Sorafenib in patients with advanced biliary tract carcinoma: a phase II trial
Sorafenib in patients with advanced biliary tract carcinoma: a phase II trial
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DOI：
10.1038/sj.bjc.6605458
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发表时间：
2010-01-05
影响因子：
8.8
通讯作者：
Conte, P.
中科院分区：
文献类型：
--
作者：
Bengala, C.;Bertolini, F.;Conte, P.
背景：晚期胆道癌预后很差，化疗是主要的治疗手段。Sorafenib是一种VEGFR-2/-3、pdgfr - β、B-Raf和C-Raf的多激酶抑制剂，已被证明在胆管癌的临床前模型中具有活性。方法：我们对晚期胆道癌患者进行了单药索拉非尼的II期试验。索拉非尼的剂量为400毫克，每天两次。主要终点是12周时的疾病控制率。结果：共治疗46例患者。总的来说，26例（56%）患者在早期接受了化疗，36例患者完成了至少45天的治疗。意向治疗分析中，客观缓解率为2%，12周时疾病控制率为32.6%。无进展生存期（PFS）为2.3个月（范围：0-12个月），中位总生存期为4.4个月（范围：0-22个月）。表现状态与PFS显著相关：ECOG 0和1的中位PFS值分别为5.7和2.1个月（P = 0.0002）。最常见的毒性是皮疹（35%）和疲劳（33%），22%的患者需要减少剂量。结论：索拉非尼单药治疗胆管癌的活性较低。表现良好的患者PFS较好。毒性是可控的。英国癌症杂志（2010）102,68-72。doi: 10.1038 / sj.bjc。6605458 www.bjcancer.com 2009年11月24日在线发布(C) 2010年英国癌症研究中心
BACKGROUND: Advanced biliary tract carcinoma has a very poor prognosis, with chemotherapy being the mainstay of treatment. Sorafenib, a multikinase inhibitor of VEGFR-2/-3, PDGFR-beta, B-Raf, and C-Raf, has shown to be active in preclinical models of cholangiocarcinoma.METHODS: We conducted a phase II trial of single-agent sorafenib in patients with advanced biliary tract carcinoma. Sorafenib was administered at a dose of 400 mg twice a day. The primary end point was the disease control rate at 12 weeks.RESULTS: A total of 46 patients were treated. In all, 26 (56%) had received chemotherapy earlier, and 36 patients completed at least 45 days of treatment. In intention-to-treat analysis, the objective response was 2% and the disease control rate at 12 weeks was 32.6%. Progression-free survival (PFS) was 2.3 months (range: 0-12 months), and the median overall survival was 4.4 months (range: 0-22 months). Performance status was significantly related to PFS: median PFS values for ECOG 0 and 1 were 5.7 and 2.1 months, respectively (P = 0.0002). The most common toxicities were skin rash (35%) and fatigue (33%), requiring a dose reduction in 22% of patients.CONCLUSIONS: Sorafenib as a single agent has a low activity in cholangiocarcinoma. Patients having a good performance status have a better PFS. The toxicity profile is manageable. British Journal of Cancer (2010) 102, 68-72. doi:10.1038/sj.bjc.6605458 www.bjcancer.com Published online 24 November 2009 (C) 2010 Cancer Research UK