Quintás-Cardama Alfonso, Cortés Jorge E, Kantarjian Hagop
Department of Leukemia, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
Clin Lymphoma Myeloma. 2008 Mar;8 Suppl 3:S82-8. doi: 10.3816/CLM.2008.s.003.
The tyrosine kinase inhibitor (TKI) imatinib constitutes the current first-line therapeutic approach for patients with chronic myeloid leukemia. The success of imatinib relies on its potent inhibitory activity against the Bcr-Abl kinase that drives the pathogenesis of this disorder. The vast majority of patients treated with imatinib as a single agent will achieve a complete cytogenetic response. However, a subset of patients will develop imatinib resistance, frequently associated with mutations within the Abl kinase domain. In this setting, treatment with the second-generation TKIs nilotinib and dasatinib has proved highly efficacious. While therapy with these Bcr-Abl TKIs is generally well tolerated, adverse events are common and can result in treatment interruptions that compromise clinical responses. Herein, we discuss some of the toxicities characteristically associated with TKI therapy and provide practical approaches to the clinical management of these adverse effects.
酪氨酸激酶抑制剂(TKI)伊马替尼是目前慢性髓性白血病患者的一线治疗方法。伊马替尼的成功依赖于其对驱动该疾病发病机制的Bcr-Abl激酶的强大抑制活性。绝大多数接受伊马替尼单药治疗的患者将实现完全细胞遗传学缓解。然而,一部分患者会出现伊马替尼耐药,这通常与Abl激酶结构域内的突变有关。在这种情况下,第二代TKI尼罗替尼和达沙替尼的治疗已被证明非常有效。虽然这些Bcr-Abl TKI的治疗通常耐受性良好,但不良事件很常见,可能导致治疗中断,从而影响临床反应。在此,我们讨论一些与TKI治疗典型相关的毒性,并提供这些不良反应临床管理的实用方法。