Shizuoka General Hospital, -27-1, Kita-ando, Aoi-ku, 420-8527, Shizuoka, Japan.
Shizuoka Cancer Center, Nagaizumi, Japan.
BMC Cancer. 2024 Feb 15;24(1):218. doi: 10.1186/s12885-024-11942-2.
Bone metastases are frequently observed in advanced cancer, and bone modifying agents are used to prevent or treat skeletal-related events. Zoledronic acid is contraindicated in patients with severe renal impairment (Ccr < 30 mL/min), but it is not completely known whether denosumab can be used in them. We aimed to determine the association between renal function and hypocalcemia development during denosumab treatment.
We included patients with solid cancer and bone metastases who started denosumab treatment between April 2017 and March 2019. They were classified into four groups based on creatinine clearance (Ccr; mL/min): normal (Ccr ≥ 80), mild (50 ≤ Ccr ˂80), moderate (30 ≤ Ccr ˂50), and severe (Ccr ˂30). Hypocalcemia was evaluated using the Common Terminology Criteria for Adverse Events (v5.0) based on the albumin-adjusted serum calcium levels; its incidence (stratified by renal function) and risk factors were investigated using a Chi-square test and logistic regression analysis.
Of 524 patients (age: 69 ± 11 years; 303 men), 153 had a normal renal function and 222, 117, and 32 had mild, moderate, and severe renal dysfunction. The albumin-adjusted serum calcium level was higher than the measured (total) calcium level in most patients. The incidence of grade ≥ 1 hypocalcemia was 32.0% in the normal group and 37.4%, 29.9%, and 62.5% in the mild, moderate, and severe renal dysfunction groups, respectively. It was, therefore, higher in the severe renal dysfunction groups than in the normal group (P = 0.002). The incidence of grade ≥ 3 hypocalcemia did not differ significantly among the groups. Pre-treatment low serum calcium levels and severe renal dysfunction were risk factors for hypocalcemia.
Evaluating denosumab-induced hypocalcemia required albumin adjustment, and its incidence was high among patients with severe renal dysfunction. Reduced serum calcium levels and severely impaired renal function were associated with an elevated hypocalcemia risk.
在晚期癌症中经常观察到骨转移，使用骨修饰剂来预防或治疗与骨骼相关的事件。对于严重肾功能不全（Ccr<30 mL/min）的患者，唑来膦酸是禁忌的，但不完全清楚地舒单抗是否可以在这些患者中使用。我们旨在确定肾功能与地舒单抗治疗期间低钙血症发展之间的关系。
我们纳入了 2017 年 4 月至 2019 年 3 月期间开始接受地舒单抗治疗的实体瘤合并骨转移患者。根据肌酐清除率（Ccr；mL/min）将患者分为四组：正常（Ccr≥80）、轻度（50≤Ccr<80）、中度（30≤Ccr<50）和重度（Ccr<30）。根据白蛋白校正的血清钙水平，使用不良事件通用术语标准（v5.0）评估低钙血症；使用卡方检验和逻辑回归分析调查其发生率（按肾功能分层）和危险因素。
在 524 名患者（年龄：69±11 岁；303 名男性）中，153 名患者肾功能正常，222 名、117 名和 32 名患者肾功能轻度、中度和重度异常。在大多数患者中，白蛋白校正的血清钙水平高于测量的（总）钙水平。正常组中，1 级及以上低钙血症的发生率为 32.0%，轻度、中度和重度肾功能不全组分别为 37.4%、29.9%和 62.5%。因此，重度肾功能不全组的发生率高于正常组（P=0.002）。各组之间 3 级及以上低钙血症的发生率无显著差异。治疗前低血清钙水平和严重肾功能不全是低钙血症的危险因素。
评估地舒单抗引起的低钙血症需要进行白蛋白校正，在严重肾功能不全患者中发生率较高。血清钙水平降低和严重肾功能不全与低钙血症风险增加相关。
