Talpaz Moshe, Silver Richard T, Druker Brian J, Goldman John M, Gambacorti-Passerini Carlo, Guilhot Francois, Schiffer Charles A, Fischer Thomas, Deininger Michael W N, Lennard Anne L, Hochhaus Andreas, Ottmann Oliver G, Gratwohl Alois, Baccarani Michele, Stone Richard, Tura Sante, Mahon Francois-Xavier, Fernandes-Reese Sofia, Gathmann Insa, Capdeville Renaud, Kantarjian Hagop M, Sawyers Charles L
M. D. Anderson Cancer Center, Houston, Texas, USA.
Blood. 2002 Mar 15;99(6):1928-37. doi: 10.1182/blood.v99.6.1928.
Chronic myelogenous leukemia (CML) is caused by expression of the BCR-ABL tyrosine kinase oncogene, the product of the t(9;22) Philadelphia translocation. Patients with CML in accelerated phase have rapidly progressive disease and are characteristically unresponsive to existing therapies. Imatinib (formerly STI571) is a rationally developed, orally administered inhibitor of the Bcr-Abl kinase. A total of 235 CML patients were enrolled in this study, of whom 181 had a confirmed diagnosis of accelerated phase. Patients were treated with imatinib at 400 or 600 mg/d and were evaluated for hematologic and cytogenetic response, time to progression, survival, and toxicity. Imatinib induced hematologic response in 82% of patients and sustained hematologic responses lasting at least 4 weeks in 69% (complete in 34%). The rate of major cytogenetic response was 24% (complete in 17%). Estimated 12-month progression-free and overall survival rates were 59% and 74%, respectively. Nonhematologic toxicity was usually mild or moderate, and hematologic toxicity was manageable. In comparison to 400 mg, imatinib doses of 600 mg/d led to more cytogenetic responses (28% compared to 16%), longer duration of response (79% compared to 57% at 12 months), time to disease progression (67% compared to 44% at 12 months), and overall survival (78% compared to 65% at 12 months), with no clinically relevant increase in toxicity. Orally administered imatinib is an effective and well-tolerated treatment for patients with CML in accelerated phase. A daily dose of 600 mg is more effective than 400 mg, with similar toxicity.
慢性粒细胞白血病（CML）由BCR-ABL酪氨酸激酶致癌基因的表达引起，该基因是t(9;22)费城染色体易位的产物。处于加速期的CML患者病情进展迅速，且对现有治疗通常无反应。伊马替尼（原STI571）是一种经合理研发的口服Bcr-Abl激酶抑制剂。本研究共纳入235例CML患者，其中181例确诊为加速期。患者接受400或600mg/d的伊马替尼治疗，并评估血液学和细胞遗传学反应、疾病进展时间、生存率及毒性。伊马替尼使82%的患者产生血液学反应，69%的患者有持续至少4周的血液学反应（34%为完全缓解）。主要细胞遗传学反应率为24%（17%为完全缓解）。估计12个月无进展生存率和总生存率分别为59%和74%。非血液学毒性通常为轻度或中度，血液学毒性可控。与400mg相比，600mg/d的伊马替尼剂量导致更多的细胞遗传学反应（28%对16%）、更长的反应持续时间（12个月时为79%对57%）、疾病进展时间（12个月时为67%对44%）和总生存率（12个月时为78%对65%）,且毒性无临床相关增加。口服伊马替尼是加速期CML患者有效且耐受性良好的治疗方法。每日600mg剂量比400mg更有效，毒性相似。
