title: Malignancy associated hypercalcaemia-responsiveness to IV bisphosphonates and prognosis in a palliative population.
abstract: BACKGROUND
  Hypercalcaemia is a potentially fatal paraneoplastic complication of malignancy. It primarily manifests during the advanced phase of cancer, with the life expectancy of patients ranging from weeks to months. The mainstay of treatment is with bisphosphonates, but these are not frequently used in a palliative population due to potential conflict with goals of care.
  
  
  OBJECTIVE
  The goals of this study was to determine the reversibility of hypercalcaemia amongst patients whose underlying malignancy is not being treated and assess whether correction results in improvement in symptoms attributable to hypercalcaemia, while identifying risk factors that can predict responsiveness.
  
  
  METHODS
  We conducted a retrospective cohort study of 63 patients aged >18 years who were admitted to the St Joseph's Palliative Care Unit, Australia between 2007 and 2013, having evidence of malignancy-associated hypercalcaemia which was treated with bisphosphonates. We assessed the response to bisphosphonates based on improvement of symptoms attributable to hypercalcaemia, as well as a reduction in serum calcium. We used the Kaplan-Meier survival method and parametric survival analysis to estimate the effect of the independent variables on time till death.
  
  
  RESULTS
  Thirty-six of sixty three patients achieved normocalcaemia following treatment with an intravenous bisphosphonate. Complete response was influenced by the number of instances of hypercalcaemia in the past and patient factors, such as age and albumin levels. We found that a reduction in calcium level was associated with a significantly prolonged survival, as well as symptomatic improvement, irrespective of whether normocalcaemia was achieved.
  
  
  CONCLUSIONS
  Our study suggests that bisphosphonates can be recommended as a palliative measure for selected patients to improve symptoms and prolong survival.
authors.affiliation: Liverpool Hospital, Elizabeth Street, Liverpool, NSW, 2170, Australia. ajcmallik@gmail.com.
authors.forename: Shreyashee
authors.identifier: http://orcid.org/0000-0003-3544-3146
authors.initials: S
authors.lastname: Mallik
authors.affiliation: School of Business, University of Western Sydney, Sydney, Australia.
authors.forename: Girijasankar
authors.initials: G
authors.lastname: Mallik
authors.affiliation: Palliative Care Unit, St Joseph's Hospital, Auburn, Australia.
authors.forename: Shireen Teves
authors.initials: ST
authors.lastname: Macabulos
authors.affiliation: Palliative Care Unit, St Joseph's Hospital, Auburn, Australia.
authors.forename: Andrew
authors.initials: A
authors.lastname: Dorigo
mesh_terms: D061605:Administration, Intravenous; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001315:Australia; D050071:Bone Density Conservation Agents / Q000008:administration & dosage; D004164:Diphosphonates / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D006934:Hypercalcemia / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications*; D010166:Palliative Care / Q000379:methods*; D010257:Paraneoplastic Syndromes / Q000188:drug therapy* / Q000209:etiology; D011379:Prognosis; D012189:Retrospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates
keywords: Bisphosphonates; Malignancy-associated hypercalcaemia; Palliative care; Prognosis