Jefferson Researcher’s Results Show Promise for Metastatic Eye Melanoma

Boosting the immune system, cutting off tumor oxygen supply, may be keys to patients living longer

When melanoma of the eye spreads to the liver, patients have few good options. Surgery is frequently impossible, and chemotherapy hasn’t proven effective. But now, by simultaneously revving up the immune system and choking off the tumor’s oxygen supply, oncologists at Jefferson Medical College and the Kimmel Cancer Center at Thomas Jefferson University in Philadelphia may have found a better way to battle this deadly cancer.

Researchers, led by Takami Sato, M.D., K. Hasumi Associate Professor of Medicine at Jefferson Medical College of Thomas Jefferson University, have shown promising results from an early, phase 1-2 clinical trial of a novel treatment for uveal melanoma that has spread to the liver.

In the procedure, called immunoembolization, Dr. Sato and his co-workers “embolize,” or block off the hepatic artery, which is a major artery feeding the liver, cutting off oxygen to liver tumors. They infuse a chemical called GM-CSF, which stimulates the immune system – specifically, cells called macrophages and dendritic cells – to produce an inflammatory reaction, and it’s hoped, fight the cancer.

In the trial, which was aimed at testing for treatment toxicity and feasibility, Dr. Sato found that 30 percent of 39 patients studied (34 of whom had uveal melanoma) had tumor shrinkage and another 30 percent had tumors that didn’t grow.

He presents his team’s findings May 17, 2005 at the annual meeting of the American Society of Clinical Oncology in Orlando.

“We have seen a surprising phenomenon,” he says. “Compared to chemoembolization (a similar, older therapy that entails giving a patient chemotherapy directly into the liver), our patients did just as well and some did better. The treatment is doing something to prolong survival.

“If we’re right,” Dr. Sato says, “we could delay metastases.”

Dr. Sato also found a response in other tumors in the body besides the liver – a potentially important finding, he says. Patients in the study lived on average about twice as long compared to those who received chemoembolization in an earlier study he and his team conducted.

Dr. Sato heads one of the few programs in the nation treating metastatic uveal melanoma, which is a melanoma originating in the eye and the most common adult eye tumor. It is very rare, affecting perhaps 6 or 7 individuals per 1 million. When it spreads to the liver, patients who do not receive treatment live on average about 6 months. The treatment Dr. Sato is testing is used for patients who are not eligible for surgery.

While the trial results show the two-pronged treatment is safe and feasible – as well as providing promising responses to metastases, Dr. Sato reaffirms the need for a larger phase 2 study, which has already opened for patients with uveal melanoma metastatic to the liver. The phase 2 trial compares immunoembolization to embolization, or cutting off the tumor’s oxygen supply. The trial is funded by an R21 grant for nearly $600,000 over two years that he recently received from the National Cancer Institute.

In the new trial, he will also monitor the immune system reaction, looking for an increase in numbers of specific immune cells. He plans to biopsy patient livers, he notes, because “If the GM-CSF is working, an inflammatory response should be seen in the liver tumor.”

The next step in the future, he says, would be to conduct a phase 3 multicenter trial comparing chemoembolization and immunoembolization. He notes that the immunoembolization procedure may be useful in treating primary liver cancer or other types of cancer that have spread to the liver as well.