单克隆抗体作为老年血液系统恶性肿瘤的靶向治疗

Rao Arati V, Schmader Kenneth

Division of Medical Oncology and Cell Therapy, Division of Geriatrics, Duke University Medical Center, Durham Veterans Affairs Medical Center, Durham, North Carolina 27710, USA.

Am J Geriatr Pharmacother. 2007 Sep;5(3):247-62. doi: 10.1016/j.amjopharm.2007.09.002.

BACKGROUND

Biological agents are proving to be increasingly useful and exciting additions to the antineoplastic armamentarium, but many clinicians are unfamiliar with the properties of these types of agents.

OBJECTIVES

This review focuses on monoclonal antibodies (MAbs) that are used in the treatment of hematologic malignancies. Our goal was to provide the reader with information on trials that led to US Food and Drug Administration (FDA) approval of commonly used MAbs in hematologic malignancies, including their mechanisms of action and pharmacokinetics, with specific emphasis on use in elderly patients; we also present data on toxicities and precautions to be aware of when administering these drugs.

METHODS

Materials for this review were gathered based on a computerized literature search (English-language articles only) using the PubMed database covering the period January 1998 to December 2005. Search terms used included the following: elderly, monoclonal antibodies, and neoplasms.

RESULTS

Alemtuzumab is a recombinant DNA-derived, humanized MAb directed against the CD52 B-cell antigen. It is indicated for the treatment of B-cell chronic lymphocytic leukemia (CLL) in patients who have been treated with alkylating agents and who have failed to respond to fludarabine therapy. Gemtuzumab ozogamicin is an MAb conjugated with a cytotoxic antitumor antibiotic, calicheamicin. It has been approved for use in patients with CD33-positive acute myeloid leukemia (AML) in first relapse who are aged > or =60 years and who are not considered candidates for other cytotoxic chemotherapy. Rituximab, one of the first MAbs approved by the FDA for use in human cancers, is an antibody directed against the CD20 antigen found on the surface of normal and malignant B lymphocytes. It is extensively used in the treatment of B-cell malignancies, such as CLL, and non-Hodgkin's lymphomas (NHLs), such as follicular lymphoma and diffuse large B-cell lymphoma.

CONCLUSIONS

It is noteworthy that while there have been a number of studies using these agents in the younger population, there continues to be a paucity of clinical trials targeting the elderly patient in particular; this continues to be an area of research interest. More clinical studies of these agents--conducted specifically in elderly patients with CLL, NHL, AML, and other hematologic malignancies--are needed.

背景

生物制剂已被证明是抗肿瘤药库中越来越有用且令人兴奋的补充药物，但许多临床医生对这类药物的特性并不熟悉。

目的

本综述聚焦于用于治疗血液系统恶性肿瘤的单克隆抗体（MAb）。我们的目标是为读者提供导致美国食品药品监督管理局（FDA）批准常用于血液系统恶性肿瘤的单克隆抗体的试验信息，包括其作用机制和药代动力学，特别强调在老年患者中的应用；我们还展示了这些药物给药时的毒性和注意事项的数据。

方法

本综述的材料是基于使用PubMed数据库进行的计算机化文献检索（仅英文文章）收集的，检索时间段为1998年1月至2005年12月。使用的检索词包括：老年人、单克隆抗体和肿瘤。

结果

阿仑单抗是一种重组DNA衍生的人源化单克隆抗体，靶向CD52 B细胞抗原。它适用于治疗接受过烷化剂治疗且对氟达拉滨治疗无效的B细胞慢性淋巴细胞白血病（CLL）患者。吉妥单抗奥佐米星是一种与细胞毒性抗肿瘤抗生素刺孢霉素偶联的单克隆抗体。它已被批准用于年龄≥60岁且不适合其他细胞毒性化疗的首次复发的CD33阳性急性髓系白血病（AML）患者。利妥昔单抗是FDA批准用于人类癌症的首批单克隆抗体之一，是一种针对正常和恶性B淋巴细胞表面发现的CD20抗原的抗体。它广泛用于治疗B细胞恶性肿瘤，如CLL，以及非霍奇金淋巴瘤（NHL），如滤泡性淋巴瘤和弥漫性大B细胞淋巴瘤。