Positive Axitinib Results in Thyroid and Pancreatic Cancers

Positive Axitinib (AG-013736) Results in Thyroid and Pancreatic Cancers
The last drug approved to treat thyroid cancer was in 1974, but doctors
may now have a new drug to successfully treat the disease. Axitinib, a
drug that inhibits the tumor-feeding vascular endothelial growth factor,
was tested in a phase II trial of 60 patients whose tumors did not respond
to conventional therapy.

Data from the single-arm study showed 18 patients (30 percent) had their
tumors shrink by at least 30 percent, while another 25 patients (42
percent) experienced slight tumor shrinkage or no progression of their
disease.

Median time to progression was 18.6 months. Side effects of axitinib
include fatigue, high blood pressure, and diarrhea. More than 30,000 new
cases of thyroid cancer will occur in 2007, according to the American
Cancer Society, and most are cured with surgery and radioactive iodine.
Adriamycin® (doxorubicin) is the only drug currently approved for
metastatic thyroid cancer, but the agent is very toxic, says Ezra Cohen,
MD, of the University of Chicago and the trial?s lead investigator, who
feels the old drug should never have been approved for thyroid cancer and
doesn?t prescribe it to his patients.
A phase III randomized trial comparing axitinib with placebo in
Adriamycin-refractory thyroid cancer is currently ongoing.

Encouraging preliminary results from a randomized phase II trial were also
presented for axitinib in advanced pancreatic cancer. Median overall
survival for patients receiving axitinib plus Gemzar® (gemcitabine) was
6.9 months compared with 5.6 months with Gemzar alone.

Axitinib is also being tested in breast, lung, and kidney cancers. ?MW

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Pfizer: axitinib shows early promise in pancreatic cancer
4th July 2007
By Fleur Pijpers
Interim study results show prolonged survival for Pfizer's axitinib in
advanced pancreatic cancer.
While final results need to be corroborated in an upcoming Phase III
study, Pfizer's axitinib shows early potential to fulfill the great unmet
need associated with pancreatic cancer. Given that OSI
Pharmaceuticals/Genentech/Roche's Tarceva was granted FDA approval in this
indication based on a two-week survival benefit, it is likely positive
results would be met with great enthusiasm.

Interim results from a Phase II trial showed the addition of axitinib to
Eli Lilly's Gemzar conferred a median overall survival of 6.9 months
compared to 5.6 months for single-agent Gemzar, which translated into a
26% reduction in the risk of death. In a subset of 94 patients with a good
performance status, the combination reduced the risk of death by 33%.


Developed by Agouron Pharmaceuticals, a wholly owned subsidiary of Pfizer,
axitinib is an orally available inhibitor of the VEGFR 1?3, PDGFR and
CSF-1 tyrosine kinases. By targeting several kinases, axitinib is able to
exert its anti-angiogenic effects and effectively starve a tumor of the
blood and nutrients required for growth.

Pancreatic cancer represents a major health issue in the developed world
and is associated with an exceedingly poor prognosis. By nature, this
tumor type is particularly aggressive with non-specific initial symptoms
and a difficult early diagnosis. In addition, pancreatic cancer is highly
resistant to conventional therapies, therefore these have little impact on
prognosis or survival. As a result, pancreatic cancer is the fourth
leading cause of cancer-related death in the Western world.

While the Phase II interim results trend towards increased survival, it
may be too early to fully analyze the potential of a Gemzar-axitinib
combination in advanced pancreatic cancer. A larger Phase III clinical
trial investigating the same combination is due to begin in August 2007,
after which more light will be shed on the drug?s full potential.

It must be noted that OSI Pharmaceuticals/Genentech/Roche's Tarceva
(erlotinib) was granted FDA approval in combination with Gemzar for the
first-line treatment of locally advanced, unresectable or metastatic
pancreatic cancer in February 2005 based on a two-week survival benefit
over Gemzar alone.

It is clear that the unmet need in pancreatic cancer is so high that if
axitinib can improve survival above and beyond that conferred by Tarceva,
uptake on approval is likely to be significant.

http://www.ama-assn.org/ama1/pub/upload/mm/365/axitinib.pdf One page
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Chemical Names and Structural formula

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