Hypercalcaemia of Malignancy Care Pathway

Review in progress

Disclaimer: The guidance contains helpful primary care information for management of referrals and up to date referral criteria. These guidelines are locality specific to best reflect local services. This guidance does not override or replace the individual responsibility of healthcare and social care professionals involved in the delivery of care to make informed professional judgements appropriate to the circumstances of the individual.


This guidance refers to:

  • Hypercalcaemia associated with malignancy only
  • Patients over 18 years of age

This guidance does not cover:

  • Patients under 18 years of age



  • Hypercalcaemia is the commonest life-threatening metabolic disorder associated with advanced cancer. It occurs in approximately 10% of patients with cancer (up to 20-30% with advanced cancer).
  • Hypercalcaemia can occur in any malignancy but is most common in cancers of the breast, squamous cell carcinomas (e.g. bronchus, upper oesophagus), lymphoma, myeloma, kidney and bladder.
  • Patients may be asymptomatic, and symptoms are often more related to the rate of rise rather than to the absolute level of the calcium. Serious or distressing symptoms may present with a relatively small elevation of the serum calcium or very high calcium may produce few symptoms.
  • It should be considered in all patients with unexplained nausea, vomiting, confusion or constipation.
  • Normal range: normal serum corrected calcium is 2.2­ - 2.6 mmol/L


  • Confusion/mental dullness
  • Constipation
  • Drowsiness
  • Fatigue, lethargy & weakness
  • Loss of appetite & anorexia
  • Dehydration & thirst
  • Nausea & vomiting
  • Polydipsia & polyuria
  • Abdominal pain
  • Ileus
  • Coma


Whether to treat?
  • A decision to treat should be based upon:
    • Degree of symptoms
    • Stage of disease and prognosis
    • Previous quality of life Patient's wishes
    • Symptomatic hypercalcaemia is often associated with a poor prognosis, and may recur rapidly even following successful initial treatment. In patients with a poor quality of life it may not be appropriate to initiate treatment.
    • Response to previous treatments in terms of symptom benefit and length of time between treatments
  • Cancer is usually advanced when hypercalcaemia develops and refractory hypercalcaemia is a poor prognostic sign
  • If the hypercalcaemia is diagnosed in the primary care setting then treatment (if appropriate) will be required as an inpatient.
  • There is no specific calcium level above which treatment will be required.
    • For most appropriate patients symptomatic hypercalcaemia over 3 mmol/L will require treatment.
    • This can be arranged via your local hospice or hospital.
  • For patients undergoing active anti-cancer treatment this may be most appropriate as a hospital inpatient.
    • Otherwise please contact your local hospice to see whether urgent admission is possible.
If you are not sure whether treatment is appropriate, please contact your local palliative care team for advice.
Fluid replacement
  • Oral fluids
    • Should be optimized but likely to be insufficient to treat even mild established hypercalcaemia.
  • Intravenous fluids
    • Re-hydrate with a minimum of 2 litres normal saline 0.9% IV during the first 24 hours
    • The volume and rate of fluid replacement will depend on the degree of dehydration, severity of hypercalcaemia and ability of the cardiovascular system to tolerate rehydration
    • Drugs which reduce renal blood flow or renal calcium excretion should be avoided and stopped where possible (e.g. NSAIDS, thiazide diuretics)
    • Following rehydration, recheck U&Es if serum creatinine was greater than 250mmol/L
Intravenous Bisphosphonates

In practice there is little to choose between bisphosphonates and local guidelines should be followed.

Zolendronic acid (Zolendronate®) (1st line)

  • Patients should be well hydrated (as above)
  • Usual dose is 4mg IV over 15 minutes
  • Doses should be reduced in patients with renal impairment

Disodium Pamidronate (Alternative)

  • Patients should be well hydrated (as above)
  • Standard and maximum recommended dose is 90mg IV treatment
  • The infusion rate should not exceed 1mg/min in patients with normal renal function
  • In patients with mild/­moderate renal impairment (creatinine clearance 30­-90mL/min) do not require dose reduction but the infusion should not exceed 90mg/4 hours
  • In palliative care patients with severe renal impairment (creatinine clearance less than 30mL/min) it is unlikely that a bisphosphonate will be started. Seek specialist advice.
  • Measure plasma creatinine before each dose, no adjustment is required in mild­moderate renal impairment.
Response to treatment
  • It takes 2-­7 days to achieve maximum effect, and corrected calcium levels should be checked after approximately 5 days. The average duration of effect is 20-­30 days.
  • If calcium does not return to within normal range and patient remains symptomatic, options include repeating bisphosphonate infusion after 1 week or changing to alternative bisphosphonate.
  • Monitor corrected calcium levels every 3-­4 weeks or when symptoms occur.
  • If needing to retreat within 3 weeks, or for patients with resistant hypercalcaemia, please seek specialist advice
  • Some patients may be receiving denosumab (Xgeva®), a monoclonal antibody treatment for bone metastatases secondary to solid tumours, as part of their oncology treatment regime. It is also an option for treating refractory hypercalcaemia of malignancy (unauthorised indication). Calcitonin is another alternative but should be considered following specialist advice.
  • Refractory hypercalcaemia is a poor prognostic indicator.


Referral Criteria

If treatment is required then this can be arranged via your local hospital or local hospice.
  • If the hypercalcaemia is diagnosed treatment (if appropriate) will be required as an inpatient.
  • There is no specific calcium level above which treatment will be required but for most appropriate patients symptomatic hypercalcaemia over 3 mmol/L will require treatment
  • For patients undergoing active anti-cancer treatment this may be most appropriate as a hospital inpatient
Wakefield CCG
  • Eligibility for referral to specialist palliative care services (including inpatient, community, day hospice or outpatient service provision) is based on patient need not diagnosis:
    • The patient has active, progressive and usually advanced disease for which the prognosis is limited (although this may be several years) and the focus of care is quality of life.
    • The patient has unresolved complex needs that cannot be met by the caring team. These needs may be physical, psychological, social and /or spiritual. Examples may include complicated symptoms, difficult family situations, or ethical issues regarding treatment decisions.
  • Patients who meet the above criteria may be admitted to any part of the specialist palliative care service as required
  • An eConsultation request can also be sent via SystmOne
  • See palliative care contact details and resources for further information
North Kirklees
  • Common eligibility criteria were agreed in 2000 by all providers of SPC (specialist palliative care) working in Calderdale and Kirklees in order to ensure equity of access. The criteria reflects those adopted by other SPC services across the country and was incorporated into the new service agreement with Kirkwood on April 2015.
  • There are three elements to the common eligibility criteria:
    • Patients should have active, progressive and potentially life-threatening illness
    • Patients should have unresolved, complex needs that cannot be met by the current caring team, or it is anticipated that the patient will develop such needs in the near future. These needs may be psychological, social, spiritual or physical
    • Patients must have been recently assessed by a member of a SPC team
  • See palliative care contact details for further information

Referral Forms

Wakefield CCG
North Kirklees CCG

Supporting Information

Shared Decision Making

  • Patients have a right to make decisions about their care and should be fully informed about the options they face. They should be provided with reliable evidence-based information on the likely benefits and harms of interventions or actions, including any uncertainties and risks, eliciting their preferences and supporting implementation.

Patient Information/Public Health/Self Care

Evidence/Supporting Informtation

Useful Links

Hospice information

Assurance & Governance

  • This guidance was developed on: 07.2017
  • This guidance was ratified by: The OSCAR Assurance Group
  • Date ratified: 09.2017
  • Publication Date: 09.2017
  • Review Date: 07.2019
  • Ref No: PL6 - 07.2017
Any feedback or suggestions to improve this guidance should be sent to: oscaradmin@this.nhs.uk
Only the electronic version is maintained, once printed this is no longer a controlled document


Home > Care Pathways > Palliative Care* > Hypercalcaemia of Malignancy Care Pathway