title: Phase II multicenter, randomized, double-blind study of recombinant mutated human tumor necrosis factor-α in combination with chemotherapies in cancer patients.
abstract: We previously prepared a tumor necrosis factor (TNF)-α mutant (rmhTNF-α) that showed higher antitumor activity and lower systemic toxicity compared with native TNF-α. The safety profile and the pharmacokinetic characteristics of rmhTNF-α were suited for clinical use according to biological Investigational New Drug application, a standard guideline for new drug investigation in China. Here, we evaluate the activity and safety of rmhTNF-α combined with chemotherapies in head/neck, lung, colorectal, stomach, and renal cancer patients. Ninety-five eligible patients received i.m. rmhTNF-α treatment combined with standard chemotherapies. Another 95 patients were treated with standard chemotherapies. After two treatment cycles, one patient achieved a complete response and 24 patients had partial response, yielding an overall response rate (complete response + partial response) of 27.47% in the rmhTNF-α plus chemotherapy cohort. The chemotherapy alone group acquired only a 11.39% response rate (P < 0.05). When compared between different cancers, a 48.89% response rate was detected in the 45 lung cancer patients of the combination cohort. The most common grade 1-2 adverse events of rmhTNF-α were drug-related fever, allergy, flu-like symptoms, and myalgia. No significant difference was found in grade 3-4 toxicities between the two cohorts. Based on the results of this research, rmhTNF-α can significantly enhance the effectiveness of chemotherapy. An extended phase III trial of rmhTNF-α combined with standard chemotherapy is warranted for evaluating its antitumor activity and toxicity in a larger cohort of tumor patients. The studies in this paper were registered with the State Food and Drug Administration of China (No. 2003S00692).
authors.affiliation: State Key Laboratory of Cancer Biology, Biotechnology Center, School of Pharmacy, Fourth Military Medical University, Xi'an, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Li
authors.forename: Tianjiao
authors.initials: T
authors.lastname: Xu
authors.forename: Zhao
authors.initials: Z
authors.lastname: Zhang
authors.forename: Xiaochang
authors.initials: X
authors.lastname: Xue
authors.forename: Cun
authors.initials: C
authors.lastname: Zhang
authors.forename: Xin
authors.initials: X
authors.lastname: Qin
authors.forename: Weina
authors.initials: W
authors.lastname: Li
authors.forename: Qiang
authors.initials: Q
authors.lastname: Hao
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Yingqi
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000188:drug therapy; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy; D008175:Lung Neoplasms / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D011994:Recombinant Proteins / Q000009:adverse effects / Q000235:genetics / Q000494:pharmacology / Q000627:therapeutic use; D013274:Stomach Neoplasms / Q000188:drug therapy; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000009:adverse effects / Q000235:genetics / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha