胸腔细管插管引流加胸腔内注射基因重组人肿瘤坏死因子治疗胸腔积液Ⅲ期临床分析

Intrathoracic Administration of Recombinant Human Tumor Necrosis Factor-alpha with Closed Small Tube Drainage for Malignant Pleural Effusions: a Phase Ⅲ Clinical Study

目的:评价胸腔细管插管加胸腔内注射基因重组人肿瘤坏死因子(rhTNF)治疗恶性胸腔积液的疗效及毒性。方法:2001年10月-2004年9月对46例中、大量恶性胸腔积液患者(原发肿瘤其中肺癌29例、乳腺癌7例、宫颈癌2例、卵巢癌1例、恶性淋巴瘤3例、胃癌4例)先用胸腔细管插管作闭式胸腔引流,待胸腔积液流完后口服消炎痛25 mg,0.5 h后向胸腔内注入TNF 300万单位,封闭引流管,24 h后将引流管接上封闭式引流瓶,如仍有积液流出,积液流完后再向胸腔内注射TNF 300万单位,每周重复上述过程3次,3-4周后拨除引流管或24 h引流量低于150 ml即拔除引流管。结果:①疗效:本组46例患者中完全缓解(CR)27例,占58.70%,部分缓解(PR)17例,占36.96%,稳定(NC)3例,占6.52%,无病情进展;有效率(CR+PR)93.48%。②副反应:胸痛19例(均为Ⅰ-Ⅱ度,占41.30%),发热9例(全部为Ⅰ度,19.56%),寒战2例(Ⅰ度,4.35%),余副反应(如气胸、感染、胸膜反应、水肿、血压下降、脉压差变小、心律失常、肝、肾功能异常等)均未发现。结论:胸腔细管插管闭式胸腔引流加脓胸内注射TNF治疗恶性胸腔积液有较高的疗效,且副反应较小。

Objective： To assess the efficacy and safety of intrathoracic administration of recombinant human tumor necrosis factor-alpha （rhTNF-α） with closed small tube drainage for the treatment of malignant pleural effusions. Methods： From October 2001 to September 2004, 46 patients with moderate to volume of malignant pleural effusions （29 cases of lung cancer, 7 breast cancer, 2 cervix cancer, 1 ovarian cancer, 3 malignant lymphoma and 4 gastric carcinoma） had been studied. Closed small tube drainage was performed in all patients. After complete drainage, 25 mg indomethacin was administered, and half an hour later, 3 million units rhTNF-α was injected intraplurally through the small tube before the drainage was closed. Twenty hours later, the effusion was drained again. If there were still effusions, the intrathoracic administration of rhTNF-α was repented. Afterwards, the above treatment was repented three times per week for ：3-4 weeks or until the drained effusions were less than 150 ml in 24 hours. Results： ① Efficacy： Of the 46 patients included, complete response （CR） was shown in 27 patients （58.70%）, partial response （PR） in 17 （36.96%）, stable disease in 3 （6.52%） and progressive disease in no patient. The overall response rate （CR＋PR） was 93.48%. ② Side-effects： 19 patients （41.30%） had chest pain （grade Ⅰ-Ⅱ ）, fever （grade Ⅰ ） and rigor （grade Ⅰ ） were observed in 9 （19.56%） and 2 patients （4.35%） respectively. Other side-effects, such as pneumothorax, infection, pleural response, edema, low blood pressure, low pulse pressure, arrhythmia, liver and kidney dysfunction, etc. , were not observed. Conclusion： Intrathoracic administration of rhTNF-α with closed small tube drainage is effective in the treatment of malignant pleural effusions and with little toxicity.