Denosumab Therapy for Refractory Hypercalcemia Secondary to Squamous Cell Carcinoma of Skin in Epidermolysis Bullosa

Dinesh Giri, Renuka Ramakrishnan, James Hayden, Lynda Brook, Urmi Das, M. Zulf Mughal, Peter Selby, Poonam Dharmaraj, Senthil Senniappan


Hypercalcemia secondary to malignancy is rare in children and the majority is caused by tumor-produced parathyroid hormone-related protein (PTHrP). We report a case of hypercalcemia refractory to bisphosphonate and corticosteroid therapy, but responsive to denosumab. A 17-year-old boy with epidermolysis bullosa (EB) and advanced squamous cell carcinoma (SCC) of the left leg was referred with severe hypercalcemia (serum calcium, 4.2 mmol/L). The serum parathyroid hormone (PTH) was 0.7 pmol/L (1.1 - 6.9 pmol/L). The hypercalcemia was initially managed with hyperhydration, prednisolone and pamidronate. Following two infusions of pamidronate (1 mg/kg/dose), serum calcium fell to 2.87 mmol/L. However the hypercalcemia relapsed within a week (serum calcium, 3.61 mmol/L) needing aggressive management with intravenous fluids, prednisolone and two further doses of pamidronate. The serum calcium fell to 2.58 mmol/L over the first 4 days, but rose to 3.39 mmol/L 3 days later. As the hypercalcemia was refractory to bisphosphonate treatment, a trial dose of subcutaneous denosumab (60 mg) was administered following which the calcium fell to 2.86 mmol/L within 24 h and normocalcemia was sustained 4 days later. We report a case of refractory hypercalcemia secondary to malignant SCC, which responded well to denosumab therapy. To our knowledge, this is the first case of hypercalcemia of malignancy in an adolescent managed with denosumab.

World J Oncol. 2015;6(2):345-348


Denosumab; Hypercalcemia; Squamous cell carcinoma

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