The recommended starting dose of bosutinib is 500 mg/day for chronic-phase (CP) or accelerated-/blast-phase Philadelphia chromosome–positive (Ph+) chronic myeloid leukemia (CML) resistant/intolerant to prior therapy. However, some patients may require dose reductions to manage the occurrences of adverse events (AEs). Bosutinib efficacy and safety were evaluated following dose reductions in a phase I/II study of Ph + patients with CP CML resistant/intolerant to imatinib or imatinib plus dasatinib and/or nilotinib, and those with accelerated-/blast-phase CML or acute lymphoblastic leukemia after at least imatinib treatment. In all, 570 patients with ≥4 years’ follow-up were included in this analysis. Among 144 patients who dose-reduced to bosutinib 400 mg/day (without reduction to 300 mg/day), 22 (15 %) had complete cytogenetic response (CCyR) before and after reduction, 40 (28 %) initially achieved CCyR after reduction, and 4 (3 %) only had CCyR before reduction. Among 95 patients who dose-reduced to bosutinib 300 mg/day, 23 (24 %) had CCyR before and after reduction, 13 (14 %) initially achieved CCyR after reduction, and 3 (3 %) only had CCyR before reduction. Results were similar to matched controls who remained on 500 mg/day, indicating dose reductions had not substantially affected efficacy. The incidence of treatment-emergent AEs was lower after dose reductions, particularly for gastrointestinal events. The incidence of hematologic toxicities generally was similar before and after dose reduction. The management of AEs with bosutinib through dose reduction can lead to improved/maintained efficacy and better tolerability; still, approximately half of patients on treatment at year 4, maintained a dose of ≥500 mg/day ClinicalTrials.gov: NCT00261846.

对于慢性期 (CP) 或加速/急变期费城染色体阳性 (Ph+) 慢性粒细胞白血病 (CML) 对先前治疗耐药/不耐受的患者，波舒替尼的推荐起始剂量为 500 mg/天。然而，一些患者可能需要减少剂量来控制不良事件 (AE) 的发生。在一项 I/II 期研究中，对伊马替尼或伊马替尼加达沙替尼和/或尼罗替尼耐药/不耐受 CP CML 的 Ph + 患者以及加速/急变期 CML 或急性淋巴细胞性白血病患者的剂量减少后评估了博舒替尼的疗效和安全性至少接受伊马替尼治疗后的白血病。总共有 570 名随访时间≥4 年的患者被纳入该分析。在将波舒替尼剂量减至 400 mg/天（未减至 300 mg/天）的 144 名患者中，22 (15 %) 人在还原前后有完全细胞遗传学反应 (CCyR)，40 (28 %) 在还原后最初达到 CCyR，4 (3 %) 在还原前只有 CCyR。在 95 名减量至 300 mg/天的波舒替尼患者中，23 名（24%）在减量前后有 CCyR，13 名（14%）在减量后最初达到 CCyR，3 名（3%）只在减量前有 CCyR。结果与保持 500 mg/天的匹配对照相似，表明剂量减少并未显着影响疗效。减少剂量后治疗中出现的 AE 发生率较低，尤其是胃肠道事件。血液学毒性的发生率在剂量减少前后大致相似。通过减少剂量使用博舒替尼管理 AE，可以提高/维持疗效和更好的耐受性；仍然，