@article{ec9924b3b15f4aeeb3b6de7f282e862f,
title = "Phase i trial of exemestane in combination with metformin and rosiglitazone in nondiabetic obese postmenopausal women with hormone receptor-positive metastatic breast cancer",
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.",
keywords = "Breast neoplasm, Exemestane, Metformin, Phase I trial, Rosiglitazone",
author = "Esteva, {Francisco J.} and Moulder, {Stacy L.} and Gonzalez-Angulo, {Ana M.} and Joe Ensor and Murray, {James L.} and Green, {Marjorie C.} and Koenig, {Kimberly B.} and Lee, {Mong Hong} and Hortobagyi, {Gabriel N.} and Yeung, {Sai Ching}",
note = "Funding Information: Acknowledgments This work was supported by a PROMISE grant from the Susan G. Komen for the Cure and by the National Institutes of Health through MD Anderson{\textquoteright}s Cancer Center Support Grant (CA016672). The authors thank Bryan Tutt from the Department of Scientific Publications at MD Anderson Cancer Center for editorial assistance. We also thank Martijn Hilhorst and Thomas Thompson from PRA International (Lenexa, KS) for measurements of exemestane in human plasma and interpretation of pharmacokinetics data, respectively. The pharmacokinetics sampling was performed in the U.T. MD Anderson Cancer Center Clinical and Translational Research Center (CTRC) and was supported by the Center for Clinical and Translational Sciences, which is funded by National Institutes of Health Clinical and Translational Science Award UL1 RR024148 and by the National Institutes of Health Cancer Center Support Grant (CCSG) award CA016672 to MD Anderson Cancer Center. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health. The Susan G. Komen for the Cure and the National Institutes of Health had no influence on the design, conduct, and interpretation of the results of this study.",
year = "2013",
month = jan,
doi = "10.1007/s00280-012-1977-9",
language = "English (US)",
volume = "71",
pages = "63--72",
journal = "Cancer Chemotherapy and Pharmacology",
issn = "0344-5704",
publisher = "Springer Science and Business Media Deutschland GmbH",
number = "1",
}