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Group name EquipeCG
Item Type Journal Article
Title Denosumab for treatment of hypercalcemia of malignancy
Creator Hu et al.
Author Mimi I. Hu
Author Ilya G. Glezerman
Author Sophie Leboulleux
Author Karl Insogna
Author Rasim Gucalp
Author Waldemar Misiorowski
Author Bennett Yu
Author Paul Zorsky
Author Diego Tosi
Author Alberto Bessudo
Author Arnaud Jaccard
Author Giuseppe Tonini
Author Wendy Ying
Author Ada Braun
Author Rajul K. Jain
Abstract CONTEXT: Hypercalcemia of malignancy (HCM) in patients with advanced cancer is often caused by excessive osteoclast-mediated bone resorption. Patients may not respond to or may relapse after iv bisphosphonate therapy. OBJECTIVE: We investigated whether denosumab, a potent inhibitor of osteoclast-mediated bone resorption, reduces serum calcium in patients with bisphosphonate-refractory HCM. DESIGN, SETTING, AND PARTICIPANTS: In this single-arm international study, participants had serum calcium levels corrected for albumin (CSC) >12.5 mg/dL (3.1 mmol/L) despite bisphosphonates given >7 and ?30 days before screening. INTERVENTION: Patients received 120 mg sc denosumab on days 1, 8, 15, and 29 and then every 4 weeks. MAIN OUTCOME MEASURES: The primary endpoint was the proportion of patients with CSC ?11.5 mg/dL (2.9 mmol/L) (response) by day 10. Secondary endpoints included response by visit, duration of response, and the proportion of patients with a complete response (CSC ?10.8 mg/dL [2.7 mmol/L]) by day 10 and during the study. RESULTS: Patients (N = 33) had solid tumors or hematologic malignancies. By day 10, 21 patients (64%) reached CSC ?11.5 mg/dL, and 12 patients (33%) reached CSC ?10.8 mg/dL. During the study, 23 patients (70%) reached CSC ?11.5 mg/dL, and 21 patients (64%) reached CSC ?10.8 mg/dL. Estimated median response duration was 104 days. The most common serious adverse events were hypercalcemia worsening (5 patients, 15%) and dyspnea (3 patients, 9%). CONCLUSIONS: In patients with HCM despite recent iv bisphosphonate treatment, denosumab lowered serum calcium in 64% of patients within 10 days, inducing durable responses. Denosumab may offer a new treatment option for HCM.
Publication The Journal of Clinical Endocrinology and Metabolism
Volume 99
Issue 9
Pages 3144-3152
Date Sep 2014
Journal Abbr J. Clin. Endocrinol. Metab.
Language eng
DOI 10.1210/jc.2014-1001
ISSN 1945-7197
Library Catalog PubMed
Extra PMID: 24915117 PMCID: PMC4154084
Tags Adult, Aged, Aged, 80 and over, Amgen, Antibodies, Monoclonal, Humanized, Bone Density Conservation Agents, Bone Resorption, clinic, Denosumab, Diphosphonates, Female, Gastrointestinal Diseases, Humans, Hypercalcemia, Hypophosphatemia, Internationality, Male, Middle Aged, Neoplasms, RANK Ligand, Serum Albumin, Therapeutics, Young Adult
Date Added 2019/05/14 - 12:26:48
Date Modified 2019/10/24 - 16:26:10
Notes and Attachments PubMed entry (Attachment)
Texte intégral (Attachment)


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