Shi-Yue Li1, Qiang Li2, Wei-Jie Guan1, Jiang Huang3, He-Ping Yang4, Guo-Ming Wu5, Fa-Guang Jin6, Cheng-Ping Hu7, Liang-An Chen8, Guo-Liang Xu9, Shou-Zhi Liu10, Chang-Gui Wu11, Bao-Hui Han12, Ying Xiang13, Jian-Ping Zhao14, Jie Wang15, Xin Zhou16, Hui-Ping Li17, Nan-Shan Zhong18. 1. State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Disease, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China. 2. Affiliated Changhai Hospital of Second Military University, Shanghai, China. 3. Sichuan People's Hospital, Chengdu, Sichuan, China. 4. First Affiliated Hospital of Third Military Medical University, Chongqing, China. 5. Second Affiliated Hospital of Third Military Medical University, Chongqing, China. 6. Second Affiliated Hospital (Tangdu Hospital) of Fourth Military Medical University, Xian, Shanxi, China. 7. Affiliated Xiangya Hospital of Central South Hospital, Changsha, Hunan, China. 8. General Hospital of People's Liberation Army, Beijing, China. 9. Affiliated Cancer Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China. 10. Affiliated West China Hospital of Sichuan University, Chengdu, Sichuan, China. 11. First Affiliated Hospital (Xijing Hospital) of Fourth Military Medical University, Xian, Shanxi, China. 12. Affiliated Chest Hospital of Shanghai Jiaotong University, Shanghai, China. 13. Chongqing Cancer Hospital, Chongqing, China. 14. Affiliated Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. 15. Beijing Cancer Hospital, Beijing, China. 16. Shanghai First People's Hospital, Shanghai, China. 17. Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China. 18. State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Disease, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China. Electronic address: nanshan@vip.163.com.
Abstract
BACKGROUND: Severe malignant airway obstruction (SMAO) is a life-threatening form of non-small cell lung carcinoma (NSCLC). OBJECTIVES: To determine the efficacy and safety of para-toluenesulfonamide (PTS) intratumoral injection in NSCLC-SMAO. METHODS: Ninety patients with NSCLC-SAO received repeated courses of PTS intratumoral injection until tumor sizes had reduced by 50% or greater. Primary endpoint was objective alleviation rate, assessed by chest computed tomography (CT) and bronchoscopy, at day 7 and 30 following final dosing. Secondary endpoints included airway obstruction, spirometry, quality-of-life and survival time. RESULTS: In full-analysis set (N=88), using RECIST criteria, PTS treatment resulted in a significant objective alleviation rate [chest CT: 59.1% (95%CI: 48.1%-69.5%), bronchoscopy: 48.9% (95%CI: 38.1%-59.8%) at day 7; chest CT: 43.2% (95%CI: 32.7%-54.2%), bronchoscopy: 29.6% (95%CI: 20.3%-40.2%) at day 30]. There was a remarkable increase in FVC (mean difference: 0.35 liters, 95%CI: 0.16-0.53 liters), FEV1 (mean difference: 0.27 liters, 95%CI: 0.07-0.48 liters), Baseline Dyspnea Index (mean difference: 64.8%, 95%CI: 53.9-74.7%) and Functional Assessment of Cancer Therapy-Lung Cancer Subscale (mean difference: 6·9, 95%CI: 3.8-9.9) at day 7 post-treatment. We noted significantly reduced prevalence of atelectasis (by 42.9%) and Eastern Cooperative Oncology Group physical performance scale (mean difference: 7.2, 95%CI: 3.9-10.5). Median survival time was 394 days in full-analysis set and 460 days in per-protocol set. Adverse events were reported in 64.0% of subjects. Seven severe adverse events (7.9%) were reported, of which three led to death (drug-related in one case). CONCLUSION: PTS intratumoral injection is effective and well tolerated for palliative therapy of NSCLC-SMAO.
BACKGROUND: Severe malignant airway obstruction (SMAO) is a life-threatening form of non-small cell lung carcinoma (NSCLC). OBJECTIVES: To determine the efficacy and safety of para-toluenesulfonamide (PTS) intratumoral injection in NSCLC-SMAO. METHODS: Ninety patients with NSCLC-SAO received repeated courses of PTS intratumoral injection until tumor sizes had reduced by 50% or greater. Primary endpoint was objective alleviation rate, assessed by chest computed tomography (CT) and bronchoscopy, at day 7 and 30 following final dosing. Secondary endpoints included airway obstruction, spirometry, quality-of-life and survival time. RESULTS: In full-analysis set (N=88), using RECIST criteria, PTS treatment resulted in a significant objective alleviation rate [chest CT: 59.1% (95%CI: 48.1%-69.5%), bronchoscopy: 48.9% (95%CI: 38.1%-59.8%) at day 7; chest CT: 43.2% (95%CI: 32.7%-54.2%), bronchoscopy: 29.6% (95%CI: 20.3%-40.2%) at day 30]. There was a remarkable increase in FVC (mean difference: 0.35 liters, 95%CI: 0.16-0.53 liters), FEV1 (mean difference: 0.27 liters, 95%CI: 0.07-0.48 liters), Baseline Dyspnea Index (mean difference: 64.8%, 95%CI: 53.9-74.7%) and Functional Assessment of Cancer Therapy-Lung Cancer Subscale (mean difference: 6·9, 95%CI: 3.8-9.9) at day 7 post-treatment. We noted significantly reduced prevalence of atelectasis (by 42.9%) and Eastern Cooperative Oncology Group physical performance scale (mean difference: 7.2, 95%CI: 3.9-10.5). Median survival time was 394 days in full-analysis set and 460 days in per-protocol set. Adverse events were reported in 64.0% of subjects. Seven severe adverse events (7.9%) were reported, of which three led to death (drug-related in one case). CONCLUSION:PTS intratumoral injection is effective and well tolerated for palliative therapy of NSCLC-SMAO.
Authors: Juan Riestra-Ayora; Carolina Sánchez-Rodríguez; Raquel Palao-Suay; Joaquín Yanes-Díaz; Ana Martín-Hita; María Rosa Aguilar; Ricardo Sanz-Fernández Journal: Drug Deliv Date: 2021-12 Impact factor: 6.819