Vriesendorp H M, Morton J D, Quadri S M
Department of Radiotherapy, University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
Cancer Res. 1995 Dec 1;55(23 Suppl):5888s-5892s.
Recurrent Hodgkin's Disease (HD) provides unique opportunities to improve radiolabeled immunoglobulin therapy (RIT). Normal tissue toxicity after RIT is limited to bone marrow damage and is well documented and quantified in HD patients. Anti-antibody formation is rare in patients with HD, allowing for multiple RIT cycles. Overall, 134 patients with recurrent HD were treated on five different studies with i.v. antiferritin, labeled with 131I or with 111In for diagnostic purposes and 90Y for therapeutic purposes. Patients with recurrent, end-stage HD obtain a 60% response rate following 90Y-labeled antiferritin. One-half of the therapy responses are complete. Responses are more common in patients with longer disease histories (> 3 years) and smaller tumor volumes (< 30 cm3) and in patients receiving at least 0.4 mCi 90Y-labeled antiferritin/kg body weight. Complete responders survive significantly longer than partial responders (2 years versus 1 year). Partial responders survive longer than patients with progressive disease (1 year versus 4 months). HD in one-third of the patients recurs in new areas. A low protein dose (2-5 mg) and a moderate specific activity (10 mCi/mg) are recommended. Results obtained with 90Y-labeled antiferritin are significantly better than results with 131I-labeled antiferritin. Further translational research in vitro in the radio pharmacy and in vivo with experimental animals is ongoing to improve the therapeutic results of RIT in HD. Obviously, many permutations of RIT cannot be explored in HD patients for ethical, financial, or logistic reasons, and predictive preclinical research is required to achieve further progress. Currently, RIT is a low-toxicity, low-cost outpatient procedure for recurrent HD with a high response rate in a patient population with an unfavorable prognosis.
复发性霍奇金淋巴瘤(HD)为改进放射性标记免疫球蛋白疗法(RIT)提供了独特的机会。RIT后的正常组织毒性仅限于骨髓损伤,并且在HD患者中已有充分记录和量化。HD患者中抗抗体形成罕见,因此可进行多个RIT周期治疗。总体而言,134例复发性HD患者参与了五项不同的研究,接受静脉注射抗铁蛋白治疗,该抗铁蛋白用131I或111In标记用于诊断目的,用90Y标记用于治疗目的。复发性终末期HD患者接受90Y标记的抗铁蛋白治疗后,缓解率为60%。其中一半的治疗反应为完全缓解。在疾病史较长(>3年)、肿瘤体积较小(<30 cm3)以及接受至少0.4 mCi 90Y标记抗铁蛋白/千克体重的患者中,反应更为常见。完全缓解者的生存期明显长于部分缓解者(2年对1年)。部分缓解者的生存期长于疾病进展患者(1年对4个月)。三分之一患者的HD会在新部位复发。建议使用低蛋白剂量(2 - 5 mg)和中等比活度(10 mCi/mg)。90Y标记抗铁蛋白的治疗效果明显优于131I标记抗铁蛋白。目前正在进行放射药学体外和实验动物体内的进一步转化研究,以改善RIT在HD中的治疗效果。显然,出于伦理、经济或后勤方面的原因,HD患者无法探索RIT的许多排列组合,因此需要进行预测性临床前研究以取得进一步进展。目前,RIT是一种低毒性、低成本的门诊治疗方法,对于预后不良的复发性HD患者具有较高的缓解率。