Taking on a trial Woman opts for experimental cancer treatment.

Byline: TIM CHRISTIE The Register-Guard

KYLA NAGEL SUFFERED a pounding, debilitating headache the afternoon of Dec. 28.

She thought maybe the stress of her busy life - taking 15 credits at the University of Oregon, working 20 hours a week in the UO housing office and caring for her 2-year-old daughter, Emma - had given her the headache. She took two aspirin, which took the edge off, and went to bed.

When the 24-year-old Springfield woman awoke about 5 a.m. Dec. 29, her body was gripped in a seizure and her life had changed forever.

Nagel doesn't remember that day. Her husband, Jered, told her later that she couldn't talk and looked at him with a weird smile he'd never seen before.

Doctors found a large tumor on her brain that turned out to be glioblastoma multiforme, a particularly aggressive, deadly form of cancer. Half the people who get the disease are dead within a year.

Dr. Andrew Kokkino performed brain surgery on Nagel on Jan. 3 at Sacred Heart Medical Center, cutting out as much of the tumor as he could reach. Nagel then underwent a six-week course of radiation and chemotherapy, plus an experimental treatment with Accutane, a drug usually used to control acne.

But the tumor had threaded into her brain like the roots of a weed. After six weeks of treatment, the tumor grew back atop her brain. The average life span for a glioblastoma patient with a regrowth of tumor is four months.

Doctors presented Nagel with three options: She could undergo brain surgery again, which would remove part of the tumor but wouldn't get the part that had grown into her brain. She could try a second, stronger dose of chemotherapy, which doesn't have a good track record. Or she could agree to be a human guinea pig.

For Nagel, it was no choice at all. She agreed to participate in a phase one clinical trial at the University of California at San Francisco Medical Center. She underwent the experimental treatment in mid-May, getting a dose of a drug called IL13-PE38QQR Cytotoxin, or IL13-toxin for short, injected directly into her brain.

"It was our only option, we felt," she said. "Basically there was no choice but to do the IL13 protocol."

Clinical trials represent the cutting edge of modern medicine. It's where doctors and researchers find out whether new drugs and treatments work as hoped.

A phase one clinical trial is the first step on a long road toward getting federal approval to put a new drug on the market. It takes an average of 15 years for an experimental drug to win approval from the U.S. Food & Drug Administration. Only five of every 5,000 compounds that are studied get approved for clinical studies, and only one in five of the drugs that are tested clinically is approved by the FDA.

The phase one trials typically involve a small number of subjects, ranging from 20 to 80. The purpose is to evaluate the safety of the experimental drugs and the methods for administering them, such as dosage and delivery.

Nagel's mother, Vonda Evans, who works at the Institute of Cognitive and Decision Sciences at the University of Oregon, found herself scrambling for information, scouring the Internet, looking for a thread of hope to throw to her daughter.

Then her boss at the University of Oregon, psychology professor Michael Posner, said he would get in touch with his brother. Dr. Jerome Posner is a leading brain researcher at one of the top cancer institutes in the country, Sloan-Kettering Cancer Center in New York.

Evans shipped a copy of her daughter's MRI to Dr. Posner in New York. He e-mailed back and advised Nagel to contact the neurologic oncology department at UCSF's Comprehensive Cancer Center, one of the top cancer research centers on the West Coast.

The Nagels went down to UCSF at spring break. Kyla was examined and interviewed, and the cancer center's "tumor board" met and decided that she was a good candidate for the trial.

In mid-May, the Nagels returned for the three-step procedure. In the first step, surgeons inserted a catheter into the tumor, and infused it with IL13-toxin for 48 hours.

Then they performed another brain surgery, opening her skull and removing as much of the tumor as they could safely reach. Then, they inserted three catheters into the surrounding brain, which inundated her brain for four days with IL13-toxin.

IL13-toxin is a combined toxin protein, said Dr. Susan Chang, Nagel's neurosurgeon at UCSF. It works by binding to receptors on the tumor with a molecule that contains a toxin that kills the tumor. It doesn't affect the healthy part of the brain because it doesn't attach to the normal brain receptors.

The trial is sponsored by a pharmaceutical company that she declined to name.

Chang said she's excited not only by the drug but the method by which the drug is delivered.

"We're looking at a totally different way of delivering drugs," she said.

Instead of giving the patient a shot or a pill and hoping some of the drug gets to the tumor in adequate concentrations - while potentially inflicting side effects on healthy organs - the catheter approach provides a direct hit, she said.

"This is one way to bypass the systemic effects and directly deliver the agent where it should be - in the tumor cells," she said.

For Nagel, what matters is that the treatment has at least given her hope. Three weeks after the procedure, she said she feels great. She looks healthy, and only when she takes off her UCSF ball cap is there evidence of what she's gone through: the scars from two brain surgeries crossing the top of her scalp like railroad tracks.

The tumor was on top of the speech center of her brain, and that sometimes makes it difficult for her to express her thoughts in words. Her speaking skills should improve as the swelling in her brain subsides. She sometimes feels exhausted and overwhelmed, particularly at the end of the day. But overall, she said, "I feel wonderful. I can concentrate and read."

She and Jered, both 1996 Thurston High School graduates, have been sweethearts since eighth grade and were married in 1998.

She has to go in for checkups once a week, including repeated visits to UCSF, which means 10-hour car trips each way to the Bay Area.

But the long trips are a small price to pay for better odds on living a longer life and to play a part in developing new treatments for cancer.

"It's amazing and a blessing," she said. "I feel like God wants me here. Hopefully with this new treatment, I'll be a longtime survivor."

It's far too soon to say how effective this experimental treatment will turn out to be for treating brain cancer. With any luck, doctors won't know for a long time.

CANCER FUND:

The Kyla Nagel Cancer Fund has been opened at Centennial Bank, P.O. Box 1560, Eugene, OR 97440, to help cover medical, travel and other expenses incurred by Kyla Nagel and her family as she undergoes experimental treatment for brain cancer. Students, staff and faculty at the University of Oregon Psychology Department recently held an auction, featuring such auctioneers as UO President Dave Frohnmayer and women's basketball coach Bev Smith, which raised about $7,000.

- The Register-Guard

CAPTION(S):

University of Oregon student Kyla Nagel snuggles with her 2-year-old daughter, Emma. Nagel goes to the University of California at San Francisco Medical Center to treat her brain tumor.