Cinacalcet attenuates hypercalcemia observed in mice bearing either Rice H-500 Leydig cell or C26-DCT colon tumors

Colloton, Matthew; Shatzen, Edward; Wiemann, B; Starnes, Charlie; Scully, Sheila; Henley, Charles M.; Martin, David P.

doi:10.1016/j.ejphar.2013.04.013

Cited by 19 publications

(21 citation statements)

References 42 publications

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“…In young animals, activation of CaSR in osteoclasts has been shown to inhibit bone resorption, resulting in increased bone anabolism (10). However, it should be noted that even in the absence of CaSR, cinacalcet found to attenuate PTHrP-mediated increase in serum calcium, in mice bearing Rice H-500 Leydig cell or C26-DCT colon tumors; interestingly, this effect was accompanied by increased plasma calcitonin (11). …”

Section: Discussionmentioning

confidence: 99%

Hypercalcemia of malignancy treated with cinacalcet

Asonitis

Kassi

Kokkinos

et al. 2017

Endocrinology, Diabetes &Amp; Metabolism Case Reports

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Hypercalcemia of malignancy is the most common cause of hypercalcemia in hospitalized patients. It is associated with a poor prognosis, since it reflects an advanced cancer stage. Among all cancer in females, breast cancer is the most common malignancy, and it has the highest prevalence of hypercalcemia. Approximately 70% of patients with breast cancer have bone metastases and 10% of them will have hypercalcemia as a complication at some point in the disease. Herein, we report a 69-year-old female patient with metastatic breast cancer, who developed severe hypercalcemia in the course of her disease and was diagnosed with humoral hypercalcemia of malignancy (HHM). Intense hydration along with corticoisteroids and antiresorptive medication (calcitonin, bisphosphonates and denosumab) were administered to the patient. Despite the above treatment, serum calcium levels remain elevated and calcimimetic cinacalcet was added. Upon discontinuation of cinacalcet, calcium levels were raised and returned back to the normal levels following re-initiation of the calcimimetic. Her calcium level restored to normal, and she was discharged with the following medical treatment: denosumab monthly, and cinacalcet at a titrated dose of 90 mg per day. The patient is followed as an outpatient and 11 months later, her calcium level remained within the normal range.Learning points:Hypercalcemia of malignancy is the most common cause of hypercalcemia in hospitalized patients.Breast cancer has the highest prevalence of hypercalcemia.The cornerstone of therapy remains the intense hydration and intravenous bisphosphonates (preferably zoledronic acid).In case of persistent hypercalcemia of malignancy, the administration of calcimimetic cinacalcet could be an additional effective therapeutic option.

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Section: Discussionmentioning

confidence: 99%

Hypercalcemia of malignancy treated with cinacalcet

Asonitis

Kassi

Kokkinos

et al. 2017

Endocrinology, Diabetes &Amp; Metabolism Case Reports

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“…Also, in both studies, cinacalcet reduced iPTH, although it persisted above normal range in a high proportion of patients. It is postulated in experimental studies that cinacalcet increases calcitonin levels and thus, decreases blood calcium levels 21 ; this could be explained by the activation of sensitive calcium receptors present in the C cells of the thyroid gland. This theory could explain why, in many studies involving cinacalcet treatment of hypercalcemia in secondary hyperparathyroidism, serum calcium levels significantly decrease without a parallel decrease in PTH.…”

Section: Discussionmentioning

confidence: 99%

A Randomized Study Comparing Parathyroidectomy with Cinacalcet for Treating Hypercalcemia in Kidney Allograft Recipients with Hyperparathyroidism

Cruzado

Moreno²,

Torregrosa

et al. 2015

JASN

133

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Tertiary hyperparathyroidism is a common cause of hypercalcemia after kidney transplant. We designed this 12-month, prospective, multicenter, open-label, randomized study to evaluate whether subtotal parathyroidectomy is more effective than cinacalcet for controlling hypercalcemia caused by persistent hyperparathyroidism after kidney transplant. Kidney allograft recipients with hypercalcemia and elevated intact parathyroid hormone (iPTH) concentration were eligible if they had received a transplant $6 months before the study and had an eGFR.30 ml/min per 1.73 m 2 . The primary end point was the proportion of patients with normocalcemia at 12 months. Secondary end points were serum iPTH concentration, serum phosphate concentration, bone mineral density, vascular calcification, renal function, patient and graft survival, and economic cost. In total, 30 patients were randomized to receive cinacalcet (n=15) or subtotal parathyroidectomy (n=15). At 12 months, ten of 15 patients in the cinacalcet group and 15 of 15 patients in the parathyroidectomy group (P=0.04) achieved normocalcemia. Normalization of serum phosphate concentration occurred in almost all patients. Subtotal parathyroidectomy induced greater reduction of iPTH and associated with a significant increase in femoral neck bone mineral density; vascular calcification remained unchanged in both groups. The most frequent adverse events were digestive intolerance in the cinacalcet group and hypocalcemia in the parathyroidectomy group. Surgery would be more cost effective than cinacalcet if cinacalcet duration reached 14 months. All patients were alive with a functioning graft at the end of follow-up. In conclusion, subtotal parathyroidectomy was superior to cinacalcet in controlling hypercalcemia in these patients with kidney transplants and persistent hyperparathyroidism.

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“…In murine models of Leydig cell and colon tumors, cinacalcet attenuated hypercalcemia without affecting the synthesis of PTR-rp mRNA by the tumor. This effect occurred in a dose-dependent manner independently from the PTH-rp administration in parathyroidectomized animals (10). Furthermore, these studies suggest that cinacalcet mediates the reduction in calcium levels, at least partially, by stimulating the release of calcitonin by C-cells.…”

Section: Case Reportmentioning

confidence: 67%

“…Furthermore, these studies suggest that cinacalcet mediates the reduction in calcium levels, at least partially, by stimulating the release of calcitonin by C-cells. Another possible mechanism yet to be investigated could be the calcium lowering effect of cinacalcet through enhanced renal excretion of calcium (10).…”

Section: Case Reportmentioning

confidence: 99%

Use of cinacalcet and sunitinib to treat hypercalcaemia due to a pancreatic neuroendocrine tumor

Valdes-Socin

Almanza

Fernández-Ladreda

et al. 2017

Arch. Endocrinol. Metab.

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SUMMARYNeuroendocrine tumors (NETs) can secrete hormones, including ectopic secretions, but they have been rarely associated with malignant hypercalcemia. A 52-year-old man with a history of diabetes mellitus was diagnosed with a pancreatic tumor. A pancreatic biopsy confirmed a well-differentiated pancreatic NET (pNET). The patient subsequently developed liver metastasis and hypercalcemia with high 1,25 OH vitamin D and suppressed parathyroid hormone (PTH) levels. Hypercalcemia was refractory to chemotherapy, intravenous saline fluids, diuretics, calcitonin and zoledronate. Cinacalcet administration (120 mg/day) resulted in a significant calcium reduction. Hypocalcemia was observed when sunitinib was added three months later and cinacalcet was stopped. Subsequently, the calcium and PTH levels normalized. After six months, we observed 20% shrinkage of the pancreatic tumor and necrosis of a liver metastasis. Cinacalcet is an allosteric activator of the calcium receptor agonist, and it is used for severe hypercalcemia in patients with primary (benign and malignant) hyperparathyroidism. In this patient, cinacalcet demonstrated a calcium lowering effect, normalized hypophosphatemia, and improved the clinical condition of the patient. The mechanism through which cinacalcet improved PTH-rp mediated hypercalcemia is still unclear, but studies have suggested that a potential mechanism is the activation of calcitonin secretion. Sunitinib is an oral multi-targeted tyrosine kinase inhibitor used to treat advanced pNETs. The hypocalcemic effects of sunitinib have not been previously described in a patient with pNET. Here, we report for the first time the successful combination of cinacalcet and sunitinib in the treatment of a pNET patient presenting with malignant hypercalcemia. Arch Endocrinol Metab. 2017;61(5):506-9

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Cinacalcet attenuates hypercalcemia observed in mice bearing either Rice H-500 Leydig cell or C26-DCT colon tumors

Cited by 19 publications

References 42 publications

Hypercalcemia of malignancy treated with cinacalcet

Hypercalcemia of malignancy treated with cinacalcet

A Randomized Study Comparing Parathyroidectomy with Cinacalcet for Treating Hypercalcemia in Kidney Allograft Recipients with Hyperparathyroidism

Use of cinacalcet and sunitinib to treat hypercalcaemia due to a pancreatic neuroendocrine tumor

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