他米巴罗汀晚期肝癌患者的I / II期研究

StephenW

Hepatology International
January 2014, Volume 8, Issue 1, pp 94-103
An open-label phase I/II study of tamibarotene in patients with advanced hepatocellular carcinoma

    Fumihiko Kanai,
    Shuntaro Obi,
    Shigetoshi Fujiyama,
    Shuichiro Shiina,
    Hideyuki Tamai,
    Hitoshi Mochizuki,
    Yukihiro Koike,
    Jun Imamura,
    Takayoshi Yamaguchi,
    Isamu Saida,
    … show all 12


Abstract
Aim

Tamibarotene is a synthetic retinoid expected to inhibit tumor-cell proliferation and to induce apoptosis by selective interaction with retinoic acid receptor α/β. We conducted an open-label phase I/II study to determine the maximum tolerated dose (MTD) and recommended dose (RD), and to evaluate the pharmacokinetics, efficacy, and safety profiles for advanced hepatocellular carcinoma (HCC).
Methods

Patients with histologically confirmed, measurable, unresectable HCC of Child-Pugh classification A or B and with no effective systemic or local therapies were eligible. In phase I, patients were assigned based on the 3 + 3 dose escalation criteria to receive tamibarotene at 8, 12, and 16 mg/day. The RD determined in phase I was employed for phase II. The planned sample size in phase II was 25, including the RD-treated patients in phase I.
Results

Thirty-six patients were enrolled. No patients experienced dose-limiting toxicity (DLT) at 8 mg/day. However, two out of six patients experienced the DLTs at 12 mg/day: one experienced thrombosis in a limb vein and pulmonary artery, and the other experienced an increase of γ-GTP. The MTD and RD were determined as 12 and 8 mg/day, respectively. In phase II, one patient achieved partial response, and seven achieved stable disease. The disease control rate was 32 % (95 % CI: 15.0–53.5). The following drug-related serious adverse events were reported: thrombosis in a limb vein, pulmonary artery, and portal vein; interstitial lung disease; and vomiting.
Conclusions

Tamibarotene demonstrated the inhibition of tumor cell growth in advanced HCC with acceptable tolerance.
The registered study number was NCT00731445 (clinicaltrials.gov).

StephenW

国际肝病
2014年1月，第8卷，第1期，页94-103
开放标签阶段他米巴罗汀患者的晚期肝癌的I / II期研究

    文彦金井，
    俊太郎奥比，
    重利富士山，
    椎名修一郎，
    玉井秀，
    仁望月，
    小池幸，
    今村俊，
    山口隆义，
    赛达勇，
    ...显示所有12


摘要
目的

他米巴罗汀是有望抑制肿瘤细胞增殖，并通过与视黄酸受体α /β的选择性相互作用，诱导细胞凋亡的合成类视黄醇。我们进行了一项开放标签的I / II期研究，以确定最大耐受剂量（MTD ）和推荐剂量（ RD） ，并评估对晚期肝细胞癌（ HCC）的药代动力学，药效和安全性配置文件。
方法

患者的病理证实，为Child-Pugh分级A或B可衡量的，不能切除的肝癌并没有有效的全身或局部治疗均符合要求。在第一阶段，将患者的基础上， 3 + 3个剂量递增的标准分配接受他米巴罗汀在8， 12 ，和16毫克/天。在我被雇用期II期的RD决定。在第二阶段的计划的样本量为25 ，包括RD治疗的患者在一期
结果

36例患者。没有患者在8毫克/天经历剂量限制性毒性（DLT） 。然而，两列的六个病人所经历的双腔管在12毫克/天：在肢体静脉和肺动脉1有经验的血栓形成，以及其他有经验的增加γ-GTP的。在MTD和RD分别确定为12和8毫克/天。在第二阶段，一名患者达到部分缓解， 7达到稳定的疾病。疾病控制率为32 ％ （ 95％CI ： 15.0-53.5 ） 。下列药物相关的严重不良事件的报告：血栓形成肢体静脉，肺动脉和门静脉，肺间质疾病，呕吐。
结论

他米巴罗汀表明肿瘤细胞生长中具有可接受的公差晚期HCC的抑制。
已注册的学号为NCT00731445 （ clinicaltrials.gov ） 。

MP4

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