Bortezomib: a valuable new antineoplastic strategy in multiple myeloma

Abstract

Although the treatment of multiple myeloma has improved over the past decade, the disease remains incurable. Bortezomib, a first-in-class selective proteasome inhibitor, was approved in the United States in 2003 and the European Union in 2004 for the treatment of relapsed and refractory multiple myeloma in patients who have received at least 2 prior therapies and demonstrated disease progression on the last therapy. In vitro, bortezomib induces apoptosis of multiple myeloma cells and inhibits cell adhesion within the bone marrow microenvironment. Preclinical and clinical data have shown that bortezomib enhances sensitivity and reverses resistance to standard therapeutic agents used in multiple myeloma. The efficacy and safety of bortezomib was established in patients with relapsed and/or refractory disease. In a large phase III trial in patients with relapsed multiple myeloma, median time to progression and overall survival were significantly improved with bortezomib compared with high-dose dexamethasone. Importantly, the preliminary results of several phase I and II studies are also showing high antimyeloma activity of bortezomib alone or in combination with dexamethasone or cytotoxic agents such as doxorubicin, melphalan, or thalidomide in patients with newly diagnosed multiple myeloma. Ideally, the introduction of bortezomib will result in a significant improvement in the future management of multiple myeloma.