title: Phase I study of Efatutazone, an oral PPARγ agonist, in patients with metastatic solid tumors.
abstract: BACKGROUND
  Efatutazone is a highly selective agonist of peroxisome proliferator-activated receptor gamma (PPARγ), a therapeutic target for carcinogenesis.
  
  
  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.
  
  
  CONCLUSIONS
  Efatutazone demonstrated acceptable toxicity and gave evidence of disease control in Japanese patients with metastatic solid tumors.
authors.affiliation: Division of Thoracic Oncology, Shizuoka Cancer Center, Shizuoka, Japan ha.murakami@scchr.jp.
authors.forename: Haruyasu
authors.initials: H
authors.lastname: Murakami
authors.affiliation: Division of Thoracic Oncology, Shizuoka Cancer Center, Shizuoka, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Ono
authors.affiliation: Division of Thoracic Oncology, Shizuoka Cancer Center, Shizuoka, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Takahashi
authors.affiliation: Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Onozawa
authors.affiliation: Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Tsushima
authors.affiliation: Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Yamazaki
authors.affiliation: Clinical Planning Department, Daiichi Sankyo Co., Ltd., Tokyo, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Jikoh
authors.affiliation: Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan Department of Clinical Oncology, St. Marianna University School of Medicine, Kanagawa, Japan.
authors.forename: Narikazu
authors.initials: N
authors.lastname: Boku
authors.affiliation: Division of Thoracic Oncology, Shizuoka Cancer Center, Shizuoka, Japan Third Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Yamamoto
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015415:Biomarkers / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000473:pathology*; D047495:PPAR gamma / Q000819:agonists; D045162:Thiazolidinediones / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; D047495:PPAR gamma; D045162:Thiazolidinediones; C510342:efatutazone
keywords: Adiponectin; Japan; PPARγ dose-escalation study; efatutazone; phase I trial