Phase i trial of exemestane in combination with metformin and rosiglitazone in nondiabetic obese postmenopausal women with hormone receptor-positive metastatic breast cancer

Francisco J. Esteva, Stacy L. Moulder, Ana M. Gonzalez-Angulo, Joe Ensor, James L. Murray, Marjorie C. Green, Kimberly B. Koenig, Mong Hong Lee, Gabriel N. Hortobagyi, Sai Ching Yeung

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

Purpose: Obese women with breast cancer have worse prognosis than women with normal body mass index. Endocrine therapy resistance is in part mediated by insulin resistance in obese women with breast cancer. We investigated the tolerability and pharmacokinetics of exemestane in combination with metformin and rosiglitazone in nondiabetic overweight and obese postmenopausal women with hormone receptor-positive metastatic breast cancer. Methods: Patients had previously received chemotherapy and endocrine therapy for breast cancer. Exemestane was given as 25 mg orally per day. Metformin (M) and rosiglitazone (R) were given twice daily. Dose level 1 consisted of M 1,500 mg/day and R 6 mg/day. Dose level 2 consisted of M 2,000 mg/day and R 8 mg/day. Plasma concentrations of exemestane were measured on days 1, 8, and 15. Results: Twenty patients were enrolled. Fourteen patients received exemestane, metformin, and rosiglitazone. Six patients received exemestane with metformin only (2,000 mg/day). Both regimens were well tolerated at the highest doses tested, and there were no notable changes in plasma exemestane levels. Six patients (30 %) had stable disease for 6 months or longer. Conclusions: Oral daily administration of exemestane (25 mg) and metformin (2,000 mg) with and without rosiglitazone (8 mg) daily was well tolerated. Exemestane pharmacokinetics were not altered by metformin and rosiglitazone.

Original languageEnglish (US)
Pages (from-to)63-72
Number of pages10
JournalCancer Chemotherapy and Pharmacology
Volume71
Issue number1
DOIs
StatePublished - Jan 2013

Keywords

  • Breast neoplasm
  • Exemestane
  • Metformin
  • Phase I trial
  • Rosiglitazone

ASJC Scopus subject areas

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)

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