The Cleveland Clinic Foundation, Cleveland, OH, USA.
Haematologica. 2010 May;95(5):845-8. doi: 10.3324/haematol.2009.008003. Epub 2010 Feb 4.
This first-in-human, phase I study evaluated the safety, maximum-tolerated dose, pharmacokinetics, and antitumor activity of dacetuzumab in 44 patients with advanced multiple myeloma. Patients received intravenous dacetuzumab, either in 4 uniform weekly doses (first 4 cohorts) or using a 5-week intrapatient dose escalation schedule (7 subsequent cohorts; the last 3 cohorts received steroid pre-medication). An initial dose of 4 mg/kg dacetuzumab exceeded the maximum-tolerated dose for uniform weekly dosing. Intrapatient dose escalation with steroid pre-medication appeared effective in reducing symptoms of cytokine release syndrome and the maximum-tolerated dose with this dosing schema was 12 mg/kg/week. Adverse events potentially related to dacetuzumab included cytokine release syndrome symptoms, non-infectious ocular inflammation, and elevated hepatic enzymes. Peak dacetuzumab blood levels increased with dose. Nine patients (20%) had a best clinical response of stable disease. The observed safety profile suggested that dacetuzumab may be combined with other multiple myeloma therapies. Two combination trials are ongoing. Clinical trials gov identifier: NCT00079716.
这项首次人体、I 期研究评估了 44 例晚期多发性骨髓瘤患者中 dacetuzumab 的安全性、最大耐受剂量、药代动力学和抗肿瘤活性。患者接受静脉内 dacetuzumab，每周 4 次（前 4 个队列）或采用 5 周的个体内剂量递增方案（随后的 7 个队列；最后 3 个队列接受类固醇预处理）。初始剂量为 4 mg/kg dacetuzumab 超过了每周均匀剂量的最大耐受剂量。使用类固醇预处理的个体内剂量递增似乎可以有效减轻细胞因子释放综合征的症状，并且这种方案的最大耐受剂量为 12 mg/kg/周。可能与 dacetuzumab 相关的不良事件包括细胞因子释放综合征症状、非传染性眼部炎症和肝酶升高。达妥昔单抗的血药峰值随剂量增加而增加。9 例患者（20%）的最佳临床反应为疾病稳定。观察到的安全性特征表明，dacetuzumab 可能与其他多发性骨髓瘤疗法联合使用。目前正在进行两项联合试验。临床试验 gov 标识符：NCT00079716。
