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New Data on Abraxane Demonstrate Almost Double the Response Rate versus Taxol in Patients with Metastatic Breast Cancer: Presented at SABCS

A Promising New Direction Emerges for One of the Most Widely Used Chemotherapies in the World, Paclitaxel

CHICAGO, IL - December 15, 2003 - Results of a Phase III head-to-head trial of the investigational drug Abraxane, the first solvent-free nanoparticle taxane, versus the solvent-based Taxol® show patients with metastatic breast cancer receiving Abraxane experienced a statistically significant higher tumor response rate and slower time to tumor progression than patients receiving Taxol, according to a presentation today at the annual San Antonio Breast Cancer Symposium.

Researchers presented data that show Abraxane patients tolerated a higher dose of paclitaxel, experienced a significantly lower incidence of neutropenia, and - even in the absence of steroid premedication - did not experience the severe hypersensitivity reactions commonly seen with Taxol. Patients in both arms of the study experienced peripheral neuropathy consistent with high doses of paclitaxel. However, in the Abraxane arm, the neuropathy was reversible and resolved significantly more rapidly versus patients receiving Taxol, who appeared to have a qualitatively different form of neuropathy with slower recovery.

"What's so intriguing is these data demonstrate that the nanoparticle albumin-based (nab) technology allows us to, for the first time, fully maximize the tried and true power of paclitaxel while minimizing the sometimes life-threatening CremophorÒ-based side effects we have grown accustomed to with Taxol," said William J. Gradishar, M.D., FACP, Associate Professor of Medicine, Division of Hematology and Medical Oncology and Co-Director, Lynn Sage Breast Cancer Program at Northwestern University in Chicago, IL. "Paclitaxel, discovered many years ago by the National Cancer Institute, was previously shown to be one of the most effective anti-cancer agents, but dosing had been limited because of the use of toxic solvents in the formulation. This solvent-free nanoparticle form of paclitaxel, using a naturally-occurring human protein, could be an important step toward advancing our approach to treating women with breast cancer."

One of every three cancers diagnosed in the United States is breast cancer. Almost 40,000 women are expected to die from breast cancer this year, with more than 210,000 new cases diagnosed. It is the leading overall cause of death in women between the ages of 20 and 59. Most women with breast cancer will have some type of surgery, often combined with radiation therapy, chemotherapy, hormone therapy and/or monoclonal antibody therapy. The class of drugs known as taxanes are the most widely used chemotherapies for breast cancer.

Abraxane, a next generation taxane, does not contain toxic solvents and/or detergents. Currently approved taxane formulations use either Cremophor® (Taxol®) or Tween® (Taxotere®) as solvents to carry the active drug to tumors. Using a proprietary technology, Abraxane combines the taxane paclitaxel with the body's natural transport protein called albumin into a nanoparticle 1/100th the size of a red blood cell. The nanoparticles permeate microvessels, rapidly carrying more drug to the tumor more quickly, and less drug indiscriminately to normal, healthy cells.

"The results of this trial provide the first clinical evidence that Cremophor may contribute to both the bone marrow suppression and the neuropathy that adversely affect some Taxol patients," continued Gradishar. "The clinical trial results support the previously reported pre-clinical studies that showed Abraxane delivers an increased amount of drug to the tumor and less drug to normal, healthy cells. The lack of severe hypersensitivity reactions and the reduction in bone marrow suppression with Abraxane may avoid the use of costly premedications necessary both before and after Taxol administration."

Study Design and Analysis

In the study presented by Joyce A. O'Shaughnessy, M.D., Co-Director, Breast Cancer Research, and Director, Breast Cancer Prevention, at Baylor-Charles A. Sammons Cancer Center, US Oncology in Dallas, Texas, 454 patients were randomized 1:1 into two arms. One group received 260 mg/m2 Abraxane administered over 30 minutes once every three weeks without premedication. The other patient group received 175 mg/m2 Taxol administered over three hours once every three weeks with steroid and antihistamine premedication.

The study found that Abraxane resulted in a significantly higher response rate than Taxol (33% vs. 19%, p<0.001) and a longer time to tumor progression than Taxol (21.9 weeks vs. 16.1 weeks, p=0.029). Grade 3 and 4 hypersensitivity reactions did not occur in the Abraxane arm despite the absence of steroid premedication. Grade 4 neutropenia occurred less frequently for Abraxane than Taxol (9% vs. 22%, p<0.001).

Consistent with higher doses of paclitaxel, incidence of Grade 3 sensory neuropathy was 10% for Abraxane versus 2% for Taxol (p<0.001), with no episodes of Grade 4 neuropathy in the Abraxane arm. Grade 3 sensory neuropathy seen in patients receiving Abraxane resolved rapidly (median 22 days) following dose interruption and was subsequently easily managed with dose reduction (usually 220 mg). This rapid recovery of neuropathy with a solvent-free paclitaxel provides the first clinical suggestion that Cremophor itself and not paclitaxel may be responsible for structural damage to nerve fibers and hence prolonged recovery associated with Taxol toxicity.

Taxol® is a registered trademark of Bristol-Myers Squibb Company.


SOURCE: Northwestern University

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