A phase II study of the proteasome inhibitor PS-341 in patients (pts) with metastatic breast cancer (MBC)

546 Background: The ubiquitin-proteasome pathway plays an essential role in eukaryotic cellular homeostasis by regulating the degradation of vital intracellular regulatory proteins that govern cell cycle, transcription factor activation and apoptosis. Blocking this proteolytic pathway leads to the elevation of cell cycle inhibitory proteins, including IΚB, whose stabilization results in NF-KB inhibition and ultimately induction of apoptosis. PS-341 (bortezomib, Velcade) is a dipeptide boronic acid derivative that acts as a potent and highly specific inhibitor of the proteasome. PS-341 has demonstrated anti-tumor activity as a single agent in preclinical breast cancer models. Methods: The primary objective of this study was to determine the objective tumor response in pts with MBC receiving PS-341. Eligibility criteria included normal organ/marrow function, measurable disease, performance status (PS) 0–2, absence of brain metastases and ≥ 1 prior chemotherapy regimen for MBC. PS-341 was administered IV, 1....