Abraxane™ (paclitaxel albumin-bound particles for injectable suspension) has become the first second-generation taxane and first drug in the category of albumin-bound nanotechnology to enter clinical practice in the United States, with its approval for patients with metastatic breast cancer resistant to taxanes.

Clinical trials of the new drug have shown that it is superior to solvent-based paclitaxel (commonly marketed as Taxol^® ) in response rate and time to tumor progression.

“Abraxane is a significant advance in how paclitaxel is delivered and provides a much-needed new option for breast cancer patients,” said Joyce A.
O’Shaughnessy, MD, co-director, US Oncology Breast Cancer Research, and director, Breast Cancer Prevention, at Baylor-Charles A. Sammons Cancer Center in Dallas, Texas.

“With this human protein nanoparticle form of paclitaxel, patients no longer require steroid premedication to avoid the sometimes life-threatening allergic reactions which occur with current solvent-based paclitaxel therapy. In our trials with weekly Abraxane, we saw fewer side effects than observed with solvent-based paclitaxel, and, even more encouraging, we saw a significant response to Abraxane in some women whose cancer had progressed through treatment with taxanes. Women taking Abraxane also spent less time in the clinic receiving their chemotherapies,” said Joanne Blum MD, principal investigator of the US Oncology clinical trial of the new drug.

To date, the formulation of insoluble tumor-fighting agents, such as paclitaxel, has required the use of solvents which, in addition to other side effects, can cause hypersensitivity reactions. For instance, in Taxol, paclitaxel must be dissolved in the solvent Cremophor-EL^® so that it can be administered to patients. To reduce the risk of allergic toxicities when receiving Taxol, patients must undergo premedication using steroids and anti-histamines and be given the drug using slow infusions.

In contrast, the new drug is engineered using a proprietary process (protein-bound nanoparticle technology) to create nanoparticles in which the active chemotherapeutic drug, paclitaxel, is bound to albumin. By using this nanotechnology, the active component (paclitaxel) can be delivered into the body without the need for solvents.

In a randomized Phase III trial, the response rate with the new drug was almost twice that of the solvent-containing drug. Because the new drug formation does not contain solvents, higher doses of paclitaxel can be given, which may account in part for its increased anti-tumor activity. In addition, albumin is a protein that normally transports nutrients to cells and has been shown to accumulate in rapidly growing tumors. Therefore, some of the increased effectiveness may also be due to preferential delivery of albumin-bound paclitaxel to cancer cells.