中医药联合辅助化疗治疗早期非小细胞肺癌的随机双盲对照临床研究

A double-blind and randomized controlled clinical trial of traditional Chinese medicine combined with adjuvant chemotherapy for early stage non-small cell lung cancer

目的探讨中医药联合辅助化疗的综合治疗方案对完全性手术切除非小细胞肺癌（NSCLC）的临床效果。方法采用前瞻性随机双盲对照研究，入组100例患者，将其随机分为中医药联合辅助化疗组（试验组）和单纯辅助化疗组（对照组）。在化疗期间前者同时服用中药颗粒制剂，后者服用安慰剂。化疗方案采用NC方案：长春瑞滨25mg／m^2第1、8天；卡铂[AUC=5mg／（ml·min）]，第1天。采用重复测量法比较两组在治疗前、第4个周期化疗后或末次化疗后第3周的生命质量评分和中医症状评分，用Kaplan—Meier法计算无病生存（DFS）期，绘制生存曲线。结果对照组的中位DFS为23．98个月，试验组中位DFS为36．00个月，两组差异有统计学意义（P=0．047）。分层分析显示，Ⅰ～Ⅱ期患者中，试验组患者的DFS（35．32个月）较对照组（28．82个月）延长（P=0．037）。在ⅢA期患者中，两组DFS差异无统计学意义（P=0．555）。试验组治疗后中医症状量表评分下降，与对照组相比，差异有统计学意义（P=0．022）。Cox多因素分析显示肿瘤分期是DFS的主要影响因素（P=0．000）。患者躯体功能、角色功能、情绪功能、总健康状况在治疗后都较治疗前有明显改善（P〈0．05）。症状相关项目中，疲乏、疼痛、失眠随术后时间的延长及辅助治疗的实施而逐渐好转，但两组生命质量差异均无统计学意义（P〉0．05）。试验组8例患者出现Ⅲ～Ⅳ度不良反应，发生率低于对照组（14例），差异有统计学意义（P=0．045）。结论中西医联合治疗能延长完全性手术切除NSCLC患者的DFS，降低复发率，减轻化疗引起的不良反应，改善临床症状和中医症状。

Objective To evaluate the efficacy of adjuvant chemotherapy combined with traditional Chinese medicine （TCM） on the prevention of the radical resected non-small cell lung cancer （NSCLC） relapse and metastasis. Methods A double-blind and randomized controlled clinical trial including 100 patients with radical resected NSCLC enrolled was designed. The subjects were randomly divided into two groups, adjuvant chemotherapy group combine with placebo （control group） and adjuvant chemotherapy combined with TCM group （trial group）. 4 cycles of adjuvant chemotherapy [NC regimen： vinorelbine 25 mg/m^2, dl and d8 combined with carboplatin AUC = 5 mg/（ml.min）, dl] were used after surgery. The curve of disease free survival （DFS） was drew by Kaplan-Meier test. Two groups＇ curative effects were compared by repeated measurement of quality of life （QOL） score and TCM symptom score before, during and after treatment. Results The median DFS of trail group was longer than that of control group （36.00 months vs 23.98 months, P = 0.047）. Stratification analysis showed that DFS of trial group was longer than that of control group for the Ⅰ -Ⅱ stage patients （35.32 months vs 28.82 months, P = 0.037）, and DFSs of both groups for patients in ⅢA stage were no difference （P = 0.555）. TCM symptom complex score of the trail group was decreased after treatment and had a significantly statistical difference （P = 0.022）. Cox multivariate analysis showed that the tumor stage was the main influence factor of DFS （P = 0.000）. Physical function, role function, emotional function, and overall health status were significantly improved after treatment （P 〈 0.05）. In the related symptoms, fatigue, pain, insomnia were gradually improved with the extension of treatment time and the implementation of the supplementary treatment, but there was no significant difference in the QOL between the two groups. In the trail group, there were 8 cases of adverse events, which was less than that in the control group （14 cases） （P = 0.045）. Conclusion Adjuvant chemotherapy combined with TCM can prolong the DFS of patients with radical resected NSCLC, reduce recurrence rate, relieve the adverse effects of chemotherapy, and improve the clinical and Chinese medical symptoms.