Pivotal Study of Iodine-131–Labeled Chimeric Tumor Necrosis Treatment Radioimmunotherapy in Patients With Advanced Lung Cancer Shaoliang Chen, Like Yu, Changying Jiang, Yan Zhao, Da Sun, Shenyu Li, Guoqing Liao, Yangchun Chen, Qing Fu, Qun Tao, Dan Ye, Peisheng Hu, Leslie A. Khawli, Clive R. Taylor, Alan L. Epstein, and Dian Wen Ju A B S T R A C T Purpose 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 and Methods 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. Results 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 radioac- tivity in tumors in both systemically and intratumorally injected patients. The most obvious adverse side effect was mild and reversible bone marrow suppression. Conclusion Radioimmunotherapy with 131 I-chTNT was well tolerated and can be used systemically or locally to treat refractory tumors of the lung. J Clin Oncol 23:1538-1547. © 2005 by American Society of Clinical Oncology INTRODUCTION Lung cancer has a worldwide incidence of 12.3% of all cancers, with an estimated 1.2 million new cases in 2000. 1 As such, it is the most common form of cancer in the world. Etiologically, to- bacco smoking is responsible for 80% to 90% of the incidence of lung cancer. 2 Although the prevalence of smoking is decreasing in the United States, in China and East Europe there is an epidemic of smoking which will result in tens of millions of new cases of lung cancer in the future. 1,3,4 Despite improvements in ther- apy, approximately 90% of lung cancer patients will die from their disease. In 2000, it was estimated that lung cancer resulted in 1.1 million deaths worldwide, or 17.8% of all can- cer deaths. 1 Because chemotherapy has added little to improve these grim statistics, only surgery with or without extended-field radio- therapy is a viable treatment option if war- ranted by the stage of the disease. From the Zhongshan Hospital and Tumor Hospital, Fudan University, Shanghai; Nanjng Chest Hospital Oncology Department, Nanjing; Zhujiang Hospital Oncology Center, First Military Medical University, Guangzhou; Second Hospital, Zhejiang University Medical School, Hangzhou; Department of Oncology, Liaoning Tumor Hospital, Shenyang; 309 Hospi- tal Oncology Department, Beijing; Shanghai MediPharm Biotech Co Ltd, Shanghai, China; and University of Southern California Keck School of Medicine, Los Angeles, CA. Submitted June 16, 2004; accepted December 13, 2004. Supported by MediPharm Biotech Co, Shanghai, China. Authors’ disclosures of potential con- flicts of interest are found at the end of this article. Address reprint requests to Dian Wen Ju, MD, Shanghai MediPharm Biotech Co Ltd, Bldg 72-2F, 887 Zu Chong Zhi Road, Zhangjiang HiTech Park, Shanghai 201203, China; e-mail: jud@vip.sina.com. © 2005 by American Society of Clinical Oncology 0732-183X/05/2307-1538/$20.00 DOI: 10.1200/JCO.2005.06.108 JOURNAL OF CLINICAL ONCOLOGY O R I G I N A L R E P O R T VOLUME 23  NUMBER 7  MARCH 1 2005 1538 Downloaded from ascopubs.org by 44.192.70.184 on June 10, 2022 from 044.192.070.184 Copyright © 2022 American Society of Clinical Oncology. All rights reserved.