Regorafenib (BAY 73-4506) in advanced colorectal cancer: a phase I study.
Regorafenib (BAY 73-4506) in advanced colorectal cancer: a phase I study.
复制标题
DOI：
10.1038/bjc.2012.153
复制
发表时间：
2012-05-22
影响因子：
8.8
通讯作者：
Mross K
中科院分区：
文献类型：
--
作者：
Strumberg D;Scheulen ME;Schultheis B;Richly H;Frost A;Büchert M;Christensen O;Jeffers M;Heinig R;Boix O;Mross K
在一项I期剂量递增研究中，瑞戈非尼在实体瘤患者中表现出耐受性和抗肿瘤活性。该研究扩展到转移性结直肠癌（CRC）患者。患者接受口服瑞戈非尼60-220 mg/天（扩展队列为160 mg/天），治疗周期为21天，停药7天。评估包括毒性、反应、药代动力学和药效学。38例接受过大量预治疗的CRC患者（中位4线既往治疗，范围0-7）入组剂量递增和扩展期; 26例患者接受瑞戈非尼160 mg每日一次治疗。中位治疗持续时间为53天（范围7-280天）。最常见的治疗相关毒性包括手足皮肤反应、疲劳、声音改变和皮疹。27例患者可评价缓解：1例达到部分缓解，19例病情稳定。中位无进展生存期为107天（95% CI，66-161）。在稳态下，瑞戈非尼及其活性代谢产物的全身暴露量相似。药效学评估表明大多数患者的肿瘤灌注减少。瑞格非尼在转移性CRC患者中显示出耐受性和抗肿瘤活性。这项扩展队列I期研究为在该患者人群中进行瑞戈非尼的进一步临床试验提供了基础。
In a phase I dose-escalation study, regorafenib demonstrated tolerability and antitumour activity in solid tumour patients. The study was expanded to focus on patients with metastatic colorectal cancer (CRC). Patients received oral regorafenib 60–220 mg daily (160 mg daily in the extension cohort) in cycles of 21 days on, 7 days off treatment. Assessments included toxicity, response, pharmacokinetics and pharmacodynamics. Thirty-eight patients with heavily pretreated CRC (median 4 prior lines of therapy, range 0–7) were enrolled in the dose-escalation and extension phases; 26 patients received regorafenib 160 mg daily. Median treatment duration was 53 days (range 7–280 days). The most common treatment-related toxicities included hand–foot skin reaction, fatigue, voice change and rash. Twenty-seven patients were evaluable for response: 1 achieved partial response and 19 had stable disease. Median progression-free survival was 107 days (95% CI, 66–161). At steady state, regorafenib and its active metabolites had similar systemic exposure. Pharmacodynamic assessment indicated decreased tumour perfusion in most patients. Regorafenib showed tolerability and antitumour activity in patients with metastatic CRC. This expanded-cohort phase I study provided the foundation for further clinical trials of regorafenib in this patient population.
登录
查看更多内容
影响因子：
8.4
作者：
Eisenhauer, E. A.;Therasse, P.;Verweij, J.
通讯作者：
Verweij, J.
影响因子：
6.4
作者：
Wilhelm, Scott M.;Dumas, Jacques;Zopf, Dieter
通讯作者：
Zopf, Dieter
影响因子：
254.7
作者：
Parkin, DM;Bray, F;Pisani, P
通讯作者：
Pisani, P
影响因子：
50.5
作者：
Van Cutsem, E.;Siena, S.;Peeters, M.
通讯作者：
Peeters, M.
影响因子：
158.5
作者：
Hurwitz, H;Fehrenbacher, L;Kabbinavar, F
通讯作者：
Kabbinavar, F