地诺单抗（denosumab，商品名：Xgeva）用以预防癌症已经转移并且损害骨质的肿瘤患者骨相关事件（SREs）。所谓骨相关事件包括癌症所致病理性骨折、高钙血症、骨的手术或放疗、脊髓压迫。但地诺单抗这一获准适用人群不包括多发性骨髓瘤或其它白血病患者。

作用机理：

地诺单抗与现已获准的减少肿瘤骨骼并发症的药物作用机制不同。它是一种特异性靶向核因子-κB受体活化因子配体（RANKL）的完全人源化单克隆抗体（IgG2单抗），阻止RANKL和其受体物质结合，抑制破骨细胞活化和发展，减少骨吸收，增加骨密度。早前地诺单抗(商品名:Prolia)被用来治疗有较高骨折风险的绝经后妇女骨质疏松症，具有较好的安全性和有效性。

临床研究：

癌症骨转移是患者疼痛重要原因，影响患者的生活质量。三项随机-双盲的临床研究证实了地诺单抗的安全性和疗效，总共有5723名患者参与研究。这些研究在乳腺癌、前列腺癌以及多种其它癌症患者身上对地诺单抗与唑来膦酸作了比较。

这些研究旨在测定由于癌症，患者最终出现骨折或脊髓压迫，或为控制疼痛需要进行放射或手术治疗间隔的时间。

在前列腺癌患者中，地诺单抗延迟SREs优于唑来膦酸。前列腺癌患者中SREs延迟时间中位值21个月，唑来膦酸为17个月。

在乳腺癌患者中，唑来膦酸使SREs延迟的中位时间为26个月，而地诺单抗没有达到这一水平。

在其它实体瘤患者中，地诺单抗和唑来膦酸使SREs延迟的中位时间不相上下。受试者主要的实体瘤为非小细胞肺癌、多发性骨髓瘤、肾癌以及小细胞肺癌。

不良反应：

地诺单抗最严重的不良反应为低钙血症和颚骨坏死。

剂量和给药方法:

推荐剂量：地诺单抗 120mg皮下注射 1/4周，于上臂、上大腿、腹部。

钙和维生素D可以治疗或预防低钙血症。

给药前，地诺单抗可能从冰箱取出，在原始容器内室温放置(直至25℃/77℉)。一般需要15至30分钟。不要用任何其它方法加温。

用27号针抽吸注射小瓶内全部内容物。不要再次进入小瓶，单次使用或进入后遗弃小瓶，

剂型和规格：120mg/1.7mL (70mg/mL)单次使用小瓶。

保存：

贮藏在冰箱内在2至8℃(36至46℉)在原始盒内。不要冻结，一旦从冰箱取出，不要暴露在温度25℃/77℉以上或光线，必须在14天内使用。

建议：

目前在预防骨相关事件的药物中，还没有足够的证据显示地诺单抗明显优于其它任一种药物，特别在延长患者生存期方面。因此，选择时，要综合考虑患者体质状况、经济状况、药物毒副反应、个人喜好等情况，以给患者带来最大的益处为准则来选用。

Indication
XGEVA® is indicated for the prevention of skeletal-related events in patients with bone metastases from solid tumors.

XGEVA® is not indicated for the prevention of skeletal-related events in patients with multiple myeloma.
Important Safety Information
Hypocalcemia
XGEVA® (denosumab) can cause severe hypocalcemia. Correct pre-existing hypocalcemia prior to XGEVA® treatment. Monitor calcium levels and administer calcium, magnesium, and vitamin D as necessary. Monitor levels more frequently when XGEVA® is administered with other drugs that can also lower calcium levels. In the postmarketing setting, severe symptomatic hypocalcemia has been reported. Advise patients to contact a healthcare professional for symptoms of hypocalcemia.
Based on clinical trials using a lower dose of denosumab, patients with a creatinine clearance less than 30 mL/min or receiving dialysis are at greater risk of severe hypocalcemia compared to patients with normal renal function. The risk of hypocalcemia at the recommended dosing schedule of 120 mg every 4 weeks has not been evaluated in patients with a creatinine clearance less than 30 mL/min or receiving dialysis.
Osteonecrosis of the Jaw (ONJ)
Osteonecrosis of the jaw (ONJ) can occur in patients receiving XGEVA® (denosumab), manifesting as jaw pain, osteomyelitis, osteitis, bone erosion, tooth or periodontal infection, toothache, gingival ulceration, or gingival erosion. Persistent pain or slow healing of the mouth or jaw after dental surgery may also be manifestations of ONJ.
Perform an oral examination and appropriate preventive dentistry prior to the initiation of XGEVA® and periodically during XGEVA® therapy. Advise patients regarding oral hygiene practices. Avoid invasive dental procedures during treatment with XGEVA®.
Patients who are suspected of having or who develop ONJ while on XGEVA® (denosumab) should receive care by a dentist or an oral surgeon. In these patients, extensive dental surgery to treat ONJ may exacerbate the condition.
Pregnancy
Women should be advised not to become pregnant when taking XGEVA® (denosumab). If the patient is pregnant or becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus.
Adverse Reactions
The most common adverse reactions in patients receiving XGEVA® (denosumab) were fatigue/asthenia, hypophosphatemia, and nausea. The most common serious adverse reaction was dyspnea. The most common adverse reactions resulting in discontinuation were osteonecrosis and hypocalcemia. During post approval use, severe symptomatic hypocalcemia, including fatal cases has been identified.