Endocrine Abstracts

Background: Although sunitinib, an oral multitargeted tyrosine kinase inhibitor of RET, VEGFR, PDGFR, c-KIT used for cancer treatment, has a reported prevalence of hypocalcemia of 35%, this has not been documented in pancreatic neuroendocrine tumour (pNETs).

Methods: We present three, out of 12, patients with pNETs treated with sunitinib who developed grade 1, 2 and 4 hypocalcemia according Common Terminology Criteria for Adverse Events v3.0 (CTCAE) criteria.

Results: A 51-year-old man with a stage IV, grade 1 pNET developed disease progression besides treatment with somatostatin analogues (SA). Nine months after sunitinib was initiated he developed symptomatic grade 2 hypocalcemia (7.2 mg/dl) necessitating treatment discontinuation and calcium supplementation. A 53-year-old man with MEN-1 with stage IV, grade 1 pNET was treated with Whipple’s operation and SA. Following disease progression he was initially treated with everolimus that was discontinued due to severe anemia and treatment with sunitinib was initiated. Nine months later he developed grade 1 hypocalcemia (8.2 mg/dl) that improved with dose reduction. A 58-year-old man with a long history of a stage IV, grade 2 pNET had received various treatments including chemotherapy, interferon, peptide receptor radionuclide therapy (PRRT) and SA. During the course of his disease he developed severe and refractory hypercalcemia due to PTHrP secretion by the tumour. Following disease progression he was treated with sunitinib and 1-month later he developed grade 4 hypocalcemia (<6 mg/dl). Following reinstitution of treatment his previous refractory hypercalcemia became easily controlled.

Conclusion: Hypocalcemia induced by sunitinib during treatment of pNET can occur relatively common with wide severity that may necessitate treatment modification. However, this potential side-effect may be of therapeutic significance in patients with refractory hypercalcemia.