Regorafenib in Japanese patients with solid tumors: phase I study of safety, efficacy, and pharmacokinetics.
Regorafenib in Japanese patients with solid tumors: phase I study of safety, efficacy, and pharmacokinetics.
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DOI：
10.1007/s10637-013-9953-8
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发表时间：
2014-02
影响因子：
3.4
通讯作者：
Sasaki, Yasutsuna
中科院分区：
文献类型：
--
作者：
Sunakawa, Yu;Furuse, Junji;Okusaka, Takuji;Ikeda, Masafumi;Nagashima, Fumio;Ueno, Hideki;Mitsunaga, Shuichi;Hashizume, Kensei;Ito, Yuichiro;Sasaki, Yasutsuna
在这项多中心、单组、I期试验中评估了多激酶抑制剂瑞戈非尼在日本患者中的安全性、药代动力学和抗肿瘤活性。15例难治性晚期实体瘤患者在每个4周周期的前3周接受瑞戈非尼160 mg每日一次治疗，直至疾病进展、不可接受的毒性或研究者或患者决定停止治疗。中位治疗持续时间为2.1个月（范围：0.9-20.1个月）。数据截止时，1例患者仍在第21周期接受瑞格非尼治疗。停药原因为疾病进展（n = 12）和不良事件（肝酶升高n = 1;贫血n = 1）。6例患者因不良事件需要降低剂量，7例患者中断每日治疗，4例患者延迟治疗周期。所有患者均发生了至少1起药物相关不良事件，特别是胃肠道（87%）、皮肤病（73%）或血液学（67%）事件。单次给药和21天连续给药之间，瑞戈非尼及其活性代谢产物M2和M5的达峰时间或终末半衰期无显著变化。与单次给药相比，连续给药后瑞戈非尼的浓度-时间曲线下面积分别高2.1倍、5.2倍和37.3倍，最大浓度分别高2.0倍、4.8倍和36.0倍。1例患者部分缓解（持续时间10.5个月），7例患者病情稳定。这项研究表明，瑞戈非尼160 mg口服每日一次（21天治疗/7天停药）可用于日本实体瘤患者，无过度毒性。
The safety, pharmacokinetics, and antitumor activity of the multikinase inhibitor regorafenib in Japanese patients was assessed in this multicenter, single-arm, phase I trial. Fifteen patients with treatment-refractory advanced solid tumors received regorafenib 160 mg once daily for the first 3 weeks of each 4-week cycle until disease progression, unacceptable toxicity, or investigator or patient decision to stop. The median duration of treatment was 2.1 months (range, 0.9–20.1 months). At data cutoff, one patient was still receiving regorafenib in cycle 21. Reasons for treatment discontinuation were disease progression (n = 12) and adverse events (liver enzyme elevation n = 1; anemia n = 1). Adverse events necessitated dose reduction in six patients, interruption of daily treatment in seven patients, and cycle delay in four patients. All patients experienced at least one drug-related adverse event, particularly gastrointestinal (87 %), dermatologic (73 %), or hematologic (67 %) events. There was no significant change in time to maximum concentration or terminal half-life of regorafenib and its active metabolites M2 and M5 between single dosing and 21-day continuous dosing. The area under the concentration–time curve was 2.1-fold higher for regorafenib, 5.2-fold higher for M2, and 37.3-fold higher for M5, and the maximum concentration was 2.0-fold, 4.8-fold, and 36.0-fold higher, respectively, after continuous dosing than after single dosing. One patient had a partial response (duration 10.5 months) and seven patients had stable disease. This study indicates that regorafenib 160 mg orally once daily (21 days on/7 days off treatment) can be given to Japanese patients who have solid tumors, without undue toxicity.
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影响因子：
8.8
作者：
Strumberg D;Scheulen ME;Schultheis B;Richly H;Frost A;Büchert M;Christensen O;Jeffers M;Heinig R;Boix O;Mross K
通讯作者：
Mross K
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：
9.8
作者：
Gotink, Kristy J.;Verheul, Henk M. W.
通讯作者：
Verheul, Henk M. W.
DOI：
10.1016/s0140-6736(12)61857-1
发表时间：
2013-01-26
期刊：
Lancet (London, England)
影响因子：
--
作者：
Demetri GD;Reichardt P;Kang YK;Blay JY;Rutkowski P;Gelderblom H;Hohenberger P;Leahy M;von Mehren M;Joensuu H;Badalamenti G;Blackstein M;Le Cesne A;Schöffski P;Maki RG;Bauer S;Nguyen BB;Xu J;Nishida T;Chung J;Kappeler C;Kuss I;Laurent D;Casali PG;GRID study investigators
通讯作者：
GRID study investigators
影响因子：
11.5
作者：
Mross, Klaus;Frost, Annette;Christensen, Olaf
通讯作者：
Christensen, Olaf