title: Recombinant mutated human TNF in combination with chemotherapy for stage IIIB/IV non-small cell lung cancer: a randomized, phase III study.
abstract: Tumor necrosis factor (TNF), an anti-angiogenic agent in cancer treatment, is limited to isolated limb perfusion due to systemic toxicities. We previously prepared a TNF mutant (rmhTNF) that significantly improved responses in lung cancer patients and exhibited a promising safety profile in phase I and II studies. To further investigate whether rmhTNF with standard chemotherapy provides a survival benefit, 529 patients with stage IIIB/IV non-small cell lung cancer (NSCLC) were randomly assigned to receive docetaxel plus carboplatin/cisplatin with rmhTNF (265) or chemotherapy alone (264). After four cycles of treatment, the median overall survival was 13.7 months in the chemotherapy plus rmhTNF group compared with 10.3 months in the chemotherapy group (hazard ratio (HR) 0.75, P = 0.001). The median progression-free survival in the chemotherapy plus rmhTNF group and the chemotherapy group was 8.6 and 4.5 months (HR 0.76, P = 0.001), respectively, with corresponding response rates of 38.5% and 27.7% (P = 0.008). Increased hyperpyrexia and pulmonary hemorrhage were associated with rmhTNF, but most effects were well tolerated. The results indicated that rmhTNF effectively potentiated chemotherapy in patients with advanced NSCLC and was comparable with bevacizumab, an angiogenesis inhibitor approved by the Food and Drug Administration (FDA) for NSCLC.
authors.affiliation: State Key Laboratory of Cancer Biology, Biotechnology Center, School of Pharmacy, The Fourth Military Medical University, Xi'an, China.
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Ma
authors.affiliation: Department of Oncology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Song
authors.affiliation: State Key Laboratory of Cancer Biology, Biotechnology Center, School of Pharmacy, The Fourth Military Medical University, Xi'an, China.
authors.forename: Kuo
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Department of Health Statistics, School of Public Health, The Fourth Military Medical University, Xi'an, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Shang
authors.affiliation: State Key Laboratory of Cancer Biology, Biotechnology Center, School of Pharmacy, The Fourth Military Medical University, Xi'an, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Gao
authors.affiliation: State Key Laboratory of Cancer Biology, Biotechnology Center, School of Pharmacy, The Fourth Military Medical University, Xi'an, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Cancer Biology, Biotechnology Center, School of Pharmacy, The Fourth Military Medical University, Xi'an, China.
authors.forename: Xiaochang
authors.initials: X
authors.lastname: Xue
authors.affiliation: The Affiliated Cancer Hospital of Xinjiang Medical University, Urumqi, China.
authors.forename: Huimin
authors.initials: H
authors.lastname: Jia
authors.affiliation: Department of Medical Oncology, General Hospital of Nanjing Military Command, Medical School of Nanjing University, Nanjing, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Geng
authors.affiliation: General Hospital of Ningxia Medical University, Yinchuan, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Cancer Center, The 323 Hospital of People's Liberation Army, Xi'an, China.
authors.forename: Yazheng
authors.initials: Y
authors.lastname: Dang
authors.affiliation: Department of Medical Oncology, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Enxiao
authors.initials: E
authors.lastname: Li
authors.affiliation: Department of Respiratory Medicine, Xijing Hospital, The Fourth Military Medical University, Xi'an, China.
authors.forename: Xinyu
authors.initials: X
authors.lastname: Ti
authors.affiliation: New Taihe Biopharmaceutical Co., Ltd., Guangzhou, China.
authors.forename: Fulin
authors.initials: F
authors.lastname: Fan
authors.affiliation: State Key Laboratory of Cancer Biology, Biotechnology Center, School of Pharmacy, The Fourth Military Medical University, Xi'an, China.
authors.forename: Yingqi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pharmacogenomics, School of Pharmacy, The Fourth Military Medical University, Xi'an, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Li
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D002945:Cisplatin / Q000627:therapeutic use; D000077143:Docetaxel; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics / Q000627:therapeutic use; D016019:Survival Analysis; D043823:Taxoids / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics / Q000627:therapeutic use*
chemical_list: D020533:Angiogenesis Inhibitors; D011994:Recombinant Proteins; C439524:TNF protein, human; D043823:Taxoids; D014409:Tumor Necrosis Factor-alpha; D000077143:Docetaxel; D016190:Carboplatin; D002945:Cisplatin