多西他赛联合表柔比星、环磷酰胺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、环磷酰胺治疗转移性乳腺癌的临床疗效及不良反应。方法:回顾性分析40例转移性乳腺癌患者的化疗资料,采用国产多西他赛75mg/m2,表柔比星70-90mg/m2静脉滴注,环磷酰胺500mg/m2每3周1次。观察每次化疗后的不良反应,完成4个疗程后观察疗效。结果:全部病例均按计划完成4个周期的化疗。完全缓解(CR)3例,部分缓解(PR)20例,稳定(SD)12例,进展(PD)5例。总有效率(CR+PR)为57.5%,控制率(CR+PR+SD)87.5%。主要不良反应为中性粒细胞减少、恶心、呕吐、腹泻等。结论:多西他赛联合表柔比星、环磷酰胺治疗转移性乳腺癌临床疗效较好,不良反应患者可以耐受。     

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。     

吉西他滨联合表柔比星治疗转移性乳腺癌

乳腺癌的辅助治疗改善了病人的生存,但肿瘤的复发和转移仍然是一个主要问题。化疗是治疗转移性乳腺癌最常用的方法。表柔比星(表阿霉素)是治疗转移性乳腺癌最有效的药物之一。临床研究显示吉西他滨在乳腺癌治疗中显示了良好的效果和耐受性。2000年5月-2002年9月我们采用吉西他滨加表阿霉素治疗31例转移性乳腺癌取得了     

CEF方案序贯多西他赛辅助化疗治疗45例淋巴结阳性乳腺癌

[目的]评价CEF方案序贯多西他赛在淋巴结阳性乳腺癌术后辅助化疗中的疗效与毒副反应。[方法]90例淋巴结阳性乳腺癌患者术后分为两组,分别给予CEF方案（A组）和CEF方案序贯多西他赛（B组）进行辅助化疗。随访时间38～48个月。[结果]A组3年无病生存率（DFS）57.8%,3年总生存率（OS）为75.6%。B组3年DFS为84.4%（38/45）,3年OS为91.1%（41/45）,两组比较差异有显著性（P值均〈0.005）。在绝经后、淋巴结转移4～9枚,T3期以及ER阴性患者中B组的3年无病生存率高于A组。多因素分析治疗方法、肿块大小及受体状况等方面与3年DFS及3年OS均相关。[结论]CEF方案序贯多西他赛的化疗方案在淋巴结阳性乳腺癌术后辅助化疗中比CEF方案得到更高的3年无病生存率及总生存率,特别是对肿块相对较小、受体阴性的患者而言获益更大。     

联合应用表柔比星与多西他赛辅助化疗三阴乳腺癌的疗效分析

三阴乳腺癌是指雌激素受体、孕激素受体、人表皮生长因子受体2均为阴性的乳腺癌［1］。可分为Luminal型、Her-2＋型及 Basal-like 型。恶性程度高,病死率高,复发转移快,无法从内分泌治疗及抗Her-2靶向治疗中受益而使得治疗手段相对其他乳腺癌受到限制［2］。本研究对我院2009年8月-2013年10月收治的80例三阴乳腺癌患者给予表柔比星联合多西他赛（ET）方案辅助化疗治疗,取得良好效果,报道如下。     

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。     

多西他赛治疗晚期乳腺癌的临床研究

目的 观察国产多西他赛注射液对一线治疗后失败的晚期乳腺癌患者的临床疗效及毒副反应,并对安全性进行评估。方法 以国产多西他赛对44例既往治疗后进展的乳腺癌患者进行70mg／m^2静脉滴注,每3周1次,单药治疗。试验中不预防使用粒细胞集落刺激因子。用世界卫生组织（WHO）的疗效及抗肿瘤药急性及亚急性毒性反应分度标准评价疗效及毒性,用卡式评分评价身体状况变化。结果 在41例可评价疗效的患者中,4例达到完全缓解,14例部分缓解,有效率达43．9％,临床获益率85．4％。不良反应主要表现为Ⅲ、Ⅳ度白细胞下降（42．9％）、脱发（7．1％）和消化道反应（4．8％）。未出现水钠潴留。结论 使用多西他赛注射液治疗化疗后进展的晚期乳腺癌患者,疗效显著,耐受性良好,可作为该类患者的治疗选择。     

吉西他滨联合表柔比星治疗转移性肝癌的临床研究

目的：观察吉西他滨联合表柔比星方案治疗转移性肝癌的疗效。方法：吉西他滨1000mg／m^2,静脉滴注,30分钟滴完,第1,8天;表柔比星60mg／m^2,静脉推注,第1天,21天为～周期。连用2—3周期。结果：45例可评价疗效患者,共化疗113个周期,肿瘤完全缓解（CR）0例,部分缓解（PR）34例,稳定（SD）7例,进展（PD）4例。总有效率为64．4％,其中鼻咽癌肝转移有效率为66．7％,胰腺癌肝转移有效率为83．3％,乳腺癌肝转移有效率80％,非小细胞性肺癌肝转移有效率52．9％,胃癌肝转移有效率62．5％。结论：吉西他滨联合表柔比星治疗转移性肝癌,是安全有效的,尤其是胰腺癌及乳腺痛肝转移疗效尤为昂著。     

吉西他滨联合表柔比星治疗转移性肝癌的临床研究

目的:观察吉西他滨联合表柔比星方案治疗转移性肝癌的疗效。方法:吉西他滨1000mg/m2,静脉滴注,30分钟滴完,第1,8天;表柔比星60mg/m2,静脉推注,第1天,21天为一周期。连用2-3周期。结果:45例可评价疗效患者,共化疗113个周期,肿瘤完全缓解(CR)0例,部分缓解(PR)34例,稳定(SD)7例,进展(PD)4例。总有效率为64.4%,其中鼻咽癌肝转移有效率为66.7%,胰腺癌肝转移有效率为83.3%,乳腺癌肝转移有效率80%,非小细胞性肺癌肝转移有效率52.9%,胃癌肝转移有效率62.5%。结论:吉西他滨联合表柔比星治疗转移性肝癌,是安全有效的,尤其是胰腺癌及乳腺癌肝转移疗效尤为显著。     

Phase II multicentre randomised study of docetaxel plus epirubicin vs 5-fluorouracil plus epirubicin and cyclophosphamide in metastatic breast cancer

The purpose of the study was to evaluate the efficacy and safety of docetaxel plus epirubicin (ET) and of 5-fluorouracil plus epirubicin and cyclophosphamide (FEC) as first-line chemotherapy for metastatic breast cancer. A total of 142 patients (intent-to-treat (ITT)) with at least one measurable lesion were randomised to receive docetaxel 75 mg m(-2) plus epirubicin 75 mg m(-2) or 5-fluorouracil 500 mg m(-2) plus epirubicin 75 mg m(-2) and cyclophosphamide 500 mg m(-2) intravenously once every 3 weeks for up to eight cycles. Prophylactic granulocyte-colony-stimulating factor was only permitted after the first cycle, if required. Per-protocol analysis (n=132) gave an overall response rate for ET of 63.1% (95% confidence interval (CI), 50-78%) and for FEC 34.3% (95% CI, 23-47%) after a median seven and six cycles, respectively. Intent-to-treat population (n=142) gave an overall response rate for ET of 59% (95% CI, 47-70%) and for FEC 32% (95% CI, 21-43%) after a median seven and six cycles, respectively. The median response duration for ET was 8.6 months (95% CI, 7.2-9.6 months) and for FEC 7.8 months (95% CI, 6.5-10.4 months). The median time to progression (ITT) for ET was 7.8 months (95% CI, 5.8-9.6 months) and for FEC 5.9 months (95% CI, 4.6-7.8 months). After a median follow-up of 23.8 months, median survival (ITT) for ET and FEC were 34 and 28 months, respectively. Nonhaematologic grade 3-4 toxicities were infrequent in both arms. Haematologic toxicity was more common with ET and febrile neutropenia was reported in 13 patients (18.6%) in the ET group. Two deaths in the ET group were possibly related to study treatment. In conclusion, both ET and FEC were associated with acceptable toxicity. ET is a highly active first-line therapy for metastatic breast cancer.     

多西紫杉醇联合表阿霉素及环磷酰胺治疗晚期乳腺癌的临床观察

目的：观察多西紫杉醇联合表阿霉素及环磷酰胺治疗晚期乳腺癌的疗效与不良反应。方法：采用多西紫杉醇联合表阿霉素及环磷酰胺治疗56例复发或转移的晚期乳腺癌患者,多西紫杉醇75mg/m2,d1,表阿霉素50mg/m2,d1,环磷酰胺500mg/m2,d1,21天为1周期,连续治疗2周期。结果：56例患者TEC方案治疗2周期后CR7例,PR22例,总有效率为51.8%。最常见不良反应为骨髓抑制、消化道反应及脱发,本组无一例发生过敏反应,其不良反应可耐受。结论：TEC方案治疗晚期乳腺癌可作为晚期乳腺癌的一线治疗方案。     

Phase I study of docetaxel in combination with cyclophosphamide as first-line chemotherapy for metastatic breast cancer

This phase I was study conducted to establish the maximum tolerated dose, dose-limiting toxicity, and recommended dose of docetaxel in combination with cyclophosphamide as first-line chemotherapy for metastatic breast cancer. Twenty-six patients were treated with cyclophosphamide (600 mg m(-2), intravenous bolus) followed by docetaxel (60, 75 or 85 mg m(-2), 1-h intravenous infusion) every 3 weeks. The maximum tolerated dose was docetaxel 85 mg m(-2) with cyclophosphamide 600 mg m(-2), the dose-limiting toxicity being febrile neutropenia. Grade 4 neutropenia was experienced by all patients, but was generally brief. Otherwise, the combination was well tolerated with few acute and no chronic non-haematological toxicities of grade 3/4. Activity was observed at all dose levels and disease sites, and the overall response rate was 42% (95% confidence interval 22-61%). The pharmacokinetics of docetaxel were not modified by cyclophosphamide coadministration. These findings establish a recommended dose of docetaxel 75 mg m(-2) in combination with cyclophosphamide 600 mg m(-2) every three weeks for phase II evaluation.     

Front-line treatment of metastatic breast cancer with docetaxel and epirubicin: A multicenter dose-escalation study

Purpose: To determine the maximum tolerable dose (MTD) and the dose-limiting toxicity (DLT) of docetaxel (D) in combination with epirubicin (Epi) in patients with advanced breast cancer.Patients and methods: Forty-seven chemotherapy-naïve metastatic breast cancer patients aged <75 years with PS (WHO) 0–2 and adequate bone marrow, renal, liver and cardiac function, were enrolled in the study. Epi was given as a five-min bolus i.v. infusion on day 1 (d1) in escalated doses with increments of 10 mg/m2; D was given in a one-hour infusion after appropriate premedication on either day 1 or on day 2 in escalated doses with increments of 10 mg/m2. The patients' median age was 60 years, 42 (89%) had a PS (WHO) 0–1, 16 (34%) were premenopausal and 25 (53%) had visceral disease.Results: When the two drugs were given on the same day, the MTD1 was reached at the doses of Epi 60 mg/m2 and D 80 mg/m2; administration of G-CSF could not result in a dose intensification. When the drugs were given on two consecutive days, the MTD2 was reached at the doses of Epi 80 mg/m2 (d1) and D 90 mg/m2 (d2). The dose-limiting events were febrile neutropenia and grade 4 neutropenia, which developed in 30 (64%) patients during the study; among 227 delivered cycles grade 3–4 neutropenia occurred in 64 (28%) cycles but only 22 (10%) of them were complicated by fever. There were no septic deaths. Grade 1–2 neurosensory toxicity occurred in nine (19%) patients, mild edema in eight (17%) and allergic reactions in five (11%). Four (9%) patients presented a greater than 10% decrease of LVEF and treatment discontinuation was required in two of them; none of the patients developed congestive heart failure. Nevertheless, one patient suddenly died 10 days after treatment initiation of myocardial ischemia, and this death is considered treatment-related. Five (14.7%) complete and thirteen (38.2%) partial responses (ORR: 53.9%; 95% confidence interval: 36.1%–69.7%) were observed in 34 evaluable patients. Ten (29.4%) and six (17.6%) patients had stable and progressive disease, respectively. The median duration of response and time to tumor progression were five and seven months, respectively. The median survival has not yet been reached.Conclusions: The combination of epirubicin and docetaxel is a feasible and well tolerated regimen, but the MTD depends on the administration schedule of the drugs.     

Treatment of advanced, refractory breast cancer with alternating docetaxel and epirubicin/cyclophosphamide plus human granulocyte colony-stimulating factor

Purpose.A phase II study was performed to investigate the efficacy and tolerance of alternating docetaxel and epirubicin/cyclophosphamide plus recombinant human granulocyte colony-stimulating factor (G-CSF) in patients with advanced breast cancer who failed previous non-anthracycline/taxane-containing palliative chemotherapy. Patients and methods.Between November 96 and June 98, a total of 45 patients participated in this trial. Chemotherapy consisted of docetaxel 100mg/m² given as a 1-h infusion on day 1, and epirubicin 100mg/m² plus cyclophosphamide 800mg/m² both adminstered on day 21. G-CSF 5g/kg/day was given subcutaneously from days 22–28 during each cycle. Treatment courses were repeated every 42 days for a total of three courses unless prior evidence of progressive disease. Results.The overall response rate was 57.8% (95% confidence interval, 42.1–72.3%), including seven complete (15.5%) and 19 partial remissions (42.3%); nine patients (20%) had stabilization of disease and 10 (22.3%) progressed. The median time to treatment failure was 7.0 months (range 1.5–26.0), and the median overall survival time 15.0 months (range 2.0–37.0+) with 12 patients (27%) currently still alive with metastatic disease. Myelosuppression was commonly observed with WHO grade 3/4 neutropenia in 20 patients (44%) complicated by septicemia in five (11%). Severe nonhematologic toxicity included stomatitis in five patients (11%), skin and peripheral neurotoxicity each in one patient; alopecia was seen in all 45 patients with complete hair loss in 26 (58%). Conclusions.Our data suggest that alternating docetaxel and epirubicin/cyclo-phosphamide plus G-CSF is an effective and tolerable second-line combination regimen for the treatment of advanced breast cancer.     

A phase II trial of cyclophosphamide, epirubicin and vinorelbine in the treatment of advanced breast cancer

Background.Vinorelbine (Navelbin®; N) has proven to be active in patients with advanced breast cancer (ABC) and cyclophosphamide (C) and epirubicin (Epiadriamycin®: E) are still among the main cytostatic agents against this tumor. On this basis was carried out a study to determine the activity and toxicity of the combination of these three agents (CEN). Patients and method.From April 1996 to March 1998, 59 patients with ABC were recruited of whom 56 were found eligible and evaluable for toxicixty and 55 for activity. The treatment regimen was C: 400mg/m², E: 30mg/m² and N: 25mg/m² administered intravenously on days 1 and 8 of a 28-day cycle. Results.The median number of cycles administered was 6 (range: 1–16). The most common hematological toxicity was grade (G) 3 and 4 neutropenia occurring in 36% of patients, associated with fever in 7% of them. Grade 3–4 thrombocytopenia and anemia occurred in 5% and 7%, respectively. Other G2–G3 non hematologic toxicities were: N/vomiting in 34%, alopecia in 73% and mucositis in 11% of patients. An objective response was achieved in 28 of 56 patients (50%) (95% confidence interval (CI): 37–63%): complete response (CR) in 9%, partial response (PR) in 41%. The median duration of response, time to progression and overall survival time was 54, 47 and 90 weeks, respectively. Conclusion.The CEN combination at these doses and treatment schedule appears to have acceptable tolerability but there is no apparent improvement in therapeutic efficacy when compared to other regimens used as first line treatment in ABC.     

Weekly epirubicin plus docetaxel as first-line treatment in metastatic breast cancer

This study was designed to evaluate the efficacy and tolerability of a weekly schedule of epirubicin in combination with docetaxel in the first-line treatment of patients with metastatic breast cancer (MBC). A total of 43 women with MBC not previously treated with chemotherapy for metastatic disease received weekly epirubicin 25 mg m(-2) and docetaxel 25 mg m(-2) for a maximum of five cycles (total cumulative epirubicin dose of < or =900 mg m(-2)). Dose reduction was not permitted. Objective response and evaluation of toxicity profile were the primary study end points; time to progression and overall survival were secondary end points. Patients were followed for a median of 21 (4-38) months. Analysis was by intent to treat; 33 patients completed five cycles of therapy, and the median dose of epirubicin administered to the 43 patients was 23 mg m(-2). Twenty-five patients (58%) achieved a partial response and one (2%) achieved a complete response. An additional 12 patients (28%) had stable disease. The median time to progression was 11 months (95% confidence intervals (CI) 7-14) overall, and 13 months (95% CI 12-14) in the 26 patients who responded to treatment. Median overall survival was 25 months for responders and 14 months for nonresponders. Grade 3/4 neutropenia occurred in 16% of patients and in 6% of cycles. One patient developed cardiac toxicity (20% reduction in left ventricular ejection fraction). The combination of epirubicin plus docetaxel is highly active in MBC, with a manageable toxicity profile. Such a weekly schedule might provide a valuable treatment option for MBC.     

Front-line treatment of advanced breast cancer with docetaxel and epirubicin: A multicenter phase II study

Purpose:In a previous phase I trial we evaluated the toxicity anddetermined the maximum tolerated doses of the docetaxel (D)–epirubicin(Epi) combination. We conducted a multicenter phase II study to evaluate theefficacy and tolerability of this regimen as front-line treatment in womenwith advanced breast cancer (ABC). Patients and methods:Fifty-four women with ABC stage IIIB (4patients) or IV (50 patients) received front-line treatment with Epi 70mg/m² on day 1 and D 90 mg/m² on day 2. The median agewas 55 years, performance status (WHO) was 0–1 in 49 patients andvisceral disease was present in 45 (83%). Results:All patients were evaluable for toxicity and 50 forresponse. In an intent-to-treat analysis complete remission was observed in5(9%) patients, partial remission in 31 (57%) (overall responserate 66%, 95% confidence interval: 54%–79%),stable disease in 9 (17%) and disease progression in 9 (17%).After a median follow-up of 11.5 months, the median duration of responses was8 months, the median time to disease progression 11.5 months and the mediansurvival has not yet been reached. The probability of one-year survival was65%. Three hundred six cycles of treatment were administered (median6 cycles per patient). Grade 3 and 4 neutropenia was observed in 8(15%) and 31 (57%) patients, respectively, and febrileneutropenia in 19 (35%). Prophylactic rh-G-CSF was used in 45(83%) patients or 226 (74%) cycles. Other hematologic ornon-hematologic toxicities were usually mild. In five (9%) patients theleft ventricular ejection fraction (LVEF) was decreased by more than10% with the treatment. Two patients died during the treatment ofrespiratory failure without associated neutropenia. Conclusions:The combination of docetaxel–epirubicin is aneffective and well tolerated front-line treatment in patients with ABC.     

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。