title: Skeletal metastases and impact of anticancer and bone-targeted agents in patients with castration-resistant prostate cancer.
abstract: Incidence of bone metastases is very high in advanced prostate cancer patients. Bone metastases likely have a significant impact on functional status and quality of life, not only related to pain, but also to the relevant risk of skeletal-related events. A better understanding of mechanisms associated with bone metastatic disease secondary to prostate cancer and more specifically to the cross-talk between tumor cells and bone microenvironment in metastatic progression represented the background for the development of new effective bone-targeted therapies. Furthermore, a better knowledge of biological mechanisms driving disease progression led to significant advances in the treatment of castration-resistant prostate cancer, with the development and approval of new effective drugs. Aim of this review is to outline the physiopathology of bone metastases in prostate cancer and summarize the main results of clinical trials conducted with different drugs to control morbidity induced by skeletal metastases and bone disease progression. For each agent, therapeutic effect on bone metastases has been measured in terms of pain control and/or incidence of skeletal-related events, usually defined as a composite endpoint, including the need for local treatment (radiation therapy or surgery), spinal cord compression, pathological bone fractures. In details, data obtained with chemotherapy (mitoxantrone, docetaxel, cabazitaxel), new generation hormonal agents (abiraterone, enzalutamide), radium-223, bone-targeted agents (zoledronic acid, denosumab) and with several experimental agents (cabozantinib, dasatinib, anti-endothelin and other agents) in patients with castration-resistant prostate cancer are reviewed.
authors.affiliation: Division of Medical Oncology, Department of Oncology, University of Turin at San Luigi Gonzaga Hospital, Orbassano, Turin, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Vignani
authors.affiliation: Division of Medical Oncology, Department of Oncology, University of Turin at San Luigi Gonzaga Hospital, Orbassano, Turin, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Bertaglia
authors.affiliation: Division of Medical Oncology, Department of Oncology, University of Turin at San Luigi Gonzaga Hospital, Orbassano, Turin, Italy.
authors.forename: Consuelo
authors.initials: C
authors.lastname: Buttigliero
authors.affiliation: Division of Medical Oncology, Department of Oncology, University of Turin at San Luigi Gonzaga Hospital, Orbassano, Turin, Italy. Electronic address: marcello.tucci@gmail.com.
authors.forename: Marcello
authors.initials: M
authors.lastname: Tucci
authors.affiliation: Division of Medical Oncology, Department of Oncology, University of Turin at San Luigi Gonzaga Hospital, Orbassano, Turin, Italy.
authors.forename: Giorgio V
authors.initials: GV
authors.lastname: Scagliotti
authors.affiliation: Division of Medical Oncology, Department of Oncology, University of Turin at San Luigi Gonzaga Hospital, Orbassano, Turin, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Di Maio
mesh_terms: D000736:Androstenes / Q000627:therapeutic use; D000813:Anilides / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000556:secondary; D002277:Carcinoma / Q000188:drug therapy* / Q000556:secondary; D000069439:Dasatinib / Q000627:therapeutic use; D000069448:Denosumab / Q000627:therapeutic use; D004164:Diphosphonates / Q000627:therapeutic use; D000077143:Docetaxel; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use; D008297:Male; D008942:Mitoxantrone / Q000627:therapeutic use; D009570:Nitriles; D010669:Phenylthiohydantoin / Q000031:analogs & derivatives / Q000627:therapeutic use; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000473:pathology; D011725:Pyridines / Q000627:therapeutic use; D011868:Radioisotopes / Q000627:therapeutic use; D011883:Radium / Q000627:therapeutic use; D043823:Taxoids / Q000627:therapeutic use; D000077211:Zoledronic Acid
chemical_list: D000736:Androstenes; D000813:Anilides; D000970:Antineoplastic Agents; D001549:Benzamides; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D009570:Nitriles; D011725:Pyridines; D011868:Radioisotopes; D043823:Taxoids; D000077143:Docetaxel; C558660:cabozantinib; D010669:Phenylthiohydantoin; D000069448:Denosumab; C552428:cabazitaxel; D000077211:Zoledronic Acid; C540278:enzalutamide; D008942:Mitoxantrone; C089740:abiraterone; D000069439:Dasatinib; C581106:radium Ra 223 dichloride; D011883:Radium
keywords: Bone metastasis; Bone-targeted therapy; Castration resistant prostate cancer; Chemotherapy; New generation hormonal agents; Skeletal related event