Department of Medical Oncology, Sletten Cancer Institute, Great Falls, Montana 59405, USA.
Clin Ther. 2012 Feb;34(2):272-81. doi: 10.1016/j.clinthera.2012.01.009. Epub 2012 Jan 27.
Imatinib is an effective treatment for patients with newly diagnosed chronic phase chronic myeloid leukemia (CML-CP), but resistance to imatinib can occur. Second-generation BCR-ABL inhibitors have shorter onset times and higher rates of complete cytogenetic response (CCyR) than imatinib. Dasatinib has a half-maximal inhibitory concentration 325 times lower than imatinib for BCR-ABL substrate phosphorylation in vitro and is less susceptible to most known molecular mechanisms of BCR-ABL imatinib resistance.
This study summarized published data on the use of dasatinib in CML-CP, reviewed the importance of early response to therapy, and discussed additional therapies for patients with newly diagnosed disease.
PubMed was searched through June 2011 for English-language publications with the following search terms: imatinib, dasatinib, nilotinib, chronic myeloid/myelogenous leukemia or CML, and clinical trial. To identify follow-up data from published trials and data on trials in progress and products in development, similar searches were conducted for abstract and clinical trial databases. Relevant articles and abstracts were identified as those reporting results of Phase II and III clinical trials, predictors of treatment response, and treatment guidelines. No prespecified inclusion or exclusion criteria were used.
Dasatinib was effective in patients resistant to imatinib and more effective than high-dose imatinib in patients with newly diagnosed CML who were resistant to standard dose imatinib. Compared with imatinib, dasatinib induced superior response rates and patient outcomes earlier in the disease. In a Phase III trial in patients with newly diagnosed CML-CP, dasatinib 100 mg once daily induced significantly higher and faster rates of confirmed CCyR and major molecular response by 12 months versus imatinib and was generally well tolerated. Early achievement of CCyR was associated with better long-term progression-free survival. Dasatinib was approved by the U.S. Food and Drug Administration and the European Medicines Agency for initial treatment of CML-CP.
Dasatinib was an effective treatment with the potential to improve long-term outcomes for patients with newly diagnosed CML-CP.
伊马替尼是治疗初诊慢性期慢性髓性白血病（CML-CP）患者的有效药物，但存在伊马替尼耐药的情况。二代 BCR-ABL 抑制剂的起效时间较伊马替尼短，完全细胞遗传学缓解（CCyR）率更高。达沙替尼在体外对 BCR-ABL 底物磷酸化的半数最大抑制浓度（IC50）比伊马替尼低 325 倍，且对大多数已知的 BCR-ABL 伊马替尼耐药的分子机制的敏感性较低。
本研究总结了达沙替尼治疗 CML-CP 的文献数据，综述了早期治疗反应的重要性，并讨论了初诊疾病患者的其他治疗选择。
通过检索 2011 年 6 月前发表的英文文献，使用以下检索词：伊马替尼、达沙替尼、尼洛替尼、慢性髓性/髓样白血病或 CML，以及临床试验。为了确定已发表试验的随访数据以及正在进行的试验和开发中的产品的数据，还对摘要和临床试验数据库进行了类似的检索。将报告 II 期和 III 期临床试验结果、治疗反应预测因素和治疗指南的相关文章和摘要确定为有意义的文献。未预设纳入或排除标准。
达沙替尼对伊马替尼耐药的患者有效，对标准剂量伊马替尼耐药的初诊 CML 患者，其疗效优于高剂量伊马替尼。与伊马替尼相比，达沙替尼更早诱导更高的缓解率和更好的患者结局。在一项初诊 CML-CP 患者的 III 期试验中，达沙替尼 100 mg 每日 1 次治疗的患者，12 个月时确认的 CCyR 和主要分子学缓解率显著更高且更快，且总体耐受性良好。早期获得 CCyR 与长期无进展生存改善相关。达沙替尼已获美国食品药品监督管理局和欧洲药品管理局批准，用于初治 CML-CP。
达沙替尼是一种有效的治疗药物，有可能改善初诊 CML-CP 患者的长期预后。
