含曲妥珠单抗二线治疗HER2阳性乳腺癌的临床价值及安全性分析

目的探讨含曲妥珠单抗二线治疗人表皮生长因子受体2(HER2)阳性乳腺癌的临床价值及安全性。方法选择采用二线方案治疗的78例HER2阳性乳腺癌患者为研究对象,根据患者治疗方式不同分为A组与B组。2组患者均接受吉西他滨联合卡培他滨二线治疗方案,B组患者同时接受曲妥珠单抗治疗。比较2组近期疗效、2年生存率及不良反应发生率。结果 A组与B组治疗有效率及临床获益率均无显著差异(P>0.05);B组2年生存率显著优于A组(P<0.05)。骨髓抑制及消化道不良反应是2组常见的化疗不良反应;曲妥珠单抗的主要不良反应为发热及疼痛,经对症治疗后均完成治疗。结论含曲妥珠单抗二线治疗方案治疗HER2阳性乳腺癌可延长患者生存期,安全性好。     

帕妥珠单抗在HER-2阳性乳腺癌治疗中的临床转化

帕妥珠单抗(pertuzumab)作为一种新的抗人表皮生长因子受体-2(human epidermal growth factor receptor,HER-2)治疗药物,其作用区域不同于曲妥珠单抗,两者联合可以发挥更全面的HER-2抑制作用,基础和临床转化研究均证实帕妥珠单抗和曲妥珠单抗有协同的抗肿瘤作用.Ⅱ期和Ⅲ期临床转化试验结果显示,抗HER-2两药治疗(帕妥珠单抗+曲妥珠单抗)联合化疗可使HER-2阳性晚期乳腺癌的中位无疾病进展时间(progression-free survival,PFS)延长到18个月以上,中位总生存时间(overall survival,OS)接近5年(56.5个月),显著改善了晚期HER-2阳性乳腺癌患者的预后.两项Ⅱ期新辅助治疗临床转化研究也确认帕妥珠单抗联合曲妥珠单抗的协同作用疗效同样突出,病理完全缓解(pathological complete response,pCR)率最高可达66.2％.安全性分析发现,即使是与蒽环类药物联用,加用帕妥珠单抗治疗也并未增加心脏毒性.本文对帕妥珠单抗在HER-2阳性乳腺癌治疗中的上述相关临床转化研究进行综述.     

以曲妥珠单抗为基础的HER-2阳性乳腺癌双靶向治疗进展

HER-2阳性乳腺癌侵袭性强、复发率高,针对HER-2的单靶向治疗虽使患者生存期得以延长,但仍有患者发生复发转移。双靶向治疗因其作用机制不重叠,具有协同作用,使患者生存期得以进一步延长。本文以曲妥珠单抗靶向治疗为基础,对与联合抗HER-2的双靶向治疗的研究现状和进展进行综述。      

曲妥珠单抗联合含长春瑞滨方案治疗人表皮生长因子受体2阳性晚期乳腺癌的研究

目的观察曲妥珠单抗联合长春瑞滨方案治疗人表皮生长因子受体2（HER-2）阳性晚期乳腺癌的疗效及安全性。方法收集中国医学科学院肿瘤医院2001年2月至2012年2月期间应用曲妥珠单抗联合含长春瑞滨化疗方案治疗的55例晚期乳腺癌患者的临床资料。回顾性分析其临床特点、药物疗效、不良反应及生存状况。结果应用曲妥珠单抗联合含长春瑞滨方案治疗的55例患者中,完全缓解（CR）2例,部分缓解（PR）24例,疾病稳定（SD）16例,疾病进展（PD）13例,总有效率为47.3%,疾病控制率为76.4%,中位PFS为8.0个月。患者中位生存时间为46.1个月,1年生存率为95.8%,2年生存率为76.8%,5年生存率为45.7%。3例心悸考虑为曲妥珠单抗相关的不良反应,患者未出现明显心功能不全。不良反应主要为化疗药物导致的血液学毒性和非血液学毒性。结论曲妥珠单抗联合含长春瑞滨方案治疗HER-2阳性的晚期乳腺癌疗效肯定,毒性可耐受。     

芹菜素与曲妥珠单抗联用对HER2阳性乳腺癌协同抗肿瘤作用

目的 探讨芹菜素与曲妥珠单抗联合应用对人表皮生长因子受体2(HER2)阳性乳腺癌细胞系BT474及SK-BR-3的抗肿瘤作用及其机制。方法 采用流式细胞术检测曲妥珠单抗与人乳腺癌细胞的结合活性;细胞计数试剂盒(CCK-8)检测芹菜素、曲妥珠单抗单药及联合应用对BT474和SK-BR-3细胞的生长抑制活性;EdU染色法检测芹菜素、曲妥珠单抗单药及联合应用对BT474和SK-BR-3细胞DNA复制的影响;蛋白质印迹法检测芹菜素、曲妥珠单抗单药及联合应用对BT474和SK-BR-3细胞中表皮生长因子受体(EGFR)、HER2、HER3、Akt等蛋白及其各自磷酸化蛋白表达水平的影响。设置芹菜素组、曲妥珠单抗组、芹菜素+曲妥珠单抗联合用药组、对照组和空白对照组。结果 生长抑制实验结果显示,芹菜素抑制BT474和SK-BR-3细胞生长的半数抑制浓度值分别为25.70和29.34μmol/L。EdU染色实验结果表明,不同浓度芹菜素(16、32、64μmol/L)单药作用于SK-BR-3和BT474细胞后,与对照组比较差异均有统计学意义,F值分别为99.25和309.10,均P<0.001。芹菜...     

曲妥珠单抗在HER-2阳性乳腺癌患者新辅助治疗中的应用研究进展

曲妥珠单抗是人表皮生长因子受体-2（human epidermal growth factor receptor-2,HER-2）的特异性抑制剂,在HER-2阳性乳腺癌患者新辅助治疗中的应用日益广泛。大规模的随机、对照临床试验证实,新辅助化疗联合曲妥珠单抗与单纯化疗比较能显著提高病理完全缓解（pathologic complete response,pCR）率。在曲妥珠单抗联合化疗的基础上加用拉帕替尼较单用曲妥珠单抗可大大提高pCR率。蒽环与非蒽环类化疗药物均可作为曲妥珠单抗的联合用药,内分泌治疗也可作为雌激素受体阳性患者的联合用药。pCR是曲妥珠单抗新辅助治疗后生存获益的独立预后因素,HER-2转阴而未达到pCR的患者为不良预后因素。本文将对曲妥珠单抗在HER-2阳性乳腺癌患者新辅助治疗中的研究进展进行综述。      

曲妥珠单抗和帕妥珠单抗联合化疗对HER2阳性乳腺癌新辅助治疗的真实世界研究

目的 分析曲妥珠单抗(H)和帕妥珠单抗(P)联合化疗对HER2阳性乳腺癌新辅助治疗的疗效和安全性.方法 回顾性分析行HP联合化疗新辅助治疗并完成手术的HER2阳性乳腺癌患者的临床资料,主要研究终点为总体病理完全缓解(tpCR)(ypT0/isypN0),次要研究终点为乳腺病理完全缓解(bpCR)(ypT0/is)和腋窝...     

曲妥珠单抗用于HER2阳性晚期胃癌治疗的近远期疗效及对患者肿瘤标志物的影响

目的 探讨曲妥珠单抗用于人表皮生长因子受体(HER2)阳性胃癌治疗的疗效及对患者血清肿瘤标志物的影响.方法 前瞻性入组HER2阳性胃癌患者80例,随机分为观察组(40例)和对照组(40例).对照组给予顺铂+卡培他滨化疗;在此治疗方案基础上,观察组于化疗第1天加用曲妥珠单抗静脉滴注,8 mg/kg.21 d为1个周期,2组均治疗6个周期.比较2组患者的临床疗效、血清肿瘤标志物水平和不良反应发生情况.结果 治疗6个周期后,观察组总有效率为55.0%,对照组总有效率为32.5%,2组差异有统计学意义(P<0.05);观察组患者的血清癌胚抗原(CEA)、单核细胞趋化因子(MCP-1)等水平均显著低于对照组,差异均有统计学意义(P<0.05).2组患者的恶心呕吐、肝功能损害等不良反应发生率均无统计学差异(P>0.05).结论 曲妥珠单抗具有较好的抗肿瘤效果,可改善HER2阳性胃癌患者的临床疗效,其机制可能与抑制IL-1β、上调MCP-1的表达有关.     

曲妥珠单抗治疗1 8 5例HER2阳性乳腺癌患者的心脏安全性评价

 目的 探讨HER2阳性乳腺癌患者应用曲妥珠单抗治疗的心脏安全性。方法 185例HER2阳性乳腺癌患者接受每3周一次的曲妥珠单抗治疗,首次以负荷剂量8 mg/kg给药,此后每3周给予6 mg/kg静脉滴注,接受治疗4~36周期,观察其心脏安全性。结果 接受曲妥珠单抗治疗的HER2阳性乳腺癌患者中位治疗周期数为17个（4~36个）,88例（47.6%）出现LVEF下降、74例（40.0%）出现瓣膜反流（新增+加重）、16例（8.0%）出现左室舒张功能下降。发生心脏毒性88例（47.6%）,其中Ⅰ级心脏毒性83例、Ⅱ级心脏毒性5例,未见Ⅲ级心脏毒性发生。结论 曲妥珠单抗对HER2阳性乳腺癌患者心脏功能有一定影响,总体安全性良好。但是,在治疗中仍需注意评估与监测。     

Safety and Tolerability of Docetaxel,Cyclophosphamide, and Trastuzumab Compared to Standard Trastuzumab-Based Chemotherapy Regimens for Early-Stage Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer

Purpose

We evaluated the tolerability and cardiac safety of docetaxel, cyclophosphamide, and trastuzumab (TCyH) for the treatment of early-stage human epidermal growth factor receptor 2 (HER2)-positive breast cancer and compared to the standard trastuzumab-based chemotherapy regimens doxorubicin with cyclophosphamide followed by paclitaxel and trastuzumab (AC-TH) and docetaxel, carboplatin, and trastuzumab (TCaH).

Methods

We retrospectively reviewed early-stage, resectable, HER2-positive breast cancer patients treated with trastuzumab-based chemotherapy at a single comprehensive cancer center between 2004 and 2011. Patient characteristics, comorbidities, relative dose intensity (RDI) of each regimen, tolerability, and cardiac toxicity were evaluated.

Results

One hundred seventy-seven patients were included in the study (AC-TH, n=114; TCaH, n=39; TCyH, n=24). TCyH was solely administered in the adjuvant setting, whereas two-thirds of the AC-TH and TCaH groups were administered postoperatively. Patients treated with TCyH tended to have a more significant underlying cardiac history, higher Charlson comorbidity index, and were of an earlier stage. All patients treated with TCyH received granulocyte colony stimulating factor primary prophylaxis. No febrile neutropenia or grade ≥3 hematologic toxicity was observed in the TCyH group as compared to the AC-TH and TCaH groups. There were no significant differences in the rates of early termination, hospitalization, dose reduction, or RDI between the regimens. The symptomatic congestive heart failure rate between AC-TH, TCaH, and TCyH groups was not significantly different (4.4% vs. 2.6% vs. 8.3%, respectively, p=0.57). There was also no significant difference in the rate of early trastuzumab termination between patients treated with each regimen.

Conclusion

TCyH is well tolerated and should be investigated as an alternative adjuvant chemotherapy option for patients who are not candidates for standard trastuzumab-containing regimens. Larger clinical trials are necessary to support the wider use of TCyH as an adjuvant regimen.     

曲妥珠单抗联合新辅助化疗对HER-2阳性乳腺癌患者近远期疗效的影响

目的 探讨曲妥珠单抗联合新辅助化疗对表皮生长因子受体-2(HER-2)阳性乳腺癌患者的疗效.方法 选取HER-2阳性乳腺癌患者58例,随机分为观察组和对照组,各29例.对照组给予表柔比星联合多西他赛的方案进行新辅助化疗,观察组在对照组的基础上给予曲妥珠单抗治疗.比较两组患者的近期、远期疗效.结果 观察组有效率(RR)及病理完全缓解(pCR)率明显优于对照组,5年总生存率(OS)及5年无病生存率(DFS)明显高于对照组.结论 曲妥珠单抗联合新辅助化疗治疗HER-2阳性乳腺癌近期疗效显著,并可有效改善患者预后,值得临床推广应用.     

Efficacy and Safety of Trastuzumab Added to Standard Treatments for HER2-positive Metastatic Breast Cancer Patients

Introduction: Trastuzumab, an HER2-targeting agents, has shown efficacy in metastatic HER2-positivebreast cancer patients. Single-agent clinical trials have evaluated therapeutic regimens using trastuzumab formetastatic breast cancer patients. The aim of our study is to evaluate the efficacy and safety of trastuzumabin combination with chemotherapy or hormone therapy in HER2-positive metastatic breast cancer patients.Methods: A literature research was conducted in PubMed and to identify appropriate studies from relevantreviews. Randomized controlled trials comparing chemotherapy or hormone therapy regimens in combinationwith trastuzumab were eligible. Dadta on clinical outcomes, including safety, efficacy, and patient characteristicswere collected. Results: Seven articles describing five trials were included in our systematic review and metaanalysis.Partners of trastuzumab included in trials were anthracycline, paclitaxel, docetaxel, anastrozole andletrozole. The addition of trastuzumab to chemotherapy improved the overall survival (HR=0.79, 95%CI 0.65-0.96), while to hormone therapy did not (HR=0.85 95%CI 0.56-1.30). All trastuzumab-containing regimensincreased cardiac toxicity (RR=3.37, 95%CI 1.26-9.02) and grade Ⅲ-Ⅳ adverse events. Conclusions: Our studysupports the addition of trastuzumab to chemotherapy which is effective and tolerated for metastatic breastcancer with HER2+ patients. Of note, more adverse events will occur followed the use of trastuzumab, especiallycardiac toxicity, with two treatment regimens.     

Escalating and de-escalating treatment in HER2-positive early breast cancer

The current standard adjuvant systemic treatment of early HER2-positive breast cancer consists of chemotherapy plus 12 months of trastuzumab, with or without endocrine therapy. Several trials have investigated modifications of the standard treatment that are shorter and less resource-demanding (de-escalation) or regimens that aim at dual HER2 inhibition or include longer than 12 months of HER2-targeted treatment (escalation). Seven randomized trials investigate shorter than 12 months of trastuzumab treatment duration. The shorter durations were not statistically inferior to the 1-year duration in the 3 trials with survival results available, but 2 of the trials were small and 1 had a relatively short follow-up time of the patients at the time of reporting. The pathological complete response (pCR) rates were numerically higher in all 9 randomized trials that compared chemotherapy plus dual HER2 inhibition consisting of trastuzumab plus either lapatinib, neratinib, or pertuzumab with chemotherapy plus trastuzumab as neoadjuvant treatments, but the superiority of chemotherapy plus dual HER2-inhibition over chemotherapy plus trastuzumab remains to be demonstrated in the adjuvant setting. One year of adjuvant trastuzumab was as effective as 2 years of trastuzumab in the HERA trial, and was associated with fewer side-effects. Extending 1-year adjuvant trastuzumab treatment with 1 year of neratinib improved disease-free survival in the ExteNET trial, but the patient follow-up times are still short, and no overall survival benefit was reported. Several important trials are expected to report results in the near future and may modify the current standard.