氟马替尼与伊马替尼治疗初诊慢性粒细胞白血病的有效性和安全性比较

摘要

Objective To compare the efficacy and safety between flumatinib and imatinib in patients with newly diagnosed chronic myeloid leukemia (CML). Methods A multi-center, randomized and parallel comparison clinical trial was conducted in 24 newly diagnosed patients with Philadelphia chromosome-positive CML-chronic phase (Ph+ CML-CP) who were treated by flumatinib 400 mg/d, 600 mg/d or imatinib for 6 cycles (24 weeks). The hematology was evaluated at pre-medication and the 2nd, 4th, 6th, 8th, 10th, 12th, 16th, 20th, 24th week of post-medication. The morphology, cytogenetics and molecular biology were evaluated at pre-medication and 12th, 24th week of post-medication. Results In terms of efficacy, the main molecular remission (MMR) rate of flumatinib 600 mg/d group was higher than that of imatinib group after 24 weeks [44.44 % (4/9) vs. 14.29 % (1/7), P=0.017]. The rate of bcr-ablIS≤10 % in flumatinib 600 mg/d group was significantly higher than that in imatinib group (P=0.002). PK/PD analysis also hinted that patients treated by flumatinib 600 mg/d was more likely to get molecular reaction in the early stage compared with those treated by flumatinib 400 mg/d. In terms of safety, there was no significant difference in grade Ⅲ-Ⅳ of adverse events among flumatinib 400 mg/d group, flumatinib 600 mg/d group and imatinib group (P >0.05). The common adverse events in flumatinib group included skin toxicity, gastrointestinal reactions and diarrhea.There was no heart and cardiovascular toxicity in flumatinib group, and incidence of edema in flumatinib group was lower than that in imatinib group. Conclusions Flumatinib is a safe and effective drug for newly diagnosed patients with Ph+ CML-CP, and 600 mg/d is the appropriate clinical starting dose. Flumatinib and imatinib have similar safety in clinic.%目的：比较氟马替尼与伊马替尼治疗初诊慢性粒细胞白血病（CML）的有效性和安全性。方法采用多中心、随机、阳性药物平行对照的研究方法，对24例符合条件的初诊费城染色体阳性 CML慢性期（Ph+ CML-CP）患者给予6个周期（24周）的氟马替尼400 mg／d、600 mg／d 和伊马替尼治疗，分别在给药前及给药后2、4、6、8、10、12、16、20、24周进行血液学评价，给药前及给药后12、24周进行形态学、细胞遗传学和分子生物学评价。结果在有效性方面，治疗6个周期，氟马替尼600 mg／d 组的主要分子学缓解（MMR）率高于伊马替尼组，差异有统计学意义[44.44%（4／9）比14.29%（1／7），P＝0.017]。治疗3个周期，氟马替尼600 mg／d 组 bcr-ablIS≤10%的患者比例高于伊马替尼组，差异有统计学意义（P＝0.002）；药代动力学／药效动力学分析也提示氟马替尼600 mg／d 较400 mg／d 更有可能使患者在早期获得分子学反应。在安全性方面，氟马替尼400 mg／d 组、氟马替尼600 mg／d 组和伊马替尼组Ⅲ～Ⅳ级不良事件的发生率差异无统计学意义（P＞0.05）。氟马替尼组较常见皮肤毒性和胃肠道反应，常见的不良事件为腹泻，未发生心脏和心血管系统不良反应，水肿的发生率低于伊马替尼组。结论氟马替尼可以安全有效地治疗初诊 Ph+ CML-CP 患者，600 mg／d 是一个较为合适的临床起始剂量。氟马替尼和伊马替尼在临床上具有相似的安全性。