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

Robert Christian Smallridge, John A III 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

Research output: Contribution to journalArticle

57 Citations (Scopus)

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 0.3mgof 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
Volume98
Issue number6
DOIs
StatePublished - Jun 2013

Fingerprint

Peroxisome Proliferator-Activated Receptors
Paclitaxel
Maximum Tolerated Dose
Anaplastic Thyroid Carcinoma
efatutazone
Anemia
Edema
Angiopoietins
Pharmacokinetics
Biopsy
Terminology
Anaphylaxis
Design of experiments
Blood
Research Design

ASJC Scopus subject areas

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

Cite this

Efatutazone, an oral PPAR- γ agonist, in combination with paclitaxel in anaplastic thyroid cancer : Results of a multicenter phase 1 trial. / Smallridge, Robert Christian; Copland, John A III; 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.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 98, No. 6, 06.2013, p. 2392-2400.

Research output: Contribution to journalArticle

Smallridge, RC, Copland, JAIII, Brose, MS, Wadsworth, JT, Houvras, Y, Menefee, ME, Bible, KC, Shah, MH, Gramza, AW, Klopper, JP, Marlow, LA, Heckman, MG & 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', Journal of Clinical Endocrinology and Metabolism, vol. 98, no. 6, pp. 2392-2400. https://doi.org/10.1210/jc.2013-1106
Smallridge, Robert Christian ; Copland, John A III ; 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. / Efatutazone, an oral PPAR- γ agonist, in combination with paclitaxel in anaplastic thyroid cancer : Results of a multicenter phase 1 trial. In: Journal of Clinical Endocrinology and Metabolism. 2013 ; Vol. 98, No. 6. pp. 2392-2400.
@article{1ea0a706781b49bcb95984fa2442309b,
title = "Efatutazone, an oral PPAR- γ 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 0.3mgof 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.",
author = "Smallridge, {Robert Christian} and Copland, {John A III} and Brose, {M. S.} and Wadsworth, {J. T.} and Y. Houvras and Menefee, {M. E.} and Bible, {K. C.} and Shah, {M. H.} and Gramza, {A. W.} and Klopper, {J. P.} and Marlow, {L. A.} and Heckman, {M. G.} and {Von Roemeling}, R.",
year = "2013",
month = "6",
doi = "10.1210/jc.2013-1106",
language = "English (US)",
volume = "98",
pages = "2392--2400",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "The Endocrine Society",
number = "6",

}

TY - JOUR

T1 - Efatutazone, an oral PPAR- γ agonist, in combination with paclitaxel in anaplastic thyroid cancer

T2 - Results of a multicenter phase 1 trial

AU - Smallridge, Robert Christian

AU - Copland, John A III

AU - Brose, M. S.

AU - Wadsworth, J. T.

AU - Houvras, Y.

AU - Menefee, M. E.

AU - Bible, K. C.

AU - Shah, M. H.

AU - Gramza, A. W.

AU - Klopper, J. P.

AU - Marlow, L. A.

AU - Heckman, M. G.

AU - Von Roemeling, R.

PY - 2013/6

Y1 - 2013/6

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84878483846&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84878483846&partnerID=8YFLogxK

U2 - 10.1210/jc.2013-1106

DO - 10.1210/jc.2013-1106

M3 - Article

C2 - 23589525

AN - SCOPUS:84878483846

VL - 98

SP - 2392

EP - 2400

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 6

ER -