曲妥珠单抗联合多西他赛和铂类对HER-2阳性转移性乳腺癌的临床疗效和不良反应

目的：探讨曲妥珠单抗联合多西他赛和铂类治疗HER-2阳性晚期转移性乳腺癌的临床疗效分析。方法：收集我院2008～2015年HER-2阳性转移性乳腺癌74例,随机分为对照组和治疗组,对照组36例,治疗组38例。对照组使用多西他赛联合卡铂、顺铂或奈达铂,治疗组在此基础上联合曲妥珠单抗靶向治疗,分析对比两组的临床疗效及不良反应情况。结果：对照组治疗有效率为41.6%,治疗组为62.8%,两组治疗效果具有显著差异（P<0.05）,具有统计学意义;两组的不良反应发生率没有明显差异,不具有统计学意义。结论：曲妥珠单抗联合多西他赛和铂类治疗HER-2阳性晚期转移性乳腺癌疗效更佳,比单纯化疗临床效果更好,不良反应发生率没有明显增加,在临床值得推广。     

乳腺癌治疗药Perjeta在日本上市

<正>2013年6月28日,Chugai制药公司宣布,日本批准Perjeta(pertuzumab,帕妥珠单抗)用于治疗此前未经化疗的类表皮生长因子受体2(HER2)阳性型转移性或局部复发而不能手术切除的乳腺癌患者。Perjeta是一种人源化单克隆抗体,通过结合HER2,阻滞了HER2与其他HER受体的杂二聚,从而减缓了肿瘤的生长。Pertuzumab与曲妥珠单抗和多西他赛联合使用,很可能将成为治疗转移性乳腺癌一线     

化疗联合曲妥珠单抗靶向治疗HER2阳性转移性乳腺癌的效果及对血清肿瘤标志物的影响

目的：研究分析人表皮生长因子受体2(HER2)阳性转移性乳腺癌患者联合应用化疗与曲妥珠单抗靶向治疗的效果。方法：采用奇偶数分组法随机将我院2018年1月～2021年6月收治的60例HER2阳性转移性乳腺癌患者分为两组,对照组采用化疗治疗,研究组采用化疗与妥珠单抗靶向治疗,观察两组治疗效果、血清肿瘤标志物水平及不良反应情况。结果：研究组患者总缓解率高于对照组（P <0.05）;治疗后研究组多肽特异性抗原（TPS）、癌胚抗原（CEA）、糖蛋白抗原125(CA125)水平均低于对照组（P <0.05）;两组不良反应发生率无明显差异（P> 0.05）。结论：联合应用化疗与曲妥珠单抗疗效更佳,可有效降低患者血清肿瘤标志物水平,安全性较高。     

帕妥珠单抗、曲妥珠单抗联合白蛋白紫杉醇治疗1例转移性乳腺癌患者致指甲脱落案例报道

<正>帕妥珠单抗于2018年12月18日在我国正式上市,帕妥珠单抗联合曲妥珠单抗和紫杉醇类药物可能作为人表皮生长因子受体-2(human epidermal growth factor receptor-2,HER2)阳性晚期乳腺癌患者的一线治疗选择~([1-4]),未来会有越来越多的转移性乳腺癌患者使用曲妥珠单抗、帕妥珠单抗联合紫杉醇类药物的治疗方案,其不良反应也可能越来越常见。本文报道1例转移性乳腺癌患者采用曲妥珠单抗、帕妥珠单抗联合白蛋白     

辅助化疗联合曲妥珠单抗治疗人表皮生长因子受体-2阳性晚期或转移性乳腺癌的系统评价

目的：系统评价辅助化疗联合曲妥珠单抗治疗人表皮生长因子受体-2（HER2）阳性晚期或转移性乳腺癌的临床效果。方法：检索国内外公开发表的关于辅助化疗联合曲妥珠单抗治疗HER2阳性晚期或转移性乳腺癌的中英文文献,对纳入的研究进行比较。结果：共纳入6篇随机对照试验（RCT）研究。辅助化疗联合曲妥珠单抗治疗HER2阳性晚期或转移性乳腺癌的反应率和病理完全缓解率的风险比（RR）分别为1.46（P=0.02）和0.98（P=0.91）。结论：尽管研究存在一定的局限性,但在不考虑治疗成本的情况下,辅助化疗联合曲妥珠单抗治疗要优于标准治疗,临床上具有较强的可替代性。     

国外新近批准主要新药（四十六）

欧盟批准曲妥珠单抗联合化疗方案一线治疗HER2阳性的转移性胃癌 Roche公司2010年1月28日宣布,欧盟委员会已批准其曲妥珠单抗（trastuzumab／Herceptin）—新适应证,即联合由氟尿嘧啶（nuomuracil）和顺铂（cisplatin）或卡培他滨（capecitabine）和顺铂组成的化疗方案一线治疗表皮生长因子受体一2表达过度（HER2阳性）的转移性胃癌。     

盘点2005年乳腺癌内科治疗进展

乳腺癌内科治疗方案的评价,如曲妥珠单抗作为乳腺癌辅助治疗的疗效和不良反应,多西他赛与紫杉醇用于转移性乳腺癌的疗效比较,贝伐单抗的一线治疗新方案,以及多柔比星 环磷酰胺与紫杉醇或多西他赛序贯的3周及每周治疗方案等的研究,成为2005年乳腺癌临床治疗的焦点。     

曲妥珠单抗联合多西他赛对乳腺癌的疗效分析

目的探讨曲妥珠单抗联合多西他赛治疗在乳腺癌中的疗效。方法选取2012年1月至2014年12月本院收治的局部浸润性乳腺癌患者120例,按随机数字表法分为观察组和对照组,每组60例,对照组采用多柔比星+环磷酰胺治疗,观察组在对照组基础上加用曲妥珠单抗联合多西他赛治疗,共治疗8个疗程。观察治疗后乳腺癌组织标本的HMGI-C基因表达和血清C反应蛋白水平,评价2组疗效。结果观察组HMGI-C阳性率显著低于对照组,其差异有统计学意义(P<0.05)。观察组平均LI值、人表皮生长因子受体-2(HER-2)阳性率、p53阳性率、雌激素受体阴性率显著高于HMGI-C阴性组,其差异有统计学意义(P<0.05);观察组血清CRP水平明显低于对照组,其差异有统计学意义(P<0.05)。结论曲妥珠单抗联合多西他赛治疗局部浸润性乳腺癌疗效好,可降低HMGI-C和CRP的表达水平,改善患者预后。     

曲妥珠单抗辅助化疗治疗HER2阳性乳腺癌有效性和安全性的Meta分析

目的 系统评价曲妥珠单抗辅助化疗治疗HER2阳性乳腺癌的有效性和安全性。方法 计算机检索国内外1996-2013年发表的曲妥珠单抗辅助化疗治疗HER2 阳性乳腺癌的前瞻性随机对照研究,对符合纳入标准的研究以Jadad评分标准进行文献质量评价,并使用Review Manager 5.3进行Meta分析。结果 共纳入4项III 期临床随机对照试验(其中有两项试验为合并分析)。Meta分析结果显示,与单纯化疗相比,曲妥珠单抗联合化疗治疗HER2 阳性乳腺癌可以显著延长患者的无病生存期DFS(HR=0.63,95%CI [0.50,0.81],P<0.001)和总生存期OS(HR=0.69,95%CI [0.56,0.86],P=0.001)。在安全性方面,曲妥珠单抗联合化疗组心脏事件(RR=5.09,95% CI [3.23,8.03],P<0.00001)及充血性心力衰竭(RR=5.32,95% CI [2.28,12.44],P=0.0001)发生率显著高于单纯化疗组,而在心脏事件导致的死亡方面,两组没有显著差异。 结论 曲妥珠单抗联合化疗治疗HER2阳性乳腺癌的疗效显著优于单纯化疗,但心脏事件也显著增加。     

曲妥珠单抗对多西他赛或长春瑞滨辅助治疗乳腺癌的不同疗效

曲妥珠单抗(trastuzumab,Herceptin)是罗氏公司开发的针对HER2蛋白的单克隆抗体。本研究对比了多西他赛(docetaxel)和长春瑞滨(vinorebine)对早期乳腺癌的辅助治疗效果,并且对其中过度表达HER2/neu的女性患者联用曲妥珠单抗与不用曲妥珠单抗治疗的疗效进行比较。随机挑选1010名     

Trastuzumab: new indication. Metastatic breast cancer, in combination with docetaxel: promising, but more evaluation is needed

(1) There is no consensus on the optimal chemotherapy for metastatic breast cancer. Patients who have never previously received chemotherapy are generally given an anthracycline-based combination of cytotoxic agents. Options for patients who have already received an anthracycline include a taxane such as paclitaxel or docetaxel. The median survival time with these treatments is only about 2 to 2.5 years. (2) Trastuzumab is a monoclonal antibody directed against HER-2, a protein overexpressed by certain tumours, including about 25% of breast tumours. In 2000, the approved indications included first-line treatment of metastatic breast cancer in combination with paclitaxel. One clinical trial had shown, albeit with a low level of evidence, a median increase in survival of about 4 to 5 months. Trastuzumab is now approved for first-line treatment of metastatic breast cancer, in combination with docetaxel. (3) Evaluation data include the results of an open-label trial comparing docetaxel + trastuzumab with docetaxel monotherapy in 186 patients. The median survival time was significantly longer with the combination (31.2 versus 22.7 months). There are no relevant comparisons with other widely used cytotoxic drugs. Indirect comparison suggests that survival is similar with docetaxel + trastuzumab and paclitaxel + trastuzumab. (4) Data on the trastuzumab-docetaxel combination confirm the known adverse effects of trastuzumab, which include heart failure and diarrhea. Trastuzumab increases the frequency of docetaxel-induced neutropenia, which carries a risk of infections. (5) In summary, the results of clinical trials show that median survival time is increased by a few months when trastuzumab is added to a cytotoxic drug. However, the best cytotoxic agent is not known, and adverse effects are poorly documented. (6) In practice, trastuzumab has only been shown to benefit a minority of women with breast cancer, namely those whose tumours overexpress HER-2. Trastuzumab therapy is an option for metastatic breast cancer treatment, provided patients are enrolled in studies designed to answer the many outstanding questions.     

Docetaxel/trastuzumab combination therapy for the treatment of breast cancer

Trastuzumab is a humanised monoclonal antibody that targets the extra cellular domain of human epidermal growth factor receptor-2 (HER-2), which is overexpressed in ~ 20% of human breast cancers. Clinical benefit has been shown in breast cancer patients with HER-2 amplification or overexpression when trastuzumab is used alone or in combination with chemotherapy. Docetaxel is one of the most potent chemotherapy agents in the treatment of patients with metastatic and early-stage breast cancer. The rationale for combining these two drugs is based not only on preclinical synergic data, but also on expanding clinical results. This article reviews the results of trials investigating this two-drug combination, as well as the triple combinations including docetaxel and trastuzumab with platinum salts. These combinations appear to be amongst the most active therapies for the treatment of patients with HER-2-positive breast cancer in metastatic and potentially adjuvant settings.     

Docetaxel/trastuzumab combination therapy for the treatment of breast cancer

Trastuzumab is a humanised monoclonal antibody that targets the extra cellular domain of human epidermal growth factor receptor-2 (HER-2), which is overexpressed in approximately 20% of human breast cancers. Clinical benefit has been shown in breast cancer patients with HER-2 amplification or overexpression when trastuzumab is used alone or in combination with chemotherapy. Docetaxel is one of the most potent chemotherapy agents in the treatment of patients with metastatic and early-stage breast cancer. The rationale for combining these two drugs is based not only on preclinical synergic data, but also on expanding clinical results. This article reviews the results of trials investigating this two-drug combination, as well as the triple combinations including docetaxel and trastuzumab with platinum salts. These combinations appear to be amongst the most active therapies for the treatment of patients with HER-2-positive breast cancer in metastatic and potentially adjuvant settings.     

Trastuzumab: a review of its use in the management of HER2-positive metastatic and early-stage breast cancer

Trastuzumab (Herceptin) is a humanised monoclonal antibody used in the treatment of breast cancer that overexpresses human epidermal growth factor receptor 2 (HER2), which is associated with clinically aggressive disease and a poor prognosis. The addition of intravenous trastuzumab to first-line chemotherapy improved the time to disease progression, objective response rate, duration of response, and overall survival in randomised, multicentre trials in women with HER2-positive metastatic breast cancer. As such, trastuzumab has become the standard of care in this setting, despite its high acquisition cost and potential for cardiac events, and is licensed for use in combination with paclitaxel (Europe and the US) or docetaxel (Europe). In addition, trastuzumab monotherapy is approved for use in patients with HER2-positive metastatic breast cancer who have previously received chemotherapy for their metastatic disease. Recent data from large phase III trials with trastuzumab in the adjuvant setting revealed significant improvements in disease-free and overall survival. Thus, trastuzumab is also rapidly becoming a standard component of adjuvant therapy for patients with HER2-positive early-stage breast cancer.     

替吉奥与卡培他滨分别联合多西他赛治疗转移性乳腺癌的临床研究

目的：比较替吉奥联合多西他赛及卡培他滨（希罗达）联合多西他赛治疗转移性乳腺癌的临床疗效。方法将88例转移性乳腺癌患者采用随机数字表法分成观察组和对照组,每组44例。治疗组应用替吉奥联合多西他赛进行治疗,对照组应用希罗达联合多西他赛进行治疗。比较两组患者临床总有效率、无进展生存期、生活质量及不良反应发生率。结果观察组总有效率为75．00％,高于对照组的38．64％（χ2＝2.199,P＜0．05）。观察组患者无进展生存期达（10．53±3．21）个月,长于对照组的（5．72±2．10）个月（t＝0.667,P＜0．05）。随访3个月后,观察组患者躯体、社会支持、心理、精神等4个因子各项评分均明显优于对照组（ t＝2．885、2．326、3．379、5．503,均P＜0．05）。结论替吉奥联合多西他赛治疗转移性乳腺癌临床疗效确切,不良反应可耐受,临床上可作为转移性乳腺癌化疗的新方案。     

多西他赛联合卡培他滨治疗复发转移乳腺癌的不良反应及药学监护

目的：针对多西他赛联合卡培他滨治疗复发转移乳腺癌的不良反应及药学监护过程,探讨临床药师在肿瘤患者药物治疗中的作用。方法：收集2011年7月-2013年3月临床药师监护下的26例复发转移乳腺癌患者,该26例患者均接受多西他赛联合卡培他滨方案化疗（第1天,多西他赛75mg／m^2,静脉滴注＋第1～14天,卡培他滨950mg／m^2,bid,口服。21d为1个周期）。临床药师在用药辅导、预服地塞米松、胃肠道反应、口腔黏膜溃疡、手足综合征、骨髓抑制等方面为患者提供药学服务,预防和解决化疗相关不良反应。结果：临床药师为患者制订了个体化治疗方案,患者在顺利完成化疗的同时,不良反应显著降低。结论：临床药师对肿瘤患者提供药学服务,可显著提高患者的生活质量。     

Recent findings with docetaxel in postoperative treatment for breast cancer

Breast cancer is the most common cancer affecting women. A comparison of docetaxel and 5-fluorouracil in women with operable node-positive breast cancer, also taking doxorubicin and cyclophosphamide, was started in 1997. The primary end point was disease-free survival; the time from randomisation to clinical relapse, a second cancer, or death. In a median follow up of 55 months, fewer events had occurred in the docetaxel (172/745) than the 5-fluorouracil group (227/746). This suggests that docetaxel should replace 5-fluorouracil, and that docetaxel, doxorubicin and cyclophosphamide should become the standard treatment of operable node-positive breast cancer. Paclitaxel and docetaxel are approved for use in patients with metastatic breast cancer. In a head-to-head trial of paclitaxel with docetaxel in patients with metastatic breast cancer, despite previous chemotherapy including anthracycline, an overall response (complete and partial) was observed in more docetaxel than paclitaxel patients. This suggests that docetaxel should be preferred to paclitaxel in this group of patients.     

多西他赛联合卡培他滨治疗复发转移乳腺癌的不良反应分析及药学监护

目的探究多西他赛联合卡培他滨治疗复发转移乳腺癌的不良反应及药学监护,研究药学监护的应用价值。方法 80例复发转移乳腺癌患者,按数字法随机分为观察组与对照组各40例,观察组给予多西他赛联合卡培他滨治疗,并由临床药师进行药学监护。对照组给予多西他赛联合卡培他滨治疗。观察两组患者不良反应情况及满意度。结果观察组患者中出现白细胞减少、手足综合征、血小板减少、恶心呕吐、迟发型腹泻、脱发等情况明显少于对照组,差异有统计学意义（P〈0.05）;观察组患者满意度明显高于对照组,差异有统计学意义（P〈0.05）。结论多西他赛联合卡培他滨治疗复发转移乳腺癌临床效果确切,且进行药学监护能给患者进行针对性指导,有效降低不良反应的发生,提高患者的满意度,值得在临床上推广与应用。     

Trastuzumab: a pharmacoeconomic review of its use in early breast cancer

Trastuzumab (Herceptin) is a monoclonal antibody approved for the treatment of breast cancer that overexpresses human epidermal growth factor receptor 2 (HER2). Well designed clinical trials in women with early breast cancer have demonstrated that 1 years' therapy with adjuvant intravenous trastuzumab (a loading dose followed by 6 mg/kg every 3 weeks or 2 mg/kg weekly) significantly improves disease-free survival and overall survival compared with observation (subsequent to chemotherapy) or chemotherapy alone in women with HER2-positive disease. In the HERA trial, disease-free survival was estimated to improve by 6.3% at 3 years in the trastuzumab group compared with the observation group. Trastuzumab is generally well tolerated. The most common adverse events are infusion-related symptoms, such as fever and chills, which usually occur with administration of the first dose. Cardiotoxicity occurs in a small proportion of patients receiving trastuzumab, particularly when coadministered with anthracyclines, and cardiac assessment is recommended for all patients at baseline and at 3-monthly intervals. In modelled cost-effectiveness analyses based on data from clinical trials in patients with HER2-positive early breast cancer, adjuvant trastuzumab was predicted to be cost effective from a healthcare payer or societal perspective in several countries. Incremental costs per QALY or life-year gained with trastuzumab administered subsequent to or concurrent with chemotherapy compared with chemotherapy alone were consistently within accepted local thresholds for cost effectiveness. Sensitivity analyses demonstrated that these results remained generally robust to plausible changes in key model assumptions. In conclusion, in patients with HER2-positive early breast cancer, the addition of adjuvant trastuzumab is clinically effective in improving disease-free survival. Available pharmacoeconomic data from several countries, despite some inherent limitations, support the use of adjuvant trastuzumab for 1 year as a cost-effective treatment relative to chemotherapy alone in this patient population.     

盐酸多柔比星联合环磷酰胺治疗乳腺癌患者的临床疗效

目的针对乳腺癌患者采用盐酸多柔比星联合环磷酰胺治疗的疗效进行分析。方法 90例乳腺癌患者,根据化疗方式不同分为对比组和观察组,每组45例。对比组患者采取常规化疗方式(多西他赛、吡柔比星联合顺铂化疗法)进行治疗,观察组患者采取新辅助化疗方式(多西他赛、盐酸多柔比星联合环磷酰胺化疗法)进行治疗。对比两组患者近期疗效、远期疗效、化疗前后血管新生指标[血管内皮生长因子A(VEGFA)、血管内皮生长因子B(VEGFB)]、化疗后不良反应发生情况。结果观察组患者近期化疗有效率为82.22%(37/45),明显高于对比组的62.22%(28/45),差异具有统计学意义(P<0.05)。观察组患者远期化疗有效率为71.11%(32/45),明显高于对比组的48.89%(22/45),差异具有统计学意义(P<0.05)。化疗后,观察组患者VEGFA为(82.63±10.63)ng/ml,低于对比组的(138.63±18.46)ng/ml,差异具有统计学意义(P<0.05)。化疗后,观察组患者VEGFB为(77.52±7.95)ng/ml,低于对比组的(126.95±5.69)ng/ml,差异具有统计学意义(P<0.05)。观察组患者不良反应发生率24.44%(11/45)低于对比组的44.44%(20/45),差异具有统计学意义(P<0.05)。结论乳腺癌患者采用盐酸多柔比星联合环磷酰胺治疗,能够有效提高患者化疗效率,改善患者临床症状,使患者血管新生指标得到改善,降低患者化疗期间的不良反应发生率,具有良好治疗价值。