Combination radium-223 therapies in patients with bone metastases from castration-resistant prostate cancer: A review

• Published in: Critical reviews in oncology/hematology Vol. 146; p. 102864
• Main Authors: Cursano, M.C., Iuliani, M., Casadei, C., Stellato, M., Tonini, G., Paganelli, G., Santini, D., De Giorgi, U.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-02-2020
• Subjects: Abiraterone; Androstenes - therapeutic use; Antineoplastic Agents - therapeutic use; Bone Density Conservation Agents - therapeutic use; Bone metastases; Bone Neoplasms - pathology; Bone Neoplasms - secondary; Bone Neoplasms - therapy; Bone protecting agents; Castration-resistant prostate cancer; Docetaxel; Docetaxel - therapeutic use; Enzalutamide; Humans; Male; Orchiectomy; Phenylthiohydantoin - analogs & derivatives; Phenylthiohydantoin - therapeutic use; Prostatic Neoplasms, Castration-Resistant - pathology; Prostatic Neoplasms, Castration-Resistant - therapy; Radioisotopes - therapeutic use; Radiopharmaceuticals - administration & dosage; Radiopharmaceuticals - therapeutic use; Radium - therapeutic use; Radium-223; Skeletal-related events; Treatment Outcome; Tumor Microenvironment; Castration-resistant prostate cancer; Abiraterone; Radium-223; Docetaxel; Enzalutamide; Skeletal-related events; Bone protecting agents; Bone metastases
• ISSN: 1040-8428; 1879-0461
• DOI: 10.1016/j.critrevonc.2020.102864

•In bone mCRPC, each treatment has an effect on PCa cells and bone microenvironment.•Clinical trials have been performed to evaluate radium 223-based combination therapies.•Pretreated and un-pretreated patients have different morbidity and clinical outcomes.•Different bone metabolic status could justify the different clinical outcomes.•Associating bone protecting agents reduce treatment-related morbidity.
Chemotherapeutic agents (docetaxel, cabazitaxel), hormonal therapies (abiraterone, enzalutamide) and radium-223 improve survival in patients with bone metastatic castration-resistant prostate cancer (mCRPC). Combinations of radium-223 with these agents or novel drugs have been investigated in order to improve survival and decrease bone-related morbidity. In mCRPC, clinical and preclinical data indicate that radium-223, abiraterone and enzalutamide have a direct effect on prostate cancer cells and bone microenvironment when administered as single agents. Initial results from studies of radium-223 and abiraterone, enzalutamide or docetaxel demonstrated efficacy without any safety concern in pre-treated mCRPC; however, this safety profile changed when radium-based combination therapies were administered in un-pretreated mCRPC. This review underline the biological rationale for combining radium strategies, investigating their effects on bone in terms of control of skeletal-related events and bone disease progression. The aim is to understand the possible reasons why different radium-based combination treatments can led to different clinical outcomes.