Background: Management of inoperable parathyroid carcinoma presents a challenge because until recently effective medical therapy was not available. Morbidity and mortality result primarily from severe hypercalcemia. We assessed the ability of the calcimimetic cinacalcet HCl to reduce serum calcium in patients with parathyroid carcinoma, as well as its effect on parathyroid hormone concentrations, bone turnover markers, safety, and health-related quality of life variables.

Methods: Twenty-nine patients with parathyroid carcinoma were enrolled in this open-label, single-arm study consisting of titration and maintenance phases. Cinacalcet doses were titrated (30 mg twice daily to 90 mg four times daily) for 16 weeks or until serum calcium was 10.0 mg/dL. The study endpoint was the proportion of patients with a 1 mg/dL reduction in serum calcium at the end of the titration phase (responders).

Results: Mean (±SE) serum calcium (14.1±0.4 mg/dL) and parathyroid hormone (697 ± 94 pg/mL) were markedly elevated at baseline. At the end of the titration period, serum calcium was reduced by 1 mg/dL in 62% of patients (mean decline to 12.4±0.5 mg/dL). In the 18 responders, serum calcium fell from 15.0±0.5 to 11.2±0.3 mg/dl (P<0.001). The greatest reductions in serum calcium were observed in patients with highest baseline calcium levels. Parathyroid hormone levels decreased, but not significantly to 635 ± 73 pg/mL (-4.6%). Adverse events included nausea, vomiting, headache, and fracture.

Conclusions: Cinacalcet effectively reduces hypercalcemia in approximately two-thirds of patients with inoperable parathyroid carcinoma and may represent an important new treatment option for these patients.