Kantarjian Hagop, Pasquini Ricardo, Hamerschlak Nelson, Rousselot Philippe, Holowiecki Jerzy, Jootar Saengsuree, Robak Tadeusz, Khoroshko Nina, Masszi Tamas, Skotnicki Aleksander, Hellmann Andrzej, Zaritsky Andrey, Golenkov Anatoly, Radich Jerald, Hughes Timothy, Countouriotis Athena, Shah Neil
Department of Leukemia, University of Texas M. D. Anderson Cancer Center, Houston, TX 77230-1402, USA.
Blood. 2007 Jun 15;109(12):5143-50. doi: 10.1182/blood-2006-11-056028. Epub 2007 Feb 22.
Therapeutic options for chronic myelogenous leukemia (CML) resistant to 400 to 600 mg imatinib are limited. Escalating imatinib doses may overcome resistance. Dasatinib, a significantly more potent inhibitor of BCR-ABL, is safe and effective in this population. Patients with imatinib-resistant chronic-phase (CP) CML were randomized 2:1 to 140 mg dasatinib (n=101) or 800 mg imatinib (n=49). With a median follow up of 15 months, complete hematologic responses were observed in 93% and 82% of patients receiving dasatinib and high-dose imatinib (P=.034), respectively. Dasatinib resulted in higher major cytogenetic response rates (52%) than high-dose imatinib (33%) (P=.023); this included complete cytogenetic response in 40% and 16% (P=.004). Major molecular responses were also more frequent with dasatinib (16% versus 4%; P=0.038). Treatment failure (hazard ratio [HR], 0.16; P<.001) and progression-free survival (HR, 0.14; P<.001) both favored dasatinib. Superficial edema (42% versus 15%) and fluid retention (45% versus 30%) were more prevalent with imatinib; pleural effusion was more common with dasatinib (17% versus 0%). Grade 3 to 4 nonhematologic toxicity was minimal. Cytopenias were more frequent and severe with dasatinib. Dasatinib represents a safe and effective therapy for CP-CML resistant to conventional imatinib doses with improved cytogenetic and molecular response rates and progression-free survival relative to high-dose imatinib.
对400至600毫克伊马替尼耐药的慢性粒细胞白血病（CML）的治疗选择有限。增加伊马替尼剂量可能克服耐药性。达沙替尼是一种效力更强的BCR-ABL抑制剂，在这一人群中安全有效。对伊马替尼耐药的慢性期（CP）CML患者按2:1随机分组，分别接受140毫克达沙替尼（n = 101）或800毫克伊马替尼（n = 49）治疗。中位随访15个月时，接受达沙替尼和高剂量伊马替尼治疗的患者中，分别有93%和82%观察到完全血液学缓解（P = 0.034）。达沙替尼导致的主要细胞遗传学缓解率（52%）高于高剂量伊马替尼（33%）（P = 0.023）；其中包括40%和16%的完全细胞遗传学缓解（P = 0.004）。达沙替尼的主要分子学缓解也更常见（分别为16%和4%；P = 0.038）。治疗失败（风险比[HR]，0.16；P < 0.001）和无进展生存期（HR，0.14；P < 0.001）均有利于达沙替尼。伊马替尼组的浅表水肿（42%对15%）和液体潴留（45%对30%）更为普遍；达沙替尼组的胸腔积液更常见（17%对0%）。3至4级非血液学毒性极小。达沙替尼导致的血细胞减少更频繁且更严重。相对于高剂量伊马替尼，达沙替尼是一种对常规伊马替尼剂量耐药的CP-CML安全有效的疗法，可提高细胞遗传学和分子学缓解率以及无进展生存期。
