不同剂量吡非尼酮防治食管癌放射性肺损伤的临床观察

Clinical Study of Different Doses of Prifenidone in the Prevention and Treatment of Radiation-induced Lung Injury in Esophageal Carcinoma

目的探讨不同剂量吡非尼酮防治食管癌放疗放射性肺损伤的疗效与安全性。方法73例食管癌患者随机分为2组,其中400 mg剂量组41例采用同步放化疗联合吡非尼酮1200 mg/d治疗,200 mg剂量组32例采用同步放化疗联合吡非尼酮600 mg/d+安慰剂6粒/d治疗;随访1年,比较2组患者的肿瘤近期疗效和放射性肺损伤发生率,以及放疗前后肺功能和血清肺损伤相关细胞因子表达水平的变化,并比较治疗不良反应发生率。结果400 mg组肿瘤治疗有效率为90.2%,与200 mg组的84.4%比较,差异无统计学意义(P>0.05)。放疗后6个月和1年400 mg组的肺纤维化发生率分别为9.8%和12.2%,低于200 mg组的28.1%和31.3%(P均<0.05)。放疗后3、6个月及1年2组的第1秒用力呼气量(FEV_(1))、用力肺活量(FVC)和一氧化碳弥散量(DLCO)均低于放疗前,但400 mg组均较同期200 mg组高(P均<0.05);放疗后3个月2组肺损伤相关细胞因子的水平均较放疗前升高,而放疗后6个月及1年均降低,但400 mg组均较同期200 mg组低(P均<0.05)。2组治疗的不良反应发生率比较,无统计学差异(P>0.05)。结论联合使用高剂量吡非尼酮1200 mg/d治疗,对防治食管癌患者放疗导致的放射性肺损伤具有更好的疗效,且耐受性良好。

Objective To evaluate the efficacy and safety of 2 different doses of pirfenidone in the treatment of radiation-induced lung injury in patients with esophageal carcinoma.Methods 73 patients with esophageal cancer were randomly divided into 2 groups,41 patients in the 400mg group were treated with concurrent chemoradiotherapy combined with pirfendione 1200 mg/d,and 32 patients in the 200mg group were treated concurrent chemoradiotherapy combined with pirfendione 600 mg/d and placebo 6 pills/d.The patients were followed up for 1 year to compare the short-term therapeutic effect of tumor and the incidence of radiation-induced lung injury,the changes of lung function and serum levels of lung injury-related cytokines before and after radiotherapy,and the incidence of adverse reactions was compared between the 2 groups.Results The effective rate of 400 mg group was 90.2%,which was not significantly different from that of 200 mg group(84.4%,P>0.05).The incidence of pulmonary fibrosis was 9.8%and 12.2%in 400mg group at 6 months and 1 year after radiotherapy,which were lower than 28.1%and 31.3%in 200mg group respectively(P<0.05).Forced expiratory volume in 1 second(FEV_(1)),forced vital capacity(FVC)and diffusion capacity of carbon monoxide(DLCO)were lower in both groups at 3,6 months and 1year after radiotherapy than those before radiotherapy,the levels of lung injury-related cytokines in 400mg group were higher than those in 200 mg group at the same time(P<0.05),and the levels of lung injury-related cytokines in both groups were higher at 3 months after radiotherapy than those before radiotherapy,and decreased at 6 months and 1 year after radiotherapy,however,the incidence of adverse reactions in the 400 mg group was lower than that in the 200 mg group(P<0.05),and there was no significant difference between the 2 group(P>0.05).Conclusion The combination of higher dose pirfenidone(1200 mg/d)has better efficancy and better tolerance for radiation-induced lung injury in patients with esophageal carcinoma.