What is the efficacy of Docetaxel (docetaxel) infusions after 6 Lutetium-177 (Lu-177) infusions for recurrent metastatic castration-resistant prostate cancer?

Efficacy of Docetaxel Following Lu-177 for Recurrent Metastatic Castration-Resistant Prostate Cancer

Docetaxel remains an effective treatment option for patients with recurrent metastatic castration-resistant prostate cancer (mCRPC) after Lu-177 therapy, with established survival benefits and manageable toxicity profiles. 1

Docetaxel Efficacy in mCRPC

• Docetaxel is a category 1 preferred option for treatment of docetaxel-naïve mCRPC, with established survival benefits demonstrated in landmark trials (TAX 327 and SWOG 9916) 1
• The standard regimen is 75 mg/m² every 3 weeks with prednisone, which showed improved overall survival compared to mitoxantrone (18.9 vs 16.5 months) 1, 2
• Alternative dosing schedules include:
  • Biweekly regimen (50 mg/m²) which may offer better tolerability with similar efficacy (19.5 vs 17.0 months survival) 1
  • Weekly regimen (30 mg/m²) which has less neutropenia but slightly reduced efficacy 2

Docetaxel After Prior Treatments

• Docetaxel rechallenge may be useful in patients who have not shown definitive evidence of progression on prior docetaxel therapy 1
• For patients who received docetaxel in the castration-sensitive setting, it can be given as a rechallenge after progression on a novel hormone in the mCRPC setting 1
• Approximately 45-50% of patients achieve a 50% decrease in PSA with the standard 3-weekly docetaxel regimen 2

Sequencing After Lu-177 Therapy

• While specific data on the sequence of Lu-177 followed by docetaxel is limited, the NCCN guidelines support docetaxel as an effective option for mCRPC patients regardless of prior treatment history 1
• Treatment with 8 or more cycles of docetaxel may be associated with better overall survival than fewer cycles in the mCRPC setting 1
• PSA response assessment should be delayed until about 12 weeks after starting docetaxel treatment, as premature assessment may lead to inappropriate treatment discontinuation due to initial PSA flare 2

Potential Combination Approaches

• Limited research suggests potential benefits of combining low-dose docetaxel with Lu-177 PSMA therapy as a radiosensitizer 3
• A phase I trial demonstrated the feasibility of combining docetaxel with Lu-177-J591 in patients with mCRPC, showing accurate targeting of disease sites and a strong preliminary efficacy signal 4
• In a case report, low-dose docetaxel (25 mg/m² weekly × 6 weeks) used as a radiosensitizer with re-challenge Lu-177 PSMA therapy showed good response with no recorded tumor resistance 3

Considerations for Treatment Selection

• Patient selection is critical when considering docetaxel after Lu-177 therapy 5
• Monitoring for myelosuppression is essential, as both therapies can cause hematologic toxicity 4, 6
• Common side effects of docetaxel include neutropenia, fatigue, and neuropathy, which should be monitored closely 1, 2
• Androgen deprivation therapy should be maintained during docetaxel treatment 2

Alternative Options After Lu-177

• For patients who progress after Lu-177 and are not candidates for docetaxel, other options include:
  • Cabazitaxel, which has shown improved overall survival compared to mitoxantrone in patients previously treated with docetaxel 1, 5
  • Enzalutamide, which has demonstrated survival benefits in the post-docetaxel setting 1
  • Clinical trials, which are encouraged given the evolving landscape of mCRPC treatment 1

Docetaxel remains a valuable treatment option for patients with mCRPC who have progressed after Lu-177 therapy, with established efficacy and well-characterized toxicity profile. The decision to use docetaxel should consider prior treatment history, response to previous therapies, and patient fitness for chemotherapy.