Use of cinacalcet and sunitinib to treat hypercalcaemia due to a pancreatic neuroendocrine tumor

Abstract

Neuroendocrine tumors (NETs) can secrete hormones, including ectopic secretions, but they have been rarely associated with malignant hypercalcemia. A 52-year-old man with a history of diabetes mellitus was diagnosed with a pancreatic tumor. A pancreatic biopsy confirmed a well-differentiated pancreatic NET (pNET). The patient subsequently developed liver metastasis and hypercalcemia with high 1,25 OH vitamin D and suppressed parathyroid hormone (PTH) levels. Hypercalcemia was refractory to chemotherapy, intravenous saline fluids, diuretics, calcitonin and zoledronate. Cinacalcet administration (120 mg/day) resulted in a significant calcium reduction. Hypocalcemia was observed when sunitinib was added three months later and cinacalcet was stopped. Subsequently, the calcium and PTH levels normalized. After six months, we observed 20% shrinkage of the pancreatic tumor and necrosis of a liver metastasis. Cinacalcet is an allosteric activator of the calcium receptor agonist, and it is used for severe hypercalcemia in patients with primary (benign and malignant) hyperparathyroidism. In this patient, cinacalcet demonstrated a calcium lowering effect, normalized hypophosphatemia, and improved the clinical condition of the patient. The mechanism through which cinacalcet improved PTH-rp mediated hypercalcemia is still unclear, but studies have suggested that a potential mechanism is the activation of calcitonin secretion. Sunitinib is an oral multi-targeted tyrosine kinase inhibitor used to treat advanced pNETs. The hypocalcemic effects of sunitinib have not been previously described in a patient with pNET. Here, we report for the first time the successful combination of cinacalcet and sunitinib in the treatment of a pNET patient presenting with malignant hypercalcemia.