Phase I trial of exemestane in combination with metformin and rosiglitazone in nondiabetic obese postmenopausal women with hormone receptor–positive metastatic breast cancer
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..
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2012 |
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| Erschienen: |
2012 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:71 |
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| Enthalten in: |
Cancer chemotherapy and pharmacology - 71(2012), 1 vom: 28. Sept., Seite 63-72 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Esteva, Francisco J. [VerfasserIn] |
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| Links: |
Volltext [lizenzpflichtig] |
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| Themen: |
Breast neoplasm |
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| Anmerkungen: |
© Springer-Verlag Berlin Heidelberg 2012 |
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| doi: |
10.1007/s00280-012-1977-9 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
SPR003603059 |
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| 100 | 1 | |a Esteva, Francisco J. |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Phase I trial of exemestane in combination with metformin and rosiglitazone in nondiabetic obese postmenopausal women with hormone receptor–positive metastatic breast cancer |
| 264 | 1 | |c 2012 | |
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| 500 | |a © Springer-Verlag Berlin Heidelberg 2012 | ||
| 520 | |a 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. | ||
| 650 | 4 | |a Breast neoplasm |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Exemestane |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Metformin |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Rosiglitazone |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Phase I trial |7 (dpeaa)DE-He213 | |
| 700 | 1 | |a Moulder, Stacy L. |4 aut | |
| 700 | 1 | |a Gonzalez-Angulo, Ana M. |4 aut | |
| 700 | 1 | |a Ensor, Joe |4 aut | |
| 700 | 1 | |a Murray, James L. |4 aut | |
| 700 | 1 | |a Green, Marjorie C. |4 aut | |
| 700 | 1 | |a Koenig, Kimberly B. |4 aut | |
| 700 | 1 | |a Lee, Mong-Hong |4 aut | |
| 700 | 1 | |a Hortobagyi, Gabriel N. |4 aut | |
| 700 | 1 | |a Yeung, Sai-Ching |4 aut | |
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