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Phase II multicenter, randomized, double‐blind study of recombinant mutated human tumor necrosis factor‐α in combination with chemotherapies in cancer patients

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). (Cancer Sci 2012; 103: 288–295)