Dasatinib induces durable cytogenetic responses in patients with chronic myelogenous leukemia in chronic phase with resistance or intolerance to imatinib
Dasatinib induces durable cytogenetic responses in patients with chronic myelogenous leukemia in chronic phase with resistance or intolerance to imatinib
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DOI：
10.1038/leu.2008.84
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发表时间：
2008-06-01
期刊：
影响因子：
11.4
通讯作者：
Kantarjian, H. M.
中科院分区：
文献类型：
--
作者：
Hochhaus, A.;Baccarani, M.;Kantarjian, H. M.
达沙替尼是一种有效的体外BCR-ABL抑制剂，对伊马替尼耐药或不耐受的慢性粒细胞白血病（CML）患者有效。为了提供一个更明确的评估达沙替尼在慢性期（CP）-CML，我们报告了延长随访的II期试验，提供了整个患者队列的数据（N=387）。达沙替尼（70 mg）每日两次给药伊马替尼耐药或不耐受的CP-CML患者。中位随访时间为15.2个月（治疗持续时间< 1-18.4个月），91%的患者达到或维持了完全血液学缓解。主要细胞遗传学缓解（MCyR）达到或维持了59%（52%伊马替尼耐药和80%伊马替尼不耐受）;这在49%的患者中完成（40%伊马替尼耐药和75%伊马替尼不耐受）。在230例达到MCyR的患者中，7例发生疾病进展。15个月无进展生存率为90%，而总生存率为96%。分别有48%和49%的患者报告了3/4级血小板减少和中性粒细胞减少。非血液学毒性（任何级别）主要包括腹泻（37%）、头痛（32%）、疲乏（31%）、呼吸困难（30%）和胸腔积液（27%）。胸腔积液在6%的报告事件中被分类为3级，没有4级发生率。达沙替尼与伊马替尼耐药或不耐受CP-CML患者的高应答率相关。
Dasatinib, a potent inhibitor of BCR-ABL in vitro, is effective for patients with chronic myelogenous leukemia (CML) resistant or intolerant to imatinib. To provide a more definitive assessment of dasatinib in chronic-phase (CP)-CML, we report extended follow-up of a phase II trial, presenting data for the entire patient cohort (N=387). Dasatinib (70 mg) twice daily was administered to patients with imatinib-resistant or -intolerant CP-CML. With median follow-up of 15.2 months (treatment duration, < 1-18.4 months), a complete hematologic response was attained or maintained in 91% of patients. A major cytogenetic response (MCyR) was attained or maintained by 59% (52% imatinib resistant and 80% imatinib intolerant); this was complete in 49% of patients (40% imatinib resistant and 75% imatinib intolerant). Of 230 patients achieving an MCyR, 7 experienced disease progression. Fifteen-month progression-free survival was 90% while overall survival was 96%. Grade 3/4 thrombocytopenia and neutropenia were reported in 48 and 49% of patients, respectively. Non-hematologic toxicity ( any grade) consisted primarily of diarrhea (37%), headache (32%), fatigue (31%), dyspnea (30%) and pleural effusion (27%). Pleural effusions were classified as grade 3 in 6% of reported events, with no incidence of grade 4. Dasatinib is associated with high response rates in patients with imatinib-resistant or -intolerant CP-CML.