一项针对晚期肝细胞癌患者的I/II期试验，该试验使用口服合成类视黄醇TAC-101。
A phase I/II trial of TAC-101, an oral synthetic retinoid, in patients with advanced hepatocellular carcinoma.
作者信息
Higginbotham Kimberly B, Lozano Richard, Brown Thomas, Patt Yehuda Z, Arima Takashi, Abbruzzese James L, Thomas Melanie B
机构信息
Department of Gastrointestinal Medical Oncology Unit 426, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA.
出版信息
J Cancer Res Clin Oncol. 2008 Dec;134(12):1325-35. doi: 10.1007/s00432-008-0406-2. Epub 2008 May 27.
PURPOSE
Preclinical models showed TAC-101 (4-[3,5-bis(trimethylsilyl) benzamide] benzoic acid), an oral synthetic retinoid, has anti-tumor activity in hepatocellular carcinoma (HCC). A phase I/II study was performed in advanced HCC patients (pts).
PATIENTS AND METHODS
Thirty-three patients were enrolled. During Phase I, pts received 40 mg daily for 14 days q3 weeks; 2 of 5 patients developed DLT so dose was reduced to 20 mg/day. Twenty-eight patients received 20 mg/day.
RESULTS
No pt had a CR or PR, but 12 of 21 (57%) had SD. Two pts (9.5%) had late PR after discontinuing TAC-101. Median survival (MS) for all 28 pts treated with 20 mg/day was 12.7 months (95% CI 8.8-22.7); MS for 21 evaluable pts was 19.2 months (95% CI 10.4-27.6).
CONCLUSIONS
20 mg of TAC- was well tolerated. Significant disease stabilization (12/21 pts, 57%), 2 late PRs, and prolonged MS (19.2 months) suggest that TAC-101 provides meaningful patient benefit.
目的
临床前模型显示，口服合成类视黄醇TAC-101（4-[3,5-双（三甲基甲硅烷基）苯甲酰胺]苯甲酸）在肝细胞癌（HCC）中具有抗肿瘤活性。对晚期HCC患者进行了一项I/II期研究。
患者与方法
共纳入33例患者。在I期，患者每3周接受40 mg/d，共14天；5例患者中有2例出现剂量限制毒性（DLT），因此剂量减至20 mg/d。28例患者接受20 mg/d治疗。
结果
无患者达到完全缓解（CR）或部分缓解（PR），但21例患者中有12例（57%）疾病稳定（SD）。2例患者（9.5%）在停用TAC-101后出现延迟PR。接受20 mg/d治疗的所有28例患者的中位生存期（MS）为12.7个月（95%CI 8.8-22.7）；21例可评估患者的MS为19.2个月（95%CI 10.4-27.6）。
结论
20 mg的TAC-耐受性良好。显著的疾病稳定（12/21例患者，57%）、2例延迟PR和延长的MS（19.2个月）表明TAC-101为患者带来了有意义的获益。
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