What are the treatment protocols for castration-resistant prostate cancer?

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

  • All patients with metastatic disease become resistant to ADT

  • Radiation may be used for palliation in patients with painful bone metastases or impending spinal cord compression

  • Surgical intervention may be necessary for weight-bearing bones involved in pathologic fracture

  • Therapeutic options are limited, and the focus is on improving quality of life using single or multimodal therapies

  • Docetaxel every 3 wk plus prednisone is the treatment of choice for men with symptomatic castration-recurrent prostate cancer; [42, 43, 44] recommended dose is docetaxel 75 mg/m2 IV on day 1 plus  prednisone 5 mg PO BID; repeat cycle every 21 days for up to a total of 10 cycles (premedicate with oral corticosteroids starting 1 day before docetaxel administration to reduce incidence of hypersensitivity reactions and fluid retention)

  • Abiraterone (Zytiga) is approved for treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) who are either chemotherapy-naïve or who have had prior docetaxel therapy; recommended dose is 1000 mg PO once daily plus  prednisone 5 mg PO BID [40, 41, 45, 46] ; in addition, de Bono et al reported that abiraterone prolonged overall survival in patients with mCRPC who had received prior chemotherapy. [47]

  • An ultramicronized abiraterone tablet (Yonsa) was approved in May 2018 for mCRPC in combination with methylprednisolone. The ultramicronized formulation may be administered with or without food, whereas, the original tablet formulation (Zytiga) must be administered 1 hour before or 2 hours after meals.

  • Abiraterone (Yonsa): 500 mg (four 125-mg ultramicronized tablets) PO daily plus methylprednisolone 4 mg PO BID

  • Cabazitaxel with prednisone can be used for patients who have hormone-refractory metastatic prostate cancer that was previously treated with a docetaxel-containing treatment regimen; cabazitaxel 25 mg/m2 IV every 3 wk; infuse IV over 1 h; use inline filter (0.22 µm) during administration plus  prednisone 10 mg PO daily; reduce cabazitaxel dose to 20 mg/m2 with prolonged or febrile neutropenia or with persistent or severe diarrhea

  • Enzalutamide (Xtandi): 160 mg PO once daily
  • Darolutamide 600 mg PO BID is indicated for nonmetastatic CRPC [30]
  • Symptomatic men who are not candidates for docetaxel-based regimens may be candidates for  mitoxantrone 12 mg/m 2 IV on day 1  plus  prednisone 5 mg PO BID daily; repeat cycle every 21 days [42, 43, 44]
  • Rucaparib 600 mg PO BID until disease progression or unacceptable toxicity for deleterious  BRCA mutation (germline and/or somatic)–associated mCRPC in patients previously treated with androgen receptor–directed therapy and taxane-based chemotherapy [48]
  • Olaparib 300 mg PO BID until disease progression or unacceptable toxicity for deleterious or suspected deleterious germline or somatic homologous recombination repair (HRR) gene-mutated mCRPC that has progressed after treatment with enzalutamide or abiraterone [49]  

Treatment recommendations for patients with castration-recurrent prostate cancer and bone metastases

Bisphosphonates are recommended for all men with hormone-refractory prostate cancer and bone metastases [50, 7] Bisphosphonates have been shown to reduce skeleton-related events such as pathologic fracture. Options are as follows:

The radiopharmaceutical radium-223 dichloride (Xofigo) is approved for men with mCRPC with symptomatic bone metastases and no known visceral metastatic disease:

  • 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 (listed in prescribing information) [51]

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