Department of Surgical and Oncological Sciences, Section of Medical Oncology; Università di Palermo, Palermo, Italy, Via del Vespro 127, 90127 Palermo, Italy.
Oncologist. 2010;15(1):85-92. doi: 10.1634/theoncologist.2009-0143. Epub 2010 Jan 5.
Sorafenib is an oral multikinase inhibitor that targets Raf kinase and receptor tyrosine kinases and has led to a longer median overall survival (OS) time and time to progression (TTP) in patients with advanced hepatocellular carcinoma (HCC). This study was conducted to assess the link between the antitumor efficacy of sorafenib and its early cutaneous side effects in advanced HCC patients.
All patients received 800 mg daily of sorafenib until progression or unacceptable toxicities. We retrospectively analyzed the incidence of rash and hand-foot skin reactions (HFSR) during the first month of treatment, comparing tumor control (partial response plus stable disease) and TTP.
Sixty-five HCC patients treated with sorafenib were included in this analysis: 47 (73.3%) received sorafenib after failure of some local treatment, whereas 18 (27.7%) received it as first-line treatment. Twenty-nine patients developed at least grade 1 skin toxicity (rash, 13; HFSR, 16). In patients who developed skin toxicity, the tumor control rate was 48.3%, versus 19.4% in patients without cutaneous side effects. The median TTP was 8.1 months in the group of patients with skin toxicity versus 4.0 months in those without skin toxicity. This difference was also statistically significant on multivariate analysis. A borderline statistically significant difference was also observed in terms of OS in patients with early skin toxicity.
Skin toxicity should be closely monitored in HCC patients treated with sorafenib in relation to its potential role as a surrogate marker of efficacy.
索拉非尼是一种口服多激酶抑制剂，可靶向 Raf 激酶和受体酪氨酸激酶，可使晚期肝细胞癌（HCC）患者的中位总生存期（OS）和进展时间（TTP）延长。本研究旨在评估索拉非尼的抗肿瘤疗效与其晚期 HCC 患者早期皮肤副作用之间的关系。
所有患者均接受 800mg 索拉非尼，每日一次，直至疾病进展或出现不可耐受的毒性。我们回顾性分析了治疗首月皮疹和手足皮肤反应（HFSR）的发生率，并比较了肿瘤控制（部分缓解加稳定疾病）和 TTP。
这项分析共纳入了 65 例接受索拉非尼治疗的 HCC 患者：47 例（73.3%）在局部治疗失败后接受了索拉非尼治疗，18 例（27.7%）作为一线治疗。29 例患者至少出现了 1 级皮肤毒性（皮疹 13 例，HFSR 16 例）。在出现皮肤毒性的患者中，肿瘤控制率为 48.3%，而无皮肤副作用的患者为 19.4%。在皮肤毒性组中，TTP 的中位数为 8.1 个月，而无皮肤毒性组为 4.0 个月。在多变量分析中，这一差异也具有统计学意义。在具有早期皮肤毒性的患者中，OS 也存在统计学上的显著差异。
在接受索拉非尼治疗的 HCC 患者中，应密切监测皮肤毒性，因为它可能是疗效的替代标志物。
