16.7 Hypercalcaemia of malignancy

Hypercalcaemia is the commonest life-threatening metabolic disorder associated with advanced cancer. It occurs in approximately 10% of patients with 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.

Normal range: normal serum corrected calcium is 2.2-2.6mmol/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.


Fluid replacement

Oral fluids

  • insufficient to treat even mild hypercalcaemia but may be useful in managing patient's symptoms at home

Intravenous fluids

  • rehydrate with a minimum of 1-2 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

Disodium Pamidronate (1st line)

See section 6.6 Drugs affecting bone metabolism

The Summary of Product Characteristics (SPC) recommends a dose dependent on the initial albumin-corrected plasma concentration:

IV pamidronate disodium for hypercalcaemia

(manufacturer's recommendations)

Corrected plasma calcium concentrationDose
less than 3 mmol/L15 or 30mg
3 – 3.5 mmol/L30 or 60mg
3.5 – 4 mmol/L60 or 90mg
greater than 4 mmol/L90mg

However, it has been suggested the higher dose should be given irrespective of the initial calcium level to increase the probability of a response and prolong its duration.

  • Patients should be well hydrated
  • Standard and maximum recommended dose is 90mg IVI 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 mild-moderate renal impairment.
Zolendronic acid (Zolendronate®) (2nd line)

See section 6.6 Drugs affecting bone metabolism

Patients should be well hydrated

Give 4mg IV in 100ml 0.9% saline or 5% glucose over 15 minutes

Measure plasma creatinine before each dose, no adjustment is required in mild-moderate 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).


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