Refractory hypercalcemia and ectopic calcitonin secretion in a malignant pancreatic neuroendocrine tumor: hypocalcemic effects on cinacalcet

Introduction: Paraneoplastic hypercalcemia is a sign of poor prognosis, as it is particularly resistant to the usual hypocalcemic treatments.

Observation: In 2009, a well differentiated pancreatic neuroendocrine tumor (Ki-67= 2%) is diagnosed in a 52-year-old diabetic man. The tumor is revealed with a splenic and hepatic carcinomatosis. Plasmatic calcium was: 3.54 mmol/L (2.15 - 2.6). Biology showed hypophosphatemia, PTH < 4 ng/ml, high 1-25 OH VitD, calcitonin: 1016 ng/ml (< 12 ng/ml). He had hypercalciuria and hypophosphaturia. He received for two years several cycles of Streptozotocin-ADRIAMYCIN and FOLFOX, with partial control of the tumor mass and calcium levels. In 2012, calcitonin levels are 29 ng/ml whereas calcemia is 3.17 mmol/L. Hypercalcemia is refractory to hyperhydration, diuretics, corticosteroids, and bisphosphonates therapy. Cinacalcet (Mimpara) is prescribed up to 120 mg/day (PO). Calcemia decreases gradually from 3 to 2.87 and then 2.76 mmol/L. PTH and calcitonin-the tumor mass remain unchanged. After two months of Cinacalcet treatment, Sunitinib (Sutent) 37.5 mg per day was added. During the third month, calcium levels dropped to 2.09 mmol/L and PTH raised to 78 pg/ml, requiring discontinuation of Mimpara. Calcitonin normalized, with a further improvement over pancreatic and metastatic lesions.

Conclusion: Cinacalcet is a Calcium Sensing Receptor oral agonist. Cinacalcet hypocalcemic effects have not been previously documented in pancreatic paraneoplastic hypercalcemia. In our patient, Cinacalcet has significantly improved cancer prognosis: this drug could be a new alternative in paraneoplastic hypercalcemia.