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单克隆抗体在癌症治疗中的应用,第2部分。

Monoclonal antibodies in the treatment of cancer, Part 2.

作者信息

Cersosimo Robert J

机构信息

Northeastern University School of Pharmacy, Boston Veterans Affairs Medical Center, Boston, MA, USA.

出版信息

Am J Health Syst Pharm. 2003 Aug 15;60(16):1631-41; quiz 1642-3.

Abstract

Monoclonal antibodies used in the treatment of cancer are discussed. Monoclonal antibodies are a new class of agents targeted at specific receptors on cancer cells. In addition to having direct cellular effects, antibodies can carry substances, such as radioactive isotopes, toxins, and antineoplastic agents, to the targeted cells. Five monoclonal antibodies--rituximab, trastuzumab, gemtuzumab ozogamicin, alemtuzumab, and ibritumomab tiuxetan--are available for clinical use. Rituximab is active against indolent lymphomas, providing a valuable alternative for patients with relapsed or refractory disease. Rituximab plus cyclophosphamide-doxorubicin-vincristine-prednisone (CHOP) increased survival over CHOP alone in patients with high-grade lymphomas. Trastuzumab has significant activity against HER-2-positive breast cancer, especially in combination with paclitaxel or an anthracycline and cyclophosphamide. Gemtuzumab ozogamicin is an active second-line therapy in older patients with acute myelogenous leukemia, but its role in combination regimens is unclear. Alemtuzumab is a valuable option for salvage therapy of patients with chronic lymphocytic leukemia. Ibritumomab tiuxetan delivers radioactive isotopes to tumor cells and is active against indolent lymphomas in patients who have relapsed after chemotherapy or rituximab therapy. The most common adverse effects of monoclonal antibodies are myelosuppression, infusion-related reactions, and hypersensitivity reactions. Rituximab may cause tumor lysis syndrome, arrhythmias, and pulmonary dysfunction. Alemtuzumab causes immunosuppression, increasing the risk of infection. Gemtuzumab ozogamicin may cause hepatotoxicity, and trastuzumab may cause significant pulmonary or cardiac toxicity. Investigational monoclonal antibodies include edrecolomab and tositumomab. Monoclonal antibodies have a significant role in the management of patients with advanced refractory or relapsed lymphomas and leukemias.

摘要

本文讨论了用于癌症治疗的单克隆抗体。单克隆抗体是一类新型药物,靶向癌细胞上的特定受体。除了具有直接的细胞效应外,抗体还可携带诸如放射性同位素、毒素和抗肿瘤药物等物质至靶向细胞。有五种单克隆抗体——利妥昔单抗、曲妥珠单抗、吉妥珠单抗奥唑米星、阿仑单抗和替伊莫单抗——可供临床使用。利妥昔单抗对惰性淋巴瘤有效,为复发或难治性疾病患者提供了一种有价值的替代疗法。在高级别淋巴瘤患者中,利妥昔单抗联合环磷酰胺-阿霉素-长春新碱-泼尼松(CHOP)方案比单纯CHOP方案提高了生存率。曲妥珠单抗对HER-2阳性乳腺癌具有显著活性,尤其是与紫杉醇或蒽环类药物及环磷酰胺联合使用时。吉妥珠单抗奥唑米星是老年急性髓性白血病患者的一种有效的二线治疗药物,但其在联合治疗方案中的作用尚不清楚。阿仑单抗是慢性淋巴细胞白血病患者挽救治疗的一个有价值的选择。替伊莫单抗将放射性同位素传递至肿瘤细胞,对化疗或利妥昔单抗治疗后复发的惰性淋巴瘤患者有效。单克隆抗体最常见的不良反应是骨髓抑制、输液相关反应和过敏反应。利妥昔单抗可能导致肿瘤溶解综合征心律失常和肺功能障碍。阿仑单抗导致免疫抑制,增加感染风险。吉妥珠单抗奥唑米星可能导致肝毒性,曲妥珠单抗可能导致严重的肺部或心脏毒性。正在研究的单克隆抗体包括依德西单抗和托西莫单抗。单克隆抗体在晚期难治性或复发性淋巴瘤和白血病患者的治疗中具有重要作用。

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