Dataset Information

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

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.

SUBMITTER: Smallridge RC

PROVIDER: S-EPMC3667260 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

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Publications

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

Smallridge R C RC Copland J A JA Brose M S MS Wadsworth J T JT Houvras Y Y Menefee M E ME Bible K C KC Shah M H MH Gramza A W AW Klopper J P JP Marlow L A LA Heckman M G MG Von Roemeling R R

The Journal of clinical endocrinology and metabolism 20130415 6

<h4>Purpose</h4>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.<h4>Experimental design</h4>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.<h4>Results</h4>Ten of 15 patients were women. Median age was 59 ...[more]

PMID: 23589525

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