From the Guidelines
The treatment for hypercalcemia of malignancy should prioritize aggressive hydration with intravenous normal saline, followed by medications that reduce calcium levels, with zoledronic acid being the preferred bisphosphonate, as recommended by the NCCN Guidelines for MM 1. The treatment approach typically includes:
- Aggressive hydration with intravenous normal saline to correct hypercalcemia-associated hypovolaemia and promote calciuresis 1
- Bisphosphonates, such as zoledronic acid (4 mg IV over 15 minutes) or pamidronate (60-90 mg IV over 2-4 hours), which inhibit bone resorption by osteoclasts 1
- Denosumab (120 mg subcutaneously), a RANK ligand inhibitor, as an effective alternative, especially in patients with renal impairment where bisphosphonates are contraindicated 1
- Calcitonin (4-8 IU/kg subcutaneously or IM every 12 hours) can be added for rapid but short-term calcium reduction while waiting for bisphosphonates to take effect 1
- In severe cases (calcium >14 mg/dL or symptomatic), hemodialysis may be necessary [@Example@]
- Loop diuretics like furosemide should only be used after adequate hydration to enhance calcium excretion [@Example@]
- Treating the underlying malignancy is crucial for long-term management [@Example@]
- Patients should be monitored with serial calcium levels, renal function tests, and electrolytes during treatment [@Example@] These interventions work by either increasing urinary calcium excretion, inhibiting bone resorption, or directly removing calcium from the bloodstream, addressing the pathophysiology of tumor-induced bone destruction and PTHrP-mediated hypercalcemia. Key considerations include:
- Zoledronic acid is preferred over pamidronate due to its equivalent benefits and potential for reduced risk of osteonecrosis of the jaw (ONJ) 1
- Denosumab is preferred in patients with renal disease, but may have a higher risk of hypocalcemia and ONJ 1
- The frequency of dosing (monthly vs every 3 months) and duration of therapy should be based on individual patient criteria and response to therapy 1
From the FDA Drug Label
1 INDICATIONS AND USAGE
1.1 Hypercalcemia of Malignancy Zoledronic acid injection is indicated for the treatment of hypercalcemia of malignancy defined as an albumin-corrected calcium (cCa) of greater than or equal to 12 mg/dL [3.0 mmol/L]
- Treatment for hypercalcemia of malignancy includes zoledronic acid injection, which is indicated for this condition.
- The dosage and administration of zoledronic acid for hypercalcemia of malignancy is not specified in the provided text, but it is indicated for the treatment of this condition.
- Another option for treatment of hypercalcemia of malignancy is denosumab, which is indicated for the treatment of hypercalcemia of malignancy refractory to bisphosphonate therapy 2.
- Pamidronate disodium is also used for the treatment of hypercalcemia of malignancy, although the provided text does not specify the dosage and administration for this condition 3.
From the Research
Treatment Overview
The treatment of hypercalcemia of malignancy (HCM) involves enhancing renal calcium excretion, primarily through hydration with isotonic fluids and the use of antiresorptive therapies 4. The goal is to lower serum calcium levels and alleviate symptoms.
First-Line Treatment
Intravenous zoledronic acid is currently the first-line treatment for HCM 4, 5, 6. It has been shown to be effective in normalizing serum calcium levels and has a faster onset of action compared to other treatments like pamidronate 5, 6.
Alternative Treatments
Subcutaneous denosumab is used for bisphosphonate-refractory hypercalcemia and in patients with renal failure 4, 7, 8. Denosumab has been shown to be effective in reducing serum calcium levels and has a lower risk of HCM compared to zoledronic acid in patients with breast cancer and multiple myeloma 4.
Adjunctive Therapies
Other treatments that can be used as adjunctive therapies include:
- Calcitonin
- Gallium nitrate
- Corticosteroids 7
- Cinacalcet, a calcimimetic 8
- Anti-PTHrP antibodies, which have been successfully used in animal models of disease 8
Treatment Approach
The treatment approach is based on the patient's symptoms and absolute serum calcium level 8. Interventions aim to lower serum calcium concentration by inhibiting bone resorption and increasing urinary calcium excretion. Aggressive hydration is also an essential part of the treatment regimen 7, 8.
Mechanistic Categories
Hypercalcemia of malignancy can be classified into four broad mechanistic categories:
- Local osteolysis secondary to metastatic cancer or multiple myeloma
- Excess parathyroid-related hormone
- Excess 1,25-dihydroxyvitamin D production
- Ectopic parathyroid hormone production 7