重组人p53腺病毒注射液联合顺铂治疗肺癌所致胸腔积液的临床研究

背景与目的：肿瘤抑制基因p53是目前研究最为广泛和系统的抑癌基因之一,p53基因突变或缺失导致肿瘤的形成。本研究评价重组人p53腺病毒注射液（rAd-p53）导入野生型p53基因抑癌基因治疗同时联合顺铂治疗肺癌所致胸腔积液的临床疗效和毒副反应。方法：将35例肺癌合并胸腔积液患者随机分为联合组和单药组两组。所有患者应用长春瑞滨25mg/m2静脉点滴,第1、8天,每3周重复一次。前述治疗基础上,联合组胸腔内灌入rAd-p531×10^12VP和顺铂注射液40mg/m2;单药组胸腔内灌入顺铂注射液40mg/m2,每周重复一次,连用4次后观察疗效。结果：联合组和单药组的有效率分别为82.35%和50.00%（P〈0.05）;联合组和单药组的一般状况改善率分别为64.70%和33.33%（P〈0.05）;两组患者主要不良反应为发热、胸痛、消化道反应及白细胞减少,联合组发热的发生率高于单药组（P〈0.05）,主要为自限性发热,36h后自行恢复正常。结论：重组人p53腺病毒注射液联合顺铂治疗肺癌所致胸腔积液疗效确切,且毒副反应较低,值得临床推广应用。

Clinical research on recombinant human Ad-p53 injection combined with cisplatin in treatment of malignant pleural effusion induced by lung cancer

Background and Objective. p53 gene is one of cancer suppressor genes and its mutation and deletion induces almost all human cancers. This study was to evaluate the clinical efficacy and toxicity of recombinant human Ad-p53 injection （rAd-p53） combined with cisplatin in treatment of malignant pleural effusion induced by lung cancer. Methods. A total of 35 cases of malignant pleural effusion were randomly divided into the combined group （n=17） and the single-agent group （n=18）. On the basis of systemic treatment （vinorelbine 25 mg/m2, Days 1-8, every 3 weeks）, the combined group were given intracavitary administration of rAd-p53 （1 ×10^12 VP） and cisplatin （40 mg/m2） once a week for 4 weeks. The single-agent group were given the same intracavitary administration as the combined group but without rAd-p53 therapy. Results： The total effective rates in the combined group and the single-agent group were 82.35% and 50.00% （P〈0.05）, respectively. The total modification rates in the combined group and the single-agent group were 64,70% and 33.33% （P〈0.05）, respectively. The toxicities in the two groups were fever, stethalgia, nausea/vomiting and leukopenia. The toxic reaction in combined group was mainly self-limited fever （P〈0.05）, which disappeared automatically after 36 h. Conclusions. rAd-p53 and cisplatin is safe and effective for malignant pleural effusion induced by lung cancer. It is worthy of application in clinical treatment.