Dermatology Service, Department of Medicine, Memorial Sloan-Kettering Cancer Center, Rockefeller Outpatient Pavilion, Suite 228 160 E 53rd St., New York, NY, USA.
Invest New Drugs. 2013 Jun;31(3):787-97. doi: 10.1007/s10637-013-9927-x. Epub 2013 Jan 24.
Axitinib is a potent, selective vascular endothelial growth factor receptor (VEGFR) inhibitor. We have performed a systematic analysis to investigate the risk of hand-foot skin reaction (HFSR) to axitinib and compare the differences in incidences between sorafenib, sunitinib, pazopanib and axitinib. Relevant studies were identified from PubMed (1998-2012). Eligible studies were limited to prospective Phase II-III clinical trials in which cancer patients were treated with axitinib monotherapy at a starting dose of 5 mg orally twice daily. Incidence, relative risk (RR), and 95 % confidence intervals were calculated using random-effects or fixed-effects models based on heterogeneity of included studies. A total of 984 patients from 6 prospective clinical trials were included in the analysis. The overall incidence of all-grade and high-grade HFSR was 29.2 % (95 % CI: 14.0-51.1 %) and 9.6 % (95 % CI: 4.2-20.7 %), respectively. The relative risks of all-grade and high-grade HFSR to axitinib compared to sorafenib were decreased for all-grade (RR=0.54, 95 % CI: 0.44-0.65, p<0.001) and high-grade HFSR (RR=0.31, 95 % CI: 0.19-0.52, p<0.001). The risk of all-grade and high-grade HFSR to axitinib, sunitinib and sorafenib was significantly higher as compared to pazopanib (RR=6.49, 95 % CI: 4.65-9.05, p<0.001; RR=6.40, 95 % CI: 3.60-11.37, p<0.001, and RR=4.20, 95 % CI: 3.07-5.75, p<0.001; RR=3.67, 95 % CI: 2.15-6.24, p<0.001, and RR=7.51, 95 % CI: 5.5-10.3, p<0.001; RR=5.93, 95 % CI: 3.5-10.0, p<0.001, respectively). Similar to sorafenib and sunitinib, axitinib is associated with a significant risk of HFSR, despite having an increased specificity for VEGF receptors. These findings underscore the importance of supportive dermatologic care in patients treated with axitinib, in order to maintain quality of life, adherence, and persistence to therapy.
阿昔替尼是一种强效、选择性的血管内皮生长因子受体（VEGFR）抑制剂。我们进行了一项系统分析，旨在研究阿昔替尼引起手足皮肤反应（HFSR）的风险，并比较索拉非尼、舒尼替尼、帕唑帕尼和阿昔替尼之间的发生率差异。从 PubMed（1998-2012 年）中检索到相关研究。符合条件的研究仅限于前瞻性 II-III 期临床试验，其中癌症患者以 5mg 口服、每日 2 次的起始剂量接受阿昔替尼单药治疗。使用随机效应或固定效应模型，根据纳入研究的异质性，计算发生率、相对风险（RR）和 95%置信区间。共有 6 项前瞻性临床试验的 984 名患者纳入分析。所有级别和高级别 HFSR 的总发生率分别为 29.2%（95%CI：14.0-51.1%）和 9.6%（95%CI：4.2-20.7%）。与索拉非尼相比，阿昔替尼发生所有级别和高级别 HFSR 的 RR 分别降低（所有级别：RR=0.54，95%CI：0.44-0.65，p<0.001；高级别：RR=0.31，95%CI：0.19-0.52，p<0.001）。与帕唑帕尼相比，阿昔替尼、舒尼替尼和索拉非尼发生所有级别和高级别 HFSR 的风险显著升高（RR=6.49，95%CI：4.65-9.05，p<0.001；RR=6.40，95%CI：3.60-11.37，p<0.001，RR=4.20，95%CI：3.07-5.75，p<0.001；RR=3.67，95%CI：2.15-6.24，p<0.001，RR=7.51，95%CI：5.5-10.3，p<0.001；RR=5.93，95%CI：3.5-10.0，p<0.001）。与索拉非尼和舒尼替尼相似，阿昔替尼与 HFSR 风险显著相关，尽管其对 VEGF 受体具有更高的特异性。这些发现强调了在接受阿昔替尼治疗的患者中进行支持性皮肤科护理的重要性，以维持生活质量、依从性和治疗持久性。
