Dancey Gairin, Violet John, Malaroda Alessandra, Green Alan J, Sharma Surinder K, Francis Roslyn, Othman Shokri, Parker Sweta, Buscombe John, Griffin Natalie, Chan Pei-San, Malhotra Anmol, Woodward Nicholas, Ramsay Alan, Ross Philip, Lister T Andrew, Amlot Peter, Begent Richard, McNamara Christopher
Authors' Affiliations: Cancer Research UK Targeting and Imaging Group, Department of Oncology, University College London Cancer Institute and Department of Histopathology, University College London Hospitals, London, United Kingdom; Departments of Nuclear Medicine and Radiology, Immunology, and Hematology, Royal Free Hospital, Hampstead, United Kingdom; Cancer Research UK Medical Oncology Unit, St Bartholomew's Hospital, London, United Kingdom; Drug Development Office, Cancer Research UK, London, United Kingdom.
Clin Cancer Res. 2009 Dec 15;15(24):7701-7710. doi: 10.1158/1078-0432.CCR-09-1421.
There is a need for new treatments for Hodgkin and T-cell lymphoma due to the development of drug resistance in a proportion of patients. This phase I study of radioimmunotherapy used CHT-25, a chimeric antibody to the alpha-chain of the interleukin-2 receptor, CD25, conjugated to iodine-131 ((131)I) in patients with refractory CD25-positive lymphomas. EXPERIMENTAL DESIGN: Fifteen patients were treated (Hodgkin lymphoma, 12; angioimmunoblastic T-cell lymphoma, 1; adult T-cell leukemia/lymphoma, 2). Tumor was monitored by computed tomography and in all but two patients by (18)F-fluorodeoxyglucose positron emission tomography. RESULTS: There were no grade 3 or 4 infusion reactions. At the maximum tolerated dose of 1,200 MBq/m(2), the major side effect was delayed myelotoxicity with the nadir for platelets at 38 days and for neutrophils at 53 days. One patient treated with 2,960 MBq/m(2) developed prolonged grade 4 neutropenia and thrombocytopenia and died of Pneumocystis jiroveci pneumonia. Nonhematologic toxicity was mild. Single photon emission computer tomography imaging showed tumor-specific uptake and retention of (131)I and no excessive retention in normal organs. Of nine patients receiving >/=1,200 MBq/m(2), six responded (three complete response and three partial response); one of six patients with administered radioactivity of </=740 MBq/m(2) had a complete response. CONCLUSIONS: CHT-25 is well tolerated with 1,200 MBq/m(2) administered radioactivity and shows clinical activity in patients who are refractory to conventional therapies. Phase II studies are justified to determine efficacy and toxicity in a broader range of clinical scenarios. (Clin Cancer Res 2009;15(24):7701-10).
由于部分患者出现耐药性，霍奇金淋巴瘤和T细胞淋巴瘤需要新的治疗方法。本I期放射免疫治疗研究在难治性CD25阳性淋巴瘤患者中使用了CHT - 25，一种与白细胞介素-2受体α链（CD25）结合的嵌合抗体，并与碘-131（¹³¹I）偶联。实验设计：15例患者接受治疗（霍奇金淋巴瘤12例；血管免疫母细胞性T细胞淋巴瘤1例；成人T细胞白血病/淋巴瘤2例）。通过计算机断层扫描监测肿瘤，除2例患者外，其余均通过¹⁸F - 氟脱氧葡萄糖正电子发射断层扫描监测。结果：无3级或4级输注反应。在最大耐受剂量1200 MBq/m²时，主要副作用是延迟性骨髓毒性，血小板最低点出现在第38天，中性粒细胞最低点出现在第53天。1例接受2960 MBq/m²治疗的患者出现了持续的4级中性粒细胞减少和血小板减少，并死于耶氏肺孢子菌肺炎。非血液学毒性较轻。单光子发射计算机断层扫描成像显示肿瘤特异性摄取和保留¹³¹I，正常器官无过度保留。在9例接受≥1200 MBq/m²治疗的患者中，6例有反应（3例完全缓解，3例部分缓解）；在6例给予放射性活度≤740 MBq/m²的患者中，1例完全缓解。结论：给予1200 MBq/m²放射性活度时，CHT - 25耐受性良好，对传统治疗难治的患者显示出临床活性。进行II期研究以确定在更广泛临床情况下的疗效和毒性是合理的。（《临床癌症研究》2009年；15(24):7701 - 10）
