Bartlett Nancy L, Younes Anas, Carabasi Matthew H, Forero Andres, Rosenblatt Joseph D, Leonard John P, Bernstein Steven H, Bociek R Gregory, Lorenz Jennie M, Hart Bruce W, Barton Jeremy
Siteman Cancer Center, Washington University School of Medicine, St Louis, MO 63110, USA.
Blood. 2008 Feb 15;111(4):1848-54. doi: 10.1182/blood-2007-07-099317. Epub 2007 Dec 13.
Phase 1 testing of SGN-30, a chimeric monoclonal antibody for the treatment of CD30(+) malignancies, was conducted in a multicenter study. To explore the safety profile and establish the maximum tolerated dose (MTD), 24 patients with refractory or relapsed Hodgkin lymphoma or CD30(+) non-Hodgkin lymphoma received 6 weekly doses of intravenous SGN-30 at 4 dose levels (2, 4, 8, or 12 mg/kg). Serum concentrations of SGN-30 rose rapidly and were dose dependent. Adverse events were mild, with nausea, fatigue, and fever attributed to study treatment. One episode of hypersensitivity rash was reported. The MTD was not reached. Serious adverse events included herpes zoster (n = 2), influenza, and pneumonia. One patient with cutaneous anaplastic large cell lymphoma (8 mg/kg) achieved a complete response. Six patients, of whom 4 had Hodgkin lymphoma, achieved stable disease with durations ranging from 6 to 16 months. The pharmacokinetic profile of SGN-30 showed a biphasic disposition, and estimated half-lives ranging between 1 to 3 weeks. The 6 weekly infusions of SGN-30 resulted in approximately 2- to 3-fold accumulation in serum exposures consistently across the dose range. These results demonstrate that weekly administration of SGN-30 is safe and has modest clinical activity in patients with CD30(+) tumors. This trial is registered at http://www.ClinicalTrials.gov as no. NCT00051597.
用于治疗CD30(+)恶性肿瘤的嵌合单克隆抗体SGN-30的1期试验在一项多中心研究中进行。为了探索安全性并确定最大耐受剂量（MTD），24例难治性或复发性霍奇金淋巴瘤或CD30(+)非霍奇金淋巴瘤患者接受了6周的静脉注射SGN-30，共4个剂量水平（2、4、8或12 mg/kg）。SGN-30的血清浓度迅速上升且呈剂量依赖性。不良事件较轻，恶心、疲劳和发热归因于研究治疗。报告了1例过敏皮疹。未达到MTD。严重不良事件包括带状疱疹（n = 2）、流感和肺炎。1例皮肤间变性大细胞淋巴瘤患者（8 mg/kg）获得完全缓解。6例患者病情稳定，其中4例为霍奇金淋巴瘤，持续时间为6至16个月。SGN-30的药代动力学特征显示为双相分布，估计半衰期在1至3周之间。每周6次输注SGN-30导致血清暴露量在整个剂量范围内持续累积约2至3倍。这些结果表明，每周给予SGN-30对CD30(+)肿瘤患者是安全的，且具有适度的临床活性。该试验已在http://www.ClinicalTrials.gov注册，编号为NCT00051597。
