Zhu Yi, Zhang Xiaochen, Lou Xiaoe, Chen Min, Luo Peihua, He Qiaojun
Zhejiang Province Key Laboratory of Anti-Cancer Drug Research, Institute of Pharmacology & Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
Department of Medical Oncology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China.
Clin Exp Pharmacol Physiol. 2018 Jul;45(7):659-667. doi: 10.1111/1440-1681.12935. Epub 2018 Apr 25.
With the use of multikinase inhibitors (MKIs) having emerged in recent years, skin toxicities such as hand-foot skin reaction (HFSR) are primary side effects, and they lack effective prediction methods. Here, we updated a previous systematic review by establishing a meta-analysis of the risk of developing HFSR among patients receiving MKIs and antivascular endothelial growth factor antibody. Publications from PubMed and abstracts presented at the American Society of Clinical Oncology Annual Meeting up to February 5, 2015, were searched to identify relevant studies, and a total of 236 patients with metastatic tumours in nine trials were included for analysis. In the meta-analysis, the pooled incidence rates of all-grade and high-grade HFSR among patients who received the combination therapy were 56.9% [95% confidence interval (CI), 45%-71.1%] and 14.3% (95% CI, 9%-24.2%), respectively, with significant differences observed with MKI monotherapy (P < .05). Further subgroup analysis demonstrated that increasing the dosages of bevacizumab (77.8% vs 51.1%, P = .04) and MKIs (64.3% vs 52.6%, P = .02) significantly increased HFSR incidence. Moreover, combination with chemotherapy exerted a minimal effect on HFSR risk (61% vs 55.3%, P = .5). This updated review and meta-analysis confirm the increased risk of HFSR incidence due to the use of MKIs and antivascular endothelial growth factor antibody. Thus, using these therapies requires safety standards.
近年来，随着多激酶抑制剂（MKIs）的应用，手足皮肤反应（HFSR）等皮肤毒性成为主要副作用，且缺乏有效的预测方法。在此，我们通过对接受MKIs和抗血管内皮生长因子抗体治疗的患者发生HFSR风险进行荟萃分析，更新了之前的系统评价。检索了截至2015年2月5日在PubMed上发表的文献以及在美国临床肿瘤学会年会上展示的摘要，以确定相关研究，共纳入9项试验中的236例转移性肿瘤患者进行分析。在荟萃分析中，接受联合治疗的患者中所有级别和高级别HFSR的合并发生率分别为56.9%[95%置信区间（CI），45%-71.1%]和14.3%（95%CI，9%-24.2%），与MKIs单药治疗相比有显著差异（P<0.05）。进一步的亚组分析表明，增加贝伐单抗（77.8%对51.1%，P=0.04）和MKIs（64.3%对52.6%，P=0.02）的剂量会显著增加HFSR的发生率。此外，联合化疗对HFSR风险的影响最小（61%对55.3%，P=0.5）。这一更新的综述和荟萃分析证实了使用MKIs和抗血管内皮生长因子抗体导致HFSR发生率增加的风险。因此，使用这些疗法需要安全标准。
