TY - JOUR
T1 - Denosumab for treatment of hypercalcemia of malignancy
AU - Hu, Mimi I.
AU - Glezerman, Ilya G.
AU - Leboulleux, Sophie
AU - Insogna, Karl
AU - Gucalp, Rasim
AU - Misiorowski, Waldemar
AU - Yu, Bennett
AU - Zorsky, Paul
AU - Tosi, Diego
AU - Bessudo, Alberto
AU - Jaccard, Arnaud
AU - Tonini, Giuseppe
AU - Ying, Wendy
AU - Braun, Ada
AU - Jain, Rajul K.
N1 - Publisher Copyright:
© 2014 by the Endocrine Society.
PY - 2014/9/1
Y1 - 2014/9/1
N2 - 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%) reachedCSC≤11.5 mg/dL,and12 patients (33%) reachedCSC≤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 in64%of patients within 10 days, inducing durable responses.Denosumabmay offer a new treatment option for HCM.
AB - 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%) reachedCSC≤11.5 mg/dL,and12 patients (33%) reachedCSC≤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 in64%of patients within 10 days, inducing durable responses.Denosumabmay offer a new treatment option for HCM.
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U2 - 10.1210/jc.2014-1001
DO - 10.1210/jc.2014-1001
M3 - Article
C2 - 24915117
AN - SCOPUS:84907200658
SN - 0021-972X
VL - 99
SP - 3144
EP - 3152
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 9
ER -