Dietzek Amanda, Connelly Kelly, Cotugno Michael, Bartel Sylvia, McDonnell Anne M
Division of Pharmacy, Dana-Farber Cancer Institute, Boston, MA, USA
Smilow Cancer Hospital at Yale New Haven, New Haven, CT, USA.
J Oncol Pharm Pract. 2015 Apr;21(2):143-7. doi: 10.1177/1078155213518361. Epub 2014 Jan 10.
Denosumab is a nuclear factor-kappa ligand monoclonal antibody whose FDA-approved indications include treatment of osteoporosis, bone loss with certain anticancer hormonal agents, and prevention of skeletal-related events in patients with bone metastases from solid tumors. In clinical trials, the incidence of severe hypocalcemia has been reported as 3.1-10.8%. To date, case reports and two clinical trials have reported the use of denosumab in the management of hypercalcemia of malignancy. No reports of denosumab-induced hypocalcemia have been reported for the hypercalcemia of malignancy population.
We performed a retrospective chart review of all patients who received denosumab for hypercalcemia of malignancy to describe the effects of denosumab on calcium levels at our institution.
Seven patients received doses of denosumab for hypercalcemia of malignancy. The most common tumor types were breast cancer (n = 3) and hematologic malignancies (n = 2). All patients had bone involvement. Two patients received single doses of 60 mg. The other five patients received 120 mg. The mean corrected calcium levels were 13.7 mg/dL and 12.24 mg/dL for the days of admission and denosumab administration, respectively (p = 0.1889). The mean corrected calcium level for the last known value was 9.92 mg/dL, while in house (p = 0.0016). Supportive care prior to denosumab included hydration (n = 7), bisphosphonates (n = 6), and calcitonin (n = 5). One patient had a calcium level of 6.6 mg/dL on day 4 after denosumab, requiring calcium supplementation and telemetry. Of the seven patients treated with denosumab for hypercalcemia of malignancy at our institution, six patients were discharged alive. Of these, one patient died two days after discharge. Last-known follow-up was a median of 26 days, range, 3-195, for all patients.
Denosumab helped decrease calcium in patients with hypercalcemia of malignancy. However, symptomatic hypocalcemia may result from denosumab in hypercalcemia of malignancy.
地诺单抗是一种核因子κB配体单克隆抗体，其获美国食品药品监督管理局批准的适应症包括治疗骨质疏松症、某些抗癌激素药物所致的骨质流失，以及预防实体瘤骨转移患者的骨相关事件。在临床试验中，严重低钙血症的发生率报告为3.1%-10.8%。迄今为止，病例报告和两项临床试验报道了地诺单抗用于治疗恶性肿瘤高钙血症。尚未有关于恶性肿瘤高钙血症患者中地诺单抗诱发低钙血症的报道。
我们对所有接受地诺单抗治疗恶性肿瘤高钙血症的患者进行了回顾性病历审查，以描述地诺单抗对我院患者钙水平的影响。
7例患者接受了地诺单抗治疗恶性肿瘤高钙血症。最常见的肿瘤类型为乳腺癌（n = 3）和血液系统恶性肿瘤（n = 2）。所有患者均有骨转移。2例患者接受了60 mg的单剂量治疗。其他5例患者接受了120 mg的治疗。入院当天和使用地诺单抗当天的平均校正钙水平分别为13.7 mg/dL和12.24 mg/dL（p = 0.1889）。最后已知值的平均校正钙水平为9.92 mg/dL，住院期间（p = 0.0016）。地诺单抗治疗前的支持性治疗包括补液（n = 7）、双膦酸盐（n = 6）和降钙素（n = 5）。1例患者在使用地诺单抗后第4天钙水平为6.6 mg/dL，需要补钙和进行遥测。在我院接受地诺单抗治疗恶性肿瘤高钙血症的7例患者中，6例患者存活出院。其中，1例患者出院后两天死亡。所有患者最后已知的随访时间中位数为26天，范围为3-195天。
地诺单抗有助于降低恶性肿瘤高钙血症患者的血钙水平。然而，地诺单抗可能导致恶性肿瘤高钙血症患者出现症状性低钙血症。
