A multicenter randomized phase Ⅲ trial of domestic product of rmhTNF in the treatment of non-small cell lung cancer

Abstract

目的 观察并比较国产注射用重组改构人肿瘤坏死因子(rmhTNF)加化疗药物和单纯化疗治疗人非小细胞肺癌的临床疗效和不良反应.方法 采用多中心、随机对照试验将200例人非小细胞肺癌患者随机分为试验组和对照组,试验组150例,对照组50例.对照组仅给予化疗,而试验组在化疗的同时,分别在第1～7天,第11～17天肌肉注射rmhTNF 4×10(6)U/m(2),两组均以21天为一周期,连用两个周期.试验结束后比较试验组和对照组的有效率和不良反应.结果 试验组有5例,对照组有3例患者因为依从性原因出组,其余患者可供临床疗效和不良反应分析.试验组有效率为46.90%(68/145),对照组为17.02%(8/47)(P＝0.001).试验组治疗后KPS评分为86.02±9.74,对照组为80.14±9.10(P＝0.025).试验组和对照组Ⅲ+Ⅳ度不良反应发生率无显著性差异(P > 0.05).与rmhTNF有关的不良反应主要有轻度发热、感冒样症状、注射局部疼痛、注射局部红肿硬结,均不需作特殊处理,治疗结束后均能自行消失.试验组和对照组均未见有严重肝肾功能、心电图异常,以及低血压等不良反应发生.结论 rmhTNF联合化疗药物治疗人非小细胞肺癌的疗效显著优于单纯化疗,rmhTNF能明显提高化疗药物的敏感性,改善晚期肺癌患者的生活质量.rmhTNF临床应用安全、有效,不良反应轻微,是一种治疗人非小细胞肺癌的新型基因工程药物.

Objective To evaluate and compare the effects and toxicity of the domestic product of recombinant mutant human tumor necrosis factor (rmhTNF) combined with chemotherapy and chemotherapy alone in the treatment of patients with non-small cell lung cancer (NSCLC). Methods Two hundred patients with NSCLC in multicenter were randomly devided into trial group (150 cases) and control group (50 cases). Chemotherapy with CAP regimen was given to the patients. Meanwhile, rmhTNF injection of 4×10(6) U/m(2) was also given from the 1st to 7th days, the 11th to 17th days on the chemotherapy cycle in the trial group. The control patients received chemotherapy alone. Twenty-one days were as a cycle, 2 cycles were given to each patient. The chemotherapeutic effects and toxicity were observed and compared between the two groups after the therapy. Results of the 200 patients, 5 cases in the trial group and 3 cases in the control group were out of the trial because of economy. The other 192 cases (145 cases in the trial group and 47 cases in the control group) could be analyzed and evaluated the clinical effects and toxicity. The response rate of chemotherapy was 46.90% (68/145) in the trial group and 17.02% (8/47) in the control group respectively ( P =0.001). The KPS scores was 86.02±9.74 in the trial group, and 80.14±9.10 in the control group ( P =0.025). No significant difference of degree Ⅲ+Ⅳ toxicity was observed between the two groups ( P > 0.05). The side effects related to rmhTNF included slight fever, cold-like symptoms, pain and red and swelling in the injection site. All of them were mild and didn’t need any treatment and disappeared after the therapy. There were no severe abnormality of liver and kidney function and ECG in both groups. Conclusion The results demonstrate that the effects of domestic rmhTNF combined with chemotherapy are remarkably higher than that of chemotherapy alone in the treatment of NSCLC. rmhTNF can increase the sensitivity to chemotherapy and improve the quality of life of the patients with slight toxicity. Hence rmhTNF is worth expanding clinical use.