Recommended Chemotherapy Regimens for Advanced Prostate Cancer
For patients with advanced prostate cancer, the recommended chemotherapy regimens include docetaxel, abiraterone, enzalutamide, or apalutamide, each administered with androgen deprivation therapy (ADT), with selection based on disease volume, risk factors, and patient characteristics. 1
First-Line Treatment Options for Metastatic Prostate Cancer
ADT Plus Docetaxel
- For high-volume disease (HVD): Docetaxel plus ADT should be offered to men with metastatic noncastrate prostate cancer with high-volume disease as defined by CHAARTED (≥4 bone metastases with ≥1 outside spine/pelvis and/or visceral disease) 1
- Recommended regimen: Six doses of docetaxel at 75 mg/m² administered every 3 weeks with or without prednisone 1, 2
- Not recommended for low-volume disease: Patients with low-volume metastatic disease should not receive docetaxel plus ADT 1
ADT Plus Abiraterone
- For high-risk disease: Abiraterone plus ADT should be offered to men with high-risk de novo metastatic noncastrate prostate cancer per LATITUDE criteria 1
- For low-risk disease: Abiraterone plus ADT may be offered to men with low-risk de novo metastatic noncastrate prostate cancer 1
- Dosage: Abiraterone 1,000 mg with prednisone or prednisolone 5 mg once daily 1
ADT Plus Enzalutamide or Apalutamide
- These represent additional standards of care for noncastrate metastatic prostate cancer when administered with ADT 1
Important Clinical Considerations
Disease Volume Assessment
- High-volume disease is defined as ≥4 bone metastases with ≥1 outside spine/pelvis and/or visceral disease 1
- Low-volume disease patients have fewer metastases and better prognosis 1
Combination Therapy Limitations
- Currently, there is insufficient evidence to recommend any particular combination or sequence of these agents 1
- No data supports using both abiraterone and docetaxel for metastatic noncastrate disease, either combined or sequentially 1
Treatment Selection Factors
- Docetaxel considerations: Associated with greater toxicity than androgen-targeted therapies, but treatment course is relatively short and generally covered by insurance 1
- Abiraterone considerations: Less acute toxicity but requires continuous administration with monitoring for side effects 1
Management of Castration-Resistant Prostate Cancer
For patients who progress to castration-resistant prostate cancer (CRPC):
- First-line chemotherapy: Docetaxel 75 mg/m² every 3 weeks with prednisone 5 mg twice daily 1, 3
- Duration of therapy: Based on assessment of benefit and toxicities; in pivotal trials, patients received up to 10 cycles if no progression or prohibitive toxicities occurred 1
- Bone health: For men with CRPC and bone metastases, zoledronic acid every 3-4 weeks is recommended to prevent skeletal complications 1
Monitoring and Response Assessment
- PSA response (≥50% decrease) occurs in approximately half of patients treated with docetaxel 3
- Formal response assessment should be delayed until approximately 12 weeks (4 cycles) 3
- At least 2 cycles (6 weeks) of docetaxel should be administered before making efficacy decisions 3
Toxicity Management
- Neutropenia: Most common grade 3/4 toxicity (85.7% in some studies) 4
- Dose adjustments: For patients who experience febrile neutropenia, neutrophils <500 cells/mm³ for more than 1 week, or severe cutaneous reactions, dosage should be reduced from 75 mg/m² to 55 mg/m² 2
- Discontinuation: Treatment should be discontinued for patients who develop ≥grade 3 peripheral neuropathy 2
Pitfalls and Caveats
Disease volume assessment is critical: Docetaxel benefit is primarily in high-volume disease; inappropriate use in low-volume disease exposes patients to toxicity without proven survival benefit 1
Monitoring beyond PSA: Clinical benefit should be assessed considering symptoms and performance status alongside PSA measurements 3
Timing of response assessment: Early discontinuation before adequate trial (minimum 2 cycles) may miss potential benefit 3
Survival benefit context: While docetaxel extends survival in appropriate patients, the benefit is modest (2-3 months in some studies) and must be weighed against potential toxicities 5