Since 1998, the standard of adjuvant care for patients with node-positive breast cancer in the United States and other parts of the world has been treatment with doxorubicin and cyclophosphamide followed by the taxane paclitaxel. This regimen was first administered on a schedule of once every three weeks and then, more recently, once every two weeks, after a comparative trial demonstrated improved efficacy (a 7 percent absolute improvement in disease-free survival and a 2 percent improvement in overall survival at three years) with the schedule involving more frequent administration (referred to as dose-dense therapy).
Abraxane is untested in the adjuvant setting. In January 2005, the U.S. Food and Drug Administration (FDA) approved the chemotherapy drug Abraxane, a new formulation of paclitaxel, for treating advanced (metastatic) breast cancer. The approval is for second-line therapy—after another chemotherapy regimen has been used and has stopped working. After failure of combination chemotherapy for metastatic breast cancer or relapse within 6 months of adjuvant chemotherapy, the recommended regimen for ABRAXANE for Injectable Suspension (paclitaxel protein-bound particles for injectable suspension) is 260 mg/m2 administered intravenously over 30 minutes every 3 weeks.
A trial: Study of Adriamycin Plus Cyclophosphamide Followed by Abraxane as Adjuvant Therapy for Patients With Breast Cancer NCT00107094 has been completed but not yet published. In this trial, the safety of combination treatment of Adriamycin plus cyclophosphamide followed by Abraxane as adjuvant therapy was be evaluated in patients with limited stage breast cancer.
In 2006, Abraxane’s manufacturer, Abraxis BioScience Inc. of Schaumburg, Illinois, submitted a drug development proposal, instead of an application, for approval of Abraxane to be used in combination with chemotherapy for the indication of adjuvant treatment for breast cancer. Adjuvant treatment is a therapy given after the main treatment to lower the chance of a cancer coming back. Abraxis argued that the drug had already been approved for metastatic breast cancer based on randomized clinical trials that compared it to the standard of care, Taxol. The ODAC did nto agree. The FDA told the ODAC that Taxol and Abraxane were distinctly different. “The two drugs have different formulations and different infusion rates,” said Richard Pazdur, M.D., director of the FDA’s Office of Oncology Drug Products. “They have different toxicity profiles. Large randomized trials provide important information to patients in making decisions regarding which drug they should take.” The ODAC advisory committee recommended by a vote of 13-1 that the FDA not approve Abraxane as adjuvant treatment for breast cancer without randomized clinical trials, and the FDA concurred.
Several studies are ongoing. There are no guidelines that currently recommend substituting Abraxane for paclitaxel in existing adjuvant protocols.
M. R. Green et al, Abraxane®, a novel Cremophor®-free, albumin-bound particle form of paclitaxel for the treatment of advanced non-small-cell lung cancer Annals of Oncology 2006 17(8):1263-1268
Abraxane, Prescribing Information 2012
Evelina Miele etaAlbumin-bound formulation of paclitaxel (Abraxane® ABI-007) in the treatment of breast cancer Int J Nanomedicine. 2009; 4: 99–105.