Dillman Robert O, Hendrix Carolyn S
Hoag Cancer Center, Newport Beach, CA.
Support Cancer Ther. 2003 Oct 1;1(1):38-48. doi: 10.3816/SCT.2003.n.003.
The "magic bullet" era of targeted cancer therapy began with the United States Food and Drug Administration approval of rituximab for the treatment of B-cell lymphoma in the late fall of 1997. Since then, several additional anticancer antibody products have received regulatory approval, including the monoclonal antibodies (MoAbs) trastuzumab for breast cancer and alemtuzumab for chronic lymphocytic leukemia, and the MoAb immunoconjugates gemtuzumab ozogamicin for acute myelogenous leukemia and yttrium 90 ibritumomab tiuxetan for B-cell lymphoma. These products are associated with adverse events that are quite different than those seen with chemotherapy. Adverse events associated with MoAb products typically have 1 of 3 etiologies: direct and indirect effects of antibody-antigen interaction, effects of toxins or radioisotopes that have been conjugated to antibodies, and allergic and hypersensitivity reactions to foreign protein. The infusion-related symptom complex is the most common and predictable side effect associated with all MoAbs that react with circulating blood cells. This pattern of various systemic effects includes flu-like symptoms such as headache, shortness of breath, fever, skin rash, hypotension, nausea, and asthenia, but usually occurs only in association with the first of any series of weekly infusions. The severity of these reactions is influenced by the rate of infusion, and the syndrome is the consequence of cytokines released from immune cells. Severe hypotension, bronchospasm, hypoxia, and even death have occurred. A true tumor lysis syndrome may occur if there are large numbers of proliferating antigen-positive cells in the blood. Symptoms related to the infusion reaction are ameliorated by slowing or stopping the infusion and administering antiinflammatory agents and antihistamines.
1997年秋末,美国食品药品监督管理局批准利妥昔单抗用于治疗B细胞淋巴瘤,开启了靶向癌症治疗的“神奇子弹”时代。从那时起,又有几种抗癌抗体产品获得了监管批准,包括用于治疗乳腺癌的单克隆抗体曲妥珠单抗、用于治疗慢性淋巴细胞白血病的阿仑单抗,以及用于治疗急性髓性白血病的单克隆抗体免疫缀合物吉妥珠单抗奥唑米星和用于治疗B细胞淋巴瘤的钇90 伊布替膦酸。这些产品所引发的不良事件与化疗所见的不良事件截然不同。与单克隆抗体产品相关的不良事件通常有3种病因之一:抗体 - 抗原相互作用的直接和间接影响、与抗体偶联的毒素或放射性同位素的影响,以及对外源蛋白的过敏和超敏反应。输液相关症状复合体是所有与循环血细胞发生反应的单克隆抗体相关的最常见且可预测的副作用。这种各种全身效应的模式包括类似流感的症状,如头痛、呼吸急促、发热、皮疹、低血压、恶心和乏力,但通常仅在每周一系列输液的第一次输液时出现。这些反应的严重程度受输液速度影响,该综合征是免疫细胞释放细胞因子的结果。曾发生过严重低血压、支气管痉挛、缺氧甚至死亡的情况。如果血液中有大量增殖的抗原阳性细胞,则可能发生真正的肿瘤溶解综合征。通过减慢或停止输液并给予抗炎药和抗组胺药,可以缓解与输液反应相关的症状。