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

Authors

• R 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

Publication/Presentation Date

6-1-2013

Abstract

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.

Volume

98

Issue

6

First Page

2392

Last Page

2400

ISSN

1945-7197

Published In/Presented At

Smallridge, R. C., Copland, J. A., Brose, M. S., Wadsworth, J. T., Houvras, Y., Menefee, M. E., Bible, K. C., Shah, M. H., Gramza, A. W., Klopper, J. P., Marlow, L. A., Heckman, M. G., & Von Roemeling, R. (2013). Efatutazone, an oral PPAR-γ agonist, in combination with paclitaxel in anaplastic thyroid cancer: results of a multicenter phase 1 trial. The Journal of clinical endocrinology and metabolism, 98(6), 2392–2400. https://doi.org/10.1210/jc.2013-1106

Disciplines

Medicine and Health Sciences

PubMedID

23589525

Department(s)

Hematology-Medical Oncology Division

Document Type

Article