Kantarjian H M, Talpaz M
Department of Leukemia and Bioimmunotherapy, M. D. Anderson Cancer Center, Houston, TX 77030, USA.
Semin Oncol. 2001 Oct;28(5 Suppl 17):9-18.
Targeted cancer therapy has long been sought by the oncology community as a potentially better approach than currently available therapies. One targeted therapy that has shown great success is the tyrosine kinase inhibitor imatinib mesylate (formerly STI571, [Gleevec]; Novartis Pharmaceuticals Corp, East Hanover, NJ) which was recently approved for the treatment of Philadelphia chromosome-positive chronic myeloid leukemia (CML). Basic scientific investigation into the molecular causes and pathogenesis of CML and encouraging preclinical investigations on the mechanism of action of imatinib mesylate led to the initiation of phase I clinical trials. Clinical development of imatinib mesylate continued with three large, multicenter, phase II trials. The majority (88%) of interferon-alpha-resistant or intolerant patients in chronic-phase CML achieved a complete hematologic response to imatinib mesylate. More importantly, approximately half of patients achieved a major cytogenetic response, a result historically associated with improved survival. Furthermore, 21% of patients in accelerated-phase CML and 13.5% of patients in blastic-phase CML (patient populations with typically poor prognosis before the advent of imatinib mesylate) achieved major cytogenetic responses. Results from ongoing studies will determine the durability of these responses and will evaluate ways to optimize treatment in advanced-stage patients using imatinib mesylate in combination with other therapies. Additional trials are planned to investigate the efficacy of imatinib mesylate to treat a variety of solid tumors whose pathogenesis is driven by the other tyrosine kinase targets, c-Kit and platelet-derived growth factor receptor.
长期以来，肿瘤学界一直在寻求靶向癌症治疗方法，认为这可能是一种比现有疗法更好的方法。一种已显示出巨大成功的靶向疗法是酪氨酸激酶抑制剂甲磺酸伊马替尼（原名STI571，[格列卫]；诺华制药公司，新泽西州东哈嫩），该药物最近被批准用于治疗费城染色体阳性的慢性髓性白血病（CML）。对CML的分子病因和发病机制进行的基础科学研究以及对甲磺酸伊马替尼作用机制的临床前研究令人鼓舞，从而启动了I期临床试验。甲磺酸伊马替尼的临床开发继续进行了三项大型多中心II期试验。慢性期CML中大多数（88%）对α干扰素耐药或不耐受的患者对甲磺酸伊马替尼实现了完全血液学缓解。更重要的是，大约一半的患者实现了主要细胞遗传学缓解，这一结果在历史上与生存率提高相关。此外，加速期CML患者中有21%、急变期CML患者中有13.5%（在甲磺酸伊马替尼出现之前，这些患者群体的预后通常较差）实现了主要细胞遗传学缓解。正在进行的研究结果将确定这些缓解的持久性，并将评估使用甲磺酸伊马替尼联合其他疗法优化晚期患者治疗的方法。还计划进行其他试验，以研究甲磺酸伊马替尼治疗多种实体瘤的疗效，这些实体瘤的发病机制是由其他酪氨酸激酶靶点c-Kit和血小板衍生生长因子受体驱动的。
