380 Background: Sunitinib malate is a tyrosine kinase inhibitor, active against tyrosine kinase receptors involved in tumour growth and angiogenesis, and is a potent substrate of p-glycoprotein. This study was conducted to assess whether sunitinib could affect phospho-calcium metabolism. This because both sunitinib and parathyroid hormone have been suggested to be substrates of p-glycoprotein. Here we report the incidence of newly onset hyperparathyroidism in a cohort of patients affected by metastatic renal cell carcinoma (mRCC), treated with sunitinib. Methods: Parathyroid and calcium metabolism function tests were prospectively evaluated in patients receiving a daily 50 mg sunitinib for mRCC according to classic 6-week schedule. Between July 2008 and July 2010, 25 patients received a sunitinib treatment at our institution and resulted eligible for evaluation. Median patients age was 64.3 years old (range 48-79). Parathyroid hormone (PTH), serum and urinary phosphate and calcium, were measured at the beginning of treatment and at the end of each sunitinib ON period. Results: During sunitinib therapy, 17 patients (68%) developed elevated serum parathyroid hormone, with low-to-normal serum calcium and phosphate. On average patients presented an elevation of PTH after 3 sunitinib cycles (range 1-5). Those presenting elevated PTH showed low or undetectable urinary calcium levels. Conclusions: Hyperparathyroidism develops in a high percentage of patients undergoing sunitinib. A similar observation was reported among patients on imatinib, due to an inhibition of PDGF receptor both on osteoclasts and osteoblasts. In these patients, a temporary decrease of serum ionized calcium was supposed as the pathogenetic mechanism of hyperparathyroidism. As sunitinib inhibits PDGF receptors', similar events could be hypothesized. This observation suggests that abnormalities in bone metabolism are a common feature of tyrosine kinases inhibitors targeting PDGF receptors. Routine monitoring of bone metabolism during sunitinib therapy is therefore recommended. No significant financial relationships to disclose.
Hypercalcemia of Malignancy with Simultaneous Elevation in Serum Parathyroid Hormone—Related Peptide and 1,25-Dihydroxyvitamin D in A Patient with Metastatic Renal Cell Carcinoma