Pivotal study of iodine-131-labeled chimeric tumor necrosis treatment radioimmunotherapy in patients with advanced lung cancer
Pivotal study of iodine-131-labeled chimeric tumor necrosis treatment radioimmunotherapy in patients with advanced lung cancer
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DOI：
10.1200/jco.2005.06.108
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发表时间：
2005-03-01
影响因子：
45.3
通讯作者：
Ju, DW
中科院分区：
文献类型：
--
作者：
Chen, SL;Yu, LK;Ju, DW
目的肿瘤坏死治疗（TNT）是利用肿瘤细胞的变性和坏死区作为放射免疫治疗的靶点。先前在动物肿瘤模型和临床试验中的研究已经证明，当与治疗性放射性核素碘-131连接时，重组嵌合TNT抗体（I-131-chTNT）可以向肿瘤递送治疗剂量，而不管恶性肿瘤的位置或类型。I-131-chTNT在晚期肺癌患者的疗效和毒性进行了研究，在这个关键的注册trial.Patients和MethodsPatients与晚期肺癌患者进行了全身或瘤内注射的I-131-chTNT在中国的8个肿瘤中心。客观反应率（ORR）被评估为主要endpoint.ResultsAll 107例患者进入研究，并完成治疗经历了治疗失败后，以前的放疗或化疗的平均三倍。结果显示，所有患者的ORR为34.6%（完全缓解3.7%;部分缓解30.8%;无变化55.1%;疾病进展10.3%），97例非小细胞肺癌患者的ORR为33%。一项生物分布研究表明，全身和瘤内注射患者的肿瘤中放射性定位良好。最明显的不良反应是轻度和可逆的骨髓抑制。结论放射免疫治疗与I-131-chTNT是耐受性良好，可用于全身或局部治疗难治性肺肿瘤。
PurposeTumor necrosis treatment (TNT) uses degenerating tumor cells and necrotic regions of tumors as targets for radioimmunotherapy. Previous studies in animal tumor models and clinical trials have demonstrated that when linked to the therapeutic radionuclide iodine-131, recombinant chimeric TNT antibody (I-131-chTNT) can deliver therapeutic doses to tumors regardless of the location or type of malignancy. Therapeutic efficacy and toxicity of I-131-chTNT in advanced lung cancer patients were studied in this pivotal registration trial.Patients and MethodsPatients with advanced lung cancer were treated with systemic or intratumoral injection of I-131-chTNT in eight oncology centers in China. The objective response rate (ORR) was assessed as the primary end point.ResultsAll 107 patients who were entered onto the study and completed therapy had experienced treatment failure after prior radiotherapy or chemotherapy a mean of three times. The results showed an ORR of 34.6% (complete response, 3.7%; partial response, 30.8%, no change, 55.1%; and progressive disease, 10.3%) in all patients and 33% in 97 non-small-cell lung cancer patients. A biodistribution study demonstrated excellent localization of the radioactivity in tumors in both systemically and intratumorally injected patients. The most obvious adverse side effect was mild and reversible bone marrow suppression.ConclusionRadioimmunotherapy with I-131-chTNT was well tolerated and can be used systemically or locally to treat refractory tumors of the lung.