What are the recommended doses of goserelin (LHRH agonist) and enzalutamide for a patient with progressive prostate cancer and retroperitoneal and bone metastasis?

Recommended Dosing for Goserelin and Enzalutamide in Metastatic Prostate Cancer

For a patient with progressive prostate cancer and retroperitoneal and bone metastases, administer goserelin 3.6 mg subcutaneously every 28 days (or 10.8 mg every 12 weeks) and enzalutamide 160 mg orally once daily. 1, 2

Goserelin Dosing

Standard Formulations

• Goserelin 3.6 mg depot: Administered subcutaneously into the upper abdominal wall every 28 days 1, 3
• Goserelin 10.8 mg depot (Zoladex LA): Administered subcutaneously every 12 weeks (3 months) as an alternative formulation 4, 5

Key Administration Details

• The 10.8 mg three-month formulation provides equivalent testosterone suppression to three consecutive doses of the 3.6 mg monthly formulation, reducing injection burden while maintaining castrate testosterone levels (< 2 nmol/L) 4, 5
• Both formulations are biodegradable depot systems that release goserelin continuously over their respective dosing intervals 1, 3
• Some patients may require local anesthetic before subcutaneous injection 3

Important Consideration for Disease Flare

• When initiating goserelin, co-administer an antiandrogen for 3-4 weeks to prevent testosterone flare, which occurs in up to 4% of patients and can cause symptom exacerbation 6, 1
• This is particularly critical in patients at risk for spinal cord compression or ureteric obstruction from metastases 1

Enzalutamide Dosing

Standard Dose

• Enzalutamide 160 mg orally once daily is the established dose for metastatic castration-resistant prostate cancer 2

Evidence for Efficacy

• In the pivotal PREVAIL trial of chemotherapy-naïve metastatic castration-resistant prostate cancer, enzalutamide 160 mg daily demonstrated:
  • 81% reduction in radiographic progression risk (HR 0.19) 2
  • 29% reduction in mortality risk (HR 0.71) 7, 2
  • 78% of patients achieved ≥50% PSA decline versus 3% with placebo 2

Common Adverse Effects to Monitor

• Fatigue is the most common adverse effect 7
• Hot flushes and diarrhea occur frequently 7
• Hypertension requires monitoring 7
• Seizures occur in 0.6% of patients—counsel patients about this risk 7

Clinical Context for This Patient

Since this patient has progressive disease with bone and retroperitoneal metastases, they likely have castration-resistant prostate cancer (CRPC) if already on androgen deprivation therapy, or metastatic hormone-sensitive prostate cancer if treatment-naïve.

If Treatment-Naïve

• Initiate goserelin (with antiandrogen coverage for 3-4 weeks) 6
• Consider adding docetaxel chemotherapy if the patient is fit enough, as ADT plus docetaxel improves outcomes in metastatic hormone-sensitive disease 6, 8

If Castration-Resistant (Progressive on ADT)

• Continue goserelin to maintain castrate testosterone levels 6
• Add enzalutamide 160 mg daily, which is recommended for asymptomatic or minimally symptomatic chemotherapy-naïve metastatic CRPC 6, 8

Bone Metastasis Management

• Add denosumab 120 mg subcutaneously every 4 weeks (preferred, category 1) or zoledronic acid 4 mg intravenously every 3-4 weeks to prevent skeletal-related events in patients with CRPC and bone metastases 9
• Ensure dental evaluation before initiating bone-targeted therapy to reduce osteonecrosis of the jaw risk 9
• Supplement with calcium and vitamin D 9