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Phase II study evaluating the efficacy and safety of sagopilone (ZK-EPO) in patients with metastatic breast cancer that has progressed following chemotherapy

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Abstract

Sagopilone is a novel, fully synthetic epothilone that has shown promising preclinical activity in a range of tumor models, including platinum-resistant ovarian cancer and metastatic breast cancer (MBC). This open-label, multicenter, Phase II study investigated the efficacy, safety, and tolerability of sagopilone administered to patients with MBC. Women with MBC whose previous chemotherapy regimen included a taxane and an anthracycline received sagopilone 16 or 22 mg/m2 as a 3-h intravenous infusion every 21 days. Efficacy (using modified Response Evaluation Criteria in Solid Tumors), safety, and tolerability were assessed in this population. A total of 65 patients received sagopilone at either 16 mg/m2 (N = 39) or 22 mg/m2 (N = 26). Patients received a median of two cycles of sagopilone. Among the 65 patients who were evaluable for efficacy, there were three confirmed tumor responses over both treatment arms; however, the primary target of the study was not reached. The main treatment-related adverse events were sensory neuropathy (81.5%) and fatigue (44.6%). There were no deaths related to the study drug. Sagopilone was moderately tolerated in both treatment arms and showed limited activity in heavily pre-treated patients with MBC.

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Abbreviations

AE:

Adverse event

MBC:

Metastatic breast cancer

modRECIST:

Modified Response Evaluation Criteria in Solid Tumors

PFS:

Progression-free survival

PPS:

Per protocol set

WHO:

World Health Organization

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Acknowledgments

The authors would like to thank Tanya Chaudry, Ph.D., at Complete HealthVizion for assistance in the preparation and revision of the draft manuscript, based on detailed discussion and feedback from the authors. Editorial assistance was supported by a grant from Bayer HealthCare Pharmaceuticals. We would also like to thank all investigators who participated in this study.

Conflict of interest

Dr. Shiuh-Wen Luoh receives research support from Glaxo Smith Kline and serves as an Institute PA for clinical trials sponsored by Glaxo Smith Kline. Dr. Teresa M. Petrella is a consultant for Glaxo Smith Kline, Merck, and Pfizer. She has received research funds from Pfizer. Dr. Marius Giurescu is an employee of Bayer Schering Pharma. Dr. Thomas Schmelter is an employee of Bayer Schering Pharma. Dr. Yao Wang is an employee of Bayer HealthCare Pharmaceuticals and owns company stocks in Bayer HealthCare Pharmaceuticals Dr. Gabriel N. Hortobagyi is a consultant for Novartis, Merck and Sanofi Aventis; he has received research support from Novartis. Dr. Linda T. Vahdat is a consultant for Bayer.

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Authors and Affiliations

  1. Department of Breast Medical Oncology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe, Box 1354, Houston, TX, 77030, USA

    Phuong K. Morrow & Gabriel N. Hortobagyi

  2. Genesis Cancer Center, Hot Springs, AR, USA

    Stephen Divers

  3. Centre des maladies du sein Deschênes-Fabia, CHA Laval University, Quebec City, Canada

    Louise Provencher

  4. Oregon Health and Science University and Portland VA Medical Center, Portland, OR, USA

    Shiuh-Wen Luoh

  5. Sunnybrook Health Science Center, Toronto, Canada

    Teresa M. Petrella

  6. Bayer Schering Pharma AG, Berlin, Germany

    Marius Giurescu & Thomas Schmelter

  7. Bayer HealthCare Pharmaceuticals, Wayne, NJ, USA

    Yao Wang

  8. Weill Cornell Medical College, New York, NY, USA

    Linda T. Vahdat

Authors
  1. Phuong K. Morrow
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  2. Stephen Divers
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  3. Louise Provencher
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  4. Shiuh-Wen Luoh
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  8. Yao Wang
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  9. Gabriel N. Hortobagyi
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  10. Linda T. Vahdat
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Correspondence to Phuong K. Morrow.

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Morrow, P.K., Divers, S., Provencher, L. et al. Phase II study evaluating the efficacy and safety of sagopilone (ZK-EPO) in patients with metastatic breast cancer that has progressed following chemotherapy. Breast Cancer Res Treat 123, 837–842 (2010). https://doi.org/10.1007/s10549-010-1102-x

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  • DOI: https://doi.org/10.1007/s10549-010-1102-x

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