Breast Cancer Research and Treatment

, Volume 132, Issue 1, pp 215–223

Phase 2 study of neoadjuvant treatment with NOV-002 in combination with doxorubicin and cyclophosphamide followed by docetaxel in patients with HER-2 negative clinical stage II–IIIc breast cancer

  • A. J. Montero
  • C. M. Diaz-Montero
  • Y. E. Deutsch
  • J. Hurley
  • L. G. Koniaris
  • T. Rumboldt
  • S. Yasir
  • M. Jorda
  • E. Garret-Mayer
  • E. Avisar
  • J. Slingerland
  • O. Silva
  • C. Welsh
  • K. Schuhwerk
  • P. Seo
  • M. D. Pegram
  • S. Glück
Clinical trial

Abstract

NOV-002 (a formulation of disodium glutathione disulfide) modulates signaling pathways involved in tumor cell proliferation and metastasis and enhances anti-tumor immune responsiveness in tumor models. The addition of NOV-002 to chemotherapy has been shown to increase anti-tumor efficacy in animal models and some early phase oncology trials. We evaluated the clinical effects of NOV-002 in primary breast cancer, whether adding NOV-002 to standard preoperative chemotherapy increased pathologic complete response rates (pCR) at surgery, and determined whether NOV-002 mitigated hematologic toxicities of chemotherapy and whether levels of myeloid derived suppressor cells (MDSC) were predictive of response. Forty-one women with newly diagnosed stages II–IIIc HER-2 negative breast cancer received doxorubicin-cyclophosphamide followed by docetaxel (AC → T) every 3 weeks and concurrent daily NOV-002 injections. The trial was powered to detect a doubling of pCR rate from 16 to 32% with NOV-002 plus AC → T (α = 0.05, β = 80%). Weekly complete blood counts were obtained as well as circulating MDSC levels on day 1 of each cycle were quantified. Of 39 patients with 40 evaluable tumors, 15 achieved a pCR (38%), meeting the primary endpoint of the trial. Concurrent NOV-002 resulted in pCR rates for AC → T chemotherapy higher than previously reported. Patients with lower levels of circulating MDSCs at baseline and on the last cycle of chemotherapy had significantly higher probability of a pCR (P = 0.02). Further evaluation of NOV-002 in a randomized study is warranted.

Keywords

Breast cancer Neoadjuvant Phase 2 NOV-002 Glutathione analog MDSC Myeloid derived suppressor cells Pathologic complete response Anthracycline Taxane 

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Copyright information

© Springer Science+Business Media, LLC. 2011

Authors and Affiliations

  • A. J. Montero
    • 1
  • C. M. Diaz-Montero
    • 1
  • Y. E. Deutsch
    • 1
  • J. Hurley
    • 1
  • L. G. Koniaris
    • 2
  • T. Rumboldt
    • 3
  • S. Yasir
    • 1
  • M. Jorda
    • 1
  • E. Garret-Mayer
    • 3
  • E. Avisar
    • 1
  • J. Slingerland
    • 1
  • O. Silva
    • 1
  • C. Welsh
    • 1
  • K. Schuhwerk
    • 4
  • P. Seo
    • 1
  • M. D. Pegram
    • 1
  • S. Glück
    • 1
  1. 1.Sylvester Comprehensive Cancer CenterUniversity of MiamiMiamiUSA
  2. 2.Jefferson University HospitalPhiladelphiaUSA
  3. 3.Hollings Cancer CenterMedical University of South CarolinaCharlestonUSA
  4. 4.Novelos Therapeutics Inc.NewtonUSA

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