Prostate cancer

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80 regimens on this page
111 variants on this page


Guidelines

ASCO

Older

ASCO & CCO

AUA

EAU/ESTRO/SIOG

ESMO

Older

NCCN

St Gallen

Definitive ADT & radiotherapy

Goserelin & RT

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RT: Radiation Therapy

Regimen

Study Evidence Comparator Efficacy
Pilepich et al. 2005 (RTOG 85-31) Phase III RT Superior DFS
Bolla et al. 1997 Phase III RT Superior OS

Endocrine & Radiotherapy

  • Goserelin (Zoladex) 3.6 mg SC once every 4 weeks, to start during the last week of radiation therapy and to continue indefinitely or until progression
  • Radiation therapy, 1.8 to 2 Gy per fraction, with an initial 44 to 46 Gy to the pelvis, then an additional boost to the prostate that resulted in a total dose of 65 to 70 Gy in definitive radiation patients; 60 to 65 Gy total dose for post-prostatectomy patients

References

  1. Pilepich MV, Caplan R, Byhardt RW, Lawton CA, Gallagher MJ, Mesic JB, Hanks GE, Coughlin CT, Porter A, Shipley WU, Grignon D. Phase III trial of androgen suppression using goserelin in unfavorable-prognosis carcinoma of the prostate treated with definitive radiotherapy: report of Radiation Therapy Oncology Group Protocol 85-31. J Clin Oncol. 1997 Mar;15(3):1013-21. link to original article contains protocol PubMed
    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 protocol 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 verified protocol PubMed
  2. Bolla M, Gonzalez D, Warde P, Dubois JB, Mirimanoff RO, Storme G, Bernier J, Kuten A, Sternberg C, Gil T, Collette L, Pierart M. Improved survival in patients with locally advanced prostate cancer treated with radiotherapy and goserelin. N Engl J Med. 1997 Jul 31;337(5):295-300. link to original article PubMed

Goserelin, Flutamide, RT

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RT: Radiation Therapy

Regimen

Study Evidence Comparator Efficacy
Pilepich et al. 2001 (RTOG 86-10) Phase III RT Seems to have superior cause-specific mortality
Hanks et al. 2003 (RTOG 92-02) Non-randomized portion of RCT
Denham et al. 2005 (TTROG 96.01) Phase III Goserelin & Flutatmide x 6m, RT Not reported
RT Superior DFS
D'Amico et al. 2008 Phase III RT Superior OS
Jones et al. 2011 Phase III RT Seems to have superior OS

Endocrine & Radiotherapy

  • Goserelin (Zoladex) 3.6 mg SC once every 4 weeks, to start 2 months prior to radiation therapy and to continue at least through the end of radiation therapy
  • Flutamide (Eulexin) 250 mg PO three times per day, to start 2 months prior to radiation therapy and to continue at least through the end of radiation therapy
  • Radiation therapy is started 2 months after start of androgen deprivation therapy (ADT), 1.8 to 2 Gy per fraction, with an initial 44 to 46 Gy to the pelvis, then an additional conedown to the prostate that resulted in a total dose of 65 to 70 Gy

Patients in RTOG 92-02 were subsequently randomized to adjuvant goserelin x 2 years versus no further treatment.

References

  1. Pilepich MV, Winter K, John MJ, Mesic JB, Sause W, Rubin P, Lawton C, Machtay M, Grignon D. Phase III radiation therapy oncology group (RTOG) trial 86-10 of androgen deprivation adjuvant to definitive radiotherapy in locally advanced carcinoma of the prostate. Int J Radiat Oncol Biol Phys. 2001 Aug 1;50(5):1243-52. link to original article contains verified protocol PubMed
    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 verified protocol PubMed
  2. Hanks GE, Pajak TF, Porter A, Grignon D, Brereton H, Venkatesan V, Horwitz EM, Lawton C, Rosenthal SA, Sandler HM, Shipley WU; Radiation Therapy Oncology Group. Phase III trial of long-term adjuvant androgen deprivation after neoadjuvant hormonal cytoreduction and radiotherapy in locally advanced carcinoma of the prostate: the Radiation Therapy Oncology Group Protocol 92-02. J Clin Oncol. 2003 Nov 1;21(21):3972-8. Erratum in: J Clin Oncol. 2004 Jan 15;22(2):386. link to original article contains protocol PubMed
    1. Update: Horwitz EM, Bae K, Hanks GE, Porter A, Grignon DJ, Brereton HD, Venkatesan V, Lawton CA, Rosenthal SA, Sandler HM, Shipley WU. Ten-year follow-up of radiation therapy oncology group protocol 92-02: a phase III trial of the duration of elective androgen deprivation in locally advanced prostate cancer. J Clin Oncol. 2008 May 20;26(15):2497-504. Epub 2008 Apr 14. link to original article contains verified protocol PubMed
    2. Update: Lawton CAF, Lin X, Hanks GE, Lepor H, Grignon DJ, Brereton HD, Bedi M, Rosenthal SA, Zeitzer KL, Venkatesan VM, Horwitz EM, Pisansky TM, Kim H, Parliament MB, Rabinovitch R, Roach M 3rd, Kwok Y, Dignam JJ, Sandler HM. Duration of androgen deprivation in locally advanced prostate cancer: Long-term update of NRG Oncology RTOG 9202. Int J Radiat Oncol Biol Phys. 2017 Jun 1;98(2):296-303. Epub 2017 Feb 12. PubMed
  3. Denham JW, Steigler A, Lamb DS, Joseph D, Mameghan H, Turner S, Matthews J, Franklin I, Atkinson C, North J, Poulsen M, Christie D, Spry NA, Tai KH, Wynne C, Duchesne G, Kovacev O, D'Este C; Trans-Tasman Radiation Oncology Group. Short-term androgen deprivation and radiotherapy for locally advanced prostate cancer: results from the Trans-Tasman Radiation Oncology Group 96.01 randomised controlled trial. Lancet Oncol. 2005 Nov;6(11):841-50. link to original article contains protocol PubMed
  4. 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
  5. Jones CU, Hunt D, McGowan DG, Amin MB, Chetner MP, Bruner DW, Leibenhaut MH, Husain SM, Rotman M, Souhami L, Sandler HM, Shipley WU. Radiotherapy and short-term androgen deprivation for localized prostate cancer. N Engl J Med. 2011 Jul 14;365(2):107-18. link to original article contains verified protocol PubMed

Leuprolide, Flutamide, RT

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RT: Radiation Therapy

Regimen

Study Evidence Comparator Efficacy
Jones et al. 2011 Phase III RT Seems to have superior OS

Endocrine & Radiotherapy

  • Leuprolide (Lupron) 7.5 mg SC once every 4 weeks x 4 months, to start 2 months prior to radiation therapy
  • Flutamide (Eulexin) 250 mg PO three times per day x 4 months, to start 2 months prior to radiation therapy
  • Radiation therapy is started 2 months after start of androgen deprivation therapy (ADT), 1.8 to 2 Gy per fraction, with an initial 44 to 46 Gy to the pelvis, then an additional conedown to the prostate that resulted in a total dose of 65 to 70 Gy

References

  1. Jones CU, Hunt D, McGowan DG, Amin MB, Chetner MP, Bruner DW, Leibenhaut MH, Husain SM, Rotman M, Souhami L, Sandler HM, Shipley WU. Radiotherapy and short-term androgen deprivation for localized prostate cancer. N Engl J Med. 2011 Jul 14;365(2):107-18. link to original article contains verified protocol PubMed

Adjuvant hormonal therapy

Goserelin monotherapy

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Regimen

Study Evidence Comparator Efficacy
Hanks et al. 2003 (RTOG 92-02) Phase III No further treatment Seems to have superior OS (*)

Efficacy based on the 2017 update.

Preceding treatment

Endocrine therapy

2-year course

References

  1. Hanks GE, Pajak TF, Porter A, Grignon D, Brereton H, Venkatesan V, Horwitz EM, Lawton C, Rosenthal SA, Sandler HM, Shipley WU; Radiation Therapy Oncology Group. Phase III trial of long-term adjuvant androgen deprivation after neoadjuvant hormonal cytoreduction and radiotherapy in locally advanced carcinoma of the prostate: the Radiation Therapy Oncology Group Protocol 92-02. J Clin Oncol. 2003 Nov 1;21(21):3972-8. Erratum in: J Clin Oncol. 2004 Jan 15;22(2):386. link to original article contains protocol PubMed
    1. Update: Horwitz EM, Bae K, Hanks GE, Porter A, Grignon DJ, Brereton HD, Venkatesan V, Lawton CA, Rosenthal SA, Sandler HM, Shipley WU. Ten-year follow-up of radiation therapy oncology group protocol 92-02: a phase III trial of the duration of elective androgen deprivation in locally advanced prostate cancer. J Clin Oncol. 2008 May 20;26(15):2497-504. Epub 2008 Apr 14. link to original article contains verified protocol PubMed
    2. Update: Lawton CAF, Lin X, Hanks GE, Lepor H, Grignon DJ, Brereton HD, Bedi M, Rosenthal SA, Zeitzer KL, Venkatesan VM, Horwitz EM, Pisansky TM, Kim H, Parliament MB, Rabinovitch R, Roach M 3rd, Kwok Y, Dignam JJ, Sandler HM. Duration of androgen deprivation in locally advanced prostate cancer: Long-term update of NRG Oncology RTOG 9202. Int J Radiat Oncol Biol Phys. 2017 Jun 1;98(2):296-303. Epub 2017 Feb 12. PubMed

Observation

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Regimen

Study Evidence Comparator Efficacy
Hanks et al. 2003 (RTOG 92-02) Phase III Goserelin Seems to have inferior OS (*)

Efficacy based on the 2017 update.

Preceding treatment

References

  1. Hanks GE, Pajak TF, Porter A, Grignon D, Brereton H, Venkatesan V, Horwitz EM, Lawton C, Rosenthal SA, Sandler HM, Shipley WU; Radiation Therapy Oncology Group. Phase III trial of long-term adjuvant androgen deprivation after neoadjuvant hormonal cytoreduction and radiotherapy in locally advanced carcinoma of the prostate: the Radiation Therapy Oncology Group Protocol 92-02. J Clin Oncol. 2003 Nov 1;21(21):3972-8. Erratum in: J Clin Oncol. 2004 Jan 15;22(2):386. link to original article contains protocol PubMed
    1. Update: Horwitz EM, Bae K, Hanks GE, Porter A, Grignon DJ, Brereton HD, Venkatesan V, Lawton CA, Rosenthal SA, Sandler HM, Shipley WU. Ten-year follow-up of radiation therapy oncology group protocol 92-02: a phase III trial of the duration of elective androgen deprivation in locally advanced prostate cancer. J Clin Oncol. 2008 May 20;26(15):2497-504. Epub 2008 Apr 14. link to original article contains verified protocol PubMed
    2. Update: Lawton CAF, Lin X, Hanks GE, Lepor H, Grignon DJ, Brereton HD, Bedi M, Rosenthal SA, Zeitzer KL, Venkatesan VM, Horwitz EM, Pisansky TM, Kim H, Parliament MB, Rabinovitch R, Roach M 3rd, Kwok Y, Dignam JJ, Sandler HM. Duration of androgen deprivation in locally advanced prostate cancer: Long-term update of NRG Oncology RTOG 9202. Int J Radiat Oncol Biol Phys. 2017 Jun 1;98(2):296-303. Epub 2017 Feb 12. PubMed

Hormonal therapy for metastatic or locally advanced disease

ADT & Abiraterone

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ADT: Androgen Deprivation Therapy

Regimen

Study Evidence Comparator Efficacy
James et al. 2017 (STAMPEDE) Phase III ADT Superior OS
Fizazi et al. 2017 (LATITUDE) Phase III ADT Superior OS

Endocrine therapy

Supportive medications

  • Prevention of mineralocorticoid excess with ONE of the following:
    • STAMPEDE except Switzerland: Prednisolone (Millipred) 5 mg PO once per day
    • LATITUDE and STAMPEDE in Switzerland: Prednisone (Sterapred) 5 mg PO once per day
      • LATITUDE: "dose increase of up to 10 mg/day is permitted to manage refractory mineralocorticoid related toxicities"

Continued until progression unless radiotherapy planned, in which case continued for up to 2 years

References

  1. James ND, de Bono JS, Spears MR, Clarke NW, Mason MD, Dearnaley DP, Ritchie AWS, Amos CL, Gilson C, Jones RJ, Matheson D, Millman R, Attard G, Chowdhury S, Cross WR, Gillessen S, Parker CC, Russell JM, Berthold DR, Brawley C, Adab F, Aung S, Birtle AJ, Bowen J, Brock S, Chakraborti P, Ferguson C, Gale J, Gray E, Hingorani M, Hoskin PJ, Lester JF, Malik ZI, McKinna F, McPhail N, Money-Kyrle J, O'Sullivan J, Parikh O, Protheroe A, Robinson A, Srihari NN, Thomas C, Wagstaff J, Wylie J, Zarkar A, Parmar MKB, Sydes MR; STAMPEDE Investigators. Abiraterone for prostate cancer not previously treated with hormone therapy. N Engl J Med. 2017 Jul 27;377(4):338-351. Epub 2017 Jun 3. link to original article link to PMC article supplementary protocol contains verified protocol in supplement PubMed
  2. Fizazi K, Tran N, Fein L, Matsubara N, Rodriguez-Antolin A, Alekseev BY, Özgüroğlu M, Ye D, Feyerabend S, Protheroe A, De Porre P, Kheoh T, Park YC, Todd MB, Chi KN; LATITUDE Investigators. Abiraterone plus prednisone in metastatic, castration-sensitive prostate cancer. N Engl J Med. 2017 Jul 27;377(4):352-360. Epub 2017 Jun 4. link to original article supplementary protocol contains verified protocol in supplement PubMed

ADT & Docetaxel

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ADT: Androgen Deprivation Therapy

Regimen

Study Evidence Comparator Efficacy
Sweeney et al. 2015 (ECOG E3805) Phase III Leuprolide Superior OS

Patients already on androgen deprivation therapy were eligible to participate in ECOG E3805 if there was no evidence of disease progression and if they had started ADT no more than 120 days before randomization.

Chemohormonal therapy

Supportive medications

21-day cycle for up to 6 cycles

References

  1. Gravis G, Fizazi K, Joly F, Oudard S, Priou F, Esterni B, Latorzeff I, Delva R, Krakowski I, Laguerre B, Rolland F, Théodore C, Deplanque G, Ferrero JM, Pouessel D, Mourey L, Beuzeboc P, Zanetta S, Habibian M, Berdah JF, Dauba J, Baciuchka M, Platini C, Linassier C, Labourey JL, Machiels JP, El Kouri C, Ravaud A, Suc E, Eymard JC, Hasbini A, Bousquet G, Soulie M. Androgen-deprivation therapy alone or with docetaxel in non-castrate metastatic prostate cancer (GETUG-AFU 15): a randomised, open-label, phase 3 trial. Lancet Oncol. 2013 Feb;14(2):149-58. Epub 2013 Jan 8. link to original article PubMed
    1. Update: Gravis G, Boher JM, Joly F, Soulié M, Albiges L, Priou F, Latorzeff I, Delva R, Krakowski I, Laguerre B, Rolland F, Théodore C, Deplanque G, Ferrero JM, Culine S, Mourey L, Beuzeboc P, Habibian M, Oudard S, Fizazi K; GETUG. Androgen deprivation therapy (ADT) plus docetaxel versus ADT alone in metastatic non castrate prostate cancer: Impact of metastatic burden and long-term survival analysis of the randomized phase 3 GETUG-AFU15 trial. Eur Urol. 2016 Aug;70(2):256-62. Epub 2015 Nov 21. link to original article PubMed
  2. Sweeney CJ, Chen YH, Carducci M, Liu G, Jarrard DF, Eisenberger M, Wong YN, Hahn N, Kohli M, Cooney MM, Dreicer R, Vogelzang NJ, Picus J, Shevrin D, Hussain M, Garcia JA, DiPaola RS. Chemohormonal therapy in metastatic hormone-sensitive prostate cancer. N Engl J Med. 2015 Aug 20;373(8):737-46. Epub 2015 Aug 5. link to original article contains verified protocol Pubmed
  3. James ND, Sydes MR, Clarke NW, Mason MD, Dearnaley DP, Spears MR, Ritchie AW, Parker CC, Russell JM, Attard G, de Bono J, Cross W, Jones RJ, Thalmann G, Amos C, Matheson D, Millman R, Alzouebi M, Beesley S, Birtle AJ, Brock S, Cathomas R, Chakraborti P, Chowdhury S, Cook A, Elliott T, Gale J, Gibbs S, Graham JD, Hetherington J, Hughes R, Laing R, McKinna F, McLaren DB, O'Sullivan JM, Parikh O, Peedell C, Protheroe A, Robinson AJ, Srihari N, Srinivasan R, Staffurth J, Sundar S, Tolan S, Tsang D, Wagstaff J, Parmar MK; STAMPEDE investigators. Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial. Lancet. 2016 Mar 19;387(10024):1163-77. Epub 2015 Dec 21. link to original article link to PMC article PubMed

Bicalutamide monotherapy

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Regimen

Study Evidence Comparator Efficacy
Tyrrell et al. 1998 Phase III Castration Not reported

Not approved for monotherapy in the United States. See combination regimens with Goserelin & Leuprolide.

Endocrine therapy

References

  1. Tyrrell CJ, Kaisary AV, Iversen P, Anderson JB, Baert L, Tammela T, Chamberlain M, Webster A, Blackledge G. A randomised comparison of 'Casodex' (bicalutamide) 150 mg monotherapy versus castration in the treatment of metastatic and locally advanced prostate cancer. Eur Urol. 1998;33(5):447-56. contains protocol PubMed
    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 verified protocol PubMed

Bicalutamide & Goserelin

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Regimen #1

Study Evidence Comparator Efficacy
Akaza et al. 2004 Phase III Leuprolide Seems to have superior TTP

Endocrine therapy

Regimen #2

Study Evidence Comparator Efficacy
Schellhammer et al. 1995 (CASODEX Combination Study Group) Phase III Bicalutamide & Leuprolide Not reported
Flutamide & Goserelin
Flutamide & Leuprolide 		Superior TTTF

Endocrine therapy

References

  1. Schellhammer P, Sharifi R, Block N, Soloway M, Venner P, Patterson AL, Sarosdy M, Vogelzang N, Jones J, Kolvenbag G. A controlled trial of bicalutamide versus flutamide, each in combination with luteinizing hormone-releasing hormone analogue therapy, in patients with advanced prostate cancer. Casodex Combination Study Group. Urology. 1995 May;45(5):745-52. link to original article PubMed
    1. Update: Schellhammer PF, Sharifi R, Block NL, Soloway MS, Venner PM, Patterson AL, Sarosdy MF, Vogelzang NJ, Chen Y, Kolvenbag GJ. A controlled trial of bicalutamide versus flutamide, each in combination with luteinizing hormone-releasing hormone analogue therapy, in patients with advanced prostate carcinoma. Analysis of time to progression. CASODEX Combination Study Group. Cancer. 1996 Nov 15;78(10):2164-9. link to original article contains protocol PubMed
    2. Update: Soloway MS, Schellhammer P, Sharifi R, Venner P, Patterson AL, Sarosdy M, Vogelzang N, Jones J, Kolvenbag G. A controlled trial of Casodex (bicalutamide) vs. flutamide, each in combination with luteinising hormone-releasing hormone analogue therapy in patients with advanced prostate cancer. Casodex Combination Study Group. Eur Urol. 1996;29 Suppl 2:105-9. contains protocol PubMed
  2. Akaza H, Yamaguchi A, Matsuda T, Igawa M, Kumon H, Soeda A, Arai Y, Usami M, Naito S, Kanetake H, Ohashi Y. Superior anti-tumor efficacy of bicalutamide 80 mg in combination with a luteinizing hormone-releasing hormone (LHRH) agonist versus LHRH agonist monotherapy as first-line treatment for advanced prostate cancer: interim results of a randomized study in Japanese patients. Jpn J Clin Oncol. 2004 Jan;34(1):20-8. link to original article contains verified protocol PubMed

Bicalutamide & Leuprolide

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Regimen #1

Study Evidence Comparator Efficacy
Akaza et al. 2004 Phase III Leuprolide Seems to have superior TTP

Endocrine therapy

Regimen #2

Study Evidence Comparator Efficacy
Schellhammer et al. 1995 (CASODEX Combination Study Group) Phase III Bicalutamide & Goserelin Not reported
Flutamide & Goserelin
Flutamide & Leuprolide 		Superior TTTF

Endocrine therapy

References

  1. Schellhammer P, Sharifi R, Block N, Soloway M, Venner P, Patterson AL, Sarosdy M, Vogelzang N, Jones J, Kolvenbag G. A controlled trial of bicalutamide versus flutamide, each in combination with luteinizing hormone-releasing hormone analogue therapy, in patients with advanced prostate cancer. Casodex Combination Study Group. Urology. 1995 May;45(5):745-52. link to original article PubMed
    1. Update: Schellhammer PF, Sharifi R, Block NL, Soloway MS, Venner PM, Patterson AL, Sarosdy MF, Vogelzang NJ, Chen Y, Kolvenbag GJ. A controlled trial of bicalutamide versus flutamide, each in combination with luteinizing hormone-releasing hormone analogue therapy, in patients with advanced prostate carcinoma. Analysis of time to progression. CASODEX Combination Study Group. Cancer. 1996 Nov 15;78(10):2164-9. link to original article contains protocol PubMed
    2. Update: Soloway MS, Schellhammer P, Sharifi R, Venner P, Patterson AL, Sarosdy M, Vogelzang N, Jones J, Kolvenbag G. A controlled trial of Casodex (bicalutamide) vs. flutamide, each in combination with luteinising hormone-releasing hormone analogue therapy in patients with advanced prostate cancer. Casodex Combination Study Group. Eur Urol. 1996;29 Suppl 2:105-9. contains protocol PubMed
  2. Akaza H, Yamaguchi A, Matsuda T, Igawa M, Kumon H, Soeda A, Arai Y, Usami M, Naito S, Kanetake H, Ohashi Y. Superior anti-tumor efficacy of bicalutamide 80 mg in combination with a luteinizing hormone-releasing hormone (LHRH) agonist versus LHRH agonist monotherapy as first-line treatment for advanced prostate cancer: interim results of a randomized study in Japanese patients. Jpn J Clin Oncol. 2004 Jan;34(1):20-8. link to original article contains verified protocol PubMed

Degarelix monotherapy

Example orders

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Regimen #1, 240/80

Study Evidence Comparator Efficacy
Klotz et al. 2008 (CS21) Phase III Degarelix 240/160 Non-inferior testosterone suppression
Leuprolide Non-inferior testosterone suppression

This is the recommended dose in package insert.

Endocrine therapy

  • Degarelix (Firmagon) 240 mg (given as 2 x 120 mg injections) SC once, then 80 mg SC once every 28 days

Regimen #2, 240/160

Study Evidence Comparator Efficacy
Klotz et al. 2008 (CS21) Phase III Degarelix 240/80 Non-inferior testosterone suppression
Leuprolide Non-inferior testosterone suppression

Endocrine therapy

  • Degarelix (Firmagon) 240 mg (given as 2 x 120 mg injections) SC once, then 160 mg SC once every 28 days

References

  1. Klotz L, Boccon-Gibod L, Shore ND, Andreou C, Persson BE, Cantor P, Jensen JK, Olesen TK, Schröder FH. The efficacy and safety of degarelix: a 12-month, comparative, randomized, open-label, parallel-group phase III study in patients with prostate cancer. BJU Int. 2008 Dec;102(11):1531-8. link to original article contains verified protocol PubMed
    1. Update: Tombal B, Miller K, Boccon-Gibod L, Schröder F, Shore N, Crawford ED, Moul J, Jensen JK, Kold Olesen T, Persson BE. Additional analysis of the secondary end point of biochemical recurrence rate in a phase 3 trial (CS21) comparing degarelix 80 mg versus leuprolide in prostate cancer patients segmented by baseline characteristics. Eur Urol. 2010 May;57(5):836-42. Epub 2009 Nov 20. link to original article contains verified protocol PubMed

Flutamide monotherapy

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Regimen

Study Evidence Comparator Efficacy
Boccon-Gibod et al. 1997 Phase III Orchiectomy Seems not superior
Fosså et al. 2001 (EORTC) Phase III Prednisone Seems not superior

Not approved for monotherapy in the United States. See combination regimens with Goserelin & Leuprolide.

Endocrine therapy

References

  1. Boccon-Gibod L, Fournier G, Bottet P, Marechal JM, Guiter J, Rischman P, Hubert J, Soret JY, Mangin P, Mallo C, Fraysse CE. Flutamide versus orchidectomy in the treatment of metastatic prostate carcinoma. Eur Urol. 1997;32(4):391-5. contains protocol PubMed
  2. 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
  3. Fosså SD, Slee PH, Brausi M, Horenblas S, Hall RR, Hetherington JW, Aaronson N, de Prijck L, Collette L. Flutamide versus prednisone in patients with prostate cancer symptomatically progressing after androgen-ablative therapy: a phase III study of the European organization for research and treatment of cancer genitourinary group. J Clin Oncol. 2001 Jan 1;19(1):62-71. link to original article contains protocol PubMed

Flutamide & Goserelin

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Regimen

Study Evidence Comparator Efficacy
Denis et al. 1993 (EORTC 30853) Phase III Bilateral orchiectomy Seems to have superior OS
Schellhammer et al. 1995 (CASODEX Combination Study Group) Phase III Bicalutamide & Goserelin
Bicalutamide & Leuprolide 		Inferior TTTF
Flutamide & Leuprolide Not reported

Endocrine therapy

References

  1. Denis LJ, Carnelro de Moura JL, Bono A, Sylvester R, Whelan P, Newling D, Depauw M. Goserelin acetate and flutamide versus bilateral orchiectomy: a phase III EORTC trial (30853). EORTC GU Group and EORTC Data Center. Urology. 1993 Aug;42(2):119-29; discussion 129-30. contains protocol PubMed
    1. Update: Denis LJ, Keuppens F, Smith PH, Whelan P, de Moura JL, Newling D, Bono A, Sylvester R. Maximal androgen blockade: final analysis of EORTC phase III trial 30853. EORTC Genito-Urinary Tract Cancer Cooperative Group and the EORTC Data Center. Eur Urol. 1998;33(2):144-51. PubMed
  2. Schellhammer P, Sharifi R, Block N, Soloway M, Venner P, Patterson AL, Sarosdy M, Vogelzang N, Jones J, Kolvenbag G. A controlled trial of bicalutamide versus flutamide, each in combination with luteinizing hormone-releasing hormone analogue therapy, in patients with advanced prostate cancer. Casodex Combination Study Group. Urology. 1995 May;45(5):745-52. link to original article PubMed
    1. Update: Schellhammer PF, Sharifi R, Block NL, Soloway MS, Venner PM, Patterson AL, Sarosdy MF, Vogelzang NJ, Chen Y, Kolvenbag GJ. A controlled trial of bicalutamide versus flutamide, each in combination with luteinizing hormone-releasing hormone analogue therapy, in patients with advanced prostate carcinoma. Analysis of time to progression. CASODEX Combination Study Group. Cancer. 1996 Nov 15;78(10):2164-9. link to original article contains protocol PubMed
    2. Update: Soloway MS, Schellhammer P, Sharifi R, Venner P, Patterson AL, Sarosdy M, Vogelzang N, Jones J, Kolvenbag G. A controlled trial of Casodex (bicalutamide) vs. flutamide, each in combination with luteinising hormone-releasing hormone analogue therapy in patients with advanced prostate cancer. Casodex Combination Study Group. Eur Urol. 1996;29 Suppl 2:105-9. contains protocol PubMed
  3. Hussain M, Tangen CM, Berry DL, Higano CS, Crawford ED, Liu G, Wilding G, Prescott S, Kanaga Sundaram S, Small EJ, Dawson NA, Donnelly BJ, Venner PM, Vaishampayan UN, Schellhammer PF, Quinn DI, Raghavan D, Ely B, Moinpour CM, Vogelzang NJ, Thompson IM Jr. Intermittent versus continuous androgen deprivation in prostate cancer. N Engl J Med. 2013 Apr 4;368(14):1314-25. link to original article link to PMC article supplementary protocol contains verified protocol in supplementary protocol PubMed

Flutamide & Leuprolide

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Regimen

Study Evidence Comparator Efficacy
Schellhammer et al. 1995 (CASODEX Combination Study Group) Phase III Bicalutamide & Goserelin
Bicalutamide & Leuprolide 		Inferior TTTF
Flutamide & Goserelin Not reported

Endocrine therapy

References

  1. Schellhammer P, Sharifi R, Block N, Soloway M, Venner P, Patterson AL, Sarosdy M, Vogelzang N, Jones J, Kolvenbag G. A controlled trial of bicalutamide versus flutamide, each in combination with luteinizing hormone-releasing hormone analogue therapy, in patients with advanced prostate cancer. Casodex Combination Study Group. Urology. 1995 May;45(5):745-52. link to original article PubMed
    1. Update: Schellhammer PF, Sharifi R, Block NL, Soloway MS, Venner PM, Patterson AL, Sarosdy MF, Vogelzang NJ, Chen Y, Kolvenbag GJ. A controlled trial of bicalutamide versus flutamide, each in combination with luteinizing hormone-releasing hormone analogue therapy, in patients with advanced prostate carcinoma. Analysis of time to progression. CASODEX Combination Study Group. Cancer. 1996 Nov 15;78(10):2164-9. link to original article contains protocol PubMed
    2. Update: Soloway MS, Schellhammer P, Sharifi R, Venner P, Patterson AL, Sarosdy M, Vogelzang N, Jones J, Kolvenbag G. A controlled trial of Casodex (bicalutamide) vs. flutamide, each in combination with luteinising hormone-releasing hormone analogue therapy in patients with advanced prostate cancer. Casodex Combination Study Group. Eur Urol. 1996;29 Suppl 2:105-9. contains protocol PubMed
  2. Hussain M, Tangen CM, Berry DL, Higano CS, Crawford ED, Liu G, Wilding G, Prescott S, Kanaga Sundaram S, Small EJ, Dawson NA, Donnelly BJ, Venner PM, Vaishampayan UN, Schellhammer PF, Quinn DI, Raghavan D, Ely B, Moinpour CM, Vogelzang NJ, Thompson IM Jr. Intermittent versus continuous androgen deprivation in prostate cancer. N Engl J Med. 2013 Apr 4;368(14):1314-25. link to original article link to PMC article supplementary protocol contains verified protocol in supplementary protocol PubMed

Goserelin monotherapy

Example orders

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Regimen

Study Evidence Comparator Efficacy
Soloway et al. 1991 (Zoladex Prostate Study Group) Phase III Bilateral orchiectomy Seems not superior
Kaisary et al. 1991 Phase III Bilateral orchiectomy Seems not superior

Endocrine therapy

References

  1. Soloway MS, Chodak G, Vogelzang NJ, Block NL, Schellhammer PF, Smith JA Jr, Scott M, Kennealey G, Gau TC. Zoladex versus orchiectomy in treatment of advanced prostate cancer: a randomized trial. Zoladex Prostate Study Group. Urology. 1991 Jan;37(1):46-51. PubMed
    1. Update: Vogelzang NJ, Chodak GW, Soloway MS, Block NL, Schellhammer PF, Smith JA Jr, Caplan RJ, Kennealey GT. Goserelin versus orchiectomy in the treatment of advanced prostate cancer: final results of a randomized trial. Zoladex Prostate Study Group. Urology. 1995 Aug;46(2):220-6. link to original article contains verified protocol PubMed
  2. Kaisary AV, Tyrrell CJ, Peeling WB, Griffiths K. Comparison of LHRH analogue (Zoladex) with orchiectomy in patients with metastatic prostatic carcinoma. Br J Urol. 1991 May;67(5):502-8. PubMed

Leuprolide monotherapy

Example orders

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Regimen #1, 1-month depot, 3.75 mg

Study Evidence Comparator Efficacy
Akaza et al. 2004 Phase III Bicalutamide & Goserelin
Bicalutamide & Leuprolide 		Seems to have inferior TTP

Endocrine therapy

Regimen #2, 1-month depot, 7.5 mg

Study Evidence Comparator Efficacy
Klotz et al. 2008 (CS21) Phase III Degarelix 240/80 Non-inferior testosterone suppression
Degarelix 240/160 Non-inferior testosterone suppression

Endocrine therapy

Regimen #3, 3-month depot

Study Evidence
Sharifi et al. 1996 Phase II

Endocrine therapy

Regimen #4, 4-month depot

Study Evidence
Sharifi et al. 1998 Phase II

Endocrine therapy

Other

Supportive medications

  • (varies depending on reference):
  • Bicalutamide (Casodex) 50 mg PO once per day for protection from testosterone flare

References

  1. Sharifi R, Bruskewitz RC, Gittleman MC, Graham SD Jr, Hudson PB, Stein B. Leuprolide acetate 22.5 mg 12-week depot formulation in the treatment of patients with advanced prostate cancer. Clin Ther. 1996 Jul-Aug;18(4):647-57. link to original article contains verified protocol PubMed
  2. Sharifi R, Knoll LD, Smith J, Kramolowsky E. Leuprolide acetate (30-mg depot every four months) in the treatment of advanced prostate cancer. Urology. 1998 Feb;51(2):271-6. link to original article PubMed
  3. Akaza H, Yamaguchi A, Matsuda T, Igawa M, Kumon H, Soeda A, Arai Y, Usami M, Naito S, Kanetake H, Ohashi Y. Superior anti-tumor efficacy of bicalutamide 80 mg in combination with a luteinizing hormone-releasing hormone (LHRH) agonist versus LHRH agonist monotherapy as first-line treatment for advanced prostate cancer: interim results of a randomized study in Japanese patients. Jpn J Clin Oncol. 2004 Jan;34(1):20-8. link to original article contains verified protocol PubMed
  4. Loblaw DA, Virgo KS, Nam R, Somerfield MR, Ben-Josef E, Mendelson DS, Middleton R, Sharp SA, Smith TJ, Talcott J, Taplin M, Vogelzang NJ, Wade JL 3rd, Bennett CL, Scher HI; American Society of Clinical Oncology. Initial hormonal management of androgen-sensitive metastatic, recurrent, or progressive prostate cancer: 2006 update of an American Society of Clinical Oncology practice guideline. J Clin Oncol. 2007 Apr 20;25(12):1596-605. Epub 2007 Apr 2. link to original article PubMed
  5. Klotz L, Boccon-Gibod L, Shore ND, Andreou C, Persson BE, Cantor P, Jensen JK, Olesen TK, Schröder FH. The efficacy and safety of degarelix: a 12-month, comparative, randomized, open-label, parallel-group phase III study in patients with prostate cancer. BJU Int. 2008 Dec;102(11):1531-8. link to original article contains verified protocol PubMed
    1. Update: Tombal B, Miller K, Boccon-Gibod L, Schröder F, Shore N, Crawford ED, Moul J, Jensen JK, Kold Olesen T, Persson BE. Additional analysis of the secondary end point of biochemical recurrence rate in a phase 3 trial (CS21) comparing degarelix 80 mg versus leuprolide in prostate cancer patients segmented by baseline characteristics. Eur Urol. 2010 May;57(5):836-42. Epub 2009 Nov 20. link to original article contains verified protocol PubMed
  6. Sweeney CJ, Chen YH, Carducci M, Liu G, Jarrard DF, Eisenberger M, Wong YN, Hahn N, Kohli M, Cooney MM, Dreicer R, Vogelzang NJ, Picus J, Shevrin D, Hussain M, Garcia JA, DiPaola RS. Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer. N Engl J Med. 2015 Aug 20;373(8):737-46. Epub 2015 Aug 5. link to original article contains verified protocol Pubmed

Nilutamide & Orchiectomy

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Regimen

Study Evidence Comparator Efficacy
Janknegt et al. 1993 (International Anandron Study Group) Phase III Orchiectomy Superior PFS

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

Endocrine therapy

References

  1. Janknegt RA, Abbou CC, Bartoletti R, Bernstein-Hahn L, Bracken B, Brisset JM, Da Silva FC, Chisholm G, Crawford ED, Debruyne FM et al. Orchiectomy and nilutamide or placebo as treatment of metastatic prostatic cancer in a multinational double-blind randomized trial. J Urol. 1993 Jan;149(1):77-82; discussion 83. PubMed
    1. Update: Janknegt RA. Total androgen blockade with the use of orchiectomy and nilutamide (Anandron) or placebo as treatment of metastatic prostate cancer. Anandron International Study Group. Cancer. 1993 Dec 15;72(12 Suppl):3874-7. PubMed
    2. Update: Dijkman GA, Janknegt RA, De Reijke TM, Debruyne FM. Long-term efficacy and safety of nilutamide plus castration in advanced prostate cancer, and the significance of early prostate specific antigen normalization. International Anandron Study Group. J Urol. 1997 Jul;158(1):160-3. PubMed
    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 verified protocol PubMed
  2. Nilutamide (Nilandron) package insert

Metastatic disease, second-line hormonal therapy

Abiraterone & Prednisone

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Regimen

Study Evidence ORR, PSA RR Comparator Comparator ORR, PSA RR Efficacy Pt Population
de Bono et al. 2011 (COU-AA-301) Phase III 14% (95% CI n/a), 29% Prednisone 3% (95% CI n/a), 6% Superior OS Chemo-exposed
Ryan et al. 2013 (COU-AA-302) Phase III 36% (95% CI n/a), 62% Prednisone 16% (95% CI n/a), 24% Seems to have superior OS Chemo-naive

Endocrine therapy

References

  1. de Bono JS, Logothetis CJ, Molina A, Fizazi K, North S, Chu L, Chi KN, Jones RJ, Goodman OB Jr, Saad F, Staffurth JN, Mainwaring P, Harland S, Flaig TW, Hutson TE, Cheng T, Patterson H, Hainsworth JD, Ryan CJ, Sternberg CN, Ellard SL, Fléchon A, Saleh M, Scholz M, Efstathiou E, Zivi A, Bianchini D, Loriot Y, Chieffo N, Kheoh T, Haqq CM, Scher HI; COU-AA-301 Investigators. Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med. 2011 May 26;364(21):1995-2005. link to original article contains verified protocol link to PMC article PubMed
    1. Update: Fizazi K, Scher HI, Molina A, Logothetis CJ, Chi KN, Jones RJ, Staffurth JN, North S, Vogelzang NJ, Saad F, Mainwaring P, Harland S, Goodman OB Jr, Sternberg CN, Li JH, Kheoh T, Haqq CM, de Bono JS; COU-AA-301 Investigators. Abiraterone acetate for treatment of metastatic castration-resistant prostate cancer: final overall survival analysis of the COU-AA-301 randomised, double-blind, placebo-controlled phase 3 study. Lancet Oncol. 2012 Oct;13(10):983-92. Epub 2012 Sep 18. link to original article contains verified protocol PubMed
    2. Update: Logothetis CJ, Basch E, Molina A, Fizazi K, North SA, Chi KN, Jones RJ, Goodman OB, Mainwaring PN, Sternberg CN, Efstathiou E, Gagnon DD, Rothman M, Hao Y, Liu CS, Kheoh TS, Haqq CM, Scher HI, de Bono JS. Effect of abiraterone acetate and prednisone compared with placebo and prednisone on pain control and skeletal-related events in patients with metastatic castration-resistant prostate cancer: exploratory analysis of data from the COU-AA-301 randomised trial. Lancet Oncol. 2012 Dec;13(12):1210-7. Epub 2012 Nov 9. link to original article contains verified protocol PubMed
  2. Ryan CJ, Smith MR, de Bono JS, Molina A, Logothetis CJ, de Souza P, Fizazi K, Mainwaring P, Piulats JM, Ng S, Carles J, Mulders PF, Basch E, Small EJ, Saad F, Schrijvers D, Van Poppel H, Mukherjee SD, Suttmann H, Gerritsen WR, Flaig TW, George DJ, Yu EY, Efstathiou E, Pantuck A, Winquist E, Higano CS, Taplin ME, Park Y, Kheoh T, Griffin T, Scher HI, Rathkopf DE; COU-AA-302 Investigators. Abiraterone in metastatic prostate cancer without previous chemotherapy. N Engl J Med. 2013 Jan 10;368(2):138-48. Epub 2012 Dec 10. link to original article contains verified protocol link to PMC article PubMed
    1. Update: Ryan CJ, Smith MR, Fizazi K, Saad F, Mulders PF, Sternberg CN, Miller K, Logothetis CJ, Shore ND, Small EJ, Carles J, Flaig TW, Taplin ME, Higano CS, de Souza P, de Bono JS, Griffin TW, De Porre P, Yu MK, Park YC, Li J, Kheoh T, Naini V, Molina A, Rathkopf DE; COU-AA-302 Investigators. Abiraterone acetate plus prednisone versus placebo plus prednisone in chemotherapy-naive men with metastatic castration-resistant prostate cancer (COU-AA-302): final overall survival analysis of a randomised, double-blind, placebo-controlled phase 3 study. Lancet Oncol. 2015 Feb;16(2):152-60. Epub 2015 Jan 16. link to original article PubMed

Antiandrogen withdrawal

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Regimen

Study Evidence Comparator Efficacy
Small et al. 2004 (CALGB 9583) Phase III Ketoconazole & Hydrocortisone Inferior PSA response

Refers to cessation of antiandrogen therapy.

References

  1. Small EJ, Halabi S, Dawson NA, Stadler WM, Rini BI, Picus J, Gable P, Torti FM, Kaplan E, Vogelzang NJ. Antiandrogen withdrawal alone or in combination with ketoconazole in androgen-independent prostate cancer patients: a phase III trial (CALGB 9583). J Clin Oncol. 2004 Mar 15;22(6):1025-33. link to original article contains verified protocol PubMed

Bicalutamide monotherapy

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Regimen

Study Evidence ORR, PSA RR Comparator Comparator ORR, PSA RR Efficacy Pt Population
Penson et al. 2016 (STRIVE) Phase II pts w/ measurable disease: 14% (95% CI n/a), 31% (95% CI n/a) Enzalutamide pts w/ measurable disease: 60% (95% CI n/a), 81% (95% CI n/a) Inferior PFS Chemo-naive, abi and keto-naive

Patients continued ADT while on study; details not provided.

Endocrine therapy

Continued until progression

References

  1. Penson DF, Armstrong AJ, Concepcion R, Agarwal N, Olsson C, Karsh L, Dunshee C, Wang F, Wu K, Krivoshik A, Phung D, Higano CS. Enzalutamide Versus Bicalutamide in Castration-Resistant Prostate Cancer: The STRIVE Trial. J Clin Oncol. 2016 Jun 20;34(18):2098-106. Epub 2016 Jan 25. link to original article contains protocol PubMed

Enzalutamide monotherapy

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Regimen

Study Evidence ORR, PSA RR Comparator Comparator ORR, PSA RR Efficacy Pt Population
Scher et al. 2012 (AFFIRM) Phase III 29% (95% CI n/a), 54% Placebo 4% (95% CI n/a), 2% Superior OS Chemo-exposed (docetaxel)
Beer et al. 2014 (PREVAIL) Phase III 59% (95% CI n/a), 78% Placebo 5% (95% CI n/a), 3% Superior OS Chemo and abiraterone naive
Penson et al. 2016 (STRIVE) Randomized Phase II 60% (95% CI n/a), 81% Bicalutamide 14% (95% CI n/a), 31% Superior PFS Chemo and bicalutamide naive

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

Endocrine therapy

Continued until progression

References

  1. Scher HI, Fizazi K, Saad F, Taplin ME, Sternberg CN, Miller K, de Wit R, Mulders P, Chi KN, Shore ND, Armstrong AJ, Flaig TW, Fléchon A, Mainwaring P, Fleming M, Hainsworth JD, Hirmand M, Selby B, Seely L, de Bono JS; AFFIRM Investigators. Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med. 2012 Sep 27;367(13):1187-97. Epub 2012 Aug 15. link to original article contains verified protocol PubMed
  2. Beer TM, Armstrong AJ, Rathkopf DE, Loriot Y, Sternberg CN, Higano CS, Iversen P, Bhattacharya S, Carles J, Chowdhury S, Davis ID, de Bono JS, Evans CP, Fizazi K, Joshua AM, Kim CS, Kimura G, Mainwaring P, Mansbach H, Miller K, Noonberg SB, Perabo F, Phung D, Saad F, Scher HI, Taplin ME, Venner PM, Tombal B; PREVAIL Investigators. Enzalutamide in metastatic prostate cancer before chemotherapy. N Engl J Med. 2014 Jul 31;371(5):424-33. Epub 2014 Jun 1. link to original article link to PMC article PubMed
  3. Penson DF, Armstrong AJ, Concepcion R, Agarwal N, Olsson C, Karsh L, Dunshee C, Wang F, Wu K, Krivoshik A, Phung D, Higano CS. Enzalutamide versus bicalutamide in castration-resistant prostate cancer: The STRIVE trial. J Clin Oncol. 2016 Jun 20;34(18):2098-106. Epub 2016 Jan 25. link to original article contains protocol PubMed

Ketoconazole & Hydrocortisone

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Regimen

Study Evidence ORR, PSA RR Comparator Comparator ORR, PSA RR Efficacy Pt Population
Small et al. 2004 (CALGB 9583) Phase III pts w/ measurable disease: 20% (95% CI 11 - 32), 27% (95% CI 20 - 35) Antiandrogen withdrawal pts w/ measurable disease: 2% (95% CI 0 - 11), 11% (95% CI 7 - 17) Superior PSA response Progression at ADT, i.e. CRPC

Endocrine therapy

References

  1. Small EJ, Halabi S, Dawson NA, Stadler WM, Rini BI, Picus J, Gable P, Torti FM, Kaplan E, Vogelzang NJ. Antiandrogen withdrawal alone or in combination with ketoconazole in androgen-independent prostate cancer patients: a phase III trial (CALGB 9583). J Clin Oncol. 2004 Mar 15;22(6):1025-33. link to original article contains verified protocol PubMed

Ketoconazole, Hydrocortisone, Dutasteride

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Regimen

Study Evidence
Taplin et al. 2009 Phase II

Endocrine therapy

References

  1. Taplin ME, Regan MM, Ko YJ, Bubley GJ, Duggan SE, Werner L, Beer TM, Ryan CW, Mathew P, Tu SM, Denmeade SR, Oh WK, Sartor O, Mantzoros CS, Rittmaster R, Kantoff PW, Balk SP. Phase II study of androgen synthesis inhibition with ketoconazole, hydrocortisone, and dutasteride in asymptomatic castration-resistant prostate cancer. Clin Cancer Res. 2009 Nov 15;15(22):7099-105. Epub 2009 Nov 3. link to original article contains verified protocol link to PMC article PubMed

Prednisone monotherapy

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Regimen #1, 5 mg BID

Study Evidence Comparator Efficacy
de Bono et al. 2011 (COU-AA-301) Phase III Abiraterone & Prednisone Inferior OS
Ryan et al. 2013 (COU-AA-302) Phase III Abiraterone & Prednisone Seems to have inferior OS
Smith et al. 2016 (COMET-1) Phase III Cabozantinib Seems not superior

Endocrine therapy

Continuously

Regimen #2, 5 mg QID

Study Evidence Comparator Efficacy
Fosså et al. 2001 (EORTC) Phase III Flutamide Seems not superior

Endocrine therapy

Continuously

References

  1. Tannock IF, Osoba D, Stockler MR, Ernst DS, Neville AJ, Moore MJ, Armitage GR, Wilson JJ, Venner PM, Coppin CM, Murphy KC. Chemotherapy with mitoxantrone plus prednisone or prednisone alone for symptomatic hormone-resistant prostate cancer: a Canadian randomized trial with palliative end points. J Clin Oncol. 1996 Jun;14(6):1756-64. link to original article PubMed
    1. HRQoL analysis: Osoba D, Tannock IF, Ernst DS, Neville AJ. Health-related quality of life in men with metastatic prostate cancer treated with prednisone alone or mitoxantrone and prednisone. J Clin Oncol. 1999 Jun;17(6):1654-63. link to original article PubMed
  2. Fosså SD, Slee PH, Brausi M, Horenblas S, Hall RR, Hetherington JW, Aaronson N, de Prijck L, Collette L. Flutamide versus prednisone in patients with prostate cancer symptomatically progressing after androgen-ablative therapy: a phase III study of the European organization for research and treatment of cancer genitourinary group. J Clin Oncol. 2001 Jan 1;19(1):62-71. link to original article contains protocol PubMed
  3. de Bono JS, Logothetis CJ, Molina A, Fizazi K, North S, Chu L, Chi KN, Jones RJ, Goodman OB Jr, Saad F, Staffurth JN, Mainwaring P, Harland S, Flaig TW, Hutson TE, Cheng T, Patterson H, Hainsworth JD, Ryan CJ, Sternberg CN, Ellard SL, Fléchon A, Saleh M, Scholz M, Efstathiou E, Zivi A, Bianchini D, Loriot Y, Chieffo N, Kheoh T, Haqq CM, Scher HI; COU-AA-301 Investigators. Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med. 2011 May 26;364(21):1995-2005. link to original article contains verified protocol link to PMC article PubMed
    1. Update: Fizazi K, Scher HI, Molina A, Logothetis CJ, Chi KN, Jones RJ, Staffurth JN, North S, Vogelzang NJ, Saad F, Mainwaring P, Harland S, Goodman OB Jr, Sternberg CN, Li JH, Kheoh T, Haqq CM, de Bono JS; COU-AA-301 Investigators. Abiraterone acetate for treatment of metastatic castration-resistant prostate cancer: final overall survival analysis of the COU-AA-301 randomised, double-blind, placebo-controlled phase 3 study. Lancet Oncol. 2012 Oct;13(10):983-92. Epub 2012 Sep 18. link to original article contains verified protocol PubMed
    2. Update: Logothetis CJ, Basch E, Molina A, Fizazi K, North SA, Chi KN, Jones RJ, Goodman OB, Mainwaring PN, Sternberg CN, Efstathiou E, Gagnon DD, Rothman M, Hao Y, Liu CS, Kheoh TS, Haqq CM, Scher HI, de Bono JS. Effect of abiraterone acetate and prednisone compared with placebo and prednisone on pain control and skeletal-related events in patients with metastatic castration-resistant prostate cancer: exploratory analysis of data from the COU-AA-301 randomised trial. Lancet Oncol. 2012 Dec;13(12):1210-7. Epub 2012 Nov 9. link to original article contains verified protocol PubMed
  4. Ryan CJ, Smith MR, de Bono JS, Molina A, Logothetis CJ, de Souza P, Fizazi K, Mainwaring P, Piulats JM, Ng S, Carles J, Mulders PF, Basch E, Small EJ, Saad F, Schrijvers D, Van Poppel H, Mukherjee SD, Suttmann H, Gerritsen WR, Flaig TW, George DJ, Yu EY, Efstathiou E, Pantuck A, Winquist E, Higano CS, Taplin ME, Park Y, Kheoh T, Griffin T, Scher HI, Rathkopf DE; COU-AA-302 Investigators. Abiraterone in metastatic prostate cancer without previous chemotherapy. N Engl J Med. 2013 Jan 10;368(2):138-48. Epub 2012 Dec 10. link to original article contains verified protocol link to PMC article PubMed
    1. Update: Ryan CJ, Smith MR, Fizazi K, Saad F, Mulders PF, Sternberg CN, Miller K, Logothetis CJ, Shore ND, Small EJ, Carles J, Flaig TW, Taplin ME, Higano CS, de Souza P, de Bono JS, Griffin TW, De Porre P, Yu MK, Park YC, Li J, Kheoh T, Naini V, Molina A, Rathkopf DE; COU-AA-302 Investigators. Abiraterone acetate plus prednisone versus placebo plus prednisone in chemotherapy-naive men with metastatic castration-resistant prostate cancer (COU-AA-302): final overall survival analysis of a randomised, double-blind, placebo-controlled phase 3 study. Lancet Oncol. 2015 Feb;16(2):152-60. Epub 2015 Jan 16. link to SD article PubMed
  5. Smith M, De Bono J, Sternberg C, Le Moulec S, Oudard S, De Giorgi U, Krainer M, Bergman A, Hoelzer W, De Wit R, Bögemann M, Saad F, Cruciani G, Thiery-Vuillemin A, Feyerabend S, Miller K, Houédé N, Hussain S, Lam E, Polikoff J, Stenzl A, Mainwaring P, Ramies D, Hessel C, Weitzman A, Fizazi K. Phase III study of cabozantinib in previously treated metastatic castration-resistant prostate cancer: COMET-1. J Clin Oncol. 2016 Sep 1;34(25):3005-13. Epub 2016 Jul 11. link to original article contains verified protocol PubMed

Chemotherapy for metastatic castrate-resistant disease

Cabazitaxel & Prednisone

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Example orders

Regimen #1, 20 mg/m2

Study Evidence Comparator Efficacy
Oudard et al. 2017 (FIRSTANA) Phase III Cabazitaxel 25 mg/m2 & Prednisone Seems not superior
Docetaxel & Prednisone Seems not superior
Eisenberger et al. 2017 (PROSELICA) Phase III Cabazitaxel 25 mg/m2 & Prednisone Non-inferior OS

Chemotherapy

21-day cycles

Regimen #2, 25 mg/m2

Study Evidence ORR, PSA RR Comparator Comparator ORR, PSA RR Efficacy Pt Population
de Bono et al. 2010 (TROPIC) Phase III 14% (95% CI 10-19)
39% (95% CI 34-44) (*) 		Mitoxantrone & Prednisone 4% (95% CI 2-7)
18% (95% CI 14-22) (*) 		Superior OS Progressed on docetaxel
Oudard et al. 2017 (FIRSTANA) Phase III Cabazitaxel 20 mg/m2 & Prednisone Seems not superior
Docetaxel & Prednisone Seems not superior
Eisenberger et al. 2017 (PROSELICA) Phase III Cabazitaxel 20 mg/m2 & Prednisone Non-inferior OS
Beer et al. 2017 (AFFINITY) Phase III Cabazitaxel, Prednisone, Custirsen Seems not superior Progressed on docetaxel

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

Chemotherapy

Supportive medications

21-day cycle for up to 10 cycles (TROPIC) or until progression (PROSELICA)

References

  1. de Bono JS, Oudard S, Ozguroglu M, Hansen S, Machiels JP, Kocak I, Gravis G, Bodrogi I, Mackenzie MJ, Shen L, Roessner M, Gupta S, Sartor AO; TROPIC Investigators. Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial. Lancet. 2010 Oct 2;376(9747):1147-54. link to original article contains verified protocol PubMed
  2. Oudard S, Fizazi K, Sengeløv L, Daugaard G, Saad F, Hansen S, Hjälm-Eriksson M, Jassem J, Thiery-Vuillemin A, Caffo O, Castellano D, Mainwaring PN, Bernard J, Shen L, Chadjaa M, Sartor O. Cabazitaxel versus docetaxel as first-line therapy for patients with metastatic castration-resistant prostate cancer: A randomized phase III Trial-FIRSTANA. J Clin Oncol. 2017 Oct 1;35(28):3189-3197. Epub 2017 Jul 28. link to original article contains verified protocol PubMed
  3. Eisenberger M, Hardy-Bessard AC, Kim CS, Géczi L, Ford D, Mourey L, Carles J, Parente P, Font A, Kacso G, Chadjaa M, Zhang W, Bernard J, de Bono J. Phase III study comparing a reduced dose of cabazitaxel (20 mg/m(2)) and the currently approved dose (25 mg/m(2)) in postdocetaxel patients with metastatic castration-resistant prostate cancer-PROSELICA. J Clin Oncol. 2017 Oct 1;35(28):3198-3206. Epub 2017 Aug 15 link to original article contains verified protocol in supplement PubMed
  4. Beer TM, Hotte SJ, Saad F, Alekseev B, Matveev V, Fléchon A, Gravis G, Joly F, Chi KN, Malik Z, Blumenstein B, Stewart PS, Jacobs CA, Fizazi K. Custirsen (OGX-011) combined with cabazitaxel and prednisone versus cabazitaxel and prednisone alone in patients with metastatic castration-resistant prostate cancer previously treated with docetaxel (AFFINITY): a randomised, open-label, international, phase 3 trial. Lancet Oncol. 2017 Nov;18(11):1532-1542. Epub 2017 Oct 9. link to original article PubMed

Cabozantinib monotherapy

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Regimen #1

Study Evidence Comparator Efficacy
Smith et al. 2016 (COMET-1) Phase III Prednisone Seems not superior

Chemotherapy

Regimen #2

Study Evidence
Smith et al. 2012 Phase II

Chemotherapy

References

  1. Smith DC, Smith MR, Sweeney C, Elfiky AA, Logothetis C, Corn PG, Vogelzang NJ, Small EJ, Harzstark AL, Gordon MS, Vaishampayan UN, Haas NB, Spira AI, Lara PN Jr, Lin CC, Srinivas S, Sella A, Schöffski P, Scheffold C, Weitzman AL, Hussain M. Cabozantinib in patients with advanced prostate cancer: results of a phase II randomized discontinuation trial. J Clin Oncol. 2013 Feb 1;31(4):412-9. Epub 2012 Nov 19. link to original article contains verified protocol link to PMC article PubMed
  2. Smith M, De Bono J, Sternberg C, Le Moulec S, Oudard S, De Giorgi U, Krainer M, Bergman A, Hoelzer W, De Wit R, Bögemann M, Saad F, Cruciani G, Thiery-Vuillemin A, Feyerabend S, Miller K, Houédé N, Hussain S, Lam E, Polikoff J, Stenzl A, Mainwaring P, Ramies D, Hessel C, Weitzman A, Fizazi K. Phase III study of cabozantinib in previously treated metastatic castration-resistant prostate cancer: COMET-1. J Clin Oncol. 2016 Sep 1;34(25):3005-13. Epub 2016 Jul 11. link to original article contains verified protocol PubMed

Carboplatin & Docetaxel

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Example orders

Regimen #1

Study Evidence
Ross et al. 2008 Phase II

Patients enrolled in the trial had hormone-refractory prostate cancer and progression of disease during docetaxel treatment or within 45 days of stopping docetaxel treatment.

Chemotherapy

Supportive medications

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

21-day cycles, given until progression of disease or unacceptable toxicity

Regimen #2, weekly docetaxel

Study Evidence
Reuter et al. 2010 Phase II

Patients enrolled in the trial had progression of disease on docetaxel chemotherapy and castration-resistant disease.

Chemotherapy

  • Carboplatin (Paraplatin) AUC 5 IV over 30 minutes once on day 1
  • Docetaxel (Taxotere) 35 mg/m2 IV over 1 hour once per day on days 1, 8, 15
    • Note: In contrast to its abstract, Reuter et al. 2010 sometimes used "days 1, 8, (15)" to describe when docetaxel was given. The paper did not specifically say what "(15)" meant, such as whether this meant that the day 15 dose was optional.
  • Prednisone (Sterapred) 5 mg PO BID on days 1 to 28

Supportive medications

  • "Standard dexamethasone premedication was used"
  • Patients continued to receive LHRH (luteinizing hormone releasing hormone) agonists
  • No routine use of granulocyte colony-stimulating factor (G-CSF)

28-day cycles, given until progression of disease or unacceptable toxicity

References

  1. Ross RW, Beer TM, Jacobus S, Bubley GJ, Taplin ME, Ryan CW, Huang J, Oh WK; Prostate Cancer Clinical Trials Consortium. A phase 2 study of carboplatin plus docetaxel in men with metastatic hormone-refractory prostate cancer who are refractory to docetaxel. Cancer. 2008 Feb 1;112(3):521-6. link to original article contains verified protocol PubMed
  2. Nakabayashi M, Sartor O, Jacobus S, Regan MM, McKearn D, Ross RW, Kantoff PW, Taplin ME, Oh WK. Response to docetaxel/carboplatin-based chemotherapy as first- and second-line therapy in patients with metastatic hormone-refractory prostate cancer. BJU Int. 2008 Feb;101(3):308-12. link to original article PubMed
  3. Reuter CW, Morgan MA, Ivanyi P, Fenner M, Ganser A, Grünwald V. Carboplatin plus weekly docetaxel as salvage chemotherapy in docetaxel-resistant and castration-resistant prostate cancer. World J Urol. 2010 Jun;28(3):391-8. Epub 2010 Mar 14. link to original article contains verified protocol PubMed

Carboplatin & Paclitaxel

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Regimen #1

Study Evidence
Kentepozidis et al. 2012 Phase II

Chemotherapy

Supportive medications

28-day cycles, given until progression of disease or unacceptable toxicity

Regimen #2

Study Evidence
Jeske et al. 2010 Retrospective

Chemotherapy

28-day cycles, given until progression of disease or unacceptable toxicity

References

  1. Jeske S, Tagawa ST, Olowokure O, Selzer J, Giannakakou P, Nanus DM. Carboplatin plus paclitaxel therapy after docetaxel in men with metastatic castrate resistant prostate cancer. Urol Oncol. 2011 Nov-Dec;29(6):676-81. Epub 2010 May 7. link to original article contains verified protocol PubMed
  2. Kentepozidis N, Soultati A, Giassas S, Vardakis N, Kalykaki A, Kotsakis A, Papadimitraki E, Pantazopoulos N, Bozionellou V, Georgoulias V. Paclitaxel in combination with carboplatin as salvage treatment in patients with castration-resistant prostate cancer: a Hellenic oncology research group multicenter phase II study. Cancer Chemother Pharmacol. 2012 Jul;70(1):161-8. Epub 2012 Jun 3. link to original article contains verified protocol PubMed

CMF

CMF: Cyclophosphamide, Methotrexate, Five-FU

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Regimen

Study Evidence
Wozniak et al. 1993 Phase II

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

Chemotherapy

7-day cycles, given until progression of disease or unacceptable toxicity

References

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

Cyclophosphamide, Prednisone, Diethylstilbestrol

CPD: Cyclophosphamide, Prednisone, Diethylstilbestrol

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Regimen

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

Chemotherapy

Supportive medications

30-day cycles, given until progression of disease or unacceptable toxicity

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 verified protocol PubMed

Docetaxel & Prednisone

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Example orders

Regimen #1, every 3-weeks schedule, indefinite, with prednisone

Study Evidence Comparator Efficacy
Tannock et al. 2013 (VENICE) Phase III Docetaxel, Prednisone, Dasatinib Seems not superior
Araujo et al. 2013 (READY) Phase III Docetaxel, Prednisone, Dasatinib Seems not superior
Petrylak et al. 2015 (MAINSAIL) Phase III Docetaxel, Prednisone, Lenalidomide Superior OS
Chi et al. 2017 (SYNERGY) Phase III Docetaxel, Prednisone, Custirsen Seems not superior
Oudard et al. 2017 (FIRSTANA) Phase III Cabazitaxel 20 mg/m2 & Prednisone Seems not superior
Cabazitaxel 25 mg/m2 & Prednisone Seems not superior

Chemotherapy

21-day cycles, given until progression of disease or unacceptable toxicity

Regimen #2, every 3-weeks schedule, indefinite, with prednisolone

Study Evidence Comparator Efficacy
Kellokumpu-Lehtinen et al. 2013 (PROSTY) Phase III Every 2-weeks Docetaxel & Prednisone Seems to have inferior TTTF

Chemotherapy

Supportive medications

  • Dexamethasone (Decadron) 7.5 to 8 mg daily, started 1 day before Docetaxel (Taxotere) and stopped 1 to 2 days after docetaxel infusion (in other words, from day -1 to day 2 or 3); reference did not specify route of administration
  • G-CSF not recommended unless patients developed febrile neutropenia or severe infection
  • "Treatment with bisphosphonates, erythropoietin, and palliative radiation therapy was allowed"

21-day cycles, given until progression of disease or unacceptable toxicity

Regimen #3, every 3-weeks schedule, limited duration

Study Evidence ORR, PSA RR Comparator Comparator ORR, PSA RR Efficacy Pt Population
Tannock et al. 2004 (TAX 327) Phase III pts w/ measurable disease:12% (95% CI 7-19), 45% (95% CI 40-51) Weekly Docetaxel & Prednisone pts w/ measurable disease:8% (95% CI 4-14), 48% (95% CI 42-54) Not reported Chemo-naive
Mitoxantrone & Prednisone pts w/ measurable disease:7% (95% CI 3-12), 32% (95% CI 26-37) Superior OS Chemo-naive

Chemotherapy

Supportive medications

21-day cycle for up to 10 cycles

Regimen #4, weekly schedule

Study Evidence Comparator Efficacy
Tannock et al. 2004 (TAX 327) Phase III Every 3-week Docetaxel & Prednisone Not reported
Mitoxantrone & Prednisone Seems not superior

Chemotherapy

Supportive medications

42-day cycle for up to 5 cycles

Regimen #5, bi-weekly

Study Evidence Comparator Efficacy
Kellokumpu-Lehtinen et al. 2013 (PROSTY Phase III Every 3-weeks Docetaxel & Prednisone Seems to have superior TTTF

Chemotherapy

Supportive medications

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

28-day cycles, given until progression of disease or unacceptable toxicity

References

  1. Tannock IF, de Wit R, Berry WR, Horti J, Pluzanska A, Chi KN, Oudard S, Théodore C, James ND, Turesson I, Rosenthal MA, Eisenberger MA; TAX 327 Investigators. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med. 2004 Oct 7;351(15):1502-12. link to original article contains verified protocol PubMed
    1. Update: Berthold DR, Pond GR, Soban F, de Wit R, Eisenberger M, Tannock IF. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer: updated survival in the TAX 327 study. J Clin Oncol. 2008 Jan 10;26(2):242-5. link to original article contains verified protocol PubMed
  2. Kellokumpu-Lehtinen PL, Harmenberg U, Joensuu T, McDermott R, Hervonen P, Ginman C, Luukkaa M, Nyandoto P, Hemminki A, Nilsson S, McCaffrey J, Asola R, Turpeenniemi-Hujanen T, Laestadius F, Tasmuth T, Sandberg K, Keane M, Lehtinen I, Luukkaala T, Joensuu H; for the PROSTY study group. 2-weekly versus 3-weekly docetaxel to treat castration-resistant advanced prostate cancer: a randomised, phase 3 trial. Lancet Oncol. 2013 Feb;14(2):117-24. Epub 2013 Jan 4. link to original article contains verified protocol PubMed
  3. Tannock IF, Fizazi K, Ivanov S, Karlsson CT, Fléchon A, Skoneczna I, Orlandi F, Gravis G, Matveev V, Bavbek S, Gil T, Viana L, Arén O, Karyakin O, Elliott T, Birtle A, Magherini E, Hatteville L, Petrylak D, Tombal B, Rosenthal M; VENICE investigators. Aflibercept versus placebo in combination with docetaxel and prednisone for treatment of men with metastatic castration-resistant prostate cancer (VENICE): a phase 3, double-blind randomised trial. Lancet Oncol. 2013 Jul;14(8):760-8. Epub 2013 Jun 4.link to original article contains protocol PubMed
  4. Araujo JC, Trudel GC, Saad F, Armstrong AJ, Yu EY, Bellmunt J, Wilding G, McCaffrey J, Serrano SV, Matveev VB, Efstathiou E, Oudard S, Morris MJ, Sizer B, Goebell PJ, Heidenreich A, de Bono JS, Begbie S, Hong JH, Richardet E, Gallardo E, Paliwal P, Durham S, Cheng S, Logothetis CJ. Docetaxel and dasatinib or placebo in men with metastatic castration-resistant prostate cancer (READY): a randomised, double-blind phase 3 trial. Lancet Oncol. 2013 Dec;14(13):1307-16. Epub 2013 Nov 8. link to original article contains protocol link to PMC article PubMed
  5. Petrylak DP, Vogelzang NJ, Budnik N, Wiechno PJ, Sternberg CN, Doner K, Bellmunt J, Burke JM, de Olza MO, Choudhury A, Gschwend JE, Kopyltsov E, Flechon A, Van As N, Houede N, Barton D, Fandi A, Jungnelius U, Li S, de Wit R, Fizazi K. Docetaxel and prednisone with or without lenalidomide in chemotherapy-naive patients with metastatic castration-resistant prostate cancer (MAINSAIL): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet Oncol. 2015 Apr;16(4):417-25. Epub 2015 Mar 3.link to original article contains protocol PubMed
  6. Chi KN, Higano CS, Blumenstein B, Ferrero JM, Reeves J, Feyerabend S, Gravis G, Merseburger AS, Stenzl A, Bergman AM, Mukherjee SD, Zalewski P, Saad F, Jacobs C, Gleave M, de Bono JS. Custirsen in combination with docetaxel and prednisone for patients with metastatic castration-resistant prostate cancer (SYNERGY trial): a phase 3, multicentre, open-label, randomised trial. Lancet Oncol. 2017 Apr;18(4):473-485. Epub 2017 Mar 8. link to original article contains protocol PubMed
  7. Oudard S, Fizazi K, Sengeløv L, Daugaard G, Saad F, Hansen S, Hjälm-Eriksson M, Jassem J, Thiery-Vuillemin A, Caffo O, Castellano D, Mainwaring PN, Bernard J, Shen L, Chadjaa M, Sartor O. Cabazitaxel versus docetaxel as first-line therapy for patients with metastatic castration-resistant prostate cancer: A randomized phase III Trial-FIRSTANA. J Clin Oncol. 2017 Oct 1;35(28):3189-3197. Epub 2017 Jul 28. link to original article contains verified protocol PubMed

Mitoxantrone & Prednisone

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Example orders

Regimen

Study Evidence ORR, PSA RR Comparator Comparator ORR, PSA RR Efficacy Pt Population
Tannock et al. 2004 (TAX 327) Phase III pts w/ measurable disease: 7% (95% CI 3-12), 32% (95% CI 26-37) Weekly Docetaxel & Prednisone pts w/ measurable disease: 8% (95% CI 4-14), 48% (95% CI 42-54) Seems not superior Chemo naive
Every 3-week Docetaxel & Prednisone pts w/ measurable disease: 12% (95% CI 7-19), 45% (95% CI 40-51) Inferior OS Chemo naive
Petrylak et al. 2004 (SWOG 99-16) Phase III Docetaxel & Estramustine Seems to have inferior OS
de Bono et al. 2010 (TROPIC) Phase III pts w/ measurable disease:
4.4% (95% CI 1.6 - 7.2), 17.8% (95% CI 13.7 - 22.0) 		Cabazitaxel & Prednisone pts w/ measurable disease:
14.4% (95% CI 9.6 - 19.3), 39.2% (95% CI 33.9 - 44.5) 		Inferior OS Progressed on docetaxel

Chemotherapy

21-day cycle for up to 10 cycles

References

  1. Tannock IF, Osoba D, Stockler MR, Ernst DS, Neville AJ, Moore MJ, Armitage GR, Wilson JJ, Venner PM, Coppin CM, Murphy KC. Chemotherapy with mitoxantrone plus prednisone or prednisone alone for symptomatic hormone-resistant prostate cancer: a Canadian randomized trial with palliative end points. J Clin Oncol. 1996 Jun;14(6):1756-64. link to original article PubMed
    1. HRQoL analysis: Osoba D, Tannock IF, Ernst DS, Neville AJ. Health-related quality of life in men with metastatic prostate cancer treated with prednisone alone or mitoxantrone and prednisone. J Clin Oncol. 1999 Jun;17(6):1654-63. link to original article PubMed
  2. Tannock IF, de Wit R, Berry WR, Horti J, Pluzanska A, Chi KN, Oudard S, Théodore C, James ND, Turesson I, Rosenthal MA, Eisenberger MA; TAX 327 Investigators. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med. 2004 Oct 7;351(15):1502-12. link to original article contains verified protocol PubMed
    1. Update: Berthold DR, Pond GR, Soban F, de Wit R, Eisenberger M, Tannock IF. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer: updated survival in the TAX 327 study. J Clin Oncol. 2008 Jan 10;26(2):242-5. link to original article contains verified protocol PubMed
  3. Petrylak DP, Tangen CM, Hussain MH, Lara PN Jr, Jones JA, Taplin ME, Burch PA, Berry D, Moinpour C, Kohli M, Benson MC, Small EJ, Raghavan D, Crawford ED. Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N Engl J Med. 2004 Oct 7;351(15):1513-20. link to original article PubMed
  4. de Bono JS, Oudard S, Ozguroglu M, Hansen S, Machiels JP, Kocak I, Gravis G, Bodrogi I, Mackenzie MJ, Shen L, Roessner M, Gupta S, Sartor AO; TROPIC Investigators. Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial. Lancet. 2010 Oct 2;376(9747):1147-54. link to original article contains verified protocol PubMed

Olaparib monotherapy

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Regimen

Study Evidence
Kaufman et al. 2014 Phase II, <20 pts in subgroup
Mateo et al. 2015 (TOPARP-A) Phase II
  • Patients in Kaufman et al. 2014 had germline BRCA1/2 mutations and had progression on hormonal and one systemic therapy.
  • Patients in Mateo et al. 2015 (TOPARP-A) who were found to have homozygous deletions, deleterious mutations, or both in DNA-repair genes were much more likely to respond to olaparib.

Chemotherapy

Given until progression of disease or unacceptable toxicity

References

  1. Kaufman B, Shapira-Frommer R, Schmutzler RK, Audeh MW, Friedlander M, Balmaña J, Mitchell G, Fried G, Stemmer SM, Hubert A, Rosengarten O, Steiner M, Loman N, Bowen K, Fielding A, Domchek SM. Olaparib monotherapy in patients with advanced cancer and a germline BRCA1/2 mutation. J Clin Oncol. 2015 Jan 20;33(3):244-50. Epub 2014 Nov 3. link to original article contains verified protocol PubMed
  2. Mateo J, Carreira S, Sandhu S, Miranda S, Mossop H, Perez-Lopez R, Nava Rodrigues D, Robinson D, Omlin A, Tunariu N, Boysen G, Porta N, Flohr P, Gillman A, Figueiredo I, Paulding C, Seed G, Jain S, Ralph C, Protheroe A, Hussain S, Jones R, Elliott T, McGovern U, Bianchini D, Goodall J, Zafeiriou Z, Williamson CT, Ferraldeschi R, Riisnaes R, Ebbs B, Fowler G, Roda D, Yuan W, Wu YM, Cao X, Brough R, Pemberton H, A'Hern R, Swain A, Kunju LP, Eeles R, Attard G, Lord CJ, Ashworth A, Rubin MA, Knudsen KE, Feng FY, Chinnaiyan AM, Hall E, de Bono JS. DNA-Repair Defects and Olaparib in Metastatic Prostate Cancer. N Engl J Med. 2015 Oct 29;373(18):1697-708. link to original article contains verified protocol link to PMC article PubMed

Immunotherapy for metastatic castrate-resistant disease

Ipilimumab & RT

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RT: Radiation Therapy

Regimen

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

Immunoradiotherapy

  • Ipilimumab (Yervoy) 10 mg/kg IV over 90 minutes once on day 1
    • Lower doses including 3 mg/kg (the FDA approved dose) were investigated, but the 10 mg/kg dose was recommended in this study
  • Concurrent radiotherapy given focally at a single dose of 8 Gy per target bone lesion for up to three bone lesions per patient at 24 to 48 h before the first ipilimumab dose.

21-day cycle for 4 cycles

References

  1. Slovin SF, Higano CS, Hamid O, Tejwani S, Harzstark A, Alumkal JJ, Scher HI, Chin K, Gagnier P, McHenry MB, Beer TM. Ipilimumab alone or in combination with radiotherapy in metastatic castration-resistant prostate cancer: results from an open-label, multicenter phase I/II study. Ann Oncol. 2013 Jul;24(7):1813-21. link to original article contains verified protocol link to PMC article PubMed

Sipuleucel-T monotherapy

Example orders

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Regimen

Study Evidence Comparator Efficacy
Kantoff et al. 2010 (IMPACT) Phase III Placebo Seems to have superior OS

Immunotherapy

  • Sipuleucel-T (Provenge): leukapheresis followed 3 days later with at least 50 million autologous CD54+ cells activated with PAP-GM-CSF, to be done on weeks 0, 2, and 4

Supportive medications

References

  1. Kantoff PW, Higano CS, Shore ND, Berger ER, Small EJ, Penson DF, Redfern CH, Ferrari AC, Dreicer R, Sims RB, Xu Y, Frohlich MW, Schellhammer PF; IMPACT Study Investigators. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med. 2010 Jul 29;363(5):411-22. link to original article contains verified protocol PubMed
  2. Safety analysis: Hall SJ, Klotz L, Pantuck AJ, George DJ, Whitmore JB, Frohlich MW, Sims RB. Integrated safety data from 4 randomized, double-blind, controlled trials of autologous cellular immunotherapy with sipuleucel-T in patients with prostate cancer. J Urol. 2011 Sep;186(3):877-81. Epub 2011 Jul 23. link to original article contains verified protocol PubMed

Radioactive agents for bony metastatic disease

Radium-223 monotherapy

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Regimen #1

Study Evidence Comparator Efficacy Toxicity
Parker et al. 2013 (ALSYMPCA) Phase III Placebo Superior OS Superior EQ-5D score

Radiotherapy

28-day cycle for 6 cycles

Regimen #2

Study Evidence Comparator Efficacy
Nilsson et al. 2007 Randomized Phase II Placebo Might have superior OS

Patients in the study had "bone pain needing EBRT" (external beam radiation therapy). Treatment with radium 223 began within 7 days after EBRT.

Radiotherapy

28-day cycle for 4 cycles

References

  1. Nilsson S, Franzén L, Parker C, Tyrrell C, Blom R, Tennvall J, Lennernäs B, Petersson U, Johannessen DC, Sokal M, Pigott K, Yachnin J, Garkavij M, Strang P, Harmenberg J, Bolstad B, Bruland OS. Bone-targeted radium-223 in symptomatic, hormone-refractory prostate cancer: a randomised, multicentre, placebo-controlled phase II study. Lancet Oncol. 2007 Jul;8(7):587-94. link to original article contains verified protocol PubMed
    1. Update: Nilsson S, Franzén L, Parker C, Tyrrell C, Blom R, Tennvall J, Lennernäs B, Petersson U, Johannessen DC, Sokal M, Pigott K, O'Bryan-Tear CG, Thuresson M, Bolstad B, Bruland ØS. Two-year survival follow-up of the randomized, double-blind, placebo-controlled phase II study of radium-223 chloride in patients with castration-resistant prostate cancer and bone metastases. Clin Genitourin Cancer. 2013 Mar;11(1):20-6. Epub 2012 Sep 26. link to original article contains verified protocol PubMed
  2. Parker C, Nilsson S, Heinrich D, Helle SI, O'Sullivan JM, Fosså SD, Chodacki A, Wiechno P, Logue J, Seke M, Widmark A, Johannessen DC, Hoskin P, Bottomley D, James ND, Solberg A, Syndikus I, Kliment J, Wedel S, Boehmer S, Dall'Oglio M, Franzén L, Coleman R, Vogelzang NJ, O'Bryan-Tear CG, Staudacher K, Garcia-Vargas J, Shan M, Bruland ØS, Sartor O; ALSYMPCA Investigators. Alpha emitter radium-223 and survival in metastatic prostate cancer. N Engl J Med. 2013 Jul 18;369(3):213-23. link to original article contains verified protocol PubMed
    1. Subgroup analysis: Prof Peter Hoskin MD, Prof Oliver Sartor MD, Prof Joe M O'Sullivan MD, Dag Clement Johannessen MD, Svein I Helle MD, John Logue FRCR, David Bottomley FRCR, Prof Sten Nilsson MD, Prof Nicholas J Vogelzang MD, Fang Fang PhD, Mona Wahba MD, Anne-Kirsti Aksnes PhD, Christopher Parker MD. Efficacy and safety of radium-223 dichloride in patients with castration-resistant prostate cancer and symptomatic bone metastases, with or without previous docetaxel use: a prespecified subgroup analysis from the randomised, double-blind, phase 3 ALSYMPCA trial. The Lancet Oncology, Volume 15, Issue 12, Pages 1397 - 1406, November 2014. link to original article
    2. HRQoL analysis: Nilsson S, Cislo P, Sartor O, Vogelzang NJ, Coleman RE, O'Sullivan JM, Reuning-Scherer J, Shan M, Zhan L, Parker C. Patient-reported quality-of-life analysis of radium-223 dichloride from the phase III ALSYMPCA study. Ann Oncol. 2016 May;27(5):868-74. Epub 2016 Feb 23. link to original article link to PMC article PubMed

Samarium-153 monotherapy

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Regimen

Study Evidence Comparator Efficacy
Resche et al. 1997 Phase III Samarium-153 0.5 mCi/kg Seems to have superior pain control at week 4
Sartor et al. 2004 (Quadramet 424Sm10/11 Study Group) Phase III Samarium-152 (non-radioactive) Seems to have superior pain control at week 4

Radiotherapy

Supportive medications

  • 1000 mL of fluid PO/IV given twice, 4 hours before and 6 hours after treatment

1 dose

References

  1. Resche I, Chatal JF, Pecking A, Ell P, Duchesne G, Rubens R, Fogelman I, Houston S, Fauser A, Fischer M, Wilkins D. A dose-controlled study of 153Sm-ethylenediaminetetramethylenephosphonate (EDTMP) in the treatment of patients with painful bone metastases. Eur J Cancer. 1997 Sep;33(10):1583-91. link to original article contains verified protocol PubMed
  2. Sartor O, Reid RH, Hoskin PJ, Quick DP, Ell PJ, Coleman RE, Kotler JA, Freeman LM, Olivier P; Quadramet 424Sm10/11 Study Group. Samarium-153-Lexidronam complex for treatment of painful bone metastases in hormone-refractory prostate cancer. Urology. 2004 May;63(5):940-5. link to original article contains verified protocol PubMed

Measuring disease progression

  • Criteria used for disease progression in prostate cancer clinical trials, Prostate Cancer Clinical Trials Working Group 2 (PCWG2):[1]
    • Castrate level of serum testosterone is less than 50 ng/dL (less than 1.7 nmol/L)
      • However, there is controversy/disagreement in other references about whether a lower level should be used, such as less than 20 ng/dL (0.7 nmol/L)[2]
    • PSA rise
      • Starting PSA of at least 2.0 ng/mL
      • Rising PSA values which are measured at least 1-week apart
      • Pretherapy PSA doubling times (PSA-DT) can be estimated if there are at least 3 PSA values measured at least 4 weeks apart
    • Bony metastases
      • At least 2 new lesions indicates progressive disease
      • It is recommended to assess ambiguous results with other imaging modalities such as CT or MRI
    • Measurable lesions (RECIST) - this is a lower priority criteria by the PCWG2 because fewer patients have measurable lesions as compared to, for example, bony metastases
      • Baseline imaging involves chest imaging with x-ray or CT, CT or MRI of the abdomen/pelvis, and radionuclide bone scan
      • It is recommended that local disease is assessed by endorectal MRI or prostatic ultrasound
      • Neurologic symptoms should be assessed with MRI of the spine and base of the skull
      • Positron emission tomography (PET) is not recommended and is considered investigational
      • Measurable lesions should be followed with RECIST criteria
      • "Up to 10 visceral and nodal lesions in total should be recorded (with a maximum of five in any one organ)"
      • It is suggested that a lymph node must be at least 2 cm in maximal dimension on spiral CT to count as a target lesion.

Statistics

Links

Quality of life assessment tools

References

  1. ↑ Scher HI, Halabi S, Tannock I, Morris M, Sternberg CN, Carducci MA, Eisenberger MA, Higano C, Bubley GJ, Dreicer R, Petrylak D, Kantoff P, Basch E, Kelly WK, Figg WD, Small EJ, Beer TM, Wilding G, Martin A, Hussain M; Prostate Cancer Clinical Trials Working Group. Design and end points of clinical trials for patients with progressive prostate cancer and castrate levels of testosterone: recommendations of the Prostate Cancer Clinical Trials Working Group. J Clin Oncol. 2008 Mar 1;26(7):1148-59. link to original article link to PMC article PubMed
  2. ↑ Oefelein MG, Feng A, Scolieri MJ, Ricchiutti D, Resnick MI. Reassessment of the definition of castrate levels of testosterone: implications for clinical decision making. Urology. 2000 Dec 20;56(6):1021-4. link to original article PubMed
  3. ↑ Stephenson AJ, Shariat SF, Zelefsky MJ, Kattan MW, Butler EB, Teh BS, Klein EA, Kupelian PA, Roehrborn CG, Pistenmaa DA, Pacholke HD, Liauw SL, Katz MS, Leibel SA, Scardino PT, Slawin KM. Salvage Radiotherapy for Recurrent Prostate Cancer After Radical Prostatectomy. JAMA. 2004 Mar 17;291(11):1325-32. link to original article PubMed
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