益中生血胶囊治疗肿瘤相关性贫血的临床研究

【作者】 田丽丽；

【导师】 陈信义；

【作者基本信息】 北京中医药大学 ， 中西医结合临床内科， 2007， 博士

【摘要】 1目的恶性肿瘤是严重危害人们身体健康的常见疾病,常常引起急、慢性失血以及营养不良性贫血,放射治疗和化学治疗是目前肿瘤治疗常用手段,骨髓抑制是它们常见的毒副作用,往往更加重患者的贫血症状,因此贫血是恶性肿瘤患者的常见症状,它不但显著降低患者的生存质量,而且严重影响放化疗效果和预后,因此成为晚期肿瘤临床治疗的一个方面。目前,输血和应用EPO(重组人红细胞生成素)是治疗肿瘤相关性贫血的重要手段,然而费用高、疗效短,副作用大,限制了其临床使用,肿瘤相关性贫血属中医的“血虚证”、“血枯”、“血劳”等证范畴,血的生成与心、肝、脾、肾等脏腑有关,而其中脾起主要作用。我们认为病机关键为脾胃虚弱、气血两虚,故采用健脾养胃,益气生血的益中生血胶囊治疗肿瘤相关性贫血,探讨中医药治疗肿瘤相关性贫血的优势。2方法根据临床研究方案,在北京地区2家三级甲等医院,经临床、病理学和/或细胞学证实为晚期肿瘤,再根据贫血严重程度、卡氏评分,将合格病例随机分试验组与空白对照组。治疗2个疗程结束时,共收集有效病例47例,试验组21例,空白组26例。空白对照组:当血红蛋白≤60g/L时可输血,除必要的对症支持治疗外,不应用其他影响疗效判定的药物(包括含益气养血类的中药汤剂)。试验组:在空白组治疗基础上,给予益中生血胶囊3粒/次,口服,一日二次,连续用药4周为一个疗程,二个疗程后判定疗效。合并化疗者,同步应用益中生血胶囊。采用前瞻性、同期、随机对照方法,在第一、二个疗程即四、八周时分别观察患者外周血象、临床主症、卡氏评分、放化疗毒副反应及完成率,客观地评价了益中生血胶囊治疗肿瘤相关性贫血的临床疗效。3结果结果发现:①中医证候:试验组患者经治疗,10例(47.62%)患者临床症状明显改善,7例(33.33%)部分改善。19例(90.48%)患者神疲乏力、少气懒言、气短、食欲不振、心悸、面色、头晕目眩等症状得到改善,生活质量提高。空白组患者经治疗,5例(19.23%)患者临床症状明显改善,8例(30.77%)部分改善。13例(50%)患者神疲乏力、少气懒言、食欲不振、心悸、面色、头晕目眩等症状得到改善。试验组中医症状的有效率明显高于对照组。②Hb:试验组Hb水平呈上升趋势,四周与治疗前相比,无统计学意义(P>0.05),八周与治疗前相比,有统计学意义(P<0.05),与治疗前相比明显上升,呈增高趋势;空白组八周时Hb水平与治疗前和4周时比较均明显下降,有统计学意义(P<0.05)。经治疗,两组的Hb水平差距逐渐加大(0.83>-0.74>-2.06)。③RDW:试验组RDW逐渐升高,八周与0周比,有统计学意义(P<0.05);空白组逐渐下降,八周与0周比,有统计学意义(P<0.05)。④外周血象:在4、8周时两组病例对比,结果均为:RBC、Hb、HCT有统计学意义(P<0.05);MCH、MCHC、MCV、RDW、WBC、PLT无统计学意义(P>0.05)。⑤QOL:试验组逐渐升高,八周与0周对比,有统计学意义(P<0.05),说明试验组在8周后生活质量上升。空白组逐渐下降,8周与0周对比,有统计学意义(P<0.05),说明空白组在8周后生活质量下降。⑥卡氏评分:治疗8周与治疗前KPS评分变化情况比较,空白组KPS评分增加者0例(0.00%),试验组增加4例(19.05%);试验组KPS评分无变化者11例(52.38%),高于空白组7例(26.92%);空白组KPS评分下降者8例(30.77%),也明显高于试验组0例(0.00%)。两组病例治疗8周与治疗前KPS评分变化比较,经χ2检验,有统计学意义(P<0.05)。试验组病例治疗后KPS评分总体增加。⑦化疗导致的白细胞减少、血红蛋白下降、血小板减少、恶心呕吐及肝肾功能损害情况两组之间均无统计学意义(P>0.05)。⑧经因子分析计算出SF-36表中试验组、空白组各个患者在0、4、8周的生活质量得分。然后进行各组自身生活质量之间的比较。试验组8周后生活质量得到明显提高,而空白组明显下降。⑨多元线性回归分析表明,血红蛋白水平与TNM分期和化疗周期均呈线性负相关。由标准回归系数看出,TNM分期对血红蛋白的影响较大。4结论根据以上结果,本项研究结论如下:①脾胃虚弱、气血两虚是肿瘤相关性贫血的重要病机特征;②益中生血胶囊能有效提高肿瘤相关性贫血患者的血红蛋白计数,并能改善患者的临床症状和生活质量,已达到统计学意义;③显示出今后治疗肿瘤相关性贫血的趋势。更多还原

【Abstract】 1 ObjectiveMalignant tumor is the common disease which seriously does harm to people’s physical health,and can usually cause acute、chronic blood loss and malnutritional anemia.Radiotherapy and chemotherapy are commonly means of oncotherapy at the present. Myelosuppression is their frequent harmful side effect,which often aggravates patient’s anemia symptom. Accordingly anemia is malignant tumor patients’the common symptom. Not only anemia can significant degrade patients’quality of life,but also seriously impact the effect and prognosis of radiotherapy and chemotherapy, therefore,it becomes a aspect of the therapy of advanced stage tumor clinic.Now blood-transfusion and the application of EPO (recombinant human erythropoietin) are the important method of the treatment of tumor-related anemia, but their cost is high , therapeutic effect is short and side effect is great,which limit their clinic usilization. In the chinese medical science tumor-related anemia belongs to the scale of“xue xu zheng”、“xue gu”、“xue lao”and so on. The production of blood has something to do with the entrails of xin、gan、pi and shen,among which pi is playing principal role. We think the key pathogenesis is the weakness of the pi and wei and the deficiency of qi and xue,so we adopt the yizhong shengxue capsule which can Jianpi Yangwei and Yiqi Shengxue to treat tumor-related anemia.By means of the capsule of Yizhong Shengxue we approach the superiority corresponding the treatment of tumor-related anemia in the field of Chinese medicine.2 MethodsOn the basis of clinical research project,qualified cases were on principle of advanced stage tumor testified by clinic、pathology and/or cytology,according to anemia severe degree、the scores of KPS ,and were randomly divided into test group and blank group in two three-grade A grade hospitals in Beijing . When two periods of treatment were over,there were 47 effective cases together.They were randomly divided into two groups including 21 cases in the test group and 26 cases blank group.Blank group:Patients were given necessarily supportive treatment including blood transfusion when their hemoglobin was not so much as 60g/L.The medicine connecting the assessment of therapeutic effect would not be applied(containing Yiqi Yangxue generic Chinese crude drug broth).On the base of the treatment of the blank group,test group were given Yizhong Shengxue capsule three grain one time two times one day by mouth. The medicine would be continuously used four weeks as one course of treatment.We objectively assessed the clinical effect of Yizhong Shengxue capsule suffering from tumor-related anemia by means of prospectively synchronized and randomized control.We observed patients’peripheral blood hemogram、clinical master sign、the score of KPS、harmful side effect and completion rate of radiotherapy and chemotherapy when they were at the first and second course of treatment or at four and eight week.3 ResultsThe results showed:①Chinese medical science symptom:Test group:After treatment 10 cases of them showed significant improvement(47.62%),7 of them had partial amendment(33.33%). The patients’symptom about 80.95% involving Shen pi Fali、Shaoqi Lanyan、Shiyu Buzhen、Xinji、Touyun Muxuan and so on had showed significant improvement. Their quality of life had been improved.Blank group: After treatment 5 cases of them showed significant improvement(19.23%),8 of them had partial amendment(30.77%). The patients’symptom about 50% involving Shen pi Fali、Shaoqi Lanyan、Shiyu Buzhen、Xinji、Touyun Muxuan and so on had showed significant improvement. Their quality of life had been improved. Effective powervival rate of Chinese medical science symptom in test group is higher than Blank group.②Hb: Test group:The level of Hb showed upgrade tendency. The statistical significance (P>0.05) wasn’t showed when the level of Hb at four week was compared to treatment before.The statistical significance (P<0.05) was showed when the level of Hb at eight week was compared to treatment before. The level of Hb at eight week was compared to treatment before and showed increased tendency. Blank group: The level of Hb at eight week was compared to treatment before and four week.Their conclusion was both obviously decreased and showed statistical significance(P<0.05).After therapy the distance of level of Hb between two groups was more and more(0.83>-0.74>-2.06).③RDW:Test group: The level of RDW showed upgrade gradually. The statistical significance (P<0.05) was showed when the level of RDW at eight week was compared to treatment before.Blank group: The level of RDW submitted fall-off .The statistical significance (P<0.05) was showed when the the level of RDW at eight week was compared to treatment before.④Peripheral hemogram: The statistical significance (P<0.05) was showed when the level of RBC、Hb and HCT of the test group at four and eight week were compared to the blank group respectively. The statistical significance (P>0.05) wasn’t showed when the level of MCH,MCHC ,MCV RDW、WBC、and PLT of the test group at four and eight week were compared to the blank group respectively.⑤The quality of life (QOL) : Test group:The level of QOL showed upgrade gradually. The statistical significance ( P<0.05) was showed when the level of QOL at eight week was compared to 0 week,which approved the QOL of the test group rose up eight weeks later;Blank group: The level of QOL submitted fall-off tendency. The statistical significance (P<0.05) was showed when the level of QOL at eight week was compared to 0 week,which approved the QOL of blank group slowed down eight weeks later.⑥The score of KPS :The variation of the comparison betweeen eight week and pro-treatment in the score of KPS as followed: There were a little increase in the score of KPS between the test group and blank group.There were 0 case for the blank group and 4 cases for the test group,19.05% and 0.00% respectively;Little change had taken place between two groups in the score of KPS. There were 7 cases for the blank group and 11 cases for the test group,26.92% and 52.38% respectively. The unvariation of the score of KPS of the test group was higher than the blank group; There was a decrease in the score of KPS integrated test and blank group,8 cases for the blank group 0 case for the test group ,30.77% and 0.00% respectively. The descender of the score of KPS of the blank group was higher than the test group. By means ofχ2 test, whole curative effect comparison betweeen eight week and pro-treatment in the score of KPS showed statistical significance (P<0.05).After treatment whole score of KPS in the cases of test group was rise up.⑦Toxic and side effects caused by chemotherapy including decrease of white blood cell count,Hb and platelet,nausea,vomit and the functional lesion of liver or kidney showed no statistical significance (P>0.05)between two groups.⑧Factor analysis calculated the grade of QOL of every patient betweeen the test group and blank group in SF-36 tab,when they were at 0、4、8 week respectively. By means of the grade of QOL of every patient ,we could made themselves comparison of the grade of QOL among each group when they were at 0、4、8 week.The QOL of the test group at eight week was obviously elevated,but the blank group was seriously breakdown.⑨Analysed by multiple linear regression , the level of Hb is negative linear correlation with TNM grade and chemotherapy cycles. From standard regression coefficient,we could know TNM grade make more action.4 ConclusionAccording to the results above-mentioned,the conclusion of the study are as the follows:①The key pathogenesis character about tumor-related anemia is Piwei Xuruo、QiXue Liangxu;②Yizhong Shengxue capsule can effectively raise hemoglobin count、alleviate symptoms and improve QOL of patients suffering from tumor-related anemia and has reached the statistical significance.③The tendency on effect for tumor-related anemia appears in the future.更多还原