Chen Zhongyan, Yang Yi, Guo Wei, Yang Rongli, Tang Xiaodong, Yan Taiqiang, Ji Tao, Xie Lu, Xu Jie, Wang Jun
Musculoskeletal Tumor Center, Peking University People's Hospital, 100044, China.
J BUON. 2018 Mar-Apr;23(2):453-459.
Denosumab, a new monoclonal antibody that inhibits receptor activator for nuclear factor Kβ ligand (RANKL), has recently been approved by FDA for the treatment of aggressive giant cell tumor of bone (GCTB). So we initiated this study to evaluate the clinical benifits of denosumab used preoperatively or postoperatively.
Patients diagnosed with classic sacral GCT without metastasis were included in this study. Patients were assigned into 3 groups according to the use of denosumab: control group 1, post-operative group 2 and neoadjuvant group 3. The latter two groups were treated with 120 mg of subcutaneous denosumab every 4 weeks with loading doses on days 8 and 15 of the first cycle. The primary endpoints were event-free-survival (EFS) and objective response rate (OPR) based on RECIST criteria. A system (MUD system) proposed by our center was applied to score the sacral nerve deficit changes before surgery in group 3.
A total 30 patients (13 men and 17 women, mean age 34.7 years, range 15-56) were enrolled from April 2014 to July 2016. Group 1 included 10 patients, group 2 9 and group 3 11. The study ended in March 01, 2017, and followup ranged from 3 to 36 months (mean 18.3). Two patients with PET-CT showed SUV max uptake down to muscle tissue level. In the neoadjuvant group 3 7 patients had partial responses and 4 stable disease (ORR 63.6%; 95% CI 35-92). Most (80%) patients achieved significant improvement in pain and great relief in the bladder and bowel functions. In 4 patients the urocatheter was removed after neoadjuvant denosumab.
Neoadjuvant therapy with denosumab can significantly relieve the symptoms and neurologic deficits.
地诺单抗是一种新型单克隆抗体，可抑制核因子κB受体活化因子配体（RANKL），最近已获美国食品药品监督管理局（FDA）批准用于治疗侵袭性骨巨细胞瘤（GCTB）。因此，我们开展了本研究以评估术前或术后使用地诺单抗的临床益处。
本研究纳入诊断为无转移的经典骶骨GCT患者。根据地诺单抗的使用情况将患者分为3组：对照组1、术后组2和新辅助组3。后两组每4周皮下注射120mg地诺单抗，在第一个周期的第8天和第15天给予负荷剂量。主要终点是基于RECIST标准的无事件生存期（EFS）和客观缓解率（OPR）。应用我们中心提出的系统（MUD系统）对3组患者术前骶神经功能缺损变化进行评分。
2014年4月至2016年7月共纳入30例患者（13例男性和17例女性，平均年龄34.7岁，范围15 - 56岁）。第1组10例患者，第2组9例，第3组11例。研究于2017年3月1日结束，随访时间为3至36个月（平均18.3个月）。2例PET - CT显示SUV最大值摄取降至肌肉组织水平。新辅助组3中，7例患者部分缓解，4例病情稳定（ORR 63.6%；95%CI 35 - 92）。大多数（80%）患者疼痛明显改善，膀胱和肠道功能得到极大缓解。4例患者在新辅助使用地诺单抗后拔除了导尿管。
地诺单抗新辅助治疗可显著缓解症状和神经功能缺损。
