Department of Internal Medicine, University of Milano Bicocca, Monza, Italy.
Am J Hematol. 2014 Oct;89(10):947-53. doi: 10.1002/ajh.23788. Epub 2014 Jul 21.
Bosutinib, an orally active, Src/Abl tyrosine kinase inhibitor, has demonstrated clinical activity and acceptable tolerability in chronic phase chronic myeloid leukemia (CP CML). This updated analysis of the BELA trial assessed the safety profile and management of toxicities of bosutinib versus imatinib in adults with newly diagnosed (≤6 months) CP CML after >30 months from accrual completion. Among patients randomized to bosutinib 500 mg/d (n = 250) or imatinib 400 mg/d (n = 252), 248 and 251, respectively, received ≥1 dose of study treatment. Adverse events (AEs; any grade) with bosutinib versus imatinib were significantly more common for certain gastrointestinal events (diarrhea, 70% vs. 26%; P < 0.001; vomiting, 33% vs. 16%; P < 0.001), alanine aminotransferase (33% vs. 9%; P < 0.001) and aspartate aminotransferase (28% vs. 10%; P < 0.001) elevations, and pyrexia (19% vs. 12%; P = 0.046). AEs significantly less common with bosutinib included edema (periorbital, 2% vs. 14%; P < 0.001; peripheral, 5% vs. 12%; P = 0.006), musculoskeletal (myalgia, 5% vs. 12%; P = 0.010; muscle cramps, 5% vs. 22%; P < 0.001; bone pain, 4% vs. 11%; P = 0.003), increased creatine phosphokinase (8% vs. 20%; P < 0.001), neutropenia (13% vs. 30%; P < 0.001), and leukopenia (9% vs. 22%; P < 0.001). Between-group differences in the incidence of cardiac and vascular AEs were not significant. Diarrhea was typically transient, mostly Grade 1/2, occurring early during treatment, and was manageable with antidiarrheal medication. Despite higher rates of aminotransferase elevation with bosutinib, events were managed in most patients with dose modification and/or concomitant medication. Bosutinib had a manageable safety profile distinct from that of imatinib in patients with newly diagnosed CP CML.
博舒替尼是一种口服活性Src/Abl 酪氨酸激酶抑制剂，在慢性期慢性髓性白血病 (CP CML) 中显示出临床疗效和可接受的耐受性。这项 BELA 试验的更新分析评估了新诊断（≤6 个月）CP CML 成人在入组完成后>30 个月时，与伊马替尼相比，博舒替尼的安全性特征和毒性管理。在随机分配至博舒替尼 500 mg/d（n = 250）或伊马替尼 400 mg/d（n = 252）的患者中，分别有 248 名和 251 名患者接受了≥1 剂研究治疗。与伊马替尼相比，博舒替尼的某些胃肠道事件（腹泻，70%比 26%；P < 0.001；呕吐，33%比 16%；P < 0.001）、丙氨酸氨基转移酶（33%比 9%；P < 0.001）和天冬氨酸氨基转移酶（28%比 10%；P < 0.001）升高以及发热（19%比 12%；P = 0.046）更为常见。博舒替尼少见的不良反应包括水肿（眶周，2%比 14%；P < 0.001；外周，5%比 12%；P = 0.006）、肌肉骨骼（肌痛，5%比 12%；P = 0.010；肌肉痉挛，5%比 22%；P < 0.001；骨痛，4%比 11%；P = 0.003）、肌酸磷酸激酶升高（8%比 20%；P < 0.001）、中性粒细胞减少（13%比 30%；P < 0.001）和白细胞减少（9%比 22%；P < 0.001）。两组间心血管不良反应的发生率无显著差异。腹泻通常是短暂的，大多为 1/2 级，发生在治疗早期，用止泻药即可控制。尽管博舒替尼的转氨酶升高发生率较高，但大多数患者通过剂量调整和/或伴随药物治疗可控制。博舒替尼在新诊断的 CP CML 患者中的安全性特征与伊马替尼不同，具有可管理性。
