应用大剂量表柔比星CEF方案行乳腺癌辅助化疗的毒副反应和临床耐受性

目的评价大剂量表柔比星(EPI)CEF方案[环磷酰胺(CTX) EPI 5-氟尿嘧啶(5-Fu)方案]在乳腺癌辅助化疗中的毒副反应和耐受性。方法将98例Ⅰ～Ⅲa期原发性乳腺癌患者随机分为大剂量EPI化疗组(CEF-100组)和常规剂量EPI化疗组(CEF-60组),CEF-100组和CEF- 60组分别给予:EPI 100和60 mg/m2,行CEF方案术后辅助化疗。21 d为1个周期,共6个周期。化疗期间给予相应的骨髓支持、保肝和止吐治疗。结果化疗各周期中,CEF-100组与CEF-60组白细胞数和中性粒细胞绝对值差异无统计学意义(均P>0.05),但CEF-100组由于白细胞减少引起的发热发生率高于CEF-60组(P<0.05)。CEF-100组比CEF-60组消化道毒副反应(恶心呕吐、口腔炎)和肝功能异常的发生率高,程度重(均P<0.05),但经对症处理均可缓解。两组均未出现严重的髓外毒副反应及心脏毒性,均未发生治疗相关死亡。结论原发性乳腺癌患者对大剂量EPI CEF方案治疗耐受性良好,远期疗效尚有待进一步随访观察。     

表柔比星联合紫杉醇对浸润性乳腺癌新辅助化疗临床研究

目的：探讨表柔比星联合紫杉醇（ET方案）对浸润性乳腺癌新辅助化疗的应用价值.方法：用ET方案对ⅡB～ⅢB期乳腺癌46例进行术前化疗2～4个周期,观察疗效及毒副反应,并分析肿瘤临床分期、激素受体表达与疗效的关系.结果：全组cCR 19例,PR 25例,无疾病进展病例,临床总有效率为95.7%.病理结果显示,化疗反应5级23.9%（11/46）,4级40.0%（17/46）.ER或PR表达与疗效有关,ER或PR阴性者疗效优于阳性,P＝0.013.主要毒副反应为周围神经损害、骨髓抑制、胃肠道反应及脱发等,但毒副反应轻多为Ⅰ度.骨髓抑制与以蒽环为主的化疗方案相似,不需要预防性G-CSF支持.心肌毒性不明显.结论：ET方案用于浸润性乳腺癌的新辅助化疗,显著提高了病理及临床缓解率,有效率高,毒副反应小,化疗未增加手术风险,近期疗效满意.ER或PR表达与疗效有关,ER或PR阴性者疗效优于阳性,肿瘤分期、HER-2表达与化疗疗效无明显相关性.     

多西紫杉醇联合表柔比星新辅助化疗治疗乳腺癌的疗效分析

目的探讨多西紫杉醇联合表柔比星(ET方案)在乳腺癌新辅助化疗应用中的临床效果。方法选取70例原发性乳腺癌患者作为研究对象,所有患者均采用ET方案进行新辅助化疗,治疗4个疗程后,分析治疗效果和不良反应的发生情况。结果 ET方案新辅助化疗治疗乳腺癌的有效率为75.8%,治疗后患者发生不同程度的呕吐、粒细胞减少和脱发等不良反应。结论对乳腺癌患者行多西紫杉醇联合表柔比星新辅助化疗能够有效提高肿瘤治疗的有效率,不良反应患者可耐受,ET方案是新辅助化疗治疗乳腺癌较为理想的选择。     

含大剂量表柔比星的联合化疗治疗晚期乳腺癌

目的：研究含大剂量表柔比星的联合化疗方案治疗晚期乳腺癌的疗效和毒副反应。方法：１６例晚期乳腺癌患者接受ＣＥＦ方案化疗：环磷酰胺（ＣＴＸ）６００ｍｇ／ｍ＾２,表柔比星（ＥＰＩ）１００ｍｇ／ｍ＾２,氟尿嘧啶（５－ＦＵ）５００ｍｇ／ｍ＾２,每２１天重复,每个病例至少应用２疗程。结果：２例获ＣＲ,９例获ＰＲ,总有效率６８．８％（１１／１６）。主要的毒性反应为白细胞下降,恶心和呕吐、脱发、均多为Ⅰ、Ⅱ级,患者可以耐受。结论：含大剂量表柔比星的联合化疗方案对晚期乳腺癌安全有效。值得临床进一步试用。     

表柔比星加紫杉醇新辅助化疗方案治疗乳腺癌

目的:研究表柔比星加紫杉醇新辅助化疗方案治疗乳腺癌的近期疗效及毒副反应。方法:用TE方案(紫杉醇加表柔比星)对Ⅱ、Ⅲ期的20例乳腺癌进行新辅助化疗,3-4周为1个周期,患者完成2-4个周期后评价疗效;并以VE方案(长春瑞滨加表柔比星)作对照组进行比较,TE方案:表柔比星(EPI)60 mg/m2,第1天,静脉注射;紫杉醇(TAX)150mg/m2,第2天,静脉点滴;3周为1个周期。VE方案:EPI 60mg/m2,第1天,静脉注射;长春瑞滨(VNR)30mg/m2,第1、8天,静脉注射;4周为1个周期。结果:TE组有效率为80％,其中临床完全缓解(cCR)3例,部分缓解(PR)13例,无变化(NC)4例,病理完全缓解(pCR)2例;VE组有效率为80％,其中cCR 3例,PR 13例,NC 4例,pCR2例。两组均无进展(PD)者。进行4周期新辅助化疗患者有效率高于2周期患者。两组白细胞下降、胃肠道反应、面色潮红和静脉炎等毒副反应相似,VE组乏力、脱发、神经毒性程度比TE组显著(P<0.05),而在关节头痛方面TE组显著(P<0.05)。结论:两组新辅助化疗方案治疗乳腺癌近期有效率较高,疗效相当;VE组毒副反应较TE组高,但均可耐受。     

高剂量表柔比星为主的联合化疗方案治疗48例晚期胸部恶性肿瘤

目的：评价高剂量表柔比星（表阿霉素）联合其他化疗药物治疗晚期胸部肿瘤的疗效及毒副反应。方法：48例可评价晚期胸部肿瘤中非小细胞癌32例;乳腺癌11例;纵隔恶性淋巴瘤5例。分别应用EMP[表柔比星（EPI）100mg/m^2联合丝裂霉素（MMC)6mg/m^2及顺铂（DDP）60mg/m^2]治疗非小细胞肺癌;应用CEF[环磷酰胺（CTX）600mg/m^2联合表柔比星100mg/m^2及氟尿嘧啶（5－FU）800mg/m^2]治疗乳腺癌。应用CEOP[环磷酰胺600mg/m^2联合表柔比星100mg/m^2、长春新碱（VCR）1mg/m^2及强的松60mg/m^2]治疗纵隔恶性淋巴瘤。3－4周重复。结果：非小细胞肺癌总有效率56．3％;乳腺癌总有效率72．7％;纵隔恶性淋巴瘤总有效率100％。白细胞减少为主要毒副反应,发生率为93．8％。未见明显心脏毒性。结论：高剂量表柔比星治疗晚期胸部恶性肿瘤安全有效。     

紫杉醇加表柔比星化疗晚期乳腺癌疗效观察

 目的 观察紫杉醇加表柔比星对晚期乳腺癌化疗疗效及毒副反应。方法 对不能手术和术后复发转移的晚期乳腺癌患者44例，以紫杉醇加表柔比星组成的TE方案进行化疗：紫杉醇135 mg／m2加入5 %葡萄糖溶液中静脉滴注3 h，第1天；表柔比星60 ~ 70 mg／m2，静脉注射，第2天。21 d为一周期。有胸腔积液者化疗前给予引流并注入胸腔硝卡芥加顺铂1 ~ 2次。按WHO实体瘤疗效标准及毒性标准评价疗效及毒副反应。结果 完全缓解9例，部分缓解26例，无变化5例，进展4例，总有效率79.5 %，其中对肺转移、胸膜转移（胸腔积液）和淋巴结转移病灶及乳腺原发病灶疗效较好。毒副反应较轻，以Ⅰ~Ⅱ度为多。结论 TE方案治疗晚期原发或术后复发转移乳腺癌疗效好，毒副反应较轻，患者可耐受且有较好的依从性，可作为一线方案使用，并值得进一步随机对照研究。     

p21在乳腺癌化疗中对表柔比星的增敏性及其作用机制的研究

背景与目的:p21是一种重要的细胞周期负性调控因子,目前对其在乳腺癌化疗过程中的作用尚不明确.本课题旨在观察将p21基因转染乳腺癌细胞后,对表柔比星敏感性的改变,以探讨新的表柔比星耐药可能的机制.方法:构建表达载体pEGFP-p21,采用脂质体转染法转入乳腺癌细胞株MCF-7中,筛选稳定表达p21的克隆;应用实时荧光定量PCR法检测转染组细胞中p21 mRNA的表达,流式细胞术和Hoechst33342荧光染色法分析细胞周期分布和凋亡变化;应用MTT法检测p21基因转染前后MCF-7细胞对表柔比星敏感性的变化,实时荧光定量PCR法(real-time fluorogent quantitative PCR,RFQ-PCR)观察survivin mRNA水平的变化.结果:pEGFP-p21载体转染MCF-7细胞后,MCF-7细胞中p21 mRNA的表达量明显增高,是空白对照组的155倍;转染后的细胞被阻滞于G0/G1期,但实验组与空白对照组相比,凋亡率改变的差异无统计学意义(P>0.05);表柔比星与p21基因转染联合作用时,p21可促进表柔比星对MCF-7细胞的杀伤作用,且细胞的抑制随作用时间的增加而增强,同时伴有survivin mRNA表达的降低,与表柔比星单独作用相比,差异有统计学意义(P<0.05).结论:p21基因能增强MCF-7细胞对表柔比星的敏感性,其作用可能是通过使细胞周期发生G0/G1期阻滞及下调survivin的表达来实现的.     

多西他赛联合表柔比星治疗转移性乳腺癌的临床观察

目的：观察多西他赛联合表柔比星治疗转移性乳腺癌的疗效和不良反应。方法：晚期转移性乳腺癌37例，采用多西他赛75mg／m^2，d1,8,或者35mg／m^2，d1,8,15静脉输注3小时。表柔比星60mg-90mg／m^2，d2静脉注射，3—4周为一疗程，所有病例均化疗2疗程。结果：37例中完全缓解3例，部分缓解18例，有效率56．8％（21／37）。主要不良反应：中性粒细胞减少，胃肠道反应。结论：多西他赛联合表柔比星治疗转移性乳腺癌的疗效高和不良反应可耐受。     

多西紫杉醇联合表柔比星新辅助化疗治疗老年局部晚期乳腺癌30例

[目的]观察多两紫杉醇联合表柔比星（TE）新辅助化疗治疗老年局部晚期乳腺癌（LABC）的客观缓解率、手术切除率及毒副反应。[方法]2005年10月至2008年8月,30例经空芯针活检组织学诊断证实的老年LABC行TE方案新辅助化疗,Ⅲa期17例,Ⅲb期11例,Ⅲc期2例,中位年龄74岁;化疗剂量为：多西紫杉醇75mg/m2,d1静滴,表柔比星60mg／m2,d1静滴,每3周为1个周期：2个周期TE方案之后对病灶进行首次评估,以决定是否再给予1～2个周期TE后再接受手术或放射治疗．[结果]30例患者接受2～4个周期TE方案的新辅助化疗,25例降低了临床分期,降期率为75．0％（25／30）：临床完全缓解率（CCR）及临床部分缓解率（CPR）分别为23．3%（7／30）、53.3％（16／30）;手术切除率为96．7％（29／30）。常见毒副反应有：中性粒细胞减少症、轻中度脱发、恶心、呕吐、体液潴留、肌肉关节疼痛等。Ⅲ、Ⅳ度中性粒细胞减少症分别为23．3％（7／30）和3.3％（1／30）。[结论]TE方案新辅助化疗治疗老年LABC患者是安全有效的,可以降低临床分期,提高患者术后的生活质量。     

Single agent epirubicin as first line chemotherapy for metastatic breast cancer patients

In order to better explore the toxicity and the activity of high dose epirubicin (120mg/m², 3 weeks) we analyzed a population of 127 metastatic breast cancer patients, treated in a randomized clinical trial conducted to evaluate the cardioprotective effect of dexrazoxane against epirubicin induced cardiotoxicity. All the patients had a diagnosis of metastatic breast cancer, an ECOG performance status 2 and normal hematologic, renal, hepatic and cardiac function. No prior adjuvant chemotherapy including anthracycline was allowed. Epirubicin was given at the dose of 120mg/m² i.v. bolus every 3 weeks. One hundred twenty five patients were evaluable for toxicity and response. Seventeen patients (11%) had a complete response and 47 patients (37%) a partial response, for an overall response rate of 48%. The median progression free and overall survivals were 8.3 months and 18.3 months, respectively. Grade 3 and 4 leukopenia were observed in 8% and 7% of the patients, respectively. The most frequent nonhematological grade 3 toxicities were alopecia (87%), nausea and vomiting (16%), and mucositis (8%). Cardiotoxicity, defined as occurrence of congestive heart failure, decrease in resting left ventricular ejection fraction (L-VEF) to 45, or 20 EF units decrease from baseline L-VEF, was observed in 19% of the patients, after a median cumulative dose of epirubicin of 720mg/m² (range 120–1440). This study confirms in a large series of patients the activity of high dose epirubicin; however, the high incidence of cardiotoxicity requires a careful evaluation of cardiac risk factors before treatment.     

三阴性乳腺癌表柔比星和环磷酰胺联合紫杉醇周疗新辅助化疗临床观察

目的观察表柔比星和环磷酰胺联合紫杉醇周疗在三阴性乳腺癌(triple-negative breast cancer,TNBC)新辅助化疗中的疗效和安全性。方法2010-01-01-2012-10-31河南省肿瘤医院经空芯针活检结合免疫组化检查诊断为TNBC患者67例,术前接受紫杉醇80mg/m2(静脉滴入,d1、d8和d15)、表柔比星75mg/m2(静脉滴入,d1)和环磷酰胺600mg/m2(静脉推注,d1)化疗,21d为1个周期,共4个周期。根据RECIST实体瘤疗效评价标准及术后病理组织学检查评价疗效,按照WHO抗癌药物不良反应分度标准评价不良反应。结果总有效率为91.0%,临床完全缓解(cCR)43.3%(29/67),部分缓解(PR)47.7%(32/67),疾病稳定(SD)9.0%(6/67),无疾病进展(PD)病例;病理完全缓解(pCR)率为41.8%(28/67)。Ⅲ~Ⅳ度中性粒细胞减少发生率为28.4%(19/67),2例(3.0%)出现中性粒细胞减少性发热。Ⅲ~Ⅳ度贫血、血小板减少、恶心呕吐、腹泻及口腔黏膜炎的发生率分别为14.9%(10/67)、3.0%(2/67)、7.5%(5/67)、4.5%(3/67)和4.5%(3/67)。治疗期间未发生严重心脏毒性病例。3年无病生存率和总生存率分别为73.6%和88.9%。结论表柔比星和环磷酰胺联合紫杉醇周疗用于TNBC的新辅助化疗,近期疗效较好,不良反应可耐受。     

多西紫杉醇联合表阿霉素治疗局部晚期乳腺癌的疗效观察

目的：了解多西紫杉醇加表阿霉素对局部晚期乳腺癌患者进行新辅助化疗的疗效及不良反应。方法：对我院治疗的63例均采用多西紫杉醇加表阿霉素（DE方案：多西紫杉醇75 mg/m2d1,表阿霉素75 mg/m2d1）化疗的局部晚期乳腺癌患进行回顾性分析,每位患者进行2-4疗程的化疗,结束后评估疗效及不良反应。结果：总有效率（CR＋PR）为68.3%,完全缓解（CR）8例,部分缓解（PR）35例,无变化（SD）13例,进展（PD）7例。术后中位随访24个月,死亡6例,复发及转移13例,健在44例。结论：多西紫杉醇联合表阿霉素术前化疗可以使患者降期,使原发灶缩小,以增加手术机会,提高生存率。     

多西紫杉醇联合表阿霉素治疗局部晚期乳腺癌的疗效观察

目的:了解多西紫杉醇加表阿霉素对局部晚期乳腺癌患者进行新辅助化疗的疗效及不良反应。方法:对我院治疗的63例均采用多西紫杉醇加表阿霉素(DE方案:多西紫杉醇75 mg/m2d1,表阿霉素75 mg/m2d1)化疗的局部晚期乳腺癌患进行回顾性分析,每位患者进行2-4疗程的化疗,结束后评估疗效及不良反应。结果:总有效率(CR+PR)为68.3%,完全缓解(CR)8例,部分缓解(PR)35例,无变化(SD)13例,进展(PD)7例。术后中位随访24个月,死亡6例,复发及转移13例,健在44例。结论:多西紫杉醇联合表阿霉素术前化疗可以使患者降期,使原发灶缩小,以增加手术机会,提高生存率。     

Activity of first-line epirubicin and paclitaxel in metastatic breast cancer is independent of type of adjuvant therapy

To evaluate the impact of prior adjuvant chemotherapy on response rate (RR), progression-free (PFS) and overall survival (OS) of metastatic breast cancer patients treated with epirubicin/paclitaxel (ET) regimens. In all, 291 patients enrolled in five studies in metastatic breast cancer were analysed: 101 (35%) were chemonaive, 109 (37%) had received adjuvant CMF and 81 (28%) adjuvant anthracyclines. Response rate to ET was 66%. Response rate was 63% for cyclophosphamide plus methotrexate plus 5-fluorouracil (CMF), 67% for prior anthracyclines and 68% in chemonaive patients (P=0.5). By multivariate analysis, adjusted odds ratio for response was 0.81 (95% CI: 0.37-1.79) for CMF and 0.92 (95% CI 0.43-2.01) for anthracyclines (P=0.86). The CR rates were 14% for both CMF and anthracyclines and 22% for chemonaive patients (P=0.2). By multivariate analysis, the relative odds of CR for CMF or anthracyclines were 0.40 and 0.39 as compared to chemonaive patients (P=0.036). The median PFS was 11.0 months for prior CMF, 10.2 months for anthracyclines and 12.5 months in chemonaive patients (P=0.33). In multivariate Cox's model, a nonsignificant increase in the risk of progression was seen in patients treated with adjuvant CMF or anthracyclines. The median OS was 23.8 months for CMF, 20.2 months for anthracyclines and 27.5 months in chemonaive patients (P=0.61). The same, nonsignificant, association was seen in multivariate analysis. The ET regimens provide satisfactory results in metastatic breast cancer, regardless of previous adjuvant chemotherapy.     

A randomized study of epirubicin monotherapy every four or every two weeks in advanced breast cancer. A Hellenic Cooperative Oncology Group study

Purpose: To evaluate the impact on the response rate in patients withadvanced breast cancer (ABC) of the doubling of the dose intensity (DI) ofepirubicin monotherapy.Patients and methods: From January 1991 until April 1996, 167 patientswith ABC were randomized to receive epirubicin (110 mg/m²)either every four (81 patients, group A) or every two weeks (86 patients,group B). Filgrastim (5 µg/kg/daily) was administered prophylacticallyon days 2–12 of each cycle.Results: The two groups were equally balanced in terms of major patientand tumor characteristics. Even though the median cumulative dose ofepirubicin was identical in the two groups (651 mg/m²), themedian DI of epirubicin was doubled in group B (27.2 vs. 52.9mg/m²/wk, respectively). The complete response (CR) rate wassignificantly increased in Group B (5%, 95% CI:0.16%–9.84% vs. 17%, 95% CI:8.9%–25.08%, P = 0.011), although overall response rateswere similar (49% vs. 53%, P = 0.5957). Also, there was nosignificant difference in the incidence of grade 3–4 toxicity betweenthe two groups. After a median follow-up of 25 months (range,0.43–43.3+) no significant difference was observed in the duration ofresponse (median, 10 months vs. 8.5 months, P = 0.5130), time to progression(median, 7.2 months vs. 7.4 months, P = 0.2970) or survival (median, 14.6months vs. 14.9 months, P = 0.4483). Logistic regression analysis showedthat performance status was a significant variable for response (P = 0.0068)and multivariate analysis using the Cox proportional hazards model revealedthat performance status was significant for survival (P = 0.0049), while thepresence of multiple metastases (P = 0.0020) was significant for time toprogression.Conclusion: Doubling the planned DI of epirubicin monotherapy significantlyincreases the CR rate but has no influence on time to progression or survivalin patients with ABC.     

Dose-dense epirubicin and paclitaxel with G-CSF: a study of decreasing intervals in metastatic breast cancer

Anthracyclines and taxanes are very effective drugs in the treatment of advanced breast cancer. With G-CSF support, the dose-intensity of this combination can be increased by reducing the interval between chemotherapy cycles, the so-called 'shortening of cycle time'. We treated 36 patients with advanced breast cancer in a multicentre phase I/II study. The treatment regimen consisted of epirubicin 75 mg m(-2) followed by paclitaxel 135 mg m(-2) (3 h) in combination with G-CSF. At least six patients were treated in each cohort and were evaluated over the first three cycles. Starting at an interval of 14 days, in subsequent cohorts of patients the interval could be shortened to 10 days. An 8-day interval was not feasible due mainly to incomplete neutrophil recovery at the day of the next scheduled cycle. In the 10-day interval cohort it was feasible to increase the paclitaxel dose to 175 mg m(-2). The haematological and non-haematological toxicity was relatively mild. No cumulative myelosuppression was observed over at least three consecutive cycles. In combination with G-CSF, epirubicin 75 mg m(-2) and paclitaxel 175 mg m(-2) could be safely administered every 10 days over at least three cycles, enabling a dose intensity of 52 and 122 mg m(-2) per week, respectively.