What is the treatment regimen for reducing Prostate-Specific Antigen (PSA) levels in patients with prostate cancer using Androgen Deprivation Therapy (ADT) and medications like leuprolide (Leuprolide) or enzalutamide (Enzalutamide)?

From the Guidelines

Androgen Deprivation Therapy (ADT) combined with enzalutamide can significantly reduce PSA levels in prostate cancer patients, with a median time to PSA progression of 37.2 months compared to 3.9 months with placebo, as shown in the PROSPER trial 1.

Treatment Regimen

The standard regimen for reducing PSA levels includes leuprolide (Lupron), administered as a depot injection of 7.5 mg monthly, 22.5 mg every 3 months, or 45 mg every 6 months, in combination with enzalutamide (Xtandi) prescribed at 160 mg daily (four 40 mg capsules) for patients with castration-resistant prostate cancer.

Key Findings

• The PROSPER trial demonstrated that enzalutamide improved the primary endpoint of metastasis-free survival over placebo, with a median metastasis-free survival of 36.6 months compared to 14.7 months with placebo 1.
• The STRIVE trial showed that enzalutamide reduced the risk of progression or death by 76% compared with bicalutamide, with a median time to progression of 15.7 months compared to 5.8 months with bicalutamide 1.
• The ARCHES clinical trial found that enzalutamide improved radiographic PFS, with a median radiographic PFS of 19.0 months compared to not reached with placebo, and a 34% reduction in the risk of death 1.

Side Effects and Management

Side effects of enzalutamide include fatigue, seizures, and hypertension, and require comprehensive management including bone health monitoring, cardiovascular risk assessment, and quality of life considerations throughout treatment.

Monitoring and Follow-up

Regular PSA monitoring is essential, typically every 3-6 months, with testosterone levels checked to confirm castrate levels (<50 ng/dL).

• The treatment duration varies based on disease stage, with ADT potentially being lifelong for metastatic disease or limited to 18-36 months when combined with radiation for localized disease.
• Enzalutamide is a category 1 option for patients with M1 castration-sensitive prostate cancer, and has been FDA approved for this indication since December 2019 1.

From the FDA Drug Label

Once daily dosing of 160 mg enzalutamide in addition to ADT reduced PSA levels to undetectable levels (< 0. 2 ng/mL) in 68% of patients with mCSPC (ARCHES).

The combination of Androgen Deprivation Therapy (ADT) and enzalutamide can reduce PSA levels to undetectable levels in a significant proportion of patients. Specifically, 68% of patients with metastatic castration-sensitive prostate cancer (mCSPC) achieved undetectable PSA levels (< 0.2 ng/mL) when treated with 160 mg of enzalutamide daily in addition to ADT.

• Key points:
  • ADT and enzalutamide: combination therapy
  • PSA reduction: 68% of patients achieved undetectable levels
  • Patient population: metastatic castration-sensitive prostate cancer (mCSPC)
  • Enzalutamide dosage: 160 mg daily 2

From the Research

Reduction of PSA Levels

• The treatment regimen for reducing Prostate-Specific Antigen (PSA) levels in patients with prostate cancer using Androgen Deprivation Therapy (ADT) and medications like leuprolide or enzalutamide can vary depending on the specific patient and disease characteristics 3, 4.
• Studies have shown that enzalutamide monotherapy can be as effective as ADT in combination with external beam radiation therapy for patients with intermediate-risk prostate cancer, with fewer side effects 3.
• The combination of enzalutamide and ADT has been shown to be effective in reducing PSA levels in patients with metastatic hormone-sensitive prostate cancer (mHSPC) 4, 5.

Timeframe for PSA Reduction

• The timeframe for reducing PSA levels can vary depending on the specific treatment regimen and patient characteristics.
• One study found that enzalutamide monotherapy resulted in PSA values ≤0.2 ng/mL in 77% of patients and ≤0.5 ng/mL in 94% of patients at the 6-month timepoint 3.
• Another study found that the 7-month PSA response rate was 94% in patients taking enzalutamide and 65% in patients taking bicalutamide, with a significant difference between the two groups (P = 0.008) 5.

Factors Affecting PSA Reduction

• The duration of response to ADT has been shown to be an independent prognostic factor for outcome in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with enzalutamide or abiraterone acetate 6.
• Patients with longer ADT response had better overall survival (OS) and progression-free survival (PFS) compared to those with shorter ADT response 6.
• The combination of enzalutamide and ADT has been shown to be effective in reducing PSA levels in Black patients with mHSPC, with a significant difference in PSA response rates compared to bicalutamide (P = 0.009) 5.