Sunitinib Induced Hypocalcemia and its Potential Role in the Treatment of Refractory Hypercalcemia

Background: Sunitinib, an oral multi-targeted tyrosine kinase inhibitor has been approved for the treatment of advanced pancreatic neuroendocrine neoplasms (pNENs). Aim: To describe a series of 12 patients with pNENs on sunitinib who developed hypocalcemia. Patients and Methods: Three patients developed hypocalcemia, grade 4, 1 and 2 respectively. Results: A 58-year-old man with a stage IV, grade 2, initially non-functioning pNEN (NFpNEN), developed disease progression with concomitant hypersecretion of parathyroid hormone related-peptide (PTHrP) and uncontrolled hypercalcemia. After one month of sunitinib treatment, grade 4 hypocalcemia (<6mg/dl) developed. Following treatment reinstitution at a lower dose, hypercalcemia became easily controlled. Another two patients with NFpNEN treated with sunitinib developed a grade 1 (8.2mg/dl) non-symptomatic and a grade 2 (7.2mg/dl) symptomatic hypocalcemia, both nine months after sunitinib was initiated. Conclusions: Sunitinib-induced hypocalcemia may be a common side-effect that could be of therapeutic significance in patients with pNEN and refractory PTHrP-related hypercalcemia.