Fighting the Evils of the Sun
Years in the sun have taken a toll on Dion Gray, a three-time member of the U.S. water polo team who now coaches at Irvine’s Woodbridge High School. Twice annually, a dozen or so precancerous lesions are removed from her face and shoulders with liquid nitrogen.
“Born with fair skin and out in the sun--not a good combination,” said Gray, 43, who knows the scaly patches can develop into a more serious problem. “I have had tons taken off, more than I can count.”
Gray’s skin maintenance regimen began 14 years ago, shortly after she had a basal cell cancer cut from her left cheek. Now, she’s in a National Cancer Institute drug trial exploring whether a salve made from a Chinese folk remedy can prevent skin cancer.
Scientists at UCI Medical Center in Orange are experimenting with a derivative of green tea in the hope it will be a painless way to eliminate the lesions--called actinic keratoses--that can mature into skin cancer. If the trial proves successful, the salve will be tested on the cancers themselves.
Improving ways to fight skin cancer, the dark side of Southern California’s outdoor lifestyle, has challenged physicians for decades.
The idea for the green tea research came from National Cancer Institute scientists who had observed that the tea is associated with a decrease in animal and some human cancers, and also has shown promise in halting cancer development in laboratory cultures.
The institute solicited research proposals, and last year selected a team headed by UCI physicians Kenneth Linden and Frank Meyskens to conduct the initial human trial. So far, about 20 people have volunteered for the 12-week course of treatment. The university is seeking 40 more subjects for the initial trial and hopes to have results later this year.
It is unclear if the active ingredient in green tea--polyphenol epigallocatechin gallate (Polyphenon E)--can successfully treat skin lesions. But this step-by-step approach, which began with improvements in lab animals and reduced cancers among people who drink green tea--typifies how such studies are conceived and developed into trials of promising anti-cancer agents.
“This is drug discovery and development,” said Dr. Jaye Viner, who is overseeing the $400,000 drug trial for the national institute. “We don’t pretend we have the answer. We are going off of strong [epidemiological and laboratory] leads.”
The American Cancer Society estimates about 1.3 million non-melanoma skin cancers (squamous or basal cell carcinoma) will be detected this year. About 1,900 people will die. That makes it the most common cancer in the United States. Non-melanoma skin cancer is highly curable if detected early.
Linden, 45, a fair-skinned man who applies sunscreen daily before leaving his Irvine home, has both a medical degree and a doctor of philosophy degree. He specializes in evaluating the effects of sunlight on the skin.
“Skin cancer is caused by a combination of genetics and exposure,” he said. “The fairer you are, the more likely you are to get sun damage and to get skin cancer.”
It is well-known that most skin cancer can be prevented by using sunscreen, wearing proper clothing and having a prudent attitude toward sun exposure. Those who don’t use caution and sunscreen probably will suffer sun damage as they age. Such damage can progress to skin lesions and then to cancer.
Actinic keratosis lesions appear as small red, scaly areas. They are rough to the touch and can be tender. Small, non-melanoma skin cancers are similar, but differ in degree and usually are larger, denser and thicker.
The most common therapies for the precancerous lesions are freezing them with liquid nitrogen--effectively burning the damaged cells that then peel off; or applying an ointment that is painful and can result in severe skin inflammation. Surgery or electrical desiccation is used if the lesions have progressed in size and depth or have turned malignant.
The goal of the study is to find better preventive therapies. In addition, surgery and cryogenic treatment can be unwieldy for patients with many lesions. The ointment, called fluorouracil, is particularly troublesome.
The salve, made from a powerful chemotherapy agent, must be applied to the lesions twice daily. The active ingredient attacks the lesions but leaves the area raw, inflamed and sometimes even weeping and crusty. It can leave a patient’s face, neck and arms “glowing like a Christmas tree,” Linden said.
“It isn’t a treatment for the fainthearted,” he said, noting that patient compliance can be a problem.
Robert Flavin, 71, of Fullerton, who joined the trial last month, is a veteran of the skin cancer wars. A retired physical eduction teacher who spent much of his career running gym classes outdoors, Flavin has had hundreds of lesions and numerous cancers removed during regular dermatology checkups.
“I go in three or four times a year to have it done,” he said.
Flavin also has used fluorouracil, which is sold under the brand name Efudex.
“It burns. . . . It is painful. It was like a pretty good sunburn,” he said, admitting that he stopped in the middle of his last six-week treatment. “I don’t remember why.”
During the NCI trial, subjects nightly apply the green tea derivative, which is mixed in a Vaseline-like base, to one arm and a placebo ointment to the other. It causes no pain or burning, according to the subjects, though the ointment is very messy.
Neither the patient nor the doctor knows which of the two small jars they are using contains the Polyphenon E.
If the trial is successful, a better vehicle for the green tea derivative will be found. The NCI does not test many skin ointments and had a San Diego company formulate a base for the drug that doesn’t match the latest dermatological standards, Linden said.
Linden and Dr. Pamela Hite, a research fellow at UCI’s College of Medicine, check patients’ progress every other week during the 12-week trial.
As part of the research, they have taken samples from several spots on the patients’ arms. The skin will be analyzed for bio-markers--changes at the molecular level--that are indicative of skin cancer. One of the goals of the study is to learn about the cancer-forming process.
“We are trying to determine the biology that turns photo-damaged skin into actinic keratoses, and what turns actinic keratoses into skin cancers,” Linden said. “If you can do that, you can understand the disease better and have a better chance of developing treatments for it. This is about more than just seeing if the ointment will work.”
During Flavin’s recent visit to the dermatology clinic on the UCI campus, doctors examined severe sun damage on his arms. Flavin’s face, neck and arms are speckled with freckles and peppered with lesions.
They compared any changes in lesions using a diagram they had traced with markers on cellophane during his first visit.
The doctors and Flavin agreed that there is big improvement in overall skin quality, certainly on one arm. But it could be due to the petroleum jelly base. That is why they test both arms in a blind trial.
Linden points to an actinic keratosis. “That is getting flatter,” he said.
Flavin, who is halfway through the trial, is interested in the results--in no small part because his last small tube of Efudex cost $140.
“If this stuff will make a difference for quite a while, it would be good,” he said.
