重组人p53腺病毒注射液联合胸腔热灌注化疗治疗肺癌所致胸腔积液的临床研究

摘要

Objective To evaluate the clinical efficacy and toxicity of recombinant human Ad p53 injection( rAdp53 )combined with continuous hyperthermic perfusion in treatment of malignant pleural effusion induced by lung cancer.Methods A total of 43 cases of malignant pleural effusion were randomly divided into the combined group( n= 22 ) and the single agent group( n =21 ). On the basis of systemic treatment( paclitaxel 135 mg/m2 on day 1, every 3 weeks ), the combined group were given intra-cavity administration of rAd-p53( 1 × 1012 VP )and coelom hyperthermia perfusion extracorporeal circulatory system in combination with cisplatin( 40 mg/m2 )once a week for 3 weeks. The single agent group was given the same intra-cavity administration as the combined group but without rAd-p53 therapy. Before and after treatment the quality of life for non-small cell lung patients were evaluated with the Chinese versions of European Organization for Research and Treatment of Cancer ( EORTC )Quality of Life Questionnaires( QLQ-C30 and QLQ-LC13 ). Results The total effective rates in the combined group and the single agent group were 86.4％ and 57.2％ respectively, there was significant difference between the two groups( P ＜ 0.05 ). After treatment, the mean scores of four functional scales( physical, emotional, cognitional and social ) and the mean score of global qualtiy of life in the combined group were improved more obviously than in the single agent group( P ＜ 0.05 ). The mean scores of main general symptoms fatigue decreased more obviously than in the single agent group, the mean scores of disease related symptoms ( coughing, dyspnea ) decreased more obviously than in the single agent group( P ＜ 0.05 ). The toxicities in the two groups were fever( P ＜ 0.05 ), nausea/vomiting and leucopenia( P ＞ 0.05 ). The toxic reaction in combined group was mainly self-limited fever, which disappeared automatically after 36 hours. Conclusion rAd-p53 in combination with continuous hyperthermic perfusion is safe and effective for malignant pleural effusion induced by lung cancer. It is worthy of application in clinical treatment.%目的 评价重组人p53 腺病毒注射液(rAd-p53)联合胸腔热灌注化疗治疗肺癌合并胸腔积液的临床疗效、不良反应及对生活质量的影响.方法 将43例肺癌合并胸腔积液患者随机分为2组:联合组(n=22)和单药组(n=21).所有患者应用紫杉醇135 mg/m2静脉滴注(第1天),每3 周重复1次;同时胸腔内给予顺铂注射液40 mg/m2热灌注化疗,每周重复1次,连用3次.联合组每次热灌注化疗后胸腔内灌入rAd-p53(1×1012 VP),每周重复1次,连用3次;对治疗前、后症状和生活质量的改变进行评价.结果 联合组和单药组的有效率分别为86.4%和57.2%,2组比较差异有统计学意义(P＜0.05);联合组患者功能状态(躯体、情感、认知、社会)及整体生活质量评分值均显著增加,与单药组相比差异有统计学意义(P<0.05).联合组治疗后乏力症状评分、肺癌相关症状(咳嗽、呼吸困难)评分均降低,与单药组相比差异均有统计学意义(P<0.05).2组患者主要不良反应为发热、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),后二者无明显差异(P﹥0.05).结论 重组人p53 腺病毒注射液联合胸腔热灌注化疗治疗肺癌所致胸腔积液疗效确切,同时可改善患者生活质量,且不良反应较少,值得临床推广应用.