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

Research output: Contribution to journalArticlepeer-review

55 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)215-223
Number of pages9
JournalBreast Cancer Research and Treatment
Volume132
Issue number1
DOIs
StatePublished - Feb 2012
Externally publishedYes

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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