Pilot study of bortezomib for patients with imatinib-refractory chronic myeloid leukemia in chronic or accelerated phase.
Pilot study of bortezomib for patients with imatinib-refractory chronic myeloid leukemia in chronic or accelerated phase.
复制标题
硼替佐米治疗伊马替尼难治性慢性粒细胞白血病慢性期或加速期患者的初步研究。
DOI：
10.1016/j.clml.2011.06.004
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发表时间：
2011-08
期刊：
影响因子：
--
通讯作者：
Cortes J
中科院分区：
文献类型：
--
作者：
Santos FP;Kantarjian H;McConkey D;O'Brien S;Faderl S;Borthakur G;Ferrajoli A;Wright J;Cortes J
蛋白酶体抑制剂是破坏蛋白酶体的蛋白水解活性并导致肿瘤细胞生长停滞和凋亡的抗癌化合物。硼替佐米是一种蛋白酶体抑制剂，目前被批准用于多发性骨髓瘤和套细胞淋巴瘤。它在体外诱导慢性粒细胞白血病（CML）细胞凋亡，但硼替佐米在伊马替尼耐药CML患者中的活性尚不清楚。我们进行了一项初步试验，以评估单一药物硼替佐米在CML中的活性。7例伊马替尼难治性CML患者接受硼替佐米治疗，剂量为1.5 mg/m2，第1、4、8和11天，每3周一次。接受的中位周期数为2。无患者出现血液学或细胞遗传学缓解。3例患者出现与硼替佐米治疗相关的嗜碱性粒细胞计数暂时性降低。6例患者发生3-4级非血液学毒性。硼替佐米在伊马替尼难治性CML患者中疗效最低，毒性相当大。进一步的研究应该集中在使用蛋白酶体抑制剂治疗CML的替代方法上，例如与酪氨酸激酶抑制剂联合使用或作为根除白血病干细胞的策略。
Proteasome inhibitors are anticancer compounds that disrupt the proteolytic activity of the proteasome and lead to tumor cell growth arrest and apoptosis. Bortezomib is a proteasome inhibitor that is currently approved for use in multiple myeloma and mantle cell lymphoma. It induces apoptosis of chronic myeloid leukemia (CML) cells in vitro, but the activity of bortezomib in patients with imatinib-resistant CML is unknown. We conducted a pilot trial to evaluate the activity of single agent bortezomib in CML. Seven patients with imatinib-refractory CML were treated with bortezomib at a dose of 1.5 mg/m2 on days 1, 4, 8 and 11 every 3 weeks. The median number of cycles received was 2. No patient had a hematologic or cytogenetic response. Three patients had a temporary decrease in basophil counts associated with therapy with bortezomib. Six patients developed grade 3-4 nonhematological toxicities. Bortezomib had minimal efficacy and considerable toxicity in patients with imatinib-refractory CML. Further studies should focus on alternative approaches to employ proteasome inhibitors in the treatment of CML, such as in combination with tyrosine kinase inhibitors or as a strategy to eradicate leukemic stem cells.
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影响因子：
10.5
作者：
Clurman, BE;Sheaff, RJ;Roberts, JM
通讯作者：
Roberts, JM
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11.4
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Hochhaus, A.;Baccarani, M.;Kantarjian, H. M.
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20.3
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