白蛋白紫杉醇用于乳腺癌新辅助化疗的二期临床研究  

A phase II clinical study of albumin-bound paclitaxel used in neoadjuvant therapy in breast cancer women

作　　者：余峰[1] 刘晶晶[1] 张晟[1] 张霄蓓[1] 张瑾[1] 

机构地区：[1]天津医科大学肿瘤医院病理科国家肿瘤临床医学研究中心乳腺癌防治教育部重点实验室,300060

出　　处：《中华乳腺病杂志（电子版）》2014年第4期9-15,共7页Chinese Journal of Breast Disease(Electronic Edition)

基　　金：天津市重大科技专项(工程)项目抗癌重大科技专项(12ZCDZSY15400)

摘　　要：目的比较白蛋白紫杉醇联合表柔比星及环磷酰胺(TEC)方案与含以聚氧乙烯蓖麻油为溶剂紫杉醇注射液的TEC方案应用于乳腺癌新辅助化疗的有效性及安全性。方法研究共纳入120名乳腺癌患者,随机分为研究组和对照组,分别给予白蛋白紫杉醇260 mg/m2+表柔比星60 mg/m2+环磷酰胺500 mg/m2的TEC新辅助化疗3周方案,和紫杉醇注射液175 mg/m2+表柔比星60 mg/m2+环磷酰胺500 mg/m2的TEC新辅助化疗3周方案。两组患者均行4个周期的化疗。观察两组的病理完全缓解率(pCR),临床完全缓解率(cCR),临床部分缓解率(cPR)和临床治疗反应率(cRR),以及用药的安全性和不良反应。同时进一步比较两组治疗前后磷脂酰肌醇3-激酶(PI3K)、蛋白激酶B(AKT)、哺乳动物雷帕霉素靶蛋白(mTOR),促凋亡基因(BAD)等的表达水平。以χ2检验进行组间率的比较及临床病理特征的分析,计量资料比较采用t检验。结果两组患者均获得良好的治疗反应率,研究组cCR率为46.7%(28/60),对照组为18.3%(11/60),差异具有统计学意义(χ2=10.978,P=0.001);其中研究组16.67%(10/60)的患者达到pCR,较对照组(5.0%,3/60)有所提高(χ2=4.227,P=0.040)。两组患者均未发生3、4度不良反应或治疗相关的死亡。研究组化疗期间主要不良反应为周围感觉神经毒性、中性粒细胞数减少、恶心呕吐;研究组患者化疗期间中性粒细胞减少的发生率为31.7%(19/60),而对照组为51.6%(31/60)(χ2=4.937,P=0.026);研究组感觉神经毒性的发生率为38.3%(23/60),对照组为51.6%(31/60)(χ2=5.910,P=0.015);两组患者左心室射血分数均在正常范围内(>50%),用药前后均未发生明显改变;研究期间两组均无因药物不良反应所致的停药、用药延迟、药量减少、药物相关高血压及手术延迟。用药前后研究组PI3K阳性率降低45.0%,mTOR阳性率降低43.3%,AKT阳性率降低41.7%,BAD的阳性率升高21.6%,差异均具有统计学意义(P均=0.000)。与对�Objective To compare the efficacy and safety of two neoadjuvant therapies： albumin-bound paclitaxel combined with epirubicin and cyclophosphamide , and cremophor-formulated paclitaxel combined with epirubicin and cyclophosphamide in breast cancer patients .Methods A total of 120 breast cancer patients were enrolled and randomly divided into study group （ n=60 ） and control group （ n=60 ） .In study group, albumin-bound paclitaxel 260 mg/m2 , epirubicin 60 mg/m2 and cyclophosphamide 500 mg/m2 were administrated every 3 weeks for 4 cycles as neoadjuvant therapy;in control group , cremophor-formulated paclitaxel 175 mg/m2 , epirubicin 60 mg/m2 and cyclophosphamide 500 mg/m2 were administrated every 3 weeks for 4 cycles as neoadjuvant therapy during the same time period .The pathologic complete response （pCR） rate, clinical complete remission （cCR） rate, clinical partial remission（cPR） rate, clinical response rates （cRR）, safety and toxicity in the two groups were recorded .The expressions of PI3K, AKT, mTOR and BAD in tumor tissue were examined and compared before and after chemotherapy in two groups .χ2 test was used for rate comparison between groups and clinicopathological analysis .t test was used for measurement data . Results The patients in two groups achieved good clinical response：28 patients （ 46.7%, 28/60 ） in study group and 11 （18.3%, 11/60） achieved cCR, the difference was statistically significant （χ2=10.978, P=0.001）.The pCR rate was 16.7%（10/60） in study group, higher than 5%（3/60） in control group （χ2=4.227 , P=0.040 ） .There were no treatment-related deaths or grade 3 and 4 toxicity in both groups .The most common adverse events in study group were periphery sensory neuropathy , neutropenia , nausea and vomiting . The neutropenia occurred in 31.7%of the patients（19/60） in study group, in 51.6%of the patients（31/60） in control group（χ2=4.937, P=0.026）.And sensory neuropathy occurred in 38.3%of the patients （23/60） in study group

关 键 词：乳腺肿瘤 化学疗法 辅助 白蛋白结合型紫杉醇 

分 类 号：R737.9[医药卫生—肿瘤]