What Is the Best Treatment of an Adult Patient with Hypercalcemia of Malignancy?

Glucocorticoids have been used to treat hypercalcemia since the 1950s. Prednisone, dexamethasone, and methylprednisolone all carry FDA indications for hypercalcemia, but data are lacking and contradictory. A small (n=28) randomized controlled trial (RCT) conducted in 1984 showed no additional efficacy of glucocorticoids with IV fluids when compared with IV fluids alone.¹⁵ Another small (n=30) RCT done in 1992 on women with metastatic breast cancer showed a significant improvement in patients treated with prednisolone, IV fluids, and furosemide when compared with IV fluids and furosemide.¹⁶ Other nonrandomized trials have shown response to be unpredictable at best.¹⁷ Despite this, glucocorticoids likely retain a limited role for treatment in specific cases, including hypercalcemia induced by lymphomas elevating levels of 1,25(OH)2 vitamin D (as this interacts with a steroid-regulated receptor), or multiple myelomas where they potentially impact disease progression.

Gallium nitrate, an anhydrous salt of a heavy metal, has been shown in several randomized trials to be an effective therapeutic agent in lowering calcium levels in hypercalcemic patients.^18,19 Furthermore, a double-blinded trial of 64 patients with hypercalcemia of malignancy showed gallium nitrate to be at least as effective as pamidronate for acute control of cancer-related hypercalcemia.²⁰ However, the need for continuous infusion over a five-day period has limited the application of this agent.

Hemodialysis with a calcium-lacking dialysate has been shown in small, nonrandomized studies to be a temporarily effective method of reducing serum calcium levels.^21,22 However, this treatment modality would best be reserved for patients with severe hypercalcemia, in whom aggressive intravascular volume repletion and bisphosphonates are not advisable (e.g. those with significant heart or kidney failure) and have an underlying etiology that is likely to be responsive to other treatment. Furthermore, consideration as to the appropriateness of such invasive temporizing procedures in patients with metastatic cancer should be undertaken.

Back to the Case

This patient had an ionized calcium level of 1.9 mmol/L (normal 1.1-1.4 mmol/L). He was started on aggressive IV hydration with normal saline and zoledronic acid. His home medications were reviewed, and it was confirmed that he was not taking such contraindicated medications as thiazides or calcium/vitamin D supplementation.

Further workup for the etiology of his hypercalcemia revealed an appropriately suppressed, intact PTH and normal 25 (OH) Vitamin D and 1,25 (OH)2 Vitamin D levels. His intact PTH-RP was elevated at 10pmol/L, and consistent with hypercalcemia of malignancy.

Oncology and palliative-care consults were requested to assist with coordination of the treatment of the patient’s underlying lung cancer; plans were made for systemic chemotherapy. His symptoms slowly improved, and 72 hours after admission, his serum calcium had normalized. He was discharged with a plan to initiate chemotherapy and continued follow-up with oncology.

Bottom Line

Acute management of hypercalcemia of malignancy focuses on lowering the serum calcium through a variety of pharmacologic agents. However, such long-term issues as treatment of the underlying malignancy and discussions about goals of care in this high-mortality patient population is paramount. TH

Dr. Hartley and Dr. Repaskey are clinical instructors in internal medicine at the University of Michigan Health System. Dr. Rohde is a clinical assistant professor of internal medicine at UMHS.

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