Daily injections of the glutathione disulfide mimetic NOV-002 ameliorates hematologic toxicities from neoadjuvant chemotherapy in breast cancer patients enrolled in the NEO-NOVO trial, and significantly increases circulating dendritic cells.

Abstract

Abstract Abstract #2141 Background: Chemotherapy induced anemia is a common problem in breast cancer. Anemic events [Hgb<10 g/dL, use of erythropoietin stimulating agents (ESAs), or transfusion] are likely to occur in 30-40% of breast cancer patients (pts) receiving doxorubicin-cyclophosphamide (AC) and docetaxel (T). Owing to the increased risk of cancer mortality, tumor progression, and thrombovascular events associated with ESAs, other alternatives are needed. Febrile neutropenia with AC-T is a dose-limiting event and occurs in 10-20% of pts without prophylactic G-CSF. NOV-002 has been previously shown to stimulate hematopoiesis and reduce chemotherapy related hematologic toxicities, as well as have immunomodulatory properties. Methods: To determine the effect of daily NOV-002 on hematopoiesis and chemotherapy induced hematologic toxicities, weekly blood counts were obtained on all pts enrolled in the NEO-NOVO trial (Montero, et. al. SABCS 2008). Pts do not receive prophylactic G-CSF in the absence of prior febrile neutropenia with chemotherapy. To determine if NOV-002 is associated with induction of circulating dendritic cells (DCs), flow cytometry analysis is performed on whole peripheral blood prior to therapy and on day 1 of each cycle. DCs are defined as: lineage-/HLA-DR+; CD11b+/CD11c+. P-values were obtained from the signed rank test. Results: Thus far, 102 chemotherapy cycles have been administered to 16 pts. Baseline (BL) hemoglobin (Hgb), absolute neutrophil counts (ANC), and DCs are listed below.
 
 No grade 3-4 anemia has been observed. ESAs have been used in 2 pts (12.5%), and no blood transfusions were required. One pt (6.25%) had febrile neutropenia (0.9% of all cycles). Grade 3 neutropenia on day 1 of cycles 1-8 occurred in 2 pts (12.5%) or 1.9% of all cycles. One pt had dose delay by 1 week due to neutropenia. Cycle 5 day 1 (C5D1) DCs were significantly higher relative to BL with a trend towards being higher at C8D1. Moreover, median ANCs were significantly higher on C8D1, while median Hgb remained stable between C5D1 and C8D1. Conclusions: Anemic events and febrile neutropenia were much lower than expected with the addition of NOV-002 to AC→T, likely due to its hematopoietic properties. DC induction may be an important anti-tumor mechanism of action of NOV-002. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 2141.