复方浙贝颗粒辅助化疗治疗难治性急性白血病临床有效性及安全性研究
摘要
目前,轮换化疗方案与加大抗癌药物用量是难治性急性白血病主要治疗方法,但临床缓解率仅30%一45%,且抗癌药物严重的不良反应可导致患者生存质量下降。因此,在难治性急性白血病治疗领域需要解决三大科学问题,其一是提高临床缓解率；其二是克服轮换化疗方案或加大抗癌药物用量导致的相关并发症；其三是改善围化疗期患者生存质量。该课题以既往临床试验为背景资料,依据“十一五”国家科技支撑计划项目需求以及项目主管部门相关规定,在反复征求多位临床、评价、统计、管理专家意见基础上,进一步优化了以“复方浙贝颗粒”为主要干预措施的临床实施方案。
研究目的：通过规范化的临床试验,验证以“复方浙贝颗粒”为主的中医干预治疗方案提高难治性急性白血病围化疗期临床缓解率疗效,并依据临床试验结果,制定难治性急性白血病围化疗期中医药干预治疗方案,为提高难治性急性白血病临床疗效提供依据。
研究方法：以难治性急性白血病患者为研究对象,依据科技部关于“国家科技支撑计划”要求与GCP规范,采用随机双盲、安慰剂对照、多中心协作临床研究原则,在围化疗期实施中医干预治疗方案与西医标准化疗方案联合应用,通过对临床缓解率(疗效评定金指标)、安全性指标进行综合分析、科学评价,为提高难治性急性白血病临床疗效提供易于推广应用的中医干预治疗方案。
研究结果：全部病例资料来自于7家三级甲等医院为2007年5月至2009年11月间所观察的病例238例难治性急性白血病患者。揭盲后,进入疗效统计的病例共197例,治疗组(复方浙贝颗粒组)98例,对照组(模拟剂组)99例。治疗组：完全缓解(CR)3例,占3.06%；骨髓象缓解(CRi)30例,占30.61%；部分缓解(PR)18例,占18.37%；未缓解(NR)47例,占47.96%；完全缓解率(CR+CRi)33例,占33.67%；总有效率(CR+CRi+PR)51例,占52.04%。对照组：完全缓解(CR)3例,占3.03%；骨髓象缓解(CRi)21例,占21.21%；部分缓解(PR)13例,占13.13%；未缓解(NR)62例,占56.88%；完全缓解率(CR+CRi)24例,占24.24%；总有效率(CR+CRi+PR)37例,占37.37%。两组病例疗效完全缓解率及总有效率比较,经卡方检验,均具有统计学意义(P<0.05),治疗组优于对照组。
结论：复方浙贝颗粒配合化疗应用可明显提高难治性急性白血病的临床缓解率,可能会减轻化疗药物的血液学毒性,临床使用中未发现其对尿常规、便常规、肝肾功能和心电图等安全性指标有不良影响,具有较好的临床安全性,应进一步进行深入研究。
创新点：①在国内按照GCP规范,通过随机双盲、安慰剂对照、多中心临床试验,系统观察复方浙贝颗粒配合化疗提RAL临床疗效。②将临床缓解率作为中医干预方案治疗RAL临床疗效评价的终极指标。③增加CRi作为评价难治性急性白血病疗效标准。
At present,the rotation of chemotherapy and increase of the dosage of anticancer drugs are the main treatment of refractory acute leukemia,but the clinical remission rate was only 30%-45%,and the serious adverse reactions caused by anti-cancer drugs are responsible of the decrease in the quality of patients' lives.Therefore, three main scientific problems exist in the treatment of refractory acute leukemia, the first is to improve the clinical remission rate;the second is to deal with the complications due to rotation of the chemotherapy or greater amount of anti-cancer drugs;the third is to improve the quality of life in patients of before and after chemotherapy.We choose previous clinical trials as the background information of the research. After repeatedly consulting a number of experts on clinic,evaluation,statistics and management, according to the requirements and the relevant provisions of the Key Projects in the National Science & Technology Pillar Program during the Eleventh Five-Year Plan Period,we further optimized the treatment regimen using Compound Fritillary Bulb Granule(CFBG) as the main clinical intervention.
Objective:Through the standardization of clinical trials,Verify the "CFBG" based intervention program to improve refractory acute leukemia clinical remission rate of around chemotherapy efficacy.And based on clinical trial results,Refractory acute leukemia developed by Chinese interventions combined with standard chemotherapy of western medicine,in order to enhance clinical efficacy in refractory acute leukemia with evidence.
Methods:the patients with refractory acute leukemia as subjects,According to the requirements of the "National Support Scheme" and GCP,using randomized double-blind,placebo-controlled and multi-center clinical research as principles, we combine Chinese interventions with standard chemotherapy of western medicine before and after chemotherapy,analyze and evaluate clinical remission rate (gold index of efficacy evaluation),in order to provide easy-to-intervention TCM program improving the clinical efficacy of refractory acute leukemia.
Results:All cases data (238 cases of patients with refractory acute leukemia) were collected from 7 tertiary hospitals from May 2007 to November 2009.After exposing blind,197 cases were statistically analyzed,including 98 cases in the treatment group (CFBG group),and 99 cases in the control group (simulated agent group).Treatment group:complete remission (CR) 3 cases,accounting for 3.06%;bone marrow remission (CRi) 30 cases,accounting for 30.61%;partial remission(PR) 18 cases,accounting for 18.37%;no remission(NR) 47 cases,accounting for 47.96%;complete remission rate (CR+CRi) 33 cases,accounting for 33.67%;the total effective rate(CR+CRi+PR) 51 cases,accounting for 52.04%.Control group:complete remission (CR) 3 cases, accounting for 3.03%;bone marrow remission (CRi) 21 cases,accounting for 21.21%; partial remission (PR) 13 cases,accounting for 13.13%;no remission (NR) 62 cases, accounting for 56.88%;complete remission rate (CR+CRi) 24 cases,accounting for 24.24%;the total effective rate (CR+CRi+PR) 37 cases,accounting for 37.37%.After chi-square test,the complete remission rate and the effect of the total effective rate of two groups were statistically significant(P<0.05),and the treatment group were higher than the control group.
Conclusion:CFBG combined with chemotherapy can improve significantly the clinical remission rate of refractory acute leukemia,and can decrease the hematological toxicity of chemotherapy.In the clinical use,no adverse affects were found in the safety index,such as urine routine,occult routine,liver and kidney function and electro-cardiogram.So we should further study on it.
Innovation:①the first time to systematically observe the clinical efficacy of CFBG combined with chemotherapy, in accordance with GCP standards and through randomized double-blind, placebo-controlled, multicenter clinical trial②the first time to use clinical remission rate as the ultimate clinical evaluation index of Chinese intervention in the treatment of the RAL.③ncrease CRi as the evaluation criteria for refractory acute leukemia.
研究目的：通过规范化的临床试验,验证以“复方浙贝颗粒”为主的中医干预治疗方案提高难治性急性白血病围化疗期临床缓解率疗效,并依据临床试验结果,制定难治性急性白血病围化疗期中医药干预治疗方案,为提高难治性急性白血病临床疗效提供依据。
研究方法：以难治性急性白血病患者为研究对象,依据科技部关于“国家科技支撑计划”要求与GCP规范,采用随机双盲、安慰剂对照、多中心协作临床研究原则,在围化疗期实施中医干预治疗方案与西医标准化疗方案联合应用,通过对临床缓解率(疗效评定金指标)、安全性指标进行综合分析、科学评价,为提高难治性急性白血病临床疗效提供易于推广应用的中医干预治疗方案。
研究结果：全部病例资料来自于7家三级甲等医院为2007年5月至2009年11月间所观察的病例238例难治性急性白血病患者。揭盲后,进入疗效统计的病例共197例,治疗组(复方浙贝颗粒组)98例,对照组(模拟剂组)99例。治疗组：完全缓解(CR)3例,占3.06%；骨髓象缓解(CRi)30例,占30.61%；部分缓解(PR)18例,占18.37%；未缓解(NR)47例,占47.96%；完全缓解率(CR+CRi)33例,占33.67%；总有效率(CR+CRi+PR)51例,占52.04%。对照组：完全缓解(CR)3例,占3.03%；骨髓象缓解(CRi)21例,占21.21%；部分缓解(PR)13例,占13.13%；未缓解(NR)62例,占56.88%；完全缓解率(CR+CRi)24例,占24.24%；总有效率(CR+CRi+PR)37例,占37.37%。两组病例疗效完全缓解率及总有效率比较,经卡方检验,均具有统计学意义(P<0.05),治疗组优于对照组。
结论：复方浙贝颗粒配合化疗应用可明显提高难治性急性白血病的临床缓解率,可能会减轻化疗药物的血液学毒性,临床使用中未发现其对尿常规、便常规、肝肾功能和心电图等安全性指标有不良影响,具有较好的临床安全性,应进一步进行深入研究。
创新点：①在国内按照GCP规范,通过随机双盲、安慰剂对照、多中心临床试验,系统观察复方浙贝颗粒配合化疗提RAL临床疗效。②将临床缓解率作为中医干预方案治疗RAL临床疗效评价的终极指标。③增加CRi作为评价难治性急性白血病疗效标准。
At present,the rotation of chemotherapy and increase of the dosage of anticancer drugs are the main treatment of refractory acute leukemia,but the clinical remission rate was only 30%-45%,and the serious adverse reactions caused by anti-cancer drugs are responsible of the decrease in the quality of patients' lives.Therefore, three main scientific problems exist in the treatment of refractory acute leukemia, the first is to improve the clinical remission rate;the second is to deal with the complications due to rotation of the chemotherapy or greater amount of anti-cancer drugs;the third is to improve the quality of life in patients of before and after chemotherapy.We choose previous clinical trials as the background information of the research. After repeatedly consulting a number of experts on clinic,evaluation,statistics and management, according to the requirements and the relevant provisions of the Key Projects in the National Science & Technology Pillar Program during the Eleventh Five-Year Plan Period,we further optimized the treatment regimen using Compound Fritillary Bulb Granule(CFBG) as the main clinical intervention.
Objective:Through the standardization of clinical trials,Verify the "CFBG" based intervention program to improve refractory acute leukemia clinical remission rate of around chemotherapy efficacy.And based on clinical trial results,Refractory acute leukemia developed by Chinese interventions combined with standard chemotherapy of western medicine,in order to enhance clinical efficacy in refractory acute leukemia with evidence.
Methods:the patients with refractory acute leukemia as subjects,According to the requirements of the "National Support Scheme" and GCP,using randomized double-blind,placebo-controlled and multi-center clinical research as principles, we combine Chinese interventions with standard chemotherapy of western medicine before and after chemotherapy,analyze and evaluate clinical remission rate (gold index of efficacy evaluation),in order to provide easy-to-intervention TCM program improving the clinical efficacy of refractory acute leukemia.
Results:All cases data (238 cases of patients with refractory acute leukemia) were collected from 7 tertiary hospitals from May 2007 to November 2009.After exposing blind,197 cases were statistically analyzed,including 98 cases in the treatment group (CFBG group),and 99 cases in the control group (simulated agent group).Treatment group:complete remission (CR) 3 cases,accounting for 3.06%;bone marrow remission (CRi) 30 cases,accounting for 30.61%;partial remission(PR) 18 cases,accounting for 18.37%;no remission(NR) 47 cases,accounting for 47.96%;complete remission rate (CR+CRi) 33 cases,accounting for 33.67%;the total effective rate(CR+CRi+PR) 51 cases,accounting for 52.04%.Control group:complete remission (CR) 3 cases, accounting for 3.03%;bone marrow remission (CRi) 21 cases,accounting for 21.21%; partial remission (PR) 13 cases,accounting for 13.13%;no remission (NR) 62 cases, accounting for 56.88%;complete remission rate (CR+CRi) 24 cases,accounting for 24.24%;the total effective rate (CR+CRi+PR) 37 cases,accounting for 37.37%.After chi-square test,the complete remission rate and the effect of the total effective rate of two groups were statistically significant(P<0.05),and the treatment group were higher than the control group.
Conclusion:CFBG combined with chemotherapy can improve significantly the clinical remission rate of refractory acute leukemia,and can decrease the hematological toxicity of chemotherapy.In the clinical use,no adverse affects were found in the safety index,such as urine routine,occult routine,liver and kidney function and electro-cardiogram.So we should further study on it.
Innovation:①the first time to systematically observe the clinical efficacy of CFBG combined with chemotherapy, in accordance with GCP standards and through randomized double-blind, placebo-controlled, multicenter clinical trial②the first time to use clinical remission rate as the ultimate clinical evaluation index of Chinese intervention in the treatment of the RAL.③ncrease CRi as the evaluation criteria for refractory acute leukemia.
引文
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