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31.
This article reviews the current state of efforts targeting human epidermal growth factor receptor-2 (erbB2/HER2)in breast cancer therapy. The results of recently conducted clinical studies with trastuzumab and several other compounds are presented. Trastuzumab, a humanised monoclonal antibody(mAb)directed against the extracellular domain of HER2, has been shown to be active against HER2-overexpressing metastatic breast cancer, either as a single agent or when used in combination with chemotherapy. In preclinical models, trastuzumab has shown additive and even synergistic anti-tumor activity with the chemotherapeutic agents. In a large, randomised, phase III trial, the combination of trastuzumab and chemotherapy was shown to improve the response rate and survival in patients with metastatic breast cancer. The high incidence of cardiotoxicity seen with the combination of trastuzumab plus anthracycline drugs prompted several clinical studies combining trastuzumab with other chemotherapeutic agents, including taxanes, vinorelbine and platinum salts. This article summarises the available data on trastuzumab-based combination chemotherapies and novel drugs targeting HER2 and signal transduction molecules for the treatment of breast cancer. 相似文献
32.
注射用曲妥珠单抗治疗晚期乳腺癌临床验证结果 总被引:10,自引:3,他引:7
目的 验证单克隆抗体制剂注射用曲妥珠单抗(trastuzumab,商品名赫赛汀^*)对晚期乳腺癌的疗效和不良反应。方法 对经病理诊断的晚期乳腺癌应用赫赛汀^*治疗。第1次给予负荷剂量4mg/kg静脉滴注,以后剂量改为2mg/kg,每周1次。注射3个月以上评价临床疗效。结果 3l例患者中,治疗后完全缓解(CR)2例,部分缓解(PR)6例,稳定(SD)7例,进展(PD)16例,CR PR共8例,有效率为25.8%(ITT分析)。患者年龄、一般状况对疗效有一定影响,而病理类型、病变部位、既往治疗和病理her-2阳性程度对疗效无明显影响。该药不良反应轻微,而且和一般化疗不同。结论 赫赛汀^*对中国乳腺癌患者疗效肯定,安全性较好,为一较安全、有效的新型乳腺癌治疗药物。 相似文献
33.
Takahashi M Inoue K Goto R Tamura M Taguchi K Takahashi H Suzuki H Katsushige K Ogita M 《Breast cancer (Tokyo, Japan)》2003,10(2):170-174
We report that single agent therapy with trastuzumab had a significant effect on metastatic breast cancer, which was confirmed to be HER2 positive by Herceptest showing 2+staining, and gene amplification positively detected by FISH analysis. A 48-year-old woman underwent extended radical mastectomy (T2N0M0 stage II). Three years after the operation supraclavicular lymph node metastasis was noted. Bone scintigraphy showed metastases to the left ribs 5 years after operation. She was treated with chemo-endocrine therapy, but nonetheless could not bear the back pain caused by the bone metastases. Another chemotherapy course could not be permitted because of leukopenia. Immunohistochemistry (IHC) analysis with Herceptest showed 2+staining for HER2 and FISH analysis showed gene amplification of HER2. We started single agent therapy with trastuzumab and she subsequently had remarkably improved back pain. Physical examination and ultrasonography showed disappearance of the previous palpable supraclaviclar lymph nodes. Serum tumor markers were also reduced after the first administration of trastuzumab. The patient is currently alive, with no further progression of the lymph node or bone metastases. 相似文献
34.
在乳腺癌治疗中,蒽环类药物、紫杉类药物和靶向治疗药物曲妥单抗均具有心脏毒性,第三代芳香化酶抑制剂会增加冠状动脉粥样硬化性心脏病(冠心病)的风险,放疗也会引起心脏毒性。尤其以蒽环类化疗药物及其联合化疗方案的心脏毒性最为突出。因此,早期心脏毒性的检测对于预防和治疗心脏损害至关重要,心脏毒性的评价方法有多种,如心电图、心肌活检、超声心动图等,常规超声心动图是最常用的方法,超声心动图及其新技术的应用对心脏毒性的检测有重要价值。 相似文献
35.
BackgroundFor human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) with progression on trastuzumab-based therapy, continuing trastuzumab beyond progression and switching to lapatinib combined with chemotherapy are both valid options. We conducted an open-label, randomized phase II trial to compare the efficacy of these strategies.Patients and methodsWomen with HER2-positive MBC previously treated with trastuzumab and taxanes were randomly assigned to receive trastuzumab plus capecitabine (HX) or lapatinib plus capecitabine (LX). The primary endpoint was progression-free survival (PFS) and the secondary endpoints included overall survival (OS) and the objective response rate (ORR). To explore the predictive value of the differential benefit of anti-HER2 drugs, PIK3CA mutations were assessed using circulating tumor DNA.ResultsEighty-six patients (43 in each arm) were enrolled. The median PFS was 6.1 months in the HX arm and 7.1 months in the LX arm (hazard ratio, 0.81; 90% CI, 0.55–1.21; p = 0.39); the median OS was 31.0 months in the HX arm and was not reached in the LX arm (hazard ratio, 0.58; 95% CI, 0.26–1.31; p = 0.18). The ORR was 40% in the HX arm and 41% in the LX arm. PIK3CA mutations were detected in 23% of the 35 analyzed patients, and in patients without PIK3CA mutations, LX yielded relatively longer PFS and OS than HX.ConclusionIn women with HER2-positive MBC previously treated with trastuzumab and taxanes, no significant differences in PFS and OS were observed between patients treated with LX and HX.Trial registration numberUMIN000005219. 相似文献
36.
37.
Cyrus Chargari Krassen M. KirovMarc A. Bollet Nicolas MagnéLionel Védrine Serge CremadesPhilippe Beuzeboc Alain FourquetYoulia M. Kirova 《Cancer treatment reviews》2011,37(4):321-330
When focusing on heart disease, most available studies split the two different parts of the adjuvant treatment, i.e., systemic therapies and radiation therapy, making it difficult to implement efficient strategies for preventing treatment-induced cardiac toxicity. This paper reviews the current understanding of treatments-induced cardiac toxicity in a global approach. Many factors should be considered when assessing the cardiac hazard. Treatment-related risk factors include heart dose exposure, chemotherapy, targeted agents such as HER2 inhibitors, but also endocrine agents, or anesthetic procedure. Patients’ characteristics should also be taken into account. Age, menopausal status, stress, previous history of cardiac disease, genetic profile, and body mass index could all impact on cardiac function after adjuvant therapies. Cardiac toxicity should not be analyzed as the consequence of a specific therapy, but should be considered as the result of additive or supra-additive toxicities. By this way, it will be possible to implement new strategies for preventing treatment-induced cardiac toxicity. 相似文献
38.
《Drug discovery today》2021,26(8):2003-2013
Biologicals undergo modifications throughout their commercial lifecycle. Major changes can unintentionally magnify their inherent physicochemical variability. Although trials comparing the pre- and the post-change versions have been requested occasionally, analytical comparison is the most sensitive approach to anticipating clinical equivalence. Therefore, it may be concluded, by means of ‘extrapolation’, that non-identical versions of a given biologic will behave equally in all indications. Despite the lessons learned with original biologics, there are still controversies around the approval of biosimilars through extrapolation. Here, a comprehensive analysis of scattered information allows for an account of cases of original biologic versions approved in some indications with no patient trials involved. Healthcare professionals can be reassured that inasmuch as extrapolation has proven valid for new versions of original biologics, the same holds for biosimilars. 相似文献
39.
近几年来赫赛汀作为针对人表皮生长因子受体2(human epidermal growth factor receptor-2,HER2)的靶向药物被广泛应用于早期、晚期乳腺癌患者,赫赛汀相关心脏毒性虽然发生率低,但对患者生命具有一定的潜在危险。无症状左室射血分数(LVEF)下降是最常见的心脏毒性事件,通常情况下是可控制和可逆的。赫赛汀相关心脏毒性发生与患者年龄、既往高血压病史和蒽环类为基础的化疗有关。赫赛汀治疗期间需要进行严密的心脏功能监测。 相似文献
40.
Elizabeth M.H. Kim Catherine Lobocki M.S. Linda Dubay M.D. Vijay K. Mittal M.D. 《American journal of surgery》2009,197(3):331-336