Originally published as JCO Early Release 10.1200/JCO.2005.04.937 on September 19 2005

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Phase III Trial of Nanoparticle Albumin-Bound Paclitaxel Compared With Polyethylated Castor Oil–Based Paclitaxel in Women With Breast Cancer

From Northwestern University, Chicago, IL; Duke University Medical Center, Durham, NC; American BioScience, Inc, Santa Monica, CA; Baylor-Charles A. Sammons Cancer Center, US Oncology, Dallas, TX; Russian Cancer Research Center, Moscow, Russia; and Broomfield Hospital, Essex, United Kingdom.

Address reprint requests to William J. Gradishar, MD, Director, Breast Oncology, Division of Hematology/Oncology, Department of Medicine & Robert H. Lurie Comprehensive Cancer Center, Northwestern University, 676 N St Clair, Ste 850, Chicago, IL 60611; e-mail: w-gradishar{at}northwestern.edu

PURPOSE: ABI-007, the first biologically interactive albumin-bound paclitaxel in a nanameter particle, free of solvents, was compared with polyethylated castor oil–based standard paclitaxel in patients with metastatic breast cancer (MBC). This phase III study was performed to confirm preclinical studies demonstrating superior efficacy and reduced toxicity of ABI-007 compared with standard paclitaxel.

PATIENTS AND METHODS: Patients were randomly assigned to 3-week cycles of either ABI-007 260 mg/m² intravenously without premedication (n = 229) or standard paclitaxel 175 mg/m² intravenously with premedication (n = 225).

RESULTS: ABI-007 demonstrated significantly higher response rates compared with standard paclitaxel (33% v 19%, respectively; P = .001) and significantly longer time to tumor progression (23.0 v 16.9 weeks, respectively; hazard ratio = 0.75; P = .006). The incidence of grade 4 neutropenia was significantly lower for ABI-007 compared with standard paclitaxel (9% v 22%, respectively; P < .001) despite a 49% higher paclitaxel dose. Febrile neutropenia was uncommon (< 2%), and the incidence did not differ between the two study arms. Grade 3 sensory neuropathy was more common in the ABI-007 arm than in the standard paclitaxel arm (10% v 2%, respectively; P < .001) but was easily managed and improved rapidly (median, 22 days). No hypersensitivity reactions occurred with ABI-007 despite the absence of premedication and shorter administration time.

CONCLUSION: ABI-007 demonstrated greater efficacy and a favorable safety profile compared with standard paclitaxel in this patient population. The improved therapeutic index and elimination of corticosteroid premedication required for solvent-based taxanes make the novel albumin-bound paclitaxel ABI-007 an important advance in the treatment of MBC.

Supported by American BioScience, Inc, Santa Monica, CA.

Presented in part at the 26th Annual San Antonio Breast Cancer Symposium, San Antonio, TX, December 3-6, 2003.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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• Nanoparticle Albumin–Bound Paclitaxel for Metastatic Breast Cancer
  Mark Harries, Paul Ellis, and Peter Harper
  JCO 2005 23: 7768-7771 [Full Text]

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