Mayo Clinic Evidence-Based Practice Center, Rochester, MN 55902, USA.
Mayo Clinic Libraries, Rochester, MN 55902, USA.
J Clin Endocrinol Metab. 2023 Feb 15;108(3):585-591. doi: 10.1210/clinem/dgac631.
Hypercalcemia is a common complication of malignancy that is associated with high morbidity and mortality.
To support development of the Endocrine Society Clinical Practice Guideline for the treatment of hypercalcemia of malignancy in adults.
We searched multiple databases for studies that addressed 8 clinical questions prioritized by a guideline panel from the Endocrine Society. Quantitative and qualitative synthesis was performed. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to assess certainty of evidence.
We reviewed 1949 citations, from which we included 21 studies. The risk of bias for most of the included studies was moderate. A higher proportion of patients who received bisphosphonate achieved resolution of hypercalcemia when compared to placebo. The incidence rate of adverse events was significantly higher in the bisphosphonate group. Comparing denosumab to bisphosphonate, there was no significant difference in the rate of patients who achieved resolution of hypercalcemia. Two-thirds of patients with refractory/recurrent hypercalcemia of malignancy who received denosumab following bisphosphonate therapy achieved resolution of hypercalcemia. Addition of calcitonin to bisphosphonate therapy did not affect the resolution of hypercalcemia, time to normocalcemia, or hypocalcemia. Only indirect evidence was available to address questions on the management of hypercalcemia in tumors associated with high calcitriol levels, refractory/recurrent hypercalcemia of malignancy following the use of bisphosphonates, and the use of calcimimetics in the treatment of hypercalcemia associated with parathyroid carcinoma. The certainty of the evidence to address all 8 clinical questions was low to very low.
The evidence summarized in this systematic review addresses the benefits and harms of treatments of hypercalcemia of malignancy. Additional information about patients' values and preferences, and other important decisional and contextual factors is needed to facilitate the development of clinical recommendations.
高钙血症是恶性肿瘤的常见并发症，与高发病率和死亡率相关。
为支持制定《内分泌学会成人恶性肿瘤高钙血症治疗临床实践指南》提供依据。
我们对内分泌学会指南小组确定的 8 个临床问题进行了检索，以搜索解决这些问题的研究。我们进行了定量和定性综合分析。采用推荐评估、制定与评价（GRADE）方法评估证据确定性。
我们共检索到 1949 篇参考文献，其中纳入 21 项研究。大多数纳入研究的偏倚风险为中度。与安慰剂相比，接受双膦酸盐治疗的患者血钙恢复正常的比例更高。双膦酸盐组不良事件发生率显著更高。与双膦酸盐相比，地舒单抗治疗恶性肿瘤高钙血症患者血钙恢复正常的比例无显著差异。在接受双膦酸盐治疗后，2/3 难治性/复发性恶性肿瘤高钙血症患者接受地舒单抗治疗后血钙恢复正常。在双膦酸盐治疗的基础上联合使用降钙素不会影响血钙恢复正常的比例、血钙恢复正常的时间或低钙血症的发生。仅有间接证据可用于解决与高钙三醇水平相关肿瘤的高钙血症、双膦酸盐治疗后难治性/复发性恶性肿瘤高钙血症以及甲状旁腺癌相关高钙血症治疗中使用钙敏感受体激动剂的问题。所有 8 个临床问题的证据确定性均为低到极低。
本系统评价总结的证据涉及恶性肿瘤高钙血症治疗的获益和危害。需要更多关于患者价值观和偏好的信息以及其他重要的决策和背景因素，以促进临床推荐的制定。
