From the Guidelines
Treatment for hormone refractory prostate cancer should prioritize sequencing of therapies, considering the optimal use of novel hormone therapies, chemotherapy, and other treatment options, with a focus on improving clinical outcomes and minimizing cross-resistance, as suggested by recent studies such as the CARD trial and the TheraP trial 1.
Sequencing of Therapy in CRPC
The optimal sequence of therapies for CRPC remains undefined, but emerging data can help with treatment selection. After abiraterone or enzalutamide, giving the alternate novel hormone therapy may not be the optimal strategy, considering the availability of other treatment options, including chemotherapy.
- The CARD trial showed that treatment with cabazitaxel significantly improved clinical outcomes over enzalutamide or abiraterone in patients with mCRPC who had been previously treated with docetaxel and the alternate hormonal therapy (abiraterone or enzalutamide) 1.
- Data suggest cross-resistance between abiraterone and enzalutamide, with results of a randomized, open-label, phase II, crossover trial suggesting that the sequence of abiraterone followed by enzalutamide is more efficacious than the reverse 1.
- Some data inform the sequencing of therapies in patients with actionable biomarkers, such as the TheraP trial, which compared PSA response after Lu-177-PSMA-617 vs cabazitaxel in patients with PSMA-positive mCRPC who previously received docetaxel, showing a higher PSA response rate and fewer grade 3-4 adverse events in the Lu-177-PSMA-617 arm 1.
Treatment Options
Treatment options for CRPC include:
- Second-generation androgen receptor inhibitors such as enzalutamide, abiraterone acetate, apalutamide, or darolutamide.
- Chemotherapy with docetaxel, particularly for rapidly progressing disease or visceral metastases.
- Radium-223 for patients with bone metastases to manage bone pain and improve survival.
- PARP inhibitors like olaparib for patients with specific genetic mutations (BRCA1/2, ATM).
- Sipuleucel-T immunotherapy for patients with minimal symptoms and no visceral metastases.
- Androgen deprivation therapy should be continued to maintain castrate testosterone levels throughout treatment.
From the FDA Drug Label
3 Prostate Cancer Docetaxel Injection in combination with prednisone is indicated for the treatment of patients with metastatic castration-resistant prostate cancer.
3 Prostate Cancer For metastatic castration-resistant prostate cancer, the recommended dose of Docetaxel Injection is 75 mg/m2 every 3 weeks as a 1 hour intravenous infusion. Prednisone 5 mg orally twice daily is administered continuously
- Treatment for hormone refractory prostate cancer: Docetaxel Injection in combination with prednisone is indicated for the treatment of patients with metastatic castration-resistant prostate cancer.
- The recommended dose is 75 mg/m2 every 3 weeks as a 1 hour intravenous infusion, with prednisone 5 mg orally twice daily administered continuously 2.
- Another option is enzalutamide (PO), which is indicated for the treatment of patients with castration-resistant prostate cancer (CRPC), with a recommended dosage of 160 mg administered orally once daily 3.
From the Research
Treatment Options for Hormone Refractory Prostate Cancer
- The main treatment options for hormone refractory prostate cancer (HRPC) include chemotherapy, bisphosphonates, palliative radiotherapy, and radioisotopes 4.
- Chemotherapy has been shown to improve overall survival, palliation of symptoms, and quality of life in patients with HRPC, with docetaxel being a key agent in this setting 4, 5.
- Docetaxel has been shown to improve overall survival compared to best standard of care, with a significant improvement in pain relief and quality of life 4, 5.
Chemotherapy Agents
- Various chemotherapy agents have been studied in the treatment of HRPC, including estramustine, 5-fluorouracil, cyclophosphamide, doxorubicin, mitoxantrone, and docetaxel 4.
- Docetaxel has been shown to be effective in improving overall survival and quality of life, with a significant improvement in pain relief compared to mitoxantrone plus prednisone 4, 5.
Sequential Therapy
- The efficacy of sequential therapy in HRPC has been studied, with docetaxel and abiraterone being compared in terms of overall survival, cancer-specific survival, and progression-free survival 6.
- The study found that docetaxel and abiraterone had comparable oncologic outcomes in terms of overall survival, cancer-specific survival, and progression-free survival, but docetaxel resulted in better 2nd and 3rd-line progression-free survival 6.
First-line Treatment for Metastatic Castration-resistant Prostate Cancer
- The efficacy of first-line abiraterone acetate or enzalutamide for metastatic castration-resistant prostate cancer after androgen deprivation therapy + docetaxel or ADT alone for metastatic hormone-sensitive prostate cancer has been studied 7.
- The study found that the efficacy of abiraterone acetate and enzalutamide was similar regardless of previous use of docetaxel, with no statistically significant difference in overall survival or time to treatment start 7.