Oral cinacalcet responsiveness in non-parathyroid hormone mediated hypercalcemia of malignancy
Oral cinacalcet responsiveness in non-parathyroid hormone mediated hypercalcemia of malignancy
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DOI：
10.1016/j.mehy.2020.110149
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发表时间：
2020-10-01
影响因子：
4.7
通讯作者：
Onitilo, Adedayo A.
中科院分区：
文献类型：
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作者：
Sheehan, Michael T.;Wermers, Robert A.;Onitilo, Adedayo A.
恶性高钙血症发生在大约20-30%的晚期癌症患者中，是一种不祥的征兆。这种情况分为三类：i）恶性体液性高钙血症（80%的病例），由全身性甲状旁腺相关蛋白介导; ii）溶骨性转移（20%的病例），由肿瘤细胞和/或肿瘤周围巨噬细胞局部释放的炎性细胞因子介导;和iii）异位产生1，25-二羟维生素D（< 1%的病例），导致肠钙吸收过度和骨吸收增加。恶性肿瘤的体液性高钙血症见于多种实体瘤，而溶骨性转移最常见于乳腺癌和多发性骨髓瘤。由1，25-二羟维生素D介导的恶性高钙血症主要见于淋巴瘤，在实体瘤中很少报道。恶性肿瘤和溶骨性转移瘤的体液性高钙血症的药理学管理主要涉及静脉注射双膦酸盐、皮下注射狄诺塞单抗和皮下注射降钙素抑制骨吸收。糖皮质激素治疗是治疗增加的1，25-二羟维生素D的主要方法。不幸的是，恶性肿瘤高钙血症的管理往往需要住院治疗的急性设置，抗吸收治疗的有效性损失是常见的。我们建议口服西那卡塞可能是一种有效的治疗恶性高钙血症与升高的1，25-二羟维生素D，我们目前的支持数据，从两个案件涉及实体瘤。此外，我们假设这种作用主要是通过西那卡塞与肠道中钙敏感受体的相互作用介导的，对骨骼和肾脏的影响较小。最后，1，25-二羟维生素D在恶性高钙血症中的作用在实体瘤中可能被低估。
Hypercalcemia of malignancy develops in approximately 20-30% of patients with advanced cancer and is an ominous sign. This condition is subdivided into three categories: i) humoral hypercalcemia of malignancy (80% of cases), mediated by systemic parathyroid hormone-related protein; ii) osteolytic metastases (20% of cases), mediated by inflammatory cytokines locally released by tumor cells and/or peri-tumor macrophages; and iii) ectopic production of 1,25-dihydroxyvitamin D (< 1% of cases), leading to intestinal hyperabsorption of calcium and increased osteoclastic bone resorption. Humoral hypercalcemia of malignancy is seen in a variety of solid tumors, while osteolytic metastases are most common in breast cancer and multiple myeloma. Hypercalcemia of malignancy mediated by 1,25-dihydroxyvitamin D is primarily seen in lymphomas, having only rarely been reported in solid tumors. Pharmacologic management of humoral hypercalcemia of malignancy and osteolytic metastases mainly involves inhibition of bone resorption with intravenous bisphosphonates, subcutaneous denosumab, and subcutaneous calcitonin. Glucocorticoid therapy is the mainstay for management of increased 1,25-dihydroxyvitamin D. Unfortunately, management of hypercalcemia of malignancy often requires inpatient admission in the acute setting, and loss of effectiveness of antiresorptive therapy is common. We propose oral cinacalcet may be an efficacious therapy for hypercalcemia of malignancy related to elevated 1,25-dihydroxyvitamin D, and we present supporting data from two cases involving solid tumors. Furthermore, we hypothesize that this effect is primarily mediated by cinacalcet's interaction with the calcium-sensing receptor in the intestine with lesser effects at bone and kidney. Lastly, the role of 1,25-dihydroxyvitamin D in hypercalcemia malignancy may be underappreciated in solid tumors.