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Advexin Ups Survival in Late-Stage Head/Neck Cancer; Other Cancers Next

By Daniel J. DeNoon
WebMD Health News

Reviewed By Louise Chang, MD

May 30, 2008 — Advexin, a genetically engineered virus carrying an anticancer gene, ups survival in late-stage head/neck cancer. It may work in other cancers, too.

Advexin carries the p53 anticancer gene. The p53 gene is the body's natural mechanism for stopping tumor growth. During many kinds of cancer, mutant versions of p53 arise. That throws a monkey wrench into the body's cancer-fighting machinery.

Using a doctored version of a common cold virus, Advexin carries a new p53 gene into tumor cells. It causes these cells to self-destruct — and also has a bystander effect that reins in neighboring tumor cells. The main drawback, so far, is that Advexin must be injected directly into tumor cells.

That's why John Nemunaitis, MD, medical director of Dallas' Mary Crowley Cancer Center, and colleagues at Introgen Therapeutics Inc. tested the treatment in patients with late-stage head and neck cancer. It's a deadly cancer, but one that's accessible to direct injection.

Their study enrolled 123 patients with recurrent squamous cell carcinoma of the head and neck whose cancers did not respond to first-line treatment. Because such cancers are almost always fatal, patients received either Advexin or chemotherapy with methotrexate.

Nobody was cured of their very late-stage cancer. And only some of the patients treated with Advexin survived longer. This is because only about half of cancer patients have the p53 mutations that Advexin is designed to fix.

Fortunately, there's a test to see which patients are most likely to respond to Advexin. And those that did have these "favorable" mutations survived longer after Advexin treatment:

• Patients with favorable p53 profiles survived 7.2 months with Advexin treatment.
• Patients with unfavorable p53 profiles survived 2.7 months with Advexin treatment.
• Patients with favorable p53 profiles survived 4.3 months with methotrexate treatment.
• Patients with unfavorable p53 profiles survived 5.9 months with methotrexate treatment.

A few extra months of life may not seem like a lot. But Nemunaitis says that if Advexin can help patients with the most severe form of cancer, it can do a lot more for patients treated at earlier stages of disease.

"As a doctor, I talk with patients and just being able to offer them several months is frustrating," he tells WebMD. "But we have some patients out nine years now as a result of early participation in our trials. I hope that by treating the most appropriate patients, earlier in their disease, we can offer them much better outcomes in the future."

Nemunaitis says it's likely that in the future, Advexin will probably have to be combined with other forms of chemotherapy to maximize its effect.

And since Advexin has far fewer side effects than traditional chemotherapy — cold-like fever and chills were the main side effects — combination therapy with the drug may be more tolerable than other combination chemotherapies.

Nemunaitis reported the findings at this week's meeting of the American Society of Gene Therapy in Boston.

SOURCES: John Nemunaitis, MD, executive director, Mary Crowley Cancer Research Center, Dallas. American Society of Gene Therapy annual meeting, Boston, May 28-June 1, 2008. Gabrilovich, D.I. Expert Opinion on Biological Therapy, August 2006; vol 6: pp 823-832.

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