Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul 135-710, Korea.
Invest New Drugs. 2012 Aug;30(4):1540-7. doi: 10.1007/s10637-011-9706-5. Epub 2011 Jun 22.
Sorafenib is a multi-kinase inhibitor, which was approved as first-line treatment for patients with advanced hepatocellular carcinoma (HCC). We conducted a phase 1 study of sorafenib plus S-1 in patients with advanced HCC.
We designed to escalate S-1 at 4 different dose levels with fixed dose of sorafenib. Four dose levels were as follows: level 1, D1-14 S-1 50 mg/m(2)/day + D1-21 sorafenib 400 mg bid; level 2, D1-14 S-1 60 mg/m(2)/day + D1-21 sorafenib 400 mg bid; level 3,, D1-14 S-1 70 mg/m(2)/day + D1-21 sorafenib 400 mg bid; level 4, D1-14 S-1 80 mg/m(2)/day + D1-21 sorafenib 400 mg bid. The treatment was repeated every 3 weeks.
From August 2009 to July 2010, 20 patients with advanced HCC were enrolled. The median age was 48 years (range, 29-74). Eighteen (90%) patients had hepatitis B viral infection and 19 (95%) patients were rated as Child-Pugh class A. The dose-limiting toxicities were grade 4 infection and thrombocytopenia. After a median follow-up duration of 8.6 months (range, 3.7-14.2 months), median PFS was 3.9 months (95% CI, 0.8-7.0 months) and median OS was 10.4 months (95% CI, 0-22.4 months). In pharmacokinetic analysis, there was no statistically significant drug interaction between sorafenib and S-1.
The combination of sorafenib and S-1 showed tolerable toxicity profile and modest clinical efficacy in patients with advanced HCC. The recommended dose of sorafenib and S-1 was 400 mg twice daily and 40 mg/m(2) twice daily, respectively.
索拉非尼是一种多激酶抑制剂，已被批准用于治疗晚期肝细胞癌（HCC）患者的一线治疗药物。我们进行了一项索拉非尼联合 S-1 治疗晚期 HCC 患者的 1 期研究。
我们设计了用固定剂量的索拉非尼递增 S-1 的 4 个不同剂量水平。4 个剂量水平如下：第 1 水平，D1-14 S-1 50mg/m2/天+D1-21 索拉非尼 400mg bid；第 2 水平，D1-14 S-1 60mg/m2/天+D1-21 索拉非尼 400mg bid；第 3 水平，D1-14 S-1 70mg/m2/天+D1-21 索拉非尼 400mg bid；第 4 水平，D1-14 S-1 80mg/m2/天+D1-21 索拉非尼 400mg bid。每 3 周重复治疗。
从 2009 年 8 月至 2010 年 7 月，共招募了 20 例晚期 HCC 患者。中位年龄为 48 岁（范围，29-74 岁）。18 例（90%）患者有乙型肝炎病毒感染，19 例（95%）患者为 Child-Pugh 分级 A。剂量限制毒性为 4 级感染和血小板减少症。中位随访时间为 8.6 个月（范围，3.7-14.2 个月），中位无进展生存期为 3.9 个月（95%CI，0.8-7.0 个月），中位总生存期为 10.4 个月（95%CI，0-22.4 个月）。在药代动力学分析中，索拉非尼和 S-1 之间没有统计学上显著的药物相互作用。
索拉非尼联合 S-1 治疗晚期 HCC 患者具有可耐受的毒性谱和适度的临床疗效。索拉非尼和 S-1 的推荐剂量分别为 400mg 每日 2 次和 40mg/m2 每日 2 次。
