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
| Autor: | Joyce M. Slingerland, Pearl Seo, Leonidas G. Koniaris, T. Rumboldt, Catherine F. Welsh, Eli Avisar, Y. E. Deutsch, S. Yasir, Alberto J. Montero, Stefan Glück, M. Jorda, Claudia Marcela Diaz-Montero, Mark D. Pegram, K. Schuhwerk, E. Garret-Mayer, Orlando Silva, Judith Hurley |
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| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Oncology
Adult Cancer Research medicine.medical_specialty Pathology Anthracycline Cyclophosphamide Adolescent Receptor ErbB-2 medicine.medical_treatment Antineoplastic Agents Breast Neoplasms Docetaxel Kaplan-Meier Estimate Article Disease-Free Survival Metastasis Young Adult Breast cancer Internal medicine Antineoplastic Combined Chemotherapy Protocols Medicine Humans Neoplasm Invasiveness Neoadjuvant therapy Mastectomy Aged Neoplasm Staging Chemotherapy Immunity Cellular Taxane Glutathione Disulfide business.industry Middle Aged medicine.disease Combined Modality Therapy Neoadjuvant Therapy Drug Combinations Treatment Outcome Doxorubicin Female Taxoids Cisplatin business medicine.drug |
| Popis: | 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, 16 achieved a pCR (40%), meeting the primary endpoint of the trial. Lower circulating levels of MDSCs at baseline and cycle 8 were associated with a pCR (P=0.02). 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. |
| Databáze: | OpenAIRE |
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