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A Phase 2 study of perifosine in advanced or metastatic breast cancer

  • Clinical Trial
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Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Background

First- and second-line chemotherapy with anthracyclines and taxanes in metastatic breast cancer yield a modest improvement in survival with potentially significant toxicity. Subsequent lines of chemotherapy yield response rates of 20–25%, with an unknown impact on survival. Perifosine, an oral alkylphospholipid structurally related to miltefosine, has marked activity against breast cancer cell lines and xenograft models, with broad spectrum cellular effects.

Objectives

To determine the efficacy and toxicity of perifosine in patients with metastatic breast cancer patients after up to 2 lines of prior chemotherapy for advanced disease.

Methods

18 patients were enrolled, and 17 treated, using a loading/maintenance dose schedule, (day 1, 300 mg, maintenance 150 mg days 2–21) every 28 days, until disease progression or unacceptable toxicity.

Results

Median age of patients was 54 (28–69), 16/17 were female, ECOG performance status was 0/1 in 16 patients. Fifteen received at least 1 prior chemotherapy regimen for metastatic disease (maximum 2). A median of 2 cycles (range 1–13) was administered per patient. Sixteen were evaluable for response: 2 had SD for 4 cycles, 1 SD for 13 cycles, 13 progressed by cycle 2. Grade 3/4 drug-related non-hematologic toxicities include: diarrhea (2), vomiting (2), nausea (2), fatigue (2) and anorexia (1). No grade 3/4 hematologic toxicities were seen. Median time to progression was 8 weeks (7–15 weeks).

Conclusion

No objective responses were seen in this group of pretreated metastatic breast cancer patients. Disease stabilization was observed in 19% at 2 months.

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Acknowledgments

We wish to thank David Kipka, Soo Chin, Robin Cheiken, Anne Iacobucci, Patricia Furlong and Dianne Robbins for data management and clinical trials nursing support, Dr. Sunil Verma (Toronto Sunnybrook Regional Cancer Centre), and Trudey Nicklee (Ontario Cancer Institute) for their support of this project.

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Authors and Affiliations

  1. Medical Oncology, Princess Margaret Hospital/University Health Network, 5-105 610 University Avenue, Toronto, ON, Canada, M5G 2M9

    Natasha B. Leighl & Gregory R. Pond

  2. Princess Margaret Hospital Phase 2 Consortium, Toronto, ON, Canada

    Susan Dent, Mark Clemons, Theodore A. Vandenberg, Richard Tozer, David G. Warr, R. Michael Crump, David Hedley & Malcolm J. Moore

  3. National Cancer Institute Cancer Therapy Evaluation Program, Bethesda, MA, USA

    Janet E. Dancey

Authors
  1. Natasha B. Leighl
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  2. Susan Dent
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  3. Mark Clemons
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  4. Theodore A. Vandenberg
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  5. Richard Tozer
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  6. David G. Warr
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  7. R. Michael Crump
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  8. David Hedley
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  9. Gregory R. Pond
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  10. Janet E. Dancey
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  11. Malcolm J. Moore
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Corresponding author

Correspondence to Natasha B. Leighl.

Additional information

Supported through NIH/NCI Phase 2 Consortium N01-CM-17107 Grant. N. B. Leighl is the principal investigator. Princess Margaret Hospital Phase 2 Consortium, Ontario, Canada includes Princess Margaret Hospital/University Health Network, Toronto; The Ottawa Hospital Regional Cancer Centre, Ottawa; London Regional Cancer Centre, London; Juravinski Cancer Centre, Hamilton.

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Leighl, N.B., Dent, S., Clemons, M. et al. A Phase 2 study of perifosine in advanced or metastatic breast cancer. Breast Cancer Res Treat 108, 87–92 (2008). https://doi.org/10.1007/s10549-007-9584-x

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  • DOI: https://doi.org/10.1007/s10549-007-9584-x

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