Efatutazone, an Oral PPAR-γ Agonist, in Combination With Paclitaxel in Anaplastic Thyroid Cancer: Results of a Multicenter Phase 1 Trial

J Clin Endocrinol Metab. 2013 Jun;98(6):2392-400. doi: 10.1210/jc.2013-1106. Epub 2013 Apr 15.


Purpose: 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.

Experimental design: 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.

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiponectin / blood
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Female
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • PPAR gamma / agonists*
  • Paclitaxel / administration & dosage
  • Paclitaxel / adverse effects
  • Thiazolidinediones / administration & dosage*
  • Thiazolidinediones / adverse effects
  • Thiazolidinediones / blood
  • Thyroid Carcinoma, Anaplastic
  • Thyroid Neoplasms / drug therapy*


  • Adiponectin
  • PPAR gamma
  • Thiazolidinediones
  • efatutazone
  • Paclitaxel