Slichenmyer W J, Fry D W
Departments of Oncology Clinical Development and Cancer Research, Pfizer Global Research and Development, Ann Arbor, MI 48105, USA.
Semin Oncol. 2001 Oct;28(5 Suppl 16):67-79. doi: 10.1016/s0093-7754(01)90284-2.
Several agents that target one or more members of the erbB family of receptor tyrosine kinases are currently undergoing clinical investigation. The monoclonal antibody trastuzumab has been shown effective in erbB2-expressing metastatic breast cancer when administered as a single agent or in combination with cytotoxic chemotherapy. Toxicities associated with trastuzumab include infusion-related fever and chills, hypersensitivity reactions, and congestive heart failure. C225 is a monoclonal antibody directed against the epidermal growth factor receptor, which has shown encouraging antitumor activity in early clinical development. The orally active tyrosine kinase inhibitors show encouraging antitumor activity in preclinical models and early clinical trials. Members of this class currently in clinical development include ZD1839, OSI-774, and CI-1033. Evidence to date suggests that the major role for erbB receptor-targeting drugs will be in combined therapy to enhance response to cytotoxic drugs, and in long-term monotherapy to maintain response and prevent disease progression or recurrence.
目前，有几种针对受体酪氨酸激酶erbB家族中一个或多个成员的药物正在进行临床研究。单克隆抗体曲妥珠单抗已被证明，无论是单独使用还是与细胞毒性化疗联合使用，对表达erbB2的转移性乳腺癌均有效。与曲妥珠单抗相关的毒性包括输液相关的发热和寒战、过敏反应以及充血性心力衰竭。C225是一种针对表皮生长因子受体的单克隆抗体，在早期临床开发中已显示出令人鼓舞的抗肿瘤活性。口服活性酪氨酸激酶抑制剂在临床前模型和早期临床试验中显示出令人鼓舞的抗肿瘤活性。目前正在进行临床开发的这类药物包括ZD1839、OSI-774和CI-1033。迄今为止的证据表明，靶向erbB受体的药物的主要作用将在于联合治疗以增强对细胞毒性药物的反应，以及长期单一治疗以维持反应并预防疾病进展或复发。
