Knox S J, Goris M L, Tempero M, Weiden P L, Gentner L, Breitz H, Adams G P, Axworthy D, Gaffigan S, Bryan K, Fisher D R, Colcher D, Horak I D, Weiner L M
Stanford University School of Medicine, Department of Radiation Oncology, California 94305, USA.
Clin Cancer Res. 2000 Feb;6(2):406-14.
A Phase II study of yttrium-90-tetra-azacyclododecanetetra-acetic acid-biotin (90Y-DOTA-biotin) pretargeted by NR-LU-10 antibody/streptavidin (SA) was performed. The primary objectives of the study were to evaluate the efficacy and safety of this therapy in patients with metastatic colon cancer. Twenty-five patients were treated with a single dose of 110 mCi/m2 (mean administered dose, 106.5 +/- 10.3 mCi/m2) of 90Y-DOTA-biotin. There were three components of the therapy. Patients first received NR-LU-10/SA on day 1. A clearing agent (biotin-galactose-human serum albumin) was administered approximately 48 h after the NR-LU-10/SA to remove residual circulating unbound NR-LU-10/SA. Lastly, 24 h after administration of clearing agent, patients received biotin-DOTA-labeled with 110 mCi/m2 90Y. All three components of the therapy were administered i.v. Both hematological and nonhematological toxicities were observed. Diarrhea was the most frequent grade 4 nonhematological toxicity (16%; with 16% grade 3 diarrhea). Hematological toxicity was less severe with 8% grade 3 and 8% grade 4 neutropenia and 8% grade 3 and 16% grade 4 thrombocytopenia. The overall response rate was 8%. Two partial responders had freedom from progression of 16 weeks. Four patients (16%) had stable disease with freedom from progression of 10-20 weeks. Despite the relatively disappointing results of this study in terms of therapeutic efficacy and toxicity, proof of principle was obtained for the pretargeting approach. In addition, valuable new information was obtained about normal tissue tolerance to low-dose-rate irradiation that will help to provide useful guidelines for future study designs.
开展了一项关于钇-90-四氮杂环十二烷四乙酸-生物素（90Y-DOTA-生物素）经NR-LU-10抗体/链霉亲和素（SA）预靶向的II期研究。该研究的主要目的是评估这种疗法对转移性结肠癌患者的疗效和安全性。25例患者接受了单剂量110 mCi/m2（平均给药剂量，106.5±10.3 mCi/m2）的90Y-DOTA-生物素治疗。该疗法有三个组成部分。患者在第1天首先接受NR-LU-10/SA。在NR-LU-10/SA给药后约48小时给予清除剂（生物素-半乳糖-人血清白蛋白），以清除残留的循环未结合NR-LU-10/SA。最后，在给予清除剂24小时后，患者接受用110 mCi/m2 90Y标记的生物素-DOTA。该疗法的所有三个组成部分均通过静脉注射给药。观察到血液学和非血液学毒性。腹泻是最常见的4级非血液学毒性（16%；16%为3级腹泻）。血液学毒性较轻，3级中性粒细胞减少症为8%，4级为8%，3级血小板减少症为8%，4级为16%。总缓解率为8%。两名部分缓解者无进展生存期为16周。4例患者（16%）病情稳定，无进展生存期为10至20周。尽管该研究在治疗效果和毒性方面结果相对令人失望，但预靶向方法的原理得到了验证。此外，还获得了关于正常组织对低剂量率照射耐受性的有价值的新信息，这将有助于为未来的研究设计提供有用的指导。
