Phase II multicenter evaluation of prolonged murine monoclonal antibody 17-1A therapy in pancreatic carcinoma.
Phase II multicenter evaluation of prolonged murine monoclonal antibody 17-1A therapy in pancreatic carcinoma.
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长期鼠单克隆抗体 17-1A 治疗胰腺癌的 II 期多中心评估。
DOI：
10.1097/00002371-199302000-00005
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发表时间：
1993
期刊：
影响因子：
--
通讯作者：
Haller,DG
中科院分区：
文献类型：
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作者：
Weiner,LM;Harvey,E;Padavic-Shaller,K;Willson,JK;Walsh,C;LaCreta,F;Khazaeli,MB;Kirkwood,JM;Haller,DG
用鼠单克隆抗体17- 1A治疗28名患有不可切除的、可测量的胰腺癌且东部肿瘤协作组（ECOG）体力状态为0或1的患者，计划每周三次静脉内施用500 mg，持续8周。治疗耐受性良好，超敏反应发生率为18%（5例患者）。所有超敏反应事件均发生在治疗的前3周，需要停止治疗。6例患者因症状性疾病进展需要提前终止治疗，1例患者因方案违背从研究中移除。16例患者接受了12 g抗体的全程治疗。1例患者表现出持久的部分缓解。在5名患者中测定抗体药代动力学。在四个病人的峰值17-1A水平平均100 μ g/ml，平均谐波uh为16.8小时，在一个房室模型。在8周治疗期间，治疗前和治疗后循环17-1A水平均无显著变化。本研究证明了重复给药未结合的鼠单克隆抗体的可行性和可接受的毒性。缺乏治疗效果表明，除了肿瘤和细胞毒性效应细胞长期暴露于鼠抗体之外，其他因素也是成功进行胰腺癌抗体治疗所必需的。
Twenty-eight patients with unresectable, measurable pancreatic carcinoma and Eastern Oncology Cooperative Group (ECOG) performance status of 0 or 1 were treated with the murine monoclonal antibody 17-1 A, planning to administer 500 mg iv three times weekly for 8 weeks. Treatment was well tolerated, with an 18% incidence (five patients) of hypersensitivity reactions. All hypersensitivity episodes occurred in the first 3 weeks of therapy and required treatment discontinuation. Six patients required early discontinuation of therapy due to symptomatic progressive disease and one patient was removed from the study due to a protocol violation. Sixteen patients received the full course of 12 g of antibody. One patient has exhibited a durable partial response. Antibody pharmacokinetics were determined in five patients. In four patients peak 17-1A levels averaged 100 fig/ml with mean harmonic uh of 16.8 h in a one-compartment model. Neither pretreatment nor posttreatment levels of circulating 17-1A changed significantly during the 8 weeks of treatment, This study demonstrates the feasibility and acceptable toxicity of repetitive dosing with an unconjugated murine monoclonal antibody. The lack of efficacy of treatment suggests that factors other than prolonged exposure of tumor and cytotoxic effector cells to murine antibody are required for successful antibody therapy of pancreatic cancer.