Phase I study of Efatutazone, an oral PPARγ agonist, in patients with metastatic solid tumors

Anticancer Res. 2014 Sep;34(9):5133-41.

Abstract

Background: Efatutazone is a highly selective agonist of peroxisome proliferator-activated receptor gamma (PPARγ), a therapeutic target for carcinogenesis.

Patients and methods: In this phase I dose-escalation study, we assessed the safety, efficacy, and pharmacokinetics of efatutazone and the recommended dose (RD) was determined in Japanese patients with metastatic solid tumors using a 3+3 design.

Results: A total of 13 patients were enrolled and received efatutazone at doses of 0.25 mg, 0.50 mg, and 0.75 mg bid for multiple 3-week cycles. No dose-limiting toxicities were observed, and the maximum tolerated dose was not reached. Partial response was confirmed in one patient and stable disease in three. Efatutazone exposure was almost dose-proportional. RD was determined to be 0.50 mg bid, corresponding to the RD in previous global phase I studies.

Conclusion: Efatutazone demonstrated acceptable toxicity and gave evidence of disease control in Japanese patients with metastatic solid tumors.

Keywords: Adiponectin; Japan; PPARγ dose-escalation study; efatutazone; phase I trial.

Publication types

  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Aged
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Biomarkers / metabolism
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasms / diagnosis
  • Neoplasms / drug therapy*
  • Neoplasms / pathology*
  • PPAR gamma / agonists
  • Thiazolidinediones / pharmacology
  • Thiazolidinediones / therapeutic use*
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Biomarkers
  • PPAR gamma
  • Thiazolidinediones
  • efatutazone