title: Efatutazone, an oral PPAR-γ agonist, in combination with paclitaxel in anaplastic thyroid cancer: results of a multicenter phase 1 trial.
abstract: OBJECTIVE
  A phase 1 study was initiated to determine the safety, potential effectiveness, and maximal tolerated dose and recommended phase 2 dose of efatutazone and paclitaxel in anaplastic thyroid cancer.
  
  
  METHODS
  Patients received efatutazone (0.15, 0.3, or 0.5 mg) orally twice daily and then paclitaxel every 3 weeks. Patient tolerance and outcomes were assessed, as were serum efatutazone pharmacokinetics.
  
  
  RESULTS
  Ten of 15 patients were women. Median age was 59 years. Seven patients received 0.15 mg of efatutazone, 6 patients received 0.3 mg, and 2 patients received 0.5 mg. One patient receiving 0.3 mg of efatutazone had a partial response from day 69 to day 175; 7 patients attained stable disease. Median times to progression were 48 and 68 days in patients receiving 0.15 mg of efatutazone and 0.3 mg of efatutazone, respectively; corresponding median survival was 98 vs 138 days. The median peak efatutazone blood level was 8.6 ng/mL for 0.15-mg dosing vs 22.0 ng/mL for 0.3-mg twice daily dosing. Ten patients had grade 3 or greater adverse events (Common Terminology Criteria for Adverse Events), with 2 of these (anemia and edema) related to efatutazone. Thirteen events of edema were reported in 8 patients, with 2 of grade 3 or greater. Eight patients had ≥1 serious adverse event, with 1 of these (anemia) attributed to efatutazone and 1 (anaphylactic reaction) related to paclitaxel. The maximal tolerated dose was not achieved. Angiopoietin-like 4 was induced by efatutazone in tissue biopsy samples of 2 patients.
  
  
  CONCLUSIONS
  Efatutazone and paclitaxel in combination were safe and tolerated and had biologic activity.
authors.affiliation: Mayo Clinic, 4500 San Pablo Road, Jacksonville, Florida 32224, USA. smallridge.robert@mayo.edu
authors.forename: R C
authors.initials: RC
authors.lastname: Smallridge
authors.forename: J A
authors.initials: JA
authors.lastname: Copland
authors.forename: M S
authors.initials: MS
authors.lastname: Brose
authors.forename: J T
authors.initials: JT
authors.lastname: Wadsworth
authors.forename: Y
authors.initials: Y
authors.lastname: Houvras
authors.forename: M E
authors.initials: ME
authors.lastname: Menefee
authors.forename: K C
authors.initials: KC
authors.lastname: Bible
authors.forename: M H
authors.initials: MH
authors.lastname: Shah
authors.forename: A W
authors.initials: AW
authors.lastname: Gramza
authors.forename: J P
authors.initials: JP
authors.lastname: Klopper
authors.forename: L A
authors.initials: LA
authors.lastname: Marlow
authors.forename: M G
authors.initials: MG
authors.lastname: Heckman
authors.forename: R
authors.initials: R
authors.lastname: Von Roemeling
mesh_terms: D052242:Adiponectin / Q000097:blood; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D047495:PPAR gamma / Q000819:agonists*; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D045162:Thiazolidinediones / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D065646:Thyroid Carcinoma, Anaplastic; D013964:Thyroid Neoplasms / Q000188:drug therapy*
chemical_list: D052242:Adiponectin; D047495:PPAR gamma; D045162:Thiazolidinediones; C510342:efatutazone; D017239:Paclitaxel