Tretinoin, the acne drug that went on to wrinkle-smoothing fame, may have yet another clinical use: Several investigators see it as a skin cancer preventive, although their evidence so far is scant.
“Retinoids act as inhibitors of tumor promotion and tumor progression,” Dr. Albert Kligman said here at the International Conference on Skin Therapy and Cosmetics. Dr. Kligman, a professor of dermatology at the University of Pennsylvania in Philadelphia, did pioneering work with tretinoin in the treatment of acne and advocates its use against photoaging. Now, he has turned to cancer research with retinoids.
Tretinoin (Retin-A, Ortho) was propelled into the consciousness of millions of potential patients earlier this year when dermatologist John Voorhees announced results of a 16-week, double-blind study with 30 patients. He reported that the drug significantly improved the appearance of photoaged skin.
Another result was normalization of irregular, precancerous epidermal cells of forearm skin.
Dr. Voorhees, dermatology chairman at the University of Michigan in Ann Arbor, predicted that a substantial number of americans will be using the drug for photoaging–and probably for actinic keratoses–in the next five years.
Steady gains. Here, he presented 10-month follow-up data on 20 of the original 30 patients and said “the majority continued to improve with no significant side effects. There was progressive improvement of the photoaging process, improvement in brown spots and in both fine and coarse wrinkles.” In an open study of 560 patients, he said, patients continue to improve at two years.
But Dr. James Leyden, a professor of dermatology at the University of Pennsylvania, deplored what he calls “Retin-A casualties” and the drug’s overuse or misuse by people who are not under the care of physicians but are using a friend’s prescription refills.
The drug also is being widely prescribed by physicians to treat photoaging even though it has not been approved for that indication.
Dr. Leyden said results from two centers that have completed a multicenter trial study showed an average improvement of 30% in skin surface topography of fine lines and wrinkles.
Cancer role. Dr. Kligman sees a significant role for tretinoin in caner prevention and possible therapy. In fact, he already tells patients who use the drug for photoaging that “it’s going to inhibit your tumors, it’s not going to support any neoplastic growths.”
He said he will soon report on a series of more than 100 patients whose actinic keratoses have been eliminated with tretinoin, and he is starting a study of dysplastic nevi, a marker for malignant melanoma.
Already, Dr. Kligman reported, he has treated three cases of early stage malignant melanoma, which resolved with tretinoin in about six months without surgery. The retinoid can inhibit malignant melanoma, he said. “We’re not killing cells, we’re reeducating them, obliging them to follow a different line of development.”
There is increasing evidence that retinoids can be useful in those who are genetically predisposed to cancer, Dr. Leyden said.
There is a biologic, scientific link between what may seem like totally different disorders–photoaging, acne, and cancer–and the effect of retinoids, he said. “Vitamin A and its derivatives affect cell growth and differentiation. So whenever you have abnormal growth and abnormal manufacturing of what cells are supposed to make, certain retinoids for certain cells will correct it.”
Keratosis study. His comments were supported by Dr. D’Anne Kleinsmith, assistant clinical professor of dermatology at the University of Michigan, who reported on use of tretinoin to treat actinic keratosis as part of a 10-center study. Patients with biopsyproven actinic keratoses received either 0.05% or 0.1% cream.
“There was a reduction in the number of actinic keratoses–about 20% fewer at the end of six months,” Dr. Kleinsmith said.
Dr. Barbara Gilchrest, a professor of dermatology at Boston University, said she found “if you take malignant cells in the culture environment and expose them to retinoic acid, they become more normal in their behavior.”
Commenting on that work, Dr. Richard Dobson, conference director and a professor of dermatology at the Medical University of South Carolina in Columbia, said, “this important laboratory finding of the tendency of malignant cells to normalize ties in with the potential use of tretinoin in dysplastic conditions,” suggesting that the logical approach is to use the drug to prevent conversion of dysplasia to cancer.