DeNardo Gerald L
Radiodiagnosis and Therapy, University of California Davis Medical Center, 1508 Alhambra Boulevard #3100, Sacramento, CA 95816, USA.
Semin Nucl Med. 2005 Jul;35(3):202-11. doi: 10.1053/j.semnuclmed.2005.02.006.
Most patients with non-Hodgkin's lymphoma (NHL) achieve remission but, despite newer drugs, the natural history of this disease has not improved during the last 20 years. Less than one half of patients with aggressive NHL are cured, and few of those with low-grade NHL are curable. Furthermore, NHL becomes progressively more chemoresistant while remaining responsive to external beam radiation therapy. Radioimmunotherapy (RIT) is a logical strategy for the treatment of NHL because this disease is multifocal and radiosensitive. Because of their remarkable effectiveness for RIT, 2 anti-CD20 monoclonal antibodies (mAbs), one labeled with (111)In for imaging or (90)Y for therapy and a second labeled with (131)I for imaging and therapy, have been approved for use in patients with NHL. These drugs have proven remarkably effective and safe. Evidence for the importance of the radionuclide is manifested by the data in the randomized pivotal phase III trial of (90)Y-ibritumomab that revealed response rates were several times greater in the (90)Y-ibritumomab arm than in the rituximab arm. A second drug for RIT, (131)I-tositumomab, was compared in a pivotal trial with the efficacy of the last chemotherapy received by each patient. Once again, response rates were much higher for RIT. Both (90)Y-ibritumomab and (131)I-tositumomab require preinfusion of several hundred milligrams of unlabeled anti-CD20 mAb to obtain "favorable" biodistribution, that is, targeting of NHL. Response rates for other mAbs and radionuclides in NHL also have been high but these drugs have not reached the approval stage. These drugs can be used safely by physicians who have suitable training and judgment. Unlike chemotherapy, RIT is not associated with mucositis, hair loss, or persistent nausea or vomiting. Although hematologic toxicity is dose limiting, hospitalization for febrile neutropenia is uncommon. Randomized trials of RIT in different formulations have not been conducted, but there is evidence to suggest that the mAb, antigen, radionuclide, chelator, linker, and dosing strategy may make a difference in the outcome.
大多数非霍奇金淋巴瘤（NHL）患者可实现缓解，但尽管有了新型药物，在过去20年里，这种疾病的自然病程并未得到改善。侵袭性NHL患者中不到一半能被治愈，低度NHL患者中几乎无人可治愈。此外，NHL对化疗的耐药性逐渐增强，而对外照射放疗仍有反应。放射免疫疗法（RIT）是治疗NHL的合理策略，因为这种疾病是多灶性且对放疗敏感。由于两种抗CD20单克隆抗体（mAb）对RIT具有显著疗效，一种用（111）铟标记用于成像或用（90）钇标记用于治疗，另一种用（131）碘标记用于成像和治疗，已被批准用于NHL患者。这些药物已被证明非常有效且安全。（90）钇-伊布替尼单抗的随机关键III期试验数据表明了放射性核素的重要性，该试验显示（90）钇-伊布替尼单抗组的缓解率比利妥昔单抗组高出数倍。在一项关键试验中，将第二种RIT药物（131）碘-托西莫单抗与每位患者接受的最后一次化疗疗效进行了比较。RIT的缓解率再次高得多。（90）钇-伊布替尼单抗和（131）碘-托西莫单抗都需要预先输注数百毫克未标记的抗CD20 mAb以获得“良好”的生物分布，即靶向NHL。NHL中其他mAb和放射性核素的缓解率也很高，但这些药物尚未达到获批阶段。经过适当培训和具备判断力的医生可以安全地使用这些药物。与化疗不同，RIT不会引起粘膜炎、脱发或持续性恶心或呕吐。虽然血液学毒性是剂量限制性的，但因发热性中性粒细胞减少而住院并不常见。尚未进行不同制剂的RIT随机试验，但有证据表明mAb、抗原、放射性核素、螯合剂、连接体和给药策略可能会对结果产生影响。
