Department of Dermatology, Showa University School of Medicine Bayer Yakuhin Ltd, Osaka, Japan.
J Dermatol. 2011 Mar;38(3):261-6. doi: 10.1111/j.1346-8138.2010.01059.x. Epub 2010 Nov 2.
Sorafenib (Nexavar) is an oral multi-kinase inhibitor that targets tumor growth and angiogenesis, having encouraging efficacy and tolerability in patients with metastatic renal cell carcinoma (RCC) and other tumors. However, hand-foot syndrome (HFS), a frequently reported adverse event under sorafenib treatment, sometimes causes interruption of the treatment or dose reduction. This study was conducted to review sorafenib-associated HSF in Japanese patients, to facilitate improvement of the management of HFS in clinical practice. We reviewed the combined results on HFS in three sorafenib studies in Japanese patients: (A) a phase II study of metastatic renal cell carcinoma; (B) a phase I study of solid tumor; and (C), phase I study of hepatocellular carcinoma. Severity of HFS was graded as 1-3 based on the modified grading scale of National Cancer Institute - Common Toxicity Criteria version 2.0 and Common Terminology Criteria for Adverse Events version 3.0. A total of 189 patients were included for analyses. The incidence of all-grade HFS was 51% (55% in A, 39% in B and 44% in C), and the incidence of grade 3 HFS was 7% (9% in A, 0% in B and 7% in C). Incidence of HFS seemed dose-dependent. These events were observed within 3-9 weeks after initiation of sorafenib treatment. The majority of HFS was manageable with symptomatic treatment and HFS caused permanent discontinuation of sorafenib in only one patient (in study A). The incidence of sorafenib-associated HFS is high compared to other adverse events. However, the present analyses showed that HFS under sorafenib treatment is well manageable in Japanese patients.
索拉非尼（多吉美）是一种口服多激酶抑制剂，能抑制肿瘤生长和血管生成，对转移性肾细胞癌（RCC）和其他肿瘤患者具有良好的疗效和耐受性。然而，手足综合征（HFS）是索拉非尼治疗中常见的不良反应，有时会导致治疗中断或剂量减少。本研究旨在回顾日本患者中索拉非尼相关的 HFS，以促进临床实践中 HFS 管理的改善。我们回顾了三项日本患者索拉非尼研究中关于 HFS 的综合结果：（A）转移性肾细胞癌的 II 期研究；（B）实体瘤的 I 期研究；和（C）肝细胞癌的 I 期研究。根据改良的国立癌症研究所-常见毒性标准 2.0 版和常见不良事件术语标准 3.0 版，将 HFS 的严重程度分为 1-3 级。共纳入 189 例患者进行分析。所有级别 HFS 的发生率为 51%（A 组为 55%，B 组为 39%，C 组为 44%），3 级 HFS 的发生率为 7%（A 组为 9%，B 组为 0%，C 组为 7%）。HFS 的发生率似乎与剂量有关。这些事件发生在索拉非尼治疗开始后 3-9 周内。大多数 HFS 通过对症治疗可控制，只有 1 例患者（A 组）因 HFS 而永久停止使用索拉非尼。与其他不良反应相比，索拉非尼相关的 HFS 发生率较高。然而，本分析显示，日本患者的 HFS 在索拉非尼治疗下易于管理。
