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Illustration of thyroid like a butterflyClinical Trials: Thyroid Cancer

by Jeff Worley

In his effort to better treat thyroid cancers, UK researcher Kenneth Ain is enlisting the aid of a drug with a universally despised reputation: thalidomide.

Thalidomide was introduced in 1957 in West Germany and was soon commonly prescribed to pregnant women as a sedative. When thalidomide was taken during the first trimester, however, the drug prevented normal growth of the fetus, resulting in horrific birth defects such as missing or shortened limbs in thousands of children around the world. These children, born in the late '50s and early '60s, became known as "thalidomide babies."

Ain, a professor of medicine in the Division of Endocrinology & Molecular Medicine at UK, believes that although thalidomide has been used inappropriately, that doesn't make it a "bad" drug. He points out that thalidomide has been FDA-approved to treat leprosy, for example, and Ain thinks the drug can help people with particularly hard-to-treat thyroid cancers.

"There has been some compelling anecdotal evidence that thalidomide given to a patient with anaplastic thyroid cancer, the most aggressive type of thyroid cancer known to man, retarded the growth of tumors for up to six months," says Ain, who came to UK in 1991 after spending four years at the National Institutes of Health. "So we wanted to do this current trial to test that out." Anaplastic thyroid cancer is rare—only 300 cases in this country each year—but it's deadly: from the time of diagnosis, even with therapy, patients typically live only four to five months.

The thyroid gland is situated in the front part of the neck below the skin and muscle layers. This gland is shaped like a butterfly, with the two wings being represented by the left and right thyroid lobes that wrap around the trachea. The function of the thyroid is to regulate the body's metabolism. Thyroid cancer affects the gland responsible for producing hormones that control heart rate, body temperature and energy. It is diagnosed in nearly 15,000 women and around 4,500 men in the United States each year.

Over the past eight years, the incidence of thyroid cancer is on the increase for reasons, Ain says, that are unclear. He adds that fighting thyroid cancer is an especially tough challenge because no chemotherapy has been found to be effective.

Thyroid cells naturally pump in iodine to make the thyroid hormone, and thyroid cancer cells often retain this ability. This fact prompted investigators more than a half century ago to treat thyroid cancer, after the removal of thyroid gland, with radioactive iodine. "Time has demonstrated the effectiveness of this approach in most patients," says Ain. "Unfortunately, a subset of patients has rapidly progressive disease that does not respond to this treatment. For these patients, there haven't been any effective therapies."

But for such patients, desperation may soon be replaced by hope.

In a recent Phase II trial using thalidomide to treat two types of thyroid cancers unresponsive to radioiodine, Ain and his team worked with patients who had rapidly progressive thyroid cancer. The participants were given up to 800 milligrams of thalidomide daily and were evaluated by CT scans every two months for a year; treatment was continued after each assessment if there was evidence that the cancer had stopped growing or had regressed. If the patient's tumor continued to grow as rapidly as before treatment, the patient was taken off this drug.

Photo of Kevin Williams and Kenneth AinKevin Williams (left), a clinical research associate, and Kenneth Ain, a professor of medicine in the Division of Endocrinology & Molecular Medicine, discuss the latest results of a clinical trial using thalidomide to help people with particularly hard-to-treat thyroid cancers. Ain is heading up this study.

Of the 17 patients who have been evaluated, 13 experienced either a plateau or a decline in tumor size, and beneficial responses to thalidomide persisted for an average of seven months in half of these patients. In addition, patients who had experienced either a plateau or decline in their tumor size but eventually noted progression of their tumors lived longer than patients who had no beneficial response from the thalidomide—approximately four and a half months longer.

"These results suggest that thalidomide is a potent inhibitor of tumor progression in some aggressive, metastic thyroid cancers," Ain says. "And patients with these advanced cancers badly need effective treatments because there are currently none available." Ain presented these findings at the Chemotherapy Foundation meeting in New York last December.

Funding for this trial came from the National Cancer Institute and the Celgene Corporation, a New Jersey-based pharmaceutical company. Further support came from UK's General Clinical Research Center, where much of this work took place. The center, located in the UK hospital, includes an outpatient clinic and a specimen-processing lab.

Ain emphasizes that the thalidomide trial is only one of several approaches under investigation at UK focused on understanding and treating thyroid cancer. This work is part of the well-established thyroid cancer program he began when he arrived at UK. The University of Kentucky Thyroid Nodule and Oncology Clinical Service, sponsored in part by the Division of Endocrinology and Molecular Medicine and UK's Markey Cancer Center, is one of only a few such programs in the United States.

Ain reaches down to the floor and wrestles up a black book that is nearly two-feet thick. "These are my patients," he says, leafing through. "Right now I have hundreds of patients, and I follow every one of them." He adds that he has one of the largest thyroid cancer practices in the world for a single doctor.

How can he work on several research projects, do the academic work required of him as a professor, and follow all these patients all at the same time?

"It's an all-consuming job, I admit it. I work every day from 7:30 a.m. until anywhere from 11 at night to one in the morning. On weekends I catch up on my sleep—maybe six hours a night." And if Ain continues to spend long hours in the office, his wife-to-be, he says, will understand.

"Sara [Rosenthal] is a thyroid cancer survivor herself and a medical writer—she's written 35 books." When she wrote a book on thyroid cancer, she asked Ain to edit it for accuracy. "In the process I met her and fell in love." Rosenthal, whose expertise is bioethics, will join the UK faculty this summer.

For information on how to participate in UK clinical thyroid cancer trials, have your physician call 859/323-3778.

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