Herpst J M, Klein J L, Leichner P K, Quadri S M, Vriesendorp H M
Division of Radiation Oncology, Johns Hopkins Hospital, Baltimore, MD, USA.
J Clin Oncol. 1995 Sep;13(9):2394-400. doi: 10.1200/JCO.1995.13.9.2394.
A follow-up study was initiated of patients with Hodgkin's disease who were treated with yttrium 90-labeled antiferritin. Prescription method, pharmacokinetics, acute and late side effects, and survival were evaluated.
Patients had measurable disease and failed > or = two multiagent chemotherapy regimens previously (N = 44). All patients received 5-mCi indium 111-labeled antiferritin 2 mg intravenously and were scanned repeatedly by gamma camera. In five patients, polyclonal antiferritin (rabbit, pig, or baboon) failed to target the tumor. Thirty-nine patients were injected intravenously with 10-, 20-, 30-, 40-, or 50-mCi yttrium 90-labeled antiferritin 2 to 5 mg. Patients received between one and five cycles. Some patients were supported with 5 x 10(7) autologous bone marrow cells per kilogram.
Yttrium 90-labeled polyclonal antiferritin does not produce immunologic, pharmacologic, or microbiologic complications in vivo. Bone marrow toxicity is the only side effect observed. Overall response rate is 20 of 39, or 51%. Two patients had stable disease. A significant positive correlation is found between blood radioactivity level 1 hour after radioimmunoconjugate administration and subsequent response of Hodgkin's disease. A dosage in millicuries per kilogram provides a higher positive correlation with blood radioactivity levels 1 hour after administration than a dosage in millicuries per square meter of body-surface area or in total millicuries. Fifty percent of patients survive for > or = 6 months.
The low-dose protein used (2 to 5 mg) indicates that the high response rate is due to radiation and not to immunologic effects of the antibody. High-activity administrations followed by bone marrow transplantation are not required for tumor response. The therapeutic ratio of radiolabeled antiferritin is higher than the therapeutic ratio observed in most phase I studies of chemotherapeutic agents. This analysis does not identify a superior mode of treatment for patients with end-stage Hodgkin's disease. However, in a heavily pretreated patient population, prolonged survival is observed after relatively inexpensive treatment. Preclinical research with yttrium 90-labeled antiferritin indicates that significant increases in tumor dose can be obtained in the future without an increase in normal tissue toxicity.
对接受钇90标记抗铁蛋白治疗的霍奇金病患者开展一项随访研究。评估了处方方法、药代动力学、急慢性副作用及生存率。
患者有可测量病灶且先前接受过≥两种多药化疗方案治疗失败（N = 44）。所有患者静脉注射5毫居里铟111标记的2毫克抗铁蛋白，并通过γ相机反复扫描。5例患者中，多克隆抗铁蛋白（兔、猪或狒狒来源）未能靶向肿瘤。39例患者静脉注射10、20、30、40或50毫居里钇90标记的2至5毫克抗铁蛋白。患者接受1至5个周期治疗。部分患者每千克体重接受5×10⁷个自体骨髓细胞支持。
钇90标记的多克隆抗铁蛋白在体内未产生免疫、药理或微生物学并发症。观察到的唯一副作用是骨髓毒性。总体缓解率为39例中的20例，即51%。2例患者病情稳定。在放射免疫缀合物给药后1小时的血液放射性水平与霍奇金病的后续缓解之间发现显著正相关。每千克体重的剂量毫居里数与给药后1小时的血液放射性水平的相关性高于每平方米体表面积的剂量毫居里数或总剂量毫居里数。50%的患者存活≥6个月。
使用的低剂量蛋白（2至5毫克）表明高缓解率是由于辐射而非抗体的免疫效应。肿瘤缓解不需要高活性给药后进行骨髓移植。放射性标记抗铁蛋白的治疗指数高于大多数化疗药物I期研究中观察到的治疗指数。该分析未确定终末期霍奇金病患者的更优治疗模式。然而，在经过大量预处理的患者群体中，相对廉价的治疗后观察到生存期延长。钇90标记抗铁蛋白的临床前研究表明，未来在不增加正常组织毒性的情况下可显著提高肿瘤剂量。
