title: Denosumab in hypercalcemia of malignancy: a case series.
abstract: BACKGROUND
  Denosumab is a nuclear factor-kappa ligand monoclonal antibody whose FDA-approved indications include treatment of osteoporosis, bone loss with certain anticancer hormonal agents, and prevention of skeletal-related events in patients with bone metastases from solid tumors. In clinical trials, the incidence of severe hypocalcemia has been reported as 3.1-10.8%. To date, case reports and two clinical trials have reported the use of denosumab in the management of hypercalcemia of malignancy. No reports of denosumab-induced hypocalcemia have been reported for the hypercalcemia of malignancy population.
  
  
  METHODS
  We performed a retrospective chart review of all patients who received denosumab for hypercalcemia of malignancy to describe the effects of denosumab on calcium levels at our institution.
  
  
  RESULTS
  Seven patients received doses of denosumab for hypercalcemia of malignancy. The most common tumor types were breast cancer (n = 3) and hematologic malignancies (n = 2). All patients had bone involvement. Two patients received single doses of 60 mg. The other five patients received 120 mg. The mean corrected calcium levels were 13.7 mg/dL and 12.24 mg/dL for the days of admission and denosumab administration, respectively (p = 0.1889). The mean corrected calcium level for the last known value was 9.92 mg/dL, while in house (p = 0.0016). Supportive care prior to denosumab included hydration (n = 7), bisphosphonates (n = 6), and calcitonin (n = 5). One patient had a calcium level of 6.6 mg/dL on day 4 after denosumab, requiring calcium supplementation and telemetry. Of the seven patients treated with denosumab for hypercalcemia of malignancy at our institution, six patients were discharged alive. Of these, one patient died two days after discharge. Last-known follow-up was a median of 26 days, range, 3-195, for all patients.
  
  
  CONCLUSIONS
  Denosumab helped decrease calcium in patients with hypercalcemia of malignancy. However, symptomatic hypocalcemia may result from denosumab in hypercalcemia of malignancy.
authors.affiliation: Division of Pharmacy, Dana-Farber Cancer Institute, Boston, MA, USA amanda_dietzek@dfci.harvard.edu.
authors.forename: Amanda
authors.initials: A
authors.lastname: Dietzek
authors.affiliation: Smilow Cancer Hospital at Yale New Haven, New Haven, CT, USA.
authors.forename: Kelly
authors.initials: K
authors.lastname: Connelly
authors.affiliation: Department of Pharmacy, Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Cotugno
authors.affiliation: Division of Pharmacy, Dana-Farber Cancer Institute, Boston, MA, USA Department of Pharmacy, Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Bartel
authors.affiliation: Department of Pharmacy, Brigham and Women's Hospital, Boston, MA, USA.
authors.forename: Anne M
authors.initials: AM
authors.lastname: McDonnell
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D050071:Bone Density Conservation Agents / Q000008:administration & dosage* / Q000009:adverse effects; D002118:Calcium / Q000097:blood; D000069448:Denosumab / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D006934:Hypercalcemia / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D008875:Middle Aged; D010257:Paraneoplastic Syndromes / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology; D012189:Retrospective Studies; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D050071:Bone Density Conservation Agents; D000069448:Denosumab; D002118:Calcium
keywords: Denosumab; hypercalcemia; hypercalcemia of malignancy