Abraxane More Effective, Less Toxic than Taxol

Jane Salodof MacNeil

December 08, 2003

Dec. 8, 2003 (San Antonio) — Abraxane (formerly ABI-007) is an old drug in a new package that promises to make chemotherapy less toxic and more effective for women with metastatic breast cancer.

The old drug is paclitaxel, the active agent in Taxol and Abraxane. In a phase III clinical trial reported here, Abraxane produced a higher overall response rate (33% vs. 19%), higher tumor response (42% vs. 27% when used as a first-line treatment), and longer median time to tumor progression (21.9 weeks vs. 16.1 weeks).

Abraxane was also significantly less toxic, causing grade 4 neutropenia in 9% of women compared with 22% of those receiving Taxol in the 454-patient study presented in a special late-breaker session at the 26th Annual San Antonio Breast Cancer Symposium.

The new agent did have a higher degree of grade 3 sensory neuropathy (10% vs. 2%), but the companies behind Abraxane say that is because of its higher delivery of paclitaxel. It employs a nanoparticle albumin-bound (nab) technology to get the insoluble drug into cells without a solvent.

"Albumin is a very underestimated molecule. People think it's everywhere — who cares about albumin? — but it has a very special function in transport: taking things from one place to another," said Neil Desai, PhD, from American Bioscience, Inc., in Santa Monica, California, in an interview with Medscape. One of albumin's jobs, he pointed out, is carrying fatty acids.

Getting paclitaxel into cells is a challenge because the compound, identified in 1962, is insoluble. Taxol delivers the taxane in a solvent called Cremophor. A highly toxic castor oil derivative, it has been up to now the only means of transport.

Abraxane binds paclitaxel to albumin in a nanoparticle that makes the drug selective for tumor cells. Normal cells are too tightly joined even for nanoparticles, but Dr. Desai said the 100- to 200-nm particles are able to navigate the "leaky junctions" between malformed tumor cells.

In a separate poster presentation at the symposium, Dr.Desai presented findings on how Abraxane gets into the cell: Albondin, also known as the gp60 receptor, has a special affinity for albumin and brings the nanoparticle inside, according to American Bioscience's researchers.

Dr. Desai said albumin is also more effective than Cremophor because the solvent has a strong affinity for paclitaxel and resists releasing it to the tumor cell. Albumin, he said, is indifferent and lets go of the drug.

The results so impressed Edith A. Perez, MD, from the Mayo Clinic in Jacksonville, Florida, and I. Craig Henderson, MD, from the University of California in San Francisco, that the two breast cancer researchers participated in a press briefing introducing Abraxane. Both said they had nothing to do with the clinical trial or the company and had only recently seen the data.

"What's important is not how much drug you give to the patient, but how much drug gets to the tumor," Dr. Henderson said, describing years of frustration with experimental regimens that increased drug doses without clinical benefits.

Dr. Perez called on the U.S. Food and Drug Administration to give swift approval to Abraxane. It will be marketed by Abraxis Oncology, a new company formed by American Pharmaceutical Partners, (APP), a publicly traded company largely owned by American Bioscience.

Dr. Desai and his colleagues, meanwhile, are attempting to apply the technology to other drugs, including docetaxel (Taxotere). About 50% of investigative drugs are insoluble and face the same problem, according to Dr. Desai.

Among these are the epitholones, a group of cancer drugs in phase II trials, but company officials declined to say which drugs they are investigating as candidates for nab. "We're working on a whole bunch of interesting molecules that could benefit from this technology," Dr.Desai said.

The studies were funded by American Pharmaceutical Partners, Inc., the maker of Abraxane.

26th Annual SABCS: Abstract 348, presented Dec 4, 2003; abstract 44, presented Dec. 5, 2003.

Reviewed by Gary D. Vogin, MD


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