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Journal of Cancer Research and Clinical Oncology

, Volume 134, Issue 12, pp 1325–1335 | Cite as

A phase I/II trial of TAC-101, an oral synthetic retinoid, in patients with advanced hepatocellular carcinoma

  • Kimberly B. Higginbotham
  • Richard Lozano
  • Thomas Brown
  • Yehuda Z. Patt
  • Takashi Arima
  • James L. Abbruzzese
  • Melanie B. ThomasEmail author
Original Paper

Abstract

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.

Keywords

Hepatocellular carcinoma Clinical trial Retinoids TAC-101 Survival 

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Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Kimberly B. Higginbotham
    • 1
  • Richard Lozano
    • 1
  • Thomas Brown
    • 1
  • Yehuda Z. Patt
    • 2
  • Takashi Arima
    • 3
  • James L. Abbruzzese
    • 1
  • Melanie B. Thomas
    • 1
    Email author
  1. 1.Department of Gastrointestinal Medical Oncology Unit 426The University of Texas M.D. Anderson Cancer CenterHoustonUSA
  2. 2.University of New Mexico Cancer Research and Treatment CenterAlbuquerqueUSA
  3. 3.Taiho Pharmaceutical Co., LtdTokyoJapan

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