Ohnishi Kazunori
Oncology Center, Hamamatsu University School of Medicine.
Gan To Kagaku Ryoho. 2007 Dec;34(13):2185-90.
Imatinib mesylate, a selective inhibitor of the ABL tyrosine kinase, has revolutionized the treatment of chronic myelogenous leukemia (CML) due to its high level of activity, low toxicity, and durability. Five-year data from the pivotal trial of imatinib, the IRIS trial, suggests durable responses in a high proportion and reduction and almost elimination of the incidence of imatinib failure over time. The imatinib dose of 400 mg is considered to be standard based on the IRIS trial. Recently, new tyrosine kinase inhibitors (TKI) have been developed, which can overcome imatinib resistance, and comparative studies between each TKI and imatinib are ongoing for imatinib-resistant CML and newly-diagnosed CML. TKI will be chosen based on the profiles of mutation of the ABL kinase domain. On the other hand, the results of hematopoietic stem cell transplantation in patients treated with imatinib were reported, and pretreatment of imatinib did not influence TRM. However, the optimal dose, duration of imatinib treatment and the indication of reduced intensity conditioning transplantation have not been established. Longer follow-up, the accumulation of results of the new TKI therapy and HSCT are required.
甲磺酸伊马替尼是一种ABL酪氨酸激酶的选择性抑制剂,因其高活性、低毒性和持久性,彻底改变了慢性粒细胞白血病(CML)的治疗方式。伊马替尼关键试验——国际随机对照试验(IRIS)的五年数据表明,大部分患者有持久反应,且随着时间推移,伊马替尼治疗失败的发生率降低并几乎消除。基于IRIS试验,400毫克的伊马替尼剂量被视为标准剂量。最近,新型酪氨酸激酶抑制剂(TKI)已被研发出来,其可克服伊马替尼耐药性,针对伊马替尼耐药的CML患者和新诊断的CML患者,各TKI与伊马替尼之间的对比研究正在进行。TKI将根据ABL激酶结构域的突变情况来选择。另一方面,有报告称伊马替尼治疗患者的造血干细胞移植结果,且伊马替尼预处理不影响移植相关死亡率(TRM)。然而,伊马替尼治疗的最佳剂量、持续时间以及减低预处理强度移植的指征尚未确定。需要更长时间的随访、新型TKI治疗结果和造血干细胞移植结果的积累。