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A phase II study of 17-allylamino-17-demethoxygeldanamycin in metastatic or locally advanced, unresectable breast cancer

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Abstract

Heat shock protein 90 (Hsp90) is an attractive target for breast cancer treatment, as it is required for the proper folding and stabilization of several proteins known to be involved in breast cancer growth and development. These proteins include the epidermal growth factor receptor, human epidermal growth factor receptor 2 (HER2), estrogen receptor (ER), progesterone receptor (PR), and src. 17-Allylamino-17-demethoxygeldanamycin (17-AAG) is an intravenous Hsp90 inhibitor in development for breast cancer treatment. We conducted a phase II study of 17-AAG 220 mg/m2 on days 1, 4, 8, and 11 every 21 days in patients with metastatic and locally advanced breast cancer. Since we expected the molecular effects of Hsp90 inhibition to extend beyond just ER, PR, and HER2 down regulation and to impact a variety of other cellular proteins, patients were not selected based on ER, PR, or HER2 status. Eleven patients, including 6 patients with triple negative breast cancer, were enrolled and treated. There were no responses and 3 patients had stable disease as their best response. Five patients developed grade 3/4 toxicities, which were primarily hepatic and pulmonary. Based on these results, we do not recommend further study of 17-AAG at this dosing schedule or in unselected breast cancer patients.

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Acknowledgment

This study was funded through a grant from the National Institutes of Health, U01 CA062487.

Ethical standards

This study was performed within and conducted in compliance with the current laws of the United States of America.

Conflict of interest

Lawrence Flaherty discloses that he has participated as an advisor to Bristol-Myers Squibb in relation to other agents. The remaining authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Karmanos Cancer Institute, Wayne State University, 4100 John R, 4HWCRC, Detroit, MI, 48201, USA

    Elaina M. Gartner, Michael Simon, Lawrence Flaherty & Patricia M. LoRusso

  2. University Hospitals Seidman Cancer Center, Case Western Reserve University, 11100 Euclid Avenue, Cleveland, OH, 44106, USA

    Paula Silverman

  3. Karmanos Cancer Institute, Wayne State University, 4100 John R, 716 HPOB, Detroit, MI, 48201, USA

    Judith Abrams

  4. Cancer Therapy Evaluation Program, National Cancer Institute, National Institutes of Health, Executive Plaza North, Suite 7130, Rockville, MD, 20852-7426, USA

    Percy Ivy

Authors
  1. Elaina M. Gartner
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  2. Paula Silverman
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  3. Michael Simon
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  4. Lawrence Flaherty
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  5. Judith Abrams
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  6. Percy Ivy
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  7. Patricia M. LoRusso
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Corresponding author

Correspondence to Elaina M. Gartner.

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Gartner, E.M., Silverman, P., Simon, M. et al. A phase II study of 17-allylamino-17-demethoxygeldanamycin in metastatic or locally advanced, unresectable breast cancer. Breast Cancer Res Treat 131, 933–937 (2012). https://doi.org/10.1007/s10549-011-1866-7

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  • DOI: https://doi.org/10.1007/s10549-011-1866-7

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