What is the treatment for hypercalcemia in malignancy?

Treatment for Hypercalcemia in Malignancy

The first-line treatment for hypercalcemia of malignancy is aggressive intravenous normal saline hydration followed by bisphosphonate therapy, with zoledronic acid 4 mg IV over 15 minutes being the most effective pharmacological intervention. 1

Initial Management

Hydration

• Begin with aggressive IV normal saline hydration to:
  • Restore extracellular volume
  • Promote calciuresis
  • Target urine output of at least 100 mL/hour (3 mL/kg/hour in children <10 kg) 2
• Patients should be adequately rehydrated prior to bisphosphonate administration 3
• Avoid overhydration in patients with cardiac failure 3

Pharmacological Treatment

1. First-line: Bisphosphonates

   • Zoledronic acid 4 mg IV over 15 minutes (preferred)
     • Normalizes calcium in 50% of patients by day 4 2
     • More effective than pamidronate (50% vs 33% normalization by day 4) 2
   • Alternative: Pamidronate 90 mg IV over 2 hours 1
     • Consider for patients with renal impairment

2. For refractory cases:

   • Denosumab (subcutaneous)
     • Particularly useful for hypercalcemia refractory to bisphosphonates 1
     • Lowers serum calcium in 64% of patients within 10 days 2
     • Consider in patients with severe renal impairment 1

Management of Specific Electrolyte Abnormalities

Hyperphosphatemia

• Mild hyperphosphatemia (<1.62 mmol/L):
  • May not require treatment or can be treated with aluminum hydroxide at 50-100 mg/kg/day divided in 4 doses 2

Hypocalcemia

• Asymptomatic hypocalcemia: No treatment required 2
• Symptomatic hypocalcemia (tetany, seizures):
  • Single dose of calcium gluconate 50-100 mg/kg, cautiously repeated if necessary 2
• Monitor calcium levels after denosumab treatment due to increased risk of hypocalcemia 2

Hyperkalemia

• Mild (<6 mmol/L) asymptomatic hyperkalemia:
  • Hydration, loop diuretics, sodium polystyrene 1 g/kg orally or by enema 2
• Severe hyperkalemia:
  • Rapid insulin (0.1 units/kg) plus glucose (25% dextrose 2 mL/kg)
  • Calcium carbonate 100-200 mg/kg/dose
  • Sodium bicarbonate to stabilize myocardial cell membrane and correct acidosis 2
  • Careful ECG monitoring

Indications for Dialysis

Consider dialysis for:

• Acute oliguric renal failure
• Severe hyperphosphatemia
• Severe electrolyte abnormalities
• Extracellular fluid volume overload 2

Monitoring

• Assess serum creatinine prior to each treatment 3
• Monitor serum calcium, creatinine, and electrolytes (particularly magnesium) during treatment 1
• Consider retreatment with zoledronic acid 4 mg if serum calcium does not normalize after initial treatment
  • Allow minimum of 7 days between treatments for full response 3

Special Considerations

• Renal function: Carefully monitor renal function in all patients receiving zoledronic acid 3
• Patients with severe renal impairment: Consider denosumab as an alternative 1
• Risk of hypocalcemia: Monitor calcium levels post-treatment, especially with denosumab 2
• Avoid diuretic therapy prior to correction of hypovolemia 3

Pitfalls to Avoid

• Overlooking renal function when dosing bisphosphonates can lead to adverse effects 1
• Failing to monitor for hypocalcemia after treatment, especially with denosumab 1
• Using diuretics before correcting hypovolemia 3
• Inadequate hydration before administering bisphosphonates 3

By following this treatment approach, hypercalcemia of malignancy can be effectively managed to reduce morbidity and improve quality of life in cancer patients.