Randomized phase II study of metronomic chemotherapy (MC) plus aromatase inhibitor (AI) versus MC alone in postmenopausal hormone receptor-positive, metastatic breast cancer (MBC), with correlative circulating endothelial cell (CEC), circulating endothelial progenitor cell (CEP), VEGF, and VEGFR levels.

TPS127 Background: Neoadjuvant AI plus MC achieves greater suppression of Ki67 and VEGF in primary breast cancer compared to AI alone (Bottini A et al. J Clin Oncol; 24: 3623, 2006). We previously showed that this combination is active in MBC even among women previously exposed to AI, and hypothesized that MC may reverse AI resistance (T Wai Ming et al. 2009 IMPAKT Breast Cancer Conference, Abstract 308). This study aims to determine if continuation of AI enhances efficacy of MC compared to MC alone in MBC progressing on AI; and whether methotrexate and prednisolone are necessary components of MC. Methods: Primary Objectives: Clinical benefit (CR+PR+SD ≥ 24 weeks) of MC plus AI versus MC alone. Secondary Objectives: PFS, safety, correlating response with angiogenesis biomarkers, contribution of methotrexate and prednisolone to MC activity assessed by change in biomarkers during serial introduction of each drug over a 6 week lead in period. Study Design: Randomized phase II design, 35 patients per arm plan...