Enzalutamide & Dutasteride/Finasteride as 1st Line Treatment for Patients =/> 65 Years Old With Prostate Cancer.

Inclusion Criteria

Histologically or cytologically confirmed adenocarcinoma of the prostate without neuroendocrine differentiation or small cell features.

Patients with systemic prostate cancer as defined by either a) hormonal naïve metastatic prostate cancer with radiographic evidence of visceral or osseous metastasis or b) biochemical recurrence prostate cancer that fulfills all of the following criteria:

A minimum of three rising prostatic-specific antigen levels with an interval of =/> 1 week between each test, The prostatic-specific antigen (PSA) value at the screening visit should be =/> 2 ng/ml prostatic-specific antigen doubling time ≤ 9 months.

Patients should be 65 years or older. Patients who are deemed "not fit" by comprehensive geriatric assessment or at high risk for side effects as determined by the treating physician. A case report form will be used to document the specifics of why each eligible patient is not considered an ideal candidate.

Serum testosterone level > 1.7 nmol/L (50 ng/dL) at the screening visit (non- castrate).

Patients could have received hormonal therapy as part of definitive treatment for previous localized prostate cancer. However, they should be off any hormonal therapy for greater than six months prior to entry to clinical trial.

Eastern Cooperative Oncology Group performance status of 0 to 2. Able to swallow the study drug and comply with study requirements.

Exclusion Criteria

Severe concurrent disease or infection that, in the judgment of the investigator, would make the patient inappropriate for enrollment.

Known brain metastases. Brain imaging studies are not required for eligibility if the patient has no neurologic signs or symptoms suggestive of brain metastasis. However, if brain imaging studies are performed, they must be negative for disease.

Patient is receiving treatment for another active malignancy excluding localized cutaneous squamous or basal cell carcinoma.

Prior treatment for systemic prostate cancer. Prior treatment with enzalutamide. Treatment with androgen receptor antagonists (bicalutamide, flutamide, nilutamide,), ketoconazole, abiraterone, finasteride, dutasteride, estrogens, or chemotherapy in an adjuvant setting within 6 months of enrollment (Day 1 visit) or plans to initiate treatment with any of these treatments.

Treatment with therapeutic immunizations for prostate cancer (e.g., PROVENGE®) or plans to initiate treatment with any of these treatments during the study period.

Use of herbal products that may decrease prostatic-specific antigen levels (e.g., saw palmetto) or systemic corticosteroids greater than the equivalent of 10 mg of prednisone/prednisolone per day within 4 weeks of enrollment (Day 1 visit) or plans to initiate treatment with any of these treatments during the study.

Radiation therapy within 3 weeks (if single fraction of radiotherapy within 2 weeks) and radioisotope therapy within 8 weeks of enrollment (Day 1 visit).

Participation in a previous clinical trial of an investigational agent that blocks androgen synthesis within six months.

Participation in a previous clinical trial of enzalutamide. Use of an investigational agent within 4 weeks of enrollment (Day 1 visit) or plans to initiate treatment with an investigational agent during the study.

Have used or plan to use from 30 days prior to enrollment (Day 1 visit) through the end of the study the following medications known to lower the seizure threshold or increase or decrease the bioavailability of the drug.

Concomitant use of strong or moderately strong Cytochrome P450 isozyme inducers:

Strong Cytochrome P450 isoenzyme 2C8 inhibitors like gemfibrozil, Strong Cytochrome P450 isoenzyme 2C8 inducers like Rifampin, Strong Cytochrome P450 isoenzyme 3A4 inhibitors like Itraconazole, Aminophylline/theophylline, Atypical antipsychotics (e.g., clozapine, olanzapine, risperidone, ziprasidone), Bupropion, Class IA and Class III antiarrhythmics (e.g., amiodarone, bretylium, dis