Sunitinib-induced hyperparathyroidism: a possible mechanism to altered bone homeostasis.

BACKGROUND: Sunitinib malate is an orally bioavailable tyrosine kinase inhibitor that is active against many tyrosine kinase receptors involving crucial pathways in both healthy tissues and malignant tissues. Because its use in clinical practice is quite recent, many of its possible side effects remain unknown. In this report, the authors describe the incidence of new-onset hyperparathyroidism in a cohort of patients with metastatic renal cell carcinoma who received treatment with sunitinib. METHODS: Twenty-six patients who received first-line sunitinib for metastatic renal cell carcinoma were enrolled in this study for a mineral and parathyroid function assessment. Plasma levels of intact parathyroid hormone; serum levels of calcium, phosphorus, 25-hydroxyvitamin D(3), and 1,25-dihydrovitamin D(3); and urinary 24-hour calcium and phosphorus excretion all were measured in each patient. Biochemical evaluations were performed before the beginning of treatment and at the end of each sunitinib treatment period. RESULTS: Eighteen of 26 patients (69.2%) developed hyperparathyroidism with normal serum calcium levels, and 6 of them developed hypophosphatemia. Patients presented with a mean elevation of parathyroid hormone after 2.2 cycles of sunitinib. The levels of 25-OH vitamin D(3) were stable over the course of treatment, whereas 1,25-OH vitamin D(3) levels were increased in 5 hyperparathyroid patients. Those who presenting with elevated parathyroid hormone levels had low or undetectable urinary calcium levels. Parathyroid hormone elevation usually persisted but did not progress during long-term therapy with sunitinib. Permanent treatment interruption resulted in a resolution of hyperparathyroidism. CONCLUSIONS: Hyperparathyroidism developed in an high percentage of patients on sunitinib. Therefore, the authors concluded that sunitinib may affect parathyroid function and bone mineral homeostasis, possibly resulting in abnormal bone remodeling.