title: Tolerability of denosumab in metastatic solid tumor patients with renal insufficiency.
abstract: OBJECTIVE
  Denosumab is approved for the prevention of skeletal-related events (SREs) in metastatic solid tumor patients with bone metastases. Limited data regarding the safety of denosumab in patients with severe renal insufficiency suggests increased rates of hypocalcemia compared to patients with normal renal function. The purpose of this study was to assess the rates of hypocalcemia and hypophosphatemia in cancer patients with severe renal impairment.
  
  
  METHODS
  In this case series, patient demographics, primary tumor site, number of denosumab doses, and episodes of hypocalcemia and hypophosphatemia were retrospectively obtained by patient chart review. Estimated glomerular filtration rate (eGFR) was calculated using the Cockcroft-Gault equation. Twenty-two metastatic solid tumor patients with severe renal insufficiency (creatinine clearance <30 mL/min) who had received denosumab at a dose of 120 mg were included.
  
  
  RESULTS
  Ten of 22 patients (45 %) experienced a hypocalcemic event of any grade. Three patients (14 %) had grade 3 hypocalcemia, and no patients had grade 4 hypocalcemia. The median number of doses of denosumab prior to calcium nadir was one. Seven of 22 patients (32 %) experienced hypophosphatemia of any grade including grade 3 events in two patients (9 %).
  
  
  CONCLUSIONS
  Denosumab resulted in increased rates of hypocalcemia when administered to metastatic solid tumor patients with severe renal impairment for the prevention of SREs compared to previously reported rates of hypocalcemia in the general population. However, all cases of hypocalcemia were asymptomatic and resolved prior to subsequent dosing. Due to a higher rate of hypocalcemia than reported in patients with normal renal function, patients with severe renal impairment should receive close monitoring of calcium levels while receiving denosumab.
authors.affiliation: University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Unit 377, Houston, TX, 77030, USA, karen.eckmann@gmail.com.
authors.forename: Karen R
authors.initials: KR
authors.lastname: Watkins
authors.forename: Jane E
authors.initials: JE
authors.lastname: Rogers
authors.forename: Bradley
authors.initials: B
authors.lastname: Atkinson
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects* / Q000627:therapeutic use; D050071:Bone Density Conservation Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000556:secondary / Q000628:therapy; D000069448:Denosumab; D004164:Diphosphonates / Q000627:therapeutic use; D005260:Female; D006801:Humans; D006996:Hypocalcemia / Q000139:chemically induced* / Q000453:epidemiology; D017674:Hypophosphatemia / Q000139:chemically induced* / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D016609:Neoplasms, Second Primary / Q000628:therapy; D051437:Renal Insufficiency / Q000150:complications*; D012189:Retrospective Studies
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D000069448:Denosumab