随机、开放、平行对照、多中心评价重组人腺病毒P53治疗恶性浆膜腔积液的临床研究

Clinical study on recombinant human P53 adenovirus in the treatment of malignant serous cavity effusion

目的探讨浆膜腔内注射重组人腺病毒P53注射液(r Ad-P53)治疗晚期肺癌恶性浆膜腔积液的临床疗效及不良反应。方法选择西安交通大学医学院第二附属医院、西安交通大学医学院第一附属医院及长安医院等多家医院2012年1月至2015年10月临床确诊晚期肺癌合并恶性浆膜腔积液患者107例,随机分为两组,Ⅰ组56例浆膜腔内注射r Ad-P53,Ⅱ组51例浆膜腔内注射顺铂和白介素-2,所有患者均可辅以放疗、化疗或靶向等全身治疗。分析两组患者治疗疗效及不良反应。结果经治疗Ⅰ组病例中有43例有效,有效率为76.8%;Ⅱ组病例中有18例有效,有效率为35.3%。Ⅰ组有效率高于Ⅱ组,差异有统计学意义(P<0.001)。Ⅰ组比Ⅱ组疗效好。I组各种不良反应发生率分别为发热30.4%(17/56)、头痛3.6%(2/56)、恶心1.8%(1/56)、白细胞减少0%(0/56)、肝功能异常7.1%(4/56),Ⅱ组各种不良反应发生率分别为发热11.8%(6/51)、头痛5.9%(3/51)、恶心11.8%(6/51)、白细胞减少7.8%(4/51)、肝功能异常15.7%(8/51),比较Ⅰ组和Ⅱ组间各种不良反应的发生率,发热和白细胞减少的发生率,差异均有统计学意义(P<0.05),而头痛、恶心、肝功能异常的发生率,差异均无统计学意义(P>0.05)。结论浆膜腔内注射r Ad-P53治疗晚期肺癌恶性浆膜腔积液是一种有效、副作用极少的治疗方法。

Objective To observe the clinical curative effect and adverse reactions of using recombinant human adenovirus P53 injection （rAd-P53） or cisplatin and IL-2 in the treatment of malignant serous cavity effusion of advanced lung cancer. Methods Total 107 patients with malignant serous cavity effusion of advanced lung cancer （ stage Ⅲ and stage Ⅳ） were choose from January 2012 to December 2015 in the Second Affiliated Hospital of Xi＇an Jiaotong University School of Medicine, the first Affiliated Hospital of Xi＇an Jiaotong University School of Medicine, Chang＇an Hospital etc as research subjects. They were randomly divided into two groups： I group and 11 group. There were 56 patients in I group who had injected the rAd- P53 to serous cavity. There were 51 patients in Ⅱ group who had injected the cisplatin and IL-2 to serous cavity. All patients accepted chemotherapy, radiation therapy, targeted therapy or other therapy. Efficacy and adverse reactions were recorded in two groups of patients. Results After treatment, 43 patients in Ⅰ group were efficiency and the effective treatment was 76.8%. 18 patients in Ⅰ group were efficiency and the effective treatment was 35.3%. There was a statistically significant difference about the effective rate between group Ⅰ and group Ⅱ by chi-square test, P〈0.001. So the clinical curative effect of using rAd-P53 in the malignant serous cavity effusion group is more effective than that using cisplatin and IL-2 group. The observed adverse reactions included fever, headache, nausea, neutropenia and abnormal liver function. Incidences of adverse effect in I group were fever 30.4%（ 17/56）, headache 3.6%（2/56）, nausea 1.8%（ 1/56）, leukopenia 0% （0/56） and abnormal liver function 7.1% （4/56）. Incidences of adverse effect in 11 group were fever 11.8% （ 6/51 ） , headache 5.9% （ 3/51 ） , nausea 11.8% （ 6/51 ） , leukopenia7.8% （ 4/51 ） and abnormal liver function 15.7% （8/51）. Incidences of adverse effect about fever in I group was higher than that of Ⅱ group, the difference were statistically significant （P〈0.05）. Incidences of adverse effect about leukopenia in I group was lower than that of Ⅱ group, the difference were statistically significant （P〈0.05）. Incidences of adverse effect about headache, nausea and abnormal liver function in l group are lower than that of Ⅱ group respectively, but the difference were not statistically significant （P〉0.05）. On the whole, adverse effect of rAd-P53 was lower than cisplatin and IL-2. Incidences of adverse effect using tAd-P53 in malignant serous cavity effusion is lower than that using cisplatin and IL-2. Conclusion Topical using rAd-P53 in treatment the malignant serous cavity effusion of the advanced lung cancer is superior to using cisplatin and IL-2 to the malignant serous cavity effusion, and has lower in some adverse reactions.