Albumin-bound formulation of paclitaxel (Abraxane ABI-007) in the treatment of breast cancer

Abstract

Breast cancer is the most common type of malignancy diagnosed in women. In the metastatic setting this disease is still uncurable. Taxanes represent an important class of antitumor agents which have proven to be fundamental in the treatment of advanced and early-stage breast cancer, but the clinical advances of taxanes have been limited by their highly hydrophobic molecular status. To overcome this poor water solubility, lipid-based solvents have been used as a vehicle, and new systemic formulations have been developed, mostly for paclitaxel, which are Cremophor-free and increase the circulation time of the drug. ABI-007 is a novel, albumin-bound, 130-nm particle formulation of paclitaxel, free from any kind of solvent. It has been demonstrated to be superior to an equitoxic dose of standard paclitaxel with a significantly lower incidence of toxicities in a large, international, randomized phase III trial. The availability of new drugs, such as Abraxane, in association with other traditional and non-traditional drugs (new antineoplastic agents and targeted molecules), will give the oncologist many different effective treatment options for patients in this setting.

Figure 1

Mechanism by which gp60 protein-albumin complex induces caveolin-1-mediated membrane internalization of plasma components across the vascular endothelium. In detail, panel I shows the bond between albumin receptor (gp60) and albumin which recruits and activates caveolin-1. In panel II caveolin-1 leads to membrane invagination and internalization of free or protein-bound plasma molecules. Panel III: the so-formed caveolae mediate transocytosis and the extravascular deposition of their content.