浙贝母颗粒干预难治性急性白血病围化疗期临床疗效研究

【作者】 李冬云；

【导师】 陈信义； 蒋红玉；

【作者基本信息】 北京中医药大学 ， 中西医结合临床， 2005， 博士

【摘要】 难治性急性白血病是临床治疗中的难题。其主要原因是白血病在接受化疗过程中产生了多药耐药性(MDR)。针对耐药白血病目前临床尚无理想的治疗药物,现有的西药逆转剂或由于脏器毒性过大,或由于作用靶点单一等原因,使临床应用受限。我们通过近些年来基础研究证实,临床常用的化痰散结中药浙贝母提取的生物碱体外及动物实验均有逆转白血病多药耐药的生物活性,其能增加耐药的急性白血病细胞内抗癌药物浓度,降低P-糖蛋白(PgP)蛋白表达。临床预实验研究也证实,常规化疗方案伍用浙贝母粉用于急性白血病临床治疗,其临床完全缓解率明显高于对照组。尤其对难治及复发白血病患者临床缓解率更佳。为系统评价浙贝母伍用化疗药物治疗难治性急性白血病临床疗效,我们在既往临床研究基础上,以浙贝母颗粒饮片替代浙贝母生药粉,以难治性急性白血病患者为研究对象,以临床缓解率为主要评价指标,并拟订统一临床观察方案与疗效评估标准,进行了多中心临床观察。论文资料来源于8家三级甲等医院于2004年1月-2005年2月间所观察的72例难治性急性白血病患者。其中,自动中止治疗2例,资料不完整6例,共有64例可统计疗效。因本课题为首发基金重大联合攻关项目,临床试验采用随机双盲、双模拟研究方法,其治疗组与对照组均为中药颗粒饮片,课题尚未完成,在无法揭盲的情况下难以区分治疗组与对照组。故只能按一组统计疗效。初步的临床研究结果显示,临床完全缓解(CR)率为34. 4%,有效率62. 5%。与国内102篇、国外68篇难治性急性白血病文献资料比较,有效率相似。浙贝母颗粒饮片实际疗效有待揭盲后评估。与国内外文献比较,本项研究创新点在于:“在国内首次以中药制剂干预难治性急性白血病围化疗期临床疗效研究,并系统评价中药伍用化疗药物治疗难治性急性白血病的临床疗效与不良反应,同时,将PgP蛋白作为探索性检测指标,采用随机双盲、多中心研究方法具有明显的科学性。其研究结果对我们后续的临床研究具有重要的指导作用”。该项研究如能获得预期结果,在丰富和发展难治性急性白血病多药耐药性发生过程中的中医“痰郁”理论、提高难治性白血病临床疗效,让更多的患者受益方面具有重要的现实意义与潜在的临床应用价值。同时,将有可能改观难治性急性白血病临床无药可医的被动局面。更多还原

【Abstract】 Refractory acute leukemia (RAL) is a tough problem in clinical treating. The first causation lies in the formation of multidrug resistance (MDR) in leukemic cell during chemotherapy process. There are no satisfactory clinical treating drugs now to aim directly at MDR. Present reversal agents of drug resistance in Western medicine are limited in clinical application because their organ noxious property is serious and only have single effect target.Our recent basal research confirms that the alkaloid extracted from Thurberg Fritillary Bulb, a frequently used Chinese medicine with function of eliminating sputum and removing stasis, possess the biological activity of reversing MDR in some vitro and animal trials, can increase the density of chemotherapeutics in leukemic cell and degrade the expression of Pgp. Clinical preliminary experiment also confirms that the complete remission (CR) rate of treat group using routine chemotherapy combined with Thurberg Fritillary Bulb flour is notable higher than control group. Especially the clinical remission rate of refractoriness and palindromic AL patient are more excellent. Based on above-mentioned findings, in order to systematically evaluate the clinical curative effect of Thurberg Fritillary Bulb combined with chemotherapy in the treatment of RAL, we substituted Thurberg Fritillary Bulb crude drug powder with Thurberg Fritillary Bulb grains cut crude drug. Taking RAL patients as object and clinical remission rate as main evaluation indicatrix, we instituted consistent clinical research schema and curative effect appraisal denom and carried out multicentre clinical observation.Thesis data came from eight third class grade A hospitals including 72 RAL cases observed from 04, Jan to 05, Feb. Among them, 2 cases discontinued treating automatically, 6 cases had no complete data. There were 64 cases total that can calculate curative effect. This test adopting random, double-blind and ambi-imitation method. Both treat group and control group are taking Chinese medicine grains cut crude drug. Because the test is still not done, it’s impossible to expose and it’s hard to discriminate treat group and control group. So we can only calculate curative effect according to group. Preliminary clinical finding demonstrates that clinical CR rate is 34.4%, effective power rate is 62.5%. The result is alike to domestic documents about RAL (102 cases) and abroad documents (68 cases).Comparing with domestic and abroad records, this research has some innovations. One is that it’s the first domestic study of clinical curative effectthat interferes mainly with Chinese medicine in RAL ambi-chemotherapy stage. At the same time, it systematically evaluates the clinical curative effect and adverse effect of Chinese medicine combined with chemotherapeutics in treating RAL. Another is that taking Pgp as an exploration detection target. Furthermore, using random, double-blind and multicentre method make this test possess conspicuous confidence. The third one is that its findings will show us the direction of our subsequent clinical research. If the test procures the expectant consequence, it will have significant practical importance and potential value of practicability in developing the theory of phlegmatic stagnation in the aspect of the occurrence of MDR in RAL, enhancing the curative effect of RAL and making more patents profit from it. All together, it’s capable to change the passive appearance that there are no appropriate drugs aimed at RAL.更多还原