Peter MacCallum Cancer Centre, East Melbourne, VIC, Australia.
Lancet Oncol. 2010 Mar;11(3):275-80. doi: 10.1016/S1470-2045(10)70010-3. Epub 2010 Feb 10.
Giant-cell tumour (GCT) of bone is a primary osteolytic bone tumour with low metastatic potential and is associated with substantial skeletal morbidity. GCT is rich in osteoclast-like giant cells and contains mononuclear (stromal) cells that express RANK ligand (RANKL), a key mediator of osteoclast activation. We investigated the potential therapeutic effect of denosumab, a fully human monoclonal antibody against RANKL, on tumour-cell survival and growth in patients with GCT.
In this open-label, single-group study, 37 patients with recurrent or unresectable GCT were enrolled and received subcutaneous denosumab 120 mg monthly (every 28 days), with loading doses on days 8 and 15 of month 1. The primary endpoint was tumour response, defined as elimination of at least 90% of giant cells or no radiological progression of the target lesion up to week 25. Study recruitment is closed; patient treatment and follow-up are ongoing. The study is registered with Clinical Trials.gov, NCT00396279.
Two patients had insufficient histology or radiology data for efficacy assessment. 30 of 35 (86%; 95% CI 70-95) of evaluable patients had a tumour response: 20 of 20 assessed by histology and 10 of 15 assessed by radiology. Adverse events were reported in 33 of 37 patients; the most common being pain in an extremity (n=7), back pain (n=4), and headache (n=4). Five patients had grade 3-5 adverse events, only one of which (grade 3 increase in human chorionic gonadotropin concentration not related to pregnancy) was deemed to be possibly treatment related. Five serious adverse events were reported although none were deemed treatment related.
Further investigation of denosumab as a therapy for GCT is warranted.
Amgen, Inc.
骨巨细胞瘤（GCT）是一种原发性溶骨性骨肿瘤，转移潜能低，与大量骨骼发病率相关。GCT 富含破骨细胞样巨细胞，并含有表达核因子-κB 受体激活配体（RANKL）的单核（基质）细胞，RANKL 是破骨细胞激活的关键介质。我们研究了 denosumab（一种针对 RANKL 的全人源单克隆抗体）对 GCT 患者肿瘤细胞存活和生长的潜在治疗效果。
在这项开放标签、单组研究中，招募了 37 名复发性或不可切除的 GCT 患者，每月接受皮下注射 denosumab 120mg（每 28 天一次），在第 1 个月的第 8 天和第 15 天给予负荷剂量。主要终点是肿瘤反应，定义为至少 90%的巨细胞消除或目标病变的影像学无进展达到第 25 周。研究招募已结束；患者正在接受治疗并进行随访。该研究在 ClinicalTrials.gov 注册，NCT00396279。
有 2 名患者的组织学或影像学数据不足以进行疗效评估。35 名可评估患者中有 30 名（86%；95%CI 70-95）有肿瘤反应：20 名通过组织学评估，10 名通过影像学评估。37 名患者中有 33 名报告了不良事件；最常见的是四肢疼痛（n=7）、背痛（n=4）和头痛（n=4）。有 5 名患者发生 3-5 级不良事件，其中只有 1 例（与妊娠无关的人绒毛膜促性腺激素浓度 3 级升高）被认为可能与治疗有关。报告了 5 例严重不良事件，但均与治疗无关。
需要进一步研究 denosumab 作为 GCT 的治疗方法。
安进公司。
