From the Guidelines
The management of metastatic Castration-Resistant Prostate Cancer (CRPC) involves a multi-faceted approach, including the use of androgen receptor inhibitors such as abiraterone acetate (1000mg orally daily) and enzalutamide (160mg orally daily), as well as taxane-based chemotherapies like docetaxel (75mg/m² intravenously every 3 weeks) and cabazitaxel (25mg/m² intravenously every 3 weeks) 1.
Treatment Options
- Abiraterone or enzalutamide are recommended for asymptomatic/mildly symptomatic men with chemotherapy-naïve metastatic CRPC 1.
- Radium-223 is recommended for men with bone-predominant, symptomatic metastatic CRPC without visceral metastases 1.
- Docetaxel is recommended for men with metastatic CRPC 1.
- Sipuleucel-T is an option in asymptomatic/mildly symptomatic patients with chemotherapy-naïve metastatic CRPC 1.
Additional Considerations
Additionally, hormonal therapies, such as luteinizing hormone-releasing hormone (LHRH) agonists or antagonists, are used to maintain castrate levels of testosterone 1.
Post-Docetaxel Setting
In patients with metastatic CRPC in the post-docetaxel setting, abiraterone, enzalutamide, cabazitaxel, and radium-223 (in those without visceral disease) are recommended options 1.
Best Supportive Care
All patients should receive best supportive care while additional therapies, including secondary hormone therapies, chemotherapies, immunotherapies, radiopharmaceuticals, and/or targeted therapies, are sequentially applied 1.
From the FDA Drug Label
XTANDI® is indicated for the treatment of patients with: • castration-resistant prostate cancer (CRPC) • metastatic castration-sensitive prostate cancer (mCSPC) • non‑metastatic castration‑sensitive prostate cancer (nmCSPC) with biochemical recurrence at high risk for metastasis (high-risk BCR)
The recommended dosage of XTANDI is 160 mg administered orally once daily with or without food [see Clinical Pharmacology (12. 3)] until disease progression or unacceptable toxicity.
Patients with CRPC or mCSPC receiving XTANDI should also receive a gonadotropic-releasing hormone (GnRH) analog concurrently or should have had bilateral orchiectomy.
The management of metastatic Castration-Resistant Prostate Cancer (CRPC) includes the use of enzalutamide (XTANDI) at a dose of 160 mg orally once daily, in combination with a gonadotropic-releasing hormone (GnRH) analog or after bilateral orchiectomy.
- The treatment should be continued until disease progression or unacceptable toxicity.
- Dose modifications may be necessary in case of adverse reactions or drug interactions.
- Docetaxel is also an option for the treatment of metastatic CRPC, as shown in the study 2, where it was administered at a dose of 75 mg/m2 every 3 weeks in combination with prednisone 5 mg twice daily.
From the Research
Management of Metastatic Castration-Resistant Prostate Cancer (CRPC)
The management of metastatic CRPC involves various therapeutic approaches.
- Androgen receptor (AR) antagonist MDV3100 is the first therapeutic approach in treating CRPC, but tumours frequently become drug resistant via multiple mechanisms including AR amplification and mutation 3.
- Ailanthone (AIL) has been identified as a potent inhibitor of both full-length AR (AR-FL) and constitutively active truncated AR splice variants (AR-Vs), and it prevents AR's interaction with HSP90, resulting in the disruption of the AR-chaperone complex 3.
- The signal transducer and activator of transcription (STAT)3 plays a crucial role in the progression of prostate cancer to metastatic CRPC, and it integrates different signaling pathways involved in the reactivation of androgen receptor pathway, stem like cells and the epithelial to mesenchymal transition 4.
- STAT3 also regulates interactions between tumor cells and the microenvironment as well as immune cell activation, making it a major factor in facilitating prostate cancer escape from detection of the immune response, promoting an immunosuppressive environment that allows growth and metastasis 4.
- Targeting STAT3 signaling may be a promising therapeutic approach to prevent prostate cancer progression, and various STAT3 inhibitors are being used in cancer therapies 4.