Clinical impact of dose reductions and interruptions of second-generation tyrosine kinase inhibitors in patients with chronic myeloid leukaemia.
Clinical impact of dose reductions and interruptions of second-generation tyrosine kinase inhibitors in patients with chronic myeloid leukaemia.
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DOI：
10.1111/j.1365-2141.2010.08245.x
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发表时间：
2010-08
影响因子：
6.5
通讯作者：
Cortes J
中科院分区：
文献类型：
--
作者：
Santos FP;Kantarjian H;Fava C;O'Brien S;Garcia-Manero G;Ravandi F;Wierda W;Thomas D;Shan J;Cortes J
第二代酪氨酸激酶抑制剂(TKI)(达沙替尼、尼洛替尼)对所有阶段的慢性粒细胞白血病(CML)患者都有效。由于毒性，经常需要减少剂量和中断治疗，但它们的意义尚不清楚。我们分析了第二代TKI的剂量减少/中断和剂量强度对反应和生存的影响。对280例慢性粒细胞白血病(CML)患者(各期)进行分析。当每日剂量低于标准剂量时，考虑减少剂量。剂量强度是根据理想剂量强度的百分比确定的。总体而言，176名患者(63%)在治疗期间需要至少一次中断治疗和/或减少剂量。剂量减少/中断被分析为时间依赖的协变量，仅在未经治疗的CML患者中与较差的无失败存活率相关。剂量强度分析没有显示在治疗期间或前6个月接受较低剂量强度(100%)的患者的反应或存活率更差。总之，CML患者第二代TKI的剂量减少和治疗中断对这些患者的应答率和生存率的影响微乎其微。需要进一步的研究来确定是否存在这些药物的最低充足剂量。
Second (2nd)-generation tyrosine kinase inhibitors (TKI) (dasatinib, nilotinib) are effective in patients with all phases of chronic myeloid leukaemia (CML). Dose reductions and treatment interruptions are frequently required due to toxicity, but their significance is unknown. We analysed the impact of dose reductions/interruptions and dose intensity of 2nd-generation TKI on response and survival. A total of 280 patients with CML (all phases) were analysed. Dose reductions were considered when the daily dose was below the standard dose. Dose intensity was determined based on the percentage of the ideal dose intensity. Overall, 176 patients (63%) required treatment interruptions and/or dose reduction at least once during therapy. Dose reductions/interruptions, analysed as a time-dependent covariate, were associated with worse failure-free survival only in patients with untreated CML. Dose intensity analysis did not reveal a worse response or survival in patients who received a lower dose intensity (<100%) during therapy or during the first 6 months. In conclusion, dose reductions and treatment interruptions of 2nd generation TKI in patients with CML have a minimal impact in the response rate and survival of these patients. Further studies are required to determine whether there might be a minimum adequate dose of these agents.
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影响因子：
45.3
作者：
Shah, Neil P.;Kantarjian, Hagop M.;Hochhaus, Andreas
通讯作者：
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Griffin, JD
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Ottmann, Oliver G.
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Baccarani, Michele;Rosti, Gianantonio;Simonsson, Bengt
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Simonsson, Bengt