Efatutazone, an oral PPAR- γ agonist, in combination with paclitaxel in anaplastic thyroid cancer: Results of a multicenter phase 1 trial

Robert C. Smallridge, J. A. Copland, M. S. Brose, J. T. Wadsworth, Y. Houvras, M. E. Menefee, K. C. Bible, M. H. Shah, A. W. Gramza, J. P. Klopper, L. A. Marlow, M. G. Heckman, R. Von Roemeling

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68 Scopus citations


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 0.3mgof 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.

Original languageEnglish (US)
Pages (from-to)2392-2400
Number of pages9
JournalJournal of Clinical Endocrinology and Metabolism
Issue number6
StatePublished - Jun 2013

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical


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