What is the difference in docetaxel administration between Hormone-Sensitive Prostate Cancer (HSPC) and Hormone-Refractory Prostate Cancer (HRPC)?

Differences in Docetaxel Administration Between HSPC and HRPC

The key difference in docetaxel administration between hormone-sensitive prostate cancer (HSPC) and hormone-refractory prostate cancer (HRPC) is the treatment duration: in HSPC, docetaxel is administered for a fixed course of 6 cycles, while in HRPC, it is given until disease progression or intolerable toxicity.

Docetaxel in Hormone-Sensitive Prostate Cancer (HSPC)

Regimen

• Standard dose: 75 mg/m² every 3 weeks for 6 cycles with ADT 1
• Can be administered with or without prednisone:
  • Without prednisone (per CHAARTED trial) 1
  • With prednisone 10 mg daily (per STAMPEDE trial) 1

Patient Selection

• Strongest evidence for benefit in patients with:
  • De novo metastatic disease 1
  • High-volume disease (defined as ≥4 bone metastases with ≥1 outside spine/pelvis, and/or visceral metastases) 1
• Not recommended for patients with low-volume metastatic disease as there is no proven survival benefit 1

Efficacy

• Improves overall survival when added to ADT in high-volume metastatic HSPC 1
• Demonstrated survival benefit in CHAARTED and STAMPEDE trials 1
• No significant survival benefit in GETUG-AFU trial 1

Docetaxel in Hormone-Refractory Prostate Cancer (HRPC)

Regimen

• Standard dose: 75 mg/m² every 3 weeks with prednisone 5 mg twice daily until disease progression 1
• Alternative regimen: 50 mg/m² biweekly, which shows improved survival (19.5 vs 17.0 months) and lower febrile neutropenia rates (4% vs 14%) compared to the every-3-week schedule 1

Treatment Duration

• Continued until disease progression or intolerable toxicity 1
• Treatment with 8 or more cycles may be associated with better overall survival than fewer cycles 1

Rechallenge Considerations

• Docetaxel rechallenge may be useful in HRPC patients who previously received docetaxel in the HSPC setting 1
• Most beneficial in patients without definitive evidence of progression on prior docetaxel therapy 1

Key Differences in Administration

1. Treatment Duration:

   • HSPC: Fixed course of 6 cycles 1
   • HRPC: Continued until disease progression 1

2. Steroid Use:

   • HSPC: Can be given with or without prednisone 1
   • HRPC: Standard administration includes prednisone 5 mg twice daily 1

3. Patient Selection:

   • HSPC: Primarily beneficial for high-volume disease 1
   • HRPC: Standard of care for all patients with mCRPC regardless of disease volume 1

4. Sequencing:

   • HSPC: Used as initial therapy alongside ADT 1
   • HRPC: May be used after progression on hormonal therapies or as rechallenge after prior docetaxel use 1

Monitoring and Response Assessment

• PSA response assessment should be delayed until about 12 weeks (4 cycles) in both settings 2
• Initial PSA rise (flare phenomenon) may occur in responding patients and does not necessarily indicate treatment failure 2
• Regular complete blood count assessment before each cycle is essential 2

Common Pitfalls to Avoid

1. Premature Discontinuation: Avoid stopping treatment based solely on early PSA values, as responses may take several cycles to manifest 2

2. Inappropriate Patient Selection: Not offering docetaxel to HSPC patients with low-volume disease where evidence doesn't support a survival benefit 1

3. Inadequate Toxicity Management: Febrile neutropenia is a significant risk, particularly with the every-3-week regimen in HRPC 1

4. Overlooking Alternative Schedules: The biweekly regimen (50 mg/m²) may offer better tolerability with similar efficacy in HRPC 1, 2