Knox S J, Goris M L, Trisler K, Negrin R, Davis T, Liles T M, Grillo-López A, Chinn P, Varns C, Ning S C, Fowler S, Deb N, Becker M, Marquez C, Levy R
Departments of Radiation Oncology, Diagnostic Radiology, Division of Nuclear Medicine, Stanford University School of Medicine, Stanford, California, 94305, USA.
Clin Cancer Res. 1996 Mar;2(3):457-70.
A Phase I/II dose escalation study of 90Y-murine anti-CD20 monoclonal antibody (mAb) in patients with recurrent B-cell lymphoma was performed. The primary objectives of the study were: (a) to determine the effect of the preinfusion of unlabeled anti-CD20 mAb on the biodistribution of 111In-anti-CD20 mAb; (b) to determine the maximal tolerated dose of 90Y-anti-CD20 mAb that does not require bone marrow transplantation; and (c) to evaluate the safety and antitumor effect of 90Y-anti-CD20 mAb in patients with recurrent B-cell lymphoma. Eighteen patients with relapsed low- or intermediate-grade non-Hodgkin's lymphoma were treated. Biodistribution studies with 111In-anti-CD20 mAb were performed prior to therapy. Groups of three or four patients were treated at dose levels of approximately 13.5, 20, 30, 40, and 50 mCi 90Y-anti-CD20 mAb. Three patients were retreated at the 40-mCi dose level. The use of unlabeled antibody affected the biodistribution favorably. Nonhematological toxicity was minimal. The only significant toxicity was myelosuppression. The overall response rate following a single dose of 90Y-anti-CD20 mAb therapy was 72%, with six complete responses and seven partial responses and freedom from progression of 3-29+ months following treatment. Radioimmunotherapy with </=50 mCi 90Y-anti-CD20 mAb resulted in minimal nonhematological toxicity and durable clinical responses in patients with recurrent B-cell lymphoma. Doses of </=40 mCi 90Y-anti-CD20 mAb were not myeloablative.
开展了一项针对复发B细胞淋巴瘤患者的90Y鼠抗CD20单克隆抗体（mAb）的I/II期剂量递增研究。该研究的主要目标为：（a）确定未标记抗CD20 mAb预输注对111In抗CD20 mAb生物分布的影响；（b）确定无需骨髓移植的90Y抗CD20 mAb的最大耐受剂量；（c）评估90Y抗CD20 mAb对复发B细胞淋巴瘤患者的安全性和抗肿瘤效果。18例复发的低级别或中级别非霍奇金淋巴瘤患者接受了治疗。治疗前进行了111In抗CD20 mAb的生物分布研究。以大约13.5、20、30、40和50 mCi的90Y抗CD20 mAb剂量水平对三或四名患者为一组进行治疗。三名患者在40 mCi剂量水平接受了再次治疗。未标记抗体的使用对生物分布产生了有利影响。非血液学毒性极小。唯一显著的毒性是骨髓抑制。单次90Y抗CD20 mAb治疗后的总体缓解率为72%，有6例完全缓解和7例部分缓解，治疗后无进展生存期为3至29 +个月。使用≤50 mCi的90Y抗CD20 mAb进行放射免疫治疗导致复发B细胞淋巴瘤患者的非血液学毒性极小且临床反应持久。≤40 mCi的90Y抗CD20 mAb剂量不会造成清髓。
