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钇标记抗铁蛋白治疗晚期霍奇金病的I-II期研究,包括放射治疗肿瘤学组87-01研究。

Phase I-II studies of yttrium-labeled antiferritin treatment for end-stage Hodgkin's disease, including Radiation Therapy Oncology Group 87-01.

作者信息

Vriesendorp H M, Herpst J M, Germack M A, Klein J L, Leichner P K, Loudenslager D M, Order S E

机构信息

Johns Hopkins Oncology Center, Baltimore, MD 21205.

出版信息

J Clin Oncol. 1991 Jun;9(6):918-28. doi: 10.1200/JCO.1991.9.6.918.

Abstract

Radiolabeled antiferritin immunoglobulin (Ig) preparations were tested in patients with advanced, end-stage Hodgkin's disease. Four patients received indium-111 (111In)-labeled monoclonal antiferritin (QCI). Targeting was not observed in tumor-bearing areas. Instead, scans showed rapid accumulation of QCI in normal liver. Forty-five patients were injected with 111In-labeled polyclonal antiferritin (rabbit, pig, or baboon). Forty (89%) patients showed tumor uptake, with dosimetric estimates ranging from 300 to 3,000 cGy in 1 week for the subsequently administered yttrium-90 (90Y)-labeled antiferritin. Yttrium-labeled antibody caused hematologic toxicity. Treatment-induced toxicity was not observed in any other organ system. Intravenous autologous bone marrow cells, 18 days after the yttrium infusion, accelerated hematopoietic recovery in eight patients receiving 30 mCi or 40 mCi. Hematopoietic recovery after a 20 mCi 90Y-labeled antiferritin infusion was not influenced by an autologous bone marrow transplant. Two patients receiving 20 mCi and one patient receiving 50 mCi remained aplastic after transplantation for unknown reasons. In 29 assessable patients, a 62% response rate was observed; nine of the 18 responses were complete. Responses ranging from 2 to 26 months were more commonly noted in patients with small tumors and long disease histories. Dosimetric calculations did not predict for responses. Recurrences frequently occurred in new areas instead of areas exhibiting bulky disease at the start of the treatment. Complete responses after 90Y antiferritin were significantly (P less than .02) more frequent than in a previous study with iodine-131 (131I) antiferritin. Further improvements are needed to make this new treatment modality curative.

摘要

用放射性标记的抗铁蛋白免疫球蛋白(Ig)制剂对晚期、终末期霍奇金病患者进行了检测。4例患者接受了铟-111(¹¹¹In)标记的单克隆抗铁蛋白(QCI)。在肿瘤区域未观察到靶向作用。相反,扫描显示QCI在正常肝脏中快速蓄积。45例患者注射了¹¹¹In标记的多克隆抗铁蛋白(兔、猪或狒狒来源)。40例(89%)患者显示肿瘤摄取,对于随后给予的钇-90(⁹⁰Y)标记的抗铁蛋白,剂量学估计在1周内为300至3000 cGy。钇标记的抗体引起血液学毒性。在任何其他器官系统均未观察到治疗诱导的毒性。在注入钇18天后静脉输注自体骨髓细胞,加速了8例接受30 mCi或40 mCi剂量患者的造血恢复。注入20 mCi ⁹⁰Y标记的抗铁蛋白后,造血恢复不受自体骨髓移植的影响。2例接受20 mCi剂量和1例接受50 mCi剂量的患者在移植后因不明原因仍处于再生障碍状态。在29例可评估患者中,观察到缓解率为62%;18例缓解中有9例为完全缓解。在肿瘤较小且病程较长的患者中,2至26个月的缓解更为常见。剂量学计算无法预测缓解情况。复发常发生在新的区域,而非治疗开始时显示有大块病变的区域。⁹⁰Y抗铁蛋白治疗后的完全缓解率显著高于(P<0.02)先前一项使用碘-131(¹³¹I)抗铁蛋白的研究。需要进一步改进以使这种新的治疗方式具有治愈性。

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