Difference between revisions of "Staging page"

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[[#top|Back to Top]]
 
[[#top|Back to Top]]
 
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The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only. As a general rule, this includes the inferior arm(s) of a randomized study, unless said regimens continue to be recommended by trustworthy sources such as the [http://www.nccn.org/professionals/physician_gls/f_guidelines.asp NCCN Guidelines]. Is there a regimen missing from this list? See the [[Prostate_cancer|main prostate cancer page]] for current regimens.
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!colspan="2" align="center" style="color:white; font-size:125%; background-color:#de2d26"|'''Section editor'''
 
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|-
 
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|style="background-color:#F0F0F0"|[[File:Sanjay_mohan.png|frameless|upright=0.3|center]]
 
−
|<big>[[User:Sanjaymohan|Sanjay R. Mohan, MD, MSCI]]<br>Vanderbilt University<br>Nashville, TN</big>
 
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{| class="wikitable" style="float:right; margin-right: 5px;"
 
{| class="wikitable" style="float:right; margin-right: 5px;"
 
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|<div style="background-color: #fee0d1; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}" align="right"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Regimen |limit=10000|format=sum}} [[Tutorial#Regimens|regimens]] on this page</b></font></div>
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|<div style="background-color: #fee0d1; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}" align="right"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Regimen |limit=10000|format=sum}} [[Tutorial#Regimens|regimens]] on this page</b></font></div>
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<div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} [[Tutorial#Variants|variants]] on this page</b></font></div>
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<div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} [[Tutorial#Variants|variants]] on this page</b></font></div>
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|}  
 
{{TOC limit|limit=3}}
 
{{TOC limit|limit=3}}
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=Guidelines=
+
=Definitive radiotherapy=
−
==ELN==
+
==Radiation therapy==
−
*'''2011:''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4979120/ Philadelphia-negative classical myeloproliferative neoplasms: critical concepts and management recommendations from European LeukemiaNet]
 
−
==ESMO==
 
−
*'''2015:''' Vannucchi et al. [https://www.esmo.org/Guidelines/Haematological-Malignancies/Philadelphia-Chromosome-Negative-Chronic-Myeloproliferative-Neoplasms Philadelphia chromosome-negative chronic myeloproliferative neoplasms: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up]
 
−
=="How I Treat"==
 
−
*'''2014:''' Vannucchi AM. How I treat polycythemia vera. Blood. 2014 Nov 20;124(22):3212-20. Epub 2014 Oct 2. [http://www.bloodjournal.org/content/124/22/3212.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/25278584 PubMed]
 
−
==[https://www.nccn.org/ NCCN]==
 
−
*[https://www.nccn.org/professionals/physician_gls/pdf/mpn.pdf NCCN Guidelines - Myeloproliferative Neoplasms]
 
−
=First-line therapy=
 
−
==Aspirin monotherapy {{#subobject:5c9446|Regimen=1}}==
 
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:3983e0|Variant=1}}===
+
===Regimen===
 
{| 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%"|Study
Line 36: Line 21:
 
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|[https://doi.org/10.1056/nejmoa035572 Landolfi et al. 2004 (ECLAP)]
+
|[https://doi.org/10.1016/s0360-3016(01)01579-6 Pilepich et al. 2001 (RTOG 86-10)]
−
|1998-2000
+
|1987-1991
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
+
|style="background-color:#1a9851"|Phase 3 (C)
−
|[[#Placebo|Placebo]]
+
|[[Prostate_cancer#Flutamide.2C_Goserelin.2C_RT|Flutamide, Goserelin, RT]]
−
| style="background-color:#91cf60" |Seems to have superior combined outcome
+
|style="background-color:#fc8d59"|Seems to have inferior cause-specific mortality
 +
|-
 +
|[https://doi.org/10.1200/jco.1997.15.3.1013 Pilepich et al. 1997 (RTOG 85-31)]
 +
|1987-1992
 +
|style="background-color:#1a9851"|Phase 3 (C)
 +
|[[Prostate_cancer#Goserelin_.26_RT|Goserelin & RT]]
 +
|style="background-color:#d73027"|Inferior DFS
 +
|-
 +
|[https://doi.org/10.1056/NEJM199707313370502 Bolla et al. 1997 (EORTC 22863)]
 +
|1987-1995
 +
|style="background-color:#1a9851"|Phase 3 (C)
 +
|[[Prostate_cancer#Goserelin_.26_RT|Goserelin & RT]]
 +
|style="background-color:#d73027"|Inferior OS
 +
|-
 +
|[https://doi.org/10.1056/NEJMoa1012348 Jones et al. 2011 (RTOG 94-08)]
 +
|1994-2001
 +
|style="background-color:#1a9851"|Phase 3 (C)
 +
|1. [[Prostate_cancer#Flutamide.2C_Goserelin.2C_RT|Flutamide, Goserelin, RT]]<br>2. [[Prostate_cancer#Flutamide.2C_Leuprolide.2C_RT|Flutamide, Leuprolide, RT]]
 +
|style="background-color:#fc8d59"|Seems to have inferior OS
 +
|-
 +
|[http://jama.ama-assn.org/content/299/3/289.long D'Amico et al. 2008 (DFCI 95-096)]
 +
|1995-2001
 +
|style="background-color:#1a9851"|Randomized (C)
 +
|[[Prostate_cancer#Flutamide.2C_Goserelin.2C_RT|Flutamide, Goserelin, RT]]
 +
|style="background-color:#d73027"|Inferior OS
 +
|-
 +
|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 3 (C)
 +
|1. [[Prostate_cancer#Flutamide.2C_Goserelin.2C_RT|Flutamide & Goserelin x 3 mo, RT]]
 +
|style="background-color:#d73027"|Inferior EFS<sup>1</sup>
 +
|-
 +
|2. [[Prostate_cancer#Flutamide.2C_Goserelin.2C_RT|Flutamide & Goserelin x 6 mo, RT]]
 +
|style="background-color:#d73027"|Inferior OS<sup>1</sup>
 +
|-
 +
|[https://doi.org/10.1002/cncr.30093 McPartlin et al. 2016 (PMH 9907)]
 +
|1999-2006
 +
|style="background-color:#1a9851"|Phase 3 (C)
 +
|[[#Bicalutamide_.26_RT_99|Bicalutamide & RT]]
 +
|style="background-color:#ffffbf"|Did not meet primary endpoint of BFI
 
|-
 
|-
 
|}
 
|}
−
<div class="toccolours" style="background-color:#b3e2cd">
+
''<sup>1</sup>Reported efficacy for TROG 96.01 is based on the 2011 update.''<br>
−
====Anticoagulation====
+
''Demonstrated to be inferior in almost all studies; here for reference purposes only.''
−
*[[Aspirin]] 100 mg PO once per day
+
====Radiotherapy====
−
'''Continued indefinitely'''
+
*[[External beam radiotherapy]] of varying doses (see papers for details)
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# '''ECLAP:''' Landolfi R, Marchioli R, Kutti J, Gisslinger H, Tognoni G, Patrono C, Barbui T; European Collaboration on Low-Dose Aspirin in Polycythemia Vera Investigators. Efficacy and safety of low-dose aspirin in polycythemia vera. N Engl J Med. 2004 Jan 8;350(2):114-24. [https://doi.org/10.1056/nejmoa035572 link to original article] [https://pubmed.ncbi.nlm.nih.gov/14711910 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 dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/9060541 PubMed]
−
==Hydroxyurea monotherapy {{#subobject:511984|Regimen=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. [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:''' 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]
 +
# '''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] NCT00849082
 +
## '''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, 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]
 +
# '''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]
 +
## '''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]
 +
# '''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
 +
## '''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]
 +
# '''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 [http://hemonc.org HemOnc.org] NCT00116220
 +
# '''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] NCT00002597
 +
# '''PMH 9907:''' McPartlin AJ, Glicksman R, Pintilie M, Tsuji D, Mok G, Bayley A, Chung P, Bristow RG, Gospodarowicz MK, Catton CN, Milosevic M, Warde PR. PMH 9907: Long-term outcomes of a randomized phase 3 study of short-term bicalutamide hormone therapy and dose-escalated external-beam radiation therapy for localized prostate cancer. Cancer. 2016 Aug 15;122(16):2595-603. Epub 2016 May 24. [https://doi.org/10.1002/cncr.30093 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27219522 PubMed]
 +
#'''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] 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]
 +
=Hormonal therapy for locally advanced or metastatic disease=
 +
==Castration==
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:84f020|Variant=1}}===
+
===Regimen===
 
{| 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%"|Study
Line 60: Line 99:
 
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|[http://www.bloodjournal.org/content/90/9/3370.long Najean et al. 1997 (FPSG)]
+
|[https://doi.org/10.1016/S0140-6736(85)90739-1 Parmar et al. 1985]
−
|1980-NR
+
|1984-1985
−
|style="background-color:#1a9851"|Phase 3 (E-switch-ic)
+
|style="background-color:#1a9851"|Phase 3 (C)
−
|[[#Pipobroman_monotherapy_88|Pipobroman]]
+
|[[#D-Trp-6-LHRH_monotherapy_77|D-Trp-6-LHRH]]
−
|style="background-color:#1a9850"|Superior OS<sup>1</sup>
+
|style="background-color:#ffffbf"|Seems not superior
 +
|-
 +
|[https://doi.org/10.1016/0090-4295(91)80077-K Soloway et al. 1991]
 +
|NR
 +
|style="background-color:#1a9851"|Phase 3 (C)
 +
|[[Prostate_cancer#Goserelin_monotherapy_2|Goserelin]]
 +
|style="background-color:#ffffbf"|Did not meet efficacy endpoints
 
|-
 
|-
−
|[https://doi.org/10.1056/nejmoa1208500 Marchioli et al. 2012 (CYTO-PV)]
+
|[https://doi.org/10.1002/1097-0142(19931215)72:12+%3C3855::aid-cncr2820721718%3E3.0.co;2-i Robinson 1993 (EORTC 30805)]
−
|2008-2012
+
|1981-1986
−
|style="background-color:#1a9851"|Phase 3 (E-esc)
+
|style="background-color:#1a9851"|Phase 3 (C)
−
|[[#Hydroxyurea_monotherapy|Hydroxyurea]]; less strict hematocrit goal
+
|1. [[#Castration_.26_Cyproterone_acetate_99|Castration & Cyproterone acetate]]<br>2. [[#DES_monotherapy|DES]]
−
|style="background-color:#1a9850"|Superior primary endpont
+
|style="background-color:#ffffbf"|Seems not superior
 
|-
 
|-
−
|[https://doi.org/10.1182/blood.2021012743 Mascarenhas et al. 2022 (MPD-RC 112)]
+
|[https://doi.org/10.1111/j.1464-410X.1991.tb15195.x Kaisary et al. 1991]
−
|2011-2016
+
|1983-1986
 
|style="background-color:#1a9851"|Phase 3 (C)
 
|style="background-color:#1a9851"|Phase 3 (C)
−
|[[#Pegintereron_alfa-2a_monotherapy_99|Peginterferon alfa-2a]]
+
|[[Prostate_cancer#Goserelin_monotherapy_2|Goserelin]]
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of CHR rate
+
|style="background-color:#ffffbf"|Did not meet efficacy endpoints
 
|-
 
|-
−
|[https://doi.org/10.1016/s2352-3026(19)30236-4 Gisslinger et al. 2020 (PROUD-PV)]
+
|[https://doi.org/10.1002/cncr.1990.66.s5.1045 Keuppens et al. 1990 (EORTC 30853)]
−
|2013-2015
+
|1986-1988
 
|style="background-color:#1a9851"|Phase 3 (C)
 
|style="background-color:#1a9851"|Phase 3 (C)
−
|[[#Ropeginterferon_alfa-2b_monotherapy_77|Ropeginterferon alfa-2b]]
+
|[[Prostate_cancer#Flutamide_.26_Goserelin|Flutamide & Goserelin]]
−
| style="background-color:#eeee01" |Seems to have non-inferior composite endpoint
+
|style="background-color:#fc8d59"|Seems to have inferior OS<sup>1</sup>
 +
|-
 +
|[https://doi.org/10.1016/s0022-5347(17)36003-2 Janknegt et al. 1993 (International Anandron Study)]
 +
|1986-NR
 +
|style="background-color:#1a9851"|Phase 3 (C)
 +
|[[Prostate_cancer#Nilutamide_.26_Orchiectomy|Nilutamide & Orchiectomy]]
 +
|style="background-color:#d73027"|Inferior PFS
 +
|-
 +
|[https://doi.org/10.3109/00365599609182309 Bruun et al. 1996]
 +
|NR
 +
|style="background-color:#1a9851"|Phase 3 (C)
 +
|1. [[#Buserelin_monotherapy_77|Buserelin]]<br>2. Estrogens
 +
|style="background-color:#ffffbf"|Seems not superior
 +
|-
 +
|[https://doi.org/10.1200/JCO.2004.11.514 Studer et al. 2004 (SAKK 08/88)]
 +
|1988-1992
 +
|style="background-color:#1a9851"|Phase 3 (C)
 +
|[[#Castration|Orchiectomy]]; deferred
 +
|style="background-color:#ffffbf"|Seems not superior
 +
|-
 +
|[https://www.karger.com/Article/Abstract/480795 Boccon-Gibod et al. 1997]
 +
|1989-1991
 +
|style="background-color:#1a9851"|Phase 3 (C)
 +
|[[Prostate_cancer#Flutamide_monotherapy|Flutamide]]
 +
|style="background-color:#ffffbf"|Seems not superior
 +
|-
 +
|[https://www.karger.com/Article/Abstract/19547 de Voogt et al. 1998 (EORTC 30843)]
 +
|NR in abstract
 +
|style="background-color:#1a9851"|Phase 3 (C)
 +
|[[#Buserelin_.26_Cyproterone_acetate_77|Buserelin & Cyproterone acetate]]
 +
|style="background-color:#ffffbf"|Seems not superior
 +
|-
 +
|[https://doi.org/10.1056/NEJM199810083391504 Eisenberger et al. 1998]
 +
|1989-1994
 +
|style="background-color:#1a9851"|Phase 3 (C)
 +
|[[#Flutamide_.26_Orchiectomy_99|Flutamide & Orchiectomy]]
 +
|style="background-color:#ffffbf"|Seems not superior
 +
|-
 +
|[https://www.karger.com/Article/Abstract/19634 Tyrrell et al. 1998]
 +
|NR in abstract
 +
|style="background-color:#1a9851"|Phase 3 (C)
 +
|[[Prostate_cancer#Bicalutamide_monotherapy|Bicalutamide]]
 +
| style="background-color:#ffffbf" |Seems not superior<sup>2</sup>
 +
|-
 +
|[https://www.auajournals.org/doi/full/10.1016/S0022-5347%2805)68191-8 de Reijke et al. 1999]
 +
|1990-1995
 +
|style="background-color:#1a9851"|Phase 3 (C)
 +
|[[#Mitomycin_.26_Orchiectomy_99|Mitomycin & Orchiectomy]]
 +
|style="background-color:#ffffbf"|Seems not superior
 +
|-
 +
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3864402/ Millikan et al. 2008 (MDA DM95-231)]
 +
|1996-2003
 +
|style="background-color:#1a9851"|Phase 3 (C)
 +
|[[#ADT_.26_KA.2FVE_99|ADT & KA/VE]]
 +
|style="background-color:#ffffbf"|Seems not superior
 +
|-
 +
|}
 +
''<sup>1</sup>Reported efficacy for EORTC 30853 is based on the 1998 final update.''<br>
 +
''<sup>2</sup>Reported efficacy for Tyrrell et al. 1998 is based on the 2000 update.''<br>
 +
''No longer widely used as monotherapy in the United States; included for reference purposes only.''
 +
====Endocrine therapy====
 +
*[[Endocrine_ablation_surgery#Bilateral_orchiectomy|Bilateral orchiectomy]]
 +
</div></div>
 +
===References===
 +
# Parmar H, Phillips RH, Lightman SL, Edwards L, Allen L, Schally AV. Randomised controlled study of orchidectomy vs long-acting D-Trp-6-LHRH microcapsules in advanced prostatic carcinoma. Lancet. 1985 Nov 30;2(8466):1201-5. [https://doi.org/10.1016/S0140-6736(85)90739-1 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2866289 PubMed]
 +
#'''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]
 +
##'''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]
 +
##'''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]
 +
# 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]
 +
# '''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]
 +
# '''EORTC 30805:''' Robinson MR. A further analysis of European Organization for Research and Treatment of Cancer protocol 30805: orchidectomy versus orchidectomy plus cyproterone acetate versus low-dose diethylstilbestrol. Cancer. 1993 Dec 15;72(12 Suppl):3855-7. [https://doi.org/10.1002/1097-0142(19931215)72:12+%3C3855::aid-cncr2820721718%3E3.0.co;2-i link to original article] [https://pubmed.ncbi.nlm.nih.gov/8252503 PubMed]
 +
## '''Update:''' Robinson MR, Smith PH, Richards B, Newling DW, de Pauw M, Sylvester R. The final analysis of the EORTC Genito-Urinary Tract Cancer Co-Operative Group phase III clinical trial (protocol 30805) comparing orchidectomy, orchidectomy plus cyproterone acetate and low dose stilboestrol in the management of metastatic carcinoma of the prostate. Eur Urol. 1995;28(4):273-83. [https://www.karger.com/Article/Abstract/475067 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8575493 PubMed]
 +
# Bruun E, Frimodt-Møller C; Danish Buserelin Study Group. The effect of Buserelin versus conventional antiandrogenic treatment in patients with T2-4NXM1 prostatic cancer; A prospective, randomized multicentre phase III trial. Scand J Urol Nephrol. 1996 Aug;30(4):291-7. [https://doi.org/10.3109/00365599609182309 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8908651 PubMed]
 +
# 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 dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/9412794 PubMed]
 +
# '''EORTC 30843:''' de Voogt HJ, Studer U, Schröder FH, Klijn JG, de Pauw M, Sylvester R; [[Study_Groups#EORTC|EORTC]] Genito-Urinary Tract Cancer Cooperative Group. Maximum androgen blockade using LHRH agonist buserelin in combination with short-term (two weeks) or long-term (continuous) cyproterone acetate is not superior to standard androgen deprivation in the treatment of advanced prostate cancer: final analysis of EORTC GU Group Trial 30843. Eur Urol. 1998;33(2):152-8. [https://www.karger.com/Article/Abstract/19547 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9519356 PubMed]
 +
# Eisenberger MA, Blumenstein BA, Crawford ED, Miller G, McLeod DG, Loehrer PJ, Wilding G, Sears K, Culkin DJ, Thompson IM Jr, Bueschen AJ, Lowe BA. Bilateral orchiectomy with or without flutamide for metastatic prostate cancer. N Engl J Med. 1998 Oct 8;339(15):1036-42. [https://doi.org/10.1056/NEJM199810083391504 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9761805 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 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://www.auajournals.org/article/S0022-5347(05)67032-2 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/11025708 PubMed]
 +
# de Reijke TM, Keuppens FI, Whelan P, Kliment J, Robinson MR, Rea LA, Sylvester RJ; European Organisation for Research in Cancer Therapy Genitourinary Group. Orchiectomy and orchiectomy plus mitomycin C for metastatic prostate cancer in patients with poor prognosis: the final results of a European Organisation for Research in Cancer Therapy Genitourinary Group trial. J Urol. 1999 Nov;162(5):1658-64. [https://www.auajournals.org/doi/full/10.1016/S0022-5347%2805)68191-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/10524892 PubMed]
 +
# '''SAKK 08/88:''' Studer UE, Hauri D, Hanselmann S, Chollet D, Leisinger HJ, Gasser T, Senn E, Trinkler FB, Tscholl RM, Thalmann GN, Dietrich D. Immediate versus deferred hormonal treatment for patients with prostate cancer who are not suitable for curative local treatment: results of the randomized trial SAKK 08/88. J Clin Oncol. 2004 Oct 15;22(20):4109-18. Erratum in: J Clin Oncol. 2005 Feb 1;23(4):936. [https://doi.org/10.1200/JCO.2004.11.514 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15483020 PubMed]
 +
# '''MDA DM95-231:''' Millikan RE, Wen S, Pagliaro LC, Brown MA, Moomey B, Do KA, Logothetis CJ. Phase III trial of androgen ablation with or without three cycles of systemic chemotherapy for advanced prostate cancer. J Clin Oncol. 2008 Dec 20;26(36):5936-42. Epub 2008 Nov 24. [https://doi.org/10.1200/JCO.2007.15.9830 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3864402/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19029421 PubMed] NCT00002855
 +
# '''ECOG E8892:''' NCT00002881
 +
==Cortisone monotherapy {{#subobject:7b59ef |Regimen=1}}==
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:4f90a2 |Variant=1}}===
 +
{| class="wikitable" style="width: 40%; text-align:center;"
 +
!style="width: 25%"|Study
 +
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
|-
 +
|[https://doi.org/10.1016/s0022-5347(17)67614-6 Miller & Hinman 1954]
 +
|style="background-color:#91cf61"|Non-randomized
 
|-
 
|-
 
|}
 
|}
−
''<sup>1</sup>Reported efficacy for FPSG is based on the 2011 update.''<br>
 
−
''Note: The following is the approach recommended by Vannucchi in How I Treat (2014).''
 
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
−
====Chemotherapy====
+
====Endocrine therapy====
−
*[[Hydroxyurea (Hydrea)]] 500 mg PO twice per day, with titration based on the target hematocrit and hematologic toxicity
+
*[[Cortisone]]
−
====Supportive therapy====
 
−
*[[Aspirin]] 81 to 100 mg PO once per day, depending on the study
 
−
'''Continued indefinitely'''
 
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# '''FPSG:''' Najean Y, Rain JD. Treatment of polycythemia vera: the use of hydroxyurea and pipobroman in 292 patients under the age of 65 years. Blood. 1997 Nov 1;90(9):3370-7. [http://www.bloodjournal.org/content/90/9/3370.long link to original article] [https://pubmed.ncbi.nlm.nih.gov/9345019 PubMed]
+
# Miller GM, Hinman F Jr. Cortisone treatment in advanced carcinoma of the prostate. J Urol. 1954 Sep;72(3):485-96. [https://doi.org/10.1016/s0022-5347(17)67614-6 link to original article] [https://pubmed.ncbi.nlm.nih.gov/13202237 PubMed]
−
## '''Update:''' Kiladjian JJ, Chevret S, Dosquet C, Chomienne C, Rain JD. Treatment of polycythemia vera with hydroxyurea and pipobroman: final results of a randomized trial initiated in 1980. J Clin Oncol. 2011 Oct 10;29(29):3907-13. Epub 2011 Sep 12. [https://doi.org/10.1200/JCO.2011.36.0792 link to original article] [https://pubmed.ncbi.nlm.nih.gov/21911721 PubMed]
+
==Cyproterone acetate monotherapy {{#subobject:785019 |Regimen=1}}==
−
# '''CYTO-PV:''' Marchioli R, Finazzi G, Specchia G, Cacciola R, Cavazzina R, Cilloni D, De Stefano V, Elli E, Iurlo A, Latagliata R, Lunghi F, Lunghi M, Marfisi RM, Musto P, Masciulli A, Musolino C, Cascavilla N, Quarta G, Randi ML, Rapezzi D, Ruggeri M, Rumi E, Scortechini AR, Santini S, Scarano M, Siragusa S, Spadea A, Tieghi A, Angelucci E, Visani G, Vannucchi AM, Barbui T; CYTO-PV Collaborative Group. Cardiovascular events and intensity of treatment in polycythemia vera. N Engl J Med. 2013 Jan 3;368(1):22-33. Epub 2012 Dec 8. [https://doi.org/10.1056/nejmoa1208500 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23216616 PubMed] NCT01645124
 
−
# '''PROUD-PV:''' Gisslinger H, Klade C, Georgiev P, Krochmalczyk D, Gercheva-Kyuchukova L, Egyed M, Rossiev V, Dulicek P, Illes A, Pylypenko H, Sivcheva L, Mayer J, Yablokova V, Krejcy K, Grohmann-Izay B, Hasselbalch HC, Kralovics R, Kiladjian JJ; PROUD-PV Study Group. Ropeginterferon alfa-2b versus standard therapy for polycythaemia vera (PROUD-PV and CONTINUATION-PV): a randomised, non-inferiority, phase 3 trial and its extension study. Lancet Haematol. 2020 Mar;7(3):e196-e208. Epub 2020 Jan 31. [https://doi.org/10.1016/s2352-3026(19)30236-4 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32014125 PubMed] NCT01949805
 
−
# '''MPD-RC 112:''' Mascarenhas J, Kosiorek HE, Prchal JT, Rambaldi A, Berenzon D, Yacoub A, Harrison CN, McMullin MF, Vannucchi AM, Ewing J, O'Connell CL, Kiladjian JJ, Mead AJ, Winton EF, Leibowitz DS, De Stefano V, Arcasoy MO, Kessler CM, Catchatourian R, Rondelli D, Silver RT, Bacigalupo A, Nagler A, Kremyanskaya M, Levine MF, Arango Ossa JE, McGovern E, Sandy L, Salama ME, Najfeld V, Tripodi J, Farnoud N, Penson AV, Weinberg RS, Price L, Goldberg JD, Barbui T, Marchioli R, Tognoni G, Rampal RK, Mesa RA, Dueck AC, Hoffman R. A randomized phase 3 trial of interferon-α vs hydroxyurea in polycythemia vera and essential thrombocythemia. Blood. 2022 May 12;139(19):2931-2941. [https://doi.org/10.1182/blood.2021012743 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/35007321/ PubMed] NCT01259856
 
−
==Placebo==
 
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen===
+
===Regimen {{#subobject:e1ee02 |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%"|Study
Line 110: Line 241:
 
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|[https://doi.org/10.1056/nejmoa035572 Landolfi et al. 2004 (ECLAP)]
+
|[https://doi.org/10.1111/j.1464-410X.1980.tb02961.x Jacobi et al. 1980]
−
|1998-2000
+
|NR
 +
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 +
|[[#Estradiol_undecylate_monotherapy_88|Estradiol undecylate]]
 +
| style="background-color:#91cf60" |Seems to have superior ORR
 +
|-
 +
|rowspan=2|[https://doi.org/10.1016/s0022-5347(17)44996-2 Pavone-Macaluso et al. 1986 (EORTC 30761)]
 +
|rowspan=2|1977-1981
 +
|rowspan=2 style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 +
|1. [[#DES_monotherapy|DES]]
 +
| style="background-color:#ffffbf" |Seems not superior
 +
|-
 +
|2. [[#Medroxyprogesterone_monotherapy_88|MPA]]
 +
| style="background-color:#91cf60" |Seems to have superior OS
 +
|-
 +
|[https://doi.org/10.1016/S0090-4295(98)00129-0 Debruyne et al. 1998]
 +
|1992-1994
 
| style="background-color:#1a9851" |Phase 3 (C)
 
| style="background-color:#1a9851" |Phase 3 (C)
−
|[[#Aspirin_monotherapy|Aspirin]]
+
|[[#Liarozole_monotherapy_77|Liarozole]]
−
| style="background-color:#fc8d59" |Seems to have inferior combined outcome
+
| style="background-color:#ffffbf" |Seems not superior
 
|-
 
|-
 
|}
 
|}
−
''No active treatment.''
+
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Endocrine therapy====
 +
*[[Cyproterone acetate (Androcur)]]
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# '''ECLAP:''' Landolfi R, Marchioli R, Kutti J, Gisslinger H, Tognoni G, Patrono C, Barbui T; European Collaboration on Low-Dose Aspirin in Polycythemia Vera Investigators. Efficacy and safety of low-dose aspirin in polycythemia vera. N Engl J Med. 2004 Jan 8;350(2):114-24. [https://doi.org/10.1056/nejmoa035572 link to original article] [https://pubmed.ncbi.nlm.nih.gov/14711910 PubMed]
+
# Jacobi GH, Altwein JE, Kurth KH, Basting R, Hohenfellner R. Treatment of advanced prostatic cancer with parenteral cyproterone acetate: a phase III randomised trial. Br J Urol. 1980 Jun;52(3):208-15. [https://doi.org/10.1111/j.1464-410X.1980.tb02961.x link to original article] [https://pubmed.ncbi.nlm.nih.gov/7000222 PubMed]
−
==Ropeginterferon alfa-2b monotherapy {{#subobject:5kgix4|Regimen=1}}==
+
# '''EORTC 30761:''' Pavone-Macaluso M, de Voogt HJ, Viggiano G, Barasolo E, Lardennois B, de Pauw M, Sylvester R. Comparison of diethylstilbestrol, cyproterone acetate and medroxyprogesterone acetate in the treatment of advanced prostatic cancer: final analysis of a randomized phase III trial of the European Organisation for Research on Treatment of Cancer Urological Group. J Urol. 1986 Sep;136(3):624-31. [https://doi.org/10.1016/s0022-5347(17)44996-2 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2942707 PubMed]
 +
# Debruyne FJ, Murray R, Fradet Y, Johansson JE, Tyrrell C, Boccardo F, Denis L, Marberger JM, Brune D, Rassweiler J, Vangeneugden T, Bruynseels J, Janssens M, De Porre P; Liarozole Study Group. Liarozole--a novel treatment approach for advanced prostate cancer: results of a large randomized trial versus cyproterone acetate. Urology. 1998 Jul;52(1):72-81. [https://doi.org/10.1016/S0090-4295(98)00129-0 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9671874 PubMed]
 +
==DES monotherapy {{#subobject:0a1860|Regimen=1}}==
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:cob120|Variant=1}}===
+
===Regimen {{#subobject:128a40|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%"|Study
Line 131: Line 281:
 
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|[https://doi.org/10.1016/s2352-3026(19)30236-4 Gisslinger et al. 2020 (PROUD-PV)]
+
|[https://www.auajournals.org/doi/abs/10.1016/S0022-5347%2817%2944995-0 Smith et al. 1986 (EORTC 30762)]
−
|2013-2015
+
|1976-1980
−
|style="background-color:#1a9851"|Phase 3 (E-switch-ooc)
+
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
−
|[[#Hydroxyurea_monotherapy|Hydroxyurea]]
+
|[[#Estramustine_monotherapy_88|Estramustine]]
−
| style="background-color:#eeee01" |Seems to have non-inferior composite endpoint
+
| style="background-color:#ffffbf" |Seems not superior
 +
|-
 +
|[https://doi.org/10.1200/JCO.1990.8.10.1675 Osborne et al. 1990 (SWOG S8219)]
 +
|1982-1986
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#AC_.26_Orchiectomy_99|AC & Orchiectomy]]
 +
| style="background-color:#ffffbf" |Seems not superior
 +
|-
 +
|[https://doi.org/10.1111/j.1464-410X.1992.tb15633.x Waymont et al. 1992]
 +
|1985-1987
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[Prostate_cancer#Goserelin_monotherapy_2|Goserelin]]
 +
| style="background-color:#fc8d59" |Seems to have inferior TTFR
 
|-
 
|-
 
|}
 
|}
−
<div class="toccolours" style="background-color:#b3e2cd">
+
''No longer used, but of historical interest.''
−
====Immunotherapy====
+
====Endocrine therapy====
−
*[[Ropeginterferon alfa-2b (Besremi)]]
+
*[[Diethylstilbestrol (DES)]]
 +
</div></div>
 +
===References===
 +
# '''EORTC 30762:''' Smith PH, Suciu S, Robinson MR, Richards B, Bastable JR, Glashan RW, Bouffioux C, Lardennois B, Williams RE, de Pauw M, Sylvester R. A comparison of the effect of diethylstilbestrol with low dose estramustine phosphate in the treatment of advanced prostatic cancer: final analysis of a phase III trial of the European Organisation for Research on Treatment of Cancer. J Urol. 1986 Sep;136(3):619-23. [https://www.auajournals.org/doi/abs/10.1016/S0022-5347%2817%2944995-0 link to original article] [https://pubmed.ncbi.nlm.nih.gov/3525866 PubMed]
 +
# '''SWOG S8219:''' Osborne CK, Blumenstein B, Crawford ED, Coltman CA Jr, Smith AY, Lambuth BW, Chapman RA. Combined versus sequential chemo-endocrine therapy in advanced prostate cancer: final results of a randomized Southwest Oncology Group study. J Clin Oncol. 1990 Oct;8(10):1675-82. [https://doi.org/10.1200/JCO.1990.8.10.1675 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2213104 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]
 +
=Chemotherapy for metastatic disease=
 +
==CMF {{#subobject:25 |Regimen=1}}==
 +
CMF: '''<u>C</u>'''yclophosphamide, '''<u>M</u>'''ethotrexate, 5-'''<u>F</u>'''luorouracil
 +
<div class="toccolours" style="background-color:#eeeeee">
 +
===Regimen {{#subobject:25 |Variant=1}}===
 +
{| class="wikitable" style="width: 40%; text-align:center;"
 +
!style="width: 25%"|Study
 +
!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 +
|-
 +
|[https://doi.org/10.1002/1097-0142(19930615)71:12%3C3975::AID-CNCR2820711229%3E3.0.CO;2-D Wozniak et al. 1993]
 +
|style="background-color:#91cf61"|Phase 2
 +
|-
 +
|}
 +
''This regimen is "minimally active in hormone-refractory metastatic prostate cancer" per Wozniak et al. 1993 and is included for historical reference only.''
 +
====Chemotherapy====
 +
*[[Cyclophosphamide (Cytoxan)]] 100 mg/m<sup>2</sup> PO once per day on days 1 to 7
 +
*[[Methotrexate (MTX)]] 15 mg/m<sup>2</sup> IV once on day 1
 +
*[[Fluorouracil (5-FU)]] 300 mg/m<sup>2</sup> IV once on day 1
 +
'''7-day cycles'''
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# '''PROUD-PV:''' Gisslinger H, Klade C, Georgiev P, Krochmalczyk D, Gercheva-Kyuchukova L, Egyed M, Rossiev V, Dulicek P, Illes A, Pylypenko H, Sivcheva L, Mayer J, Yablokova V, Krejcy K, Grohmann-Izay B, Hasselbalch HC, Kralovics R, Kiladjian JJ; PROUD-PV Study Group. Ropeginterferon alfa-2b versus standard therapy for polycythaemia vera (PROUD-PV and CONTINUATION-PV): a randomised, non-inferiority, phase 3 trial and its extension study. Lancet Haematol. 2020 Mar;7(3):e196-e208. Epub 2020 Jan 31. [https://doi.org/10.1016/s2352-3026(19)30236-4 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32014125 PubMed] NCT01949805
+
# Wozniak AJ, Blumenstein BA, Crawford ED, Boileau M, Rivkin SE, Fletcher WS; [[Study_Groups#SWOG|SWOG]]. Cyclophosphamide, methotrexate, and 5-fluorouracil in the treatment of metastatic prostate cancer: a Southwest Oncology Group study. Cancer. 1993 Jun 15;71(12):3975-8. [https://doi.org/10.1002/1097-0142(19930615)71:12%3C3975::AID-CNCR2820711229%3E3.0.CO;2-D link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/8508363 PubMed]
−
=Relapsed, refractory, or intolerant=
+
==Suramin monotherapy{{#subobject:1d9f88 |Regimen=1}}==
−
==Anagrelide monotherapy {{#subobject:7c6a2d|Regimen=1}}==
 
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:50dda2|Variant=1}}===
+
===Regimen {{#subobject:gd1534 |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%"|Study
Line 155: Line 340:
 
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4358820/ Vannucchi et al. 2015 (RESPONSE)]
+
|[https://doi.org/10.1200/jco.2002.10.022 Small et al. 2002 (CALGB 9480)]
−
|2010-2013
+
|1995-1996
−
|style="background-color:#1a9851"|Phase 3 (C)
+
| style="background-color:#1a9851" |Phase 3 (C)
−
|[[#Ruxolitinib_monotherapy|Ruxolitinib]]
+
|[[#Suramin_monotherapy|Suramin]]; other doses
−
|style="background-color:#d73027"|Inferior disease control
+
| style="background-color:#ffffbf" |Did not meet primary endpoint of RR
 
|-
 
|-
 
|}
 
|}
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
−
====Anticoagulation====
+
====Chemotherapy====
−
*[[Anagrelide (Agrylin)]]
+
*[[Suramin (Antrypol)]]
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# '''RESPONSE:''' Vannucchi AM, Kiladjian JJ, Griesshammer M, Masszi T, Durrant S, Passamonti F, Harrison CN, Pane F, Zachee P, Mesa R, He S, Jones MM, Garrett W, Li J, Pirron U, Habr D, Verstovsek S. Ruxolitinib versus standard therapy for the treatment of polycythemia vera. N Engl J Med. 2015 Jan 29;372(5):426-35. [https://doi.org/10.1056/NEJMoa1409002 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4358820/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25629741 PubMed] NCT01243944
+
#'''CALGB 9480:''' Small EJ, Halabi S, Ratain MJ, Rosner G, Stadler W, Palchak D, Marshall E, Rago R, Hars V, Wilding G, Petrylak D, Vogelzang NJ. Randomized study of three different doses of suramin administered with a fixed dosing schedule in patients with advanced prostate cancer: results of intergroup 0159, cancer and leukemia group B 9480. J Clin Oncol. 2002 Aug 15;20(16):3369-75. [https://doi.org/10.1200/jco.2002.10.022 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12177096/ PubMed] NCT00002723
−
## '''Update:''' Verstovsek S, Vannucchi AM, Griesshammer M, Masszi T, Durrant S, Passamonti F, Harrison CN, Pane F, Zachee P, Kirito K, Besses C, Hino M, Moiraghi B, Miller CB, Cazzola M, Rosti V, Blau I, Mesa R, Jones MM, Zhen H, Li J, Francillard N, Habr D, Kiladjian JJ. Ruxolitinib versus best available therapy in patients with Polycythemia Vera: 80 Week follow up from the RESPONSE trial. Haematologica. 2016 Jul;101(7):821-9. Epub 2016 Apr 21. [http://www.haematologica.org/content/101/7/821 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5004461/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27102499 PubMed]
+
=Therapy for metastatic castrate-resistant disease=
−
## '''Update:''' Kiladjian JJ, Zachee P, Hino M, Pane F, Masszi T, Harrison CN, Mesa R, Miller CB, Passamonti F, Durrant S, Griesshammer M, Kirito K, Besses C, Moiraghi B, Rumi E, Rosti V, Blau IW, Francillard N, Dong T, Wroclawska M, Vannucchi AM, Verstovsek S. Long-term efficacy and safety of ruxolitinib versus best available therapy in polycythaemia vera (RESPONSE): 5-year follow up of a phase 3 study. Lancet Haematol. 2020 Mar;7(3):e226-e237. Epub 2020 Jan 23. [https://doi.org/10.1016/s2352-3026(19)30207-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31982039 PubMed]
+
==Aspirin & Dexamethasone {{#subobject:bd6fcb |Regimen=1}}==
−
==Hydroxyurea monotherapy {{#subobject:82ab4d|Regimen=1}}==
+
DA: '''<u>D</u>'''examethasone & '''<u>A</u>'''spirin
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:14ace8|Variant=1}}===
+
===Regimen {{#subobject:bae48c |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%"|Study
Line 180: Line 365:
 
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4358820/ Vannucchi et al. 2015 (RESPONSE)]
+
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3049603/ Shamash et al. 2011 (BARTS-DAVDAS)]
−
|2010-2013
+
|2001-2008
−
|style="background-color:#1a9851"|Phase 3 (C)
+
| style="background-color:#1a9851" |Phase 3 (C)
−
|[[#Ruxolitinib_monotherapy|Ruxolitinib]]
+
|[[#Aspirin.2C_Dexamethasone.2C_Diethylstilbestrol_99|Aspirin, Dexamethasone, Diethylstilbestrol]]
−
|style="background-color:#d73027"|Inferior disease control
+
| style="background-color:#ffffbf" |Seems not superior
 
|-
 
|-
 
|}
 
|}
−
''Note: The following is the approach recommended by Vannucchi in How I Treat (2014).''
 
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
−
====Chemotherapy====
+
====Endocrine therapy====
−
*[[Hydroxyurea (Hydrea)]] 500 mg PO twice per day, with titration based on the target hematocrit and hematologic toxicity
+
*[[Dexamethasone (Decadron)]] 2 mg PO once per day
 +
====Supportive therapy====
 +
*[[Aspirin]] 75 mg PO once per day
 +
*[[Ranitidine (Zantac)]] 150 mg PO twice per day
 
'''Continued indefinitely'''
 
'''Continued indefinitely'''
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# '''RESPONSE:''' Vannucchi AM, Kiladjian JJ, Griesshammer M, Masszi T, Durrant S, Passamonti F, Harrison CN, Pane F, Zachee P, Mesa R, He S, Jones MM, Garrett W, Li J, Pirron U, Habr D, Verstovsek S. Ruxolitinib versus standard therapy for the treatment of polycythemia vera. N Engl J Med. 2015 Jan 29;372(5):426-35. [https://doi.org/10.1056/NEJMoa1409002 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4358820/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25629741 PubMed] NCT01243944
+
# '''BARTS-DAVDAS:''' Shamash J, Powles T, Sarker SJ, Protheroe A, Mithal N, Mills R, Beard R, Wilson P, Tranter N, O'Brien N, McFaul S, Oliver T. A multi-centre randomised phase III trial of dexamethasone vs dexamethasone and diethylstilbestrol in castration-resistant prostate cancer: immediate vs deferred diethylstilbestrol. Br J Cancer. 2011 Feb 15;104(4):620-8. Epub 2011 Feb 1. [https://www.nature.com/articles/bjc20117 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3049603/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21285990 PubMed] NCT00316927
−
## '''Update:''' Verstovsek S, Vannucchi AM, Griesshammer M, Masszi T, Durrant S, Passamonti F, Harrison CN, Pane F, Zachee P, Kirito K, Besses C, Hino M, Moiraghi B, Miller CB, Cazzola M, Rosti V, Blau I, Mesa R, Jones MM, Zhen H, Li J, Francillard N, Habr D, Kiladjian JJ. Ruxolitinib versus best available therapy in patients with Polycythemia Vera: 80 Week follow up from the RESPONSE trial. Haematologica. 2016 Jul;101(7):821-9. Epub 2016 Apr 21. [http://www.haematologica.org/content/101/7/821 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5004461/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27102499 PubMed]
+
==Cyclophosphamide monotherapy {{#subobject:8e2679 |Regimen=1}}==
−
## '''Update:''' Kiladjian JJ, Zachee P, Hino M, Pane F, Masszi T, Harrison CN, Mesa R, Miller CB, Passamonti F, Durrant S, Griesshammer M, Kirito K, Besses C, Moiraghi B, Rumi E, Rosti V, Blau IW, Francillard N, Dong T, Wroclawska M, Vannucchi AM, Verstovsek S. Long-term efficacy and safety of ruxolitinib versus best available therapy in polycythaemia vera (RESPONSE): 5-year follow up of a phase 3 study. Lancet Haematol. 2020 Mar;7(3):e226-e237. Epub 2020 Jan 23. [https://doi.org/10.1016/s2352-3026(19)30207-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31982039 PubMed]
 
−
==Lenalidomide monotherapy {{#subobject:0dd38f|Regimen=1}}==
 
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:b51df3|Variant=1}}===
+
===Regimen {{#subobject:f36bde |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%"|Study
Line 207: Line 392:
 
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4358820/ Vannucchi et al. 2015 (RESPONSE)]
+
|[https://doi.org/10.1002/1097-0142(19921115)70:10%3C2488::AID-CNCR2820701016%3E3.0.CO;2-9 Saxman et al. 1992]
−
|2010-2013
+
|1984-1989
−
|style="background-color:#1a9851"|Phase 3 (C)
+
| style="background-color:#1a9851" |Phase 3 (C)
−
|[[#Ruxolitinib_monotherapy|Ruxolitinib]]
+
|[[#CAM_99|CAM]]
−
|style="background-color:#d73027"|Inferior disease control
+
| style="background-color:#ffffbf" |Seems not superior
 
|-
 
|-
 
|}
 
|}
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
−
====Targeted therapy====
+
====Chemotherapy====
−
*[[Lenalidomide (Revlimid)]]
+
*[[Cyclophosphamide (Cytoxan)]]
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# '''RESPONSE:''' Vannucchi AM, Kiladjian JJ, Griesshammer M, Masszi T, Durrant S, Passamonti F, Harrison CN, Pane F, Zachee P, Mesa R, He S, Jones MM, Garrett W, Li J, Pirron U, Habr D, Verstovsek S. Ruxolitinib versus standard therapy for the treatment of polycythemia vera. N Engl J Med. 2015 Jan 29;372(5):426-35. [https://doi.org/10.1056/NEJMoa1409002 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4358820/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25629741 PubMed] NCT01243944
+
# Saxman S, Ansari R, Drasga R, Miller M, Wheeler B, McClean J, Einhorn L; Hoosier Oncology Group. Phase III trial of cyclophosphamide versus cyclophosphamide, doxorubicin, and methotrexate in hormone-refractory prostatic cancer: a Hoosier Oncology Group study. Cancer. 1992 Nov 15;70(10):2488-92. [https://doi.org/10.1002/1097-0142(19921115)70:10%3C2488::AID-CNCR2820701016%3E3.0.CO;2-9 link to original article] [https://pubmed.ncbi.nlm.nih.gov/1423178 PubMed]
−
## '''Update:''' Verstovsek S, Vannucchi AM, Griesshammer M, Masszi T, Durrant S, Passamonti F, Harrison CN, Pane F, Zachee P, Kirito K, Besses C, Hino M, Moiraghi B, Miller CB, Cazzola M, Rosti V, Blau I, Mesa R, Jones MM, Zhen H, Li J, Francillard N, Habr D, Kiladjian JJ. Ruxolitinib versus best available therapy in patients with Polycythemia Vera: 80 Week follow up from the RESPONSE trial. Haematologica. 2016 Jul;101(7):821-9. Epub 2016 Apr 21. [http://www.haematologica.org/content/101/7/821 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5004461/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27102499 PubMed]
+
==Cyclophosphamide, Prednisone, Diethylstilbestrol {{#subobject:26 |Regimen=1}}==
−
## '''Update:''' Kiladjian JJ, Zachee P, Hino M, Pane F, Masszi T, Harrison CN, Mesa R, Miller CB, Passamonti F, Durrant S, Griesshammer M, Kirito K, Besses C, Moiraghi B, Rumi E, Rosti V, Blau IW, Francillard N, Dong T, Wroclawska M, Vannucchi AM, Verstovsek S. Long-term efficacy and safety of ruxolitinib versus best available therapy in polycythaemia vera (RESPONSE): 5-year follow up of a phase 3 study. Lancet Haematol. 2020 Mar;7(3):e226-e237. Epub 2020 Jan 23. [https://doi.org/10.1016/s2352-3026(19)30207-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31982039 PubMed]
+
CPD: '''<u>C</u>'''yclophosphamide, '''<u>P</u>'''rednisone, '''<u>D</u>'''iethylstilbestrol
−
==Peginterferon alfa-2a monotherapy {{#subobject:2519d0|Regimen=1}}==
 
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen variant #1, 45 mcg starting dose {{#subobject:8615e6|Variant=1}}===
+
===Regimen {{#subobject:26 |Variant=1}}===
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"  
+
{| class="wikitable" style="width: 60%; text-align:center;"  
−
!style="width: 33%"|Study
+
! style="width: 33%" |Study
−
!style="width: 33%"|Years of enrollment
+
! style="width: 33%" |[[Levels_of_Evidence#Evidence|Evidence]]
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+
! style="width: 33%" |[[Levels_of_Evidence#Efficacy|Efficacy]]
 
|-
 
|-
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6839950/ Yacoub et al. 2019 (MPD-RC-111)]
+
|[https://doi.org/10.1002/cncr.11686 Hellerstedt et al. 2003]
−
|2012-2015
+
| style="background-color:#91cf61" |Phase 2
−
|style="background-color:#91cf61"|Phase 2
+
|50% or greater decline in PSA: 42%
 
|-
 
|-
 
|}
 
|}
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
−
====Immunotherapy====
+
====Chemotherapy====
−
*[[Peginterferon alfa-2a (Pegasys)]] 45 mcg SC once per day on days 1, 8, 15, 22
+
*[[Cyclophosphamide (Cytoxan)]] 100 mg PO once per day on days 1 to 20
−
**Titrated up by 45 mcg every month in the absence of toxicity to goal dose of 180 mcg
+
====Endocrine therapy====
−
'''28-day cycles'''
+
*[[Prednisone (Sterapred)]] 10 mg PO once per day
−
</div></div><br>
+
*[[Diethylstilbestrol (DES)]] 1 mg PO once per day
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 90 mcg starting dose {{#subobject:868ce6|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[http://www.bloodjournal.org/content/112/8/3065.long Kiladjian et al. 2008 (PVN1)]
 
−
|2004-2005
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4881362/ Quintás-Cardama et al. 2009 (MDACC DM03-0109)]
 
−
|2005-2009
 
−
|style="background-color:#91cf61"|Phase 2
 
−
|-
 
−
|}
 
−
''Note: Quintás-Cardama et al. 2009 does not provide guidance on dose escalation or target dosing. Kiladjian et al. 2008 does not provide details on the dose escalation procedure.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Immunotherapy====
 
−
*[[Peginterferon alfa-2a (Pegasys)]] 90 mcg SC once per day on days 1, 8, 15, 22
 
−
**Titrated up every two weeks in the absence of toxicity to 135 mcg SC once per day on days 1, 8, 15, 22
 
−
**In the absence of hematologic response, dose increased to 180 mcg SC once per day on days 1, 8, 15, 22
 
 
====Supportive therapy====
 
====Supportive therapy====
−
*[[Aspirin]] 100 mg PO once per day unless intolerant (Kiladjian et al. 2008)
+
*[[Warfarin (Coumadin)]] 1 mg PO once per day to decrease risk of DVT
−
'''28-day cycles'''
+
'''30-day cycles'''
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
<!-- no pre-pub disclosed -->
+
#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://doi.org/10.1002/cncr.11686 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/14534875 PubMed]
−
# '''PVN1:''' Kiladjian JJ, Cassinat B, Chevret S, Turlure P, Cambier N, Roussel M, Bellucci S, Grandchamp B, Chomienne C, Fenaux P. Pegylated interferon-alfa-2a induces complete hematologic and molecular responses with low toxicity in polycythemia vera. Blood. 2008 Oct 15;112(8):3065-72. Epub 2008 Jul 23. [http://www.bloodjournal.org/content/112/8/3065.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18650451 PubMed] NCT00241241
+
==Doxorubicin monotherapy {{#subobject:061c25 |Regimen=1}}==
−
<!-- no pre-pub disclosed -->
 
−
# '''MDACC DM03-0109:''' Quintás-Cardama A, Kantarjian H, Manshouri T, Luthra R, Estrov Z, Pierce S, Richie MA, Borthakur G, Konopleva M, Cortes J, Verstovsek S. Pegylated interferon alfa-2a yields high rates of hematologic and molecular response in patients with advanced essential thrombocythemia and polycythemia vera. J Clin Oncol. 2009 Nov 10;27(32):5418-24. Epub 2009 Oct 13. [https://doi.org/10.1200/jco.2009.23.6075 link to original article] '''contains dosing details in abstract''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4881362/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19826111 PubMed] NCT00452023
 
−
## '''Update:''' Quintás-Cardama A, Abdel-Wahab O, Manshouri T, Kilpivaara O, Cortes J, Roupie AL, Zhang SJ, Harris D, Estrov Z, Kantarjian H, Levine RL, Verstovsek S. Molecular analysis of patients with polycythemia vera or essential thrombocythemia receiving pegylated interferon α-2a. Blood. 2013 Aug 8;122(6):893-901. Epub 2013 Jun 19. [http://www.bloodjournal.org/content/122/6/893.long link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3739035/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23782935 PubMed]
 
−
## '''Update:''' Masarova L, Patel KP, Newberry KJ, Cortes J, Borthakur G, Konopleva M, Estrov Z, Kantarjian H, Verstovsek S. Pegylated interferon alfa-2a in patients with essential thrombocythaemia or polycythaemia vera: a post-hoc, median 83 month follow-up of an open-label, phase 2 trial. Lancet Haematol. 2017 Apr;4(4):e165-e175. Epub 2017 Mar 10. [https://doi.org/10.1016/S2352-3026(17)30030-3 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5421384/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28291640 PubMed]
 
−
# '''MPD-RC-111:''' Yacoub A, Mascarenhas J, Kosiorek H, Prchal JT, Berenzon D, Baer MR, Ritchie E, Silver RT, Kessler C, Winton E, Finazzi MC, Rambaldi A, Vannucchi AM, Leibowitz D, Rondelli D, Arcasoy MO, Catchatourian R, Vadakara J, Rosti V, Hexner E, Kremyanskaya M, Sandy L, Tripodi J, Najfeld V, Farnoud N, Papaemmanuil E, Salama M, Singer-Weinberg R, Rampal R, Goldberg JD, Barbui T, Mesa R, Dueck AC, Hoffman R. Pegylated interferon alfa-2a for polycythemia vera or essential thrombocythemia resistant or intolerant to hydroxyurea. Blood. 2019 Oct 31;134(18):1498-1509. [https://doi.org/10.1182/blood.2019000428 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6839950/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31515250 PubMed] NCT01259856
 
−
==Pipobroman monotherapy {{#subobject:f9eb67|Regimen=1}}==
 
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:26b5d3|Variant=1}}===
+
===Regimen {{#subobject:472ea8 |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%"|Study
Line 285: Line 441:
 
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4358820/ Vannucchi et al. 2015 (RESPONSE)]
+
|[https://link.springer.com/article/10.1385%2FMO%3A20%3A2%3A137 Leaf et al. 2003 (ECOG E3882)]
−
|2010-2013
+
|1983-1986
−
|style="background-color:#1a9851"|Phase 3 (C)
+
| style="background-color:#1a9851" |Phase 3 (C)
−
|[[#Ruxolitinib_monotherapy|Ruxolitinib]]
+
|[[#Doxorubicin_.26_DES_99|Doxorubicin & DES]]
−
|style="background-color:#d73027"|Inferior disease control
+
| style="background-color:#ffffbf" |Seems not superior
 +
|-
 +
|[https://doi.org/10.1016/s0140-6736(00)03639-4 Tu et al. 2001]
 +
|1996-1999
 +
| style="background-color:#1a9851" |Randomized Phase 2 (C)
 +
|[[#Doxorubicin_.26_Strontium-89|Doxorubicin & Strontium-89]]
 +
| style="background-color:#d73027" |Inferior OS
 
|-
 
|-
 
|}
 
|}
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
 
====Chemotherapy====
 
====Chemotherapy====
−
*[[Pipobroman (Vercyte)]]
+
*[[Doxorubicin (Adriamycin)]]
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# '''Review:''' Passamonti F, Lazzarino M. Treatment of polycythemia vera and essential thrombocythemia: the role of pipobroman. Leuk Lymphoma. 2003 Sep;44(9):1483-8. [http://www.tandfonline.com/doi/full/10.3109/10428190309178768 link to original article] [https://pubmed.ncbi.nlm.nih.gov/14565648 PubMed]
+
# Tu SM, Millikan RE, Mengistu B, Delpassand ES, Amato RJ, Pagliaro LC, Daliani D, Papandreou CN, Smith TL, Kim J, Podoloff DA, Logothetis CJ. Bone-targeted therapy for advanced androgen-independent carcinoma of the prostate: a randomised phase II trial. Lancet. 2001 Feb 3;357(9253):336-41. Erratum in: Lancet 2001 Apr 14;357(9263):1210. [https://doi.org/10.1016/s0140-6736(00)03639-4 link to original article] [https://pubmed.ncbi.nlm.nih.gov/11210994 PubMed]
−
# '''RESPONSE:''' Vannucchi AM, Kiladjian JJ, Griesshammer M, Masszi T, Durrant S, Passamonti F, Harrison CN, Pane F, Zachee P, Mesa R, He S, Jones MM, Garrett W, Li J, Pirron U, Habr D, Verstovsek S. Ruxolitinib versus standard therapy for the treatment of polycythemia vera. N Engl J Med. 2015 Jan 29;372(5):426-35. [https://doi.org/10.1056/NEJMoa1409002 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4358820/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25629741 PubMed] NCT01243944
+
# '''ECOG E3882:''' Leaf AN, Propert K, Corcoran C, Catalano PJ, Trump DL, Harris JE, Davis TE. Phase III study of combined chemohormonal therapy in metastatic prostate cancer (ECOG 3882): an Eastern Cooperative Oncology Group study. Med Oncol. 2003;20(2):137-46. [https://link.springer.com/article/10.1385%2FMO%3A20%3A2%3A137 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12835516 PubMed]
−
## '''Update:''' Verstovsek S, Vannucchi AM, Griesshammer M, Masszi T, Durrant S, Passamonti F, Harrison CN, Pane F, Zachee P, Kirito K, Besses C, Hino M, Moiraghi B, Miller CB, Cazzola M, Rosti V, Blau I, Mesa R, Jones MM, Zhen H, Li J, Francillard N, Habr D, Kiladjian JJ. Ruxolitinib versus best available therapy in patients with Polycythemia Vera: 80 Week follow up from the RESPONSE trial. Haematologica. 2016 Jul;101(7):821-9. Epub 2016 Apr 21. [http://www.haematologica.org/content/101/7/821 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5004461/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27102499 PubMed]
+
==Doxorubicin & Strontium-89 {{#subobject:9b4d29 |Regimen=1}}==
−
## '''Update:''' Kiladjian JJ, Zachee P, Hino M, Pane F, Masszi T, Harrison CN, Mesa R, Miller CB, Passamonti F, Durrant S, Griesshammer M, Kirito K, Besses C, Moiraghi B, Rumi E, Rosti V, Blau IW, Francillard N, Dong T, Wroclawska M, Vannucchi AM, Verstovsek S. Long-term efficacy and safety of ruxolitinib versus best available therapy in polycythaemia vera (RESPONSE): 5-year follow up of a phase 3 study. Lancet Haematol. 2020 Mar;7(3):e226-e237. Epub 2020 Jan 23. [https://doi.org/10.1016/s2352-3026(19)30207-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31982039 PubMed]
 
−
==Ruxolitinib monotherapy {{#subobject:f35a21|Regimen=1}}==
 
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:364cac|Variant=1}}===
+
===Regimen {{#subobject:083cec |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%"|Study
Line 311: Line 471:
 
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4231215/ Verstovsek et al. 2014 (INCB18424-256)]
+
|[https://doi.org/10.1016/s0140-6736(00)03639-4 Tu et al. 2001]
−
|2008-NR
+
|1996-1999
−
|style="background-color:#91cf61"|Phase 2
+
| style="background-color:#1a9851" |Randomized Phase 2 (E-esc)
−
|style="background-color:#d3d3d3"|
+
|[[#Doxorubicin_monotherapy|Doxorubicin]]
−
|style="background-color:#d3d3d3"|
+
| style="background-color:#1a9850" |Superior OS
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4358820/ Vannucchi et al. 2015 (RESPONSE)]
 
−
|2010-2013
 
−
|style="background-color:#1a9851"|Phase 3 (E-RT-switch-ooc)
 
−
|Standard therapy
 
−
|style="background-color:#1a9850"|Superior disease control
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(16)30558-7 Passamonti et al. 2016 (RESPONSE-2)]
 
−
|2014-2015
 
−
|style="background-color:#1a9851"|Phase 3b (E-switch-ooc)
 
−
|Standard therapy
 
−
|style="background-color:#1a9850"|Superior disease control
 
 
|-
 
|-
 
|}
 
|}
−
''There were several doses evaluated in INCB18424-256; the median total daily dose was 21.7 mg corresponding to approximately 10 mg PO twice per day. The most common comparator in RESPONSE and RESPONSE-2 was [[#Hydroxyurea_monotherapy_2|hydroxyurea]].''
+
<div class="toccolours" style="background-color:#cbd5e8">
−
====Targeted therapy====
+
====Preceding treatment====
−
*[[Ruxolitinib (Jakafi)]] 10 mg PO twice per day
+
*[[#Doxorubicin_.26_Ketoconazole.2FEstramustine_.26_Vinblastine_99|Doxorubicin & Ketoconazole alternating with Estramustine & Vinblastine]]
−
'''Continued indefinitely'''
+
</div>
 +
<div class="toccolours" style="background-color:#b3e2cd">
 +
====Chemotherapy====
 +
*[[Doxorubicin (Adriamycin)]]
 +
====Radiotherapy====
 +
*[[Strontium-89 (Metastron)]]
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# '''INCB18424-256:''' Verstovsek S, Passamonti F, Rambaldi A, Barosi G, Rosen PJ, Rumi E, Gattoni E, Pieri L, Guglielmelli P, Elena C, He S, Contel N, Mookerjee B, Sandor V, Cazzola M, Kantarjian HM, Barbui T, Vannucchi AM. A phase 2 study of ruxolitinib, an oral JAK1 and JAK2 Inhibitor, in patients with advanced polycythemia vera who are refractory or intolerant to hydroxyurea. Cancer. 2014 Feb 15;120(4):513-20. [https://doi.org/10.1002/cncr.28441 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4231215/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24258498 PubMed] content property of [http://hemonc.org HemOnc.org] NCT00726232
+
# Tu SM, Millikan RE, Mengistu B, Delpassand ES, Amato RJ, Pagliaro LC, Daliani D, Papandreou CN, Smith TL, Kim J, Podoloff DA, Logothetis CJ. Bone-targeted therapy for advanced androgen-independent carcinoma of the prostate: a randomised phase II trial. Lancet. 2001 Feb 3;357(9253):336-41. Erratum in: Lancet 2001 Apr 14;357(9263):1210. [https://doi.org/10.1016/s0140-6736(00)03639-4 link to original article] [https://pubmed.ncbi.nlm.nih.gov/11210994 PubMed]
−
# '''RESPONSE:''' Vannucchi AM, Kiladjian JJ, Griesshammer M, Masszi T, Durrant S, Passamonti F, Harrison CN, Pane F, Zachee P, Mesa R, He S, Jones MM, Garrett W, Li J, Pirron U, Habr D, Verstovsek S. Ruxolitinib versus standard therapy for the treatment of polycythemia vera. N Engl J Med. 2015 Jan 29;372(5):426-35. [https://doi.org/10.1056/NEJMoa1409002 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4358820/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25629741 PubMed] NCT01243944
+
==Vinblastine monotherapy {{#subobject:1d9e22 |Regimen=1}}==
−
<!-- ## '''Update: Abstract:''' Jean-Jacques Kiladjian, Alessandro M. Vannucchi, Martin Griesshammer, Tamas Masszi, Simon Durrant, Francesco Passamonti, Claire N. Harrison, Fabrizio Pane, Pierre Zachee, Keita Kirito, Mario Cazzola, Carlos Besses, Igor Blau, Ruben Mesa, Mark M. Jones, Shui He, Huiling Zhen, Jingjin Li, Nathalie Francillard, Dany Habr, Srdan Verstovsek. Ruxolitinib versus best available therapy in patients with polycythemia vera: 80-week follow-up from the response trial. EHA 2015 Abstract: S447 [http://learningcenter.ehaweb.org/eha/2015/20th/103108/jean-jacques.kiladjian.ruxolitinib.versus.best.available.therapy.in.patients.html?f=l5449p16m3 link to abstract] -->
 
−
## '''Update:''' Verstovsek S, Vannucchi AM, Griesshammer M, Masszi T, Durrant S, Passamonti F, Harrison CN, Pane F, Zachee P, Kirito K, Besses C, Hino M, Moiraghi B, Miller CB, Cazzola M, Rosti V, Blau I, Mesa R, Jones MM, Zhen H, Li J, Francillard N, Habr D, Kiladjian JJ. Ruxolitinib versus best available therapy in patients with Polycythemia Vera: 80 Week follow up from the RESPONSE trial. Haematologica. 2016 Jul;101(7):821-9. Epub 2016 Apr 21. [http://www.haematologica.org/content/101/7/821 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5004461/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27102499 PubMed]
 
−
## '''Update:''' Kiladjian JJ, Zachee P, Hino M, Pane F, Masszi T, Harrison CN, Mesa R, Miller CB, Passamonti F, Durrant S, Griesshammer M, Kirito K, Besses C, Moiraghi B, Rumi E, Rosti V, Blau IW, Francillard N, Dong T, Wroclawska M, Vannucchi AM, Verstovsek S. Long-term efficacy and safety of ruxolitinib versus best available therapy in polycythaemia vera (RESPONSE): 5-year follow up of a phase 3 study. Lancet Haematol. 2020 Mar;7(3):e226-e237. Epub 2020 Jan 23. [https://doi.org/10.1016/s2352-3026(19)30207-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31982039 PubMed]
 
−
# '''RESPONSE-2:''' Passamonti F, Griesshammer M, Palandri F, Egyed M, Benevolo G, Devos T, Callum J, Vannucchi AM, Sivgin S, Bensasson C, Khan M, Mounedji N, Saydam G. Ruxolitinib for the treatment of inadequately controlled polycythaemia vera without splenomegaly (RESPONSE-2): a randomised, open-label, phase 3b study. Lancet Oncol. 2017 Jan;18(1):88-99. Epub 2016 Dec 2. [https://doi.org/10.1016/S1470-2045(16)30558-7 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/27916398 PubMed] NCT02038036
 
−
##'''Update:''' Passamonti F, Palandri F, Saydam G, Callum J, Devos T, Guglielmelli P, Vannucchi AM, Zor E, Zuurman M, Gilotti G, Zhang Y, Griesshammer M. Ruxolitinib versus best available therapy in inadequately controlled polycythaemia vera without splenomegaly (RESPONSE-2): 5-year follow up of a randomised, phase 3b study. Lancet Haematol. 2022 Jul;9(7):e480-e492. Epub 2022 May 18. [https://doi.org/10.1016/s2352-3026(22)00102-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/35597252/ PubMed]
 
−
==Thalidomide monotherapy {{#subobject:cfd2c6|Regimen=1}}==
 
 
<div class="toccolours" style="background-color:#eeeeee">
 
<div class="toccolours" style="background-color:#eeeeee">
−
===Regimen {{#subobject:63b4bf|Variant=1}}===
+
===Regimen {{#subobject:81db34 |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%"|Study
Line 353: Line 500:
 
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
|-
 
|-
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4358820/ Vannucchi et al. 2015 (RESPONSE)]
+
|[https://doi.org/10.1200/JCO.1999.17.10.3160 Hudes et al. 1999]
−
|2010-2013
+
|1993-1995
−
|style="background-color:#1a9851"|Phase 3 (C)
+
| style="background-color:#1a9851" |Phase 3 (C)
−
|[[#Ruxolitinib_monotherapy|Ruxolitinib]]
+
|[[#Estramustine_.26_Vinblastine_88|Estramustine & Vinblastine]]
−
|style="background-color:#d73027"|Inferior disease control
+
| style="background-color:#fee08b" |Might have inferior OS
 
|-
 
|-
 
|}
 
|}
 
<div class="toccolours" style="background-color:#b3e2cd">
 
<div class="toccolours" style="background-color:#b3e2cd">
−
====Targeted therapy====
+
====Chemotherapy====
−
*[[Thalidomide (Thalomid)]]
+
*[[Vinblastine (Velban)]]
 
</div></div>
 
</div></div>
 
===References===
 
===References===
−
# '''RESPONSE:''' Vannucchi AM, Kiladjian JJ, Griesshammer M, Masszi T, Durrant S, Passamonti F, Harrison CN, Pane F, Zachee P, Mesa R, He S, Jones MM, Garrett W, Li J, Pirron U, Habr D, Verstovsek S. Ruxolitinib versus standard therapy for the treatment of polycythemia vera. N Engl J Med. 2015 Jan 29;372(5):426-35. [https://doi.org/10.1056/NEJMoa1409002 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4358820/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25629741 PubMed] NCT01243944
+
# Hudes G, Einhorn L, Ross E, Balsham A, Loehrer P, Ramsey H, Sprandio J, Entmacher M, Dugan W, Ansari R, Monaco F, Hanna M, Roth B; Hoosier Oncology Group; Fox Chase Network. Vinblastine versus vinblastine plus oral estramustine phosphate for patients with hormone-refractory prostate cancer: A Hoosier Oncology Group and Fox Chase Network phase III trial. J Clin Oncol. 1999 Oct;17(10):3160-6. [https://doi.org/10.1200/JCO.1999.17.10.3160 link to original article] [https://pubmed.ncbi.nlm.nih.gov/10506613 PubMed]
−
## '''Update:''' Verstovsek S, Vannucchi AM, Griesshammer M, Masszi T, Durrant S, Passamonti F, Harrison CN, Pane F, Zachee P, Kirito K, Besses C, Hino M, Moiraghi B, Miller CB, Cazzola M, Rosti V, Blau I, Mesa R, Jones MM, Zhen H, Li J, Francillard N, Habr D, Kiladjian JJ. Ruxolitinib versus best available therapy in patients with Polycythemia Vera: 80 Week follow up from the RESPONSE trial. Haematologica. 2016 Jul;101(7):821-9. Epub 2016 Apr 21. [http://www.haematologica.org/content/101/7/821 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5004461/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27102499 PubMed]
+
[[Category:Prostate cancer regimens]]
−
## '''Update:''' Kiladjian JJ, Zachee P, Hino M, Pane F, Masszi T, Harrison CN, Mesa R, Miller CB, Passamonti F, Durrant S, Griesshammer M, Kirito K, Besses C, Moiraghi B, Rumi E, Rosti V, Blau IW, Francillard N, Dong T, Wroclawska M, Vannucchi AM, Verstovsek S. Long-term efficacy and safety of ruxolitinib versus best available therapy in polycythaemia vera (RESPONSE): 5-year follow up of a phase 3 study. Lancet Haematol. 2020 Mar;7(3):e226-e237. Epub 2020 Jan 23. [https://doi.org/10.1016/s2352-3026(19)30207-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31982039 PubMed]
+
[[Category:Historical regimens]]
−
=Response criteria=
 
−
==ELN==
 
−
*'''2009:''' [http://www.bloodjournal.org/content/113/20/4829.long Response criteria for essential thrombocythemia and polycythemia vera: result of a European LeukemiaNet consensus conference]
 
−
[[Category:Polycythemia vera regimens]]
 
 
[[Category:Disease-specific pages]]
 
[[Category:Disease-specific pages]]
−
[[Category:Myeloproliferative neoplasms]]
+
[[Category:Genitourinary cancers]]

Revision as of 12:43, 2 January 2023

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The purpose of this page is to provide references to regimens that are obsolete, outdated, or of historical interest only. As a general rule, this includes the inferior arm(s) of a randomized study, unless said regimens continue to be recommended by trustworthy sources such as the NCCN Guidelines. Is there a regimen missing from this list? See the main prostate cancer page for current regimens.

0 regimens on this page
0 variants on this page


Definitive radiotherapy

Radiation therapy

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Pilepich et al. 2001 (RTOG 86-10) 1987-1991 Phase 3 (C) Flutamide, Goserelin, RT Seems to have inferior cause-specific mortality
Pilepich et al. 1997 (RTOG 85-31) 1987-1992 Phase 3 (C) Goserelin & RT Inferior DFS
Bolla et al. 1997 (EORTC 22863) 1987-1995 Phase 3 (C) Goserelin & RT Inferior OS
Jones et al. 2011 (RTOG 94-08) 1994-2001 Phase 3 (C) 1. Flutamide, Goserelin, RT
2. Flutamide, Leuprolide, RT 		Seems to have inferior OS
D'Amico et al. 2008 (DFCI 95-096) 1995-2001 Randomized (C) Flutamide, Goserelin, RT Inferior OS
Denham et al. 2005 (TROG 96.01) 1996-2000 Phase 3 (C) 1. Flutamide & Goserelin x 3 mo, RT Inferior EFS1
2. Flutamide & Goserelin x 6 mo, RT Inferior OS1
McPartlin et al. 2016 (PMH 9907) 1999-2006 Phase 3 (C) Bicalutamide & RT Did not meet primary endpoint of BFI

1Reported efficacy for TROG 96.01 is based on the 2011 update.
Demonstrated to be inferior in almost all studies; here for reference purposes only.

Radiotherapy

References

  1. 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
  2. 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
  3. 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
  4. 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
  5. 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
  6. 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
  7. PMH 9907: McPartlin AJ, Glicksman R, Pintilie M, Tsuji D, Mok G, Bayley A, Chung P, Bristow RG, Gospodarowicz MK, Catton CN, Milosevic M, Warde PR. PMH 9907: Long-term outcomes of a randomized phase 3 study of short-term bicalutamide hormone therapy and dose-escalated external-beam radiation therapy for localized prostate cancer. Cancer. 2016 Aug 15;122(16):2595-603. Epub 2016 May 24. link to original article PubMed
  8. 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

Hormonal therapy for locally advanced or metastatic disease

Castration

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Parmar et al. 1985 1984-1985 Phase 3 (C) D-Trp-6-LHRH Seems not superior
Soloway et al. 1991 NR Phase 3 (C) Goserelin Did not meet efficacy endpoints
Robinson 1993 (EORTC 30805) 1981-1986 Phase 3 (C) 1. Castration & Cyproterone acetate
2. DES 		Seems not superior
Kaisary et al. 1991 1983-1986 Phase 3 (C) Goserelin Did not meet efficacy endpoints
Keuppens et al. 1990 (EORTC 30853) 1986-1988 Phase 3 (C) Flutamide & Goserelin Seems to have inferior OS1
Janknegt et al. 1993 (International Anandron Study) 1986-NR Phase 3 (C) Nilutamide & Orchiectomy Inferior PFS
Bruun et al. 1996 NR Phase 3 (C) 1. Buserelin
2. Estrogens 		Seems not superior
Studer et al. 2004 (SAKK 08/88) 1988-1992 Phase 3 (C) Orchiectomy; deferred Seems not superior
Boccon-Gibod et al. 1997 1989-1991 Phase 3 (C) Flutamide Seems not superior
de Voogt et al. 1998 (EORTC 30843) NR in abstract Phase 3 (C) Buserelin & Cyproterone acetate Seems not superior
Eisenberger et al. 1998 1989-1994 Phase 3 (C) Flutamide & Orchiectomy Seems not superior
Tyrrell et al. 1998 NR in abstract Phase 3 (C) Bicalutamide Seems not superior2
de Reijke et al. 1999 1990-1995 Phase 3 (C) Mitomycin & Orchiectomy Seems not superior
Millikan et al. 2008 (MDA DM95-231) 1996-2003 Phase 3 (C) ADT & KA/VE Seems not superior

1Reported efficacy for EORTC 30853 is based on the 1998 final update.
2Reported efficacy for Tyrrell et al. 1998 is based on the 2000 update.
No longer widely used as monotherapy in the United States; included for reference purposes only.

Endocrine therapy

References

  1. Parmar H, Phillips RH, Lightman SL, Edwards L, Allen L, Schally AV. Randomised controlled study of orchidectomy vs long-acting D-Trp-6-LHRH microcapsules in advanced prostatic carcinoma. Lancet. 1985 Nov 30;2(8466):1201-5. link to original article PubMed
  2. 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
  3. 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
  4. 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
  5. 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
  6. EORTC 30805: Robinson MR. A further analysis of European Organization for Research and Treatment of Cancer protocol 30805: orchidectomy versus orchidectomy plus cyproterone acetate versus low-dose diethylstilbestrol. Cancer. 1993 Dec 15;72(12 Suppl):3855-7. link to original article PubMed
    1. Update: Robinson MR, Smith PH, Richards B, Newling DW, de Pauw M, Sylvester R. The final analysis of the EORTC Genito-Urinary Tract Cancer Co-Operative Group phase III clinical trial (protocol 30805) comparing orchidectomy, orchidectomy plus cyproterone acetate and low dose stilboestrol in the management of metastatic carcinoma of the prostate. Eur Urol. 1995;28(4):273-83. link to original article PubMed
  7. Bruun E, Frimodt-Møller C; Danish Buserelin Study Group. The effect of Buserelin versus conventional antiandrogenic treatment in patients with T2-4NXM1 prostatic cancer; A prospective, randomized multicentre phase III trial. Scand J Urol Nephrol. 1996 Aug;30(4):291-7. link to original article PubMed
  8. 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
  9. EORTC 30843: de Voogt HJ, Studer U, Schröder FH, Klijn JG, de Pauw M, Sylvester R; EORTC Genito-Urinary Tract Cancer Cooperative Group. Maximum androgen blockade using LHRH agonist buserelin in combination with short-term (two weeks) or long-term (continuous) cyproterone acetate is not superior to standard androgen deprivation in the treatment of advanced prostate cancer: final analysis of EORTC GU Group Trial 30843. Eur Urol. 1998;33(2):152-8. link to original article PubMed
  10. Eisenberger MA, Blumenstein BA, Crawford ED, Miller G, McLeod DG, Loehrer PJ, Wilding G, Sears K, Culkin DJ, Thompson IM Jr, Bueschen AJ, Lowe BA. Bilateral orchiectomy with or without flutamide for metastatic prostate cancer. N Engl J Med. 1998 Oct 8;339(15):1036-42. link to original article PubMed
  11. 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
  12. de Reijke TM, Keuppens FI, Whelan P, Kliment J, Robinson MR, Rea LA, Sylvester RJ; European Organisation for Research in Cancer Therapy Genitourinary Group. Orchiectomy and orchiectomy plus mitomycin C for metastatic prostate cancer in patients with poor prognosis: the final results of a European Organisation for Research in Cancer Therapy Genitourinary Group trial. J Urol. 1999 Nov;162(5):1658-64. link to original article PubMed
  13. SAKK 08/88: Studer UE, Hauri D, Hanselmann S, Chollet D, Leisinger HJ, Gasser T, Senn E, Trinkler FB, Tscholl RM, Thalmann GN, Dietrich D. Immediate versus deferred hormonal treatment for patients with prostate cancer who are not suitable for curative local treatment: results of the randomized trial SAKK 08/88. J Clin Oncol. 2004 Oct 15;22(20):4109-18. Erratum in: J Clin Oncol. 2005 Feb 1;23(4):936. link to original article PubMed
  14. MDA DM95-231: Millikan RE, Wen S, Pagliaro LC, Brown MA, Moomey B, Do KA, Logothetis CJ. Phase III trial of androgen ablation with or without three cycles of systemic chemotherapy for advanced prostate cancer. J Clin Oncol. 2008 Dec 20;26(36):5936-42. Epub 2008 Nov 24. link to original article link to PMC article PubMed NCT00002855
  15. ECOG E8892: NCT00002881

Cortisone monotherapy

Regimen

Study Evidence
Miller & Hinman 1954 Non-randomized

Endocrine therapy

References

  1. Miller GM, Hinman F Jr. Cortisone treatment in advanced carcinoma of the prostate. J Urol. 1954 Sep;72(3):485-96. link to original article PubMed

Cyproterone acetate monotherapy

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Jacobi et al. 1980 NR Phase 3 (E-switch-ic) Estradiol undecylate Seems to have superior ORR
Pavone-Macaluso et al. 1986 (EORTC 30761) 1977-1981 Phase 3 (E-switch-ic) 1. DES Seems not superior
2. MPA Seems to have superior OS
Debruyne et al. 1998 1992-1994 Phase 3 (C) Liarozole Seems not superior

Endocrine therapy

References

  1. Jacobi GH, Altwein JE, Kurth KH, Basting R, Hohenfellner R. Treatment of advanced prostatic cancer with parenteral cyproterone acetate: a phase III randomised trial. Br J Urol. 1980 Jun;52(3):208-15. link to original article PubMed
  2. EORTC 30761: Pavone-Macaluso M, de Voogt HJ, Viggiano G, Barasolo E, Lardennois B, de Pauw M, Sylvester R. Comparison of diethylstilbestrol, cyproterone acetate and medroxyprogesterone acetate in the treatment of advanced prostatic cancer: final analysis of a randomized phase III trial of the European Organisation for Research on Treatment of Cancer Urological Group. J Urol. 1986 Sep;136(3):624-31. link to original article PubMed
  3. Debruyne FJ, Murray R, Fradet Y, Johansson JE, Tyrrell C, Boccardo F, Denis L, Marberger JM, Brune D, Rassweiler J, Vangeneugden T, Bruynseels J, Janssens M, De Porre P; Liarozole Study Group. Liarozole--a novel treatment approach for advanced prostate cancer: results of a large randomized trial versus cyproterone acetate. Urology. 1998 Jul;52(1):72-81. link to original article PubMed

DES monotherapy

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Smith et al. 1986 (EORTC 30762) 1976-1980 Phase 3 (E-switch-ic) Estramustine Seems not superior
Osborne et al. 1990 (SWOG S8219) 1982-1986 Phase 3 (C) AC & Orchiectomy Seems not superior
Waymont et al. 1992 1985-1987 Phase 3 (C) Goserelin Seems to have inferior TTFR

No longer used, but of historical interest.

Endocrine therapy

References

  1. EORTC 30762: Smith PH, Suciu S, Robinson MR, Richards B, Bastable JR, Glashan RW, Bouffioux C, Lardennois B, Williams RE, de Pauw M, Sylvester R. A comparison of the effect of diethylstilbestrol with low dose estramustine phosphate in the treatment of advanced prostatic cancer: final analysis of a phase III trial of the European Organisation for Research on Treatment of Cancer. J Urol. 1986 Sep;136(3):619-23. link to original article PubMed
  2. SWOG S8219: Osborne CK, Blumenstein B, Crawford ED, Coltman CA Jr, Smith AY, Lambuth BW, Chapman RA. Combined versus sequential chemo-endocrine therapy in advanced prostate cancer: final results of a randomized Southwest Oncology Group study. J Clin Oncol. 1990 Oct;8(10):1675-82. link to original article PubMed
  3. 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

Chemotherapy for metastatic disease

CMF

CMF: Cyclophosphamide, Methotrexate, 5-Fluorouracil

Regimen

Study Evidence
Wozniak et al. 1993 Phase 2

This regimen is "minimally active in hormone-refractory metastatic prostate cancer" per Wozniak et al. 1993 and is included for historical reference only.

Chemotherapy

7-day cycles

References

  1. Wozniak AJ, Blumenstein BA, Crawford ED, Boileau M, Rivkin SE, Fletcher WS; SWOG. Cyclophosphamide, methotrexate, and 5-fluorouracil in the treatment of metastatic prostate cancer: a Southwest Oncology Group study. Cancer. 1993 Jun 15;71(12):3975-8. link to original article contains dosing details in manuscript PubMed

Suramin monotherapy

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Small et al. 2002 (CALGB 9480) 1995-1996 Phase 3 (C) Suramin; other doses Did not meet primary endpoint of RR

Chemotherapy

References

  1. CALGB 9480: Small EJ, Halabi S, Ratain MJ, Rosner G, Stadler W, Palchak D, Marshall E, Rago R, Hars V, Wilding G, Petrylak D, Vogelzang NJ. Randomized study of three different doses of suramin administered with a fixed dosing schedule in patients with advanced prostate cancer: results of intergroup 0159, cancer and leukemia group B 9480. J Clin Oncol. 2002 Aug 15;20(16):3369-75. link to original article PubMed NCT00002723

Therapy for metastatic castrate-resistant disease

Aspirin & Dexamethasone

DA: Dexamethasone & Aspirin

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Shamash et al. 2011 (BARTS-DAVDAS) 2001-2008 Phase 3 (C) Aspirin, Dexamethasone, Diethylstilbestrol Seems not superior

Endocrine therapy

Supportive therapy

Continued indefinitely

References

  1. BARTS-DAVDAS: Shamash J, Powles T, Sarker SJ, Protheroe A, Mithal N, Mills R, Beard R, Wilson P, Tranter N, O'Brien N, McFaul S, Oliver T. A multi-centre randomised phase III trial of dexamethasone vs dexamethasone and diethylstilbestrol in castration-resistant prostate cancer: immediate vs deferred diethylstilbestrol. Br J Cancer. 2011 Feb 15;104(4):620-8. Epub 2011 Feb 1. link to original article link to PMC article contains dosing details in manuscript PubMed NCT00316927

Cyclophosphamide monotherapy

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Saxman et al. 1992 1984-1989 Phase 3 (C) CAM Seems not superior

Chemotherapy

References

  1. Saxman S, Ansari R, Drasga R, Miller M, Wheeler B, McClean J, Einhorn L; Hoosier Oncology Group. Phase III trial of cyclophosphamide versus cyclophosphamide, doxorubicin, and methotrexate in hormone-refractory prostatic cancer: a Hoosier Oncology Group study. Cancer. 1992 Nov 15;70(10):2488-92. link to original article PubMed

Cyclophosphamide, Prednisone, Diethylstilbestrol

CPD: Cyclophosphamide, Prednisone, Diethylstilbestrol

Regimen

Study Evidence Efficacy
Hellerstedt et al. 2003 Phase 2 50% or greater decline in PSA: 42%

Chemotherapy

Endocrine therapy

Supportive therapy

30-day cycles

References

  1. Hellerstedt B, Pienta KJ, Redman BG, Esper P, Dunn R, Fardig J, Olson K, Smith DC. Phase II trial of oral cyclophosphamide, prednisone, and diethylstilbestrol for androgen-independent prostate carcinoma. Cancer. 2003 Oct 15;98(8):1603-10. link to original article contains dosing details in manuscript PubMed

Doxorubicin monotherapy

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Leaf et al. 2003 (ECOG E3882) 1983-1986 Phase 3 (C) Doxorubicin & DES Seems not superior
Tu et al. 2001 1996-1999 Randomized Phase 2 (C) Doxorubicin & Strontium-89 Inferior OS

Chemotherapy

References

  1. Tu SM, Millikan RE, Mengistu B, Delpassand ES, Amato RJ, Pagliaro LC, Daliani D, Papandreou CN, Smith TL, Kim J, Podoloff DA, Logothetis CJ. Bone-targeted therapy for advanced androgen-independent carcinoma of the prostate: a randomised phase II trial. Lancet. 2001 Feb 3;357(9253):336-41. Erratum in: Lancet 2001 Apr 14;357(9263):1210. link to original article PubMed
  2. ECOG E3882: Leaf AN, Propert K, Corcoran C, Catalano PJ, Trump DL, Harris JE, Davis TE. Phase III study of combined chemohormonal therapy in metastatic prostate cancer (ECOG 3882): an Eastern Cooperative Oncology Group study. Med Oncol. 2003;20(2):137-46. link to original article PubMed

Doxorubicin & Strontium-89

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Tu et al. 2001 1996-1999 Randomized Phase 2 (E-esc) Doxorubicin Superior OS

Preceding treatment

Chemotherapy

Radiotherapy

References

  1. Tu SM, Millikan RE, Mengistu B, Delpassand ES, Amato RJ, Pagliaro LC, Daliani D, Papandreou CN, Smith TL, Kim J, Podoloff DA, Logothetis CJ. Bone-targeted therapy for advanced androgen-independent carcinoma of the prostate: a randomised phase II trial. Lancet. 2001 Feb 3;357(9253):336-41. Erratum in: Lancet 2001 Apr 14;357(9263):1210. link to original article PubMed

Vinblastine monotherapy

Regimen

Study Years of enrollment Evidence Comparator Comparative Efficacy
Hudes et al. 1999 1993-1995 Phase 3 (C) Estramustine & Vinblastine Might have inferior OS

Chemotherapy

References

  1. Hudes G, Einhorn L, Ross E, Balsham A, Loehrer P, Ramsey H, Sprandio J, Entmacher M, Dugan W, Ansari R, Monaco F, Hanna M, Roth B; Hoosier Oncology Group; Fox Chase Network. Vinblastine versus vinblastine plus oral estramustine phosphate for patients with hormone-refractory prostate cancer: A Hoosier Oncology Group and Fox Chase Network phase III trial. J Clin Oncol. 1999 Oct;17(10):3160-6. link to original article PubMed
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