Albumin delivery improves breast cancer therapy

A widely used drug to treat breast cancer has been significantly improved by the use of a new technology that binds it to albumin, a common constituent of human blood.

American Pharmaceutical Partners and its partner American Bioscience have just received approval for the new version of paclitaxel from the US Food and Drug Administration (FDA).

The approval marks the debut of a new class of 'protein-bound particle' drugs, made possible by the use of American Bioscience's proprietary nanoparticle albumin-bound (nab) technology. This is particularly suited to cancer drugs because it is believed to exploit an inherent pathway for albumin receptor-mediated transport of drugs across the endothelial cell walls of blood vessels in tumours. This pathway is thought to be a means by which the malignant cell inherently supplies itself with nutrients and energy for rapid growth.

Paclitaxel, originally developed by Bristol-Myers Squibb but now available generically in many markets around the world, is a mainstay of breast cancer therapy. But the downside of paclitaxel therapy has always been the relatively high risk of side effects, from the drug itself but also from the solvents (Cremophor-EL and alcohol) used in its formulation, which can cause hypersensitivity reactions.

The new product - called Abraxane - does away with the need for this solvent and so reduces the side effects of paclitaxel treatment. But is has other advantages, including an increase in effectiveness in combating cancer and more patient-friendly administration.

In trials, Abraxane has demonstrated a superior response rate to Taxol, B-MS' formulation of paclitaxel, with an almost doubling of the target lesion response rate in a trial of 460 patients with metastatic breast cancer.

"Because it contains no toxic solvents, this next-generation taxane product enables the administration of 50 per cent more chemotherapy with a well-tolerated safety profile," according to the company. Moreover, it requires no premedication to prevent hypersensitivity reactions - usually patients receiving Taxol are given steroids to guard against reactions.

Abraxane can be given over 30 minutes, in contrast to Taxol which requires extended infusion times to limit the risk of side effects developing..And it can also be delivered using standard intravenous tubing, while the solvents in Taxol require the use of specialised iv tubing sets to avoid leaching of plasticisers into the patient.

The FDA has approved Abraxane (paclitaxel albumin-bound particles for injectable suspension) for patients with metastatic breast cancer. The product is indicated for the treatment of breast cancer after failure of combination chemotherapy for metastatic disease or relapse within six months of adjuvant chemotherapy. Prior therapy should have included an anthracycline unless clinically contraindicated.

American Bioscience is responsible for the clinical development and registration of Abraxane, while APP has licensed exclusive North American manufacturing and marketing rights for the product.