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Experiment at Stony Brook delivers drugs into arteries that feed the brain, targeting aggressive tumors

Posted on: 01/17/2007

An innovation in chemo

Experiment at Stony Brook delivers drugs into arteries that feed the brain, targeting aggressive tumors

Newsday Staff Writer

January 17, 2007

Four years ago, Kathleen Jack of Hauppauge got out of bed on the wrong foot. In fact, she stumbled a lot that day before she discovered that a deadly tumor was growing in her brain, knocking her body and her life off center.

Jack became one of dozens of brain tumor patients at Stony Brook University Medical Center who received an experimental procedure to deliver potent chemotherapy into the arteries that feed the brain. The average survival for patients with her type of aggressive tumor - glioblastoma multiforme - is a year.

She has outpaced the odds, but recently a new tumor appeared elsewhere in her brain. With no symptoms this time around, Jack went through surgery again, and last month a cocktail of chemotherapeutic drugs was infused through her intracarotid arteries yet again.

"I am very hopeful," said Jack, 54, a mother of three. "I am counting on it."

The doctor who spearheaded this novel approach is Stefan Madajewicz, a professor of medicine at Stony Brook and chairman of its cancer center clinical trials committee.

Madajewicz started investigating in-tracarotid infusions of chemotherapeutic agents in the late 1970s at the Roswell Park Cancer Institute in Buffalo. The work began in animals and by the early 1980s it was tried in patients. But it became clear quickly that the chemotherapeutic agent delivered directly into the brain caused disturbing side effects like blindness and mental confusion.

But Madajewicz believed that it was the toxicity of the drug, not the delivery system. The cancer doctor moved to Stony Brook and began studying a combination of cisplatin and etoposide - an intracarotid chemo cocktail. Since 1988, almost 80 patients have gone through the treatment protocol, which includes three infusions delivered in a two-month period, on the heels of surgery and before radiation.

In a 2000 paper published in the journal Cancer, the Stony Brook researchers analyzed the fruits of their research and found that the average patient survival doubled in their hands. Those patients, who are routinely given a year to live, are now living, on average, 20 to 22 months. Further results from their ongoing studies were presented at the American Society of Clinical Oncology Meeting last year. The median survival is 25 months and counting, Madajewicz said, and a third of patients survived at least three years.

At Stony Brook, doctors also have added an oral cancer drug called Temodar to the treatment.

Dr. Keith Black, chairman of neurosurgery at Cedars-Sinai Medical Center in Los Angeles, said the procedure allows patients to withstand a high-dose targeted treatment that might otherwise be toxic. "You can get a much higher concentration of drug into brain tissue," he said. Black is developing the first vaccine treatment for brain tumors that also is showing great promise.

Madajewicz said it takes a lot of skill and practice to prevent complications of the intracarotid procedure, which can include stroke or brain bleeds in 1 percent of patients. (Only one of their 100 or so patients suffered a stroke.) Other transient side effects include eye pain and nausea.

Only a handful of hospitals are using the procedure, including a group in Quebec that replicated the Stony Brook team's survival rates.

Each year, about 40,000 people in the United States are diagnosed with a primary brain tumor, said Mary Lovely of the National Brain Tumor Foundation in San Francisco. "We are in an age where there are a lot of innovative approaches and we just have to see what works," she said.

Dr. Patrick Kelly, an endowed professor of neurosurgery at NYU School of Medicine, who has been operating on aggressive brain tumors for decades, said he has learned that long-term survival is not necessarily proof that a treatment works. But he still says he believes the research envelope has to be pushed. "If we didn't try new things, we'd still be scratching our heads over these tumors. In fact, we are still scratching our heads."

Copyright 2007 Newsday Inc.

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