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姑息肿瘤学:地诺单抗

Palliative Oncology: Denosumab.

作者信息

Prommer Eric

机构信息

Division of Hematology/Oncology, Mayo Clinic College of Medicine, Mayo Clinic Hospital, Scottsdale, AZ, USA

出版信息

Am J Hosp Palliat Care. 2015 Aug;32(5):568-72. doi: 10.1177/1049909114539035. Epub 2014 Jun 13.

Abstract

Bone metastases cause devastating clinical complications leading patients to have pain, poor quality of life, loss of mobility, and autonomy. Complications from osseous metastases cause a big economic burden reflected by repeated admissions for uncontrolled symptoms. Management of symptoms associated with bone metastasis includes systemic analgesics, glucocorticoids, radiation (external beam radiation and radiopharmaceuticals), ablative techniques (radiofrequency ablation and cryoablation), chemotherapeutic agents, hormonal therapies, interventional techniques (eg, kyphoplasty), and surgical approaches. Bisphosphonates have become a standard therapy for bony metastasis. They bind to bone eventually inhibiting osteoclast action. Bisphosphonates decrease fractures when given routinely. Adverse effects of bisphosphonates include osteonecrosis of the jaw and renal insufficiency. Late last year, the Food and Drug Administration approved denosumab to prevent skeletal-related events (SREs) associated with metastatic solid tumors. This drug is a monoclonal antibody that inhibits the receptor activator of nuclear factor κB (RANK)-RANK ligand interaction. Clinical trials have shown superiority over bisphosphonates for the prevention of SREs. This article reviews the mechanism of action, pharmacology, adverse effects, and clinical trial evidence for this new drug.

摘要

骨转移会引发严重的临床并发症,导致患者出现疼痛、生活质量下降、行动不便和失去自主能力。骨转移引起的并发症造成了巨大的经济负担,表现为因症状无法控制而反复住院。骨转移相关症状的管理包括全身镇痛药、糖皮质激素、放疗(外照射放疗和放射性药物)、消融技术(射频消融和冷冻消融)、化疗药物、激素疗法、介入技术(如椎体成形术)和手术方法。双膦酸盐已成为骨转移的标准治疗方法。它们与骨结合,最终抑制破骨细胞的作用。常规使用双膦酸盐可减少骨折。双膦酸盐的不良反应包括颌骨坏死和肾功能不全。去年年底,美国食品药品监督管理局批准了地诺单抗用于预防与转移性实体瘤相关的骨相关事件(SREs)。这种药物是一种单克隆抗体,可抑制核因子κB受体激活剂(RANK)-RANK配体相互作用。临床试验表明,在预防SREs方面,它优于双膦酸盐。本文综述了这种新药的作用机制、药理学、不良反应和临床试验证据。

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