`Albumin delivery improves breast cancer

therapy
10-Jan-2005

Related topics: Materials & Formulation, Drug delivery systems

A widely used drug to treat breast cancer has been significantly improved by the use of a
new technology that binds it to albumin, a common constituent of human blood.

American Pharmaceutical Partners and its partner American Bioscience have just received
approval for the new version of paclitaxel from the US Food and Drug Administration (FDA).

The approval marks the debut of a new class of 'protein-bound particle' drugs, made possible by
the use of American Bioscience's proprietary nanoparticle albumin-bound (nab) technology. This
is particularly suited to cancer drugs because it is believed to exploit an inherent pathway for
albumin receptor-mediated transport of drugs across the endothelial cell walls of blood vessels in
tumours. This pathway is thought to be a means by which the malignant cell inherently supplies
itself with nutrients and energy for rapid growth.

Paclitaxel, originally developed by Bristol-Myers Squibb but now available generically in many
markets around the world, is a mainstay of breast cancer therapy. But the downside of paclitaxel
therapy has always been the relatively high risk of side effects, from the drug itself but also from
the solvents (Cremophor-EL and alcohol) used in its formulation, which can cause
hypersensitivity reactions.

The new product - called Abraxane - does away with the need for this solvent and so reduces the
side effects of paclitaxel treatment. But is has other advantages, including an increase in
effectiveness in combating cancer and more patient-friendly administration.

In trials, Abraxane has demonstrated a superior response rate to Taxol, B-MS' formulation of
paclitaxel, with an almost doubling of the target lesion response rate in a trial of 460 patients
with metastatic breast cancer.

"Because it contains no toxic solvents, this next-generation taxane product enables the
administration of 50 per cent more chemotherapy with a well-tolerated safety profile," according
to the company. Moreover, it requires no premedication to prevent hypersensitivity reactions -
usually patients receiving Taxol are given steroids to guard against reactions.

Abraxane can be given over 30 minutes, in contrast to Taxol which requires extended infusion
times to limit the risk of side effects developing..And it can also be delivered using standard
intravenous tubing, while the solvents in Taxol require the use of specialised iv tubing sets to
avoid leaching of plasticisers into the patient.
The FDA has approved Abraxane (paclitaxel albumin-bound particles for injectable suspension)
for patients with metastatic breast cancer. The product is indicated for the treatment of breast
cancer after failure of combination chemotherapy for metastatic disease or relapse within six
months of adjuvant chemotherapy. Prior therapy should have included an anthracycline unless
clinically contraindicated.

American Bioscience is responsible for the clinical development and registration of

Abraxane, while APP has licensed exclusive North American manufacturing and marketing

Bevacizumab and albumin-bound

rights for the product.

paclitaxel treatment in metastatic breast

cancer.
Link JS, Waisman JR, Nguyen B, Jacobs CI.

Breastlink Medical Group, Barbara K Robinson Breast Cancer Research Program, Todd Cancer
Institute, Long Beach Memorial Medical Center, Long Beach, CA 90806, USA.

Abstract

BACKGROUND: Miller et al demonstrated that the combination of bevacizumab and paclitaxel

has significant activity in metastatic breast cancer (MBC). Because albumin-bound paclitaxel has
been shown to have less toxicity, a better tumor delivery, and possibly better response for MBC,
we combined it with bevacizumab to treat women with MBC.

PATIENTS AND METHODS: This is a retrospective analysis. Billing records from March 2005
through December 2006 were reviewed to identify all patients treated with a combination of
albumin-bound paclitaxel/bevacizumab. A total of 40 women were identified. They received a
minimum of 2 courses. Patients with measurable disease were monitored for response using
Response Evaluation Criteria in Solid Tumors. Women with bone-only disease were monitored
with positron emission tomography (PET)/computed tomography/magnetic resonance imaging
and tumor markers. All response data were confirmed by independent review.

RESULTS: Of 33 women with measurable disease, 16 had objective responses to the albumin-
bound paclitaxel/bevacizumab regimen (3 complete responses and 13 partial responses) for an
overall response rate (ORR) of 48.5%. Median time to progression for responders was 128 days.
Another 5 women had stable disease (SD) with a median duration of 135 days. Of 7 patients with
bone-only disease, 2 had almost complete resolution of PET activity and 4 had SD (median, 148
days). Toxicity was acceptable with fatigue, neuropathy, pain, and hypertension being the most
common complaints.

CONCLUSION: In our limited series of women with advanced, heavily pretreated MBC treated
with albumin-bound paclitaxel/bevacizumab, we saw a 48.5% ORR. The regimen was well
tolerated. Randomized studies are needed to confirm efficacy and safety of this combination in
treating breast cancer.