From the Guidelines
Cinacalcet should not be used as a first-line treatment for hypercalcemia of malignancy, but it may be considered in cases refractory to standard therapies such as bisphosphonates or denosumab. The primary approach to managing hypercalcemia of malignancy involves aggressive hydration and the use of bisphosphonates like zoledronic acid or denosumab, as these have been shown to effectively control hypercalcemia and are recommended by clinical guidelines 1. Bisphosphonates, such as i.v. pamidronate and zoledronic acid, are preferred for their ability to control hypercalcemia and potentially reverse associated symptoms like delirium 1. Denosumab, a RANKL inhibitor, is also effective in lowering serum calcium in patients with hypercalcemia refractory to bisphosphonate treatment, although it requires careful monitoring of calcium levels due to the risk of hypocalcemia 1. Given the availability and efficacy of these treatments, cinacalcet's role is more limited to specific cases where these primary options are not effective or suitable. In such scenarios, cinacalcet could be considered due to its mechanism of action, which involves increasing the sensitivity of calcium-sensing receptors on the parathyroid gland, thereby reducing parathyroid hormone secretion and subsequently lowering serum calcium levels. However, the decision to use cinacalcet should be based on a thorough evaluation of the patient's condition, the underlying cause of hypercalcemia, and the potential benefits and risks associated with its use. Regular monitoring of serum calcium levels and patient tolerance is crucial when initiating cinacalcet therapy, which typically starts at a lower dose and can be titrated based on response and side effects. It's also important to note that while cinacalcet may offer a therapeutic option for managing hypercalcemia of malignancy in specific cases, the current guidelines and evidence base primarily support the use of bisphosphonates and denosumab as first-line treatments 1.
From the FDA Drug Label
1.2 Parathyroid Carcinoma Cinacalcet tablets are indicated for the treatment of hypercalcemia in adult patients with Parathyroid Carcinoma 1.3 Primary Hyperparathyroidism Cinacalcet tablets are indicated for the treatment of severe hypercalcemia in adult patients with primary HPT who are unable to undergo parathyroidectomy
The primary indications for cincalcet are secondary hyperparathyroidism in patients with chronic kidney disease on dialysis, parathyroid carcinoma, and primary hyperparathyroidism.
- Hypercalcemia of malignancy is not explicitly listed as an indication for cincalcet. However, cincalcet can be used to treat hypercalcemia in certain conditions, such as parathyroid carcinoma. Since hypercalcemia of malignancy is a different condition, the FDA drug label does not directly answer the question of whether cincalcet can be used to treat it 2.
From the Research
Use of Cinacalcet in Hypercalcemia of Malignancy
- Cinacalcet can be used to treat hypercalcemia of malignancy, as evidenced by several case reports and studies 3, 4, 5, 6.
- The medication has been shown to be effective in reducing calcium levels in patients with humoral hypercalcemia of malignancy (HHM) and those with hypercalcemia mediated by elevated 1,25-dihydroxyvitamin D 3, 4.
- Cinacalcet's mechanism of action in this setting is thought to involve its interaction with the calcium-sensing receptor in the intestine, as well as potential effects on renal calcium excretion 3, 4.
Efficacy and Safety
- Studies have reported that cinacalcet is well-tolerated and can maintain serum calcium levels in the normal range, allowing for the use of targeted cancer treatments 5, 6.
- The use of cinacalcet has been associated with improved quality of life and reduced morbidity in patients with malignancy-associated hypercalcemia 5.
- However, the exact mechanism of action of cinacalcet in reducing calcium levels in this setting is not fully understood and requires further study 5.
Comparison with Other Treatments
- Cinacalcet has been used in combination with other treatments, such as denosumab and bisphosphonates, to manage hypercalcemia of malignancy 6, 7.
- Denosumab has been shown to be effective in controlling refractory hypercalcemia associated with parathyroid carcinoma, and its use has been endorsed in the management of hypercalcemia in patients with parathyroid carcinoma and perhaps other conditions with PTH-induced hypercalcemia 7.