Georgia Cancer Center at Augusta University, Augusta, GA, USA.
Universitätsklinikum Aachen, RWTH Aachen, Germany; Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany.
Leuk Res. 2021 Dec;111:106690. doi: 10.1016/j.leukres.2021.106690. Epub 2021 Aug 21.
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.
博舒替尼的推荐起始剂量为 500mg/天，用于对先前治疗耐药/不耐受的慢性期（CP）或加速/急变期费城染色体阳性（Ph+）慢性髓性白血病（CML）。然而，一些患者需要减少剂量以控制不良反应（AE）的发生。在一项针对对伊马替尼或伊马替尼加达沙替尼和/或尼洛替尼耐药/不耐受的 CP CML 患者以及至少接受伊马替尼治疗后发生加速/急变期 CML 或急性淋巴细胞白血病的 Ph+患者的 I/II 期研究中，评估了博舒替尼剂量减少后的疗效和安全性。在这项分析中，共有 570 例随访时间≥4 年的患者纳入研究。在 144 例剂量减少至博舒替尼 400mg/天（未减少至 300mg/天）的患者中，22 例（15%）在减少前后达到完全细胞遗传学缓解（CCyR），40 例（28%）在减少后首次达到 CCyR，4 例（3%）仅在减少前达到 CCyR。在 95 例剂量减少至博舒替尼 300mg/天的患者中，23 例（24%）在减少前后达到 CCyR，13 例（14%）在减少后首次达到 CCyR，3 例（3%）仅在减少前达到 CCyR。结果与维持 500mg/天的匹配对照相似，表明剂量减少并未显著影响疗效。减少剂量后治疗中出现的 AE 的发生率较低，尤其是胃肠道事件。减少剂量后，血液学毒性的发生率通常相似。通过减少剂量管理博舒替尼的 AE 可导致疗效改善/维持和更好的耐受性；尽管如此，大约一半的患者在第 4 年仍维持 500mg/天以上的剂量。ClinicalTrials.gov：NCT00261846。
