Department of Medicine, Beth Israel Medical Center, University Hospital, New York, USA.
Cancer Treat Rev. 2013 Nov;39(7):818-30. doi: 10.1016/j.ctrv.2013.01.004. Epub 2013 Feb 28.
The incidence and risk of unique toxicities associated with a multi-targeted tyrosine kinase inhibitor sunitinib, such as hypertension and thromboembolic events, have been previously reported. However, the incidence and risk of hematologic toxicities have been less well characterized. We performed an up-to-date meta-analysis of trials to evaluate the risk of sunitinib-related hematologic toxicities.
We searched Medline and the American Society of Clinical Oncology online database of meeting abstracts up to July 2012 for relevant clinical trials. Eligible studies included phase II and III trials and expanded access programs of sunitinib that reported adequate safety data profile reporting neutropenia, thrombocytopenia or anemia. The summary incidence, relative risk (RR) and 95% confidence intervals (CIs) were calculated.
A total of 8,526 patients from 60 trials of sunitinib as a single agent revealed that the incidence of sunitinib-associated all-grade and high-grade (Grades 3 and 4) hematologic toxicities were, respectively: neutropenia: 42.1% and 12.8%; thrombocytopenia: 44.7% and 10.7% and anemia: 50.4% and 6.2%. Sunitinib-treated patients (2667 subjects from 10 randomized trials) had a significantly increased risk of all-grade (RR=3.58; 95% CI, 1.71-7.49) and high-grade (RR=3.32; 95% CI, 1.60-6.90) neutropenia, all-grade (RR=4.59; 95% CI, 2.76-7.63) and high-grade (RR=5.84; 95% CI, 2.22-15.41) thrombocytopenia and all-grade anemia (RR=1.15; 95% CI, 1.00-1.31).
Sunitinib is associated with a significant increase in the risk of developing all-grade and high-grade neutropenia and thrombocytopenia and all-grade anemia compared with control.
先前已有报道称，多靶点酪氨酸激酶抑制剂舒尼替尼会引起一些独特的毒性反应，如高血压和血栓栓塞事件，但其血液学毒性的发生率和风险特征尚不明确。我们对相关试验进行了最新的荟萃分析，以评估舒尼替尼相关血液学毒性的风险。
我们检索了 Medline 和美国临床肿瘤学会在线数据库中截至 2012 年 7 月的会议摘要，以寻找相关临床试验。合格的研究包括舒尼替尼的 II 期和 III 期试验及扩大使用计划，这些研究报告了足够的中性粒细胞减少、血小板减少或贫血安全性数据。计算汇总发生率、相对风险（RR）和 95%置信区间（CI）。
来自 60 项舒尼替尼单药治疗试验的 8526 例患者的数据显示，舒尼替尼相关的所有级别和 3/4 级（Grades 3 and 4）血液学毒性的发生率分别为：中性粒细胞减少症：42.1%和 12.8%；血小板减少症：44.7%和 10.7%；贫血症：50.4%和 6.2%。与对照组相比，接受舒尼替尼治疗的患者（来自 10 项随机试验的 2667 例患者）发生所有级别（RR=3.58；95%CI，1.71-7.49）和 3/4 级（RR=3.32；95%CI，1.60-6.90）中性粒细胞减少症、所有级别（RR=4.59；95%CI，2.76-7.63）和 3/4 级（RR=5.84；95%CI，2.22-15.41）血小板减少症以及所有级别贫血症的风险显著增加（RR=1.15；95%CI，1.00-1.31）。
与对照组相比，舒尼替尼会显著增加发生所有级别和 3/4 级中性粒细胞减少症、血小板减少症和所有级别贫血症的风险。
