Novel First-Line Therapy for Advanced Breast Cancer Buoys Physicians' Hopes

May 31, 2007
Naomi Pfeiffer

Internal Medicine World Report, April 2007, Volume 0, Issue 0

From the San Antonio Breast Cancer Symposium

SAN ANTONIO—A new study cited as one of the “hottest” head-to-head trials presented at the annual San Antonio Breast Cancer Symposium showed that weekly injections of paclitaxel protein-bound particles (Abraxane) as first-line treatment of metastatic breast cancer boosted the tumor response rate by more than 60%?compared with standard docetaxel (Taxotere) injections given once every 3 weeks.?

The FDA approved the new formulation of paclitaxel in 2005 as second-line treatment for breast cancer. It took many years to design a way to safely deliver its active ingredient.

IMWR

“When the FDA approved Abraxane, it ushered in a new class of therapeutic compounds,” lead investigator William Gradisher, MD, FACP, director of breast medical oncology at Northwestern University in Chicago, told . “Abraxane was the first approved compound in this new class of drugs and represents the next-generation taxane.” It eliminates the toxic effects associated with the older taxanes.

The taxanes—paclitaxel (Taxol) and docetaxel—are among the most effective and widely used chemotherapies for a variety of malignancies, he noted. However, they are water-insoluble and must be combined with powerful solvents, such as polyethylated castor oil, to allow administration. “These solvents are highly toxic and known to cause significant side effects beyond those associated with the actual medication,” said Dr Gradisher.

Special Delivery System

Paclitaxel is a naturally derived product with antitumor activity. “By wrapping another natural human protein, albumin, around the active drug, scientists created a [unique proprietary] way to deliver drugs as particles with a mean particle size of about 130 nanometers—only one hundredth the size of a red blood cell,” Dr Gradisher explained. “Millions of these paclitaxel particles can be injected in a single dose of medication. The tiny size of the particles eliminates the need for dangerous solvents,” he added.

Albumin helps move the active drug through the bloodstream, across blood vessel walls, and into the tumors, where the active ingredient kills cancerous cells. “Without altering the drug or the protein, this breakthrough technology improves the therapeutic effect of taxane chemotherapy and eliminates many of the side effects that currently limit the effectiveness of the drug,” he said.

Promising Results

The results of this study support the increasingly popular “dose-density hypothesis,” which suggests that certain chemotherapy drugs are most effective when given at the highest dose possible as often as possible, Dr Gradisher pointed out.

Some 300 chemotherapy-naïve patients with stage 4 metastatic breast cancer were assigned to 1 of 4 regimens: Abraxane 300 mg/m2 dosed every 3 weeks, Abraxane 100 or 150 mg/m2 dosed weekly for 3 of 4 weeks, or docetaxel 100 mg/m2 dosed in the standard manner once every 3 weeks.

“We evaluated each regimen’s toxicity and tumor response data, probed the results of once-weekly versus once-every-3-weeks dosing of Abraxane, and compared a high and low dose of the study drug,” explained Dr Gradisher.

The new drug, given weekly, was “superior in virtually all respects to docetaxel,” Dr Gradisher noted. “This is very encouraging, as docetaxel is generally considered the best chemotherapy agent available for treating metastatic breast cancer.”

Dr Gradisher reported that all 3 Abraxane regimens offered longer progression-free survival times than the docetaxel regimen. In fact, he said, “To date, twice as many patients receiving Taxotere have progressed and/or died compared to those on each Abraxane arm.”

Abraxane was better tolerated as well. Dr Gradisher said, “There were significantly fewer reports of neutropenia, febrile neutropenia, and mucositis—which traditionally cause serious trouble, including hospitalizations and discontinuation of therapy, for patients on standard treatment.”

These promising results have prompted the manufacturer to launch a large international phase 3 trial that will compare weekly Abraxane injections with docetaxel injections every 3 weeks as first-line treatment of metastatic breast cancer.