The Combination Therapy With Ra-223 and Enzalutamide

Inclusion Criteria:

1. Patients diagnosed as CRPC
2. Surgical or those who will be treated with luteinizing hormone-releasing hormone (LHRH) agonists throughout the study period,
3. Patients who had \>30% of PSA response to enzalutamide prior to enrollment,
4. Interval between PSA progression and enrollment is up to 3 months,
5. With bone metastases (≥ 2 hot spots) on bone scintigraphy within previous 24 weeks,
6. No intention to use anti-cancer chemotherapy within the next 6 months,
7. Eastern Cooperative Oncology Group performance status (ECOG-PS): 0-1,
8. Life expectancy ≥ 6 months,
9. Laboratory requirements within 30 days before enrollment:

   * Absolute neutrophil count (ANC) ≥ 1.5 x 10e9/L,
   * Platelet count ≥ 100 x 10e9/L,
   * Hemoglobin ≥ 10.0 g/dL,
   * Total bilirubin level ≤1.5 institutional upper limit of normal (ULN),
   * Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤ 2.5 ULN,
   * Creatinine ≤ 1.5ULN, and estimated glomerular filtration rate (GFR) ≥ 30 mL/min/1.73 m2,
10. Age ≥ 20,
11. Ability to understand and the willingness to sign a written informed consent (IC).

Exclusion Criteria:

1. Prior chemotherapy or planned treatment with chemotherapy,
2. PSA progression within 3 months after initiation of enzalutamide
3. Prior treatment with corticosteroids, estramustine or abiraterone acetate,
4. Any systemic radiotherapy with strontium-89, samarium-153, rhenium-186 or rhenium-188 for the treatment of bone metastases,
5. Had history of gastrointestinal bleeding or ulcer within 3 months prior to study entry,
6. History of visceral metastasis, or presence of visceral metastasis detected by screening imaging examinations,
7. History of or known brain metastasis,
8. Malignant lymphadenopathy ≧1.5 cm in short axis,
9. Imminent or established spinal cord compression based on clinical findings and/or MRI (Magnetic Resonance Imaging),
10. Any other serious illness or medical condition
11. Substance abuse, medical, psychological, or social conditions that might interfere with the subject's participation in the study or evaluation of the study Results
12. Those who judged to be inappropriate by the principal investigator or co-investigator.