*[[:Category:Androgen-deprivation therapy|ADT]]
-*[[Degarelix (Firmagon)]] as follows:
+*[[Enzalutamide (Xtandi)]] 160 mg PO once per day
-**Cycle 1: 240 mg SC once on day 1
+====Targeted therapy====
-**Cycle 2 onwards: 480 mg SC once on day 1
+*[[Talazoparib (Talzenna)]] 0.5 mg PO once per day
+'''Continued indefinitely'''
-'''28-day cycle for 1 cycle, then 12-week cycles'''
+</div></div>
 ===References===
+#'''TALAPRO-2:''' Agarwal N, Azad AA, Carles J, Fay AP, Matsubara N, Heinrich D, Szczylik C, De Giorgi U, Young Joung J, Fong PCC, Voog E, Jones RJ, Shore ND, Dunshee C, Zschäbitz S, Oldenburg J, Lin X, Healy CG, Di Santo N, Zohren F, Fizazi K. Talazoparib plus enzalutamide in men with first-line metastatic castration-resistant prostate cancer (TALAPRO-2): a randomised, placebo-controlled, phase 3 trial. Lancet. 2023 Jul 22;402(10398):291-303. Epub 2023 Jun 4. Erratum in: Lancet. 2023 Jul 22;402(10398):290. [https://doi.org/10.1016/s0140-6736(23)01055-3 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/37285865/ PubMed] [https://clinicaltrials.gov/study/NCT03395197 NCT03395197]
-#'''CS21:''' 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. [https://onlinelibrary.wiley.com/doi/10.1111/j.1464-410X.2008.08183.x/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19035858 PubMed]
+==ADT & Flutamide {{#subobject:8y4q3c|Regimen=1}}==
-##'''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. [http://www.europeanurology.com/article/S0302-2838%2809%2901171-3 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19962227 PubMed]
+ADT & Flutamide: '''<u>A</u>'''ndrogen '''<u>D</u>'''eprivation '''<u>T</u>'''herapy & Flutamide
-#'''3550-CL-0010:''' Ozono S, Tsukamoto T, Naito S, Horie S, Ohashi Y, Uemura H, Yokomizo Y, Fukasawa S, Kusuoka H, Akazawa R, Saito M, Akaza H. Efficacy and safety of 3-month dosing regimen of degarelix in Japanese subjects with prostate cancer: a phase III study. Cancer Sci. 2018 Jun;109(6):1920-1929. Epub 2018 May 23. [https://onlinelibrary.wiley.com/doi/abs/10.1111/cas.13600 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5989846/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/29624800 PubMed] NCT01964170
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:29jx89|Variant=1}}===
-==Flutamide monotherapy {{#subobject:8 |Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
-===Regimen {{#subobject:8 |Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 ! style="width: 20%" |Study
-! style="width: 20%" |Years of enrollment
+! style="width: 20%" |Dates of enrollment
 ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 ! style="width: 20%" |Comparator
 ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.karger.com/Article/Abstract/480795 Boccon-Gibod et al. 1997]
+|[https://doi.org/10.1056/NEJMoa1903835 Davis et al. 2019 (ENZAMET)]
-|1989-1991
+|2014-2017
-| style="background-color:#1a9851" |Phase III (E-switch-ic)
+| style="background-color:#1a9851" |Phase 3 (C)
-|[[Prostate_cancer_-_historical#Castration|Bilateral orchiectomy]]
+|[[#ADT_.26_Enzalutamide_2|ADT & Enzalutamide]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
+| style="background-color:#d73027" |Inferior OS<sup>1</sup>
-|-
-|[https://doi.org/10.1200/JCO.2001.19.1.62 Fosså et al. 2001 (EORTC 30903)]
-|1992-1998
-| style="background-color:#1a9851" |Phase III (E-switch-ic)
-|[[#Prednisone_monotherapy|Prednisone]]
-| style="background-color:#ffffbf" |Did not meet primary endpoints of TTP/OS
 |-
 |}
-''Not approved for monotherapy in the United States. See combination regimens with Goserelin & Leuprolide.''
+''<sup>1</sup>Reported efficacy is based on the 2023 update.''<br>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Endocrine therapy====
+*[[:Category:Androgen-deprivation therapy|ADT]]
 *[[Flutamide (Eulexin)]] 250 mg PO three times per day
+'''Continued indefinitely'''
+</div></div>
-'''Continued indefinitely'''
 ===References===
+#'''ENZAMET:''' Davis ID, Martin AJ, Stockler MR, Begbie S, Chi KN, Chowdhury S, Coskinas X, Frydenberg M, Hague WE, Horvath LG, Joshua AM, Lawrence NJ, Marx G, McCaffrey J, McDermott R, McJannett M, North SA, Parnis F, Parulekar W, Pook DW, Reaume MN, Sandhu SK, Tan A, Tan TH, Thomson A, Tu E, Vera-Badillo F, Williams SG, Yip S, Zhang AY, Zielinski RR, Sweeney CJ; ENZAMET Trial Investigators and the Australian and New Zealand Urogenital and Prostate Cancer Trials Group. Enzalutamide with standard first-line therapy in metastatic prostate cancer. N Engl J Med. 2019 Jul 11;381(2):121-131. Epub 2019 Jun 2. [https://doi.org/10.1056/NEJMoa1903835 link to original article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/31157964/ PubMed] [https://clinicaltrials.gov/study/NCT02446405 NCT02446405]
-#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. [https://www.karger.com/Article/Abstract/480795 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/9412794 PubMed]
+##'''Update:''' Sweeney CJ, Martin AJ, Stockler MR, Begbie S, Cheung L, Chi KN, Chowdhury S, Frydenberg M, Horvath LG, Joshua AM, Lawrence NJ, Marx G, McCaffrey J, McDermott R, McJannett M, North SA, Parnis F, Parulekar W, Pook DW, Reaume MN, Sandhu SK, Tan A, Tan TH, Thomson A, Vera-Badillo F, Williams SG, Winter D, Yip S, Zhang AY, Zielinski RR, Davis ID; ENZAMET trial investigators and Australian and New Zealand Urogenital and Prostate Cancer Trials Group. Testosterone suppression plus enzalutamide versus testosterone suppression plus standard antiandrogen therapy for metastatic hormone-sensitive prostate cancer (ENZAMET): an international, open-label, randomised, phase 3 trial. Lancet Oncol. 2023 Apr;24(4):323-334. [https://doi.org/10.1016/s1470-2045(23)00063-3 link to original article] [https://pubmed.ncbi.nlm.nih.gov/36990608/ PubMed]
-#'''EORTC 30903:''' 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. [https://doi.org/10.1200/JCO.2001.19.1.62 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/11134196 PubMed]
+==ADT & Nilutamide {{#subobject:8ymx2c|Regimen=1}}==
+ADT & Nilutamide: '''<u>A</u>'''ndrogen '''<u>D</u>'''eprivation '''<u>T</u>'''herapy & Nilutamide
-==Flutamide & Goserelin {{#subobject:11 |Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
-{| class="wikitable" style="float:right; margin-left: 5px;"
+===Regimen {{#subobject:ceex89|Variant=1}}===
-|-
-|[[#top|back to top]]
-|}
-===Regimen {{#subobject:11 |Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 ! style="width: 20%" |Study
-! style="width: 20%" |Years of enrollment
+! style="width: 20%" |Dates of enrollment
 ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 ! style="width: 20%" |Comparator
 ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1002/cncr.1990.66.s5.1058 Iversen et al. 1990]
+|[https://doi.org/10.1056/NEJMoa1903835 Davis et al. 2019 (ENZAMET)]
-|1986-1987
+|2014-2017
-| style="background-color:#1a9851" |Phase III (E-switch-ic)
+| style="background-color:#1a9851" |Phase 3 (C)
-|[[Prostate_cancer_-_historical#Castration|Bilateral orchiectomy]]
+|[[#ADT_.26_Enzalutamide_2|ADT & Enzalutamide]]
-| style="background-color:#ffffbf" |Did not meet primary endpoints of OS/PFS/TTP
+| style="background-color:#d73027" |Inferior OS<sup>1</sup>
-|-
-|[https://doi.org/10.1002/cncr.1990.66.s5.1045 Keuppens et al. 1990 (EORTC 30853)]
-|1986-1988
-| style="background-color:#1a9851" |Phase III (E-switch-ic)
-|[[Prostate_cancer_-_historical#Castration|Bilateral orchiectomy]]
-| style="background-color:#91cf60" |Seems to have superior OS<sup>1</sup>
-|-
-| rowspan="2" |[http://www.goldjournal.net/article/S0090-4295(99)80077-6/abstract Schellhammer et al. 1995]
-| rowspan="2" |1992-1993
-| rowspan="2" style="background-color:#1a9851" |Phase III (C)
-|1. [[#Bicalutamide_.26_Goserelin_2|Bicalutamide & Goserelin]]<br> 2. [[#Bicalutamide_.26_Leuprolide|Bicalutamide & Leuprolide]]
-| style="background-color:#eeee01" |Equivalent TTP<sup>2</sup>
-|-
-|3. [[#Flutamide_.26_Leuprolide|Flutamide & Leuprolide]]
-| style="background-color:#d3d3d3" |Not reported
-|-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3682658/ Hussain et al. 2013 (SWOG-9346)]
-|1995-2008
-| style="background-color:#1a9851" |Phase III (C)
-|[[#Intermittent_ADT|Intermittent ADT]]
-| style="background-color:#ffffbf" |Inconclusive whether non-inferior OS
 |-
 |}
-''<sup>1</sup>Reported efficacy for EORTC 30853 is based on the 1998 final update.''<br>
+''<sup>1</sup>Reported efficacy is based on the 2023 update.''<br>
-''<sup>2</sup>Reported efficacy for Schellhammer et al. 1995 is based on the 1997 final update.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Endocrine therapy====
+*[[:Category:Androgen-deprivation therapy|ADT]]
+*[[Nilutamide (Nilandron)]] 150 mg PO once per day
+'''Continued indefinitely'''
+</div></div>
-*[[Flutamide (Eulexin)]] 250 mg PO three times per day
-*[[Goserelin (Zoladex)]] 3.6 mg SC once on day 1
-'''28-day cycles'''
 ===References===
-#'''EORTC 30853:''' Keuppens F, Denis L, Smith P, Carvalho AP, Newling D, Bond A, Sylvester R, De Pauw M, Vermeylen K, Ongena P; EORTC GU Group. Zoladex and flutamide versus bilateral orchiectomy: a randomized phase III EORTC 30853 study. Cancer. 1990 Sep 1;66(5 Suppl):1045-57. [https://doi.org/10.1002/cncr.1990.66.s5.1045 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2144206/ PubMed]
+#'''ENZAMET:''' Davis ID, Martin AJ, Stockler MR, Begbie S, Chi KN, Chowdhury S, Coskinas X, Frydenberg M, Hague WE, Horvath LG, Joshua AM, Lawrence NJ, Marx G, McCaffrey J, McDermott R, McJannett M, North SA, Parnis F, Parulekar W, Pook DW, Reaume MN, Sandhu SK, Tan A, Tan TH, Thomson A, Tu E, Vera-Badillo F, Williams SG, Yip S, Zhang AY, Zielinski RR, Sweeney CJ; ENZAMET Trial Investigators and the Australian and New Zealand Urogenital and Prostate Cancer Trials Group. Enzalutamide with standard first-line therapy in metastatic prostate cancer. N Engl J Med. 2019 Jul 11;381(2):121-131. Epub 2019 Jun 2. [https://doi.org/10.1056/NEJMoa1903835 link to original article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/31157964/ PubMed] [https://clinicaltrials.gov/study/NCT02446405 NCT02446405]
-##'''Update:''' Denis LJ, Carnelro de Moura JL, Bono A, Sylvester R, Whelan P, Newling D, Depauw M; [[Study_Groups#EORTC|EORTC]] GU Group. Goserelin acetate and flutamide versus bilateral orchiectomy: a phase III EORTC trial (30853). Urology. 1993 Aug;42(2):119-29. [https://www.goldjournal.net/article/0090-4295(93)90634-M/pdf link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/8367920 PubMed]
+##'''Update:''' Sweeney CJ, Martin AJ, Stockler MR, Begbie S, Cheung L, Chi KN, Chowdhury S, Frydenberg M, Horvath LG, Joshua AM, Lawrence NJ, Marx G, McCaffrey J, McDermott R, McJannett M, North SA, Parnis F, Parulekar W, Pook DW, Reaume MN, Sandhu SK, Tan A, Tan TH, Thomson A, Vera-Badillo F, Williams SG, Winter D, Yip S, Zhang AY, Zielinski RR, Davis ID; ENZAMET trial investigators and Australian and New Zealand Urogenital and Prostate Cancer Trials Group. Testosterone suppression plus enzalutamide versus testosterone suppression plus standard antiandrogen therapy for metastatic hormone-sensitive prostate cancer (ENZAMET): an international, open-label, randomised, phase 3 trial. Lancet Oncol. 2023 Apr;24(4):323-334. [https://doi.org/10.1016/s1470-2045(23)00063-3 link to original article] [https://pubmed.ncbi.nlm.nih.gov/36990608/ PubMed]
-##'''Update:''' Denis LJ, Keuppens F, Smith PH, Whelan P, de Moura JL, Newling D, Bono A, Sylvester R; [[Study_Groups#EORTC|EORTC]] Genito-Urinary Tract Cancer Cooperative Group and the EORTC Data Center. Maximal androgen blockade: final analysis of EORTC phase III trial 30853. Eur Urol. 1998;33(2):144-51. [https://doi.org/10.1159/000019546 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/9519355 PubMed]
+==Bicalutamide monotherapy {{#subobject:5 |Regimen=1}}==
-#Iversen P, Christensen MG, Friis E, Hornbøl P, Hvidt V, Iversen HG, Klarskov P, Krarup T, Lund F, Mogensen P, et al. A phase III trial of zoladex and flutamide versus orchiectomy in the treatment of patients with advanced carcinoma of the prostate. Cancer. 1990 Sep 1;66(5 Suppl):1058-66. [https://doi.org/10.1002/cncr.1990.66.s5.1058 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/2144207/ PubMed]
+<div class="toccolours" style="background-color:#eeeeee">
-#Schellhammer P, Sharifi R, Block N, Soloway M, Venner P, Patterson AL, Sarosdy M, Vogelzang N, Jones J, Kolvenbag G; Casodex Combination Study Group. A controlled trial of bicalutamide versus flutamide, each in combination with luteinizing hormone-releasing hormone analogue therapy, in patients with advanced prostate cancer. Urology. 1995 May;45(5):745-52. [http://www.goldjournal.net/article/S0090-4295(99)80077-6/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/7538237 PubMed]
+===Regimen {{#subobject:5 |Variant=1}}===
-##'''Update:''' Schellhammer PF, Sharifi R, Block NL, Soloway MS, Venner PM, Patterson AL, Sarosdy MF, Vogelzang NJ, Chen Y, Kolvenbag GJ; CASODEX Combination Study Group. 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. Cancer. 1996 Nov 15;78(10):2164-9. [https://onlinelibrary.wiley.com/doi/10.1002/(SICI)1097-0142(19961115)78:10%3C2164::AID-CNCR18%3E3.0.CO;2-X/abstract link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/8918410 PubMed]
-##'''Update:''' Soloway MS, Schellhammer P, Sharifi R, Venner P, Patterson AL, Sarosdy M, Vogelzang N, Jones J, Kolvenbag G; Casodex Combination Study Group. A controlled trial of Casodex (bicalutamide) vs flutamide, each in combination with luteinising hormone-releasing hormone analogue therapy in patients with advanced prostate cancer. Eur Urol. 1996;29 Suppl 2:105-9. [https://doi.org/10.1159/000473848 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/8717471 PubMed]
-##'''Update:''' Schellhammer PF, Sharifi R, Block NL, Soloway MS, Venner PM, Patterson AL, Sarosdy MF, Vogelzang NJ, Schellenger JJ, Kolvenbag GJ; Casodex Combination Study Group. Clinical benefits of bicalutamide compared with flutamide in combined androgen blockade for patients with advanced prostatic carcinoma: final report of a double-blind, randomized, multicenter trial. Urology. 1997 Sep;50(3):330-6. [https://www.goldjournal.net/article/S0090-4295(97)00279-3/pdf link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/9301693 PubMed]
-#'''SWOG-9346:''' 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. [https://www.nejm.org/doi/full/10.1056/NEJMoa1212299 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3682658/ link to PMC article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1212299/suppl_file/nejmoa1212299_protocol.pdf supplementary protocol] '''contains verified protocol in supplementary protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23550669 PubMed] NCT00002651
-==Flutamide & Leuprolide {{#subobject:14 |Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
-===Regimen variant #1, daily Lupron {{#subobject:5b0861 |Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 ! style="width: 20%" |Study
-! style="width: 20%" |Years of enrollment
+! style="width: 20%" |Dates of enrollment
 ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 ! style="width: 20%" |Comparator
 ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.nejm.org/doi/full/10.1056/NEJM198908173210702 Crawford et al. 1989 (SWOG-8494)]
+|[https://doi.org/10.1159/000019634 Tyrrell et al. 1998]
-|1985-1986
+|NR in abstract
-| style="background-color:#1a9851" |Phase III (E-RT-esc)
+| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
-|[[#Leuprolide_monotherapy_2|Leuprolide]]
+|[[Prostate_cancer_-_historical#Castration|Castration]]
-| style="background-color:#91cf60" |Seems to have superior OS
+| style="background-color:#ffffbf" |Did not meet co-primary endpoints of PFS/OS<sup>1</sup>
+|-
+|[https://doi.org/10.1016/s0302-2838(02)00311-1 Iversen et al. 2002 (SPCG-6)]
+|1995-1998
+| style="background-color:#1a9851" |Phase 3 (E-esc)
+|[[Prostate_cancer_-_null_regimens#Placebo_3|Placebo]]
+| style="background-color:#1a9850" |Superior OS<sup>2</sup><br>(HR 0.77, 95% CI 0.63-0.94)
 |-
 |}
-''Note: this is likely of historic importance only, given the formulation of leuoprolide.''
+''<sup>1</sup>Reported efficacy for Tyrrell et al. 1998 is based on the 2000 update.''<br>
+''<sup>2</sup>Reported efficacy for SPCG-6 is based on the 2015 update and is only for the locally advanced subgroup.''<br>
+''Note: Bicalutamide is not approved for monotherapy in the United States. See combination regimens with goserelin & leuprolide.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Endocrine therapy====
+*[[Bicalutamide (Casodex)]] 150 mg PO once per day
-*[[Flutamide (Eulexin)]] 250 mg PO three times per day
-*[[Leuprolide (Lupron)]] 1 mg SC once per day
 '''Continued indefinitely'''
+</div></div>
+===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. [https://doi.org/10.1159/000019634 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/9643663/ 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. [https://doi.org/10.1016/S0022-5347(05)67032-2 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/11025708/ PubMed]
+#'''SPCG-6:''' Iversen P, Tammela TL, Vaage S, Lukkarinen O, Lodding P, Bull-Njaa T, Viitanen J, Hoisaeter P, Lundmo P, Rasmussen F, Johansson JE, Persson BE, Carroll K; Scandinavian Prostatic Cancer Group. A randomised comparison of bicalutamide ('Casodex') 150 mg versus placebo as immediate therapy either alone or as adjuvant to standard care for early non-metastatic prostate cancer: first report from the Scandinavian Prostatic Cancer Group Study No 6. Eur Urol. 2002 Sep;42(3):204-11. [https://doi.org/10.1016/s0302-2838(02)00311-1 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12234503/ PubMed] [https://clinicaltrials.gov/study/NCT00672282 NCT00672282]
+##'''Update:''' Iversen P, Johansson JE, Lodding P, Lukkarinen O, Lundmo P, Klarskov P, Tammela TL, Tasdemir I, Morris T, Carroll K; Scandinavian Prostatic Cancer Group. Bicalutamide (150 mg) versus placebo as immediate therapy alone or as adjuvant to therapy with curative intent for early nonmetastatic prostate cancer: 5.3-year median followup from the Scandinavian Prostate Cancer Group Study Number 6. J Urol. 2004 Nov;172(5 Pt 1):1871-6. [https://www.auajournals.org/article/S0022-5347(05)60880-4 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15540741/ PubMed]
+##'''Update:''' Iversen P, Johansson JE, Lodding P, Kylmälä T, Lundmo P, Klarskov P, Tammela TL, Tasdemir I, Morris T, Armstrong J; Scandinavian Prostate Cancer Group. Bicalutamide 150 mg in addition to standard care for patients with early non-metastatic prostate cancer: updated results from the Scandinavian Prostate Cancer Period Group-6 Study after a median follow-up period of 7.1 years. Scand J Urol Nephrol. 2006;40(6):441-52. [https://doi.org/10.1080/00365590601017329 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17130095/ PubMed]
+##'''Update:''' Thomsen FB, Brasso K, Christensen IJ, Johansson JE, Angelsen A, Tammela TL, Iversen P; Scandinavian Prostate Cancer Group. Survival benefit of early androgen receptor inhibitor therapy in locally advanced prostate cancer: long-term follow-up of the SPCG-6 study. Eur J Cancer. 2015 Jul;51(10):1283-92. Epub 2015 Apr 16. [https://doi.org/10.1016/j.ejca.2015.03.021 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25892647/ PubMed]
-===Regimen variant #2, 1-month depot Lupron {{#subobject:14 |Variant=1}}===
+==Bicalutamide & Goserelin {{#subobject:10 |Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #1, 50/3.6 {{#subobject:10 |Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 ! style="width: 20%" |Study
-! style="width: 20%" |Years of enrollment
+! style="width: 20%" |Dates of enrollment
 ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 ! style="width: 20%" |Comparator
 ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-| rowspan="2" |[http://www.goldjournal.net/article/S0090-4295(99)80077-6/abstract Schellhammer et al. 1995]
+| rowspan="2" |[https://doi.org/10.1016/s0090-4295(99)80077-6 Schellhammer et al. 1995]
-| rowspan="2" |1992-1993
+| rowspan="2" |1992-01 to 1993-09
-| rowspan="2" style="background-color:#1a9851" |Phase III (C)
+| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-RT-switch-ic)
-|1. [[#Bicalutamide_.26_Goserelin_2|Bicalutamide & Goserelin]]<br> 2. [[#Bicalutamide_.26_Leuprolide|Bicalutamide & Leuprolide]]
+|1. [[#Bicalutamide_.26_Leuprolide|Bicalutamide & Leuprolide]]
+| style="background-color:#d3d3d3" |Not reported
+|-
+|2. [[#Flutamide_.26_Goserelin_2|Flutamide & Goserelin]]<br> 3. [[#Flutamide_.26_Leuprolide|Flutamide & Leuprolide]]
 | style="background-color:#eeee01" |Equivalent TTP<sup>1</sup>
 |-
-|3. [[#Flutamide_.26_Goserelin_2|Flutamide & Goserelin]]
+|}
-| style="background-color:#d3d3d3" |Not reported
-|-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3682658/ Hussain et al. 2013 (SWOG-9346)]
-|1995-2008
-| style="background-color:#1a9851" |Phase III (C)
-|[[#Intermittent_ADT|Intermittent ADT]]
-| style="background-color:#ffffbf" |Inconclusive whether non-inferior OS
-|-
-|}
 ''<sup>1</sup>Reported efficacy for Schellhammer et al. 1995 is based on the 1997 final update.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Endocrine therapy====
+*[[Bicalutamide (Casodex)]] 50 mg PO once per day on days 1 to 28
-*[[Flutamide (Eulexin)]] 250 mg PO three times per day
+*[[Goserelin (Zoladex)]] 3.6 mg SC once on day 1
-*[[Leuprolide (Lupron)|Leuprolide (Lupron) 1-month depot]] 7.5 mg IM once on day 1
 '''28-day cycles'''
-===References===
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
-#'''SWOG-8494:''' Crawford ED, Eisenberger MA, McLeod DG, Spaulding JT, Benson R, Dorr FA, Blumenstein BA, Davis MA, Goodman PJ. A controlled trial of leuprolide with and without flutamide in prostatic carcinoma. N Engl J Med. 1989 Aug 17;321(7):419-24. Erratum in: N Engl J Med 1989 Nov 16;321(20):1420. [https://www.nejm.org/doi/full/10.1056/NEJM198908173210702 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/2503724 PubMed]
+===Regimen variant #2, 80/3.6 {{#subobject:a8fe78|Variant=1}}===
-#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. [http://www.goldjournal.net/article/S0090-4295(99)80077-6/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/7538237 PubMed]
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-##'''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. [https://onlinelibrary.wiley.com/doi/10.1002/(SICI)1097-0142(19961115)78:10%3C2164::AID-CNCR18%3E3.0.CO;2-X/abstract link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/8918410 PubMed]
+! style="width: 20%" |Study
-##'''Update:''' Soloway MS, Schellhammer P, Sharifi R, Venner P, Patterson AL, Sarosdy M, Vogelzang N, Jones J, Kolvenbag G; Casodex Combination Study Group. A controlled trial of Casodex (bicalutamide) vs flutamide, each in combination with luteinising hormone-releasing hormone analogue therapy in patients with advanced prostate cancer. Eur Urol. 1996;29 Suppl 2:105-9. [https://doi.org/10.1159/000473848 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/8717471 PubMed]
+! style="width: 20%" |Dates of enrollment
-##'''Update:''' Schellhammer PF, Sharifi R, Block NL, Soloway MS, Venner PM, Patterson AL, Sarosdy MF, Vogelzang NJ, Schellenger JJ, Kolvenbag GJ; Casodex Combination Study Group. Clinical benefits of bicalutamide compared with flutamide in combined androgen blockade for patients with advanced prostatic carcinoma: final report of a double-blind, randomized, multicenter trial. Urology. 1997 Sep;50(3):330-6. [https://www.goldjournal.net/article/S0090-4295(97)00279-3/pdf link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/9301693 PubMed]
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
-#'''SWOG-9346:''' 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. [https://www.nejm.org/doi/full/10.1056/NEJMoa1212299 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3682658/ link to PMC article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1212299/suppl_file/nejmoa1212299_protocol.pdf supplementary protocol] '''contains verified protocol in supplementary protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23550669 PubMed] NCT00002651
+! style="width: 20%" |Comparator
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-==Goserelin monotherapy {{#subobject:9 |Regimen=1}}==
+|-
-{| class="wikitable" style="float:right; margin-left: 5px;"
+|[http://jjco.oxfordjournals.org/content/34/1/20.full Akaza et al. 2004]
+|2000-02 to 2001-12
+| style="background-color:#1a9851" |Phase 3 (E-esc)
+|1. [[#Goserelin_monotherapy_2|Goserelin]]<br>2. [[#Leuprolide_monotherapy_3|Leuprolide]]
+| style="background-color:#91cf60" |Seems to have superior OS<sup>1</sup> (secondary endpoint)<br><br>Superior 12-week PSA normalization rate (primary endpoint)
 |-
-|[[#top|back to top]]
 |}
-===Example orders===
+''<sup>1</sup>Reported efficacy is based on the 2009 update.''
+<div class="toccolours" style="background-color:#b3e2cd">
+====Endocrine therapy====
+*[[Bicalutamide (Casodex)]] 80 mg PO once per day on days 1 to 28
+*[[Goserelin (Zoladex)]] 3.6 mg SC once on day 1
+'''28-day cycles'''
+</div></div>
-*[[Example orders for Goserelin (Zoladex) in prostate cancer]]
+===References===
+#Schellhammer P, Sharifi R, Block N, Soloway M, Venner P, Patterson AL, Sarosdy M, Vogelzang N, Jones J, Kolvenbag G; Casodex Combination Study Group. A controlled trial of bicalutamide versus flutamide, each in combination with luteinizing hormone-releasing hormone analogue therapy, in patients with advanced prostate cancer. Urology. 1995 May;45(5):745-52. [https://doi.org/10.1016/s0090-4295(99)80077-6 link to original article] [https://pubmed.ncbi.nlm.nih.gov/7538237/ PubMed]
-===Regimen variant #1, 28-day cycles {{#subobject:9 |Variant=1}}===
+##'''Update:''' Schellhammer PF, Sharifi R, Block NL, Soloway MS, Venner PM, Patterson AL, Sarosdy MF, Vogelzang NJ, Chen Y, Kolvenbag GJ; CASODEX Combination Study Group. 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. Cancer. 1996 Nov 15;78(10):2164-9. [https://doi.org/10.1002/(SICI)1097-0142(19961115)78:10%3C2164::AID-CNCR18%3E3.0.CO;2-X link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/8918410/ PubMed]
+##'''Update:''' Soloway MS, Schellhammer P, Sharifi R, Venner P, Patterson AL, Sarosdy M, Vogelzang N, Jones J, Kolvenbag G; Casodex Combination Study Group. A controlled trial of Casodex (bicalutamide) vs flutamide, each in combination with luteinising hormone-releasing hormone analogue therapy in patients with advanced prostate cancer. Eur Urol. 1996;29 Suppl 2:105-9. [https://doi.org/10.1159/000473848 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/8717471/ PubMed]
+##'''Update:''' Schellhammer PF, Sharifi R, Block NL, Soloway MS, Venner PM, Patterson AL, Sarosdy MF, Vogelzang NJ, Schellenger JJ, Kolvenbag GJ; Casodex Combination Study Group. Clinical benefits of bicalutamide compared with flutamide in combined androgen blockade for patients with advanced prostatic carcinoma: final report of a double-blind, randomized, multicenter trial. Urology. 1997 Sep;50(3):330-6. [https://doi.org/10.1016/S0090-4295(97)00279-3 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9301693/ 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. [http://jjco.oxfordjournals.org/content/34/1/20.full link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15020659/ PubMed]
+##'''Update:''' Akaza H, Hinotsu S, Usami M, Arai Y, Kanetake H, Naito S, Hirao Y; Study Group for the Combined Androgen Blockade Therapy of Prostate Cancer. Combined androgen blockade with bicalutamide for advanced prostate cancer: long-term follow-up of a phase 3, double-blind, randomized study for survival. Cancer. 2009 Aug 1;115(15):3437-45. [https://doi.org/10.1002/cncr.24395 link to original article] [https://pubmed.ncbi.nlm.nih.gov/19536889/ PubMed]
+==Bicalutamide & Leuprolide {{#subobject:13 |Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #1, 50 + 1 mo depot {{#subobject:13 |Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 ! style="width: 20%" |Study
-! style="width: 20%" |Years of enrollment
+! style="width: 20%" |Dates of enrollment
 ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 ! style="width: 20%" |Comparator
 ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.goldjournal.net/article/0090-4295(91)80077-K/pdf Soloway et al. 1991]
+| rowspan="2" |[https://doi.org/10.1016/s0090-4295(99)80077-6 Schellhammer et al. 1995]
-|NR
+| rowspan="2" |1992-01 to 1993-09
-| style="background-color:#1a9851" |Phase III (E-switch-ic)
+| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-RT-switch-ic)
-|[[Prostate_cancer_-_historical#Castration|Bilateral orchiectomy]]
+|1. [[#Bicalutamide_.26_Goserelin_3|Bicalutamide & Goserelin]]
-| style="background-color:#ffffbf" |Did not meet efficacy endpoints
+| style="background-color:#d3d3d3" |Not reported
 |-
-|[https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1464-410X.1991.tb15195.x Kaisary et al. 1991]
+|2. [[#Flutamide_.26_Goserelin_2|Flutamide & Goserelin]]<br> 3. [[#Flutamide_.26_Leuprolide|Flutamide & Leuprolide]]
-|1983-1986
+| style="background-color:#eeee01" |Equivalent TTP<sup>1</sup>
-| style="background-color:#1a9851" |Phase III (E-switch-ic)
-|[[Prostate_cancer_-_historical#Castration|Bilateral orchiectomy]]
-| style="background-color:#ffffbf" |Did not meet efficacy endpoints
 |-
-|[https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1464-410X.1992.tb15633.x Waymont et al. 1992]
+|[https://www.auajournals.org/doi/full/10.1016/S0022-5347%2805)65175-0 Trachtenberg et al. 2002]
-|1985-1987
+|NR
-| style="background-color:#1a9851" |Phase III (E-switch-ic)
+| style="background-color:#1a9851" |Phase 3 (C)
-|DES
+|[[#Abarelix_monotherapy_888|Abarelix]]
-| style="background-color:#91cf60" |Seems to have superior time to first response
+| style="background-color:#d73027" |Inferior primary endpoint
-|-
-|[https://doi.org/10.1016/s0022-5347(17)38080-1 Tyrrell et al. 1991 (IPCSG)]
-|1986-1987
-| style="background-color:#1a9851" |Phase III (C)
-|[[#Flutamide_.26_Goserelin_2|Flutamide & Goserelin]]
-| style="background-color:#ffffbf" |Did not meet efficacy endpoints
-|-
-|[https://www.ejcancer.com/article/S0959-8049(05)80293-X/abstract Boccardo et al. 1993 (PONCAP)]
-|1987-1990
-| style="background-color:#1a9851" |Phase III (C)
-|[[#Flutamide_.26_Goserelin_2|Flutamide & Goserelin]]
-| style="background-color:#fee08b" |Might have inferior PFS50%
 |-
 |}
+''<sup>1</sup>Reported efficacy for Schellhammer et al. 1995 is based on the 1997 final update.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Endocrine therapy====
+*[[Bicalutamide (Casodex)]] 50 mg PO once per day on days 1 to 28
-*[[Goserelin (Zoladex)]] 3.6 mg SC once on day 1
+*[[Leuprolide (Lupron)|Leuprolide (Lupron) 1-month depot]] 7.5 mg IM once on day 1
 '''28-day cycles'''
+</div></div><br>
-===Regimen variant #2, 12-week cycles {{#subobject:7afffe |Variant=1}}===
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #2, 50 + 3 mo depot {{#subobject:13ugj1 |Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 ! style="width: 20%" |Study
-! style="width: 20%" |Years of enrollment
+! style="width: 20%" |Dates of enrollment
 ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 ! style="width: 20%" |Comparator
 ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5989846/ Ozono et al. 2018 (3550-CL-0010)]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9553390/ Agarwal et al. 2022 (SWOG S1216)]
-|2015-NR
+|2013-2017
-| style="background-color:#1a9851" |Phase III (C)
+| style="background-color:#1a9851" |Phase 3 (C)
-|[[#Degarelix_monotherapy|Degarelix]]
+|[[#ADT_.26_Orteronel_999|ADT & Orteronel]]
-| style="background-color:#eeee01" |Non-inferior testosterone suppression
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Endocrine therapy====
+*[[Bicalutamide (Casodex)]] 50 mg PO once per day on days 1 to 90
-*[[Goserelin (Zoladex)]] as follows:
+*[[Leuprolide (Lupron)|Leuprolide (Lupron) 3-month depot]] 22.5 mg IM once on day 1
-**Cycle 1: 3.6 mg SC once on day 1
+'''90-day cycles'''
-**Cycle 2 onwards: 10.8 mg SC once on day 1
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
-'''28-day cycle for 1 cycle, then 12-week cycles'''
+===Regimen variant #3, 80 + 1 mo depot {{#subobject:28699c|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-===References===
+! style="width: 20%" |Study
+! style="width: 20%" |Dates of enrollment
-#Soloway MS, Chodak G, Vogelzang NJ, Block NL, Schellhammer PF, Smith JA Jr, Scott M, Kennealey G, Gau TC; Zoladex Prostate Study Group. Zoladex versus orchiectomy in treatment of advanced prostate cancer: a randomized trial. Urology. 1991 Jan;37(1):46-51. [https://www.goldjournal.net/article/0090-4295(91)80077-K/pdf link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/1824732 PubMed]
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
-##'''Update:''' Vogelzang NJ, Chodak GW, Soloway MS, Block NL, Schellhammer PF, Smith JA Jr, Caplan RJ, Kennealey GT; Zoladex Prostate Study Group. Goserelin versus orchiectomy in the treatment of advanced prostate cancer: final results of a randomized trial. Urology. 1995 Aug;46(2):220-6. [http://www.goldjournal.net/article/S0090-4295(99)80197-6/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/7624991 PubMed]
+! style="width: 20%" |Comparator
-#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. [https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1464-410X.1991.tb15195.x link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/1828183 PubMed]
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-#'''IPCSG:''' Tyrrell CJ, Altwein JE, Klippel F, Varenhorst E, Lunglmayr G, Boccardo F, Holdaway IM, Haefliger JM, Jordaan JP; International Prostate Cancer Study Group. A multicenter randomized trial comparing the luteinizing hormone-releasing hormone analogue goserelin acetate alone and with flutamide in the treatment of advanced prostate cancer. J Urol. 1991 Nov;146(5):1321-6. [https://doi.org/10.1016/s0022-5347(17)38080-1 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/1834864 PubMed]
-#Waymont B, Lynch TH, Dunn JA, Emtage LA, Arkell DG, Wallace DM, Blackledge GR. Phase III randomised study of zoladex versus stilboestrol in the treatment of advanced prostate cancer. Br J Urol. 1992 Jun;69(6):614-20. [https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1464-410X.1992.tb15633.x link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/1386272 PubMed]
-#'''PONCAP:''' Boccardo F, Pace M, Rubagotti A, Guarneri D, Decensi A, Oneto F, Martorana G, Giuliani L, Selvaggi F, Battaglia M, Delli Ponti U, Petracco S, Cortellini P, Ziveri M, Ferraris V, Bruttini GP, Epis R, Comeri G, Gallo G; Italian Prostatic Cancer Project (PONCAP) Study Group. Goserelin acetate with or without flutamide in the treatment of patients with locally advanced or metastatic prostate cancer. Eur J Cancer. 1993;29A(8):1088-93. [https://www.ejcancer.com/article/S0959-8049(05)80293-X/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/8518017 PubMed]
-#'''3550-CL-0010:''' Ozono S, Tsukamoto T, Naito S, Horie S, Ohashi Y, Uemura H, Yokomizo Y, Fukasawa S, Kusuoka H, Akazawa R, Saito M, Akaza H. Efficacy and safety of 3-month dosing regimen of degarelix in Japanese subjects with prostate cancer: a phase III study. Cancer Sci. 2018 Jun;109(6):1920-1929. Epub 2018 May 23. [https://onlinelibrary.wiley.com/doi/abs/10.1111/cas.13600 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5989846/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/29624800 PubMed] NCT01964170
-==Histrelin monotherapy {{#subobject:97agub |Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
 |-
-|[[#top|back to top]]
+|[http://jjco.oxfordjournals.org/content/34/1/20.full Akaza et al. 2004]
-|}
+|2000-02 to 2001-12
-===Regimen {{#subobject:918gya|Variant=1}}===
+| style="background-color:#1a9851" |Phase 3 (E-esc)
-{| class="wikitable" style="width: 50%; text-align:center;"
+|1. [[#Goserelin_monotherapy|Goserelin]]<br>2. [[#Leuprolide_monotherapy_3|Leuprolide]]
-! style="width: 33%" |Study
+| style="background-color:#91cf60" |Seems to have superior OS<sup>1</sup> (secondary endpoint)
-! style="width: 33%" |Years of enrollment
-! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]
-|-
-|[https://www.auajournals.org/doi/full/10.1016/S0022-5347%2805%2900649-X Schlegel 2006]
-|NR
-| style="background-color:#91cf61" |Non-randomized (RT)
 |-
 |}
+''<sup>1</sup>Reported efficacy is based on the 2009 update.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Endocrine therapy====
+*[[Bicalutamide (Casodex)]] 80 mg PO once per day on days 1 to 28
-*[[Histrelin (Vantas)]]
+*[[Leuprolide (Lupron)|Leuprolide (Lupron) 1-month depot]] 3.75 mg SC once on day 1
+'''28-day cycles'''
+</div></div>
 ===References===
+#Schellhammer P, Sharifi R, Block N, Soloway M, Venner P, Patterson AL, Sarosdy M, Vogelzang N, Jones J, Kolvenbag G; Casodex Combination Study Group. A controlled trial of bicalutamide versus flutamide, each in combination with luteinizing hormone-releasing hormone analogue therapy, in patients with advanced prostate cancer. Urology. 1995 May;45(5):745-52. [https://doi.org/10.1016/s0090-4295(99)80077-6 link to original article] [https://pubmed.ncbi.nlm.nih.gov/7538237/ PubMed]
+##'''Update:''' Schellhammer PF, Sharifi R, Block NL, Soloway MS, Venner PM, Patterson AL, Sarosdy MF, Vogelzang NJ, Chen Y, Kolvenbag GJ; CASODEX Combination Study Group. 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. Cancer. 1996 Nov 15;78(10):2164-9. [https://doi.org/10.1002/(SICI)1097-0142(19961115)78:10%3C2164::AID-CNCR18%3E3.0.CO;2-X link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/8918410/ PubMed]
+##'''Update:''' Soloway MS, Schellhammer P, Sharifi R, Venner P, Patterson AL, Sarosdy M, Vogelzang N, Jones J, Kolvenbag G; Casodex Combination Study Group. A controlled trial of Casodex (bicalutamide) vs flutamide, each in combination with luteinising hormone-releasing hormone analogue therapy in patients with advanced prostate cancer. Eur Urol. 1996;29 Suppl 2:105-9. [https://doi.org/10.1159/000473848 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/8717471/ PubMed]
+##'''Update:''' Schellhammer PF, Sharifi R, Block NL, Soloway MS, Venner PM, Patterson AL, Sarosdy MF, Vogelzang NJ, Schellenger JJ, Kolvenbag GJ; Casodex Combination Study Group. Clinical benefits of bicalutamide compared with flutamide in combined androgen blockade for patients with advanced prostatic carcinoma: final report of a double-blind, randomized, multicenter trial. Urology. 1997 Sep;50(3):330-6. [https://doi.org/10.1016/S0090-4295(97)00279-3 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9301693/ PubMed]
+#Trachtenberg J, Gittleman M, Steidle C, Barzell W, Friedel W, Pessis D, Fotheringham N, Campion M, Garnick MB; Abarelix Study Group. A phase 3, multicenter, open label, randomized study of abarelix versus leuprolide plus daily antiandrogen in men with prostate cancer. J Urol. 2002 Apr;167(4):1670-4. [https://www.auajournals.org/doi/full/10.1016/S0022-5347%2805)65175-0 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/11912385/ 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. [http://jjco.oxfordjournals.org/content/34/1/20.full link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15020659/ PubMed]
+##'''Update:''' Akaza H, Hinotsu S, Usami M, Arai Y, Kanetake H, Naito S, Hirao Y; Study Group for the Combined Androgen Blockade Therapy of Prostate Cancer. Combined androgen blockade with bicalutamide for advanced prostate cancer: long-term follow-up of a phase 3, double-blind, randomized study for survival. Cancer. 2009 Aug 1;115(15):3437-45. [https://doi.org/10.1002/cncr.24395 link to original article] [https://pubmed.ncbi.nlm.nih.gov/19536889/ PubMed]
+#'''SWOG S1216:''' Agarwal N, Tangen CM, Hussain MHA, Gupta S, Plets M, Lara PN, Harzstark AL, Twardowski PW, Paller CJ, Zylla D, Zibelman MR, Levine E, Roth BJ, Goldkorn A, Vaena DA, Kohli M, Crispino T, Vogelzang NJ, Thompson IM Jr, Quinn DI. Orteronel for Metastatic Hormone-Sensitive Prostate Cancer: A Multicenter, Randomized, Open-Label Phase III Trial (SWOG-1216). J Clin Oncol. 2022 Oct 1;40(28):3301-3309. Epub 2022 Apr 21. [https://doi.org/10.1200/jco.21.02517 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9553390/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/35446628/ PubMed] [https://clinicaltrials.gov/study/NCT01809691 NCT01809691]
+##'''Subgroup analysis:''' Sayegh N, Swami U, Jo Y, Gebrael G, Haaland B, Gupta S, Plets M, Hussain MHA, Quinn DI, Lara PN Jr, Thompson IM Jr, Agarwal N. Race and Treatment Outcomes in Patients With Metastatic Castration-Sensitive Prostate Cancer: A Secondary Analysis of the SWOG 1216 Phase 3 Trial. JAMA Netw Open. 2023 Aug 1;6(8):e2326546. [https://doi.org/10.1001/jamanetworkopen.2023.26546 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc10394570/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/37526936/ PubMed]
-#Schlegel PN; Histrelin Study Group. Efficacy and safety of histrelin subdermal implant in patients with advanced prostate cancer. J Urol. 2006 Apr;175(4):1353-8. [https://www.auajournals.org/doi/full/10.1016/S0022-5347%2805%2900649-X link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/16515997 PubMed]
+==Degarelix monotherapy {{#subobject:7 |Regimen=1}}==
+===Example orders===
-==Intermittent ADT==
+*[[Example orders for Degarelix (Firmagon) in prostate cancer]]
-{| class="wikitable" style="float:right; margin-left: 5px;"
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #1, 240/80 {{#subobject:7 |Variant=1}}===
+{| class="wikitable" style="color:white; background-color:#404040"
+|<small>'''FDA-recommended dose'''</small>
 |-
-|[[#top|back to top]]
 |}
-IHT: '''<u>I</u>'''ntermittent '''<u>H</u>'''ormone '''<u>T</u>'''herapy
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-===Regimen===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
 ! style="width: 20%" |Study
-! style="width: 20%" |Years of enrollment
+! style="width: 20%" |Dates of enrollment
 ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 ! style="width: 20%" |Comparator
 ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.europeanurology.com/article/S0302-2838(09)00159-6/fulltext Calais da Silva et al. 2009 (SEUG 9401)]
+| rowspan="2" |[https://doi.org/10.1111/j.1464-410X.2008.08183.x Klotz et al. 2008 (CS21)]
-|NR
+| rowspan="2" |2006-02 to 2007-10
-| style="background-color:#1a9851" |Phase III (E-de-esc)
+| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-RT-switch-ic)
-|Continuous ADT
+|1. [[#Degarelix_monotherapy_2|Degarelix]]; 240/160
-| style="background-color:#ffffbf" |Did not meet primary endpoint of TTP
+| style="background-color:#eeee01" |Non-inferior testosterone suppression (primary endpoint)
+|-
+|2. [[#Leuprolide_monotherapy_3|Leuprolide]]
+| style="background-color:#eeee01" |Non-inferior testosterone suppression (primary endpoint)
 |-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3682658/ Hussain et al. 2013 (SWOG-9346)]
+|}
-|1995-2008
+<div class="toccolours" style="background-color:#b3e2cd">
-| style="background-color:#1a9851" |Phase III (E-de-esc)
+====Endocrine therapy====
-|Continuous ADT
+*[[Degarelix (Firmagon)]] as follows:
-| style="background-color:#ffffbf" |Inconclusive whether non-inferior OS
+**Cycle 1: 240 mg SC once on day 1
+**Cycle 2 onwards: 80 mg SC once on day 1
+'''28-day cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #2, 240/160 {{#subobject:7b |Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+! style="width: 20%" |Study
+! style="width: 20%" |Dates of enrollment
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |Comparator
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3521033/ Crook et al. 2012 (NCIC-CTG PR.7)]
+| rowspan="2" |[https://doi.org/10.1111/j.1464-410X.2008.08183.x Klotz et al. 2008 (CS21)]
-|1999-2005
+| rowspan="2" |2006-02 to 2007-10
-| style="background-color:#1a9851" |Phase III (E-de-esc)
+| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-RT-switch-ic)
-|Continuous ADT
+|1. [[#Degarelix_monotherapy_2|Degarelix]]; 240/80
-| style="background-color:#eeee01" |Non-inferior OS
+| style="background-color:#eeee01" |Non-inferior testosterone suppression (primary endpoint)
 |-
-|[https://www.europeanurology.com/article/S0302-2838(13)00342-4/fulltext Calais da Silva et al. 2013 (SEUG 9901)]
+|2. [[#Leuprolide_monotherapy_3|Leuprolide]]
-|2000-2007
+| style="background-color:#eeee01" |Non-inferior testosterone suppression (primary endpoint)
-| style="background-color:#1a9851" |Phase III (E-de-esc)
-|Continuous ADT
-| style="background-color:#eeee01" |Non-inferior OS
 |-
 |}
-''See papers for details about treatment holidays.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Endocrine therapy====
+*[[Degarelix (Firmagon)]] as follows:
-*[[:Category:GnRH agonists|LHRH agonist]]
+**Cycle 1: 240 mg SC once on day 1
-*[[:Category:Nonsteroidal_antiandrogens|Nonsteroidal antiandrogen]] for at least 4 weeks
+**Cycle 2 onwards: 160 mg SC once on day 1
+'''28-day cycles'''
-'''8-month cycles'''
+</div></div><br>
-===References===
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #3, 240/480 {{#subobject:01864f |Variant=1}}===
-#'''SEUG 9401:''' Calais da Silva FE, Bono AV, Whelan P, Brausi M, Marques Queimadelos A, Martin JA, Kirkali Z, Calais da Silva FM, Robertson C. Intermittent androgen deprivation for locally advanced and metastatic prostate cancer: results from a randomised phase 3 study of the South European Uroncological Group. Eur Urol. 2009 Jun;55(6):1269-77. Epub 2009 Feb 21. [https://www.europeanurology.com/article/S0302-2838(09)00159-6/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/19249153 PubMed]
-#'''NCIC-CTG PR.7:''' Crook JM, O'Callaghan CJ, Duncan G, Dearnaley DP, Higano CS, Horwitz EM, Frymire E, Malone S, Chin J, Nabid A, Warde P, Corbett T, Angyalfi S, Goldenberg SL, Gospodarowicz MK, Saad F, Logue JP, Hall E, Schellhammer PF, Ding K, Klotz L. Intermittent androgen suppression for rising PSA level after radiotherapy. N Engl J Med. 2012 Sep 6;367(10):895-903. Erratum in: N Engl J Med. 2012 Dec 6;367(23):2262. [https://www.nejm.org/doi/full/10.1056/NEJMoa1201546 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3521033/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/22931259 PubMed] NCT00003653
-#'''SWOG-9346:''' 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. [https://www.nejm.org/doi/full/10.1056/NEJMoa1212299 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3682658/ link to PMC article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1212299/suppl_file/nejmoa1212299_protocol.pdf supplementary protocol] '''contains verified protocol in supplementary protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23550669 PubMed] NCT00002651
-#'''SEUG 9901:''' Calais da Silva F, Calais da Silva FM, Gonçalves F, Santos A, Kliment J, Whelan P, Oliver T, Antoniou N, Pastidis S, Marques Queimadelos A, Robertson C. Locally advanced and metastatic prostate cancer treated with intermittent androgen monotherapy or maximal androgen blockade: results from a randomised phase 3 study by the South European Uroncological Group. Eur Urol. 2014 Aug;66(2):232-9. Epub 2013 Apr 4. [https://www.europeanurology.com/article/S0302-2838(13)00342-4/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/23582949 PubMed]
-==Leuprolide monotherapy {{#subobject:12 |Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
-===Example orders===
-*[[Example orders for Leuprolide (Lupron) in prostate cancer]]
-===Regimen variant #1, daily {{#subobject:c6f258 |Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
-! style="width: 17%" |Study
+! style="width: 20%" |Study
-! style="width: 15%" |Years of enrollment
+! style="width: 20%" |Dates of enrollment
-! style="width: 17%" |[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
-! style="width: 17%" |Comparator
+! style="width: 20%" |Comparator
-! style="width: 17%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-! style="width: 17%" |[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 |-
-|[https://www.nejm.org/doi/full/10.1056/NEJM198411153112004 Garnick et al. 1984]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5989846/ Ozono et al. 2018 (3550-CL-0010)]
-|1981-NR
+|2013-NR
-| style="background-color:#1a9851" |Phase III (E-switch-ic)
+| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
-|DES
+|[[#Goserelin_monotherapy_2|Goserelin]]
-| style="background-color:#ffffbf" |Did not meet efficacy endpoints
+| style="background-color:#eeee01" |Non-inferior testosterone suppression (primary endpoint)
-| style="background-color:#1a9850" |Less toxic
-|-
-|[https://www.nejm.org/doi/full/10.1056/NEJM198908173210702 Crawford et al. 1989 (SWOG-8494)]
-|1985-1986
-| style="background-color:#1a9851" |Phase III (C)
-|[[#Flutamide_.26_Leuprolide|Flutamide & Leuprolide]]
-| style="background-color:#fc8d59" |Seems to have inferior OS
-|
 |-
 |}
-''Note: this is of historic importance only, given the wide availability of depot formulations of leuoprolide.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Endocrine therapy====
+*[[Degarelix (Firmagon)]] as follows:
-*[[Leuprolide (Lupron)]] 1 mg SC once per day
+**Cycle 1: 240 mg SC once on day 1
+**Cycle 2 onwards: 480 mg SC once on day 1
-'''Continued indefinitely'''
+'''28-day course, then 12-week cycles'''
+</div></div>
-===Regimen variant #2, 1-month depot, 3.75 mg {{#subobject:172cb3|Variant=1}}===
+===References===
+#'''CS21:''' 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. [https://doi.org/10.1111/j.1464-410X.2008.08183.x link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19035858/ PubMed] [https://clinicaltrials.gov/study/NCT00295750 NCT00295750]
+##'''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. [https://doi.org/10.1016/j.eururo.2009.11.029 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19962227/ PubMed]
+#'''3550-CL-0010:''' Ozono S, Tsukamoto T, Naito S, Horie S, Ohashi Y, Uemura H, Yokomizo Y, Fukasawa S, Kusuoka H, Akazawa R, Saito M, Akaza H. Efficacy and safety of 3-month dosing regimen of degarelix in Japanese subjects with prostate cancer: a phase III study. Cancer Sci. 2018 Jun;109(6):1920-1929. Epub 2018 May 23. [https://doi.org/10.1111/cas.13600 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5989846/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29624800/ PubMed] [https://clinicaltrials.gov/study/NCT01964170 NCT01964170]
+==Docetaxel, Estramustine, Goserelin {{#subobject:7nc12c|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:3ac6bc|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 ! style="width: 20%" |Study
-! style="width: 20%" |Years of enrollment
+! style="width: 20%" |Dates of enrollment
 ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 ! style="width: 20%" |Comparator
 ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[http://jjco.oxfordjournals.org/content/34/1/20.full Akaza et al. 2004]
+|[https://doi.org/10.1016/S1470-2045(15)00011-X Fizazi et al. 2015 (GETUG 12)]
-|2000-2001
+|2002-2006
-| style="background-color:#1a9851" |Phase III (C)
+| style="background-color:#1a9851" |Phase 3 (E-esc)
-|1. [[#Bicalutamide_.26_Goserelin_2|Bicalutamide & Goserelin]]<br> 2. [[#Bicalutamide_.26_Leuprolide|Bicalutamide & Leuprolide]]
+|[[#ADT_5|ADT]]
-| style="background-color:#fc8d59" |Seems to have inferior OS<sup>1</sup>
+| style="background-color:#1a9850" |Superior RFS (primary endpoint)<br>RFS96: 62% vs 50%<br>(HR 0.71, 95% CI 0.54-0.94)
 |-
 |}
-''<sup>1</sup>Reported efficacy is based on the 2009 update.''
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Docetaxel (Taxotere)]] 70 mg/m<sup>2</sup> IV once on day 2
+*[[Estramustine (Emcyt)]] 10 mg/kg/day PO on days 1 to 5
+'''21-day cycle for 4 cycles'''
 ====Endocrine therapy====
+*[[Goserelin (Zoladex)]] 10.8 mg SC once on day 1
+'''3-month cycle for 12 cycles (3 years)'''
+</div></div>
+===References===
+#'''GETUG 12:''' Fizazi K, Faivre L, Lesaunier F, Delva R, Gravis G, Rolland F, Priou F, Ferrero JM, Houede N, Mourey L, Theodore C, Krakowski I, Berdah JF, Baciuchka M, Laguerre B, Fléchon A, Ravaud A, Cojean-Zelek I, Oudard S, Labourey JL, Chinet-Charrot P, Legouffe E, Lagrange JL, Linassier C, Deplanque G, Beuzeboc P, Davin JL, Martin AL, Habibian M, Laplanche A, Culine S. Androgen deprivation therapy plus docetaxel and estramustine versus androgen deprivation therapy alone for high-risk localised prostate cancer (GETUG 12): a phase 3 randomised controlled trial. Lancet Oncol. 2015 Jul;16(7):787-94. Epub 2015 May 28. [https://doi.org/10.1016/S1470-2045(15)00011-X link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/26028518/ PubMed] [https://clinicaltrials.gov/study/NCT00055731 NCT00055731]
-*[[Leuprolide (Lupron)|Leuprolide (Lupron) 1-month depot]] 3.75 mg SC once on day 1
+==Flutamide monotherapy {{#subobject:8 |Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
-'''28-day cycles'''
+===Regimen {{#subobject:8 |Variant=1}}===
-===Regimen variant #3, 1-month depot, 7.5 mg {{#subobject:172cb4|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 ! style="width: 20%" |Study
-! style="width: 20%" |Years of enrollment
+! style="width: 20%" |Dates of enrollment
 ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 ! style="width: 20%" |Comparator
 ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.auajournals.org/doi/abs/10.1016/S0022-5347%2817%2939868-3 Sharifi & Soloway 1990]
+|[https://doi.org/10.1159/000480795 Boccon-Gibod et al. 1997]
-|1986-NR
+|1989-1991
-| style="background-color:#91cf61" |Non-randomized (RT)
+| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
-| style="background-color:#d3d3d3" |
+|[[Prostate_cancer_-_historical#Castration|Bilateral orchiectomy]]
-| style="background-color:#d3d3d3" |
+| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 |-
-| rowspan="2" |[https://onlinelibrary.wiley.com/doi/10.1111/j.1464-410X.2008.08183.x/full Klotz et al. 2008 (CS21)]
+|[https://doi.org/10.1200/JCO.2001.19.1.62 Fosså et al. 2001 (EORTC 30903)]
-| rowspan="2" |2006-2007
+|1992-1998
-| rowspan="2" style="background-color:#1a9851" |Phase III (C)
+| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
-|1. [[#Degarelix_monotherapy|Degarelix 240/80]]
+|[[#Prednisone_monotherapy|Prednisone]]
-| style="background-color:#eeee01" |Non-inferior testosterone suppression
+| style="background-color:#ffffbf" |Did not meet co-primary endpoints of TTP/OS
-|-
-|2. [[#Degarelix_monotherapy|Degarelix 240/160]]
-| style="background-color:#eeee01" |Non-inferior testosterone suppression
 |-
 |}
+''Note: Flutamide is not approved for monotherapy in the United States. See combination regimens with goserelin & leuprolide.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Endocrine therapy====
+*[[Flutamide (Eulexin)]] 250 mg PO three times per day
+'''Continued indefinitely'''
+</div></div>
+===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. [https://doi.org/10.1159/000480795 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/9412794/ PubMed]
+#'''EORTC 30903:''' 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. [https://doi.org/10.1200/JCO.2001.19.1.62 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/11134196/ PubMed]
-*[[Leuprolide (Lupron)|Leuprolide (Lupron) 1-month depot]] 7.5 mg IM once on day 1
+==Flutamide & Goserelin {{#subobject:11 |Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
-'''28-day cycles'''
+===Regimen {{#subobject:11 |Variant=1}}===
-===Regimen variant #4, 3-month depot {{#subobject:5415fc |Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
+! style="width: 20%" |Study
-!style="width: 20%"|Years of enrollment
+! style="width: 20%" |Dates of enrollment
-!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 20%"|Comparator
+! style="width: 20%" |Comparator
-!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[http://www.clinicaltherapeutics.com/article/S0149-2918(96)80215-3/pdf Sharifi et al. 1996]
+|[https://doi.org/10.1002/cncr.1990.66.s5.1058 Iversen et al. 1990]
-|NR
+|1986-06 to 1987-12
-| style="background-color:#91cf61" |Phase II (RT)
+| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
-| style="background-color:#d3d3d3" |
+|[[Prostate_cancer_-_historical#Castration|Bilateral orchiectomy]]
-| style="background-color:#d3d3d3" |
+| style="background-color:#ffffbf" |Did not meet co-primary endpoints of OS/PFS/TTP
 |-
-|[https://pubmed.ncbi.nlm.nih.gov/32469183/ Shore et al. 2020 (HERO)]
+|[https://doi.org/10.1002/cncr.1990.66.s5.1045 Keuppens et al. 1990 (EORTC 30853)]
-|2017-2018
+|1986-1988
-| style="background-color:#1a9851" |Phase III (C)
+| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
-|[[#Relugolix_monotherapy|Relugolix]]
+|[[Prostate_cancer_-_historical#Castration|Bilateral orchiectomy]]
-| style="background-color:#d73027" |Inferior testosterone suppression
+| style="background-color:#91cf60" |Seems to have superior OS<sup>1</sup>
 |-
-|}
+| rowspan="2" |[https://doi.org/10.1016/s0090-4295(99)80077-6 Schellhammer et al. 1995]
-====Endocrine therapy====
+| rowspan="2" |1992-01 to 1993-09
+| rowspan="2" style="background-color:#1a9851" |Phase 3 (C)
-*[[Leuprolide (Lupron)|Leuprolide (Lupron) 3-month depot]] 22.5 mg IM once on day 1
+|1. [[#Bicalutamide_.26_Goserelin_3|Bicalutamide & Goserelin]]<br>2. [[#Bicalutamide_.26_Leuprolide|Bicalutamide & Leuprolide]]
+| style="background-color:#eeee01" |Equivalent TTP<sup>2</sup>
-'''84-day cycles'''
-===Regimen variant #5, 4-month depot {{#subobject:21b60f |Variant=1}}===
-{| class="wikitable" style="width: 50%; text-align:center;"
-! style="width: 33%" |Study
-! style="width: 33%" |Years of enrollment
-! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
-|[http://www.goldjournal.net/article/S0090-4295(97)00500-1/pdf Sharifi et al. 1998]
+|3. [[#Flutamide_.26_Leuprolide|Flutamide & Leuprolide]]
-|NR
+| style="background-color:#d3d3d3" |Not reported
-| style="background-color:#91cf61" |Phase II (RT)
 |-
-|}
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3682658/ Hussain et al. 2013 (SWOG-9346)]
-====Endocrine therapy====
+|1995-2008
+| style="background-color:#1a9851" |Phase 3 (C)
-*[[Leuprolide (Lupron)|Leuprolide (Lupron) 4-month depot]] 30 mg IM once on day 1
+|[[#Intermittent_ADT|Intermittent ADT]]
+| style="background-color:#ffffbf" |Inconclusive whether non-inferior OS
-'''16-week cycles'''
-===Regimen variant #6, 6-month depot {{#subobject:21720f |Variant=1}}===
-{| class="wikitable" style="width: 50%; text-align:center;"
-! style="width: 33%" |Study
-! style="width: 33%" |Years of enrollment
-! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]
-|-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3278745/ Spitz et al. 2011 (L-PC07-169)]
-|2008-2009
-| style="background-color:#91cf61" |Non-randomized (RT)
 |-
 |}
+''<sup>1</sup>Reported efficacy for EORTC 30853 is based on the 1998 final update.''<br>
+''<sup>2</sup>Reported efficacy for Schellhammer et al. 1995 is based on the 1997 final update.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Endocrine therapy====
+*[[Flutamide (Eulexin)]] 250 mg PO three times per day on days 1 to 28
-*[[Leuprolide (Lupron)|Leuprolide (Lupron) 6-month depot]] 45 mg IM once on day 1
+*[[Goserelin (Zoladex)]] 3.6 mg SC once on day 1
+'''28-day cycles'''
-'''26-week cycles'''
+</div></div>
 ===References===
+#'''EORTC 30853:''' Keuppens F, Denis L, Smith P, Carvalho AP, Newling D, Bond A, Sylvester R, De Pauw M, Vermeylen K, Ongena P; EORTC GU Group. Zoladex and flutamide versus bilateral orchiectomy: a randomized phase III EORTC 30853 study. Cancer. 1990 Sep 1;66(5 Suppl):1045-57. [https://doi.org/10.1002/cncr.1990.66.s5.1045 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2144206/ PubMed]
-#Garnick MB, Glode LM; Leuprolide Study Group. Leuprolide versus diethylstilbestrol for metastatic prostate cancer. N Engl J Med. 1984 Nov 15;311(20):1281-6. [https://www.nejm.org/doi/full/10.1056/NEJM198411153112004 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/6436700 PubMed]
+##'''Update:''' Denis LJ, Carnelro de Moura JL, Bono A, Sylvester R, Whelan P, Newling D, De Pauw M; [[Study_Groups#EORTC|EORTC]] GU Group. Goserelin acetate and flutamide versus bilateral orchiectomy: a phase III EORTC trial (30853). Urology. 1993 Aug;42(2):119-29. [https://doi.org/10.1016/0090-4295(93)90634-M link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/8367920/ PubMed]
-#'''SWOG-8494:''' Crawford ED, Eisenberger MA, McLeod DG, Spaulding JT, Benson R, Dorr FA, Blumenstein BA, Davis MA, Goodman PJ. A controlled trial of leuprolide with and without flutamide in prostatic carcinoma. N Engl J Med. 1989 Aug 17;321(7):419-24. Erratum in: N Engl J Med 1989 Nov 16;321(20):1420. [https://www.nejm.org/doi/full/10.1056/NEJM198908173210702 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/2503724 PubMed]
+##'''Update:''' Denis LJ, Keuppens F, Smith PH, Whelan P, de Moura JL, Newling D, Bono A, Sylvester R; [[Study_Groups#EORTC|EORTC]] Genito-Urinary Tract Cancer Cooperative Group and the EORTC Data Center. Maximal androgen blockade: final analysis of EORTC phase III trial 30853. Eur Urol. 1998;33(2):144-51. [https://doi.org/10.1159/000019546 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9519355/ PubMed]
-#Sharifi R, Soloway M; Leuprolide Study Group. Clinical study of leuprolide depot formulation in the treatment of advanced prostate cancer. J Urol. 1990 Jan;143(1):68-71. [https://www.auajournals.org/doi/abs/10.1016/S0022-5347%2817%2939868-3 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/2104638 PubMed]
+#Iversen P, Christensen MG, Friis E, Hornbøl P, Hvidt V, Iversen HG, Klarskov P, Krarup T, Lund F, Mogensen P, Pedersen T, Rasmussen F, Rose C, Skaarup P, Wolf H. A phase III trial of zoladex and flutamide versus orchiectomy in the treatment of patients with advanced carcinoma of the prostate. Cancer. 1990 Sep 1;66(5 Suppl):1058-66. [https://doi.org/10.1002/cncr.1990.66.s5.1058 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/2144207/ PubMed]
-#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. [http://www.clinicaltherapeutics.com/article/S0149-2918(96)80215-3/pdf link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/8879893 PubMed]
+#Schellhammer P, Sharifi R, Block N, Soloway M, Venner P, Patterson AL, Sarosdy M, Vogelzang N, Jones J, Kolvenbag G; Casodex Combination Study Group. A controlled trial of bicalutamide versus flutamide, each in combination with luteinizing hormone-releasing hormone analogue therapy, in patients with advanced prostate cancer. Urology. 1995 May;45(5):745-52. [https://doi.org/10.1016/s0090-4295(99)80077-6 link to original article] [https://pubmed.ncbi.nlm.nih.gov/7538237/ 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. [http://www.goldjournal.net/article/S0090-4295(97)00500-1/pdf link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/9495710 PubMed]
+##'''Update:''' Schellhammer PF, Sharifi R, Block NL, Soloway MS, Venner PM, Patterson AL, Sarosdy MF, Vogelzang NJ, Chen Y, Kolvenbag GJ; CASODEX Combination Study Group. 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. Cancer. 1996 Nov 15;78(10):2164-9. [https://doi.org/10.1002/(SICI)1097-0142(19961115)78:10%3C2164::AID-CNCR18%3E3.0.CO;2-X link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/8918410/ 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. [http://jjco.oxfordjournals.org/content/34/1/20.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15020659 PubMed]
+##'''Update:''' Soloway MS, Schellhammer P, Sharifi R, Venner P, Patterson AL, Sarosdy M, Vogelzang N, Jones J, Kolvenbag G; Casodex Combination Study Group. A controlled trial of Casodex (bicalutamide) vs flutamide, each in combination with luteinising hormone-releasing hormone analogue therapy in patients with advanced prostate cancer. Eur Urol. 1996;29 Suppl 2:105-9. [https://doi.org/10.1159/000473848 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/8717471/ PubMed]
-##'''Update:''' Akaza H, Hinotsu S, Usami M, Arai Y, Kanetake H, Naito S, Hirao Y; Study Group for the Combined Androgen Blockade Therapy of Prostate Cancer. Combined androgen blockade with bicalutamide for advanced prostate cancer: long-term follow-up of a phase 3, double-blind, randomized study for survival. Cancer. 2009 Aug 1;115(15):3437-45. [https://onlinelibrary.wiley.com/doi/full/10.1002/cncr.24395 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/19536889 PubMed]
+##'''Update:''' Schellhammer PF, Sharifi R, Block NL, Soloway MS, Venner PM, Patterson AL, Sarosdy MF, Vogelzang NJ, Schellenger JJ, Kolvenbag GJ; Casodex Combination Study Group. Clinical benefits of bicalutamide compared with flutamide in combined androgen blockade for patients with advanced prostatic carcinoma: final report of a double-blind, randomized, multicenter trial. Urology. 1997 Sep;50(3):330-6. [https://doi.org/10.1016/S0090-4295(97)00279-3 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9301693/ PubMed]
-#'''CS21:''' 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. [https://onlinelibrary.wiley.com/doi/10.1111/j.1464-410X.2008.08183.x/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19035858 PubMed]
+#'''SWOG-9346:''' 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. [https://doi.org/10.1056/NEJMoa1212299 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3682658/ link to PMC article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1212299/suppl_file/nejmoa1212299_protocol.pdf supplementary protocol] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/23550669/ PubMed] [https://clinicaltrials.gov/study/NCT00002651 NCT00002651]
-##'''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. [http://www.europeanurology.com/article/S0302-2838%2809%2901171-3 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19962227 PubMed]
+==Flutamide & Leuprolide {{#subobject:14 |Regimen=1}}==
-#'''L-PC07-169:''' Spitz A, Young JM, Larsen L, Mattia-Goldberg C, Donnelly J, Chwalisz K. Efficacy and safety of leuprolide acetate 6-month depot for suppression of testosterone in patients with prostate cancer. Prostate Cancer Prostatic Dis. 2012 Mar;15(1):93-9. Epub 2011 Oct 25. [https://www.nature.com/articles/pcan201150 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3278745/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/22025196 PubMed]
+<div class="toccolours" style="background-color:#eeeeee">
-#'''HERO:''' Shore ND, Saad F, Cookson MS, George DJ, Saltzstein DR, Tutrone R, Akaza H, Bossi A, van Veenhuyzen DF, Selby B, Fan X, Kang V, Walling J, Tombal B; HERO Study Investigators. Oral Relugolix for Androgen-Deprivation Therapy in Advanced Prostate Cancer. N Engl J Med. 2020 Jun 4;382(23):2187-2196. [https://doi.org/10.1056/NEJMoa2004325 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/32469183/ PubMed] NCT03085095
+===Regimen variant #1, daily Lupron {{#subobject:5b0861 |Variant=1}}===
-==Nilutamide & Orchiectomy {{#subobject:15 |Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
-===Regimen {{#subobject:15 |Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 ! style="width: 20%" |Study
-! style="width: 20%" |Years of enrollment
+! style="width: 20%" |Dates of enrollment
 ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 ! style="width: 20%" |Comparator
 ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1016/s0022-5347(17)36003-2 Janknegt et al. 1993 (International Anandron Study)]
+|[https://doi.org/10.1056/NEJM198908173210702 Crawford et al. 1989 (SWOG-8494)]
-|1986-NR
+|1985-01 to 1986-04
-| style="background-color:#1a9851" |Phase III (E-RT-esc)
+| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
-|[[Prostate_cancer_-_historical#Castration|Bilateral orchiectomy]]
+|[[#Leuprolide_monotherapy_3|Leuprolide]]
-| style="background-color:#1a9850" |Superior PFS
+| style="background-color:#91cf60" |Seems to have superior OS
 |-
 |}
-''Nilutamide to start the day of, or day after surgical castration/orchiectomy.''
+''Note: this is likely of historic importance only, given the formulation of leuoprolide.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Endocrine therapy====
+*[[Flutamide (Eulexin)]] 250 mg PO three times per day
-*[[Nilutamide (Nilandron)]] 300 mg PO once per day x 1 month, then 150 mg PO once per day
+*[[Leuprolide (Lupron)]] 1 mg SC once per day
-*[[Endocrine_ablation_surgery#Bilateral_orchiectomy|Bilateral orchiectomy]]
 '''Continued indefinitely'''
+</div></div><br>
-===References===
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #2, 1-month depot Lupron {{#subobject:14 |Variant=1}}===
-#'''International Anandron Study:''' Janknegt RA, Abbou CC, Bartoletti R, Bernstein-Hahn L, Bracken B, Brisset JM, Da Silva FC, Chisholm G, Crawford ED, Debruyne FM, Dijkman GD, Frick J, Goedhals J, Knönagel H, Venner PM. 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. [https://doi.org/10.1016/s0022-5347(17)36003-2 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/7678043 PubMed]
-##'''Update:''' Janknegt RA; Anandron International Study Group. Total androgen blockade with the use of orchiectomy and nilutamide (Anandron) or placebo as treatment of metastatic prostate cancer. Cancer. 1993 Dec 15;72(12 Suppl):3874-7. [https://www.ncbi.nlm.nih.gov/pubmed/8252507 PubMed]
-##'''Update:''' Dijkman GA, Janknegt RA, De Reijke TM, Debruyne FM; International Anandron Study Group. Long-term efficacy and safety of nilutamide plus castration in advanced prostate cancer, and the significance of early prostate specific antigen normalization. J Urol. 1997 Jul;158(1):160-3. [https://www.ncbi.nlm.nih.gov/pubmed/9186345 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. [http://www.europeanurology.com/article/S0302-2838%2802%2900272-5 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12160584 PubMed]
-==Relugolix monotherapy {{#subobject:5jagu9 |Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
-===Regimen {{#subobject:gaghc5 |Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
+! style="width: 20%" |Study
-!style="width: 20%"|Years of enrollment
+! style="width: 20%" |Dates of enrollment
-!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 20%"|Comparator
+! style="width: 20%" |Comparator
-!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+| rowspan="2" |[https://doi.org/10.1016/s0090-4295(99)80077-6 Schellhammer et al. 1995]
+| rowspan="2" |1992-01 to 1993-09
+| rowspan="2" style="background-color:#1a9851" |Phase 3 (C)
+|1. [[#Bicalutamide_.26_Goserelin_3|Bicalutamide & Goserelin]]<br>2. [[#Bicalutamide_.26_Leuprolide|Bicalutamide & Leuprolide]]
+| style="background-color:#eeee01" |Equivalent TTP<sup>1</sup>
+|-
+|3. [[#Flutamide_.26_Goserelin_2|Flutamide & Goserelin]]
+| style="background-color:#d3d3d3" |Not reported
 |-
-|[https://pubmed.ncbi.nlm.nih.gov/32469183/ Shore et al. 2020 (HERO)]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3682658/ Hussain et al. 2013 (SWOG-9346)]
-|2017-2018
+|1995-2008
-| style="background-color:#1a9851" |Phase III (C)
+| style="background-color:#1a9851" |Phase 3 (C)
-|[[#Leuprolide_monotherapy_2|Leuprolide]]
+|[[#Intermittent_ADT|Intermittent ADT]]
-| style="background-color:#1a9850" |Superior testosterone suppression
+| style="background-color:#ffffbf" |Inconclusive whether non-inferior OS
 |-
 |}
+''<sup>1</sup>Reported efficacy for Schellhammer et al. 1995 is based on the 1997 final update.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Endocrine therapy====
-*[[Relugolix (Orgovyx)]] 360 mg PO once on day 1, then 120 mg PO once per day
+*[[Flutamide (Eulexin)]] 250 mg PO three times per day on days 1 to 28
+*[[Leuprolide (Lupron)|Leuprolide (Lupron) 1-month depot]] 7.5 mg IM once on day 1
-'''48-week course'''
+'''28-day cycles'''
+</div></div>
 ===References===
-#'''HERO:''' Shore ND, Saad F, Cookson MS, George DJ, Saltzstein DR, Tutrone R, Akaza H, Bossi A, van Veenhuyzen DF, Selby B, Fan X, Kang V, Walling J, Tombal B; HERO Study Investigators. Oral Relugolix for Androgen-Deprivation Therapy in Advanced Prostate Cancer. N Engl J Med. 2020 Jun 4;382(23):2187-2196. [https://doi.org/10.1056/NEJMoa2004325 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/32469183/ PubMed] NCT03085095
+#'''SWOG-8494:''' Crawford ED, Eisenberger MA, McLeod DG, Spaulding JT, Benson R, Dorr FA, Blumenstein BA, Davis MA, Goodman PJ. A controlled trial of leuprolide with and without flutamide in prostatic carcinoma. N Engl J Med. 1989 Aug 17;321(7):419-24. Erratum in: N Engl J Med 1989 Nov 16;321(20):1420. [https://doi.org/10.1056/NEJM198908173210702 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/2503724/ PubMed]
+#Schellhammer P, Sharifi R, Block N, Soloway M, Venner P, Patterson AL, Sarosdy M, Vogelzang N, Jones J, Kolvenbag G; Casodex Combination Study Group. A controlled trial of bicalutamide versus flutamide, each in combination with luteinizing hormone-releasing hormone analogue therapy, in patients with advanced prostate cancer. Urology. 1995 May;45(5):745-52. [https://doi.org/10.1016/s0090-4295(99)80077-6 link to original article] [https://pubmed.ncbi.nlm.nih.gov/7538237/ PubMed]
-==Triptorelin monotherapy {{#subobject:15acjb |Regimen=1}}==
+##'''Update:''' Schellhammer PF, Sharifi R, Block NL, Soloway MS, Venner PM, Patterson AL, Sarosdy MF, Vogelzang NJ, Chen Y, Kolvenbag GJ; CASODEX Combination Study Group. 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. Cancer. 1996 Nov 15;78(10):2164-9. [https://doi.org/10.1002/(SICI)1097-0142(19961115)78:10%3C2164::AID-CNCR18%3E3.0.CO;2-X link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/8918410/ PubMed]
-{| class="wikitable" style="float:right; margin-left: 5px;"
+##'''Update:''' Soloway MS, Schellhammer P, Sharifi R, Venner P, Patterson AL, Sarosdy M, Vogelzang N, Jones J, Kolvenbag G; Casodex Combination Study Group. A controlled trial of Casodex (bicalutamide) vs flutamide, each in combination with luteinising hormone-releasing hormone analogue therapy in patients with advanced prostate cancer. Eur Urol. 1996;29 Suppl 2:105-9. [https://doi.org/10.1159/000473848 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/8717471/ PubMed]
-|-
+##'''Update:''' Schellhammer PF, Sharifi R, Block NL, Soloway MS, Venner PM, Patterson AL, Sarosdy MF, Vogelzang NJ, Schellenger JJ, Kolvenbag GJ; Casodex Combination Study Group. Clinical benefits of bicalutamide compared with flutamide in combined androgen blockade for patients with advanced prostatic carcinoma: final report of a double-blind, randomized, multicenter trial. Urology. 1997 Sep;50(3):330-6. [https://doi.org/10.1016/S0090-4295(97)00279-3 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9301693/ PubMed]
-|[[#top|back to top]]
+#'''SWOG-9346:''' 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. [https://doi.org/10.1056/NEJMoa1212299 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3682658/ link to PMC article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1212299/suppl_file/nejmoa1212299_protocol.pdf supplementary protocol] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/23550669/ PubMed] [https://clinicaltrials.gov/study/NCT00002651 NCT00002651]
-|}
+==Goserelin monotherapy {{#subobject:9 |Regimen=1}}==
-===Regimen {{#subobject:1596sc |Variant=1}}===
+===Example orders===
+*[[Example orders for Goserelin (Zoladex) in prostate cancer]]
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #1, 28-day cycles {{#subobject:9 |Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 ! style="width: 20%" |Study
-! style="width: 20%" |Years of enrollment
+! style="width: 20%" |Dates of enrollment
 ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 ! style="width: 20%" |Comparator
 ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://onlinelibrary.wiley.com/doi/full/10.1046/j.1464-410X.2003.04308.x Heyns et al. 2003]
+|[https://doi.org/10.1016/0090-4295(91)80077-K Soloway et al. 1991]
 |NR
-| style="background-color:#1a9851" |Phase III (E-RT-switch-ic)
+| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
-|[[#Leuprolide_monotherapy_2|Leuprolide]]
+|[[Prostate_cancer_-_historical#Castration|Bilateral orchiectomy]]
-| style="background-color:#91cf60" |Seems to have superior 9-month OS<sup>1</sup>
+| style="background-color:#ffffbf" |Did not meet efficacy endpoints
+|-
+|[https://doi.org/10.1111/j.1464-410X.1991.tb15195.x Kaisary et al. 1991]
+|1983-1986
+| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
+|[[Prostate_cancer_-_historical#Castration|Bilateral orchiectomy]]
+| style="background-color:#ffffbf" |Did not meet efficacy endpoints
+|-
+|[https://doi.org/10.1111/j.1464-410X.1992.tb15633.x Waymont et al. 1992]
+|1985-1987
+| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
+|[[#DES_monotherapy_888|DES]]
+| style="background-color:#91cf60" |Seems to have superior time to first response
+|-
+|[https://doi.org/10.1016/s0022-5347(17)38080-1 Tyrrell et al. 1991 (IPCSG)]
+|1986-01 to 1987-07
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#Flutamide_.26_Goserelin_2|Flutamide & Goserelin]]
+| style="background-color:#ffffbf" |Did not meet efficacy endpoints
+|-
+|[https://doi.org/10.1016/s0959-8049(05)80293-x Boccardo et al. 1993 (PONCAP)]
+|1987-1990
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#Flutamide_.26_Goserelin_2|Flutamide & Goserelin]]
+| style="background-color:#fee08b" |Might have inferior PFS50%
 |-
 |}
-''<sup>1</sup>Survival was a secondary endpoint.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Endocrine therapy====
+*[[Goserelin (Zoladex)]] 3.6 mg SC once on day 1
-*[[Triptorelin (Trelstar LA)]] 3.75 mg IM once on day 1
+'''28-day cycles'''
+</div></div><br>
-'''28-day cycle for 9 cycles'''
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #2, 12-week cycles {{#subobject:7afffe |Variant=1}}===
-===References===
-#Heyns CF, Simonin MP, Grosgurin P, Schall R, Porchet HC; South African Triptorelin Study Group. Comparative efficacy of triptorelin pamoate and leuprolide acetate in men with advanced prostate cancer. BJU Int. 2003 Aug;92(3):226-31. [https://onlinelibrary.wiley.com/doi/full/10.1046/j.1464-410X.2003.04308.x link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12887472 PubMed]
-=Metastatic disease, second-line hormonal therapy=
-==Abiraterone monotherapy {{#subobject:16 |Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
-===Regimen {{#subobject:16 |Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 ! style="width: 20%" |Study
-! style="width: 20%" |Years of enrollment
+! style="width: 20%" |Dates of enrollment
 ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 ! style="width: 20%" |Comparator
 ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-![[Overall response rate|'''ORR''', PSA RR]]
-!Comparator [[Overall response rate|'''ORR''', PSA RR]]
-!Pt Population
 |-
-|[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/PMC5989846/ Ozono et al. 2018 (3550-CL-0010)]
-|2008-2009
+|2013-NR
-| style="background-color:#1a9851" |Phase III (E-RT-esc)
+| style="background-color:#1a9851" |Phase 3 (C)
-|[[#Prednisone_monotherapy|Prednisone]]
+|[[#Degarelix_monotherapy_2|Degarelix]]
-| style="background-color:#1a9850" |Superior OS
+| style="background-color:#eeee01" |Non-inferior testosterone suppression
-|14% (95% CI n/a), 29%
-|3% (95% CI n/a), 6%
-|Chemo-exposed
 |-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3683570/ Ryan et al. 2013 (COU-AA-302)]
+|}
-|2009-2010
+<div class="toccolours" style="background-color:#b3e2cd">
-| style="background-color:#1a9851" |Phase III (E-RT-esc)
+====Endocrine therapy====
-|[[#Prednisone_monotherapy|Prednisone]]
+*[[Goserelin (Zoladex)]] as follows:
-| style="background-color:#91cf60" |Seems to have superior OS
+**Cycle 1: 3.6 mg SC once on day 1
-|36% (95% CI n/a), 62%
+**Cycle 2 onwards: 10.8 mg SC once on day 1
-|16% (95% CI n/a), 24%
+'''28-day course, then 12-week cycles'''
-|Chemo-naive
+</div></div>
+===References===
+#Soloway MS, Chodak G, Vogelzang NJ, Block NL, Schellhammer PF, Smith JA Jr, Scott M, Kennealey G, Gau TC; Zoladex Prostate Study Group. Zoladex versus orchiectomy in treatment of advanced prostate cancer: a randomized trial. Urology. 1991 Jan;37(1):46-51. [https://doi.org/10.1016/0090-4295(91)80077-K link to original article] [https://pubmed.ncbi.nlm.nih.gov/1824732/ PubMed]
+##'''Update:''' Vogelzang NJ, Chodak GW, Soloway MS, Block NL, Schellhammer PF, Smith JA Jr, Caplan RJ, Kennealey GT; Zoladex Prostate Study Group. Goserelin versus orchiectomy in the treatment of advanced prostate cancer: final results of a randomized trial. Urology. 1995 Aug;46(2):220-6. [https://doi.org/10.1016/s0090-4295(99)80197-6 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/7624991/ 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. [https://doi.org/10.1111/j.1464-410X.1991.tb15195.x link to original article] [https://pubmed.ncbi.nlm.nih.gov/1828183/ PubMed]
+#'''IPCSG:''' Tyrrell CJ, Altwein JE, Klippel F, Varenhorst E, Lunglmayr G, Boccardo F, Holdaway IM, Haefliger JM, Jordaan JP; International Prostate Cancer Study Group. A multicenter randomized trial comparing the luteinizing hormone-releasing hormone analogue goserelin acetate alone and with flutamide in the treatment of advanced prostate cancer. J Urol. 1991 Nov;146(5):1321-6. [https://doi.org/10.1016/s0022-5347(17)38080-1 link to original article] [https://pubmed.ncbi.nlm.nih.gov/1834864/ PubMed]
+#Waymont B, Lynch TH, Dunn JA, Emtage LA, Arkell DG, Wallace DM, Blackledge GR. Phase III randomised study of zoladex versus stilboestrol in the treatment of advanced prostate cancer. Br J Urol. 1992 Jun;69(6):614-20. [https://doi.org/10.1111/j.1464-410X.1992.tb15633.x link to original article] [https://pubmed.ncbi.nlm.nih.gov/1386272/ PubMed]
+#'''PONCAP:''' Boccardo F, Pace M, Rubagotti A, Guarneri D, Decensi A, Oneto F, Martorana G, Giuliani L, Selvaggi F, Battaglia M, Delli Ponti U, Petracco S, Cortellini P, Ziveri M, Ferraris V, Bruttini GP, Epis R, Comeri G, Gallo G; Italian Prostatic Cancer Project (PONCAP) Study Group. Goserelin acetate with or without flutamide in the treatment of patients with locally advanced or metastatic prostate cancer. Eur J Cancer. 1993;29A(8):1088-93. [https://doi.org/10.1016/s0959-8049(05)80293-x link to original article] [https://pubmed.ncbi.nlm.nih.gov/8518017/ PubMed]
+#'''3550-CL-0010:''' Ozono S, Tsukamoto T, Naito S, Horie S, Ohashi Y, Uemura H, Yokomizo Y, Fukasawa S, Kusuoka H, Akazawa R, Saito M, Akaza H. Efficacy and safety of 3-month dosing regimen of degarelix in Japanese subjects with prostate cancer: a phase III study. Cancer Sci. 2018 Jun;109(6):1920-1929. Epub 2018 May 23. [https://doi.org/10.1111/cas.13600 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5989846/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29624800/ PubMed] [https://clinicaltrials.gov/study/NCT01964170 NCT01964170]
+==Histrelin monotherapy {{#subobject:97agub |Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:918gya|Variant=1}}===
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
+!style="width: 33%"|Study
+!style="width: 33%"|Dates of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 |-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5717983/ Ye et al. 2017 (ABI-PRO-3002)]
+|[https://www.auajournals.org/doi/full/10.1016/S0022-5347%2805)00649-X Schlegel 2006]
-|2012-2013
+|NR
-| style="background-color:#1a9851" |Phase III (E-esc)
+| style="background-color:#91cf61" |Non-randomized (RT)
-|[[#Prednisone_monotherapy|Prednisone]]
-| style="background-color:#1a9850" |Superior TTPP
-|
-|
-|Chemo-naive
-|-
-|[https://doi.org/10.1200/JCO.2018.77.9827 Attard et al. 2018 (PLATO)]
-|2013-NR
-| style="background-color:#1a9851" |Phase III (C)
-|Abiraterone, Enzalutamide, Prednisone
-| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
-|
-|
-|Chemo-naive
-|-
-|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(18)30860-X/fulltext Smith et al. 2019 (ERA 223)]
-|2014-2016
-| style="background-color:#1a9851" |Phase III (C)
-|Abiraterone, Radium-223, Prednisone
-| style="background-color:#ffffbf" |Did not meet primary endpoint of symptomatic skeletal EFS
-|
-|
-|Chemo-naive
 |-
 |}
-====Preceding treatment====
+<div class="toccolours" style="background-color:#b3e2cd">
-*PLATO: [[#Enzalutamide_monotherapy_2|Enzalutamide]], with rising PSA
 ====Endocrine therapy====
+*[[Histrelin (Vantas)]]
-*[[Abiraterone (Zytiga)]] 1000 mg PO once per day, 1 hour before or 2 hours after meals
+</div></div>
-====Supportive medications====
-*[[Prednisone (Sterapred)]] 5 mg PO twice per day
-'''Continued indefinitely'''
 ===References===
+#Schlegel PN; Histrelin Study Group. Efficacy and safety of histrelin subdermal implant in patients with advanced prostate cancer. J Urol. 2006 Apr;175(4):1353-8. [https://www.auajournals.org/doi/full/10.1016/S0022-5347%2805)00649-X link to original article] [https://pubmed.ncbi.nlm.nih.gov/16515997/ PubMed]
-#'''COU-AA-301:''' 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. [https://www.nejm.org/doi/full/10.1056/NEJMoa1014618 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3471149/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/21612468 PubMed] NCT00638690
+==Intermittent ADT==
-##'''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. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(12)70379-0/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22995653 PubMed]
+IHT: '''<u>I</u>'''ntermittent '''<u>H</u>'''ormone '''<u>T</u>'''herapy
-##'''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. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(12)70473-4/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23142059 PubMed]
+<div class="toccolours" style="background-color:#eeeeee">
-#'''COU-AA-302:''' 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. [https://www.nejm.org/doi/full/10.1056/NEJMoa1209096 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3683570/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/23228172 PubMed] NCT00887198
+===Regimen===
-##'''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. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)71205-7/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/25601341 PubMed]
-#'''ABI-PRO-3002:''' Ye D, Huang Y, Zhou F, Xie K, Matveev V, Li C, Alexeev B, Tian Y, Qiu M, Li H, Zhou T, De Porre P, Yu M, Naini V, Liang H, Wu Z, Sun Y. A phase 3, double-blind, randomized placebo-controlled efficacy and safety study of abiraterone acetate in chemotherapy-naïve patients with mCRPC in China, Malaysia, Thailand and Russia. Asian J Urol. 2017 Apr;4(2):75-85. Epub 2017 Jan 23. [https://doi.org/10.1016/j.ajur.2017.01.002 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5717983/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/29264210 PubMed] NCT01591122
-#'''PLATO:''' Attard G, Borre M, Gurney H, Loriot Y, Andresen-Daniil C, Kalleda R, Pham T, Taplin ME; PLATO collaborators. Abiraterone alone or in combination with enzalutamide in metastatic castration-resistant prostate cancer with rising prostate-specific antigen during enzalutamide treatment. J Clin Oncol. 2018 Sep 1;36(25):2639-2646. Epub 2018 Jul 20. [https://doi.org/10.1200/JCO.2018.77.9827 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/30028657 PubMed] NCT01995513
-#'''ERA 223:''' Smith M, Parker C, Saad F, Miller K, Tombal B, Ng QS, Boegemann M, Matveev V, Piulats JM, Zucca LE, Karyakin O, Kimura G, Matsubara N, Nahas WC, Nolè F, Rosenbaum E, Heidenreich A, Kakehi Y, Zhang A, Krissel H, Teufel M, Shen J, Wagner V, Higano C. Addition of radium-223 to abiraterone acetate and prednisone or prednisolone in patients with castration-resistant prostate cancer and bone metastases (ERA 223): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2019 Mar;20(3):408-419. Epub 2019 Feb 6. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(18)30860-X/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/30738780 PubMed] NCT02043678
-#'''PROfound:''' de Bono J, Mateo J, Fizazi K, Saad F, Shore N, Sandhu S, Chi KN, Sartor O, Agarwal N, Olmos D, Thiery-Vuillemin A, Twardowski P, Mehra N, Goessl C, Kang J, Burgents J, Wu W, Kohlmann A, Adelman CA, Hussain M. Olaparib for Metastatic Castration-Resistant Prostate Cancer. N Engl J Med. 2020 May 28;382(22):2091-2102. Epub 2020 Apr 28. [http://doi.org/10.1056/NEJMoa1911440 link to original article] '''contains verified protocol''' [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1911440/suppl_file/nejmoa1911440_appendix.pdf link to supplementary appendix] [https://pubmed.ncbi.nlm.nih.gov/32343890/ PubMed] NCT02987543
-#'''PROpel:''' NCT03732820
-#'''KEYLYNK-010:''' NCT03834519
-#'''AMPLITUDE:''' NCT04497844
-==Antiandrogen withdrawal {{#subobject:17 |Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
-===Regimen {{#subobject:17 |Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 ! style="width: 20%" |Study
-! style="width: 20%" |Years of enrollment
+! style="width: 20%" |Dates of enrollment
 ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 ! style="width: 20%" |Comparator
 ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1200/jco.2004.06.037 Small et al. 2004 (CALGB 9583)]
+|[https://doi.org/10.1016/j.eururo.2009.02.016 Calais da Silva et al. 2009 (SEUG 9401)]
 |NR
-| style="background-color:#1a9851" |Phase III (C)
+| style="background-color:#1a9851" |Phase 3 (E-de-esc)
-|[[#Ketoconazole_.26_Hydrocortisone|Ketoconazole & Hydrocortisone]]
+|[[#ADT_5|Continuous ADT]]
-| style="background-color:#d73027" |Inferior PSA response
+| style="background-color:#ffffbf" |Did not meet primary endpoint of TTP
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3682658/ Hussain et al. 2013 (SWOG-9346)]
+|1995-2008
+| style="background-color:#1a9851" |Phase 3 (E-de-esc)
+|[[#ADT_5|Continuous ADT]]
+| style="background-color:#ffffbf" |Inconclusive whether non-inferior OS (co-primary endpoint)
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3521033/ Crook et al. 2012 (NCIC-CTG PR.7)]
+|1999-2005
+| style="background-color:#1a9851" |Phase 3 (E-de-esc)
+|[[#ADT_5|Continuous ADT]]
+| style="background-color:#eeee01" |Non-inferior OS (primary endpoint)<br>Median OS: 8.8 vs 9.1 y<br>(HR 1.02, 95% CI 0.86-1.21)
+|-
+|[https://doi.org/10.1016/j.eururo.2013.03.055 Calais da Silva et al. 2013 (SEUG 9901)]
+|2000-2007
+| style="background-color:#1a9851" |Phase 3 (E-de-esc)
+|[[#ADT_5|Continuous ADT]]
+| style="background-color:#eeee01" |Non-inferior OS (primary endpoint)
 |-
 |}
+''Note: See papers for details about treatment holidays.''
-''Refers to cessation of antiandrogen therapy.''
+<div class="toccolours" style="background-color:#b3e2cd">
+====Endocrine therapy====
-===References===
+*[[:Category:GnRH agonists|LHRH agonist]]
+*[[:Category:Nonsteroidal_antiandrogens|Nonsteroidal antiandrogen]] for at least 4 weeks
-#'''CALGB 9583:''' 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. [https://doi.org/10.1200/jco.2004.06.037 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15020604 PubMed]
+'''8-month cycles'''
+</div></div>
-==Apalutamide monotherapy {{#subobject:acc40a |Regimen=1}}==
+===References===
-{| class="wikitable" style="float:right; margin-left: 5px;"
+#'''SEUG 9401:''' Calais da Silva FE, Bono AV, Whelan P, Brausi M, Marques Queimadelos A, Martin JA, Kirkali Z, Calais da Silva FM, Robertson C. Intermittent androgen deprivation for locally advanced and metastatic prostate cancer: results from a randomised phase 3 study of the South European Uroncological Group. Eur Urol. 2009 Jun;55(6):1269-77. Epub 2009 Feb 21. [https://doi.org/10.1016/j.eururo.2009.02.016 link to original article] [https://pubmed.ncbi.nlm.nih.gov/19249153/ PubMed]
+#'''NCIC-CTG PR.7:''' Crook JM, O'Callaghan CJ, Duncan G, Dearnaley DP, Higano CS, Horwitz EM, Frymire E, Malone S, Chin J, Nabid A, Warde P, Corbett T, Angyalfi S, Goldenberg SL, Gospodarowicz MK, Saad F, Logue JP, Hall E, Schellhammer PF, Ding K, Klotz L. Intermittent androgen suppression for rising PSA level after radiotherapy. N Engl J Med. 2012 Sep 6;367(10):895-903. Erratum in: N Engl J Med. 2012 Dec 6;367(23):2262. [https://doi.org/10.1056/NEJMoa1201546 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3521033/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22931259/ PubMed] [https://clinicaltrials.gov/study/NCT00003653 NCT00003653]
+#'''SWOG-9346:''' 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. [https://doi.org/10.1056/NEJMoa1212299 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3682658/ link to PMC article] [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1212299/suppl_file/nejmoa1212299_protocol.pdf supplementary protocol] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/23550669/ PubMed] [https://clinicaltrials.gov/study/NCT00002651 NCT00002651]
+#'''SEUG 9901:''' Calais da Silva F, Calais da Silva FM, Gonçalves F, Santos A, Kliment J, Whelan P, Oliver T, Antoniou N, Pastidis S, Marques Queimadelos A, Robertson C. Locally advanced and metastatic prostate cancer treated with intermittent androgen monotherapy or maximal androgen blockade: results from a randomised phase 3 study by the South European Uroncological Group. Eur Urol. 2014 Aug;66(2):232-9. Epub 2013 Apr 4. [https://doi.org/10.1016/j.eururo.2013.03.055 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23582949/ PubMed] [https://clinicaltrials.gov/study/NCT00363285 NCT00363285]
+==Leuprolide monotherapy {{#subobject:12 |Regimen=1}}==
+===Example orders===
+*[[Example orders for Leuprolide (Lupron) in prostate cancer]]
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #1, daily {{#subobject:c6f258 |Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+! style="width: 17%" |Study
+! style="width: 15%" |Dates of enrollment
+! style="width: 17%" |[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 17%" |Comparator
+! style="width: 17%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 17%" |[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 |-
-|[[#top|back to top]]
+|[https://doi.org/10.1056/NEJM198411153112004 Garnick et al. 1984]
-|}
+|1981-NR
-===Regimen {{#subobject:cf9ghi|Variant=1}}===
+| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
-{| class="wikitable" style="width: 50%; text-align:center;"
+|[[#DES_monotherapy_888|DES]]
-! style="width: 25%" |Study
+| style="background-color:#ffffbf" |Did not meet efficacy endpoints
-! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
+| style="background-color:#1a9850" |Less toxic
 |-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5543693/ Rathkopf et al. 2017 (ARN-509-001)]
+|[https://doi.org/10.1056/NEJM198908173210702 Crawford et al. 1989 (SWOG-8494)]
-| style="background-color:#91cf61" |Non-randomized
+|1985-01 to 1986-04
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#Flutamide_.26_Leuprolide|Flutamide & Leuprolide]]
+| style="background-color:#fc8d59" |Seems to have inferior OS
+|
 |-
 |}
+''Note: this is of historic importance only, given the wide availability of depot formulations of leuoprolide.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Endocrine therapy====
+*[[Leuprolide (Lupron)]] 1 mg SC once per day
-*[[Apalutamide (Erleada)]] 240 mg PO once per day
 '''Continued indefinitely'''
+</div></div><br>
-===References===
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #2, 1-month depot, 3.75 mg {{#subobject:172cb3|Variant=1}}===
-#'''ARN-509-001:''' Rathkopf DE, Antonarakis ES, Shore ND, Tutrone RF, Alumkal JJ, Ryan CJ, Saleh M, Hauke RJ, Bandekar R, Maneval EC, de Boer CJ, Yu MK, Scher HI. Safety and Antitumor Activity of Apalutamide (ARN-509) in Metastatic Castration-Resistant Prostate Cancer with and without Prior Abiraterone Acetate and Prednisone. Clin Cancer Res. 2017 Jul 15;23(14):3544-3551. Epub 2017 Feb 17. [http://clincancerres.aacrjournals.org/content/23/14/3544.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5543693/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/28213364 PubMed]
-==BAT {{#subobject:aoc10a |Regimen=1}}==
-BAT: '''<u>B</u>'''ipolar '''<u>A</u>'''ndrogen '''<u>T</u>'''herapy
-===Regimen {{#subobject:#e085c7 |Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 ! style="width: 20%" |Study
-! style="width: 20%" |Years of enrollment
+! style="width: 20%" |Dates of enrollment
 ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 ! style="width: 20%" |Comparator
 ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1200/jco.20.02759 Denmeade et al. 2021 (TRANSFORMER)]
+|[http://jjco.oxfordjournals.org/content/34/1/20.full Akaza et al. 2004]
-|2015-2018
+|2000-02 to 2001-12
-| style="background-color:#1a9851" |Randomized Phase II (E-esc)
+| style="background-color:#1a9851" |Phase 3 (C)
-|[[Prostate_cancer#Enzalutamide_monotherapy|Enzalutamide]]
+|1. [[#Bicalutamide_.26_Goserelin_3|Bicalutamide & Goserelin]]<br>2. [[#Bicalutamide_.26_Leuprolide|Bicalutamide & Leuprolide]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS<sup>1</sup>
+| style="background-color:#fc8d59" |Seems to have inferior OS<sup>1</sup>
 |-
 |}
-{| class="wikitable" style="width: 75%; text-align:center;"
+''<sup>1</sup>Reported efficacy is based on the 2009 update.''
-! style="width: 33%" |Progression-free survival
+<div class="toccolours" style="background-color:#b3e2cd">
-! style="width: 33%" |Comparator progression-free survival
-! style="width: 33%" |Pt Population
-|-
-|5.7 months
-|5.7 months
-|Castrate-resistant, metastatic, asymptomatic, progressed after abiraterone
-|-
-|}
-''<sup>1</sup>Study not powered for equivalency. Secondary endpoint of PFS2 after crossover was superior in BAT to enzalutamide arm.''
 ====Endocrine therapy====
-*ADT: All patients maintained on continuous testosterone suppression via surgical castration or [[:Category:GnRH_agonists|GnRH agonist]] or [[:Category:GnRH antagonists|GnRH antagonist]]
+*[[Leuprolide (Lupron)|Leuprolide (Lupron) 1-month depot]] 3.75 mg SC once on day 1
-*Bipolar Androgen Therapy (BAT): [[Testosterone cypionate]] 400 mg IM once every 28 days
+'''28-day cycles'''
-*[[Enzalutamide_(Xtandi)|Enzalutamide]]: 160 mg by mouth daily
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
-====Subsequent treatment====
+===Regimen variant #3, 1-month depot, 7.5 mg {{#subobject:172cb4|Variant=1}}===
-*At progression, asymptomatic patients were allowed to cross over to alternative therapy
-===References===
-# '''TRANSFORMER:''' Denmeade SR, Wang H, Agarwal N, Smith D, Schweizer MT, Stein MN, Assikis V, Twardowski P, Flaig T, Szmulewitz R, Holzbeierlein J, Hauke R, Sonpavde G, Garcia J, Hussain A, Sartor O, Mao S, Cao H, Fu W, Wang T, Abdallah R, Lim SJ, Bolejack V, Paller C, Carducci M, Markowski MC, Eisenberger MA, Antonarakis ES; TRANSFORMER investigators. TRANSFORMER: A Randomized Phase II Study Comparing Bipolar Androgen Therapy Versus Enzalutamide in Asymptomatic Men With Castration-Resistant Prostate Cancer. J Clin Oncol. Epub 2021 Feb 22  [https://doi.org/10.1200/jco.20.02759 link to original article] [https://ascopubs.org/doi/suppl/10.1200/JCO.20.02759 link to protocol] [https://pubmed.ncbi.nlm.nih.gov/33617303/ PubMed] NCT02286921
-==Bicalutamide monotherapy {{#subobject:abb40a |Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
-===Regimen {{#subobject:cf9def|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 ! style="width: 20%" |Study
-! style="width: 20%" |Years of enrollment
+! style="width: 20%" |Dates of enrollment
 ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 ! style="width: 20%" |Comparator
 ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-![[Overall response rate|'''ORR''', PSA RR]]
-!Comparator [[Overall response rate|'''ORR''', PSA RR]]
-!Pt Population
 |-
-|[https://doi.org/10.1200/jco.2015.64.9285 Penson et al. 2016 (STRIVE)]
+|[https://www.auajournals.org/doi/abs/10.1016/S0022-5347%2817%2939868-3 Sharifi & Soloway 1990]
-|2012-2014
+|1986-NR
-| style="background-color:#1a9851" |Randomized Phase II (C)
+| style="background-color:#91cf61" |Non-randomized (RT)
-|[[#Enzalutamide_monotherapy_2|Enzalutamide]]
+| style="background-color:#d3d3d3" |
-| style="background-color:#d73027" |Inferior PFS
+| style="background-color:#d3d3d3" |
-|pts w/ measurable disease: '''14%''' (95% CI n/a), '''31%''' (95% CI n/a)
+|-
-|pts w/ measurable disease: '''60%''' (95% CI n/a), '''81%''' (95% CI n/a)
+|[https://doi.org/10.1046/j.1464-410x.2003.04308.x Heyns et al. 2003]
-|Chemo-naive, abi and keto-naive
+|NR
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#Triptorelin_monotherapy|Triptorelin]]
+| style="background-color:#fc8d59" |Seems to have inferior 9-month OS
+|-
+| rowspan="2" |[https://doi.org/10.1111/j.1464-410X.2008.08183.x Klotz et al. 2008 (CS21)]
+| rowspan="2" |2006-02 to 2007-10
+| rowspan="2" style="background-color:#1a9851" |Phase 3 (C)
+|1. [[#Degarelix_monotherapy_2|Degarelix]]; 240/80
+| style="background-color:#eeee01" |Non-inferior testosterone suppression (primary endpoint)
+|-
+|2. [[#Degarelix_monotherapy_2|Degarelix]]; 240/160
+| style="background-color:#eeee01" |Non-inferior testosterone suppression (primary endpoint)
 |-
 |}
-''Patients continued ADT while on study; details not provided.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Endocrine therapy====
+*[[Leuprolide (Lupron)|Leuprolide (Lupron) 1-month depot]] 7.5 mg IM once on day 1
-*[[Bicalutamide (Casodex)]] 50 mg PO once per day
+'''28-day cycles'''
+</div></div><br>
-'''Continued indefinitely'''
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #4, 3-month depot {{#subobject:5415fc |Variant=1}}===
-===References===
-<!-- Presented in part at the American Urological Association 2015 Annual Meeting, New Orleans, LA, May 15-19, 2015. -->
-#'''STRIVE:''' 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. [https://doi.org/10.1200/jco.2015.64.9285 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/26811535 PubMed] NCT01664923
-==Enzalutamide monotherapy {{#subobject:18 |Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
-===Regimen variant #1, 160 mg/day {{#subobject:18 |Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
-! style="width: 20%" |Study
+!style="width: 20%"|Study
-! style="width: 20%" |Years of enrollment
+!style="width: 20%"|Dates of enrollment
-! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
-! style="width: 20%" |Comparator
+!style="width: 20%"|Comparator
-! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-![[Levels_of_Evidence#Efficacy|Efficacy]], PSA RR
-!Comparator [[Overall response rate|'''ORR''']], PSA RR
-!Pt Population
 |-
-|[https://www.nejm.org/doi/full/10.1056/NEJMoa1207506 Scher et al. 2012 (AFFIRM)]
+|[http://www.clinicaltherapeutics.com/article/S0149-2918(96)80215-3 Sharifi et al. 1996]
-|2009-2010
+|NR
-| style="background-color:#1a9851" |Phase III (E-RT-esc)
+| style="background-color:#91cf61" |Phase 2 (RT)
-|[[Prostate_cancer_-_null_regimens#Placebo_3|Placebo]]
-| style="background-color:#1a9850" |Superior OS
-|29% (95% CI n/a), 54%
-|4% (95% CI n/a), 2%
-|Chemo-exposed (docetaxel)
-|-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4418931/ Beer et al. 2014 (PREVAIL)]
-|2010-2012
-| style="background-color:#1a9851" |Phase III (E-RT-esc)
-|[[Prostate_cancer_-_null_regimens#Placebo_3|Placebo]]
-| style="background-color:#1a9850" |Superior OS
-|59% (95% CI n/a), 78%
-|5% (95% CI n/a), 3%
-|Chemo and abiraterone naive
-|-
-|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00518-5/fulltext Shore et al. 2016 (TERRAIN)]
-|2011-2013
-| style="background-color:#1a9851" |Randomized Phase II (E-RT-switch-ic)
-|[[#Bicalutamide_monotherapy_2|Bicalutamide]]
-| style="background-color:#1a9850" |Superior PFS
-|
-|
-|
-|-
-|[https://doi.org/10.1200/jco.2015.64.9285 Penson et al. 2016 (STRIVE)]
-|2012-2014
-| style="background-color:#1a9851" |Randomized Phase II (E-switch-ic)
-|[[#Bicalutamide_monotherapy_2|Bicalutamide]]
-| style="background-color:#1a9850" |Superior PFS
-|60% (95% CI n/a), 81%
-|14% (95% CI n/a), 31%
-|Chemo and bicalutamide naive
-|-
-|[https://doi.org/10.1200/JCO.2018.77.9827 Attard et al. 2018 (PLATO)]
-|2013-NR
-| style="background-color:#91cf61" |Non-randomized portion of RCT
-| style="background-color:#d3d3d3" |
 | style="background-color:#d3d3d3" |
 | style="background-color:#d3d3d3" |
-| style="background-color:#d3d3d3" |
-|Chemo-naive
 |-
-|[https://ascopubs.org/doi/abs/10.1200/JCO.20.02759 Denmeade et al. 2021 (TRANSFORMER)]
+|[https://doi.org/10.1056/NEJMoa2004325 Shore et al. 2020 (HERO)]
-|2015-2018
+|2017-04 to 2018-10
-| style="background-color:#1a9851" |Randomized Phase II (C)
+| style="background-color:#1a9851" |Phase 3 (C)
-|[[Prostate_cancer#BAT|BAT]]
+|[[#Relugolix_monotherapy|Relugolix]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
+| style="background-color:#d73027" |Inferior testosterone suppression
-| style="background-color:#d3d3d3" |
-| style="background-color:#d3d3d3" |
-| Post-abiraterone, asymptomatic
 |-
 |}
-''Patients in STRIVE, PLATO, & TRANSFORMER continued ADT while on study or had a history of bilateral orchiectomy; details not provided.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Endocrine therapy====
+*[[Leuprolide (Lupron)|Leuprolide (Lupron) 3-month depot]] 22.5 mg IM once on day 1
-*[[Enzalutamide (Xtandi)]] 160 mg PO once per day
+'''84-day cycles'''
+</div></div><br>
-'''Continued indefinitely'''
+<div class="toccolours" style="background-color:#eeeeee">
-====Subsequent treatment====
+===Regimen variant #5, 4-month depot {{#subobject:21b60f |Variant=1}}===
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
-*PLATO, with rising PSA: [[#Abiraterone_monotherapy|Abiraterone]] versus [[Stub#Abiraterone_.26_Enzalutamide|Abiraterone & Enzalutamide]]
+!style="width: 33%"|Study
-*TRANSFORMER, asymptomatic PSA or radiographic progression: crossover to alternative arm. Secondary endpoint of PFS2 was statistically longer with BAT to Enzalutamide compared to Enzalutamide to BAT
+!style="width: 33%"|Dates of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
-===Regimen variant #2, 240 mg/day {{#subobject:7bf35b |Variant=1}}===
+|-
-{| class="wikitable" style="width: 50%; text-align:center;"
+|[https://doi.org/10.1016/s0090-4295(97)00500-1 Sharifi et al. 1998]
-! style="width: 25%" |Study
+|NR
-! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
+| style="background-color:#91cf61" |Phase 2 (RT)
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Endocrine therapy====
+*[[Leuprolide (Lupron)|Leuprolide (Lupron) 4-month depot]] 30 mg IM once on day 1
+'''16-week cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #6, 6-month depot {{#subobject:21720f |Variant=1}}===
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
+!style="width: 33%"|Study
+!style="width: 33%"|Dates of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 |-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2948179/ Scher et al. 2010 (S-3100-1-01)]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3278745/ Spitz et al. 2011 (L-PC07-169)]
-| style="background-color:#91cf61" |Phase I/II
+|2008-2009
+| style="background-color:#91cf61" |Non-randomized phase 3 (RT)
 |-
 |}
-''Note: this is the reported MTD from the phase I portion of the trial; however, it is NOT the dose used in subsequent phase III studies.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Endocrine therapy====
+*[[Leuprolide (Lupron)|Leuprolide (Lupron) 6-month depot]] 45 mg IM once on day 1
-*[[Enzalutamide (Xtandi)]] 240 mg PO once per day
+'''26-week cycles'''
+</div></div>
-'''Continued indefinitely'''
 ===References===
+#Garnick MB, Glode LM; Leuprolide Study Group. Leuprolide versus diethylstilbestrol for metastatic prostate cancer. N Engl J Med. 1984 Nov 15;311(20):1281-6. [https://doi.org/10.1056/NEJM198411153112004 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/6436700/ PubMed]
+#'''SWOG-8494:''' Crawford ED, Eisenberger MA, McLeod DG, Spaulding JT, Benson R, Dorr FA, Blumenstein BA, Davis MA, Goodman PJ. A controlled trial of leuprolide with and without flutamide in prostatic carcinoma. N Engl J Med. 1989 Aug 17;321(7):419-24. Erratum in: N Engl J Med 1989 Nov 16;321(20):1420. [https://doi.org/10.1056/NEJM198908173210702 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/2503724/ PubMed]
+#Sharifi R, Soloway M; Leuprolide Study Group. Clinical study of leuprolide depot formulation in the treatment of advanced prostate cancer. J Urol. 1990 Jan;143(1):68-71. [https://www.auajournals.org/doi/abs/10.1016/S0022-5347%2817%2939868-3 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2104638/ PubMed]
+#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. [http://www.clinicaltherapeutics.com/article/S0149-2918(96)80215-3 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/8879893/ 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. [https://doi.org/10.1016/s0090-4295(97)00500-1 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9495710/ PubMed]
+#Heyns CF, Simonin MP, Grosgurin P, Schall R, Porchet HC; South African Triptorelin Study Group. Comparative efficacy of triptorelin pamoate and leuprolide acetate in men with advanced prostate cancer. BJU Int. 2003 Aug;92(3):226-31. [https://doi.org/10.1046/j.1464-410x.2003.04308.x link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/12887472/ 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. [http://jjco.oxfordjournals.org/content/34/1/20.full link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15020659/ PubMed]
+##'''Update:''' Akaza H, Hinotsu S, Usami M, Arai Y, Kanetake H, Naito S, Hirao Y; Study Group for the Combined Androgen Blockade Therapy of Prostate Cancer. Combined androgen blockade with bicalutamide for advanced prostate cancer: long-term follow-up of a phase 3, double-blind, randomized study for survival. Cancer. 2009 Aug 1;115(15):3437-45. [https://doi.org/10.1002/cncr.24395 link to original article] [https://pubmed.ncbi.nlm.nih.gov/19536889/ PubMed]
+#'''CS21:''' 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. [https://doi.org/10.1111/j.1464-410X.2008.08183.x link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19035858/ PubMed] [https://clinicaltrials.gov/study/NCT00295750 NCT00295750]
+##'''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. [https://doi.org/10.1016/j.eururo.2009.11.029 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19962227/ PubMed]
+#'''L-PC07-169:''' Spitz A, Young JM, Larsen L, Mattia-Goldberg C, Donnelly J, Chwalisz K. Efficacy and safety of leuprolide acetate 6-month depot for suppression of testosterone in patients with prostate cancer. Prostate Cancer Prostatic Dis. 2012 Mar;15(1):93-9. Epub 2011 Oct 25. [https://www.nature.com/articles/pcan201150 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3278745/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22025196/ PubMed] [https://clinicaltrials.gov/study/NCT00626431 NCT00626431]
+#'''HERO:''' Shore ND, Saad F, Cookson MS, George DJ, Saltzstein DR, Tutrone R, Akaza H, Bossi A, van Veenhuyzen DF, Selby B, Fan X, Kang V, Walling J, Tombal B; HERO Study Investigators. Oral Relugolix for Androgen-Deprivation Therapy in Advanced Prostate Cancer. N Engl J Med. 2020 Jun 4;382(23):2187-2196. Epub 2020 May 29. [https://doi.org/10.1056/NEJMoa2004325 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32469183/ PubMed] [https://clinicaltrials.gov/study/NCT03085095 NCT03085095]
+##'''HRQoL analysis:''' Tombal B, Collins S, Morgans AK, Hunsche E, Brown B, Zhu E, Bossi A, Shore N. Impact of Relugolix Versus Leuprolide on the Quality of Life of Men with Advanced Prostate Cancer: Results from the Phase 3 HERO Study. Eur Urol. 2023 Dec;84(6):579-587. Epub 2023 Oct 11. [https://doi.org/10.1016/j.eururo.2023.09.007 link to original article] [https://pubmed.ncbi.nlm.nih.gov/37833178/ PubMed]
-#'''S-3100-1-01:''' Scher HI, Beer TM, Higano CS, Anand A, Taplin ME, Efstathiou E, Rathkopf D, Shelkey J, Yu EY, Alumkal J, Hung D, Hirmand M, Seely L, Morris MJ, Danila DC, Humm J, Larson S, Fleisher M, Sawyers CL; Prostate Cancer Foundation/Department of Defense Prostate Cancer Clinical Trials Consortium. Antitumour activity of MDV3100 in castration-resistant prostate cancer: a phase 1-2 study. Lancet. 2010 Apr 24;375(9724):1437-46. Epub 2010 Apr 14. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)60172-9/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2948179/ link to PMC article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/20398925 PubMed] NCT00510718
+==Nilutamide & Orchiectomy {{#subobject:15 |Regimen=1}}==
-#'''AFFIRM:''' 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. [https://www.nejm.org/doi/full/10.1056/NEJMoa1207506 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22894553 PubMed] NCT00974311
+<div class="toccolours" style="background-color:#eeeeee">
-<!-- # Beer TM, Armstrong AJ, Sternberg CN, Higano CS, Iversen P, Loriot Y, et al. Enzalutamide in men with chemotherapy-naive metastatic prostate cancer (mCRPC): Results of phase III PREVAIL study. ASCO Meeting Abstracts. 2014 February 5, 2014;32(4_suppl):LBA1. [http://abstracts.asco.org/142/AbstView_142_123836.html link to original article] '''contains verified protocol''' -->
+===Regimen {{#subobject:15 |Variant=1}}===
-#'''PREVAIL:''' 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. [https://www.nejm.org/doi/full/10.1056/NEJMoa1405095 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4418931/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/24881730 PubMed] NCT01212991
-##'''Update:''' Beer TM, Armstrong AJ, Rathkopf D, Loriot Y, Sternberg CN, Higano CS, Iversen P, Evans CP, Kim CS, Kimura G, Miller K, Saad F, Bjartell AS, Borre M, Mulders P, Tammela TL, Parli T, Sari S, van Os S, Theeuwes A, Tombal B. Enzalutamide in men with chemotherapy-naïve metastatic castration-resistant prostate cancer: Extended analysis of the phase 3 PREVAIL study. Eur Urol. 2017 Feb;71(2):151-154. Epub 2016 Jul 28. [http://www.europeanurology.com/article/S0302-2838(16)30437-7/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5570461/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/27477525 PubMed]
-##'''HRQoL analysis:''' Devlin N, Herdman M, Pavesi M, Phung D, Naidoo S, Beer TM, Tombal B, Loriot Y, Ivanescu C, Parli T, Balk M, Holmstrom S. Health-related quality of life effects of enzalutamide in patients with metastatic castration-resistant prostate cancer: an in-depth post hoc analysis of EQ-5D data from the PREVAIL trial. Health Qual Life Outcomes. 2017 Jun 23;15(1):130. [https://hqlo.biomedcentral.com/articles/10.1186/s12955-017-0704-y link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5481866/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/28645287 PubMed]
-#'''TERRAIN:''' Shore ND, Chowdhury S, Villers A, Klotz L, Siemens DR, Phung, van Os S, Hasabou N, Wang F, Bhattacharya S, Heidenreich A. Efficacy and safety of enzalutamide versus bicalutamide for patients with metastatic prostate cancer (TERRAIN): a randomised, double-blind, phase 2 study. Lancet Oncol. 2016 Feb;17(2):153-163. Epub 2016 Jan 14. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)00518-5/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/26774508 PubMed] NCT01288911
-<!-- Presented in part at the American Urological Association 2015 Annual Meeting, New Orleans, LA, May 15-19, 2015. -->
-#'''STRIVE:''' 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. [https://doi.org/10.1200/jco.2015.64.9285 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/26811535 PubMed] NCT01664923
-#'''PLATO:''' Attard G, Borre M, Gurney H, Loriot Y, Andresen-Daniil C, Kalleda R, Pham T, Taplin ME; PLATO collaborators. Abiraterone alone or in combination with enzalutamide in metastatic castration-resistant prostate cancer with rising prostate-specific antigen during enzalutamide treatment. J Clin Oncol. 2018 Sep 1;36(25):2639-2646. Epub 2018 Jul 20. [https://doi.org/10.1200/JCO.2018.77.9827 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/30028657 PubMed] NCT01995513
-#'''PROfound:''' de Bono J, Mateo J, Fizazi K, Saad F, Shore N, Sandhu S, Chi KN, Sartor O, Agarwal N, Olmos D, Thiery-Vuillemin A, Twardowski P, Mehra N, Goessl C, Kang J, Burgents J, Wu W, Kohlmann A, Adelman CA, Hussain M. Olaparib for Metastatic Castration-Resistant Prostate Cancer. N Engl J Med. 2020 May 28;382(22):2091-2102. Epub 2020 Apr 28. [http://doi.org/10.1056/NEJMoa1911440 link to original article] '''contains verified protocol''' [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1911440/suppl_file/nejmoa1911440_appendix.pdf link to supplementary appendix] [https://pubmed.ncbi.nlm.nih.gov/32343890/ PubMed] NCT02987543
-# '''TRANSFORMER:''' Denmeade SR, Wang H, Agarwal N, Smith D, Schweizer MT, Stein MN, Assikis V, Twardowski P, Flaig T, Szmulewitz R, Holzbeierlein J, Hauke R, Sonpavde G, Garcia J, Hussain A, Sartor O, Mao S, Cao H, Fu W, Wang T, Abdallah R, Lim SJ, Bolejack V, Paller C, Carducci M, Markowski MC, Eisenberger MA, Antonarakis ES; TRANSFORMER investigators. TRANSFORMER: A Randomized Phase II Study Comparing Bipolar Androgen Therapy Versus Enzalutamide in Asymptomatic Men With Castration-Resistant Prostate Cancer. J Clin Oncol. Epub 2021 Feb 22  [https://doi.org/10.1200/jco.20.02759 link to original article] [https://ascopubs.org/doi/suppl/10.1200/JCO.20.02759 link to protocol] [https://pubmed.ncbi.nlm.nih.gov/33617303/ PubMed] NCT02286921
-#'''CASPAR:''' NCT04455750
-#'''KEYLYNK-010:''' NCT03834519
-==Hydrocortisone monotherapy {{#subobject:f48fb4 |Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
-===Regimen {{#subobject:da4be9 |Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 ! style="width: 20%" |Study
-! style="width: 20%" |Years of enrollment
+! style="width: 20%" |Dates of enrollment
 ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 ! style="width: 20%" |Comparator
 ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1200/JCO.1999.17.8.2506 Kantoff et al. 1999 (CALGB 9182)]
+|[https://doi.org/10.1016/s0022-5347(17)36003-2 Janknegt et al. 1993 (International Anandron Study)]
-|1992-1995
+|1986-NR
-| style="background-color:#1a9851" |Phase III (C)
+| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
-|[[Stub#Mitoxantrone_.26_Hydrocortisone|Mitoxantrone & Hydrocortisone]]
+|[[Prostate_cancer_-_historical#Castration|Bilateral orchiectomy]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+| style="background-color:#1a9850" |Superior PFS
-|-
-|[https://doi.org/10.1200/JCO.2000.18.7.1440 Small et al. 2000]
-|1994-1996
-| style="background-color:#1a9851" |Phase III (C)
-|Suramin & Hydrocortisone
-| style="background-color:#d73027" |Inferior TTP
-|-
-|[https://doi.org/10.1093/annonc/mdh429 Abratt et al. 2004]
-|1997-2001
-| style="background-color:#1a9851" |Phase III (C)
-|[[Stub#Vinorelbine_.26_Hydrocortisone|Vinorelbine & Hydrocortisone]]
-| style="background-color:#fee08b" |Might have inferior PFS
 |-
 |}
+''Note: Nilutamide was to start the day of, or day after surgical castration/orchiectomy.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Endocrine therapy====
+*[[Nilutamide (Nilandron)]] as follows:
-*[[Hydrocortisone (Cortef)]] 40 mg/day PO
+**Cycle 1: 300 mg PO once per day
+**Cycle 2 onwards: 150 mg PO once per day
-'''Continued indefinitely'''
+*[[Bilateral_orchiectomy|Bilateral orchiectomy]]
+'''One-month cycles'''
+</div></div>
 ===References===
+#'''International Anandron Study:''' Janknegt RA, Abbou CC, Bartoletti R, Bernstein-Hahn L, Bracken B, Brisset JM, Da Silva FC, Chisholm G, Crawford ED, Debruyne FM, Dijkman GD, Frick J, Goedhals J, Knönagel H, Venner PM. 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. [https://doi.org/10.1016/s0022-5347(17)36003-2 link to original article] [https://pubmed.ncbi.nlm.nih.gov/7678043/ PubMed]
+## '''Update:''' Janknegt RA; Anandron International Study Group. Total androgen blockade with the use of orchiectomy and nilutamide (Anandron) or placebo as treatment of metastatic prostate cancer. Cancer. 1993 Dec 15;72(12 Suppl):3874-7. [https://doi.org/10.1002/1097-0142(19931215)72:12+%3C3874::aid-cncr2820721722%3E3.0.co;2-# link to original article] [https://pubmed.ncbi.nlm.nih.gov/8252507/ PubMed]
+## '''Update:''' Dijkman GA, Janknegt RA, De Reijke TM, Debruyne FM; International Anandron Study Group. Long-term efficacy and safety of nilutamide plus castration in advanced prostate cancer, and the significance of early prostate specific antigen normalization. J Urol. 1997 Jul;158(1):160-3. [https://doi.org/10.1097/00005392-199707000-00051 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9186345/ 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. [https://doi.org/10.1016/s0302-2838(02)00272-5 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12160584/ PubMed]
-#'''CALGB 9182:''' Kantoff PW, Halabi S, Conaway M, Picus J, Kirshner J, Hars V, Trump D, Winer EP, Vogelzang NJ. Hydrocortisone with or without mitoxantrone in men with hormone-refractory prostate cancer: results of the Cancer and Leukemia Group B 9182 study. J Clin Oncol. 1999 Aug;17(8):2506-13. [https://doi.org/10.1200/JCO.1999.17.8.2506 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/10561316 PubMed]
+==Relugolix monotherapy {{#subobject:5jagu9 |Regimen=1}}==
-#Small EJ, Meyer M, Marshall ME, Reyno LM, Meyers FJ, Natale RB, Lenehan PF, Chen L, Slichenmyer WJ, Eisenberger M. Suramin therapy for patients with symptomatic hormone-refractory prostate cancer: results of a randomized phase III trial comparing suramin plus hydrocortisone to placebo plus hydrocortisone. J Clin Oncol. 2000 Apr;18(7):1440-50. [https://doi.org/10.1200/JCO.2000.18.7.1440 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/10735891 PubMed]
+<div class="toccolours" style="background-color:#eeeeee">
-#Abratt RP, Brune D, Dimopoulos MA, Kliment J, Breza J, Selvaggi FP, Beuzeboc P, Demkow T, Oudard S. Randomised phase III study of intravenous vinorelbine plus hormone therapy versus hormone therapy alone in hormone-refractory prostate cancer. Ann Oncol. 2004 Nov;15(11):1613-21. [https://doi.org/10.1093/annonc/mdh429 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15520061 PubMed]
+===Regimen {{#subobject:gaghc5 |Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-==Ketoconazole & Hydrocortisone {{#subobject:19 |Regimen=1}}==
+!style="width: 20%"|Study
-{| class="wikitable" style="float:right; margin-left: 5px;"
+!style="width: 20%"|Dates of enrollment
-|-
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
-|[[#top|back to top]]
+!style="width: 20%"|Comparator
-|}
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-===Regimen {{#subobject:19 |Variant=1}}===
+|-
+|[https://doi.org/10.1056/NEJMoa2004325 Shore et al. 2020 (HERO)]
+<!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
+|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-321-1 <span style="color:white;">ESMO-MCBS (4)</span>]'''
+|-
+|} -->
+|2017-04 to 2018-10
+| style="background-color:#1a9851" |Phase 3 (E-RT-switch-ic)
+|[[#Leuprolide_monotherapy_3|Leuprolide]]
+| style="background-color:#1a9850" |Superior testosterone suppression (primary endpoint)
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Endocrine therapy====
+*[[Relugolix (Orgovyx)]] 360 mg PO once on day 1, then 120 mg PO once per day
+'''48-week course'''
+</div></div>
+===References===
+#'''HERO:''' Shore ND, Saad F, Cookson MS, George DJ, Saltzstein DR, Tutrone R, Akaza H, Bossi A, van Veenhuyzen DF, Selby B, Fan X, Kang V, Walling J, Tombal B; HERO Study Investigators. Oral Relugolix for Androgen-Deprivation Therapy in Advanced Prostate Cancer. N Engl J Med. 2020 Jun 4;382(23):2187-2196. Epub 2020 May 29. [https://doi.org/10.1056/NEJMoa2004325 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32469183/ PubMed] [https://clinicaltrials.gov/study/NCT03085095 NCT03085095]
+##'''HRQoL analysis:''' Tombal B, Collins S, Morgans AK, Hunsche E, Brown B, Zhu E, Bossi A, Shore N. Impact of Relugolix Versus Leuprolide on the Quality of Life of Men with Advanced Prostate Cancer: Results from the Phase 3 HERO Study. Eur Urol. 2023 Dec;84(6):579-587. Epub 2023 Oct 11. [https://doi.org/10.1016/j.eururo.2023.09.007 link to original article] [https://pubmed.ncbi.nlm.nih.gov/37833178/ PubMed]
+==Triptorelin monotherapy {{#subobject:15acjb |Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:1596sc |Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 ! style="width: 20%" |Study
-! style="width: 20%" |Years of enrollment
+! style="width: 20%" |Dates of enrollment
 ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 ! style="width: 20%" |Comparator
 ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-![[Overall response rate|'''ORR''', PSA RR]]
-!Comparator [[Overall response rate|'''ORR''', PSA RR]]
-!Pt Population
-|-
-|[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(84)92909-X/fulltext Trachtenberg & Pont 1984]
-|NR
-| style="background-color:#ffffbe" |Pilot
-| style="background-color:#d3d3d3" |
-| style="background-color:#d3d3d3" |
-|
-|
-|
 |-
-|[https://doi.org/10.1200/jco.2004.06.037 Small et al. 2004 (CALGB 9583)]
+|[https://doi.org/10.1046/j.1464-410x.2003.04308.x Heyns et al. 2003]
 |NR
-| style="background-color:#1a9851" |Phase III (E-esc)
+| style="background-color:#1a9851" |Phase 3 (E-RT-switch-ic)
-|[[#Antiandrogen_withdrawal|Antiandrogen withdrawal]]
+|[[#Leuprolide_monotherapy_3|Leuprolide]]
-| style="background-color:#1a9850" |Superior PSA response
+| style="background-color:#91cf60" |Seems to have superior 9-month OS (secondary endpoint)<br><br>Equivalent rates of castrate testosterone levels (primary endpoint)
-|pts w/ measurable disease: '''20%''' (95% CI 11 - 32), '''27%''' (95% CI 20 - 35)
-|pts w/ measurable disease: '''2%''' (95% CI 0 - 11), '''11%''' (95% CI 7 - 17)
-|Progression at ADT, i.e. CRPC
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Endocrine therapy====
+*[[Triptorelin (Trelstar LA)]] 3.75 mg IM once on day 1
-*[[Ketoconazole (Nizoral)]] 400 mg PO three times per day
+'''28-day cycle for 9 cycles'''
-*[[Hydrocortisone (Cortef)]] 30 mg PO QAM and 10 mg PO QPM
+</div></div>
-'''Continued indefinitely'''
 ===References===
+#Heyns CF, Simonin MP, Grosgurin P, Schall R, Porchet HC; South African Triptorelin Study Group. Comparative efficacy of triptorelin pamoate and leuprolide acetate in men with advanced prostate cancer. BJU Int. 2003 Aug;92(3):226-31. [https://doi.org/10.1046/j.1464-410x.2003.04308.x link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12887472/ PubMed]
-#Trachtenberg J, Pont A. Ketoconazole therapy for advanced prostate cancer. Lancet. 1984 Aug 25;2(8400):433-5. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(84)92909-X/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/6147504 PubMed]
+=Metastatic disease, second-line hormonal therapy=
-#'''CALGB 9583:''' 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. [https://doi.org/10.1200/jco.2004.06.037 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15020604 PubMed]
+==Abiraterone monotherapy {{#subobject:16 |Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
-==Ketoconazole, Hydrocortisone, Dutasteride {{#subobject:20 |Regimen=1}}==
+===Regimen {{#subobject:16 |Variant=1}}===
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
-===Regimen {{#subobject:20 |Variant=1}}===
-{| class="wikitable" style="width: 50%; text-align:center;"
-! style="width: 25%" |Study
-! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-|-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3644858/ Taplin et al. 2009]
-| style="background-color:#91cf61" |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
-'''Continued indefinitely'''
-===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. [http://clincancerres.aacrjournals.org/content/15/22/7099.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3644858/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/19887483 PubMed]
-==Prednisone monotherapy {{#subobject:22 |Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
-===Regimen variant #1, 5 mg twice per day {{#subobject:22 |Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 ! style="width: 20%" |Study
-! style="width: 20%" |Years of enrollment
+! style="width: 20%" |Dates of enrollment
 ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 ! style="width: 20%" |Comparator
 ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1200/jco.1989.7.5.590 Tannock et al. 1989]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3471149/ de Bono et al. 2011 (COU-AA-301)]
-|1976-1980
+<!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
-| style="background-color:#ffffbe" |Retrospective
+|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-98-1 <span style="color:white;">ESMO-MCBS (4)</span>]'''
-| style="background-color:#d3d3d3" |
-| style="background-color:#d3d3d3" |
 |-
-|[https://doi.org/10.1200/JCO.1996.14.6.1756 Tannock et al. 1996 (CCI-NOV22)]
+|} -->
-|1990-1994
+|2008-05 to 2009-07
-| style="background-color:#1a9851" |Phase III (C)
+| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
-|[[#Mitoxantrone_.26_Prednisone|Mitoxantrone & Prednisone]]
+|[[#Prednisone_monotherapy|Prednisone]]
-| style="background-color:#d73027" |Inferior palliation
+| style="background-color:#1a9850" |Superior OS<sup>1</sup> (primary endpoint)<br>Median OS: 15.8 vs 11.2 mo<br>(HR 0.74, 95% CI 0.64-0.86)
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3683570/ Ryan et al. 2013 (COU-AA-302)]
+|2009-04 to 2010-06
+| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
+|[[#Prednisone_monotherapy|Prednisone]]
+| style="background-color:#1a9850" |Superior OS<sup>2</sup> (co-primary endpoint)<br>Median OS: 34.7 vs 30.3 mo<br>(HR 0.81, 95% CI 0.70-0.93)
 |-
-|[https://www.auajournals.org/doi/abs/10.1016/S0022-5347%2805%2964163-8 Berry et al. 2002]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5717983/ Ye et al. 2017 (ABI-PRO-3002)]
-|1997-1999
+|2012-03-27 to 2013-02-14
-| style="background-color:#1a9851" |Phase III (C)
+| style="background-color:#1a9851" |Phase 3 (E-esc)
-|[[#Mitoxantrone_.26_Prednisone|Mitoxantrone & Prednisone]]
+|[[#Prednisone_monotherapy|Prednisone]]
-| style="background-color:#fc8d59" |Seems to have inferior TTTF
+| style="background-color:#1a9850" |Superior TTPP (primary endpoint)
 |-
-|[https://doi.org/10.1200/JCO.2008.20.1228 Sternberg et al. 2009 (SPARC)]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6118405/ Attard et al. 2018 (PLATO)]
-|2003-2006
+|2013-NR
-| style="background-color:#1a9851" |Phase III (C)
+| style="background-color:#1a9851" |Phase 3 (C)
-|Satraplatin & Prednisone
+|[[#Abiraterone.2C_Enzalutamide.2C_Prednisone_999|Abiraterone, Enzalutamide, Prednisone]]
-| style="background-color:#d73027" |Inferior PFS
+| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 |-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3471149/ de Bono et al. 2011 (COU-AA-301)]
+|[https://doi.org/10.1016/S1470-2045(18)30860-X Smith et al. 2019 (ERA 223)]
-|2008-2009
+|2014-2016
-| style="background-color:#1a9851" |Phase III (C)
+| style="background-color:#1a9851" |Phase 3 (C)
-|[[#Abiraterone_monotherapy|Abiraterone]]
+|[[#Abiraterone.2C_Radium-223.2C_Prednisone_999|Abiraterone, Radium-223, Prednisone]]
-| style="background-color:#d73027" |Inferior OS
+| style="background-color:#ffffbf" |Did not meet primary endpoint of symptomatic skeletal EFS
 |-
-|[https://doi.org/10.1200/JCO.2012.48.5268 Michaelson et al. 2013 (SUN 1120)]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9377412/ Saad et al. 2021 (ACIS)]
-|2008-2010
+|2014-2016
-| style="background-color:#1a9851" |Phase III (C)
+| style="background-color:#1a9851" |Phase 3 (C)
-|Sunitinib & Prednisone
+|[[#Abiraterone_.26_Apalutamide|Abiraterone & Apalutamide]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+| style="background-color:#d73027" |Inferior rPFS
 |-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3683570/ Ryan et al. 2013 (COU-AA-302)]
+|[https://doi.org/10.1056/NEJMoa1911206 de Wit et al. 2019 (CARD)]
-|2009-2010
+|2015-2018
-| style="background-color:#1a9851" |Phase III (C)
+| style="background-color:#1a9851" |Phase 3 (C)
-|[[#Abiraterone_monotherapy|Abiraterone]]
+|[[#Cabazitaxel_.26_Prednisone|Cabazitaxel & Prednisone]]
-| style="background-color:#fc8d59" |Seems to have inferior OS
+| style="background-color:#d73027" |Inferior PFSi/OS
 |-
-|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)70027-6/fulltext Saad et al. 2015 (ELM-PC 4)]
+|[https://doi.org/10.1016/s0140-6736(21)00580-8 Sweeney et al. 2021 (IPATential150)]
-|2010-2012
+|2017-2019
-| style="background-color:#1a9851" |Phase III (C)
+| style="background-color:#1a9851" |Phase 3 (C)
-|Orteronel & Prednisone
+|[[#Abiraterone_.26_Ipatasertib_777|Abiraterone & Ipatasertib]]
-| style="background-color:#d73027" |Inferior PFS
+| style="background-color:#fc8d59" |Seems to have inferior rPFS
 |-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4879718/ Fizazi et al. 2015 (ELM-PC 5)]
+|[https://doi.org/10.1056/EVIDoa2200043 Clarke et al. 2022 (PROpel)]
-|2010-NR
+|2018-2020
-| style="background-color:#1a9851" |Phase III (C)
+| style="background-color:#1a9851" |Phase 3 (C)
-|Orteronel & Prednisone
+|[[#Abiraterone_.26_Olaparib|Abiraterone & Olaparib]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+| style="background-color:#fee08b" |Might have inferior OS<sup>3</sup>
 |-
-|[https://doi.org/10.1200/JCO.2015.65.5597 Smith et al. 2016 (COMET-1)]
+|[https://doi.org/10.1200/jco.23.00233 Antonarakis et al. 2023 (KEYLYNK-010)]
-|2012-2014
+|2019-05-30 to 2021-07-16
-| style="background-color:#1a9851" |Phase III (C)
+| style="background-color:#1a9851" |Phase 3 (C)
-|[[#Cabozantinib_monotherapy|Cabozantinib]]
+|[[#Olaparib_.26_Pembrolizumab_999|Olaparib & Pembrolizumab]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+| style="background-color:#ffffbf" |Did not meet co-primary endpoints of rPFS/OS
 |-
 |}
+''<sup>1</sup>Reported efficacy for COU-AA-301 is based on the 2012 update.''<br>
+''<sup>2</sup>Reported efficacy for COU-AA-302 is based on the 2015 update.''<br>
+''<sup>3</sup>Reported efficacy for PROpel is based on the 2023 update.''
+<div class="toccolours" style="background-color:#fdcdac">
+====Prior treatment criteria====
+*COU-AA-301: Chemotherapy exposure
+*COU-AA-302, ABI-PRO-3002, PLATO, ERA 223, ACIS, IPATential150: Chemotherapy naive
+*KEYLYNK-010: Enzalutamide exposure
+</div>
+<div class="toccolours" style="background-color:#cbd5e8">
+====Preceding treatment====
+*PLATO: First-line [[#Enzalutamide_monotherapy_3|enzalutamide]], with rising PSA
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Endocrine therapy====
+*[[Abiraterone (Zytiga)]] 1000 mg PO once per day on days 1 to 28
+====Supportive therapy====
+*One of the following:
+**[[Prednisone (Sterapred)]] 5 mg PO twice per day on days 1 to 28
+**[[Prednisolone (Millipred)]] 5 mg PO twice per day on days 1 to 28
+'''28-day cycles'''
+</div></div>
+===References===
+#'''COU-AA-301:''' 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. [https://doi.org/10.1056/NEJMoa1014618 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3471149/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21612468/ PubMed] [https://clinicaltrials.gov/study/NCT00638690 NCT00638690]
+##'''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. [https://doi.org/10.1016/S1470-2045(12)70379-0 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22995653/ 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. [https://doi.org/10.1016/S1470-2045(12)70473-4 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23142059/ PubMed]
+#'''COU-AA-302:''' 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. [https://doi.org/10.1056/NEJMoa1209096 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3683570/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23228172/ PubMed] [https://clinicaltrials.gov/study/NCT00887198 NCT00887198]
+##'''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. [https://doi.org/10.1016/S1470-2045(14)71205-7 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25601341/ PubMed]
+#'''ABI-PRO-3002:''' Ye D, Huang Y, Zhou F, Xie K, Matveev V, Li C, Alexeev B, Tian Y, Qiu M, Li H, Zhou T, De Porre P, Yu M, Naini V, Liang H, Wu Z, Sun Y. A phase 3, double-blind, randomized placebo-controlled efficacy and safety study of abiraterone acetate in chemotherapy-naïve patients with mCRPC in China, Malaysia, Thailand and Russia. Asian J Urol. 2017 Apr;4(2):75-85. Epub 2017 Jan 23. [https://doi.org/10.1016/j.ajur.2017.01.002 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5717983/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/29264210/ PubMed] [https://clinicaltrials.gov/study/NCT01591122 NCT01591122]
+#'''PLATO:''' Attard G, Borre M, Gurney H, Loriot Y, Andresen-Daniil C, Kalleda R, Pham T, Taplin ME; PLATO collaborators. Abiraterone alone or in combination with enzalutamide in metastatic castration-resistant prostate cancer with rising prostate-specific antigen during enzalutamide treatment. J Clin Oncol. 2018 Sep 1;36(25):2639-2646. Epub 2018 Jul 20. [https://doi.org/10.1200/JCO.2018.77.9827 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6118405/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30028657/ PubMed] [https://clinicaltrials.gov/study/NCT01995513 NCT01995513]
+#'''ERA 223:''' Smith M, Parker C, Saad F, Miller K, Tombal B, Ng QS, Boegemann M, Matveev V, Piulats JM, Zucca LE, Karyakin O, Kimura G, Matsubara N, Nahas WC, Nolè F, Rosenbaum E, Heidenreich A, Kakehi Y, Zhang A, Krissel H, Teufel M, Shen J, Wagner V, Higano C. Addition of radium-223 to abiraterone acetate and prednisone or prednisolone in patients with castration-resistant prostate cancer and bone metastases (ERA 223): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2019 Mar;20(3):408-419. Epub 2019 Feb 6. [https://doi.org/10.1016/S1470-2045(18)30860-X link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/30738780/ PubMed] [https://clinicaltrials.gov/study/NCT02043678 NCT02043678]
+#'''CARD:''' de Wit R, de Bono J, Sternberg CN, Fizazi K, Tombal B, Wülfing C, Kramer G, Eymard JC, Bamias A, Carles J, Iacovelli R, Melichar B, Sverrisdóttir Á, Theodore C, Feyerabend S, Helissey C, Ozatilgan A, Geffriaud-Ricouard C, Castellano D; CARD Investigators. Cabazitaxel versus Abiraterone or Enzalutamide in Metastatic Prostate Cancer. N Engl J Med. 2019 Dec 26;381(26):2506-2518. Epub 2019 Sep 30. [https://doi.org/10.1056/NEJMoa1911206 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/31566937/ PubMed] [https://clinicaltrials.gov/study/NCT02485691 NCT02485691]
+##'''HRQoL analysis:''' Fizazi K, Kramer G, Eymard JC, Sternberg CN, de Bono J, Castellano D, Tombal B, Wülfing C, Liontos M, Carles J, Iacovelli R, Melichar B, Sverrisdóttir Á, Theodore C, Feyerabend S, Helissey C, Oudard S, Facchini G, Poole EM, Ozatilgan A, Geffriaud-Ricouard C, Bensfia S, de Wit R. Quality of life in patients with metastatic prostate cancer following treatment with cabazitaxel versus abiraterone or enzalutamide (CARD): an analysis of a randomised, multicentre, open-label, phase 4 study. Lancet Oncol. 2020 Nov;21(11):1513-1525. Epub 2020 Sep 11. [https://doi.org/10.1016/s1470-2045(20)30449-6 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32926841/ PubMed]
+# '''IPATential150:''' Sweeney C, Bracarda S, Sternberg CN, Chi KN, Olmos D, Sandhu S, Massard C, Matsubara N, Alekseev B, Parnis F, Atduev V, Buchschacher GL Jr, Gafanov R, Corrales L, Borre M, Stroyakovskiy D, Alves GV, Bournakis E, Puente J, Harle-Yge ML, Gallo J, Chen G, Hanover J, Wongchenko MJ, Garcia J, de Bono JS. Ipatasertib plus abiraterone and prednisolone in metastatic castration-resistant prostate cancer (IPATential150): a multicentre, randomised, double-blind, phase 3 trial. Lancet. 2021 Jul 10;398(10295):131-142. [https://doi.org/10.1016/s0140-6736(21)00580-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/34246347/ PubMed] [https://clinicaltrials.gov/study/NCT03072238 NCT03072238]
+# '''ACIS:''' Saad F, Efstathiou E, Attard G, Flaig TW, Franke F, Goodman OB Jr, Oudard S, Steuber T, Suzuki H, Wu D, Yeruva K, De Porre P, Brookman-May S, Li S, Li J, Thomas S, Bevans KB, Mundle SD, McCarthy SA, Rathkopf DE; ACIS Investigators. Apalutamide plus abiraterone acetate and prednisone versus placebo plus abiraterone and prednisone in metastatic, castration-resistant prostate cancer (ACIS): a randomised, placebo-controlled, double-blind, multinational, phase 3 study. Lancet Oncol. 2021 Nov;22(11):1541-1559. Epub 2021 Sep 30. [https://doi.org/10.1016/s1470-2045(21)00402-2 link to original article] '''contains dosing details in abstract''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9377412/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34600602/ PubMed] [https://clinicaltrials.gov/study/NCT02257736 NCT02257736]
+#'''PROpel:''' Clarke NW, Armstrong AJ, Thiery-Vuillemin A, Oya M, Shore N, Loredo E, Procopio G, de Menezes J, Girotto G, Arslan C, Mehra N, Parnis F, Brown E, Schlürmann F, Joung JY, Sugimoto M, Virizuela JA, Emmenegger U, Navratil J, Buchschacher GL, Poehlein C, Harrington EA, Desai C, Kang J, Saad F; PROpel Investigators. Abiraterone and Olaparib for Metastatic Castration-Resistant Prostate Cancer. NEJM Evidence. 2022 Sep;1(9):EVIDoa2200043. Epub 2022 Jun 3. [https://doi.org/10.1056/EVIDoa2200043 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/38319800/ PubMed] [https://clinicaltrials.gov/study/NCT03732820 NCT03732820]
+##'''Update:''' Saad F, Clarke NW, Oya M, Shore N, Procopio G, Guedes JD, Arslan C, Mehra N, Parnis F, Brown E, Schlürmann F, Joung JY, Sugimoto M, Sartor O, Liu YZ, Poehlein C, Barker L, Del Rosario PM, Armstrong AJ. Olaparib plus abiraterone versus placebo plus abiraterone in metastatic castration-resistant prostate cancer (PROpel): final prespecified overall survival results of a randomised, double-blind, phase 3 trial. Lancet Oncol. 2023 Oct;24(10):1094-1108. Epub 2023 Sep 12. [https://doi.org/10.1016/s1470-2045(23)00382-0 link to original article] [https://pubmed.ncbi.nlm.nih.gov/37714168/ PubMed]
+#'''KEYLYNK-010:''' Antonarakis ES, Park SH, Goh JC, Shin SJ, Lee JL, Mehra N, McDermott R, Sala-Gonzalez N, Fong PC, Greil R, Retz M, Sade JP, Yanez P, Huang YH, Begbie SD, Gafanov RA, De Santis M, Rosenbaum E, Kolinsky MP, Rey F, Chiu KY, Roubaud G, Kramer G, Sumitomo M, Massari F, Suzuki H, Qiu P, Zhang J, Kim J, Poehlein CH, Yu EY. Pembrolizumab Plus Olaparib for Patients With Previously Treated and Biomarker-Unselected Metastatic Castration-Resistant Prostate Cancer: The Randomized, Open-Label, Phase III KEYLYNK-010 Trial. J Clin Oncol. 2023 Aug 1;41(22):3839-3850. Epub 2023 Jun 8. [https://doi.org/10.1200/jco.23.00233 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/37290035/ PubMed] [https://clinicaltrials.gov/study/NCT03834519 NCT03834519]
+#'''AMPLITUDE:''' [https://clinicaltrials.gov/study/NCT04497844 NCT04497844]
-*[[Prednisone (Sterapred)]] 5 mg PO twice per day
+==Abiraterone & Apalutamide {{#subobject:16ugh2 |Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
-'''Continued indefinitely'''
+===Regimen {{#subobject:gjagd16 |Variant=1}}===
-===Regimen variant #2, 5 mg QID {{#subobject:5055a7 |Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 ! style="width: 20%" |Study
-! style="width: 20%" |Years of enrollment
+! style="width: 20%" |Dates of enrollment
 ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 ! style="width: 20%" |Comparator
 ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1200/JCO.2001.19.1.62 Fosså et al. 2001 (EORTC 30903)]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9377412/ Saad et al. 2021 (ACIS)]
-|1992-1998
+|2014-2016
-| style="background-color:#1a9851" |Phase III (C)
+| style="background-color:#1a9851" |Phase 3 (E-esc)
-|[[#Flutamide_monotherapy|Flutamide]]
+|[[#Abiraterone_monotherapy|Abiraterone]]
-| style="background-color:#ffffbf" |Did not meet primary endpoints of TTP/OS
+| style="background-color:#1a9850" |Superior rPFS (primary endpoint)<br>Median rPFS: 24 vs 16.6 mo<br>(HR 0.70, 95% CI 0.60-0.83)
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Endocrine therapy====
+*[[Abiraterone (Zytiga)]] 1000 mg PO once per day on days 1 to 28
-*[[Prednisone (Sterapred)]] 5 mg PO four times per day
+*[[Apalutamide (Erleada)]] 240 mg PO once per day on days 1 to 28
+====Supportive therapy====
-'''Continued indefinitely'''
+*[[Prednisone (Sterapred)]] 5 mg PO twice per day on days 1 to 28
+'''28-day cycles'''
+</div></div>
 ===References===
+# '''ACIS:''' Saad F, Efstathiou E, Attard G, Flaig TW, Franke F, Goodman OB Jr, Oudard S, Steuber T, Suzuki H, Wu D, Yeruva K, De Porre P, Brookman-May S, Li S, Li J, Thomas S, Bevans KB, Mundle SD, McCarthy SA, Rathkopf DE; ACIS Investigators. Apalutamide plus abiraterone acetate and prednisone versus placebo plus abiraterone and prednisone in metastatic, castration-resistant prostate cancer (ACIS): a randomised, placebo-controlled, double-blind, multinational, phase 3 study. Lancet Oncol. 2021 Nov;22(11):1541-1559. Epub 2021 Sep 30. [https://doi.org/10.1016/s1470-2045(21)00402-2 link to original article] '''contains dosing details in abstract''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9377412/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34600602/ PubMed] [https://clinicaltrials.gov/study/NCT02257736 NCT02257736]
-#Tannock I, Gospodarowicz M, Meakin W, Panzarella T, Stewart L, Rider W. Treatment of metastatic prostatic cancer with low-dose prednisone: evaluation of pain and quality of life as pragmatic indices of response. J Clin Oncol. 1989 May;7(5):590-7. [https://doi.org/10.1200/jco.1989.7.5.590 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/2709088 PubMed]
+==Abiraterone & Olaparib {{#subobject:23ugc1 |Regimen=1}}==
-#'''CCI-NOV22:''' 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. [https://doi.org/10.1200/JCO.1996.14.6.1756 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/8656243 PubMed]
+<div class="toccolours" style="background-color:#eeeeee">
-##'''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. [https://doi.org/10.1200/JCO.1999.17.6.1654 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/10561201 PubMed]
+===Regimen {{#subobject:hgi1cc |Variant=1}}===
-#'''EORTC 30903:''' 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. [https://doi.org/10.1200/JCO.2001.19.1.62 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/11134196 PubMed]
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-#Berry W, Dakhil S, Modiano M, Gregurich M, Asmar L. Phase III study of mitoxantrone plus low dose prednisone versus low dose prednisone alone in patients with asymptomatic hormone refractory prostate cancer. J Urol. 2002 Dec;168(6):2439-43. [https://www.auajournals.org/doi/abs/10.1016/S0022-5347%2805%2964163-8 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12441935 PubMed]
+! style="width: 20%" |Study
-#'''SPARC:''' Sternberg CN, Petrylak DP, Sartor O, Witjes JA, Demkow T, Ferrero JM, Eymard JC, Falcon S, Calabrò F, James N, Bodrogi I, Harper P, Wirth M, Berry W, Petrone ME, McKearn TJ, Noursalehi M, George M, Rozencweig M. Multinational, double-blind, phase III study of prednisone and either satraplatin or placebo in patients with castrate-refractory prostate cancer progressing after prior chemotherapy: the SPARC trial. J Clin Oncol. 2009 Nov 10;27(32):5431-8. Epub 2009 Oct 5. [https://doi.org/10.1200/JCO.2008.20.1228 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19805692 PubMed] NCT00069745
+! style="width: 20%" |Dates of enrollment
-#'''COU-AA-301:''' 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. [https://www.nejm.org/doi/full/10.1056/NEJMoa1014618 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3471149/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/21612468 PubMed] NCT00638690
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
-##'''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. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(12)70379-0/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22995653 PubMed]
+! style="width: 20%" |Comparator
-##'''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. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(12)70473-4/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23142059 PubMed]
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-#'''COU-AA-302:''' 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. [https://www.nejm.org/doi/full/10.1056/NEJMoa1209096 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3683570/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/23228172 PubMed] NCT00887198
+|-
-##'''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. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)71205-7/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/25601341 PubMed]
+|[https://doi.org/10.1056/EVIDoa2200043 Clarke et al. 2022 (PROpel)]
-#'''SUN 1120:''' Michaelson MD, Oudard S, Ou YC, Sengeløv L, Saad F, Houede N, Ostler P, Stenzl A, Daugaard G, Jones R, Laestadius F, Ullèn A, Bahl A, Castellano D, Gschwend J, Maurina T, Chow Maneval E, Wang SL, Lechuga MJ, Paolini J, Chen I. Randomized, placebo-controlled, phase III trial of sunitinib plus prednisone versus prednisone alone in progressive, metastatic, castration-resistant prostate cancer. J Clin Oncol. 2014 Jan 10;32(2):76-82. Epub 2013 Dec 9. [https://doi.org/10.1200/JCO.2012.48.5268 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24323035 PubMed] NCT00676650
+<!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
-#'''ELM-PC 5:''' Fizazi K, Jones R, Oudard S, Efstathiou E, Saad F, de Wit R, De Bono J, Cruz FM, Fountzilas G, Ulys A, Carcano F, Agarwal N, Agus D, Bellmunt J, Petrylak DP, Lee SY, Webb IJ, Tejura B, Borgstein N, Dreicer R. Phase III, randomized, double-blind, multicenter trial comparing orteronel (TAK-700) plus prednisone with placebo plus prednisone in patients with metastatic castration-resistant prostate cancer that has progressed during or after docetaxel-based therapy: ELM-PC 5. J Clin Oncol. 2015 Mar 1;33(7):723-31. Epub 2015 Jan 26. [https://doi.org/10.1200/JCO.2014.56.5119 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4879718/ link to PMC article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25624429 PubMed] NCT01193257
+|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-365-1 <span style="color:white;">ESMO-MCBS (2)</span>]'''
-#'''ELM-PC 4:''' Saad F, Fizazi K, Jinga V, Efstathiou E, Fong PC, Hart LL, Jones R, McDermott R, Wirth M, Suzuki K, MacLean DB, Wang L, Akaza H, Nelson J, Scher HI, Dreicer R, Webb IJ, de Wit R; ELM-PC 4 investigators. Orteronel plus prednisone in patients with chemotherapy-naive metastatic castration-resistant prostate cancer (ELM-PC 4): a double-blind, multicentre, phase 3, randomised, placebo-controlled trial. Lancet Oncol. 2015 Mar;16(3):338-48. Epub 2015 Feb 18. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)70027-6/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25701170 PubMed] NCT01193244
+|-
-#'''COMET-1:''' 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. [https://doi.org/10.1200/JCO.2015.65.5597 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/27400947 PubMed] NCT01605227
+|} -->
+|2018-2020
-=Chemotherapy for metastatic castrate-sensitive disease=
+| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
-==Cabazitaxel & Prednisone {{#subobject:23jbuz |Regimen=1}}==
+|[[#Abiraterone_monotherapy|Abiraterone]]
-{| class="wikitable" style="float:right; margin-left: 5px;"
+| style="background-color:#d9ef8b" |Might have superior OS (secondary endpoint)<br>Median OS: 42.1 vs 34.7 mo<br>(HR 0.81, 95% CI 0.67-1.00)<br><br>Superior ibPFS (primary endpoint)<br>Median ibPFS: 24.8 vs 16.6 mo<br>(HR 0.66, 95% CI 0.54-0.81)
 |-
-|[[#top|back to top]]
 |}
-===Example orders===
+''<sup>1</sup>Reported efficacy is based on the 2023 update.''<br>
+<div class="toccolours" style="background-color:#b3e2cd">
+====Endocrine therapy====
+*[[Abiraterone (Zytiga)]] 1000 mg PO once per day
+====Targeted therapy====
+*[[Olaparib (Lynparza)]] 300 mg PO twice per day
+====Supportive therapy====
+*One of the following:
+**[[Prednisone (Sterapred)]] 5 mg PO twice per day
+**[[Prednisolone (Millipred)]] 5 mg PO twice per day
+'''21-day cycle for up to 10 cycles'''
+</div></div>
+===References===
+#'''PROpel:''' Clarke NW, Armstrong AJ, Thiery-Vuillemin A, Oya M, Shore N, Loredo E, Procopio G, de Menezes J, Girotto G, Arslan C, Mehra N, Parnis F, Brown E, Schlürmann F, Joung JY, Sugimoto M, Virizuela JA, Emmenegger U, Navratil J, Buchschacher GL, Poehlein C, Harrington EA, Desai C, Kang J, Saad F; PROpel Investigators. Abiraterone and Olaparib for Metastatic Castration-Resistant Prostate Cancer. NEJM Evidence. 2022 Sep;1(9):EVIDoa2200043. Epub 2022 Jun 3. [https://doi.org/10.1056/EVIDoa2200043 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/38319800/ PubMed] [https://clinicaltrials.gov/study/NCT03732820 NCT03732820]
+##'''Update:''' Saad F, Clarke NW, Oya M, Shore N, Procopio G, Guedes JD, Arslan C, Mehra N, Parnis F, Brown E, Schlürmann F, Joung JY, Sugimoto M, Sartor O, Liu YZ, Poehlein C, Barker L, Del Rosario PM, Armstrong AJ. Olaparib plus abiraterone versus placebo plus abiraterone in metastatic castration-resistant prostate cancer (PROpel): final prespecified overall survival results of a randomised, double-blind, phase 3 trial. Lancet Oncol. 2023 Oct;24(10):1094-1108. Epub 2023 Sep 12. [https://doi.org/10.1016/s1470-2045(23)00382-0 link to original article] [https://pubmed.ncbi.nlm.nih.gov/37714168/ PubMed]
-*[[Example orders for Cabazitaxel (Jevtana) in prostate cancer]]
+==Antiandrogen withdrawal {{#subobject:17 |Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:2hcb1b |Variant=1}}===
+===Regimen {{#subobject:17 |Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 ! style="width: 20%" |Study
-! style="width: 20%" |Years of enrollment
+! style="width: 20%" |Dates of enrollment
 ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 ! style="width: 20%" |Comparator
 ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.nejm.org/doi/full/10.1056/NEJMoa1911206 de Wit et al. 2019 (CARD)]
+|[https://doi.org/10.1200/jco.2004.06.037 Small et al. 2004 (CALGB 9583)]
-|2015-2018
+|NR
-| style="background-color:#1a9851" |Phase III (E-switch-ooc)
+| style="background-color:#1a9851" |Phase 3 (C)
-|1. [[#Abiraterone_monotherapy|Abiraterone]]<br> 2. [[#Enzalutamide_monotherapy|Enzalutamide]]
+|[[#Ketoconazole_.26_Hydrocortisone|Ketoconazole & Hydrocortisone]]
-| style="background-color:#1a9850" |Superior OS
+| style="background-color:#d73027" |Inferior PSA response
+|-
+|}
+''Refers to cessation of antiandrogen therapy.''
+</div></div>
+===References===
+#'''CALGB 9583:''' 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. [https://doi.org/10.1200/jco.2004.06.037 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15020604/ PubMed] [https://clinicaltrials.gov/study/NCT00002760 NCT00002760]
+==Apalutamide monotherapy {{#subobject:acc40a |Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:cf9ghi|Variant=1}}===
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
+!style="width: 33%"|Study
+!style="width: 33%"|Dates of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5543693/ Rathkopf et al. 2017 (ARN-509-001)]
+|2011-2012
+| style="background-color:#91cf61" |Non-randomized
 |-
 |}
-''Note: patients in CARD had already received and progressed on the alternate androgen signaling targeted inhibitor.''
+<div class="toccolours" style="background-color:#b3e2cd">
-====Chemotherapy====
-*[[Cabazitaxel (Jevtana)]] 25 mg/m<sup>2</sup> IV over 60 minutes once on day 1
 ====Endocrine therapy====
+*[[Apalutamide (Erleada)]] 240 mg PO once per day
-*[[Prednisone (Sterapred)]] 10 mg PO once per day
+'''Continued indefinitely'''
+</div></div>
-====Supportive medications====
-*[[:Category:Antihistamines|Antihistamine]] once on day 1, at least 30 minutes prior to [[Cabazitaxel (Jevtana)]]
-*[[:Category:Steroids|Corticosteroid]] ([[Dexamethasone (Decadron)|dexamethasone]] 8 mg or equivalent) once on day 1, at least 30 minutes prior to [[Cabazitaxel (Jevtana)]]
-*[[:Category:Antihistamines|Histamine H2-antagonist]] (except cimetidine) once on day 1, at least 30 minutes prior to [[Cabazitaxel (Jevtana)]]
-'''21-day cycles'''
 ===References===
+#'''ARN-509-001:''' Rathkopf DE, Antonarakis ES, Shore ND, Tutrone RF, Alumkal JJ, Ryan CJ, Saleh M, Hauke RJ, Bandekar R, Maneval EC, de Boer CJ, Yu MK, Scher HI. Safety and Antitumor Activity of Apalutamide (ARN-509) in Metastatic Castration-Resistant Prostate Cancer with and without Prior Abiraterone Acetate and Prednisone. Clin Cancer Res. 2017 Jul 15;23(14):3544-3551. Epub 2017 Feb 17. [http://clincancerres.aacrjournals.org/content/23/14/3544.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5543693/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28213364/ PubMed] [https://clinicaltrials.gov/study/NCT01171898 NCT01171898]
-#'''CARD:''' de Wit R, de Bono J, Sternberg CN, Fizazi K, Tombal B, Wülfing C, Kramer G, Eymard JC, Bamias A, Carles J, Iacovelli R, Melichar B, Sverrisdóttir Á, Theodore C, Feyerabend S, Helissey C, Ozatilgan A, Geffriaud-Ricouard C, Castellano D; CARD Investigators. Cabazitaxel versus Abiraterone or Enzalutamide in Metastatic Prostate Cancer. N Engl J Med. 2019 Dec 26;381(26):2506-2518. Epub 2019 Sep 30. [https://www.nejm.org/doi/full/10.1056/NEJMoa1911206 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/31566937 PubMed]
+==BAT {{#subobject:aoc10a |Regimen=1}}==
+BAT: '''<u>B</u>'''ipolar '''<u>A</u>'''ndrogen '''<u>T</u>'''herapy
-=Chemotherapy for metastatic castrate-resistant disease=
+<div class="toccolours" style="background-color:#eeeeee">
-==Cabazitaxel & Prednisolone {{#subobject:23aug19 |Regimen=1}}==
+===Regimen {{#subobject:#e085c7 |Variant=1}}===
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
-===Example orders===
-*[[Example orders for Cabazitaxel (Jevtana) in prostate cancer]]
-===Regimen {{#subobject:fa5jfa |Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 ! style="width: 20%" |Study
-! style="width: 20%" |Years of enrollment
+! style="width: 20%" |Dates of enrollment
 ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 ! style="width: 20%" |Comparator
 ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1016/s0140-6736(21)00237-3 Hofman et al. 2021 (TheraP)]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8274807/ Denmeade et al. 2021 (TRANSFORMER)]
-|2018-2019
+|2015-2018
-| style="background-color:#1a9851" |Randomized Phase II (C)
+| style="background-color:#1a9851" |Randomized Phase 2 (E-esc)
-|[<sup>177</sup>Lu]Lu-PSMA-617
+|[[Prostate_cancer#Enzalutamide_monotherapy|Enzalutamide]]
-| style="background-color:#d73027" |Inferior PSA response
+| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS<sup>1</sup><br>Median PFS: 5.7 vs 5.7 mo
 |-
 |}
-====Chemotherapy====
+''<sup>1</sup>Study not powered for equivalency. Secondary endpoint of PFS2 after crossover was superior in BAT to enzalutamide arm.''
+<div class="toccolours" style="background-color:#fdcdac">
-*[[Cabazitaxel (Jevtana)]] 20 mg/m<sup>2</sup> IV once on day 1
+====Eligibility criteria====
+*Castrate-resistant, metastatic, asymptomatic
+====Prior treatment criteria====
+*Abiraterone, with progression
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Endocrine therapy====
+*ADT: All patients maintained on continuous testosterone suppression via surgical castration or [[:Category:GnRH_agonists|GnRH agonist]] or [[:Category:GnRH antagonists|GnRH antagonist]]
-*[[Prednisolone (Millipred)]] 10 mg PO once per day
+*Bipolar Androgen Therapy (BAT): [[Testosterone cypionate]] 400 mg IM once every 28 days
+*[[Enzalutamide_(Xtandi)|Enzalutamide]]: 160 mg by mouth daily
-'''21-day cycle for up to 10 cycles'''
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
+====Subsequent treatment====
+*At progression, asymptomatic patients were allowed to cross over to alternative therapy
+</div></div>
 ===References===
-# '''TheraP:''' Hofman MS, Emmett L, Sandhu S, Iravani A, Joshua AM, Goh JC, Pattison DA, Tan TH, Kirkwood ID, Ng S, Francis RJ, Gedye C, Rutherford NK, Weickhardt A, Scott AM, Lee ST, Kwan EM, Azad AA, Ramdave S, Redfern AD, Macdonald W, Guminski A, Hsiao E, Chua W, Lin P, Zhang AY, McJannett MM, Stockler MR, Violet JA, Williams SG, Martin AJ, Davis ID; TheraP Trial Investigators and the Australian and New Zealand Urogenital and Prostate Cancer Trials Group. [177Lu]Lu-PSMA-617 versus cabazitaxel in patients with metastatic castration-resistant prostate cancer (TheraP): a randomised, open-label, phase 2 trial. Lancet. 2021 Feb 11:S0140-6736(21)00237-3. Epub ahead of print. [https://doi.org/10.1016/s0140-6736(21)00237-3 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33581798/ PubMed] NCT03392428
+# '''TRANSFORMER:''' Denmeade SR, Wang H, Agarwal N, Smith D, Schweizer MT, Stein MN, Assikis V, Twardowski P, Flaig T, Szmulewitz R, Holzbeierlein J, Hauke R, Sonpavde G, Garcia J, Hussain A, Sartor O, Mao S, Cao H, Fu W, Wang T, Abdallah R, Lim SJ, Bolejack V, Paller C, Carducci M, Markowski MC, Eisenberger MA, Antonarakis ES; TRANSFORMER investigators. TRANSFORMER: A Randomized Phase II Study Comparing Bipolar Androgen Therapy Versus Enzalutamide in Asymptomatic Men With Castration-Resistant Prostate Cancer. J Clin Oncol. 2021 Apr 20;39(12):1371-1382. Epub 2021 Feb 22. [https://doi.org/10.1200/jco.20.02759 link to original article] [https://ascopubs.org/doi/suppl/10.1200/JCO.20.02759 link to protocol] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8274807/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33617303/ PubMed] [https://clinicaltrials.gov/study/NCT02286921 NCT02286921]
+==Bicalutamide monotherapy {{#subobject:abb40a |Regimen=1}}==
-==Cabazitaxel & Prednisone {{#subobject:23 |Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
-{| class="wikitable" style="float:right; margin-left: 5px;"
+===Regimen {{#subobject:cf9def|Variant=1}}===
-|-
-|[[#top|back to top]]
-|}
-===Example orders===
-*[[Example orders for Cabazitaxel (Jevtana) in prostate cancer]]
-===Regimen variant #1, 20/10, indefinite {{#subobject:fa59fa |Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 ! style="width: 20%" |Study
-! style="width: 20%" |Years of enrollment
+! style="width: 20%" |Dates of enrollment
 ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 ! style="width: 20%" |Comparator
 ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-| rowspan="2" |[https://doi.org/10.1200/JCO.2016.72.1068 Oudard et al. 2017 (FIRSTANA)]
+|[https://doi.org/10.1016/S1470-2045(15)00518-5 Shore et al. 2016 (TERRAIN)]
-| rowspan="2" |2011-2013
+|2011-2013
-| rowspan="2" style="background-color:#1a9851" |Phase III (E-switch-ic)
+| style="background-color:#1a9851" |Randomized Phase 2 (C)
-|[[#Cabazitaxel_.26_Prednisone_2|Cabazitaxel & Prednisone]]; 25/10
+|[[#Enzalutamide_monotherapy|Enzalutamide]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+| style="background-color:#d73027" |Inferior PFS
 |-
-|[[#Docetaxel_.26_Prednisone|Docetaxel & Prednisone]]
+|[https://doi.org/10.1200/jco.2015.64.9285 Penson et al. 2016 (STRIVE)]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+|2012-2014
-|-
+| style="background-color:#1a9851" |Randomized Phase 2 (C)
-|[https://doi.org/10.1200/JCO.2016.72.1076 Eisenberger et al. 2017 (PROSELICA)]
+|[[#Enzalutamide_monotherapy|Enzalutamide]]
-|2011-2013
+| style="background-color:#d73027" |Inferior PFS
-| style="background-color:#1a9851" |Phase III (E-RT-de-esc)
-|[[#Cabazitaxel_.26_Prednisone_2|Cabazitaxel & Prednisone]]; 25/10
-| style="background-color:#eeee01" |Non-inferior OS
 |-
 |}
-====Chemotherapy====
+''Note: Patients enrollend in STRIVE continued ADT while on study; details not provided.''
+<div class="toccolours" style="background-color:#fdcdac">
+====Prior treatment criteria====
+*No prior chemotherapy, abiraterone, or ketoconazole
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
+====Endocrine therapy====
+*[[Bicalutamide (Casodex)]] 50 mg PO once per day
+'''Continued indefinitely'''
+</div></div>
+===References===
+#'''TERRAIN:''' Shore ND, Chowdhury S, Villers A, Klotz L, Siemens DR, Phung D, van Os S, Hasabou N, Wang F, Bhattacharya S, Heidenreich A. Efficacy and safety of enzalutamide versus bicalutamide for patients with metastatic prostate cancer (TERRAIN): a randomised, double-blind, phase 2 study. Lancet Oncol. 2016 Feb;17(2):153-163. Epub 2016 Jan 14. [https://doi.org/10.1016/S1470-2045(15)00518-5 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26774508/ PubMed] [https://clinicaltrials.gov/study/NCT01288911 NCT01288911]
+<!-- Presented in part at the American Urological Association 2015 Annual Meeting, New Orleans, LA, May 15-19, 2015. -->
+#'''STRIVE:''' 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. [https://doi.org/10.1200/jco.2015.64.9285 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/26811535/ PubMed] [https://clinicaltrials.gov/study/NCT01664923 NCT01664923]
-*[[Cabazitaxel (Jevtana)]] 20 mg/m<sup>2</sup> IV once on day 1
+==Enzalutamide monotherapy {{#subobject:18 |Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
-====Endocrine therapy====
+===Regimen variant #1, 160 mg/day {{#subobject:18 |Variant=1}}===
-*[[Prednisone (Sterapred)]] 10 mg PO once per day
-'''21-day cycles'''
-===Regimen variant #2, 25/10 x 10 {{#subobject:23 |Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 ! style="width: 20%" |Study
-! style="width: 20%" |Years of enrollment
+! style="width: 20%" |Dates of enrollment
 ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 ! style="width: 20%" |Comparator
 ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-![[Overall response rate|'''ORR''', PSA RR]]
-!Comparator [[Overall response rate|'''ORR''', PSA RR]]
-!Pt Population
 |-
-|[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2810%2961389-X/fulltext de Bono et al. 2010 (TROPIC)]
+|[https://doi.org/10.1056/NEJMoa1207506 Scher et al. 2012 (AFFIRM)]
-|2007-2008
+<!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
-| style="background-color:#1a9851" |Phase III (E-RT-switch-ic)
+|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-99-1 <span style="color:white;">ESMO-MCBS (4)</span>]'''
-|[[#Mitoxantrone_.26_Prednisone|Mitoxantrone & Prednisone]]
+|-
-| style="background-color:#1a9850" |Superior OS
+|} -->
-|14% (95% CI 10-19)<br> 39% (95% CI 34-44)<sup>1</sup>
+|2009-09 to 2010-11
-|4% (95% CI 2-7)<br> 18% (95% CI 14-22)<sup>1</sup>
+| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
-|Progressed on docetaxel
+|[[Prostate_cancer_-_null_regimens#Placebo_3|Placebo]]
+| style="background-color:#1a9850" |Superior OS (primary endpoint)<br>Median OS: 18.4 vs 13.6 mo<br>(HR 0.63, 95% CI 0.53-0.75)
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4418931/ Beer et al. 2014 (PREVAIL)]
+<!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
+|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-100-1 <span style="color:white;">ESMO-MCBS (4)</span>]'''
+|-
+|} -->
+|2010-2012
+| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
+|[[Prostate_cancer_-_null_regimens#Placebo_3|Placebo]]
+| style="background-color:#1a9850" |Superior rPFS<sup>1</sup> (co-primary endpoint)<br>Median rPFS: 20 vs 5.4 mo<br>(HR 0.32, 95% CI 0.28-0.37)<br><br>Superior OS<sup>2</sup> (co-primary endpoint)<br>Median OS: 36 vs 31 mo<br>(HR 0.83, 95% CI 0.75-0.93)
+|-
+|[https://doi.org/10.1016/S1470-2045(15)00518-5 Shore et al. 2016 (TERRAIN)]
+|2011-2013
+| style="background-color:#1a9851" |Randomized Phase 2 (E-RT-switch-ic)
+|[[#Bicalutamide_monotherapy_2|Bicalutamide]]
+| style="background-color:#1a9850" |Superior PFS (primary endpoint)<br>Median PFS: 15.7 vs 5.8 mo<br>(HR 0.44, 95% CI 0.34-0.57)
 |-
-|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30605-8/fulltext Beer et al. 2017 (AFFINITY)]
+|[https://doi.org/10.1200/jco.2015.64.9285 Penson et al. 2016 (STRIVE)]
 |2012-2014
-| style="background-color:#1a9851" |Phase III (C)
+| style="background-color:#1a9851" |Randomized Phase 2 (E-switch-ic)
-|Cabazitaxel, Prednisone, Custirsen
+|[[#Bicalutamide_monotherapy_2|Bicalutamide]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+| style="background-color:#1a9850" |Superior PFS (primary endpoint)<br>Median PFS: 19.4 vs 5.7 mo<br>(HR 0.24, 95% CI 0.18-0.32)
-|
-|
-|Progressed on docetaxel
 |-
-|}
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6118405/ Attard et al. 2018 (PLATO)]
-''<sup>1</sup>ORRs in TROPIC were only reported for patients with measurable disease.''
+|2013-NR
-====Chemotherapy====
+| style="background-color:#91cf61" |Non-randomized part of phase 3 RCT
+| style="background-color:#d3d3d3" |
-*[[Cabazitaxel (Jevtana)]] 25 mg/m<sup>2</sup> IV over 60 minutes once on day 1
+| style="background-color:#d3d3d3" |
+|-
-====Endocrine therapy====
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc10414728/ Morris et al. 2023 (Alliance A031201)]
+|2014-01-28 to 2016-08-31
-*[[Prednisone (Sterapred)]] 10 mg PO once per day
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#Abiraterone_.26_Enzalutamide_333|Abiraterone & Enzalutamide]]
-====Supportive medications====
+| style="background-color:#fee08b" |Might have inferior OS (primary endpoint)<br>Median OS: 32.7 vs 34.2 mo<br>(HR 1.12, 95% CI 0.99-1.28)
-*[[:Category:Antihistamines|Antihistamine]] once on day 1, at least 30 minutes prior to [[Cabazitaxel (Jevtana)]]
-*[[:Category:Steroids|Corticosteroid]] ([[Dexamethasone (Decadron)|dexamethasone]] 8 mg or equivalent) once on day 1, at least 30 minutes prior to [[Cabazitaxel (Jevtana)]]
-*[[:Category:Antihistamines|Histamine H2-antagonist]] (except cimetidine) once on day 1, at least 30 minutes prior to [[Cabazitaxel (Jevtana)]]
-'''21-day cycle for up to 10 cycles'''
-===Regimen variant #3, 25/10, indefinite {{#subobject:23sa2b |Variant=1}}===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
-! style="width: 20%" |Study
-! style="width: 20%" |Years of enrollment
-! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
-! style="width: 20%" |Comparator
-! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-| rowspan="2" |[https://doi.org/10.1200/JCO.2016.72.1068 Oudard et al. 2017 (FIRSTANA)]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9123068/ Pu et al. 2022 (9785-CL-0232)]
-| rowspan="2" |2011-2013
+|2014-04-23 to 2015-09-20
-| rowspan="2" style="background-color:#1a9851" |Phase III (E-switch-ic)
+| style="background-color:#1a9851" |Phase 3 (E-esc)
-|[[#Cabazitaxel_.26_Prednisone_2|Cabazitaxel & Prednisone]]; 20/10
+|[[Prostate_cancer_-_null_regimens#Placebo_3|Placebo]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+| style="background-color:#1a9850" |Superior OS (secondary endpoint)<br>Median OS: NYR vs NYR<br>(HR 0.33, 95% CI 0.16-0.67)<br><br>Superior time to PSA progression (primary endpoint)<br>Median time to PSA progression: 8.31 vs 2.86 mo<br>(HR 0.38, 95% CI 0.27-0.52)
 |-
-|[[#Docetaxel_.26_Prednisone|Docetaxel & Prednisone]]
+|[https://doi.org/10.1056/NEJMoa1911206 de Wit et al. 2019 (CARD)]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+|2015-2018
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#Cabazitaxel_.26_Prednisone|Cabazitaxel & Prednisone]]
+| style="background-color:#d73027" |Inferior PFSi/OS
 |-
-|[https://doi.org/10.1200/JCO.2016.72.1076 Eisenberger et al. 2017 (PROSELICA)]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8274807/ Denmeade et al. 2021 (TRANSFORMER)]
-|2011-2013
+|2015-2018
-| style="background-color:#1a9851" |Phase III (C)
+| style="background-color:#1a9851" |Randomized Phase 2 (C)
-|[[#Cabazitaxel_.26_Prednisone_2|Cabazitaxel & Prednisone]]; 20/10
+|[[Prostate_cancer#BAT|Bipolar androgen therapy]]
-| style="background-color:#eeee01" |Non-inferior OS
+| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9406237/ Powles et al. 2022 (IMbassador250)]
+|2017-06 to 2018-05
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#Enzalutamide_.26_Atezolizumab_999|Enzalutamide & Atezolizumab]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+|-
+|[https://doi.org/10.1200/jco.23.00233 Antonarakis et al. 2023 (KEYLYNK-010)]
+|2019-05-30 to 2021-07-16
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#Olaparib_.26_Pembrolizumab_999|Olaparib & Pembrolizumab]]
+| style="background-color:#ffffbf" |Did not meet co-primary endpoints of rPFS/OS
 |-
 |}
-====Chemotherapy====
+''<sup>1</sup>Reported efficacy for rPFS in PREVAIL is based on the 2016 update.''<br>
+''<sup>1</sup>Reported efficacy for OS in PREVAIL is based on the 2020 update.''<br>
-*[[Cabazitaxel (Jevtana)]] 25 mg/m<sup>2</sup> IV over 60 minutes once on day 1
+''Note: Patients in STRIVE, PLATO, & TRANSFORMER continued ADT while on study or had a history of bilateral orchiectomy; details not provided.''
+<div class="toccolours" style="background-color:#fdcdac">
+====Prior treatment criteria====
+*AFFIRM: Exposure to docetaxel
+*PREVAIL: Chemotherapy and abiraterone naive
+*STRIVE: Chemotherapy and bicalutamide naive
+*PLATO & 9785-CL-0232: Chemotherapy naive
+*TRANSFORMER & KEYLYNK-010: Exposure to abiraterone
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Endocrine therapy====
+*[[Enzalutamide (Xtandi)]] 160 mg PO once per day
-*[[Prednisone (Sterapred)]] 10 mg PO once per day
+'''Continued indefinitely'''
+</div>
-====Supportive medications====
+<div class="toccolours" style="background-color:#cbd5e7">
+====Subsequent treatment====
-*[[:Category:Antihistamines|Antihistamine]] once on day 1, at least 30 minutes prior to [[Cabazitaxel (Jevtana)]]
+*PLATO, with rising PSA: [[#Abiraterone_monotherapy|Abiraterone]] versus [[Stub#Abiraterone_.26_Enzalutamide|Abiraterone & Enzalutamide]]
-*[[:Category:Steroids|Corticosteroid]] ([[Dexamethasone (Decadron)|dexamethasone]] 8 mg or equivalent) once on day 1, at least 30 minutes prior to [[Cabazitaxel (Jevtana)]]
+*TRANSFORMER, asymptomatic PSA or radiographic progression: crossover to alternative arm. Secondary endpoint of PFS2 was statistically longer with BAT to Enzalutamide compared to Enzalutamide to BAT
-*[[:Category:Antihistamines|Histamine H2-antagonist]] (except cimetidine) once on day 1, at least 30 minutes prior to [[Cabazitaxel (Jevtana)]]
+</div></div><br>
+<div class="toccolours" style="background-color:#ee6b6e">
-'''21-day cycles'''
+===Regimen variant #2, 240 mg/day {{#subobject:7bf35b |Variant=1}}===
+{| class="wikitable" style="color:white; background-color:#f01e2c"
-===References===
+|<small><span style="color:white;">'''Historic variant'''</span></small>
-#'''TROPIC:''' 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. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2810%2961389-X/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/20888992 PubMed] NCT00417079
-#'''FIRSTANA:''' 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. [https://doi.org/10.1200/JCO.2016.72.1068 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28753384 PubMed] NCT01308567
-#'''PROSELICA:''' 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 [https://doi.org/10.1200/JCO.2016.72.1076 link to original article] '''contains verified protocol in supplement''' [https://www.ncbi.nlm.nih.gov/pubmed/28809610 PubMed]
-#'''AFFINITY:''' 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. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30605-8/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/29033099 PubMed] NCT01578655
-==Cabozantinib monotherapy {{#subobject:a20f66 |Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
 |-
-|[[#top|back to top]]
 |}
-===Regimen variant #1, 60 mg/day {{#subobject:0eb568 |Variant=1}}===
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 33%"|Study
-! style="width: 20%" |Study
+!style="width: 33%"|Dates of enrollment
-! style="width: 20%" |Years of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
-! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
-! style="width: 20%" |Comparator
-! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1200/JCO.2015.65.5597 Smith et al. 2016 (COMET-1)]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2948179/ Scher et al. 2010 (S-3100-1-01)]
-|2012-2014
+|2007-2008
-| style="background-color:#1a9851" |Phase III (E-switch-ooc)
+| style="background-color:#91cf61" |Phase 1/2
-|[[#Prednisone_monotherapy|Prednisone]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 |-
 |}
-====Targeted therapy====
+''Note: this is the reported MTD from the phase 1 portion of the trial; however, it is NOT the dose used in subsequent phase 3 studies.''
+<div class="toccolours" style="background-color:#b3e2cd">
-*[[Cabozantinib (Cometriq)]] 60 mg PO once per day
+====Endocrine therapy====
+*[[Enzalutamide (Xtandi)]] 240 mg PO once per day
-===Regimen variant #2, 100 mg/day {{#subobject:2efaa6 |Variant=1}}===
-{| class="wikitable" style="width: 50%; text-align:center;"
-! style="width: 25%" |Study
-! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-|-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4110249/ Smith et al. 2012 (XL184-203)]
-| style="background-color:#91cf61" |Phase II
-|-
-|}
-====Targeted therapy====
-*[[Cabozantinib (Cometriq)]] 100 mg PO once per day
 '''Continued indefinitely'''
+</div></div>
 ===References===
+#'''S-3100-1-01:''' Scher HI, Beer TM, Higano CS, Anand A, Taplin ME, Efstathiou E, Rathkopf D, Shelkey J, Yu EY, Alumkal J, Hung D, Hirmand M, Seely L, Morris MJ, Danila DC, Humm J, Larson S, Fleisher M, Sawyers CL; Prostate Cancer Foundation/Department of Defense Prostate Cancer Clinical Trials Consortium. Antitumour activity of MDV3100 in castration-resistant prostate cancer: a phase 1-2 study. Lancet. 2010 Apr 24;375(9724):1437-46. Epub 2010 Apr 14. [https://doi.org/10.1016/S0140-6736(10)60172-9 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2948179/ link to PMC article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/20398925/ PubMed] [https://clinicaltrials.gov/study/NCT00510718 NCT00510718]
+#'''AFFIRM:''' 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. [https://doi.org/10.1056/NEJMoa1207506 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22894553/ PubMed] [https://clinicaltrials.gov/study/NCT00974311 NCT00974311]
+<!-- # Beer TM, Armstrong AJ, Sternberg CN, Higano CS, Iversen P, Loriot Y, et al. Enzalutamide in men with chemotherapy-naive metastatic prostate cancer (mCRPC): Results of phase III PREVAIL study. ASCO Meeting Abstracts. 2014 February 5, 2014;32(4_suppl):LBA1. [http://abstracts.asco.org/142/AbstView_142_123836.html link to original article] '''contains dosing details in manuscript''' -->
+#'''PREVAIL:''' 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. [https://doi.org/10.1056/NEJMoa1405095 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4418931/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24881730/ PubMed] [https://clinicaltrials.gov/study/NCT01212991 NCT01212991]
+##'''HRQoL analysis:''' Loriot Y, Miller K, Sternberg CN, Fizazi K, De Bono JS, Chowdhury S, Higano CS, Noonberg S, Holmstrom S, Mansbach H, Perabo FG, Phung D, Ivanescu C, Skaltsa K, Beer TM, Tombal B. Effect of enzalutamide on health-related quality of life, pain, and skeletal-related events in asymptomatic and minimally symptomatic, chemotherapy-naive patients with metastatic castration-resistant prostate cancer (PREVAIL): results from a randomised, phase 3 trial. Lancet Oncol. 2015 May;16(5):509-21. Epub 2015 Apr 14. [https://doi.org/10.1016/s1470-2045(15)70113-0 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25888263/ PubMed]
+##'''Update:''' Beer TM, Armstrong AJ, Rathkopf D, Loriot Y, Sternberg CN, Higano CS, Iversen P, Evans CP, Kim CS, Kimura G, Miller K, Saad F, Bjartell AS, Borre M, Mulders P, Tammela TL, Parli T, Sari S, van Os S, Theeuwes A, Tombal B. Enzalutamide in men with chemotherapy-naïve metastatic castration-resistant prostate cancer: Extended analysis of the phase 3 PREVAIL study. Eur Urol. 2017 Feb;71(2):151-154. Epub 2016 Jul 28. [https://doi.org/10.1016/j.eururo.2016.07.032 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5570461/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27477525/ PubMed]
+##'''HRQoL analysis:''' Devlin N, Herdman M, Pavesi M, Phung D, Naidoo S, Beer TM, Tombal B, Loriot Y, Ivanescu C, Parli T, Balk M, Holmstrom S. Health-related quality of life effects of enzalutamide in patients with metastatic castration-resistant prostate cancer: an in-depth post hoc analysis of EQ-5D data from the PREVAIL trial. Health Qual Life Outcomes. 2017 Jun 23;15(1):130. [https://hqlo.biomedcentral.com/articles/10.1186/s12955-017-0704-y link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5481866/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28645287/ PubMed]
+##'''Update:''' Armstrong AJ, Lin P, Tombal B, Saad F, Higano CS, Joshua AM, Parli T, Rosbrook B, van Os S, Beer TM. Five-year Survival Prediction and Safety Outcomes with Enzalutamide in Men with Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer from the PREVAIL Trial. Eur Urol. 2020 Sep;78(3):347-357. Epub 2020 Jun 9. [https://doi.org/10.1016/j.eururo.2020.04.061 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32527692/ PubMed]
+#'''TERRAIN:''' Shore ND, Chowdhury S, Villers A, Klotz L, Siemens DR, Phung D, van Os S, Hasabou N, Wang F, Bhattacharya S, Heidenreich A. Efficacy and safety of enzalutamide versus bicalutamide for patients with metastatic prostate cancer (TERRAIN): a randomised, double-blind, phase 2 study. Lancet Oncol. 2016 Feb;17(2):153-163. Epub 2016 Jan 14. [https://doi.org/10.1016/S1470-2045(15)00518-5 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26774508/ PubMed] [https://clinicaltrials.gov/study/NCT01288911 NCT01288911]
+<!-- Presented in part at the American Urological Association 2015 Annual Meeting, New Orleans, LA, May 15-19, 2015. -->
+#'''STRIVE:''' 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. [https://doi.org/10.1200/jco.2015.64.9285 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/26811535/ PubMed] [https://clinicaltrials.gov/study/NCT01664923 NCT01664923]
+#'''PLATO:''' Attard G, Borre M, Gurney H, Loriot Y, Andresen-Daniil C, Kalleda R, Pham T, Taplin ME; PLATO collaborators. Abiraterone alone or in combination with enzalutamide in metastatic castration-resistant prostate cancer with rising prostate-specific antigen during enzalutamide treatment. J Clin Oncol. 2018 Sep 1;36(25):2639-2646. Epub 2018 Jul 20. [https://doi.org/10.1200/JCO.2018.77.9827 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6118405/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30028657/ PubMed] [https://clinicaltrials.gov/study/NCT01995513 NCT01995513]
+#'''CARD:''' de Wit R, de Bono J, Sternberg CN, Fizazi K, Tombal B, Wülfing C, Kramer G, Eymard JC, Bamias A, Carles J, Iacovelli R, Melichar B, Sverrisdóttir Á, Theodore C, Feyerabend S, Helissey C, Ozatilgan A, Geffriaud-Ricouard C, Castellano D; CARD Investigators. Cabazitaxel versus Abiraterone or Enzalutamide in Metastatic Prostate Cancer. N Engl J Med. 2019 Dec 26;381(26):2506-2518. Epub 2019 Sep 30. [https://doi.org/10.1056/NEJMoa1911206 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/31566937/ PubMed] [https://clinicaltrials.gov/study/NCT02485691 NCT02485691]
+##'''HRQoL analysis:''' Fizazi K, Kramer G, Eymard JC, Sternberg CN, de Bono J, Castellano D, Tombal B, Wülfing C, Liontos M, Carles J, Iacovelli R, Melichar B, Sverrisdóttir Á, Theodore C, Feyerabend S, Helissey C, Oudard S, Facchini G, Poole EM, Ozatilgan A, Geffriaud-Ricouard C, Bensfia S, de Wit R. Quality of life in patients with metastatic prostate cancer following treatment with cabazitaxel versus abiraterone or enzalutamide (CARD): an analysis of a randomised, multicentre, open-label, phase 4 study. Lancet Oncol. 2020 Nov;21(11):1513-1525. Epub 2020 Sep 11. [https://doi.org/10.1016/s1470-2045(20)30449-6 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32926841/ PubMed]
+# '''TRANSFORMER:''' Denmeade SR, Wang H, Agarwal N, Smith D, Schweizer MT, Stein MN, Assikis V, Twardowski P, Flaig T, Szmulewitz R, Holzbeierlein J, Hauke R, Sonpavde G, Garcia J, Hussain A, Sartor O, Mao S, Cao H, Fu W, Wang T, Abdallah R, Lim SJ, Bolejack V, Paller C, Carducci M, Markowski MC, Eisenberger MA, Antonarakis ES; TRANSFORMER investigators. TRANSFORMER: A Randomized Phase II Study Comparing Bipolar Androgen Therapy Versus Enzalutamide in Asymptomatic Men With Castration-Resistant Prostate Cancer. J Clin Oncol. 2021 Apr 20;39(12):1371-1382. Epub 2021 Feb 22. [https://doi.org/10.1200/jco.20.02759 link to original article] [https://ascopubs.org/doi/suppl/10.1200/JCO.20.02759 link to protocol] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8274807/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33617303/ PubMed] [https://clinicaltrials.gov/study/NCT02286921 NCT02286921]
+#'''IMbassador250:''' Powles T, Yuen KC, Gillessen S, Kadel EE 3rd, Rathkopf D, Matsubara N, Drake CG, Fizazi K, Piulats JM, Wysocki PJ, Buchschacher GL Jr, Alekseev B, Mellado B, Karaszewska B, Doss JF, Rasuo G, Datye A, Mariathasan S, Williams P, Sweeney CJ. Atezolizumab with enzalutamide versus enzalutamide alone in metastatic castration-resistant prostate cancer: a randomized phase 3 trial. Nat Med. 2022 Jan;28(1):144-153. Epub 2022 Jan 10. [https://doi.org/10.1038/s41591-021-01600-6 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9406237/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/35013615/ PubMed] [https://clinicaltrials.gov/study/NCT03016312 NCT03016312]
+#'''9785-CL-0232:''' Pu YS, Ahn H, Han W, Huang SP, Wu HC, Ma L, Yamada S, Suga K, Xie LP. Enzalutamide in Chemotherapy-Naïve Metastatic Castration-Resistant Prostate Cancer: An Asian Multiregional, Randomized Study. Adv Ther. 2022 Jun;39(6):2641-2656. Epub 2022 Apr 10. [https://doi.org/10.1007/s12325-022-02140-2 link to original article] '''contains dosing details in abstract''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9123068/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/35397772/ PubMed] [https://clinicaltrials.gov/study/NCT02294461 NCT02294461]
+#'''KEYLYNK-010:''' Antonarakis ES, Park SH, Goh JC, Shin SJ, Lee JL, Mehra N, McDermott R, Sala-Gonzalez N, Fong PC, Greil R, Retz M, Sade JP, Yanez P, Huang YH, Begbie SD, Gafanov RA, De Santis M, Rosenbaum E, Kolinsky MP, Rey F, Chiu KY, Roubaud G, Kramer G, Sumitomo M, Massari F, Suzuki H, Qiu P, Zhang J, Kim J, Poehlein CH, Yu EY. Pembrolizumab Plus Olaparib for Patients With Previously Treated and Biomarker-Unselected Metastatic Castration-Resistant Prostate Cancer: The Randomized, Open-Label, Phase III KEYLYNK-010 Trial. J Clin Oncol. 2023 Aug 1;41(22):3839-3850. Epub 2023 Jun 8. [https://doi.org/10.1200/jco.23.00233 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/37290035/ PubMed] [https://clinicaltrials.gov/study/NCT03834519 NCT03834519]
+#'''Alliance A031201:''' Morris MJ, Heller G, Hillman DW, Bobek O, Ryan C, Antonarakis ES, Bryce AH, Hahn O, Beltran H, Armstrong AJ, Schwartz L, Lewis LD, Beumer JH, Langevin B, McGary EC, Mehan PT, Goldkorn A, Roth BJ, Xiao H, Watt C, Taplin ME, Halabi S, Small EJ. Randomized Phase III Study of Enzalutamide Compared With Enzalutamide Plus Abiraterone for Metastatic Castration-Resistant Prostate Cancer (Alliance A031201 Trial). J Clin Oncol. 2023 Jun 20;41(18):3352-3362. Epub 2023 Mar 30. [https://doi.org/10.1200/JCO.22.02394 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc10414728/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/36996380/ PubMed] [https://clinicaltrials.gov/study/NCT01949337 NCT01949337]
+#'''CASPAR:''' [https://clinicaltrials.gov/study/NCT04455750 NCT04455750]
+#'''TALAPRO-2:''' [https://clinicaltrials.gov/study/NCT03395197 NCT03395197]
-#'''XL184-203:''' 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. [https://doi.org/10.1200/jco.2012.45.0494 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4110249/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/23169517 PubMed] NCT00940225
+==Hydrocortisone monotherapy {{#subobject:f48fb4 |Regimen=1}}==
-#'''COMET-1:''' 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. [https://doi.org/10.1200/JCO.2015.65.5597 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/27400947 PubMed] NCT01605227
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:da4be9 |Variant=1}}===
-==Carboplatin & Docetaxel {{#subobject:28 |Regimen=1}}==
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-{| class="wikitable" style="float:right; margin-left: 5px;"
+! style="width: 20%" |Study
+! style="width: 20%" |Dates of enrollment
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |Comparator
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1200/JCO.1999.17.8.2506 Kantoff et al. 1999 (CALGB 9182)]
+|1992-1995
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[Stub#Mitoxantrone_.26_Hydrocortisone|Mitoxantrone & Hydrocortisone]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 |-
-|[[#top|back to top]]
+|[https://doi.org/10.1200/JCO.2000.18.7.1440 Small et al. 2000]
-|}
+|1994-1996
+| style="background-color:#1a9851" |Phase 3 (C)
-===Example orders===
+|[[Prostate_cancer_-_historical#Suramin_.26_Hydrocortisone|Suramin & Hydrocortisone]]
+| style="background-color:#d73027" |Inferior TTP
-*[[Example orders for Docetaxel & Carboplatin in prostate cancer]]
-===Regimen {{#subobject:31 |Variant=1}}===
-{| class="wikitable" style="width: 50%; text-align:center;"
-! style="width: 25%" |Study
-! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
-|[https://onlinelibrary.wiley.com/doi/10.1002/cncr.23195/full Ross et al. 2008]
+|[https://doi.org/10.1093/annonc/mdh429 Abratt et al. 2004]
-| style="background-color:#91cf61" |Phase II
+|1997-2001
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[Stub#Vinorelbine_.26_Hydrocortisone|Vinorelbine & Hydrocortisone]]
+| style="background-color:#fee08b" |Might have inferior PFS
 |-
 |}
-''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.''
+<div class="toccolours" style="background-color:#b3e2cd">
-====Chemotherapy====
+====Endocrine therapy====
+*[[Hydrocortisone (Cortef)]] 30 mg PO once per day, taken in the morning
-*[[Carboplatin (Paraplatin)]] AUC 4 (Calvert formula) IV over 60 minutes once on day 1, '''given second'''
+*[[Hydrocortisone (Cortef)]] 10 mg PO once per day, taken in the evening
-*[[Docetaxel (Taxotere)]] 60 mg/m<sup>2</sup> IV over 60 minutes once on day 1, '''given first'''
+'''Continued indefinitely'''
+</div></div>
-====Supportive medications====
-*"Standard dexamethasone premedication was used"
-*Patients continued to receive androgen deprivation therapy
-'''21-day cycles'''
 ===References===
+#'''CALGB 9182:''' Kantoff PW, Halabi S, Conaway M, Picus J, Kirshner J, Hars V, Trump D, Winer EP, Vogelzang NJ. Hydrocortisone with or without mitoxantrone in men with hormone-refractory prostate cancer: results of the Cancer and Leukemia Group B 9182 study. J Clin Oncol. 1999 Aug;17(8):2506-13. [https://doi.org/10.1200/JCO.1999.17.8.2506 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/10561316/ PubMed]
+#Small EJ, Meyer M, Marshall ME, Reyno LM, Meyers FJ, Natale RB, Lenehan PF, Chen L, Slichenmyer WJ, Eisenberger M. Suramin therapy for patients with symptomatic hormone-refractory prostate cancer: results of a randomized phase III trial comparing suramin plus hydrocortisone to placebo plus hydrocortisone. J Clin Oncol. 2000 Apr;18(7):1440-50. [https://doi.org/10.1200/JCO.2000.18.7.1440 link to original article] [https://pubmed.ncbi.nlm.nih.gov/10735891/ PubMed]
+#Abratt RP, Brune D, Dimopoulos MA, Kliment J, Breza J, Selvaggi FP, Beuzeboc P, Demkow T, Oudard S. Randomised phase III study of intravenous vinorelbine plus hormone therapy versus hormone therapy alone in hormone-refractory prostate cancer. Ann Oncol. 2004 Nov;15(11):1613-21. [https://doi.org/10.1093/annonc/mdh429 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15520061/ PubMed]
-#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. [https://onlinelibrary.wiley.com/doi/10.1002/cncr.23195/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18085595 PubMed]
+==Ketoconazole & Hydrocortisone {{#subobject:19 |Regimen=1}}==
-#'''Retrospective:''' 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. [https://onlinelibrary.wiley.com/doi/10.1111/j.1464-410X.2007.07331.x/full link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/18184327 PubMed]
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:19 |Variant=1}}===
-==Carboplatin, Docetaxel, Prednisone {{#subobject:28a1b4 |Regimen=1}}==
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-{| class="wikitable" style="float:right; margin-left: 5px;"
+! style="width: 20%" |Study
-|-
+! style="width: 20%" |Dates of enrollment
-|[[#top|back to top]]
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |Comparator
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1016/S0140-6736(84)92909-X Trachtenberg & Pont 1984]
+|NR
+| style="background-color:#ffffbe" |Pilot
+| style="background-color:#d3d3d3" |
+| style="background-color:#d3d3d3" |
+|-
+|[https://doi.org/10.1200/jco.2004.06.037 Small et al. 2004 (CALGB 9583)]
+|NR
+| style="background-color:#1a9851" |Phase 3 (E-esc)
+|[[#Antiandrogen_withdrawal|Antiandrogen withdrawal]]
+| style="background-color:#1a9850" |Superior PSA response
+|-
 |}
-===Regimen {{#subobject:32 |Variant=1}}===
+<div class="toccolours" style="background-color:#b3e2cd">
-{| class="wikitable" style="width: 50%; text-align:center;"
+====Endocrine therapy====
-! style="width: 25%" |Study
+*[[Ketoconazole (Nizoral)]] 400 mg PO three times per day
-! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
+*[[Hydrocortisone (Cortef)]] 30 mg PO QAM and 10 mg PO QPM
+'''Continued indefinitely'''
+</div></div>
+===References===
+#Trachtenberg J, Pont A. Ketoconazole therapy for advanced prostate cancer. Lancet. 1984 Aug 25;2(8400):433-5. [https://doi.org/10.1016/S0140-6736(84)92909-X link to original article] [https://pubmed.ncbi.nlm.nih.gov/6147504/ PubMed]
+#'''CALGB 9583:''' 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. [https://doi.org/10.1200/jco.2004.06.037 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15020604/ PubMed] [https://clinicaltrials.gov/study/NCT00002760 NCT00002760]
+==Ketoconazole, Hydrocortisone, Dutasteride {{#subobject:20 |Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:20 |Variant=1}}===
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
+!style="width: 33%"|Study
+!style="width: 33%"|Dates of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 |-
-|[http://link.springer.com/article/10.1007%2Fs00345-010-0527-5 Reuter et al. 2010]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3644858/ Taplin et al. 2009]
-| style="background-color:#91cf61" |Phase II
+|2005-2007
+| style="background-color:#91cf61" |Phase 2
 |-
 |}
-''Patients enrolled in the trial had progression of disease on docetaxel chemotherapy and castration-resistant disease.''
+<div class="toccolours" style="background-color:#b3e2cd">
-====Chemotherapy====
-*[[Carboplatin (Paraplatin)]] AUC 5 IV over 30 minutes once on day 1
-*[[Docetaxel (Taxotere)]] 35 mg/m<sup>2</sup> IV over 60 minutes 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.
 ====Endocrine therapy====
+*[[Ketoconazole (Nizoral)]] 400 mg PO three times per day
-*[[Prednisone (Sterapred)]] 5 mg PO twice per day
+*[[Hydrocortisone (Cortef)]] 30 mg PO QAM and 10 mg PO QPM
+*[[Dutasteride (Avodart)]] 0.5 mg PO once per day
-====Supportive medications====
+'''Continued indefinitely'''
+</div></div>
-*"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'''
 ===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. [https://doi.org/10.1158/1078-0432.CCR-09-1722 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3644858/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19887483/ 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. [http://link.springer.com/article/10.1007%2Fs00345-010-0527-5 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/20229232 PubMed]
+==Prednisone monotherapy {{#subobject:22 |Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
-==Carboplatin & Paclitaxel (CP) {{#subobject:30 |Regimen=1}}==
+===Regimen variant #1, 5 mg twice per day {{#subobject:22 |Variant=1}}===
-{| class="wikitable" style="float:right; margin-left: 5px;"
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+! style="width: 20%" |Study
+! style="width: 20%" |Dates of enrollment
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |Comparator
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[[#top|back to top]]
+|[https://doi.org/10.1200/jco.1989.7.5.590 Tannock et al. 1989]
-|}
+|1976-1980
-===Regimen variant #1 {{#subobject:34 |Variant=1}}===
+| style="background-color:#ffffbe" |Retrospective
-{| class="wikitable" style="width: 50%; text-align:center;"
+| style="background-color:#d3d3d3" |
-! style="width: 25%" |Study
+| style="background-color:#d3d3d3" |
-! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
-|[http://link.springer.com/article/10.1007%2Fs00280-012-1896-9 Kentepozidis et al. 2012]
+|[https://doi.org/10.1200/JCO.1996.14.6.1756 Tannock et al. 1996 (CCI-NOV22)]
-| style="background-color:#91cf61" |Phase II
+|1990-1994
-|-
+| style="background-color:#1a9851" |Phase 3 (C)
-|}
+|[[#Mitoxantrone_.26_Prednisone|Mitoxantrone & Prednisone]]
-====Chemotherapy====
+| style="background-color:#d73027" |Inferior palliation
+|-
-*[[Carboplatin (Paraplatin)]] AUC 3 (Calvert formula) IV once per day on days 1 & 15, '''given second'''
+|[https://www.auajournals.org/doi/abs/10.1016/S0022-5347%2805)64163-8 Berry et al. 2002]
-*[[Paclitaxel (Taxol)]] 135 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 & 15, '''given first'''
+|1997-1999
+| style="background-color:#1a9851" |Phase 3 (C)
-====Supportive medications====
+|[[#Mitoxantrone_.26_Prednisone|Mitoxantrone & Prednisone]]
+| style="background-color:#fc8d59" |Seems to have inferior TTTF
-*"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 per day on days 1 & 15, "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 per day on days 1 & 15, "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'''
-===Regimen variant #2 {{#subobject:35 |Variant=1}}===
-{| class="wikitable" style="width: 50%; text-align:center;"
-! style="width: 25%" |Study
-! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
-|[http://www.urologiconcology.org/article/S1078-1439%2810%2900003-7/abstract Jeske et al. 2010]
+|[https://doi.org/10.1200/JCO.2008.20.1228 Sternberg et al. 2009 (SPARC)]
-| style="background-color:#ffffbe" |Retrospective
+|2003-2006
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#Satraplatin_.26_Prednisone_777|Satraplatin & Prednisone]]
+| style="background-color:#d73027" |Inferior PFS
 |-
-|}
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3471149/ de Bono et al. 2011 (COU-AA-301)]
-====Chemotherapy====
+|2008-05 to 2009-07
+| style="background-color:#1a9851" |Phase 3 (C)
-*[[Carboplatin (Paraplatin)]] AUC 4 to 6 IV once on day 1
+|[[#Abiraterone_monotherapy|Abiraterone]]
-*[[Paclitaxel (Taxol)]] 60 to 80 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
+| style="background-color:#d73027" |Inferior OS
+|-
-'''28-day cycles'''
+|[https://doi.org/10.1200/JCO.2012.48.5268 Michaelson et al. 2013 (SUN 1120)]
+|2008-2010
-===References===
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#Sunitinib_.26_Prednisone_999|Sunitinib & Prednisone]]
-#'''Retrospective:''' 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. [http://www.urologiconcology.org/article/S1078-1439%2810%2900003-7/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/20451413 PubMed]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
-#Kentepozidis N, Soultati A, Giassas S, Vardakis N, Kalykaki A, Kotsakis A, Papadimitraki E, Pantazopoulos N, Bozionellou V, Georgoulias V; Hellenic Oncology Research Group. 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. [http://link.springer.com/article/10.1007%2Fs00280-012-1896-9 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22660737 PubMed]
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3683570/ Ryan et al. 2013 (COU-AA-302)]
-==Cyclophosphamide, Prednisone, Diethylstilbestrol {{#subobject:26 |Regimen=1}}==
+|2009-04 to 2010-06
-CPD: '''<u>C</u>'''yclophosphamide, '''<u>P</u>'''rednisone, '''<u>D</u>'''iethylstilbestrol
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#Abiraterone_monotherapy|Abiraterone]]
-{| class="wikitable" style="float:right; margin-left: 5px;"
+| style="background-color:#d73027" |Inferior OS
+|-
+|[https://doi.org/10.1016/S1470-2045(15)70027-6 Saad et al. 2015 (ELM-PC 4)]
+|2010-2012
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#Orteronel_.26_Prednisone_777|Orteronel & Prednisone]]
+| style="background-color:#d73027" |Inferior PFS
 |-
-|[[#top|back to top]]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4879718/ Fizazi et al. 2015 (ELM-PC 5)]
-|}
+|2010-NR
-===Regimen {{#subobject:26 |Variant=1}}===
+| style="background-color:#1a9851" |Phase 3 (C)
-{| class="wikitable" style="width: 75%; text-align:center;"
+|[[#Orteronel_.26_Prednisone_999|Orteronel & Prednisone]]
-! style="width: 33%" |Study
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
-! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]
-! style="width: 33%" |[[Levels_of_Evidence#Efficacy|Efficacy]]
 |-
-|[https://onlinelibrary.wiley.com/doi/10.1002/cncr.11686/abstract Hellerstedt et al. 2003]
+|[https://doi.org/10.1200/JCO.2015.65.5597 Smith et al. 2016 (COMET-1)]
-| style="background-color:#91cf61" |Phase II
+|2012-2014
-|50% or greater decline in PSA: 42%
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#Cabozantinib_monotherapy|Cabozantinib]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 |-
 |}
-====Chemotherapy====
+<div class="toccolours" style="background-color:#b3e2cd">
-*[[Cyclophosphamide (Cytoxan)]] 100 mg PO once per day on days 1 to 20
 ====Endocrine therapy====
+*[[Prednisone (Sterapred)]] 5 mg PO twice per day
-*[[Prednisone (Sterapred)]] 10 mg PO once per day
+'''Continued indefinitely'''
-*[[Diethylstilbestrol (DES)]] 1 mg PO once per day
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
-====Supportive medications====
+===Regimen variant #2, 5 mg QID {{#subobject:5055a7 |Variant=1}}===
-*[[Warfarin (Coumadin)]] 1 mg PO once per day to decrease risk of DVT
-'''30-day cycles'''
-===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. [https://onlinelibrary.wiley.com/doi/10.1002/cncr.11686/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/14534875 PubMed]
-==Docetaxel & Estramustine {{#subobject:27a1bc |Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
-===Regimen {{#subobject:51bc1c |Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 ! style="width: 20%" |Study
-! style="width: 20%" |Years of enrollment
+! style="width: 20%" |Dates of enrollment
 ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 ! style="width: 20%" |Comparator
 ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.nejm.org/doi/full/10.1056/NEJMoa041318 Petrylak et al. 2004 (SWOG S9916)]
+|[https://doi.org/10.1200/JCO.2001.19.1.62 Fosså et al. 2001 (EORTC 30903)]
-|1999-2003
+|1992-1998
-| style="background-color:#1a9851" |Phase III (E-switch-ic)
+| style="background-color:#1a9851" |Phase 3 (C)
-|[[#Mitoxantrone_.26_Prednisone|Mitoxantrone & Prednisone]]
+|[[#Flutamide_monotherapy|Flutamide]]
-| style="background-color:#91cf60" |Seems to have superior OS
+| style="background-color:#ffffbf" |Did not meet co-primary endpoints of TTP/OS
 |-
 |}
-====Chemotherapy====
+<div class="toccolours" style="background-color:#b3e2cd">
-*[[Docetaxel (Taxotere)]]
 ====Endocrine therapy====
+*[[Prednisone (Sterapred)]] 5 mg PO four times per day
-*[[Estramustine (Emcyt)]]
+'''Continued indefinitely'''
+</div></div>
 ===References===
+#Tannock I, Gospodarowicz M, Meakin W, Panzarella T, Stewart L, Rider W. Treatment of metastatic prostatic cancer with low-dose prednisone: evaluation of pain and quality of life as pragmatic indices of response. J Clin Oncol. 1989 May;7(5):590-7. [https://doi.org/10.1200/jco.1989.7.5.590 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2709088/ PubMed]
+#'''CCI-NOV22:''' 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. [https://doi.org/10.1200/JCO.1996.14.6.1756 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/8656243/ 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. [https://doi.org/10.1200/JCO.1999.17.6.1654 link to original article] [https://pubmed.ncbi.nlm.nih.gov/10561201/ PubMed]
+#'''EORTC 30903:''' 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. [https://doi.org/10.1200/JCO.2001.19.1.62 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/11134196/ PubMed]
+#Berry W, Dakhil S, Modiano M, Gregurich M, Asmar L. Phase III study of mitoxantrone plus low dose prednisone versus low dose prednisone alone in patients with asymptomatic hormone refractory prostate cancer. J Urol. 2002 Dec;168(6):2439-43. [https://www.auajournals.org/doi/abs/10.1016/S0022-5347%2805)64163-8 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/12441935/ PubMed]
+#'''SPARC:''' Sternberg CN, Petrylak DP, Sartor O, Witjes JA, Demkow T, Ferrero JM, Eymard JC, Falcon S, Calabrò F, James N, Bodrogi I, Harper P, Wirth M, Berry W, Petrone ME, McKearn TJ, Noursalehi M, George M, Rozencweig M. Multinational, double-blind, phase III study of prednisone and either satraplatin or placebo in patients with castrate-refractory prostate cancer progressing after prior chemotherapy: the SPARC trial. J Clin Oncol. 2009 Nov 10;27(32):5431-8. Epub 2009 Oct 5. [https://doi.org/10.1200/JCO.2008.20.1228 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/19805692/ PubMed] [https://clinicaltrials.gov/study/NCT00069745 NCT00069745]
+#'''COU-AA-301:''' 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. [https://doi.org/10.1056/NEJMoa1014618 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3471149/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21612468/ PubMed] [https://clinicaltrials.gov/study/NCT00638690 NCT00638690]
+##'''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. [https://doi.org/10.1016/S1470-2045(12)70379-0 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22995653/ 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. [https://doi.org/10.1016/S1470-2045(12)70473-4 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23142059/ PubMed]
+#'''COU-AA-302:''' 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. [https://doi.org/10.1056/NEJMoa1209096 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3683570/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23228172/ PubMed] [https://clinicaltrials.gov/study/NCT00887198 NCT00887198]
+##'''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. [https://doi.org/10.1016/S1470-2045(14)71205-7 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25601341/ PubMed]
+#'''SUN 1120:''' Michaelson MD, Oudard S, Ou YC, Sengeløv L, Saad F, Houede N, Ostler P, Stenzl A, Daugaard G, Jones R, Laestadius F, Ullèn A, Bahl A, Castellano D, Gschwend J, Maurina T, Chow Maneval E, Wang SL, Lechuga MJ, Paolini J, Chen I. Randomized, placebo-controlled, phase III trial of sunitinib plus prednisone versus prednisone alone in progressive, metastatic, castration-resistant prostate cancer. J Clin Oncol. 2014 Jan 10;32(2):76-82. Epub 2013 Dec 9. [https://doi.org/10.1200/JCO.2012.48.5268 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/24323035/ PubMed] [https://clinicaltrials.gov/study/NCT00676650 NCT00676650]
+#'''ELM-PC 5:''' Fizazi K, Jones R, Oudard S, Efstathiou E, Saad F, de Wit R, De Bono J, Cruz FM, Fountzilas G, Ulys A, Carcano F, Agarwal N, Agus D, Bellmunt J, Petrylak DP, Lee SY, Webb IJ, Tejura B, Borgstein N, Dreicer R. Phase III, randomized, double-blind, multicenter trial comparing orteronel (TAK-700) plus prednisone with placebo plus prednisone in patients with metastatic castration-resistant prostate cancer that has progressed during or after docetaxel-based therapy: ELM-PC 5. J Clin Oncol. 2015 Mar 1;33(7):723-31. Epub 2015 Jan 26. [https://doi.org/10.1200/JCO.2014.56.5119 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4879718/ link to PMC article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/25624429/ PubMed] [https://clinicaltrials.gov/study/NCT01193257 NCT01193257]
+#'''ELM-PC 4:''' Saad F, Fizazi K, Jinga V, Efstathiou E, Fong PC, Hart LL, Jones R, McDermott R, Wirth M, Suzuki K, MacLean DB, Wang L, Akaza H, Nelson J, Scher HI, Dreicer R, Webb IJ, de Wit R; ELM-PC 4 investigators. Orteronel plus prednisone in patients with chemotherapy-naive metastatic castration-resistant prostate cancer (ELM-PC 4): a double-blind, multicentre, phase 3, randomised, placebo-controlled trial. Lancet Oncol. 2015 Mar;16(3):338-48. Epub 2015 Feb 18. [https://doi.org/10.1016/S1470-2045(15)70027-6 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/25701170/ PubMed] [https://clinicaltrials.gov/study/NCT01193244 NCT01193244]
+#'''COMET-1:''' 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. [https://doi.org/10.1200/JCO.2015.65.5597 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/27400947/ PubMed] [https://clinicaltrials.gov/study/NCT01605227 NCT01605227]
-#'''SWOG S9916:''' 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. [https://www.nejm.org/doi/full/10.1056/NEJMoa041318 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15470214 PubMed]
+=Chemotherapy for metastatic castrate-sensitive disease=
+==Cabazitaxel & Prednisone {{#subobject:23jbuz |Regimen=1}}==
-==Docetaxel & Prednisone {{#subobject:27 |Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
 ===Example orders===
+*[[Example orders for Cabazitaxel (Jevtana) in prostate cancer]]
-*[[Example orders for Docetaxel (Taxotere) in prostate cancer]]
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:2hcb1b |Variant=1}}===
-===Regimen variant #1, 30 mg/m<sup>2</sup> weekly {{#subobject:29 |Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
 ! style="width: 20%" |Study
-! style="width: 20%" |Years of enrollment
+! style="width: 20%" |Dates of enrollment
 ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 ! style="width: 20%" |Comparator
 ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-| rowspan="2" |[https://www.nejm.org/doi/full/10.1056/NEJMoa040720 Tannock et al. 2004 (TAX 327)]
+|[https://doi.org/10.1056/NEJMoa1911206 de Wit et al. 2019 (CARD)]
-| rowspan="2" |2000-2002
+<!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
-| rowspan="2" style="background-color:#1a9851" |Phase III (E-RT-switch-ic)
+|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-139-1 <span style="color:white;">ESMO-MCBS (3)</span>]'''
-|1. [[#Docetaxel_.26_Prednisone|Docetaxel & Prednisone]]; q3wk
-| style="background-color:#d3d3d3" |Not reported
 |-
-|2. [[#Mitoxantrone_.26_Prednisone|Mitoxantrone & Prednisone]]
+|} -->
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+|2015-2018
+| style="background-color:#1a9851" |Phase 3 (E-RT-switch-ooc)
+|1a. [[#Abiraterone_monotherapy|Abiraterone]]<br>1b. [[#Enzalutamide_monotherapy|Enzalutamide]]
+| style="background-color:#1a9850" |Superior PFSi (primary endpoint)<br>Median PFSi: 8 vs 3.7 mo<br>(HR 0.54, 95% CI 0.40-0.73)<br><br>Superior OS (secondary endpoint)<br>Median OS: 13.6 vs 11 mo<br>(HR 0.64, 95% CI 0.46-0.89)
 |-
 |}
+''Note: patients in CARD had already received and progressed on the alternate androgen signaling targeted inhibitor.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
+*[[Cabazitaxel (Jevtana)]] 25 mg/m<sup>2</sup> IV over 60 minutes once on day 1
-*[[Docetaxel (Taxotere)]] 30 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1, 8, 15, 22, 29
 ====Endocrine therapy====
+*[[Prednisone (Sterapred)]] 10 mg PO once per day on days 1 to 21
+====Supportive therapy====
+*[[:Category:Antihistamines|Antihistamine]] once on day 1, at least 30 minutes prior to cabazitaxel
+*[[:Category:Steroids|Corticosteroid]] ([[Dexamethasone (Decadron)|dexamethasone]] 8 mg or equivalent) once on day 1, at least 30 minutes prior to cabazitaxel
+*[[:Category:Antihistamines|Histamine H2-antagonist]] (except cimetidine) once on day 1, at least 30 minutes prior to cabazitaxel
+'''21-day cycles'''
+</div></div>
+===References===
+#'''CARD:''' de Wit R, de Bono J, Sternberg CN, Fizazi K, Tombal B, Wülfing C, Kramer G, Eymard JC, Bamias A, Carles J, Iacovelli R, Melichar B, Sverrisdóttir Á, Theodore C, Feyerabend S, Helissey C, Ozatilgan A, Geffriaud-Ricouard C, Castellano D; CARD Investigators. Cabazitaxel versus Abiraterone or Enzalutamide in Metastatic Prostate Cancer. N Engl J Med. 2019 Dec 26;381(26):2506-2518. Epub 2019 Sep 30. [https://doi.org/10.1056/NEJMoa1911206 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/31566937/ PubMed] [https://clinicaltrials.gov/study/NCT02485691 NCT02485691]
+##'''HRQoL analysis:''' Fizazi K, Kramer G, Eymard JC, Sternberg CN, de Bono J, Castellano D, Tombal B, Wülfing C, Liontos M, Carles J, Iacovelli R, Melichar B, Sverrisdóttir Á, Theodore C, Feyerabend S, Helissey C, Oudard S, Facchini G, Poole EM, Ozatilgan A, Geffriaud-Ricouard C, Bensfia S, de Wit R. Quality of life in patients with metastatic prostate cancer following treatment with cabazitaxel versus abiraterone or enzalutamide (CARD): an analysis of a randomised, multicentre, open-label, phase 4 study. Lancet Oncol. 2020 Nov;21(11):1513-1525. Epub 2020 Sep 11. [https://doi.org/10.1016/s1470-2045(20)30449-6 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32926841/ PubMed]
-*[[Prednisone (Sterapred)]] 5 mg PO twice per day
+=Chemotherapy for metastatic castrate-resistant disease=
+==Cabazitaxel & Prednisolone {{#subobject:23aug19 |Regimen=1}}==
-====Supportive medications====
+===Example orders===
+*[[Example orders for Cabazitaxel (Jevtana) in prostate cancer]]
-*[[Dexamethasone (Decadron)]] 8 mg (route not specified) once 1 hour before [[Docetaxel (Taxotere)]]
+<div class="toccolours" style="background-color:#eeeeee">
-*Antiemetics "according to local practice"
+===Regimen variant #1, 16/10 {{#subobject:fa5uhc |Variant=1}}===
-'''42-day cycle for up to 5 cycles'''
-===Regimen variant #2, 75 mg/m<sup>2</sup> q3wk x 10 {{#subobject:27 |Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
-! style="width: 20%" |Study
+!style="width: 17%"|Study
-! style="width: 20%" |Years of enrollment
+!style="width: 15%"|Dates of enrollment
-! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
-! style="width: 20%" |Comparator
+!style="width: 17%"|Comparator
-! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-![[Overall response rate|'''ORR''', PSA RR]]
+!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
-!Comparator [[Overall response rate|'''ORR''', PSA RR]]
-!Pt Population
 |-
-| rowspan="2" |[https://www.nejm.org/doi/full/10.1056/NEJMoa040720 Tannock et al. 2004 (TAX 327)]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10603579/ Oudard et al. 2023 (CABASTY)]
-| rowspan="2" |2000-2002
+|NR
-| rowspan="2" style="background-color:#1a9851" |Phase III (E-RT-switch-ic)
+| style="background-color:#1a9851" |Phase 3 (E-de-esc)
-|1. [[#Docetaxel_.26_Prednisone|Docetaxel & Prednisone]]; weekly
+|[[#Cabazitaxel_.26_Prednisolone|Cabazitaxel & Prednisone]]; q3wk
-| style="background-color:#d3d3d3" |Not reported
-| rowspan="2" |pts w/ measurable disease:'''12%''' (95% CI, 7-19), '''45%''' (95% CI, 40-51)
-|pts w/ measurable disease:'''8%''' (95% CI, 4-14), '''48%''' (95% CI, 42-54)
-|Chemo-naive
-|-
-|2. [[#Mitoxantrone_.26_Prednisone|Mitoxantrone & Prednisone]]
-| style="background-color:#1a9850" |Superior OS
-|pts w/ measurable disease:'''7%''' (95% CI, 3-12), '''32%''' (95% CI, 26-37)
-|Chemo-naive
-|-
-|[https://doi.org/10.1200/JCO.2006.06.8197 Beer et al. 2011 (ASCENT)]
-|2002-2004
-| style="background-color:#1a9851" |Phase III (C)
-|Calcitriol, Docetaxel, Prednisone
-| style="background-color:#1a9850" |Superior OS<sup>1</sup>
-|
-|
-|
-|-
-|[https://www.ejcancer.com/article/S0959-8049(12)00428-5/fulltext Meulenbeld et al. 2012 (NePro)]
-|2004-2010
-| style="background-color:#1a9851" |Phase II/III (C)
-|Docetaxel, Prednisone, Risedronate
-| style="background-color:#ffffbf" |Did not meet primary endpoint of TTP
-|
-|
 |
+| style="background-color:#1a9850" |Superior grade 3 or higher neutropenia and/or neutropenic complications (primary endpoint)
 |-
 |}
-''<sup>1</sup>Reported efficacy for ASCENT is based on the 2011 update.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
+*[[Cabazitaxel (Jevtana)]] 16 mg/m<sup>2</sup> IV over 60 minutes once on day 1
-*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV over 60 minutes once on day 1
 ====Endocrine therapy====
+*[[Prednisolone (Millipred)]] 10 mg PO once per day
-*[[Prednisone (Sterapred)]] 5 mg PO twice per day
+====Supportive therapy====
+*[[:Category:Granulocyte_colony-stimulating_factors|G-CSF]] (dose not specified) once per day on days 3 to 7
-====Supportive medications====
+'''14-day cycle for up to 20 cycles'''
+</div></div><br>
-*[[Dexamethasone (Decadron)]] 8 mg PO given three times; 12 hours, 3 hours, and 1 hour before [[Docetaxel (Taxotere)]]
+<div class="toccolours" style="background-color:#eeeeee">
-*[[:Category:Emesis_prevention|Antiemetics]] "according to local practice"
+===Regimen variant #2, 20/10 {{#subobject:fa5jfa |Variant=1}}===
-'''21-day cycle for up to 10 cycles'''
-===Regimen variant #3, 75 mg/m<sup>2</sup> q3wk x 12 {{#subobject:27a1bc |Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 ! style="width: 20%" |Study
-! style="width: 20%" |Years of enrollment
+! style="width: 20%" |Dates of enrollment
 ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 ! style="width: 20%" |Comparator
 ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4277263/ Quinn et al. 2013 (SWOG S0421)]
+|[https://doi.org/10.1016/s0140-6736(21)00237-3 Hofman et al. 2021 (TheraP)]
-|2006-2010
+|2018-2019
-| style="background-color:#1a9851" |Phase III (C)
+| style="background-color:#1a9851" |Randomized Phase 2 (C)
-|Atrasentan, Docetaxel, Prednisone
+|[[#Lutetium_Lu_177_vipivotide_tetraxetan_monotherapy|Lu-177 Lu-PSMA-617]]
-| style="background-color:#ffffbf" |Did not meet primary endpoints of PFS/OS
+| style="background-color:#d73027" |Inferior PSA response
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
+*[[Cabazitaxel (Jevtana)]] 20 mg/m<sup>2</sup> IV once on day 1
-*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV over 60 minutes once on day 1
+====Endocrine therapy====
+*[[Prednisolone (Millipred)]] 10 mg PO once per day
+'''21-day cycle for up to 10 cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #3, 25/10 {{#subobject:fa5hwa |Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 17%"|Study
+!style="width: 15%"|Dates of enrollment
+!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 17%"|Comparator
+!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10603579/ Oudard et al. 2023 (CABASTY)]
+|NR
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#Cabazitaxel_.26_Prednisolone|Cabazitaxel & Prednisone]]; q2wk
+|
+| style="background-color:#d73027" |Inferior grade 3 or higher neutropenia and/or neutropenic complications
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Cabazitaxel (Jevtana)]] 25 mg/m<sup>2</sup> IV over 60 minutes once on day 1
 ====Endocrine therapy====
+*[[Prednisolone (Millipred)]] 10 mg PO once per day
+====Supportive therapy====
+*[[:Category:Granulocyte_colony-stimulating_factors|G-CSF]] (dose not specified) once per day on days 3 to 7
+'''21-day cycle for up to 10 cycles'''
+</div></div>
+===References===
+# '''TheraP:''' Hofman MS, Emmett L, Sandhu S, Iravani A, Joshua AM, Goh JC, Pattison DA, Tan TH, Kirkwood ID, Ng S, Francis RJ, Gedye C, Rutherford NK, Weickhardt A, Scott AM, Lee ST, Kwan EM, Azad AA, Ramdave S, Redfern AD, Macdonald W, Guminski A, Hsiao E, Chua W, Lin P, Zhang AY, McJannett MM, Stockler MR, Violet JA, Williams SG, Martin AJ, Davis ID; TheraP Trial Investigators and the Australian and New Zealand Urogenital and Prostate Cancer Trials Group. [177Lu]Lu-PSMA-617 versus cabazitaxel in patients with metastatic castration-resistant prostate cancer (TheraP): a randomised, open-label, phase 2 trial. Lancet. 2021 Feb 27;397(10276):797-804. Epub 2021 Feb 11. [https://doi.org/10.1016/s0140-6736(21)00237-3 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/33581798/ PubMed] [https://clinicaltrials.gov/study/NCT03392428 NCT03392428]
+##'''Update:''' Hofman MS, Emmett L, Sandhu S, Iravani A, Buteau JP, Joshua AM, Goh JC, Pattison DA, Tan TH, Kirkwood ID, Ng S, Francis RJ, Gedye C, Rutherford NK, Weickhardt A, Scott AM, Lee ST, Kwan EM, Azad AA, Ramdave S, Redfern AD, Macdonald W, Guminski A, Hsiao E, Chua W, Lin P, Zhang AY, Stockler MR, Williams SG, Martin AJ, Davis ID; TheraP Trial Investigators and the Australian and New Zealand Urogenital and Prostate Cancer Trials Group. Overall survival with [177Lu]Lu-PSMA-617 versus cabazitaxel in metastatic castration-resistant prostate cancer (TheraP): secondary outcomes of a randomised, open-label, phase 2 trial. Lancet Oncol. 2024 Jan;25(1):99-107. Epub 2023 Nov 30. [https://doi.org/10.1016/s1470-2045(23)00529-6 link to original article] [https://pubmed.ncbi.nlm.nih.gov/38043558/ PubMed]
+#'''CABASTY:''' Oudard S, Ratta R, Voog E, Barthelemy P, Thiery-Vuillemin A, Bennamoun M, Hasbini A, Aldabbagh K, Saldana C, Sevin E, Amela E, Von Amsberg G, Houede N, Besson D, Feyerabend S, Boegemann M, Pfister D, Schostak M, Huillard O, Di Fiore F, Quivy A, Lange C, Phan L, Belhouari H, Tran Y, Kotti S, Helissey C. Biweekly vs Triweekly Cabazitaxel in Older Patients With Metastatic Castration-Resistant Prostate Cancer: The CABASTY Phase 3 Randomized Clinical Trial. JAMA Oncol. 2023 Dec 1;9(12):1629-1638. Epub 2023 Oct 26. [https://doi.org/10.1001/jamaoncol.2023.4255 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10603579/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/37883073/ PubMed] [https://clinicaltrials.gov/study/NCT02961257 NCT02961257]
-*[[Prednisone (Sterapred)]] 5 mg PO twice per day
+==Cabazitaxel & Prednisone {{#subobject:23 |Regimen=1}}==
+===Example orders===
-====Supportive medications====
+*[[Example orders for Cabazitaxel (Jevtana) in prostate cancer]]
+<div class="toccolours" style="background-color:#eeeeee">
-*[[Dexamethasone (Decadron)]] 8 mg PO given three times; 12 hours, 3 hours, and 1 hour before [[Docetaxel (Taxotere)]]
+===Regimen variant #1, 20/10, indefinite {{#subobject:fa59fa |Variant=1}}===
-*[[:Category:Emesis_prevention|Antiemetics]] "according to local practice"
-'''21-day cycle for up to 12 cycles'''
-===Regimen variant #4, 75 mg/m<sup>2</sup> q3wk, indefinite {{#subobject:ea941e |Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 ! style="width: 20%" |Study
-! style="width: 20%" |Years of enrollment
+! style="width: 20%" |Dates of enrollment
 ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 ! style="width: 20%" |Comparator
 ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3383121/ Kelly et al. 2012 (CALGB 90401)]
+| rowspan="2" |[https://doi.org/10.1200/JCO.2016.72.1068 Oudard et al. 2017 (FIRSTANA)]
-|2005-2007
+| rowspan="2" |2011-2013
-| style="background-color:#1a9851" |Phase III (C)
+| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-switch-ic)
-|Docetaxel, Prednisone, Bevacizumab
+|1. [[#Cabazitaxel_.26_Prednisone_2|Cabazitaxel & Prednisone]]; 25 mg/m<sup>2</sup>/10 mg
 | style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 |-
-|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70184-0/abstract Tannock et al. 2013 (VENICE)]
+|2. [[#Docetaxel_.26_Prednisone|Docetaxel & Prednisone]]
-|2007-2010
-| style="background-color:#1a9851" |Phase III (C)
-|Aflibercept, Docetaxel, Prednisone
 | style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 |-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5478530/ Araujo et al. 2013 (READY)]
+|[https://doi.org/10.1200/JCO.2016.72.1076 Eisenberger et al. 2017 (PROSELICA)]
-|2008-2011
+|2011-2013
-| style="background-color:#1a9851" |Phase III (C)
+| style="background-color:#1a9851" |Phase 3 (E-RT-de-esc)
-|Dasatinib, Docetaxel, Prednisone
+|[[#Cabazitaxel_.26_Prednisone_2|Cabazitaxel & Prednisone]]; 25 mg/m<sup>2</sup>/10 mg
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+| style="background-color:#eeee01" |Non-inferior OS (primary endpoint)<br>Median OS: 13.4 vs 14.5 mo<br>(HR 1.024, 98.89% CI 1.184)
 |-
-|[https://doi.org/10.1200/JCO.2012.46.4149 Fizazi et al. 2013 (ENTHUSE)]
+|}
-|2008-NR
+<div class="toccolours" style="background-color:#b3e2cd">
-| style="background-color:#1a9851" |Phase III (C)
+====Chemotherapy====
-|Docetaxel, Prednisone, Zibotentan
+*[[Cabazitaxel (Jevtana)]] 20 mg/m<sup>2</sup> IV once on day 1
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+====Endocrine therapy====
+*[[Prednisone (Sterapred)]] 10 mg PO once per day on days 1 to 21
+'''21-day cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #2, 25/10 x 10 {{#subobject:23 |Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+! style="width: 20%" |Study
+! style="width: 20%" |Dates of enrollment
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |Comparator
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)70025-2/abstract Petrylak et al. 2015 (MAINSAIL)]
+|[https://doi.org/10.1016/S0140-6736(10)61389-X de Bono et al. 2010 (TROPIC)]
-|2009-2011
+<!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
-| style="background-color:#1a9851" |Phase III (C)
+|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-102-1 <span style="color:white;">ESMO-MCBS (2)</span>]'''
-|Docetaxel, Lenalidomide, Prednisone
-| style="background-color:#1a9850" |Superior OS
 |-
-|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30168-7/fulltext Chi et al. 2017 (SYNERGY)]
+|} -->
-|2010-2012
+|2007-01-02 to 2008-10-23
-| style="background-color:#1a9851" |Phase III (C)
+| style="background-color:#1a9851" |Phase 3 (E-RT-switch-ic)
-|Custirsen, Docetaxel, Prednisone
+|[[#Mitoxantrone_.26_Prednisone|Mitoxantrone & Prednisone]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+| style="background-color:#1a9850" |Superior OS (primary endpoint)<br>Median OS: 15.1 vs 12.7 mo<br>(HR 0.70, 95% CI 0.59-0.83)
 |-
-| rowspan="2" |[https://doi.org/10.1200/JCO.2016.72.1068 Oudard et al. 2017 (FIRSTANA)]
+|[https://doi.org/10.1016/S1470-2045(17)30605-8 Beer et al. 2017 (AFFINITY)]
-| rowspan="2" |2011-2013
+|2012-2014
-| rowspan="2" style="background-color:#1a9851" |Phase III (C)
+| style="background-color:#1a9851" |Phase 3 (C)
-|[[#Cabazitaxel_.26_Prednisone_2|Cabazitaxel 20 mg/m<sup>2</sup> & Prednisone]]
+|[[#Cabazitaxel.2C_Custirsen.2C_Prednisone_999|Cabazitaxel, Prednisone, Custirsen]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
-|-
-|[[#Cabazitaxel_.26_Prednisone_2|Cabazitaxel 25 mg/m<sup>2</sup> & Prednisone]]
 | style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 |-
 |}
-''Note: patients in CALGB 90401 discontinued treatment after a maximum of 2 years.''
+''<sup>1</sup>ORRs in TROPIC were only reported for patients with measurable disease.''
+<div class="toccolours" style="background-color:#fdcdac">
+====Prior treatment criteria====
+*TROPIC: Previous endocrine therapy, and failure of a docetaxel-containing regimen
+*AFFINITY: Castration-resistant prostate cancer and failure of a docetaxel-containing regimen
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
+*[[Cabazitaxel (Jevtana)]] 25 mg/m<sup>2</sup> IV over 60 minutes once on day 1
-*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV once on day 1
 ====Endocrine therapy====
+*[[Prednisone (Sterapred)]] 10 mg PO once per day
+====Supportive therapy====
+*[[:Category:Antihistamines|Antihistamine]] once on day 1, at least 30 minutes prior to cabazitaxel
+*[[:Category:Steroids|Corticosteroid]] ([[Dexamethasone (Decadron)|dexamethasone]] 8 mg or equivalent) once on day 1, at least 30 minutes prior to cabazitaxel
+*[[:Category:Antihistamines|Histamine H2-antagonist]] (except cimetidine) once on day 1, at least 30 minutes prior to cabazitaxel
+'''21-day cycle for up to 10 cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
-*[[Prednisone (Sterapred)]] as follows:
+===Regimen variant #3, 25/10, indefinite {{#subobject:23sa2b |Variant=1}}===
-**CALGB 90401: 5 mg PO once per day
-**Others: 10 mg/day; some regimens give as 5 mg PO twice per day, some as 10 mg PO once per day
-'''21-day cycles'''
-===References===
-#'''TAX 327:''' 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. [https://www.nejm.org/doi/full/10.1056/NEJMoa040720 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15470213 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. [https://doi.org/10.1200/jco.2007.12.4008 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18182665 PubMed]
-#'''ASCENT:''' Beer TM, Ryan CW, Venner PM, Petrylak DP, Chatta GS, Ruether JD, Redfern CH, Fehrenbacher L, Saleh MN, Waterhouse DM, Carducci MA, Vicario D, Dreicer R, Higano CS, Ahmann FR, Chi KN, Henner WD, Arroyo A, Clow FW; ASCENT Investigators. Double-blinded randomized study of high-dose calcitriol plus docetaxel compared with placebo plus docetaxel in androgen-independent prostate cancer: a report from the ASCENT Investigators. J Clin Oncol. 2007 Feb 20;25(6):669-74. [https://doi.org/10.1200/JCO.2006.06.8197 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/17308271 PubMed] NCT00273338
-##'''Update:''' Scher HI, Jia X, Chi K, de Wit R, Berry WR, Albers P, Henick B, Waterhouse D, Ruether DJ, Rosen PJ, Meluch AA, Nordquist LT, Venner PM, Heidenreich A, Chu L, Heller G. Randomized, open-label phase III trial of docetaxel plus high-dose calcitriol versus docetaxel plus prednisone for patients with castration-resistant prostate cancer. J Clin Oncol. 2011 Jun 1;29(16):2191-8. Epub 2011 Apr 11. [https://doi.org/10.1200/JCO.2010.32.8815 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/21483004 PubMed]
-<!-- Presented in part at the 48th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, June 4-8, 2010. -->
-#'''CALGB 90401:''' Kelly WK, Halabi S, Carducci M, George D, Mahoney JF, Stadler WM, Morris M, Kantoff P, Monk JP, Kaplan E, Vogelzang NJ, Small EJ. Randomized, double-blind, placebo-controlled phase III trial comparing docetaxel and prednisone with or without bevacizumab in men with metastatic castration-resistant prostate cancer: CALGB 90401. J Clin Oncol. 2012 May 1;30(13):1534-40. Epub 2012 Mar 26. [https://doi.org/10.1200/JCO.2011.39.4767 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3383121/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/22454414 PubMed] NCT00110214
-#'''NePro:''' Meulenbeld HJ, van Werkhoven ED, Coenen JL, Creemers GJ, Loosveld OJ, de Jong PC, Ten Tije AJ, Fosså SD, Polee M, Gerritsen W, Dalesio O, de Wit R. Randomised phase II/III study of docetaxel with or without risedronate in patients with metastatic Castration Resistant Prostate Cancer (CRPC), the Netherlands Prostate Study (NePro). Eur J Cancer. 2012 Nov;48(16):2993-3000. Epub 2012 Jun 6. [https://www.ejcancer.com/article/S0959-8049(12)00428-5/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/22677260 PubMed]
-#'''VENICE:''' 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.[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70184-0/abstract link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23742877 PubMed] NCT00519285
-#'''SWOG S0421:''' Quinn DI, Tangen CM, Hussain M, Lara PN Jr, Goldkorn A, Moinpour CM, Garzotto MG, Mack PC, Carducci MA, Monk JP, Twardowski PW, Van Veldhuizen PJ, Agarwal N, Higano CS, Vogelzang NJ, Thompson IM Jr. Docetaxel and atrasentan versus docetaxel and placebo for men with advanced castration-resistant prostate cancer (SWOG S0421): a randomised phase 3 trial. Lancet Oncol. 2013 Aug;14(9):893-900. Epub 2013 Jul 17. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70294-8/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4277263/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23871417 PubMed] NCT00134056
-#'''READY:''' 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. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70479-0/abstract link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5478530/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/24211163 PubMed] NCT00744497
-#'''MAINSAIL:''' 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.[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)70025-2/abstract link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25743937 PubMed] NCT00988208
-#'''SYNERGY:''' 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. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30168-7/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28283282 PubMed] NCT01188187
-#'''FIRSTANA:''' 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. [https://doi.org/10.1200/JCO.2016.72.1068 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28753384 PubMed] NCT01308567
-#'''TRITON3:''' NCT02975934
-==Docetaxel & Prednisolone {{#subobject:8jfyz3 |Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
-===Example orders===
-*[[Example orders for Docetaxel (Taxotere) in prostate cancer]]
-===Regimen variant #1, 50 mg/m<sup>2</sup> bi-weekly {{#subobject:30 |Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 ! style="width: 20%" |Study
-! style="width: 20%" |Years of enrollment
+! style="width: 20%" |Dates of enrollment
 ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 ! style="width: 20%" |Comparator
 ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2812%2970537-5/abstract Kellokumpu-Lehtinen et al. 2013 (PROSTY)]
+| rowspan="2" |[https://doi.org/10.1200/JCO.2016.72.1068 Oudard et al. 2017 (FIRSTANA)]
-|2004-2009
+| rowspan="2" |2011-2013
-| style="background-color:#1a9851" |Phase III (E-switch-ic)
+| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-switch-ic)
-|[[#Docetaxel_.26_Prednisolone|Docetaxel & Prednisolone]]; q3wk
+|1. [[#Cabazitaxel_.26_Prednisone_2|Cabazitaxel & Prednisone]]; 20 mg/m<sup>2</sup>/10 mg
-| style="background-color:#91cf60" |Seems to have superior TTTF
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+|-
+|2. [[#Docetaxel_.26_Prednisone|Docetaxel & Prednisone]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 |-
-|}
+|[https://doi.org/10.1200/JCO.2016.72.1076 Eisenberger et al. 2017 (PROSELICA)]
-====Chemotherapy====
+|2011-2013
+| style="background-color:#1a9851" |Phase 3 (C)
-*[[Docetaxel (Taxotere)]] 50 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 & 15
+|[[#Cabazitaxel_.26_Prednisone_2|Cabazitaxel & Prednisone]]; 20 mg/m<sup>2</sup>/10 mg
+| style="background-color:#eeee01" |Non-inferior OS
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Cabazitaxel (Jevtana)]] 25 mg/m<sup>2</sup> IV over 60 minutes once on day 1
 ====Endocrine therapy====
+*[[Prednisone (Sterapred)]] 10 mg PO once per day on days 1 to 21
-*[[Prednisolone (Millipred)]] 10 mg PO once per day
+====Supportive therapy====
+*[[:Category:Antihistamines|Antihistamine]] once on day 1, at least 30 minutes prior to cabazitaxel
-====Supportive medications====
+*[[:Category:Steroids|Corticosteroid]] ([[Dexamethasone (Decadron)|dexamethasone]] 8 mg or equivalent) once on day 1, at least 30 minutes prior to cabazitaxel
+*[[:Category:Antihistamines|Histamine H2-antagonist]] (except cimetidine) once on day 1, at least 30 minutes prior to cabazitaxel
-*[[Dexamethasone (Decadron)]] 7.5 to 8 mg (route not specified) 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)
+'''21-day cycles'''
-*G-CSF not recommended unless patients developed febrile neutropenia or severe infection
+</div></div>
-*"Treatment with bisphosphonates, erythropoietin, and palliative radiation therapy was allowed"
+===References===
+#'''TROPIC:''' 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. [https://doi.org/10.1016/S0140-6736(10)61389-X link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20888992/ PubMed] [https://clinicaltrials.gov/study/NCT00417079 NCT00417079]
-'''28-day cycles'''
+#'''FIRSTANA:''' 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. [https://doi.org/10.1200/JCO.2016.72.1068 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28753384/ PubMed] [https://clinicaltrials.gov/study/NCT01308567 NCT01308567]
+#'''PROSELICA:''' 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 [https://doi.org/10.1200/JCO.2016.72.1076 link to original article] '''contains dosing details in supplement''' [https://pubmed.ncbi.nlm.nih.gov/28809610/ PubMed] [https://clinicaltrials.gov/study/NCT01308580 NCT01308580]
-===Regimen variant #2, 75 mg/m<sup>2</sup> q3wk, indefinite {{#subobject:28 |Variant=1}}===
+#'''AFFINITY:''' 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. [https://doi.org/10.1016/S1470-2045(17)30605-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29033099/ PubMed] [https://clinicaltrials.gov/study/NCT01578655 NCT01578655]
+==Cabozantinib monotherapy {{#subobject:a20f66 |Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #1, 60 mg/day {{#subobject:0eb568 |Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 ! style="width: 20%" |Study
-! style="width: 20%" |Years of enrollment
+! style="width: 20%" |Dates of enrollment
 ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 ! style="width: 20%" |Comparator
 ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2812%2970537-5/abstract Kellokumpu-Lehtinen et al. 2013 (PROSTY)]
+|[https://doi.org/10.1200/JCO.2015.65.5597 Smith et al. 2016 (COMET-1)]
-|2004-2009
+|2012-2014
-| style="background-color:#1a9851" |Phase III (C)
+| style="background-color:#1a9851" |Phase 3 (E-switch-ooc)
-|[[#Docetaxel_.26_Prednisolone|Docetaxel & Prednisolone]]; q2wk
+|[[#Prednisone_monotherapy|Prednisone]]
-| style="background-color:#fc8d59" |Seems to have inferior TTTF
-|-
-|[https://doi.org/10.1200/JCO.2012.46.4149 Fizazi et al. 2013 (ENTHUSE)]
-|2008-NR
-| style="background-color:#1a9851" |Phase III (C)
-|Docetaxel, Zibotentan, Prednisolone
 | style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 |-
 |}
-====Chemotherapy====
+<div class="toccolours" style="background-color:#b3e2cd">
+====Targeted therapy====
-*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV over 60 minutes once on day 1
+*[[Cabozantinib (Cometriq)|Cabozantinib (Cabometyx)]] 60 mg PO once per day on days 1 to 28
+'''28-day cycles'''
-====Endocrine therapy====
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
-*[[Prednisolone (Millipred)]] 10 mg PO once per day
+===Regimen variant #2, 100 mg/day {{#subobject:2efaa6 |Variant=1}}===
-**Fizazi et al. 2013: Given as 5 mg PO twice per day
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
+!style="width: 33%"|Study
-====Supportive medications====
+!style="width: 33%"|Dates of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
-*[[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
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4110249/ Smith et al. 2012 (XL184-203)]
-*"Treatment with bisphosphonates, erythropoietin, and palliative radiation therapy was allowed"
+|2009-2011
+| style="background-color:#91cf61" |Phase 2
-'''21-day cycles'''
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Targeted therapy====
+*[[Cabozantinib (Cometriq)|Cabozantinib (Cabometyx)]] 100 mg PO once per day
+'''Continued indefinitely'''
+</div></div>
 ===References===
+#'''XL184-203:''' 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. [https://doi.org/10.1200/jco.2012.45.0494 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4110249/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23169517/ PubMed] [https://clinicaltrials.gov/study/NCT00940225 NCT00940225]
+#'''COMET-1:''' 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. [https://doi.org/10.1200/JCO.2015.65.5597 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/27400947/ PubMed] [https://clinicaltrials.gov/study/NCT01605227 NCT01605227]
-#'''PROSTY:''' 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; 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. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2812%2970537-5/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23294853 PubMed] NCT00255606
+==Carboplatin & Docetaxel {{#subobject:28 |Regimen=1}}==
-#'''ENTHUSE:''' Fizazi K, Higano CS, Nelson JB, Gleave M, Miller K, Morris T, Nathan FE, McIntosh S, Pemberton K, Moul JW. Phase III, randomized, placebo-controlled study of docetaxel in combination with zibotentan in patients with metastatic castration-resistant prostate cancer. J Clin Oncol. 2013 May 10;31(14):1740-7. Epub 2013 Apr 8. Erratum in: J Clin Oncol. 2014 Oct 20;32(30):3461. Fizazi, Karim S [Corrected to Fizazi, Karim]. [https://doi.org/10.1200/JCO.2012.46.4149 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23569308 PubMed] NCT00617669
+===Example orders===
+*[[Example orders for Docetaxel & Carboplatin in prostate cancer]]
-==Mitoxantrone & Hydrocortisone {{#subobject:f4eqv4 |Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
-{| class="wikitable" style="float:right; margin-left: 5px;"
+===Regimen {{#subobject:31 |Variant=1}}===
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
+!style="width: 33%"|Study
+!style="width: 33%"|Dates of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+|-
+|[https://doi.org/10.1002/cncr.23195 Ross et al. 2008]
+|2004-2006
+| style="background-color:#91cf61" |Phase 2
 |-
-|[[#top|back to top]]
 |}
-===Regimen {{#subobject:da47uz |Variant=1}}===
+<div class="toccolours" style="background-color:#fdcdac">
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
+====Eligibility criteria====
-! style="width: 20%" |Study
+*Hormone-refractory prostate cancer and progression of disease during docetaxel treatment or within 45 days of stopping docetaxel treatment
-! style="width: 20%" |Years of enrollment
+</div>
-! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
+<div class="toccolours" style="background-color:#b3e2cd">
-! style="width: 20%" |Comparator
+====Chemotherapy====
-! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+*[[Carboplatin (Paraplatin)]] AUC 4 (Calvert formula) IV over 60 minutes once on day 1, '''given second'''
+*[[Docetaxel (Taxotere)]] 60 mg/m<sup>2</sup> IV over 60 minutes once on day 1, '''given first'''
+====Supportive therapy====
+*"Standard dexamethasone premedication was used"
+*Patients continued to receive androgen deprivation therapy
+'''21-day cycles'''
+</div></div>
+===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. [https://doi.org/10.1002/cncr.23195 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18085595/ PubMed]
+#'''Retrospective:''' 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. [https://doi.org/10.1111/j.1464-410X.2007.07331.x link to original article] [https://pubmed.ncbi.nlm.nih.gov/18184327/ PubMed]
+==Carboplatin, Docetaxel, Prednisone {{#subobject:28a1b4 |Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:32 |Variant=1}}===
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
+!style="width: 33%"|Study
+!style="width: 33%"|Dates of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 |-
-|[https://doi.org/10.1200/JCO.1999.17.8.2506 Kantoff et al. 1999 (CALGB 9182)]
+|[https://doi.org/10.1007/s00345-010-0527-5 Reuter et al. 2010]
-|1992-1995
+|2005-NR
-| style="background-color:#1a9851" |Phase III (E-RT-esc)
+| style="background-color:#91cf61" |Phase 2
-|[[#Hydrocortisone_monotherapy|Hydrocortisone]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 |-
 |}
+<div class="toccolours" style="background-color:#fdcdac">
+====Prior treatment criteria====
+*Docetaxel exposure with progression and castration-resistant disease
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
+*[[Carboplatin (Paraplatin)]] AUC 5 IV over 30 minutes once on day 1
-*[[Mitoxantrone (Novantrone)]]
+*[[Docetaxel (Taxotere)]] 35 mg/m<sup>2</sup> IV over 60 minutes 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.
 ====Endocrine therapy====
+*[[Prednisone (Sterapred)]] 5 mg PO twice per day on days 1 to 28
-*[[Hydrocortisone (Cortef)]]
+====Supportive therapy====
+*"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'''
+</div></div>
 ===References===
+#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. [https://doi.org/10.1007/s00345-010-0527-5 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20229232/ PubMed]
-#'''CALGB 9182:''' Kantoff PW, Halabi S, Conaway M, Picus J, Kirshner J, Hars V, Trump D, Winer EP, Vogelzang NJ. Hydrocortisone with or without mitoxantrone in men with hormone-refractory prostate cancer: results of the Cancer and Leukemia Group B 9182 study. J Clin Oncol. 1999 Aug;17(8):2506-13. [https://doi.org/10.1200/JCO.1999.17.8.2506 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/10561316 PubMed]
+==Carboplatin & Paclitaxel (CP) {{#subobject:30 |Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
-==Mitoxantrone & Prednisone {{#subobject:29 |Regimen=1}}==
+===Regimen variant #1 {{#subobject:34 |Variant=1}}===
-{| class="wikitable" style="float:right; margin-left: 5px;"
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
+!style="width: 33%"|Study
+!style="width: 33%"|Dates of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+|-
+|[http://link.springer.com/article/10.1007/s00280-012-1896-9 Kentepozidis et al. 2012]
+|2006-2009
+| style="background-color:#91cf61" |Phase 2
 |-
-|[[#top|back to top]]
 |}
-===Example orders===
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
-*[[Example orders for Mitoxantrone (Novantrone) in prostate cancer]]
+*[[Carboplatin (Paraplatin)]] AUC 3 (Calvert formula) IV once per day on days 1 & 15, '''given second'''
+*[[Paclitaxel (Taxol)]] 135 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 & 15, '''given first'''
-===Regimen {{#subobject:33 |Variant=1}}===
+====Supportive therapy====
+*"All patients received a concomitant anti-emetic prophylaxis"
+*[[Dexamethasone (Decadron)]] 20 mg PO given twice, 12 and 6 hours prior to paclitaxel
+*[[Diphenhydramine (Benadryl)]] 50 mg IV once per day on days 1 & 15, "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)
+*[[Cimetidine (Tagamet)]] 300 mg IV once per day on days 1 & 15, "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)
+*No prophylactic G-CSF
+'''28-day cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #2 {{#subobject:35 |Variant=1}}===
+{| class="wikitable" style="width: 40%; text-align:center;"
+! style="width: 25%" |Study
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
+|-
+|[http://www.urologiconcology.org/article/S1078-1439%2810)00003-7 Jeske et al. 2010]
+| style="background-color:#ffffbe" |Retrospective
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Carboplatin (Paraplatin)]] AUC 4 to 6 IV once on day 1
+*[[Paclitaxel (Taxol)]] 60 to 80 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
+'''28-day cycles'''
+</div></div>
+===References===
+#'''Retrospective:''' 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. [http://www.urologiconcology.org/article/S1078-1439%2810)00003-7 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20451413/ PubMed]
+#Kentepozidis N, Soultati A, Giassas S, Vardakis N, Kalykaki A, Kotsakis A, Papadimitraki E, Pantazopoulos N, Bozionellou V, Georgoulias V; Hellenic Oncology Research Group. 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. [http://link.springer.com/article/10.1007/s00280-012-1896-9 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22660737/ PubMed]
+==Docetaxel, Enzalutamide, Prednisolone {{#subobject:8jig9c |Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:jbzc38 |Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 ! style="width: 20%" |Study
-! style="width: 20%" |Years of enrollment
+! style="width: 20%" |Dates of enrollment
 ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 ! style="width: 20%" |Comparator
 ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-![[Overall response rate|'''ORR''', PSA RR]]
-!Comparator [[Overall response rate|'''ORR''', PSA RR]]
-!Pt Population
 |-
-|[https://doi.org/10.1200/JCO.1994.12.4.689 Moore et al. 1994]
+|[https://doi.org/10.1016/s1470-2045(22)00560-5 Merseburger et al. 2022 (PRESIDE)]
-|NR
+|2014-2016
-| style="background-color:#91cf61" |Phase II (RT)
+| style="background-color:#1a9851" |Phase 3 (E-esc)
-| style="background-color:#d3d3d3" |
+|[[#Docetaxel_.26_Prednisolone|Docetaxel & Prednisolone]]
-| style="background-color:#d3d3d3" |
+| style="background-color:#91cf60" |Seems to have superior PFS (primary endpoint)<br>Median PFS: 9.5 vs 8.3 mo<br>(HR 0.72, 95% CI 0.53-0.96)
-|
-|
-|
 |-
-|[https://doi.org/10.1200/JCO.1996.14.6.1756 Tannock et al. 1996 (CCI-NOV22)]
+|}
-|1990-1994
+<div class="toccolours" style="background-color:#b3e2cd">
-| style="background-color:#1a9851" |Phase III (E-RT-esc)
+====Chemotherapy====
-|[[#Prednisone_monotherapy|Prednisone]]
+*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV once on day 1
-| style="background-color:#1a9850" |Superior palliation
+====Endocrine therapy====
-|
+*[[Enzalutamide (Xtandi)]] 160 mg PO once per day
-|
+*[[Prednisolone (Millipred)]] 10 mg PO once per day
-|
+'''21-day cycle for up to 10 cycles'''
-|-
+</div></div>
-|[https://www.auajournals.org/doi/abs/10.1016/S0022-5347%2805%2964163-8 Berry et al. 2002]
+===References===
-|1997-1999
+#'''PRESIDE:''' Merseburger AS, Attard G, Åström L, Matveev VB, Bracarda S, Esen A, Feyerabend S, Senkus E, López-Brea Piqueras M, Boysen G, Gourgioti G, Martins K, Chowdhury S. Continuous enzalutamide after progression of metastatic castration-resistant prostate cancer treated with docetaxel (PRESIDE): an international, randomised, phase 3b study. Lancet Oncol. 2022 Nov;23(11):1398-1408. Epub 2022 Oct 18. [https://doi.org/10.1016/s1470-2045(22)00560-5 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/36265504/ PubMed] [https://clinicaltrials.gov/study/NCT02288247 NCT02288247]
-| style="background-color:#1a9851" |Phase III (E-esc)
-|[[#Prednisone_monotherapy|Prednisone]]
+==Docetaxel & Estramustine {{#subobject:27a1bc |Regimen=1}}==
-| style="background-color:#91cf60" |Seems to have superior TTTF
+<div class="toccolours" style="background-color:#eeeeee">
-|
+===Regimen {{#subobject:51bc1c |Variant=1}}===
-|
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-|
+! style="width: 20%" |Study
+! style="width: 20%" |Dates of enrollment
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |Comparator
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.nejm.org/doi/full/10.1056/NEJMoa041318 Petrylak et al. 2004 (SWOG S9916)]
+|[https://doi.org/10.1056/NEJMoa041318 Petrylak et al. 2004 (SWOG S9916)]
 |1999-2003
-| style="background-color:#1a9851" |Phase III (C)
+| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
-|[[#Docetaxel_.26_Estramustine|Docetaxel & Estramustine]]
+|[[#Mitoxantrone_.26_Prednisone|Mitoxantrone & Prednisone]]
-| style="background-color:#fc8d59" |Seems to have inferior OS
+| style="background-color:#91cf60" |Seems to have superior OS (primary endpoint)<br>Median OS: 17.5 vs 15.6 mo<br>(HR 0.80, 95% CI 0.67-0.97)
-|
-|
-|
 |-
-| rowspan="2" |[https://www.nejm.org/doi/full/10.1056/NEJMoa040720 Tannock et al. 2004 (TAX 327)]
+|}
-| rowspan="2" |2000-2002
+<div class="toccolours" style="background-color:#fdcdac">
-| rowspan="2" style="background-color:#1a9851" |Phase III (C)
+====Prior treatment criteria====
-|1. [[#Docetaxel_.26_Prednisone|Weekly Docetaxel & Prednisone]]
+*SWOG S9916: Hormone-independent prostate cancer
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+</div>
-| rowspan="2" |pts w/ measurable disease: '''7%''' (95% CI 3-12), '''32%''' (95% CI 26-37)
+<div class="toccolours" style="background-color:#b3e2cd">
-|pts w/ measurable disease: '''8%''' (95% CI 4-14), '''48%''' (95% CI 42-54)
+====Chemotherapy====
-|Chemo naive
+*[[Docetaxel (Taxotere)]] 60 mg/m<sup>2</sup> IV once on day 2
-|-
+*[[Estramustine (Emcyt)]] 280 mg PO three times per day on days 1 to 5
-|2. [[#Docetaxel_.26_Prednisone|Every 3-week Docetaxel & Prednisone]]
+'''21-day cycles'''
-| style="background-color:#d73027" |Inferior OS
+</div></div>
-|pts w/ measurable disease: '''12%''' (95% CI 7-19), '''45%''' (95% CI 40-51)
-|Chemo naive
-|-
-|[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2810%2961389-X/fulltext de Bono et al. 2010 (TROPIC)]
-|2007-2008
-| style="background-color:#1a9851" |Phase III (C)
-|[[#Cabazitaxel_.26_Prednisone_2|Cabazitaxel & Prednisone]]
-| style="background-color:#d73027" |Inferior OS
-|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>'''14.4%''' (95% CI 9.6 - 19.3), '''39.2%''' (95% CI 33.9 - 44.5)
-|Progressed on docetaxel
-|-
-|}
-====Chemotherapy====
-*[[Mitoxantrone (Novantrone)]] 12 mg/m<sup>2</sup> IV over 15 to 30 minutes once on day 1
-====Endocrine therapy====
-*[[Prednisone (Sterapred)]] 10 mg PO once per day on days 1 to 21
-**Some protocols give 5 mg PO twice per day
-'''21-day cycle for up to 10 cycles'''
 ===References===
+#'''SWOG S9916:''' 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. [https://doi.org/10.1056/NEJMoa041318 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/15470214/ PubMed] [https://clinicaltrials.gov/study/NCT00004001 NCT00004001]
+#'''ECOG E1899:''' [https://clinicaltrials.gov/study/NCT00027859 NCT00027859]
-#Moore MJ, Osoba D, Murphy K, Tannock IF, Armitage A, Findlay B, Coppin C, Neville A, Venner P, Wilson J. Use of palliative end points to evaluate the effects of mitoxantrone and low-dose prednisone in patients with hormonally resistant prostate cancer. J Clin Oncol. 1994 Apr;12(4):689-94. [https://doi.org/10.1200/JCO.1994.12.4.689 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/7512127 PubMed]
+==Docetaxel & Prednisone {{#subobject:27 |Regimen=1}}==
-#'''CCI-NOV22:''' 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. [https://doi.org/10.1200/JCO.1996.14.6.1756 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/8656243 PubMed]
+===Example orders===
-##'''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. [https://doi.org/10.1200/JCO.1999.17.6.1654 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/10561201 PubMed]
+*[[Example orders for Docetaxel (Taxotere) in prostate cancer]]
-#Berry W, Dakhil S, Modiano M, Gregurich M, Asmar L. Phase III study of mitoxantrone plus low dose prednisone versus low dose prednisone alone in patients with asymptomatic hormone refractory prostate cancer. J Urol. 2002 Dec;168(6):2439-43. [https://www.auajournals.org/doi/abs/10.1016/S0022-5347%2805%2964163-8 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12441935 PubMed]
+<div class="toccolours" style="background-color:#eeeeee">
-#'''TAX 327:''' 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. [https://www.nejm.org/doi/full/10.1056/NEJMoa040720 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15470213 PubMed]
+===Regimen variant #1, 30 mg/m<sup>2</sup> weekly {{#subobject:29 |Variant=1}}===
-##'''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. [https://doi.org/10.1200/jco.2007.12.4008 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18182665 PubMed]
-#'''SWOG S9916:''' 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. [https://www.nejm.org/doi/full/10.1056/NEJMoa041318 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15470214 PubMed]
-#'''TROPIC:''' 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. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2810%2961389-X/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/20888992 PubMed] NCT00417079
-==Olaparib monotherapy {{#subobject:defe72|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
-===Regimen Variant #1, 300 mg BID {{#subobject:8979a4|Variant=1}}===
-{| class="wikitable sortable" style="color:white; background-color:#404040"
-|<small>'''FDA-recommended dose'''</small>
-|-
-|}
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 ! style="width: 20%" |Study
-! style="width: 20%" |Years of enrollment
+! style="width: 20%" |Dates of enrollment
 ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 ! style="width: 20%" |Comparator
 ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-![[Levels_of_Evidence#Efficacy|Efficacy]], PFS
-!Comparator [[Overall response rate|'''ORR''']], PFS
-!Pt Population
 |-
-|[http://doi.org/10.1056/NEJMoa1911440 de Bono et al. 2020 (PROfound)]
+| rowspan="2" |[https://doi.org/10.1056/NEJMoa040720 Tannock et al. 2004 (TAX 327)]
-|2017-2018
+| rowspan="2" |2000-2002
-| style="background-color:#1a9851" |Phase III (E-RT-ooc)
+| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-RT-switch-ic)
-|1. [[#Abiraterone_monotherapy|Abiraterone]]<br> 2. [[#Enzalutamide_monotherapy|Enzalutamide]]
+|1. [[#Docetaxel_.26_Prednisone|Docetaxel & Prednisone]]; q3wk
-| style="background-color:#1a9850" |Superior PFS<sup>1</sup>
+| style="background-color:#d3d3d3" |Not reported
-|7.4 months (95% CI 0.25 to 0.47, p<0.001)
+|-
-|3.6 months
+|2. [[#Mitoxantrone_.26_Prednisone|Mitoxantrone & Prednisone]]
-|Progressed on abiraterone or enzalutamide, at least one alteration in BRCA1, BRCA2, or ATM
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS<br>Median OS: 17.4 vs 16.5 mo<br>(HR 0.91, 95% CI 0.75-1.11)
 |-
 |}
-''<sup>1</sup>Patients in Cohort A seemed to have superior OS in the 2020 update.''
+<div class="toccolours" style="background-color:#fdcdac">
-====Biomarker eligibility criteria====
+====Prior treatment criteria====
+*TAX 327: Disease progression during hormonal therapy
-*Cohort A: 1+ alterations in BRCA1, BRCA2, or ATM
+</div>
-*Cohort B: 1+ alterations in BRIP1, BARD1, CDK12, CHEK1, CHEK2, FANCL, PALB2, PPP2R2A, RAD51B, RAD51C, RAD51D, or RAD54L
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
-====Targeted therapy====
+*[[Docetaxel (Taxotere)]] 30 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1, 8, 15, 22, 29
+====Endocrine therapy====
-*[[Olaparib (Lynparza)]] 300 mg PO twice per day
+*[[Prednisone (Sterapred)]] 5 mg PO twice per day
+====Supportive therapy====
-'''Continued indefinitely'''
+*[[Dexamethasone (Decadron)]] 8 mg (route not specified) once 1 hour prior to docetaxel
+*Antiemetics "according to local practice"
-===Regimen Variant #2, 400 mg BID {{#subobject:8979a3|Variant=1}}===
+'''42-day cycle for up to 5 cycles'''
-{| class="wikitable" style="width: 50%; text-align:center;"
+</div></div><br>
-! style="width: 25%" |Study
+<div class="toccolours" style="background-color:#eeeeee">
-! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
+===Regimen variant #2, 75 mg/m<sup>2</sup> q3wk x 10 {{#subobject:27 |Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+! style="width: 20%" |Study
+! style="width: 20%" |Dates of enrollment
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |Comparator
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+| rowspan="2" |[https://doi.org/10.1056/NEJMoa040720 Tannock et al. 2004 (TAX 327)]
+<!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
+|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-101-1 <span style="color:white;">ESMO-MCBS (3)</span>]'''
 |-
-|[http://www.ncbi.nlm.nih.gov/pmc/articles/pmc6057749/ Kaufman et al. 2014 (Study 42)]
+|} -->
-| style="background-color:#ffffbe" |Phase II, <20 pts in subgroup
+| rowspan="2" |2000-2002
+| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-RT-switch-ic)
+|1. [[#Docetaxel_.26_Prednisone|Docetaxel & Prednisone]]; weekly
+| style="background-color:#d3d3d3" |Not reported
 |-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5228595/ Mateo et al. 2015 (TOPARP-A)]
+|2. [[#Mitoxantrone_.26_Prednisone|Mitoxantrone & Prednisone]]
-| style="background-color:#91cf61" |Phase II
+| style="background-color:#1a9850" |Superior OS (primary endpoint)<br>Median OS: 18.9 vs 16.5 mo<br>(HR 0.76, 95% CI 0.62-0.94)
 |-
-|}
+|[https://doi.org/10.1200/JCO.2006.06.8197 Beer et al. 2011 (ASCENT<sub>PRCA</sub>)]
-====Biomarker eligibility criteria====
+|2002-2004
-*Study 42: Germline BRCA1/2 mutations and had progression on hormonal and one systemic therapy
+| style="background-color:#1a9851" |Phase 3 (C)
-*TOPARP-A: Patients who were found to have homozygous deletions, deleterious mutations, or both in DNA-repair genes were much more likely to respond to olaparib
+|[[#Calcitriol.2C_Docetaxel.2C_Prednisone_999|Calcitriol, Docetaxel, Prednisone]]
+| style="background-color:#1a9850" |Superior OS<sup>1</sup>
-====Targeted therapy====
+|-
+|[https://doi.org/10.1016/j.ejca.2012.05.014 Meulenbeld et al. 2012 (NePro)]
-*[[Olaparib (Lynparza)]] 400 mg PO twice per day
+|2004-2010
+| style="background-color:#1a9851" |Phase 2/3 (C)
-'''Continued indefinitely'''
+|[[#Docetaxel.2C_Prednisone.2C_Risedronate_999|Docetaxel, Prednisone, Risedronate]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of TTP
-===References===
-<!-- Presented at the 49th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, May 31-June 4, 2013. -->
-#'''Study 42:''' 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. [https://doi.org/10.1200/jco.2014.56.2728 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pmc/articles/pmc6057749/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/25366685 PubMed] NCT01078662
-#'''TOPARP-A:''' 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. [https://www.nejm.org/doi/full/10.1056/NEJMoa1506859Top link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5228595/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26510020 PubMed] NCT01682772
-#'''PROfound:''' de Bono J, Mateo J, Fizazi K, Saad F, Shore N, Sandhu S, Chi KN, Sartor O, Agarwal N, Olmos D, Thiery-Vuillemin A, Twardowski P, Mehra N, Goessl C, Kang J, Burgents J, Wu W, Kohlmann A, Adelman CA, Hussain M. Olaparib for Metastatic Castration-Resistant Prostate Cancer. N Engl J Med. 2020 May 28;382(22):2091-2102. Epub 2020 Apr 28. [http://doi.org/10.1056/NEJMoa1911440 link to original article] '''contains verified protocol''' [https://www.nejm.org/doi/suppl/10.1056/NEJMoa1911440/suppl_file/nejmoa1911440_appendix.pdf link to supplementary appendix] [https://pubmed.ncbi.nlm.nih.gov/32343890/ PubMed] NCT02987543
-## ''Update:''' Hussain M, Mateo J, Fizazi K, Saad F, Shore N, Sandhu S, Chi KN, Sartor O, Agarwal N, Olmos D, Thiery-Vuillemin A, Twardowski P, Roubaud G, Özgüroğlu M, Kang J, Burgents J, Gresty C, Corcoran C, Adelman CA, de Bono J; PROfound Trial Investigators. Survival with Olaparib in Metastatic Castration-Resistant Prostate Cancer. N Engl J Med. 2020 Dec 10;383(24):2345-2357. Epub 2020 Sep 20. [https://doi.org/10.1056/nejmoa2022485 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32955174 PubMed]
-=Immunotherapy for metastatic castrate-resistant disease=
-==Ipilimumab & RT {{#subobject:33 |Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
 |-
-|[[#top|back to top]]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc4307981/ Zhou et al. 2015 (DOCET_L_01833)]
-|}
+|2007-2010
-Ipilimumab & RT: Ipilimumab & '''<u>R</u>'''adiation '''<u>T</u>'''herapy
+| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
+|[[#Mitoxantrone_.26_Prednisone|Mitoxantrone & Prednisone]]
-===Regimen {{#subobject:38 |Variant=1}}===
+| style="background-color:#1a9850" |Superior OS (primary endpoint)<br>Median OS: 21.9 vs 13.7 mo<br>(HR 0.63, 95% CI 0.46-0.86)
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
-! style="width: 25%" |Study
-! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
-! style="width: 25%" |[[Levels_of_Evidence#Efficacy|Efficacy]]
-! style="width: 25%" |Patient population
 |-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3707423/ Slovin et al. 2013]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8832307/ Vogelzang et al. 2022 (VIABLE)]
-| style="background-color:#91cf61" |Phase I/II
+|2014-2017
-|ORR: 4% (95% CI n/a), PSA RR: 16%;
+| style="background-color:#1a9851" |Phase 3 (C)
-|Most had ADT, some had docetaxel use. 10 mg/kg cohort reported here.
+|[[#Docetaxel.2C_Prednisone.2C_DCVAC/PCa_999|Docetaxel, Prednisone, DCVAC/PCa]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 |-
 |}
-====Immunotherapy====
+''<sup>1</sup>Reported efficacy for ASCENT is based on the 2011 update.''<br>
+''Note: ASCENT is labeled ASCENT<sub>PRCA</sub> to distinguish from the trial by the same name in TNBC.''
-*[[Ipilimumab (Yervoy)]] 10 mg/kg IV over 90 minutes once on day 1
+<div class="toccolours" style="background-color:#fdcdac">
-**Lower doses including 3 mg/kg (the FDA approved dose) were investigated, but the 10 mg/kg dose was recommended in this study
+====Prior treatment criteria====
+*TAX 327: Disease progression during hormonal therapy
-====Radiotherapy====
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
-*[[External_beam_radiotherapy|Radiation therapy]] given focally at a single dose of 8 Gy per target bone lesion for up to three bone lesions per patient, '''given 24 to 48 h before the first ipilimumab dose'''
+====Chemotherapy====
+*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV over 60 minutes once on day 1
-'''21-day cycle for 4 cycles'''
+====Endocrine therapy====
+*[[Prednisone (Sterapred)]] 5 mg PO twice per day or 10 mg PO once per day
-===References===
+====Supportive therapy====
+*[[Dexamethasone (Decadron)]] 8 mg PO given three times; 12 hours, 3 hours, and 1 hour prior to docetaxel
-#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. [https://doi.org/10.1093/annonc/mdt107 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3707423/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/23535954 PubMed] NCT00323882
+*[[:Category:Emesis_prevention|Antiemetics]] "according to local practice"
+'''21-day cycle for up to 10 cycles'''
-==Sipuleucel-T monotherapy {{#subobject:32 |Regimen=1}}==
+</div></div><br>
-{| class="wikitable" style="float:right; margin-left: 5px;"
+<div class="toccolours" style="background-color:#eeeeee">
-|-
+===Regimen variant #3, 75 mg/m<sup>2</sup> q3wk x 12 {{#subobject:27a1bc |Variant=1}}===
-|[[#top|back to top]]
-|}
-===Example orders===
-*[[Example orders for Sipuleucel-T (Provenge) in prostate cancer]]
-===Regimen {{#subobject:37 |Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 ! style="width: 20%" |Study
-! style="width: 20%" |Years of enrollment
+! style="width: 20%" |Dates of enrollment
 ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 ! style="width: 20%" |Comparator
 ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1200/JCO.2005.04.5252 Small et al. 2006 (D9901)]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4277263/ Quinn et al. 2013 (SWOG S0421)]
-|2000-2001
+|2006-2010
-| style="background-color:#1a9851" |Phase III (E-RT-esc)
+| style="background-color:#1a9851" |Phase 3 (C)
-|[[Prostate_cancer_-_null_regimens#Placebo_3|Placebo]]
+|[[#Atrasentan.2C_Docetaxel.2C_Prednisone_999|Atrasentan, Docetaxel, Prednisone]]
-| style="background-color:#d9ef8b" |Might have superior TTP
+| style="background-color:#ffffbf" |Did not meet co-primary endpoints of PFS/OS
-|-
-|[https://onlinelibrary.wiley.com/doi/full/10.1002/cncr.24429 Higano et al. 2009 (D9902A)]
-|2000-2003
-| style="background-color:#1a9851" |Phase III (E-esc)
-|[[Prostate_cancer_-_null_regimens#Placebo_3|Placebo]]
-| style="background-color:#d9ef8b" |Might have superior TTP
-|-
-|[https://www.nejm.org/doi/full/10.1056/NEJMoa1001294 Kantoff et al. 2010 (IMPACT<sub>prostate</sub>)]
-|2003-2007
-| style="background-color:#1a9851" |Phase III (E-RT-esc)
-|[[Prostate_cancer_-_null_regimens#Placebo_3|Placebo]]
-| style="background-color:#91cf60" |Seems to have superior OS
 |-
 |}
-''Note: Higano et al. 2009 was a pooled update but also the first publication to describe results of D9902A. IMPACT should not be confused with the studies of the same name in breast cancer and colorectal cancer.''
+<div class="toccolours" style="background-color:#b3e2cd">
-====Immunotherapy====
+====Chemotherapy====
+*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV over 60 minutes once on day 1
-*[[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
+====Endocrine therapy====
+*[[Prednisone (Sterapred)]] 5 mg PO twice per day
-====Supportive medications====
+====Supportive therapy====
+*[[Dexamethasone (Decadron)]] 8 mg PO given three times; 12 hours, 3 hours, and 1 hour prior to docetaxel
-*[[Acetaminophen (Tylenol)]] PO once per week on weeks 0, 2, 4; 30 minutes prior to [[Sipuleucel-T (Provenge)]]
+*[[:Category:Emesis_prevention|Antiemetics]] "according to local practice"
-*[[:Category:Antihistamines|Antihistamine]] PO once per week on weeks 0, 2, 4; 30 minutes prior to [[Sipuleucel-T (Provenge)]]
+'''21-day cycle for up to 12 cycles'''
+</div></div><br>
-'''One course'''
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #4, 75 mg/m<sup>2</sup> q3wk, indefinite {{#subobject:ea941e |Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+! style="width: 20%" |Study
+! style="width: 20%" |Dates of enrollment
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |Comparator
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3383121/ Kelly et al. 2012 (CALGB 90401)]
+|2005-2007
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#Docetaxel.2C_Prednisone.2C_Bevacizumab_999|Docetaxel, Prednisone, Bevacizumab]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+|-
+|[https://doi.org/10.1016/S1470-2045(13)70184-0 Tannock et al. 2013 (VENICE)]
+|2007-2010
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#Aflibercept.2C_Docetaxel.2C_Prednisone_999|Aflibercept, Docetaxel, Prednisone]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5478530/ Araujo et al. 2013 (READY)]
+|2008-2011
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#Dasatinib.2C_Docetaxel.2C_Prednisone_999|Dasatinib, Docetaxel, Prednisone]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+|-
+|[https://doi.org/10.1200/JCO.2012.46.4149 Fizazi et al. 2013 (ENTHUSE)]
+|2008-NR
+| style="background-color:#1a9851" |Phase 3 (C)
+|1a. [[#Docetaxel.2C_Prednisolone.2C_Zibotentan_999|Docetaxel, Prednisolone, Zibotentan]]<br>1b. [[#Docetaxel.2C_Prednisone.2C_Zibotentan_999|Docetaxel, Prednisone, Zibotentan]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+|-
+|[https://doi.org/10.1016/S1470-2045(15)70025-2 Petrylak et al. 2015 (MAINSAIL)]
+|2009-2011
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#Docetaxel.2C_Lenalidomide.2C_Prednisone_999|Docetaxel, Lenalidomide, Prednisone]]
+| style="background-color:#1a9850" |Superior OS
+|-
+|[https://doi.org/10.1016/S1470-2045(17)30168-7 Chi et al. 2017 (SYNERGY)]
+|2010-2012
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#Custirsen.2C_Docetaxel.2C_Prednisone_999|Custirsen, Docetaxel, Prednisone]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+|-
+| rowspan="2" |[https://doi.org/10.1200/JCO.2016.72.1068 Oudard et al. 2017 (FIRSTANA)]
+| rowspan="2" |2011-2013
+| rowspan="2" style="background-color:#1a9851" |Phase 3 (C)
+|1. [[#Cabazitaxel_.26_Prednisone_2|Cabazitaxel & Prednisone]]; 20 mg/m<sup>2</sup>/10 mg
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+|-
+|2. [[#Cabazitaxel_.26_Prednisone_2|Cabazitaxel & Prednisone]]; 25 mg/m<sup>2</sup>/10 mg
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+|-
+|}
+''Note: patients in CALGB 90401 discontinued treatment after a maximum of 2 years.''
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV once on day 1
+====Endocrine therapy====
+*[[Prednisone (Sterapred)]] by the following study-specific criteria:
+**CALGB 90401: 5 mg PO once per day on days 1 to 21
+**Others: 10 mg/day; some regimens give as 5 mg PO twice per day, some as 10 mg PO once per day
+'''21-day cycles'''
+</div></div>
 ===References===
+#'''TAX 327:''' 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. [https://doi.org/10.1056/NEJMoa040720 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15470213/ 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. [https://doi.org/10.1200/jco.2007.12.4008 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18182665/ PubMed]
+#'''ASCENT<sub>PRCA</sub>:''' Beer TM, Ryan CW, Venner PM, Petrylak DP, Chatta GS, Ruether JD, Redfern CH, Fehrenbacher L, Saleh MN, Waterhouse DM, Carducci MA, Vicario D, Dreicer R, Higano CS, Ahmann FR, Chi KN, Henner WD, Arroyo A, Clow FW; ASCENT Investigators. Double-blinded randomized study of high-dose calcitriol plus docetaxel compared with placebo plus docetaxel in androgen-independent prostate cancer: a report from the ASCENT Investigators. J Clin Oncol. 2007 Feb 20;25(6):669-74. [https://doi.org/10.1200/JCO.2006.06.8197 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17308271/ PubMed] [https://clinicaltrials.gov/study/NCT00273338 NCT00273338]
+##'''Update:''' Scher HI, Jia X, Chi K, de Wit R, Berry WR, Albers P, Henick B, Waterhouse D, Ruether DJ, Rosen PJ, Meluch AA, Nordquist LT, Venner PM, Heidenreich A, Chu L, Heller G. Randomized, open-label phase III trial of docetaxel plus high-dose calcitriol versus docetaxel plus prednisone for patients with castration-resistant prostate cancer. J Clin Oncol. 2011 Jun 1;29(16):2191-8. Epub 2011 Apr 11. [https://doi.org/10.1200/JCO.2010.32.8815 link to original article] [https://pubmed.ncbi.nlm.nih.gov/21483004/ PubMed]
+<!-- Presented in part at the 48th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, June 4-8, 2010. -->
+#'''CALGB 90401:''' Kelly WK, Halabi S, Carducci M, George D, Mahoney JF, Stadler WM, Morris M, Kantoff P, Monk JP, Kaplan E, Vogelzang NJ, Small EJ. Randomized, double-blind, placebo-controlled phase III trial comparing docetaxel and prednisone with or without bevacizumab in men with metastatic castration-resistant prostate cancer: CALGB 90401. J Clin Oncol. 2012 May 1;30(13):1534-40. Epub 2012 Mar 26. [https://doi.org/10.1200/JCO.2011.39.4767 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3383121/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22454414/ PubMed] [https://clinicaltrials.gov/study/NCT00110214 NCT00110214]
+#'''NePro:''' Meulenbeld HJ, van Werkhoven ED, Coenen JL, Creemers GJ, Loosveld OJ, de Jong PC, Ten Tije AJ, Fosså SD, Polee M, Gerritsen W, Dalesio O, de Wit R. Randomised phase II/III study of docetaxel with or without risedronate in patients with metastatic Castration Resistant Prostate Cancer (CRPC), the Netherlands Prostate Study (NePro). Eur J Cancer. 2012 Nov;48(16):2993-3000. Epub 2012 Jun 6. [https://doi.org/10.1016/j.ejca.2012.05.014 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22677260/ PubMed]
+#'''VENICE:''' 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. [https://doi.org/10.1016/S1470-2045(13)70184-0 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/23742877/ PubMed] [https://clinicaltrials.gov/study/NCT00519285 NCT00519285]
+#'''SWOG S0421:''' Quinn DI, Tangen CM, Hussain M, Lara PN Jr, Goldkorn A, Moinpour CM, Garzotto MG, Mack PC, Carducci MA, Monk JP, Twardowski PW, Van Veldhuizen PJ, Agarwal N, Higano CS, Vogelzang NJ, Thompson IM Jr. Docetaxel and atrasentan versus docetaxel and placebo for men with advanced castration-resistant prostate cancer (SWOG S0421): a randomised phase 3 trial. Lancet Oncol. 2013 Aug;14(9):893-900. Epub 2013 Jul 17. [https://doi.org/10.1016/S1470-2045(13)70294-8 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4277263/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23871417/ PubMed] [https://clinicaltrials.gov/study/NCT00134056 NCT00134056]
+#'''READY:''' 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. [https://doi.org/10.1016/S1470-2045(13)70479-0 link to original article] '''contains dosing details in abstract''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5478530/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24211163/ PubMed] [https://clinicaltrials.gov/study/NCT00744497 NCT00744497]
+#'''DOCET_L_01833:''' Zhou T, Zeng SX, Ye DW, Wei Q, Zhang X, Huang YR, Ye ZQ, Yang Y, Zhang W, Tian Y, Zhou FJ, Jie J, Chen SP, Sun Y, Xie LP, Yao X, Na YQ, Sun YH. A multicenter, randomized clinical trial comparing the three-weekly docetaxel regimen plus prednisone versus mitoxantone plus prednisone for Chinese patients with metastatic castration refractory prostate cancer. PLoS One. 2015 Jan 27;10(1):e0117002. [https://doi.org/10.1371/journal.pone.0117002 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc4307981/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25625938/ PubMed] [https://clinicaltrials.gov/study/NCT00436839 NCT00436839]
+#'''MAINSAIL:''' 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. [https://doi.org/10.1016/S1470-2045(15)70025-2 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/25743937/ PubMed] [https://clinicaltrials.gov/study/NCT00988208 NCT00988208]
+#'''SYNERGY:''' 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. [https://doi.org/10.1016/S1470-2045(17)30168-7 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/28283282/ PubMed] [https://clinicaltrials.gov/study/NCT01188187 NCT01188187]
+#'''FIRSTANA:''' 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. [https://doi.org/10.1200/JCO.2016.72.1068 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28753384/ PubMed] [https://clinicaltrials.gov/study/NCT01308567 NCT01308567]
+#Bianchi S, Mosca A, Dalla Volta A, Prati V, Ortega C, Buttigliero C, Fea E, Vanella P, Valcamonico F, Zamparini M, Sirotova Z, Chiappino I, Dal Canton O, Masini C, Sacco C, Amoroso D, Montagnani F, Comandone A, Bellissimo AR, Ciccone G, Baier S, Gennari A, Tucci M, Berruti A. Maintenance versus discontinuation of androgen deprivation therapy during continuous or intermittent docetaxel administration in castration-resistant prostate cancer patients: A multicentre, randomised Phase III study by the Piemonte Oncology Network. Eur J Cancer. 2021 Sep;155:127-135. Epub 2021 Aug 6. [https://doi.org/10.1016/j.ejca.2021.06.034 link to original article] [https://pubmed.ncbi.nlm.nih.gov/34371442/ PubMed]
+#'''VIABLE:''' Vogelzang NJ, Beer TM, Gerritsen W, Oudard S, Wiechno P, Kukielka-Budny B, Samal V, Hajek J, Feyerabend S, Khoo V, Stenzl A, Csöszi T, Filipovic Z, Goncalves F, Prokhorov A, Cheung E, Hussain A, Sousa N, Bahl A, Hussain S, Fricke H, Kadlecova P, Scheiner T, Korolkiewicz RP, Bartunkova J, Spisek R; VIABLE Investigators. Efficacy and Safety of Autologous Dendritic Cell-Based Immunotherapy, Docetaxel, and Prednisone vs Placebo in Patients With Metastatic Castration-Resistant Prostate Cancer: The VIABLE Phase 3 Randomized Clinical Trial. JAMA Oncol. 2022 Apr 1;8(4):546-552. [https://doi.org/10.1001/jamaoncol.2021.7298 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8832307/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/35142815/ PubMed] [https://clinicaltrials.gov/study/NCT02111577 NCT02111577]
+#'''DORA:''' [https://clinicaltrials.gov/study/NCT03574571 NCT03574571]
-#'''D9901:''' Small EJ, Schellhammer PF, Higano CS, Redfern CH, Nemunaitis JJ, Valone FH, Verjee SS, Jones LA, Hershberg RM. Placebo-controlled phase III trial of immunologic therapy with sipuleucel-T (APC8015) in patients with metastatic, asymptomatic hormone refractory prostate cancer. J Clin Oncol. 2006 Jul 1;24(19):3089-94. [https://doi.org/10.1200/JCO.2005.04.5252 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/16809734 PubMed]
+==Docetaxel & Prednisolone {{#subobject:8jfyz3 |Regimen=1}}==
-##'''Pooled Update:''' Higano CS, Schellhammer PF, Small EJ, Burch PA, Nemunaitis J, Yuh L, Provost N, Frohlich MW. Integrated data from 2 randomized, double-blind, placebo-controlled, phase 3 trials of active cellular immunotherapy with sipuleucel-T in advanced prostate cancer. Cancer. 2009 Aug 15;115(16):3670-9. [https://onlinelibrary.wiley.com/doi/full/10.1002/cncr.24429 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/19536890 PubMed]
+===Example orders===
-#'''D9902A:''' Higano CS, Schellhammer PF, Small EJ, Burch PA, Nemunaitis J, Yuh L, Provost N, Frohlich MW. Integrated data from 2 randomized, double-blind, placebo-controlled, phase 3 trials of active cellular immunotherapy with sipuleucel-T in advanced prostate cancer. Cancer. 2009 Aug 15;115(16):3670-9. [https://onlinelibrary.wiley.com/doi/full/10.1002/cncr.24429 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/19536890 PubMed]
+*[[Example orders for Docetaxel (Taxotere) in prostate cancer]]
-#'''IMPACT:''' 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. [https://www.nejm.org/doi/full/10.1056/NEJMoa1001294 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/20818862 PubMed]
+<div class="toccolours" style="background-color:#eeeeee">
-#'''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. [http://www.auajournals.org/article/S0022-5347(11)03851-1/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21788048 PubMed]
+===Regimen variant #1, 50 mg/m<sup>2</sup> bi-weekly {{#subobject:30 |Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-=Radioactive agents for bony metastatic disease=
+! style="width: 20%" |Study
+! style="width: 20%" |Dates of enrollment
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |Comparator
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1016/S1470-2045%2812%2970537-5 Kellokumpu-Lehtinen et al. 2013 (PROSTY)]
+|2004-2009
+| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
+|[[#Docetaxel_.26_Prednisolone|Docetaxel & Prednisolone]]; q3wk
+| style="background-color:#1a9850" |Superior TTTF (primary endpoint)<br>Median TTTF: 5.6 vs 4.9 mo<br>(HR 0.77, 95% CI 0.625-0.91)
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Docetaxel (Taxotere)]] 50 mg/m<sup>2</sup> IV over 60 minutes once on day 1
+====Endocrine therapy====
+*[[Prednisolone (Millipred)]] 10 mg PO once per day on days 1 to 14
+====Supportive therapy====
+*[[Dexamethasone (Decadron)]] 7.5 to 8 mg (route not specified) once per day, started 1 day prior to docetaxel and stopped 1 to 2 days after docetaxel infusion (in other words, from day -1 to day 2 or 3)
+*G-CSF not recommended unless patients developed febrile neutropenia or severe infection
+*"Treatment with bisphosphonates, erythropoietin, and palliative radiation therapy was allowed"
+'''14-day cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #2, 75 mg/m<sup>2</sup> q3wk, 10 cycles {{#subobject:agck28 |Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+! style="width: 20%" |Study
+! style="width: 20%" |Dates of enrollment
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |Comparator
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1016/s1470-2045(22)00560-5 Merseburger et al. 2022 (PRESIDE)]
+|2014-2016
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#Docetaxel.2C_Enzalutamide.2C_Prednisolone|Docetaxel, Enzalutamide, Prednisolone]]
+| style="background-color:#fc8d59" |Seems to have inferior PFS
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV once on day 1
+====Endocrine therapy====
+*[[Prednisolone (Millipred)]] 10 mg PO once per day on days 1 to 21
+'''21-day cycle for up to 10 cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #3, 75 mg/m<sup>2</sup> q3wk, indefinite {{#subobject:28 |Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+! style="width: 20%" |Study
+! style="width: 20%" |Dates of enrollment
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |Comparator
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1016/S1470-2045%2812%2970537-5 Kellokumpu-Lehtinen et al. 2013 (PROSTY)]
+|2004-2009
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#Docetaxel_.26_Prednisolone|Docetaxel & Prednisolone]]; q2wk
+| style="background-color:#d73027" |Inferior TTTF
+|-
+|[https://doi.org/10.1200/JCO.2012.46.4149 Fizazi et al. 2013 (ENTHUSE)]
+|2008-NR
+| style="background-color:#1a9851" |Phase 3 (C)
+|1a. [[#Docetaxel.2C_Prednisolone.2C_Zibotentan_999|Docetaxel, Prednisolone, Zibotentan]]<br>1b. [[#Docetaxel.2C_Prednisone.2C_Zibotentan_999|Docetaxel, Prednisone, Zibotentan]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV over 60 minutes once on day 1
+====Endocrine therapy====
+*[[Prednisolone (Millipred)]] 10 mg PO once per day on days 1 to 21
+**Alternative dosing in Fizazi et al. 2013: 5 mg PO twice per day
+====Supportive therapy====
+*[[Dexamethasone (Decadron)]] 7.5 to 8 mg daily, started 1 day prior to docetaxel 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'''
+</div></div>
+===References===
+#'''PROSTY:''' 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; 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. [https://doi.org/10.1016/S1470-2045%2812%2970537-5 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23294853/ PubMed] [https://clinicaltrials.gov/study/NCT00255606 NCT00255606]
+#'''ENTHUSE:''' Fizazi K, Higano CS, Nelson JB, Gleave M, Miller K, Morris T, Nathan FE, McIntosh S, Pemberton K, Moul JW. Phase III, randomized, placebo-controlled study of docetaxel in combination with zibotentan in patients with metastatic castration-resistant prostate cancer. J Clin Oncol. 2013 May 10;31(14):1740-7. Epub 2013 Apr 8. Erratum in: J Clin Oncol. 2014 Oct 20;32(30):3461. Fizazi, Karim S [Corrected to Fizazi, Karim]. [https://doi.org/10.1200/JCO.2012.46.4149 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23569308/ PubMed] [https://clinicaltrials.gov/study/NCT00617669 NCT00617669]
+#'''PRESIDE:''' Merseburger AS, Attard G, Åström L, Matveev VB, Bracarda S, Esen A, Feyerabend S, Senkus E, López-Brea Piqueras M, Boysen G, Gourgioti G, Martins K, Chowdhury S. Continuous enzalutamide after progression of metastatic castration-resistant prostate cancer treated with docetaxel (PRESIDE): an international, randomised, phase 3b study. Lancet Oncol. 2022 Nov;23(11):1398-1408. Epub 2022 Oct 18. [https://doi.org/10.1016/s1470-2045(22)00560-5 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/36265504/ PubMed] [https://clinicaltrials.gov/study/NCT02288247 NCT02288247]
+==Mitoxantrone & Hydrocortisone {{#subobject:f4eqv4 |Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:da47uz |Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+! style="width: 20%" |Study
+! style="width: 20%" |Dates of enrollment
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |Comparator
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1200/JCO.1999.17.8.2506 Kantoff et al. 1999 (CALGB 9182)]
+|1992-1995
+| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
+|[[#Hydrocortisone_monotherapy|Hydrocortisone]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Mitoxantrone (Novantrone)]] 14 mg/m<sup>2</sup> IV once on day 1
+====Endocrine therapy====
+*[[Hydrocortisone (Cortef)]] 30 mg PO once per day on days 1 to 21, taken in the morning
+*[[Hydrocortisone (Cortef)]] 10 mg PO once per day on days 1 to 21, taken in the evening
+'''21-day cycles'''
+</div></div>
+===References===
+#'''CALGB 9182:''' Kantoff PW, Halabi S, Conaway M, Picus J, Kirshner J, Hars V, Trump D, Winer EP, Vogelzang NJ. Hydrocortisone with or without mitoxantrone in men with hormone-refractory prostate cancer: results of the Cancer and Leukemia Group B 9182 study. J Clin Oncol. 1999 Aug;17(8):2506-13. [https://doi.org/10.1200/JCO.1999.17.8.2506 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/10561316/ PubMed]
-==Radium-223 monotherapy {{#subobject:35 |Regimen=1}}==
+==Mitoxantrone & Prednisone {{#subobject:29 |Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
+===Example orders===
+*[[Example orders for Mitoxantrone (Novantrone) in prostate cancer]]
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:33 |Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+! style="width: 20%" |Study
+! style="width: 20%" |Dates of enrollment
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |Comparator
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1200/JCO.1994.12.4.689 Moore et al. 1994]
+|NR
+| style="background-color:#91cf61" |Phase 2 (RT)
+| style="background-color:#d3d3d3" |
+| style="background-color:#d3d3d3" |
+|-
+|[https://doi.org/10.1200/JCO.1996.14.6.1756 Tannock et al. 1996 (CCI-NOV22)]
+|1990-1994
+| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
+|[[#Prednisone_monotherapy|Prednisone]]
+| style="background-color:#1a9850" |Superior palliation
+|-
+|[https://www.auajournals.org/doi/abs/10.1016/S0022-5347%2805)64163-8 Berry et al. 2002]
+|1997-1999
+| style="background-color:#1a9851" |Phase 3 (E-esc)
+|[[#Prednisone_monotherapy|Prednisone]]
+| style="background-color:#91cf60" |Seems to have superior TTTF
+|-
+|[https://doi.org/10.1056/NEJMoa041318 Petrylak et al. 2004 (SWOG S9916)]
+|1999-2003
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#Docetaxel_.26_Estramustine|Docetaxel & Estramustine]]
+| style="background-color:#fc8d59" |Seems to have inferior OS
+|-
+| rowspan="2" |[https://doi.org/10.1056/NEJMoa040720 Tannock et al. 2004 (TAX 327)]
+| rowspan="2" |2000-2002
+| rowspan="2" style="background-color:#1a9851" |Phase 3 (C)
+|1. [[#Docetaxel_.26_Prednisone|Weekly Docetaxel & Prednisone]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+|-
+|2. [[#Docetaxel_.26_Prednisone|Every 3-week Docetaxel & Prednisone]]
+| style="background-color:#d73027" |Inferior OS
+|-
+|[https://doi.org/10.1016/S0140-6736(10)61389-X de Bono et al. 2010 (TROPIC)]
+|2007-01-02 to 2008-10-23
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#Cabazitaxel_.26_Prednisone_2|Cabazitaxel & Prednisone]]
+| style="background-color:#d73027" |Inferior OS
+|-
+|}
+<div class="toccolours" style="background-color:#fdcdac">
+====Prior treatment criteria====
+*SWOG S9916: Hormone-independent prostate cancer
+*TAX 327: Disease progression during endocrine therapy, and no prior chemotherapy
+*TROPIC: Previous endocrine therapy, and failure of a docetaxel-containing regimen
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Mitoxantrone (Novantrone)]] 12 mg/m<sup>2</sup> IV over 15 to 30 minutes once on day 1
+====Endocrine therapy====
+*[[Prednisone (Sterapred)]] 10 mg PO once per day on days 1 to 21
+**Some protocols give 5 mg PO twice per day
+'''21-day cycle for up to 10 cycles'''
+</div></div>
+===References===
+#Moore MJ, Osoba D, Murphy K, Tannock IF, Armitage A, Findlay B, Coppin C, Neville A, Venner P, Wilson J. Use of palliative end points to evaluate the effects of mitoxantrone and low-dose prednisone in patients with hormonally resistant prostate cancer. J Clin Oncol. 1994 Apr;12(4):689-94. [https://doi.org/10.1200/JCO.1994.12.4.689 link to original article] [https://pubmed.ncbi.nlm.nih.gov/7512127/ PubMed]
+#'''CCI-NOV22:''' 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. [https://doi.org/10.1200/JCO.1996.14.6.1756 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8656243/ 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. [https://doi.org/10.1200/JCO.1999.17.6.1654 link to original article] [https://pubmed.ncbi.nlm.nih.gov/10561201/ PubMed]
+#Berry W, Dakhil S, Modiano M, Gregurich M, Asmar L. Phase III study of mitoxantrone plus low dose prednisone versus low dose prednisone alone in patients with asymptomatic hormone refractory prostate cancer. J Urol. 2002 Dec;168(6):2439-43. [https://www.auajournals.org/doi/abs/10.1016/S0022-5347%2805)64163-8 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/12441935/ PubMed]
+#'''TAX 327:''' 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. [https://doi.org/10.1056/NEJMoa040720 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15470213/ 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. [https://doi.org/10.1200/jco.2007.12.4008 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18182665/ PubMed]
+#'''SWOG S9916:''' 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. [https://doi.org/10.1056/NEJMoa041318 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15470214/ PubMed] [https://clinicaltrials.gov/study/NCT00004001 NCT00004001]
+#'''TROPIC:''' 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. [https://doi.org/10.1016/S0140-6736(10)61389-X link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20888992/ PubMed] [https://clinicaltrials.gov/study/NCT00417079 NCT00417079]
+=Immunotherapy for metastatic castrate-resistant disease=
+==Ipilimumab & RT {{#subobject:33 |Regimen=1}}==
+Ipilimumab & RT: Ipilimumab & '''<u>R</u>'''adiation '''<u>T</u>'''herapy
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:38 |Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+! style="width: 25%" |Study
+! style="width: 25%" |[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 25%" |[[Levels_of_Evidence#Efficacy|Efficacy]]
+! style="width: 25%" |Patient population
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3707423/ Slovin et al. 2013 (CA184-017)]
+| style="background-color:#91cf61" |Phase 1/2
+|ORR: 4% (95% CI n/a), PSA RR: 16%;
+|Most had ADT, some had docetaxel use. 10 mg/kg cohort reported here.
+|-
+|}
+''Note: Lower doses of ipilimumab including 3 mg/kg (the FDA approved dose) were investigated, but the 10 mg/kg dose was recommended in this study.''
+<div class="toccolours" style="background-color:#b3e2cd">
+====Immunotherapy====
+*[[Ipilimumab (Yervoy)]] 10 mg/kg IV over 90 minutes once on day 1
+====Radiotherapy====
+*[[External_beam_radiotherapy|Radiation therapy]] given focally at a single dose of 800 cGy per target bone lesion for up to three bone lesions per patient, '''given 24 to 48 h before the first ipilimumab dose'''
+'''21-day cycle for 4 cycles'''
+</div></div>
+===References===
+#'''CA184-017:''' 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. Epub 2013 Mar 27. [https://doi.org/10.1093/annonc/mdt107 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3707423/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23535954/ PubMed] [https://clinicaltrials.gov/study/NCT00323882 NCT00323882]
+==Sipuleucel-T monotherapy {{#subobject:32 |Regimen=1}}==
+===Example orders===
+*[[Example orders for Sipuleucel-T (Provenge) in prostate cancer]]
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:37 |Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+! style="width: 20%" |Study
+! style="width: 20%" |Dates of enrollment
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |Comparator
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1200/JCO.2005.04.5252 Small et al. 2006 (D9901)]
+|2000-01 to 2001-10
+| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
+|[[Prostate_cancer_-_null_regimens#Placebo_3|Placebo]]
+| style="background-color:#d9ef8b" |Might have superior TTP (primary endpoint)
+|-
+|[https://doi.org/10.1002/cncr.24429 Higano et al. 2009 (D9902A)]
+|2000-2003
+| style="background-color:#1a9851" |Phase 3 (E-esc)
+|[[Prostate_cancer_-_null_regimens#Placebo_3|Placebo]]
+| style="background-color:#d9ef8b" |Might have superior TTP (primary endpoint)
+|-
+|[https://doi.org/10.1056/NEJMoa1001294 Kantoff et al. 2010 (IMPACT<sub>prostate</sub>)]
+|2003-2007
+| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
+|[[Prostate_cancer_-_null_regimens#Placebo_3|Placebo]]
+| style="background-color:#91cf60" |Seems to have superior OS (primary endpoint)<br>Median OS: 25.8 vs 21.7 mo<br>(HR 0.78, 95% CI 0.61-0.98)
+|-
+|}
+''Note: Higano et al. 2009 was a pooled update but also the first publication to describe results of D9902A. IMPACT should not be confused with the studies of the same name in breast cancer and colorectal cancer.''
+<div class="toccolours" style="background-color:#b3e2cd">
+====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 therapy====
+*[[Acetaminophen (Tylenol)]] PO once per week on weeks 0, 2, 4; 30 minutes prior to sipuleucel-T
+*[[:Category:Antihistamines|Antihistamine]] PO once per week on weeks 0, 2, 4; 30 minutes prior to sipuleucel-T
+'''One course'''
+</div></div>
+===References===
+#'''D9901:''' Small EJ, Schellhammer PF, Higano CS, Redfern CH, Nemunaitis JJ, Valone FH, Verjee SS, Jones LA, Hershberg RM. Placebo-controlled phase III trial of immunologic therapy with sipuleucel-T (APC8015) in patients with metastatic, asymptomatic hormone refractory prostate cancer. J Clin Oncol. 2006 Jul 1;24(19):3089-94. [https://doi.org/10.1200/JCO.2005.04.5252 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16809734/ PubMed] [https://clinicaltrials.gov/study/NCT00005947 NCT00005947]
+##'''Pooled update:''' Higano CS, Schellhammer PF, Small EJ, Burch PA, Nemunaitis J, Yuh L, Provost N, Frohlich MW. Integrated data from 2 randomized, double-blind, placebo-controlled, phase 3 trials of active cellular immunotherapy with sipuleucel-T in advanced prostate cancer. Cancer. 2009 Aug 15;115(16):3670-9. [https://doi.org/10.1002/cncr.24429 link to original article] [https://pubmed.ncbi.nlm.nih.gov/19536890/ PubMed]
+#'''D9902A:''' Higano CS, Schellhammer PF, Small EJ, Burch PA, Nemunaitis J, Yuh L, Provost N, Frohlich MW. Integrated data from 2 randomized, double-blind, placebo-controlled, phase 3 trials of active cellular immunotherapy with sipuleucel-T in advanced prostate cancer. Cancer. 2009 Aug 15;115(16):3670-9. [https://doi.org/10.1002/cncr.24429 link to original article] [https://pubmed.ncbi.nlm.nih.gov/19536890/ PubMed] [https://clinicaltrials.gov/study/NCT01133704 NCT01133704]
+#'''IMPACT:''' 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. [https://doi.org/10.1056/NEJMoa1001294 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20818862/ PubMed] [https://clinicaltrials.gov/study/NCT00065442 NCT00065442]
+#'''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. [http://www.auajournals.org/article/S0022-5347(11)03851-1 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21788048/ PubMed]
+=Radioactive agents for bony metastatic disease=
+==Lutetium Lu 177 vipivotide tetraxetan monotherapy {{#subobject:9ab9ad |Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:03a24b |Variant=1}}===
+{| class="wikitable" style="color:white; background-color:#404040"
+|<small>'''FDA-recommended dose'''</small>
+|-
+|}
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+! style="width: 17%" |Study
+! style="width: 15%" |Dates of enrollment
+! style="width: 17%" |[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 17%" |Comparator
+! style="width: 17%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8446332/ Sartor et al. 2021 (VISION<sub>PrCA</sub>)]
+<!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
+|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-329-1 <span style="color:white;">ESMO-MCBS (4)</span>]'''
+|-
+|} -->
+|2018-06 to 2019-10
+| style="background-color:#1a9851" |Phase 3 (E-RT-switch-ooc)
+|Standard of care (excluding chemotherapy, immunotherapy, or Radium-223)
+| style="background-color:#1a9850" |Superior OS (co-primary endpoint)<br>Median OS: 15.3 vs 11.3 mo<br>(HR 0.62, 95% CI 0.52-0.74)
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Radiotherapy====
+*[[Lutetium Lu 177 vipivotide tetraxetan (Pluvicto)]] 7.4 GBq IV once on day 1
+'''6-week cycles for 6 cycles'''
+</div></div>
+===References===
+# '''TheraP:''' Hofman MS, Emmett L, Sandhu S, Iravani A, Joshua AM, Goh JC, Pattison DA, Tan TH, Kirkwood ID, Ng S, Francis RJ, Gedye C, Rutherford NK, Weickhardt A, Scott AM, Lee ST, Kwan EM, Azad AA, Ramdave S, Redfern AD, Macdonald W, Guminski A, Hsiao E, Chua W, Lin P, Zhang AY, McJannett MM, Stockler MR, Violet JA, Williams SG, Martin AJ, Davis ID; TheraP Trial Investigators and the Australian and New Zealand Urogenital and Prostate Cancer Trials Group. [177Lu]Lu-PSMA-617 versus cabazitaxel in patients with metastatic castration-resistant prostate cancer (TheraP): a randomised, open-label, phase 2 trial. Lancet. 2021 Feb 27;397(10276):797-804. Epub 2021 Feb 11. [https://doi.org/10.1016/s0140-6736(21)00237-3 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33581798/ PubMed] [https://clinicaltrials.gov/study/NCT03392428 NCT03392428]
+##'''Update:''' Hofman MS, Emmett L, Sandhu S, Iravani A, Buteau JP, Joshua AM, Goh JC, Pattison DA, Tan TH, Kirkwood ID, Ng S, Francis RJ, Gedye C, Rutherford NK, Weickhardt A, Scott AM, Lee ST, Kwan EM, Azad AA, Ramdave S, Redfern AD, Macdonald W, Guminski A, Hsiao E, Chua W, Lin P, Zhang AY, Stockler MR, Williams SG, Martin AJ, Davis ID; TheraP Trial Investigators and the Australian and New Zealand Urogenital and Prostate Cancer Trials Group. Overall survival with [177Lu]Lu-PSMA-617 versus cabazitaxel in metastatic castration-resistant prostate cancer (TheraP): secondary outcomes of a randomised, open-label, phase 2 trial. Lancet Oncol. 2024 Jan;25(1):99-107. Epub 2023 Nov 30. [https://doi.org/10.1016/s1470-2045(23)00529-6 link to original article] [https://pubmed.ncbi.nlm.nih.gov/38043558/ PubMed]
+#'''VISION<sub>PrCA</sub>:''' Sartor O, de Bono J, Chi KN, Fizazi K, Herrmann K, Rahbar K, Tagawa ST, Nordquist LT, Vaishampayan N, El-Haddad G, Park CH, Beer TM, Armour A, Pérez-Contreras WJ, DeSilvio M, Kpamegan E, Gericke G, Messmann RA, Morris MJ, Krause BJ; VISION Investigators. Lutetium-177-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer. N Engl J Med. 2021 Sep 16;385(12):1091-1103. Epub 2021 Jun 23. [https://doi.org/10.1056/nejmoa2107322 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8446332/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34161051/ PubMed] [https://clinicaltrials.gov/study/NCT03511664 NCT03511664]
+##'''HRQoL analysis:''' Fizazi K, Herrmann K, Krause BJ, Rahbar K, Chi KN, Morris MJ, Sartor O, Tagawa ST, Kendi AT, Vogelzang N, Calais J, Nagarajah J, Wei XX, Koshkin VS, Beauregard JM, Chang B, Ghouse R, DeSilvio M, Messmann RA, de Bono J. Health-related quality of life and pain outcomes with [177Lu]Lu-PSMA-617 plus standard of care versus standard of care in patients with metastatic castration-resistant prostate cancer (VISION): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2023 Jun;24(6):597-610. [https://doi.org/10.1016/s1470-2045(23)00158-4 link to original article] [https://pubmed.ncbi.nlm.nih.gov/37269841/ PubMed]
+==Radium-223 monotherapy {{#subobject:35 |Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #1 {{#subobject:40 |Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+! style="width: 17%" |Study
+! style="width: 15%" |Dates of enrollment
+! style="width: 17%" |[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 17%" |Comparator
+! style="width: 17%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 17%" |[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 |-
-|[[#top|back to top]]
+|[https://doi.org/10.1056/NEJMoa1213755 Parker et al. 2013 (ALSYMPCA)]
-|}
+<!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
-===Regimen variant #1 {{#subobject:40 |Variant=1}}===
+|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-97-1 <span style="color:white;">ESMO-MCBS (5)</span>]'''
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
-! style="width: 17%" |Study
-! style="width: 15%" |Years of enrollment
-! style="width: 17%" |[[Levels_of_Evidence#Evidence|Evidence]]
-! style="width: 17%" |Comparator
-! style="width: 17%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-! style="width: 17%" |[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 |-
-|[https://www.nejm.org/doi/full/10.1056/NEJMoa1213755 Parker et al. 2013 (ALSYMPCA)]
+|} -->
 |2008-2011
-| style="background-color:#1a9851" |Phase III (E-RT-esc)
+| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
 |[[Prostate_cancer_-_null_regimens#Placebo_3|Placebo]]
-| style="background-color:#1a9850" |Superior OS
+| style="background-color:#1a9850" |Superior OS (primary endpoint)<br>Median OS: 14 vs 11.2 mo<br>(HR 0.70, 95% CI 0.55-0.88)
 | style="background-color:#1a9850" |Superior EQ-5D score
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Radiotherapy====
 *[[Radium-223 (Xofigo)]] 50 kBq/kg IV once on day 1
 '''28-day cycle for 6 cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
 ===Regimen variant #2 {{#subobject:41 |Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 ! style="width: 20%" |Study
-! style="width: 20%" |Years of enrollment
+! style="width: 20%" |Dates of enrollment
 ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 ! style="width: 20%" |Comparator
 ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(07)70147-X/abstract Nilsson et al. 2007]
+|[https://doi.org/10.1016/S1470-2045(07)70147-X Nilsson et al. 2007]
 |2004-2005
-| style="background-color:#1a9851" |Randomized Phase II (E-esc)
+| style="background-color:#1a9851" |Randomized Phase 2 (E-esc)
 |[[Prostate_cancer_-_null_regimens#Placebo_3|Placebo]]
-| style="background-color:#d9ef8b" |Might have superior OS
+| style="background-color:#d9ef8b" |Might have superior OS (secondary endpoint)
 |-
 |}
-''Patients in the study had "bone pain needing EBRT" (external beam radiation therapy). Treatment with radium 223 began within 7 days after EBRT.''
+''Note: Patients in the study had "bone pain needing EBRT" (external beam radiation therapy). Treatment with radium 223 began within 7 days after EBRT.''
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Radiotherapy====
 *[[Radium-223 (Xofigo)]] 50 kBq/kg IV once on day 1
 '''28-day cycle for 4 cycles'''
+</div></div>
 ===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. [https://doi.org/10.1016/S1470-2045(07)70147-X link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17544845/ PubMed]
-#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. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(07)70147-X/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17544845 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. [https://doi.org/10.1016/j.clgc.2012.07.002 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23021204/ 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. [http://www.clinical-genitourinary-cancer.com/article/S1558-7673(12)00168-1/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23021204 PubMed]
 <!--
 # Chris Parker, Sten Nilsson, Daniel Heinrich, Joe M. O'Sullivan, Sophie D. Fossa, Ales Chodacki, Pawel J. Wiechno, John P. Logue, Mihalj Seke, Anders Widmark, Dag Clement Johannessen, Peter Hoskin, David Bottomley, Robert Edward Coleman, Nicholas J. Vogelzang, C. Gillies O'Bryan-Tear, Jose E. Garcia-Vargas, Minghua Shan, A. Oliver Sartor. Updated analysis of the phase III, double-blind, randomized, multinational study of radium-223 chloride in castration-resistant prostate cancer (CRPC) patients with bone metastases (ALSYMPCA). 2012 ASCO Annual Meeting Abstract LBA4512. [http://meetinglibrary.asco.org/content/95649-114 link to abstract] [http://meetinglibrary.asco.org/content/74842 link to oral abstract session]
@@ Line 3,915: / Line 4,376: @@
 # Nicholas J. Vogelzang, Chris Parker, Sten Nilsson, Robert Edward Coleman, C. Gillies O'Bryan-Tear, Minghua Shan, A. Oliver Sartor. Updated analysis of radium-223 dichloride (Ra-223) impact on skeletal-related events (SRE) in patients with castration-resistant prostate cancer (CRPC) and bone metastases from the phase III randomized trial (ALSYMPCA). 2013 ASCO Genitourinary Cancers Symposium Abstract 11. [https://meetinglibrary.asco.org/content/107117-134 link to abstract]
 # Sten Nilsson, A. Oliver Sartor, Oyvind S. Bruland, Fang Fang, Anne-Kirsti Aksnes, Chris Parker. Pain analysis from the phase III randomized ALSYMPCA study with radium-223 dichloride (Ra-223) in patients with castration-resistant prostate cancer (CRPC) with bone metastases. 2013 ASCO Genitourinary Cancers Symposium Abstract 19. [http://meetinglibrary.asco.org/content/107297-134 link to abstract]
-# '''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. [http://www.clinical-genitourinary-cancer.com/article/S1558-7673(12)00168-1/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23021204 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. [https://doi.org/10.1016/j.clgc.2012.07.002 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23021204/ PubMed]
 -->
-#'''ALSYMPCA:''' 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. [https://www.nejm.org/doi/full/10.1056/NEJMoa1213755 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23863050 PubMed]
+#'''ALSYMPCA:''' 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. [https://doi.org/10.1056/NEJMoa1213755 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23863050/ PubMed] [https://clinicaltrials.gov/study/NCT00699751 NCT00699751]
-##'''Subgroup analysis:''' Sartor O, Coleman R, Nilsson S, Heinrich D, Helle SI, O'Sullivan JM, Fosså SD, Chodacki A, Wiechno P, Logue J, Widmark A, Johannessen DC, Hoskin P, James ND, Solberg A, Syndikus I, Vogelzang NJ, O'Bryan-Tear CG, Shan M, Bruland ØS, Parker C. Effect of radium-223 dichloride on symptomatic skeletal events in patients with castration-resistant prostate cancer and bone metastases: results from a phase 3, double-blind, randomised trial. Lancet Oncol. 2014 Jun;15(7):738-46. Epub 2014 May 13. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70183-4/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/24836273 PubMed]
+##'''Subgroup analysis:''' Sartor O, Coleman R, Nilsson S, Heinrich D, Helle SI, O'Sullivan JM, Fosså SD, Chodacki A, Wiechno P, Logue J, Widmark A, Johannessen DC, Hoskin P, James ND, Solberg A, Syndikus I, Vogelzang NJ, O'Bryan-Tear CG, Shan M, Bruland ØS, Parker C. Effect of radium-223 dichloride on symptomatic skeletal events in patients with castration-resistant prostate cancer and bone metastases: results from a phase 3, double-blind, randomised trial. Lancet Oncol. 2014 Jun;15(7):738-46. Epub 2014 May 13. [https://doi.org/10.1016/S1470-2045(14)70183-4 link to original article] [https://pubmed.ncbi.nlm.nih.gov/24836273/ PubMed]
-##'''Subgroup analysis:''' Hoskin P, Sartor O, O'Sullivan JM, Johannessen DC, Helle SI, Logue J, Bottomley D, Nilsson S, Vogelzang NJ, Fang F, Wahba M, Aksnes AK, Parker C. 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. Lancet Oncol. 2014 Nov;15(12):1397-406. Epub 2014 Oct 17. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2814%2970474-7/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/25439694 PubMed]
+##'''Subgroup analysis:''' Hoskin P, Sartor O, O'Sullivan JM, Johannessen DC, Helle SI, Logue J, Bottomley D, Nilsson S, Vogelzang NJ, Fang F, Wahba M, Aksnes AK, Parker C. 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. Lancet Oncol. 2014 Nov;15(12):1397-406. Epub 2014 Oct 17. [https://doi.org/10.1016/S1470-2045%2814%2970474-7 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25439694/ PubMed]
-##'''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. [https://doi.org/10.1093/annonc/mdw065 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4843190/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/26912557 PubMed]
+##'''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. [https://doi.org/10.1093/annonc/mdw065 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4843190/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26912557/ PubMed]
 ==Samarium-153 monotherapy {{#subobject:36 |Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
+<div class="toccolours" style="background-color:#eeeeee">
-|-
-|[[#top|back to top]]
-|}
 ===Regimen {{#subobject:42 |Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 ! style="width: 20%" |Study
-! style="width: 20%" |Years of enrollment
+! style="width: 20%" |Dates of enrollment
 ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 ! style="width: 20%" |Comparator
 ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.ejcancer.com/article/S0959-8049(97)00155-X/pdf Resche et al. 1997]
+|[https://doi.org/10.1016/s0959-8049(97)00155-x Resche et al. 1997]
 |NR
-| style="background-color:#1a9851" |Phase III (E-esc)
+| style="background-color:#1a9851" |Phase 3 (E-esc)
 |[[#Samarium-153_monotherapy|Samarium-153]]; 0.5 mCi/kg
 | 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]
+|[https://doi.org/10.1016/j.urology.2004.01.034 Sartor et al. 2004]
 |NR
-| style="background-color:#1a9851" |Phase III (E-esc)
+| style="background-color:#1a9851" |Phase 3 (E-esc)
-|Samarium-152 (non-radioactive)
+|[[Prostate_cancer_-_null_regimens#Placebo_3|Samarium-152 (non-radioactive)]]
 | style="background-color:#91cf60" |Seems to have superior pain control at week 4
 |-
 |}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Radiotherapy====
 *[[Samarium-153 (Quadramet)]] 1 mCi/kg IV over 1 minute once on day 1
+====Supportive therapy====
-====Supportive medications====
 *1000 mL of fluid IV or PO given twice, 4 hours before and 6 hours after treatment
 '''1 dose'''
+</div></div>
 ===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. [https://doi.org/10.1016/s0959-8049(97)00155-x link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/9389919/ PubMed]
-#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. [https://www.ejcancer.com/article/S0959-8049(97)00155-X/pdf link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/9389919 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. [https://doi.org/10.1016/j.urology.2004.01.034 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15134985/ 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. [http://www.goldjournal.net/article/S0090-4295%2804%2900143-8/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15134985 PubMed]
 =Measuring disease progression=
+*Criteria used for disease progression in prostate cancer clinical trials, Prostate Cancer Clinical Trials Working Group 2 (PCWG2):<ref>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. [https://doi.org/10.1200/jco.2007.12.4487 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4010133/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/18309951/ PubMed]</ref>
-*Criteria used for disease progression in prostate cancer clinical trials, Prostate Cancer Clinical Trials Working Group 2 (PCWG2):<ref>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. [https://doi.org/10.1200/jco.2007.12.4487 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4010133/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/18309951 PubMed]</ref>
 **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)<ref>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. [http://www.goldjournal.net/article/S0090-4295%2800%2900793-7/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/11113751 PubMed]</ref>
+***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)<ref>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. [https://doi.org/10.1016/s0090-4295(00)00793-7 link to original article] [https://pubmed.ncbi.nlm.nih.gov/11113751/ PubMed]</ref>
 **PSA rise
 ***Starting PSA of at least 2 ng/mL
@@ Line 3,983: / Line 4,435: @@
 ***"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.
 =Statistics=
+*[http://jama.jamanetwork.com/article.aspx?articleid=198392 Four-Year Actuarial Progression-Free Probability (PFP) After Salvage Radiotherapy based on Gleason score, PSA, positive margins, etc.]<ref>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. [http://jama.jamanetwork.com/article.aspx?articleid=198392 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15026399/ PubMed]</ref> (flowchart is in Figure 2)
-*[http://jama.jamanetwork.com/article.aspx?articleid=198392 Four-Year Actuarial Progression-Free Probability (PFP) After Salvage Radiotherapy based on Gleason score, PSA, positive margins, etc.]<ref>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. [http://jama.jamanetwork.com/article.aspx?articleid=198392 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/15026399 PubMed]</ref> (flowchart is in Figure 2)
 *[http://seer.cancer.gov/statfacts/html/prost.html SEER Stat Fact Sheets: Prostate Cancer]
 *[http://www.cdc.gov/CANCER/prostate/statistics/ CDC Prostate Cancer Statistics]
 *[http://www.cancer.net/cancer-types/prostate-cancer/statistics Cancer.Net Prostate Cancer Statistics]
 =Links=
 *[http://genomedx.com/decipher-test/ 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)."
@@ Line 4,005: / Line 4,453: @@
 *[https://www.roswellpark.org/apps/prostate_cancer_estimator/ 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]
 *[http://urology.ucsf.edu/research/cancer/prostate-cancer-risk-assessment-and-the-ucsf-capra-score UCSF-CAPRA score]
+*[https://www.hemeoncnotes.com/oncology/introdcutory-lectures-hdrl7-b26ry-e5lyb-ldhb6 Heme Onc Notes GU page]
 =Quality of life assessment tools=
 *[http://www.bidmc.org/~/media/Files/Centers%20and%20Departments/CancerCenter/prostateCancer/EPIC%20CP.pdf EPIC-CP: Expanded Prostate Cancer Index Composite for Clinical Practice] ([http://www.bidmc.org/epic twice per dayMC])
 *[http://www.oregonurology.com/pdfs/aua-symptom-score.pdf AUA Symptom Score (OR)] [//hemonc.org/w/images/1/1c/AUA-Symptom-Score_OR.pdf (local backup)]; [http://www.purclinic.com/wp-content/uploads/2014/05/AUA-Symptom-Score.pdf AUA Symptom Score (UCF)] [//hemonc.org/w/images/b/b0/AUA-Symptom-Score.pdf (local backup)]. Also known as International Prostate Symptom Score (I-PSS/IPSS) or AUASS
 =References=
 <references />
 [[Category:Prostate cancer regimens]]
 [[Category:Disease-specific pages]]
-[[Category:Genitourinary cancers]]
+[[Category:Male genital cancers]]

Difference between revisions of "Prostate cancer"

Latest revision as of 01:28, 26 June 2024

Living Interactive Systematic Reviews

Guidelines

ASCO

ASCO & CCO

AUA

AUA/ASCO/SUO

ASTRO/ASCO/AUA

EAU/ESTRO/SIOG

ESMO

NCCN

SIOG

SITC

St Gallen

Induction ADT

ADT

Regimen

Endocrine therapy

Subsequent treatment

References

Bicalutamide & Goserelin

Regimen

Endocrine therapy

Subsequent treatment

References

Degarelix monotherapy

Regimen

Endocrine therapy

Subsequent treatment

References

Flutamide & Goserelin

Regimen

Endocrine therapy

Subsequent treatment

References

Leuprolide monotherapy

Regimen

Endocrine therapy

Subsequent treatment

References

Definitive therapy, including active surveillance

Active surveillance

Regimen

References

ADT

Regimen

Endocrine therapy

References

ADT & RT

Regimen

Preceding treatment

Endocrine therapy

Radiotherapy

Subsequent treatment

References

Flutamide, Goserelin, RT

Regimen

Endocrine therapy

Radiotherapy

Subsequent treatment

References

Flutamide, Leuprolide, RT

Regimen variant #1, 4 months of ADT

Endocrine therapy

Radiotherapy

Regimen variant #2, 3 years of ADT

Endocrine therapy

Radiotherapy

Regimen variant #3, indefinite ADT, monthly leuprolide

Endocrine therapy

Radiotherapy

Regimen variant #4, indefinite ADT, 3-monthly leuprolide

Endocrine therapy

Radiotherapy

References

Goserelin & RT

Regimen

Endocrine therapy

Radiotherapy