贝伐珠单抗联合紫杉类药物一线治疗局部复发或转移性乳腺癌患者的安全性及疗效

[目的]研究贝伐珠单抗联合紫杉类药物一线治疗Her-2阴性的局部复发或转移性乳腺癌患者的安全性和疗效。[方法]32例Her-2阴性的复发或转移性乳腺癌患者,一线接受贝伐珠单抗联合紫杉类方案的化疗,直至疾病进展或不良反应不能耐受或患者要求出组。研究者选择化疗方案：贝伐珠单抗15mg／kg静滴d1,多西他赛75mg／m^2,静滴d1,21d为一个周期;或贝伐珠单抗10mg／kg静滴d1,15紫杉醇80mg／m^2,静滴d1,8,15,为一个周期。每3个周期评价疗效。[结果]32例可评价疗效和副作用,PR16例,SD15例,PD1例,总有效率50％,中位TTP为7.25个月。3级以上不良反应为阴道出血、粒细胞下降以及腹泻。[结论]贝伐珠单抗联合紫杉类药物治疗晚期乳腺癌不良反应可以耐受,具有一定疗效。     

多西他赛联合贝伐珠单抗及其单药维持治疗转移性乳腺癌的临床观察

目的 探讨多西他赛联合贝伐珠单抗一线治疗序贯应用贝伐珠单抗单药维持治疗转移性乳腺癌的疗效和安全性。方法 8例转移性乳腺癌患者均为女性,年龄34～62岁,中位年龄为53岁,均经改良根治术后病理组织学确诊,免疫组化检查HER-2为（-）或（+）。治疗方案：贝伐珠单抗15mg／kg d1,多西他赛 75mg／m2 d1,3周为1周期。治疗6个周期未出现病情进展者应用贝伐珠单抗（15mg/kg）单药维持治疗,每3周1次。结果 全组8例中获CR 1例,PR 3例,SD 4例。有效率（RR）为50％,疾病控制率（DCR）为100％。7例经联合治疗6～9个周期后用贝伐珠单抗维持治疗,维持治疗时间为2～31.3个月,中位维持治疗时间为15.3个月,中位无进展生存期为22.3个月。全组5例发生3、4级中性粒细胞减少,其中2例伴发热;5例患者出现指甲毒性,其中3例1、2级,2例3级。贝伐珠单抗应用4～36.5个月过程中,1例发生血栓3级,1例高血压2级,1例高血压3级,2例蛋白尿2级。结论 多西他赛联合贝伐珠单抗一线治疗序贯应用贝伐珠单抗单药维持治疗HER 2阴性转移性乳腺癌的疗效好,毒副反应可耐受,值得临床进一步应用。     

贝伐珠单抗联合多西他赛治疗HER-2阴性复发转移性乳腺癌的临床疗效

目的 观察贝伐珠单抗联合多西他赛治疗人表皮生长因子受体-2（human epidermal growth factor receptor-2,HER-2）阴性复发转移性乳腺癌的临床疗效。方法  79例HER-2阴性复发转移性乳腺癌患者根据不同化疗方案分为两组,观察组42例给予贝伐珠单抗联合多西他赛治疗,对照组37例给予多西他赛单药治疗,观察两组患者治疗后的临床疗效和1年、2年生存率及生存期。 结果 观察组总有效率为59.52%,对照组为37.84%,两组比较差异无统计学意义（P＞0.05）;观察组患者部分缓解率为47.62%,显著高于对照组的24.32%（P＜0.05）;观察组患者2年生存率为40.28%,高于对照组的16.22%（P＜0.05）;观察组患者贫血、血小板减少的发生率显著高于对照组（P＜0.05）。 结论 贝伐珠单抗联合多西他赛治疗HER-2阴性复发转移性乳腺癌的疗效较好,可提高患者生存率和生存期,但对患者血液系统影响较为明显,值得临床重视。     

多西他赛联合希罗达治疗蒽环类失败复发转移性乳腺癌的疗效评价

背景与目的:随着蒽环类药物在乳腺癌治疗中的广泛应用,对蒽环类耐药患者日渐增多,如何治疗蒽环类耐药的复发转移性乳腺癌已成为临床难题.本研究初步探讨了多西他赛联合希罗达治疗蒽环类药物治疗失败的复发转移性乳腺癌的疗效和安全性.方法:回顾性分析64例蒽环类药物治疗失败的复发转移性乳腺癌患者接受多西他赛联合希罗达方案的治疗情况.其中多西他赛75 mg/m2,静脉滴注第1天;希罗达1250 mg/m2,口服,每日2次,第1～14天,每21 d为1个周期.每2个周期评价疗效同时记录不良事件.结果:对64例患者评价疗效,完全缓解(CR)6例,部分缓解(PR)33例,有效率(CR+PR)60.9%(39/64):64例患者可评价不良反应,无严重不良事件导致死亡的患者,主要的不良反应为乏力、骨髓抑制、胃肠道反应和黏膜炎等,其中粒细胞减少Ⅲ～Ⅳ度为45.8%.结论:多西他赛联合希罗达是治疗蒽环类失败复发转移性乳腺癌的有效方案,其不良反应能够耐受.     

曲妥珠单抗联合多西紫杉醇治疗Her-2/neu高表达转移性乳腺癌的疗效和不良反应

背景与目的:大约有20%～30%的乳腺癌患者Her-2/neu高表达,Her-2/neu高表达与患者的不良预后密切相关.化疗药物联合曲妥珠单抗可以显著提高Her-2/neu高表达乳腺癌患者的化疗有效率和生存率,多西紫杉醇是近年来治疗乳腺癌有效的化疗药物之一.本研究旨在观察曲妥珠单抗联合多西紫杉醇治疗Her-2/neu高表达转移性乳腺癌的疗效与不良反应.方法:22例Her-2/neu高表达转移性乳腺癌患者接受曲妥珠单抗联合多西紫杉醇方案治疗,曲妥珠单抗的首次剂量为8 mg/kg,以后的剂量为6 mg/kg.多西紫杉醇75mg/m2,每21 d重复一次.按WHO疗效评价标准评价疗效,按WHO化疗药物急性和亚急性不良反应评价标准评价不良反应.结果:全组22例患者共完成96个周期化疗(中位数3周期,范围2～6周期),所有患者均可评价疗效.22例患者中完全缓解2例,部分缓解12例,病情稳定4例,病情进展4例,客观有效率(CR PR)63.64%,中位疾病进展时间5.4个月,1年生存率59%.全组患者均可评价不良反应,主要不良反应为骨髓抑制,其中Ⅲ～Ⅳ度白细胞减少发生率为54.5%,部分患者有发热(第一次输注曲妥珠单抗时出现)和轻度的心肌劳损.结论:曲妥珠单抗联合多西紫杉醇方案治疗Her-2/neu高表达转移性乳腺癌近期疗效较高,不良反应轻,患者可以耐受.     

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。     

贝伐珠单抗联合化疗治疗转移性结直肠癌的近期效果及安全性

目的 研究贝伐珠单抗（bevacizumab,Bev）联合化疗治疗转移性结直肠癌的近期疗效和安全性.方法 对43例接受贝伐珠单抗联合化疗治疗的晚期结直肠癌患者进行回顾分析,评价联合治疗的近期疗效及不良反应.结果 43例患者中部分缓解（PR）17例,疾病稳定（SD）19例,疾病进展（PD）7例;中位无进展生存（PFS）为10.3个月.3～4度不良反应主要为白细胞和粒细胞减少及恶心、呕吐.与贝伐珠单抗相关的不良反应为蛋白尿、高血压、鼻出血、经血增加、肠道出血、肠穿孔及静脉血栓等.结论 贝伐珠单抗联合化疗治疗晚期结直肠癌近期疗效较好,不良反应可耐受,远期疗效有待进一步观察.     

多西他赛联合希罗达治疗蒽环类失败的转移性乳腺癌的临床研究

目的 研究多西他赛（docetaxel）联合希罗达（Xeloda）治疗蒽环类治疗失败的转移性乳腺癌的疗效及可行性.方法 对12例含蒽环类方案治疗失败的复发转移性乳腺癌患者,采用多西他赛联合希罗达方案治疗,多西他赛37.5 mg/m^2静脉滴注,第1、8天;希罗达900 mg/m^2 ,口服,每日2次,第1～14天,每3周为1个周期.每个周期评价疗效,记录不良反应.结果 12例患者均可评价疗效,2例（16.7%）完全缓解（CR）,5例（41.7%）部分缓解（PR）,4例（33.3%）疾病稳定（SD）,1例（8.3%）疾病进展 （PD）,总有效率（CR＋PR）为58.3%,肿瘤控制率（CR＋PR＋SD）为91.7%.不良反应主要为骨髓抑制、胃肠道反应和手足综合征,均可耐受,无治疗相关死亡患者.结论 多西他赛联合希罗达治疗蒽环类治疗失败的转移性乳腺癌有较好的疗效,不良反应可以耐受,可以作为转移性乳腺癌的解救化疗方案.     

多西他赛联合顺铂治疗转移性乳腺癌的临床观察

目的:观察多西他赛联合顺铂治疗转移性乳腺癌的疗效及不良反应.方法:选择我科2005年6月-2008年6月收治的31例转移性乳腺癌患者,给予多西他赛联合顺铂(TP方案)化疗,21d为1个周期,2周期后评价疗效.有效者给予6周期的化疗.结果:31例患者有效率51.6%,其中CR2例,PR14例.中位疾病进展时间8.6个月,中位生存时间19.2个月.主要不良反应为骨髓抑制及消化道反应和脱发.其中Ⅲ度以上白细胞减少的发生率26.0%.结论:多西他赛联合顺铂治疗转移性乳腺癌的疗效确切,不良反应可以耐受.     

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。     

DC方案与DE方案一线治疗转移性乳腺癌的对比研究

目的　比较多西紫杉醇联合卡培他滨（ＤＣ方案）与多西紫杉醇联合表柔比星（ＤＥ方案）一线治疗转移性乳腺癌的疗效及不良反应。方法　６５例转移性乳腺癌患者分别接受ＤＣ方案和ＤＥ方案治疗。ＤＣ方案组：多西紫杉醇７５ｍｇ／ｍ２静滴,ｄ１;卡培他滨２０００ｍｇ／（ｍ２·ｄ）,分两次口服,ｄ１～ｄ１４。ＤＥ方案组：多西紫杉醇７５ｍｇ／ｍ２静滴,ｄ１;表柔比星７５ｍｇ／ｍ２静推,ｄ１。两方案均以２１天为１个周期。结果　ＤＣ方案组有效率高于ＤＥ方案组（６０.６％ ｖｓ．４６.９％,Ｐ＞０.０５）,其中ＤＣ方案组完全缓解率高于ＤＥ方案组（２４.２％ ｖｓ．６.３％）,两组比较差异有统计学意义（Ｐ＜０.０５）。ＤＣ方案组的６个月后疾病无进展率（ＰＦＲ）优于ＤＥ方案组（７２.７％ ｖｓ．６２.５％,Ｐ＞０.０５）。中位无进展生存期（ＰＦＳ）ＤＣ方案组长于ＤＥ方案组（１１.４个月ｖｓ．７.６个月）,两组比较差异有统计学意义（Ｐ＜０.０５）。不良反应以骨髓抑制、胃肠道反应和脱发为主,３、４级手足综合征发生率ＤＣ方案组（２７.３％,９／３３）高于ＤＥ方案组（０）,差异有统计学意义（Ｐ＜０.０５）。结论　ＤＣ方案及ＤＥ方案一线治疗转移性乳腺癌均取得较好疗效,ＤＣ方案可以作为非蒽环类药物有效的一线治疗方案。     

多西紫杉醇不同给药方案治疗老年转移性乳腺癌临床观察

目的:比较多西紫杉醇每周方案及每3周方案治疗老年转移性乳腺癌的疗效与毒性.方法: 41例老年转移性乳腺癌患者,随机分组后,分别接受不同方案多西紫杉醇治疗.多西紫杉醇3周方案组22例,剂量为75mg/m2/3周;每周方案组19例,每次剂量为25mg/m2×3周,休息1周.评估多西紫杉醇不同用药方案疗效与毒性.结果: 单药多西紫杉醇治疗老年转移性乳腺癌的总有效率为34.1%.每周方案组与接受常规治疗方案组(多西紫杉醇每3周1次)的病人相比,有效率(RR)为36.8% vs 31.8%(P=0.504),两者比较差异无统计学意义;两组中Ⅲ-IV度骨髓抑制率为63.6%:31.6%(P<0.01).但每周方案中III- IV度神经病变高于每3周方案组,为26.3%:18.2%.结论: 单药多西紫杉醇治疗老年转移性乳腺癌有效.每周方案与每3周方案比较,有效率相近,但其血液学毒性低于每三周多西紫杉醇方案.每周方案对老年转移性乳腺癌患者是一较好的选择,可提高老年患者的生活质量.     

A Phase I study of docetaxel plus cyclophosphamide in solid tumors followed by a Phase II study as first-line therapy in metastatic breast cancer.

PURPOSE: In Phase I, the purpose was to determine the maximum tolerated dose and pharmacokinetics of docetaxel plus cyclophosphamide (DC) with and without granulocyte colony-stimulating factor in the treatment of patients with solid tumors. For Phase II, the purpose was to determine the safety and efficacy of this combination as first-line treatment in patients with metastatic breast cancer (MBC). EXPERIMENTAL DESIGN: In Phase I (45 patients), docetaxel was escalated from 60 mg/m(2) to 85 mg/m(2), and cyclophosphamide from 600 mg/m(2) to 800 mg/m(2). Pharmacokinetic evaluation of docetaxel was performed in 19 patients with MBC. In Phase II (34 patients), patients received cyclophosphamide (600 mg/m(2)) followed by docetaxel (75 mg/m(2)), i.v. RESULTS: In Phase I, the dose-limiting toxicity was neutropenia-related events. The maximum tolerated dose for DC was 75 mg/m(2)/700 mg/m(2) in solid tumor patients treated previously and 75 mg/m(2)/800 mg/m(2) for patients not treated previously for MBC. Dose escalation of docetaxel >75 mg/m(2) was not tolerated, despite prophylactic granulocyte colony-stimulating factor treatment. In Phase II, 71% of patients received prior anthracycline therapy. Neutropenic fever requiring i.v. antibiotics occurred in 6 patients (19%). One patient had grade 3 neuropathy. There was no cardiotoxicity. The overall Phase II intent-to-treat objective response rate was 65% (complete responses, 12%). The median overall survival was 22 months, and the median time to progression was 6 months. CONCLUSIONS: DC combination therapy is an active regimen with acceptable toxicity and is appropriate regardless of prior anthracycline therapy. In view of the high activity and lack of cardiotoxicity, this combination warrants additional investigation in early stage breast cancer and in combination with trastuzumab.     

A phase II feasibility trial of dose-dense docetaxel followed by doxorubicin/cyclophosphamide as adjuvant or neoadjuvant treatment for women with node-positive or high-risk node-negative breast cancer

PURPOSE: Dose-dense adjuvant chemotherapy with doxorubicin/cyclophosphamide (AC) followed by paclitaxel has improved results compared with standard dosing at 3-week intervals. Because docetaxel might be more active than paclitaxel in the treatment of metastatic breast cancer, we explored the feasibility of substituting docetaxel for paclitaxel in dose-dense adjuvant therapy. PATIENTS AND METHODS: Seventy-six patients with node-positive breast cancer received treatment with 4 cycles of docetaxel followed by 4 cycles of AC administered with pegfilgrastim at 2-week intervals. When treatment proved difficult for the first 33 patients, 2 additional cohorts were treated: first, with a reduction of pegfilgrastim and dexamethasone prophylaxis doses (cohort 2) and then with a reduction of docetaxel from 100 mg/m2 to 75 mg/m2 (cohort 3). RESULTS: Treatment with dose-dense docetaxel at 100 mg/m2 resulted in unacceptable toxicity (24% of patients required hospitalization) and compromised subsequent dosing of AC as a result of neutropenia on the day of scheduled treatment. Only 21 patients (40%) who received docetaxel 100 mg/m2 were able to receive all 8 doses at full dose and on schedule. Reduction of docetaxel to 75 mg/m2 allowed 74% of patients to receive all 8 doses as scheduled. Delivery of AC as scheduled occurred in 82% of patients who received docetaxel 75 mg/m2 versus 40% when docetaxel 100 mg/m2 was administered. CONCLUSION: Full-dose docetaxel is difficult to administer as part of this dose-dense treatment regimen. Docetaxel 75 mg/m2 can be administered with improved subsequent delivery of 4 courses of dose-dense AC. Until comparative clinical studies are available, docetaxel should not be substituted for paclitaxel in dose-dense adjuvant chemotherapy for patients with high-risk breast cancer.     

多西紫杉醇联合卡培他滨治疗转移性乳腺癌的临床研究

背景与目的:对于既往使用过含蒽环、紫杉醇药物方案化疗失败的复发转移性乳腺癌,可用的药物不多.多西紫杉醇(docetaxel)联合卡培他滨(capecitabine)是近年来治疗转移性乳腺癌一个较新的方案,本研究初步探讨多西紫杉醇联合卡培他滨(DC)治疗转移性乳腺癌的近期疗效和安全性情况.方法:31例女性转移性乳腺癌患者接受多西紫杉醇联合卡培他滨方案化疗.卡培他滨2 500 mg·(m2·d)-1,第1～14天,分2次饭后30 min口服;多西紫杉醇75 mg/m2静滴1 h,第1天.方案21天重复循环.在多西紫杉醇用药前1天,开始口服地塞米松8 mg,每天2次,连用3天.结果:31例患者使用DC方案化疗共116疗程,中位疗程数为3.7个.总有效率(response rate,RR)为41.9%(13/31),完全缓解(complete remission,CR)3例(9.6%).主要不良反应为乏力、骨髓抑制、胃肠道反应、手足综合征、粘膜炎等.中位随访时间10.8个月(2～23个月),死亡2例(均死于肿瘤进展),中位无进展生存期(progression-free survival,PFS)5.7个月(2～12个月).结论:多西紫杉醇与卡培他滨联合治疗转移性乳腺癌,有效率高、疗效肯定、不良反应可以耐受,为治疗转移性乳腺癌的有效方案.     

Docetaxel in combination with 5-fluorouracil in patients with metastatic breast cancer previously treated with anthracycline-based chemotherapy: a phase I, dose-finding study

This phase I study evaluated the maximum tolerated dose, dose-limiting toxicity and recommended dose of docetaxel in combination with 5-fluorouracil (5-FU) in patients with metastatic breast cancer previously treated with anthracycline-based chemotherapy. 32 patients received docetaxel at 60, 75, 85 or 100 mg/m(2) by 1-h intravenous (i.v.) infusion, followed, after a 1-h interval, by 5-FU at 250, 350, 500 or 750 mg/m(2)/day by continuous infusion over 5 days every 3 weeks. Dose-limiting stomatitis defined the maximum tolerated dose at a docetaxel dose of 100 mg/m(2) with 5-FU 750 mg/m(2)/day. None of 5 patients treated at the previous dose level (docetaxel 85 mg/m(2) with 5-FU 750 mg/m(2)/day) had a dose-limiting toxicity in the first cycle, and this was, therefore, considered the recommended dose. The combination was generally well tolerated. Grade 4 neutropenia was common (29 patients; 91%), but no patient experienced febrile neutropenia of duration >3 days requiring i.v. antibiotics. An objective response was achieved by 18 patients overall (56%), and in 4 out of 5 patients treated with the determined recommended dose. No pharmacokinetic interaction between docetaxel and 5-fluorouracil was apparent. The activity of docetaxel 85 mg/m(2) with 5-fluorouracil 750 mg/m(2)/day will be explored more extensively in phase II studies of patients with metastatic breast cancer previously treated with anthracycline-based chemotherapy.     

Phase I trial of pegylated liposomal doxorubicin and docetaxel in advanced breast cancer.

PURPOSE: To develop a combination of pegylated liposomal doxorubicin (Doxil; Alza Pharmaceuticals, Palo Alto, CA) and docetaxel (Taxotere; Aventis Pharmaceutical, Parsipanny, NJ) that can be safely used for the treatment of advanced breast cancer. PATIENTS AND METHODS: Forty-one patients with locally advanced (n = 10) or metastatic (n = 31) breast cancer received Doxil (30-, 40-, or 45-mg/m(2) intravenous [IV] infusion over 30 to 60 minutes), followed 1 hour later by docetaxel (60 or 75 mg/m(2) by IV infusion over 1 hour) in cohorts of three to six patients. Dose-limiting toxicity (DLT) was defined as febrile neutropenia, prolonged neutropenia, or grade 3 to 4 nonhematologic toxicity that occurred during cycle 1. RESULTS: In conjunction with docetaxel 75 mg/m(2) every 4 weeks, the MTD of Doxil was 30 mg/m(2) and required granulocyte colony-stimulating factor (G-CSF) to prevent febrile neutropenia. Without G-CSF, the MTD was docetaxel 60 mg/m(2) and Doxil 30 mg/m(2) every 3 weeks; only 1 (7%) out of 15 patients treated at this dose level had cycle 1 DLT. Infusion reactions were common with Doxil with the recommended infusion schedule during the first cycle (55%) but were reduced with a modified schedule (7%). There was no clinically significant cardiac toxicity. Objective response occurred in eight of nine assessable patients with stage III disease and in 16 (52%) of 31 patients (95% confidence interval, 34% to 70%) with stage IV disease. CONCLUSION: The recommended dose and schedule of this combination for further evaluation is Doxil 30 mg/m(2) and docetaxel 60 mg/m(2) given every 3 weeks without G-CSF. When used with G-CSF, it is Doxil 30 mg/m(2) and docetaxel 75 mg/m(2) every 4 weeks.     

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.