Hematology Research Unit, Biomedicum Helsinki, Helsinki University Central Hospital, P.O. Box 700, FIN-00029 HUCH, Helsinki, Finland.
Cancer. 2010 Jan 15;116(2):377-86. doi: 10.1002/cncr.24734.
Dasatinib, a highly potent BCR-ABL inhibitor, is an effective treatment for patients with chronic myeloid leukemia in chronic phase (CML CP) after resistance, suboptimal response, or intolerance to prior imatinib. In a phase 3 dose optimization trial in patients with CML CP (CA180-034), the occurrence of pleural effusion was significantly minimized with dasatinib 100 mg once daily (QD) compared with other treatment arms (70 mg twice daily [twice daily], 140 mg QD, or 50 mg twice daily).
To investigate the occurrence and management of pleural effusion during dasatinib treatment, and efficacy in patients with or without pleural effusion, data from CA180-034 were analyzed.
With 24-month minimum follow-up, 14% of patients treated with dasatinib 100 mg QD incurred pleural effusion (grade 3: 2%; grade 4: 0%) compared with 23% to 26% in other study arms. The pleural effusion rate showed only a minimal increment from 12 to 24 months. In the 100 mg QD study arm, median time to pleural effusion (any grade) was 315 days, and after pleural effusion, 52% of patients had a transient dose interruption, 35% had a dose reduction, 57% received a diuretic, and 26% received a corticosteroid. Three patients in the 100 mg QD study arm discontinued treatment after pleural effusion. Across all study arms, patients with or without pleural effusion demonstrated similar progression-free and overall survival, and cytogenetic response rates were higher in patients with a pleural effusion.
Pleural effusion is minimized with dasatinib 100 mg QD dosing and its occurrence does not affect short- or long-term efficacy.
达沙替尼是一种高效的 BCR-ABL 抑制剂，对于先前接受伊马替尼治疗后耐药、反应不佳或不耐受的慢性髓性白血病慢性期（CML CP）患者，是一种有效的治疗方法。在一项 CML CP 患者的 3 期剂量优化试验（CA180-034）中，与其他治疗组相比（每日两次 70mg[bid]、每日一次 140mg[qd]或每日两次 50mg[bid]），达沙替尼 100mg qd 可显著减少胸腔积液的发生。
为了研究达沙替尼治疗过程中胸腔积液的发生和管理情况，以及胸腔积液患者和无胸腔积液患者的疗效，对 CA180-034 的数据进行了分析。
在 24 个月的最小随访中，接受达沙替尼 100mg qd 治疗的患者中有 14%发生胸腔积液（3 级：2%；4 级：0%），而其他研究组为 23%至 26%。胸腔积液发生率从 12 个月到 24 个月仅略有增加。在 100mg qd 研究组中，胸腔积液（任何级别）的中位发生时间为 315 天，发生胸腔积液后，52%的患者短暂中断剂量，35%的患者减少剂量，57%的患者使用利尿剂，26%的患者使用皮质类固醇。在 100mg qd 研究组中有 3 名患者在发生胸腔积液后停止治疗。在所有研究组中，有胸腔积液和无胸腔积液的患者的无进展生存期和总生存期相似，并且有胸腔积液的患者的细胞遗传学缓解率更高。
达沙替尼 100mg qd 剂量可最大限度地减少胸腔积液的发生，且其发生并不影响短期或长期疗效。
