Chen Shaoliang, Yu Like, Jiang Changying, Zhao Yan, Sun Da, Li Shenyu, Liao Guoqing, Chen Yangchun, Fu Qing, Tao Qun, Ye Dan, Hu Peisheng, Khawli Leslie A, Taylor Clive R, Epstein Alan L, Ju Dian Wen
Zhongshan Hospital and Tumor Hospital, Fudan University, Shanghai, China.
J Clin Oncol. 2005 Mar 1;23(7):1538-47. doi: 10.1200/JCO.2005.06.108.
Tumor 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 ((131)I-chTNT) can deliver therapeutic doses to tumors regardless of the location or type of malignancy. Therapeutic efficacy and toxicity of (131)I-chTNT in advanced lung cancer patients were studied in this pivotal registration trial.
Patients with advanced lung cancer were treated with systemic or intratumoral injection of (131)I-chTNT in eight oncology centers in China. The objective response rate (ORR) was assessed as the primary end point.
All 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.
Radioimmunotherapy with (131)I-chTNT was well tolerated and can be used systemically or locally to treat refractory tumors of the lung.
肿瘤坏死治疗（TNT）以退化的肿瘤细胞和肿瘤坏死区域作为放射免疫治疗的靶点。先前在动物肿瘤模型中的研究和临床试验表明，当与治疗性放射性核素碘-131连接时，重组嵌合TNT抗体（（131）I-chTNT）能够将治疗剂量输送至肿瘤，而不论恶性肿瘤的位置或类型如何。在这项关键的注册试验中研究了（131）I-chTNT在晚期肺癌患者中的治疗效果和毒性。
在中国的八个肿瘤中心，对晚期肺癌患者进行全身或瘤内注射（131）I-chTNT治疗。将客观缓解率（ORR）评估为主要终点。
所有纳入研究并完成治疗的107例患者在先前平均接受三次放疗或化疗后均经历了治疗失败。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%；病情稳定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，在全身和瘤内注射的患者中，放射性在肿瘤中均有良好的定位。最明显的不良反应是轻度且可逆的骨髓抑制。
（131）I-chTNT放射免疫治疗耐受性良好，可全身或局部用于治疗难治性肺癌。
