(1) Patients who require dialysis for
chronic renal failure develop phosphocalcium metabolic disorders that often lead to
secondary hyperparathyroidism. Standard treatment consists of a
phosphate chelator and
vitamin D, along with the use of an appropriate
calcium concentration in the dialysis bath, but is difficult to manage. (2)
Parathyroid cancer is a rare
malignancy frequently associated with hypercalcaemia. (3)
Cinacalcet is a calcimimetic agent that reduces the
parathormone level. Clinical evaluation includes more than a dozen dose-finding studies and clinical trials. The optimal dose seems to range from 30 to 180 mg/day and varies widely from one patient to another. (4) 3 double-blind placebo-controlled trials, lasting for a maximum of one year and involving a total of 1136 dialysis patients with
chronic renal failure, showed no improvement in quality of life with
cinacalcet. The target
parathormone level was reached by 40% of patients on
cinacalcet versus 5% of patients on placebo, while the effects of
cinacalcet on
calcium levels (-7%) and
phosphate levels (-8%) were modest. No impact on bone complications is mentioned in available reports. (5) The assessment of treatment of
parathyroid cancer is limited to one ongoing non comparative trial involving 21 patients. (6) During clinical trials, 11% of dialysis patients had low
parathormone levels, creating a risk of adynamic
bone disease and fractures, but available data are sparse. (7) Two-thirds of patients receiving
cinacalcet have episodes of hypocalcaemia, which may in part account for reports of
seizures (1.4% of patients),
nausea (31%) and
vomiting (27%). Many adverse effects seen in animal studies have not been adequately investigated in the clinical setting, such as an increase in the QT interval, thyroid disorders, and sexual dysfunction.
Cinacalcet is a powerful
CYP 2D6 inhibitor and is also metabolised by
isoenzymes CYP 3A4 and
CYP 1A2, creating an increased risk of drug interactions. (8) In practice, treatment with
cinacalcet seems difficult to manage and to provide only limited benefits. Available assessment reports leave many questions unanswered, and this is a further reason not to use this product outside of clinical trials, either after failure of
phosphate chelator and
vitamin D therapy (especially as an alternative to surgery) or in
parathyroid cancer.