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Although in its early stages breast cancer is highly curable, in the later stages of disease, when distant metastases are present, cure becomes less likely and few patients are rendered free of disease. Therapy in the advanced, metastatic setting then focuses on prolonging life and managing disease-and treatment-related adverse events. Over the past decade, the taxane chemotherapy class has proved to be fundamental in the treatment of breast cancer.

Although the taxanes are a valuable treatment option for women with metastatic breast cancer, the toxicities and inconvenience of administration associated with these agents appear to have limited their utility. As highly hydrophobic compounds, both paclitaxel and docetaxel (Taxotere) require synthetic solvents for parenteral administration; the solvents in commercially available preparations can cause potentially life-threatening adverse effects and decreased treatment efficacy. 

Thus, investigators have attempted to improve these agents, overcoming resistance, enhancing therapeutic efficacy and drug delivery, as well as minimizing toxic effects. In turn, these efforts have led to the development of enhanced delivery taxanes (EDTs). The goals of these newly formulated taxanes are to remove the conventional solvents that compromise drug delivery and contribute to systemic toxicity, use endogenous mechanisms for targeted drug delivery, and reduce infusion times. The use of EDTs appears to promote a more favorable and predictable pharmacokinetic profile with increased bioavailability of taxanes at the tumor site. 

Nanoparticle albumin-bound (nab)-paclitaxel (ABI-007), the first-generation EDT, is indicated for second-line treatment of metastatic breast cancer. Rather than carried via a chemical solvent, nab-paclitaxel is delivered using human serum albumin. By eliminating the Cremophor solvent, nab-paclitaxel is intended to overcome the adverse reactions often associated with this solvent, such as micelle trapping, leaching of plastic from standard IV tubing, hypersensitivity reactions, complement activation, axonal swelling, demyelination, and, possibly, reduced cell penetration. 

Ongoing and future studies of first-generation EDTs are focusing on their use in newer combination regimens. For instance, a phase III trial sponsored by CALGB and NCCTG is evaluating paclitaxel, nab-paclitaxel, and ixabepilone (Ixempra) combined with bevacizumab (Avastin) in 900 patients with metastatic breast cancer. Studies are also progressing with the second-generation EDTs; paclitaxel poliglumex (with a polyglutamate carrier) and paclitaxel injectable emulsion (with a vitamin E carrier). These new formulations of taxanes, particularly in targeted combinations, may be found to improve antitumor activity as well as survival for both early and metastatic breast cancer. 

In conclusion, the taxanes are a fundamental component of contemporary treatment of metastatic breast cancer. The EDTs represent a new generation of taxanes designed to improve patient outcomes and administration while reducing the adverse effects of the traditional taxanes. The benefits of these agents, particularly in targeted combinations, continue to be explored in both early and advanced breast cancer settings. Assembling a myriad of research findings into some type of practical, clinical focus is a daunting task for most hematologists-oncologists, hospital administrators, nurses, and pharmacists. Thus, a continuing education program that explores the evolving role of the novel taxanes in breast cancer treatment would be of great benefit to these clinical professionals. 

This activity has been planned and implemented in accordance with the Essential Areas and Policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of the Elsevier Office of Continuing Medical Education (EOCME) and Elsevier Oncology. The EOCME is accredited by the ACCME to provide continuing medical education (CME) for physicians.

The EOCME designates this educational activity for a maximum of 1.5 AMA PRA Category 1 Credit(s). Physicians should only claim credit commensurate with the extent of their participation in the activity.

The EOCME has implemented a process to resolve conflict of interest for each CME activity. In order to help ensure content objectivity, independence, and fair balance, and to ensure that the content is aligned with the interest of the public, the EOCME has resolved the conflict by external content review.

This activity has been developed for medical oncologists and other health professionals involved in the care of patients with advanced-stage breast cancer.

• Discuss data showing differences between conventional paclitaxel and docetaxel with regard to dose response and administration schedule.
• Identify the effects of solvents on taxane antitumor activity and toxicity. 
• Recognize the mechanisms of improved tumor exposure to paclitaxel using the nanoparticle albumin-bound drug platform. 
• Discuss data from clinical trials of nab-paclitaxel in metastatic breast cancer.                                        

This CME activity is supported by an educational grant from Abraxis BioScience and AstraZeneca.

Copyright © 2008 by Elsevier Inc. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopy, recording, or any information storage and retrieval system, without written permission from the Publisher.

We encourage participation by all individuals. If you have any special needs, please contact Kelley Moore at (901) 603-7376, or k.moore@supportiveoncology.net for assistance.