Hypercalcemia of malignancy treated with cinacalcet

Asonitis, Nikolaos; Kassi, Eva; Kokkinos, Michalis; Giovanopoulos, Ilias; Petychaki, Foteini; Gogas, Helen

doi:10.1530/edm-17-0118

Cited by 14 publications

(10 citation statements)

References 10 publications

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“…As shown, our patient did respond to cinacalcet treatment. We are aware of only 3 similar cases previously reported in the literature [2,7,8]. Our patient's response persisted even in the face of disease progression, marked by a further rise in PTHrP.…”

Section: Discussionsupporting

confidence: 62%

“…There are no clinical trials of cinacalcet in HCM beyond the setting of parathyroid carcinoma. In each of the 3 previously published cases involving a patient with HHM refractory to BP with or without denosumab therapy, calcium levels were successfully managed with cinacalcet, although the mechanism by which cinacalcet may have worked was not fully discussed even theoretically [2,7,8]. In one case, the authors considered the improvement to be related to a cinacalcet-induced decrease in PTHrP itself, although that effect was more likely the result of ongoing chemotherapy [7].…”

Section: Oral Cinacalcetmentioning

confidence: 99%

“…In another, no mechanism was postulated [2]. In the third case, the authors suggested the possible interaction of cinacalcet with CaSR in bone and/or the kidneys as the mechanism, but they did not elaborate this more fully [8].…”

Section: Oral Cinacalcetmentioning

confidence: 99%

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Cinacalcet for the Treatment of Humoral Hypercalcemia of Malignancy: An Introductory Case Report with a Pathophysiologic and Therapeutic Review

Sheehan

Tanimu

et al. 2020

Case Rep Oncol

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Hypercalcemia is an ominous development in the course of malignancy associated with a mean survival of only several months. A majority of cases of hypercalcemia are related to humoral hypercalcemia of malignancy (HHM), where hypercalcemia is caused by increased levels of circulating parathyroid hormone-related protein (PTHrP). Mainstay treatments in the management of HHM are intravenous fluids, intravenous bisphosphonates, and subcutaneous denosumab, although hypercalcemia oftentimes recurs despite these efforts. We present a case of advanced non-small cell lung cancer with PTHrP-mediated hypercalcemia that proved resistant to standard therapy. A trial of oral cinacalcet was initiated and improved calcium levels for 2 months despite a progressive rise in PTHrP and prior to subsequent disease progression. Based on the current body of literature, we propose that this calcium-lowering effect of cinacalcet occurs due to a potential effect on renal calcium excretion.Abnormal Renal Calcium Handling Related to PTHrP HHM is the most common etiology of malignancy-related calcium dysregulation and accounts for ∼80% of HCM cases [1,2]. Most often, it occurs in solid tumors of the lung, head and neck, esophagus, skin, cervix, breast, kidneys, prostate, and bladder [1, 2]. These patients do not have bone metastases, and hypercalcemia occurs via PTHrP actions in both the bones and kidneys [1,2]. PTHrP has some homology with PTH, especially at the amino-terminus, and binds to the PTH-1 receptor, resulting in increased skeletal efflux of calcium and increased renal reabsorption of calcium by the mechanisms described earlier for PTH ( Fig. 1A, 2, 3A).The relative contribution of each of these processes to hypercalcemia is unknown, but it is estimated that up to 1,000 mg of calcium per day may be mobilized from the skeleton in HHM [2]. Additionally, there is an underappreciated renal contribution to HHM, as evidenced by studies in both animals and humans. In rats with HHM refractory to bone resorption inhibitors, anti-PTHrP antibodies resulted in a marked decrease in blood calcium coinciding with a 2-to 3-fold increase in fractional excretion of calcium [13]. Furthermore, in normal human subjects infused with PTHrP, the fractional excretion of calcium (control group: ∼2%) increased by ∼50% less (∼2.5-3.7%) than the increase induced by a similar rise in serum

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Section: Discussionsupporting

confidence: 62%

Section: Oral Cinacalcetmentioning

confidence: 99%

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Cinacalcet for the Treatment of Humoral Hypercalcemia of Malignancy: An Introductory Case Report with a Pathophysiologic and Therapeutic Review

Sheehan

Tanimu

et al. 2020

Case Rep Oncol

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“…The successful use of calcimimetics in PTHrPmediated hypercalcemia has been described in case reports, through a mechanism yet to be fully elucidated (15)(16)(17). In murine parathyroidectomized models, cinacalcet decreased calcium in a dose-dependent manner without altering PTHrP levels; increased calcitonin secretion appears to play a role (18).…”

Section: Discussionmentioning

confidence: 99%

Hypercalcemia of Malignancy in a Case of Peripheral Nerve Sheath Tumor: Elucidating the Roles of Simultaneous Mechanisms

Ganesh

Baim

2020

AACE Clinical Case Reports

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Objective: Hypercalcemia of malignancy (HCM) is caused by 1 of 5 known mechanisms including systemic release of ectopic parathyroid hormone (PTH)-related protein (PTHrP), calcitriol, PTH, cytokines, or destruction of bone by osteolytic metastases. We report the first case of 2 simultaneous mechanisms for HCM in a patient with a peripheral nerve sheath tumor (PNST) Methods: PubMed and Google Scholar searches were performed using “hypercalcemia of malignancy” as the search term. Results: A 26-year-old woman with neurofibromatosis presented with worsening left hip pain. Magnetic resonance imaging showed a large left paraspinal mass, subtotal resection of which confirmed PNST. Despite chemo-radiation therapy, the tumor progressed over 16 months, requiring tumor debulking and L3–4 lumbar laminectomy. The patient developed progressive bilateral lower extremity weakness due to direct tumor invasion of the lumbosacral vertebrae with concurrent hypercalcemia. Ionized calcium was 1.47 mmol/dL (reference range is 0.95 to 1.32 mmol/dL), PTH was <4.0 pg/mL (reference range is 8 to 85 pg/mL), 25-hydroxyvitamin D was 14 ng/mL, calcitriol was <8.0 pg/mL (reference range is 18 to 78 pg/mL), PTHrP was 40 pg/mL(reference range is 14 to 27 pg/mL), urinary calcium was <2.0 mg/24 hours, serum C-telopeptide was 1,008 pg/mL (reference range is 64 to 640 pg/mL), and bone-specific alkaline phosphatase was 15.7 μg/L (reference range is 4.7 to 17.8 μg/L). Her serum magnesium, phosphorus, and creatinine levels were normal. Intravenous zoledronic acid and hydration resulted in a normal ionized calcium. Additional imaging revealed extensive tumor invasion of L3-S1 vertebrae. Due to her poor response to all cancer therapies, the patient was discharged to home hospice services. Conclusion: HCM due to PTHrP and osteolytic metastases has not been independently reported to our knowledge in association with malignant PNST as in our patient. The therapeutic importance of characterizing the mechanism of HCM is further discussed in detail.

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“…Cinacalcet has recently been approved by FDA for the treatment of hypercalcemia in patients with severe primary hyperparathyroidism (PHPT) when parathyroidectomy is contraindicated, those with parathyroid carcinoma, and finally for the treatment of patients with end stage renal disease on maintenance dialysis therapy and secondary hyperparathyroidism [26,89]. To date two cases have been reported for hypercalcemia of malignancy treated with cinacalcet and it could be used as an additional effective therapeutic option, though not approved by FDA [26,88,90].…”

Section: Duration Of Actionmentioning

confidence: 99%

Diagnosis, Pathophysiology and Management of Hypercalcemia in Malignancy: A Review of the Literature

et al. 2019

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Hypercalcemia of malignancy is the most common life-threatening metabolic disorder in patients with advanced stage cancers and is a sign of poor prognosis. It usually presents with markedly elevated calcium level and is severely symptomatic. It is associated with hematological malignancies, such as multiple myeloma, non-Hodgkin lymphoma, leukemias and solid cancers, particularly renal and breast carcinomas as well as squamous cell carcinomas of any organ. Several mechanisms have been implicated in the development of hypercalcemia of malignancy amongst them the osteolytic related hypercalcemia, parathyroid hormone-related peptide (PTHrP) mediated hypercalcemia, extrarenal 1,25 dixydroxyvitamin D (calcitriol) mediated hypercalcemia and parathyroid hormone (PTH) related hypercalcemia either ectopic in origin or in patients with parathyroid carcinoma. Clinical history and and physical examination could point towards the correct diagnosis confirmed by the above-mentioned biochemical mediators of hypercalcemia. Early diagnosis and treatment lowering calcium levels in the blood can improve symptoms and the quality of life of these patients and avoid delays for further antitumor therapy.

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Hypercalcemia of malignancy treated with cinacalcet

Cited by 14 publications

References 10 publications

Cinacalcet for the Treatment of Humoral Hypercalcemia of Malignancy: An Introductory Case Report with a Pathophysiologic and Therapeutic Review

Cinacalcet for the Treatment of Humoral Hypercalcemia of Malignancy: An Introductory Case Report with a Pathophysiologic and Therapeutic Review

Hypercalcemia of Malignancy in a Case of Peripheral Nerve Sheath Tumor: Elucidating the Roles of Simultaneous Mechanisms

Diagnosis, Pathophysiology and Management of Hypercalcemia in Malignancy: A Review of the Literature

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