ALS Drug Slows Melanoma Growth
Study Shows Riluzole Shrinks Tumors Without Toxic Side Effects
By Charlene Laino
WebMD Medical News
Reviewed by Louise Chang, MD
April 15, 2008 (San Diego) -- A drug used to treat Lou Gehrig's disease appears to curb the growth of melanoma, the most deadly form of skincancer, a small study shows.

New Jersey researchers studied riluzole, which is used to treat amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease.




Tumors were completely wiped out in three of nine people with advanced melanoma who were given the drug for two weeks.

"Their tumors, which you could see outside the body before treatment, completely disappeared," James Goydos, MD, tells WebMD. Goydos is a surgical oncologist at the University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School in New Brunswick.

In two more patients, imaging scans showed that tumors had shrunk. Three more patients remained stable. One patient got worse, with signs of tumor growth.

The researchers tracked the patients' progress before and after the treatment with biopsies and PET scans, a form of nuclear-medicine imaging typically used to detect cancer.

The results were presented at the annual meeting of the American Association for Cancer Research.

Riluzole Lowers Glutamate Levels
Each year, more than 53,600 people in the U.S. are diagnosed with melanoma, according to the National Cancer Institute (NCI). In the past 30 years, the number of Americans who develop melanoma annually has more than doubled.

In about 70% of cases, people with melanoma develop lesions in body areas that are exposed to the sun. The cancer can then spread to other parts of the body -- typically the lymph nodes first and then other organs.

The new study involved people whose disease had spread, or metastasized, to the lymph nodes.

The work builds on the research team's earlier discovery that melanoma cells release a lot of a substance called glutamate.

Too much glutamate can overstimulate brain cells to the point that they burn out -- a possible explanation of what happens in ALS, says Suzie Chen, PhD, a professor of chemical biology at Rutgers University.

Riluzole, also sold as Rilutek, fights ALS by lowering glutamate levels. "So my collaborators said, let's test it against melanoma. And much to our surprise, the drug slowed the growth rate of melanoma cells [in the test tube]," Chen says.

In animal studies, riluzole again suppressed tumor cell growth and progression, she says. The researchers were then able to secure an NCI grant to perform a new type of first-in-human study; it's designed to validate if a drug will perform as expected in humans -- "to see if you are hitting your targets," Goydos says.

"This is the very first time we have treated melanoma patients with drugs that target [glutamate] and a significant number of patients responded," he says. The only significant side effect was dizziness, according to Chen.

Goydos says that he was amazed at some of the results. One of the first patients "had a large growth in the groin area," he says. "When the pathologists examined the tissue after the treatment, all they could see was scar tissue -- there was no tumor. We thought there was a mistake."

Another patient had a "large painful lymph node on his neck and could barely move his head. One week in, the node shrank, and he was very comfortable, even without pain medication," Goydos says.




Other researchers are enthusiastic about the approach. "What is exciting about these very preliminary results is that it is an outgrowth of a novel observation that showed that melanoma appears to be dependent on glutamate," says Stuart Lessin, MD, head of dermatology at Fox Chase Cancer Center in Philadelphia.

"As far as metastatic disease goes, metastatic melanoma is very recalcitrant to treatment. This really provides a potential new avenue, a new target for treatment. [It] could work by itself or more likely in combination with other treatments," he tells WebMD.

The next step will be a study of even sicker patients -- those whose disease has spread to other organs, like the liver. The dosage will gradually be increased to determine the most effective dose and identify possible toxic side effects.

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