Multicenter phase Ⅱclinical trial of rhTNF-NC injection in the treatment of malignant tumors

ZHANG Weijing; KE Xiaoyan; WANG Jiejun; WANG Mei; ZHU Jun; ZHANG Shucai; ZHANG Qiaohua; YU Ding; RAO Zhiguo; YU Shiying; XIE Conghua

Abstract：Objective To investigate the clinical efficacy, safety and life quality improvement of recombinant mutant human?NC( rhTNF?NC) in the treatment of malignant tumors or pleural effusions and ascites. Methods A total of 320 patients with malignant tumors or pleural effusions and ascites were enrolled into this multicenter, open and non?randomized phaseⅡ clinical trial, including malignant lymphoma( n=71) , malignant pleural effusions and ascites( n=169) , malignant melanoma( n=18) , lung cancer( n=20) , liver cancer( n=12) , breast cancer( n=10) , colon cancer( n=7) and renal cell carcinoma( n=3) . For malignant tumors, rhTNF?NC was intravenously dropped at a dose of 600?900 KU/m2 every day for 28 days. For malignant pleural effusions and ascites, rhTNF?NC was infused intralpeurally at a dose of 2000?3000 KU a time, 1?2 times per week for 2?3 weeks. For melanoma, intratumor injection was combined with intravenous injection at a dose of 500?1000 KU/time, 2?3 times per week. Results Three hundred and ten patients could be evaluated, including 169 cases of malignant pleural effusions and ascites, and 141 cases of solid tumors. In solid tumor pa?tients, 2 cases got CR, 21 in PR, with reponse rate(RR) of 16?3%(23/141) and disease control rate(DCR) of 79?4%(112/141). The malignant lymphoma?s RR was 28?2%(20/71), and DCR was 84?5%(60/71). Malignant melanoma?s RR was 11?1%(2/18), and DCR was 83?3%(15/18). In lung cancer, no one got CR, 1 in PR, and 2 in MR. 1 case of MR was in renal cell carcinoma. It showed no significant effect in liver cancer, colon cancer and breast cancer. In malignant pleural effusions and ascites, 15 got CR, 102 in PR with RR of 69?2%(117/169) and DCR of 98?8%(167/169). Among them, the malignant pleural effusions?s RR was 74?5%(105/141), and the malignant ascites?s RR was 42?9%(12/28).The KPS score of the whole group increased significantly after treat?ment(P=0?013), especially in the subgroup of malignant pleural effusion patients. The major adverse reaction was fever(38?8%) and shiver( 23?5%) mainly in grade 1 and 2. Conclusion The rhTNF?NC injection is effective in the control of various malignant tumors and malignant pleural effusions and ascites, with mild and tolerable adverse effects, and can dramatically improve the patients?quality of life.