Medical Oncology and Hematology Unit, Cancer Center, Humanitas Clinical and Research Center, Rozzano, Milan, Italy.
Oncologist. 2013;18(4):379-80. doi: 10.1634/theoncologist.2012-0221. Epub 2013 Apr 11.
Sorafenib has proven survival benefits in patients with advanced hepatocellular carcinoma (HCC). The viability of continuing sorafenib at a higher dosage in patients who experienced radiologic disease progression was investigated.
Patients who experienced disease progression while on sorafenib 400 mg twice daily were randomized to sorafenib 600 mg twice daily (n = 49) or best supportive care (n = 52). The primary end point was progression-free survival (PFS). Time to progression, overall survival, and safety were also evaluated.
The study did not meet its primary end point. The difference in PFS between the sorafenib arm (3.91 months) and the best supportive care arm (2.69 months) did not reach statistical significance (p = 0.086). Adverse events were mainly grade 1-2 and similar across both groups. In the sorafenib arm, the most frequent events were diarrhea (80%), weight loss (75%), fatigue (67%), hand-foot-skin reaction (49%), abdominal pain (37%), and stomatitis (26%).
Escalated-dose sorafenib in patients with advanced HCC who progressed while on sorafenib, failed to provide any clinical benefit. Second-line treatment still remains an open issue to be explored in appropriate clinical trials.
索拉非尼已被证明可使晚期肝细胞癌（HCC）患者获益生存。本研究旨在探索对接受索拉非尼 400mg 每日两次治疗后出现影像学疾病进展的患者增加剂量继续使用索拉非尼的疗效。
在接受索拉非尼 400mg 每日两次治疗期间疾病进展的患者中，按 2:1 的比例随机分为索拉非尼 600mg 每日两次组（n=49）或最佳支持治疗组（n=52）。主要终点为无进展生存期（PFS）。同时评估了进展时间、总生存期和安全性。
本研究未达到主要终点。与最佳支持治疗组（2.69 个月）相比，索拉非尼组的 PFS（3.91 个月）差异无统计学意义（p=0.086）。两组不良反应主要为 1-2 级，且相似。在索拉非尼组中，最常见的事件是腹泻（80%）、体重减轻（75%）、乏力（67%）、手足皮肤反应（49%）、腹痛（37%）和口腔炎（26%）。
对接受索拉非尼治疗后进展的晚期 HCC 患者增加剂量使用索拉非尼并未带来任何临床获益。二线治疗仍然是一个有待在适当临床试验中探索的开放性问题。
