What are the recommendations for androgen deprivation therapy (ADT) to treat advanced or metastatic prostate cancer?

Updated: Dec 29, 2020
  • Author: Winston W Tan, MD, FACP; Chief Editor: E Jason Abel, MD  more...
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Answer

Answer

See the list below:

  • ADT is a preferred initial treatment for symptomatic metastatic prostate cancer because androgenic effects promote the growth and malignant transformation of prostatic tissue [31]

  • ADTs include luteinizing hormone (LH) receptor agonists (eg, histrelin, leuprolide), gonadotropin-releasing hormone (GnRH) receptor agonists (eg, goserelin, histrelin, leuprolide, triptorelin) and antagonists (eg, degarelix, relugolix), and complete androgen blockade (CAB)

  • CAB includes medical castration with an oral antiandrogen (eg, bicalutamide, flutamide, nilutamide) or surgical castration [32]

  • Patients who do not show an adequate suppression of serum testosterone (< 50 ng/dL) may be considered for CAB

  • Monotherapy with nonsteroidal antiandrogens is less effective but these agents are associated with fewer hot flashes and fatigue and do not impair libido

  • If hormone therapy fails, that therapy should be continued into and through the next hormone manipulation

Gonadotropin-releasing hormone agonists:

  • Therapy with GnRH analogs may induce medical castration by suppressing luteinizing hormone (LH) production

  • These agonists can potentially cause a transient surge of LH when therapy is initiated before the LH levels fall (flare phenomenon)

  • GnRH agonists are offered in 1 mo, 3 mo, and once-yearly depots; premedication with antiandrogen is necessary to prevent flare phenomenon

  • Leuprolide: 7.5 mg intramuscularly (IM) monthly or  22.5 mg IM every 3 mo or  30 mg IM every 4 mo or  45 mg intravenously (IV) every 6 mo or

  • Histrelin: one 50-mg subcutaneous (SC) implant every 12 mo [33] ; continue therapy until disease progression or

  • Goserelin: 3.6-mg implant SC monthly or  a 10.8-mg implant [33] SC every 3 mo or

  • Triptorelin: 3.75 mg IM monthly or  11.25 mg IM every 3 mo or 22.5 mg IM every 6 mo

Gonadotropin-releasing hormone antagonists:

  • Pure GnRH antagonists suppress testosterone and avoid the flare phenomenon associated with GnRH agonists
  • Important for patients with no prior hormone treatment who are diagnosed with significant metastasis.
  • Degarelix: 120 mg SC × two doses (ie, two separate injections totaling 240 mg),  then, after 28 days, monthly maintenance doses of 80 mg SC
  • Relugolix: Loading dose of 360 mg PO × 1, then 120 mg PO once daily [34]

Nonsteroidal antiandrogens for non–castrate-resistant disease:

  • Antiandrogens bind to androgen receptors and competitively inhibit their interaction with testosterone and dihydrotestosterone

  • These agents do not decrease LH levels and androgen production

  • Antiandrogens are usually used in combination with a GnRH agonist, to prevent a disease flare caused by the transient increase in testosterone levels

  • Flutamide 250 mg orally (PO) TID or

  • Bicalutamide 50 mg PO daily; patients refractory to other antiandrogen agents may start with 150 mg PO daily or

  • Nilutamide 300 mg PO daily for 30 days, and then  150 mg PO daily or

  • Enzalutamide (160 mg PO daily), which was previously indicated only for metastatic castration-resistant prostate cancer in patients who had received docetaxel, is now approved also for patients who have not received chemotherapy [35]

Chemohormonal therapy for hormone-sensitive metastatic disease

  • Docetaxel 75 mg/m 2 IV with dexamethasone premedication 8 mg PO at 12 hours, 3 hours, and 1 hour before docetaxel infusion; repeat cycle every 21 days for up to a total of 6 cycles [36]
  • Abiraterone (Zytiga) 1000 PO once daily  plus prednisone 5 mg PO BID  or  abiraterone (Yonsa) 500 mg PO once daily  plus methylprednisolone 4 mg BID
  • Enzalutamide 160 mg PO once daily; administer with GnRH analog concurrently, unless the patient has had bilateral orchiectomy [37]

Castrate-resistant metastatic disease

  • Docetaxel 75 mg/m  2 IV, with dexamethasone premedication 8 mg PO at 12 hours, 3 hours, and 1 hour before docetaxel infusion; repeat cycle every 21 days for up to a total of 10 cycles
  • Abiraterone 1000 mg (Zytiga; two 500-mg tablets or four 250-mg tablets) PO daily  plus  prednisone 5 mg PO BID  or  abiraterone 500 mg (Yonsa; four 125-mg ultramicronized tablets) PO daily  plus methylprednisolone 4 mg PO BID 
  • Enzalutamide 160 mg (four 40-mg tablets) PO daily
  • Radium-223 50 kBq (1.36 microcurie) per kg IV infused over 1 minute; repeat q 4 wk for six cycles total; dosage calculation must be based on decay correction factor of radium-223
  • Sipuleucel-T therapy comprises three complete doses IV given at approximately 2-wk intervals (median dosing interval, 2 wk; range, 1-15 wk); infuse IV over 60 min; premedicate with oral  acetaminophen and an antihistamine approximately 30 min before administration. [38, 39, 40, 41]  Men with less advanced disease, good performance status, life expectancy > 6 mo, no visceral disease, and no or minimal symptoms and who are resistant to standard hormone treatment may be candidates for autologous immunotherapy with sipuleucel-T [38]

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