Campus Virchow Klinikum, Charité Universitätsmedizin, Berlin, Germany.
Clin Cancer Res. 2010 Mar 15;16(6):1771-80. doi: 10.1158/1078-0432.CCR-09-2760. Epub 2010 Mar 2.
The biology of chronic myeloid leukemia (CML) has enabled pioneering studies with targeted therapies. BCR-ABL inhibition with imatinib results in high levels of efficacy in patients with newly diagnosed CML in chronic phase (CP), but an estimated 35% of patients could benefit from more effective treatment. Several novel treatment strategies are being investigated in newly diagnosed CML-CP. These strategies include upfront treatment with next-generation tyrosine kinase inhibitors, such as dasatinib, nilotinib, or bosutinib, which also target BCR-ABL but with increased in vitro potency compared with imatinib, and possibly a reduced potential for resistance. Recent in vitro studies have shown that short-term exposure to dasatinib or continuous exposure to imatinib result in equivalent levels of apoptosis, indicating that potent intermittent inhibition is a successful strategy for improving dasatinib tolerability. Modified imatinib regimens are also being investigated in newly diagnosed CML-CP, including higher doses and combination with alternative classes of agents, such as interferon. Existing data suggest that both newer agents and combination approaches can improve treatment responses compared with standard imatinib treatment, although further data are needed, particularly from ongoing phase 3 trials, before the standard of care is revised.
慢性髓性白血病（CML）的生物学特性使得针对该疾病的靶向治疗研究成为可能。伊马替尼抑制 BCR-ABL 在慢性期（CP）初诊 CML 患者中具有很高的疗效，但估计仍有 35%的患者需要更有效的治疗。目前正在研究几种新的治疗策略来治疗初诊 CML-CP。这些策略包括使用下一代酪氨酸激酶抑制剂（如达沙替尼、尼洛替尼或博舒替尼）进行一线治疗，这些药物也靶向 BCR-ABL，但与伊马替尼相比，体外活性更强，潜在耐药性更低。最近的体外研究表明，短期暴露于达沙替尼或持续暴露于伊马替尼可导致凋亡水平相当，表明强烈的间歇性抑制是提高达沙替尼耐受性的成功策略。新型伊马替尼方案也正在初诊 CML-CP 中进行研究，包括更高的剂量和与其他类药物联合，如干扰素。现有数据表明，与标准伊马替尼治疗相比，新型药物和联合治疗方法均能改善治疗反应，但需要更多数据，特别是正在进行的 3 期临床试验数据，以修订治疗标准。
