NAPLES, FLA. — Retinoids, NSAIDs, and perhaps statins lead the increasingly long list of possible skin cancer chemopreventive agents, James Spencer, M.D., said at the annual meeting of the Florida Society for Dermatology and Dermatologic Surgery.
In a wide-ranging discussion of the highly active field of cancer chemoprevention, Dr. Spencer made the following comments about the more notable, possible agents:
▸ Retinoids. Without a doubt, retinoids have been shown to prevent the development of skin cancer, said Dr. Spencer, the director of Mohs micrographic surgery at the Mt. Sinai Medical Center, New York. But they may never be an agent for the general, average patient.
Oral retinoids have been most thoroughly investigated in studies with solid organ transplant patients, who are extremely prone to the development of skin cancers.
In one study of Australian renal transplant patients followed for 20 years, 70% had developed skin cancers, and in a study that looked specifically at what caused death in heart transplant patients who had survived for 4 years, skin cancer was the cause of death in one-third of them.
Transplant-patient studies have been conducted with both etretinate and acitretin, with acitretin being the more commonly used drug now, at a dose of 30 mg/day. In a blinded trial in which 38 renal transplant patients received either drug or placebo for just 6 months, 11% of the acitretin-treated patients developed new squamous cell carcinomas vs. 47% of the placebo patients, and there was a 41% decline in keratotic skin lesions.
Unfortunately, transplant patients who take a retinoid have retinoid side effects, and it is not clear how low a dose they can be given to minimize those side effects, Dr. Spencer said. One trial of 10 mg/day was not effective.
Moreover, the evidence suggests that retinoids do not kill cancers, but simply halt their development during the drug's course. In one study of patients with xeroderma pigmentosum, isotretinoin significantly reduced the development of skin cancer, and it did so extremely rapidly, with a decrease in the incidence of skin cancer within 2 months of starting the drug. But the study also showed that the beneficial effect went away just as rapidly. Cancerous lesions began to reappear within 3 months of stopping the drug, too soon for it to be likely that the lesions were brand new malignancies that sprang up after the drug was stopped.
▸ Vitamin D. Vitamin D is being touted as having several health benefits, including cancer chemoprevention, and this is calling into question the wisdom of sunscreen use. The issue is being covered in the media, and the concept is being taken seriously enough by endocrinologists and oncologists that a recent paper (Cancer 2002;94:1864–75) actually tried to calculate how many excess deaths occur annually in the United States due to inadequate vitamin D. It estimated 21,000 excess deaths.
The major evidence for vitamin D chemoprevention comes from the epidemiologic observation that colon, breast, and prostate cancer incidences are lower in the lower latitudes and higher in the northern latitudes.
However, in the United States, that pattern is true in the East, but it is not so clearly apparent in the West, Dr. Spencer said.
The amount of vitamin D thought to be necessary to prevent cancer is very high, and some endocrinologists who advocate vitamin D are actually calling for amounts three times above the generally recommended minimum daily requirement. At the same time, it is known that too much vitamin D can have adverse health effects, including causing kidney stones, Dr. Spencer noted.
Because the evidence is so tentative, Dr. Spencer said he would advise patients who were worried about vitamin D not to give up sunscreen and instead take a supplement at a rational dose.
▸ NSAIDs. Ample evidence suggests that nonsteroidal anti-inflammatory drugs can prevent colon cancer, among other malignancies. A case-control study has suggested that they may protect against melanoma (Oncol. Rep. 2001;8:655–7).
Two large trials of NSAID prevention of skin cancer are underway, and they should be completed in the next year or so, Dr. Spencer said.
“This would be so simple, because you have NSAIDs in your medicine cabinet at home right now,” he said.
▸ Statins. Epidemiologic evidence has suggested that statin use is associated with decreased risk of breast, advanced prostate, lung, esophageal, colon, and pancreatic cancers. Laboratory evidence suggests that statins have this effect because they interfere with two oncogenes, Ras and Rho. Those oncogenes are involved in most melanomas.
▸ Vitamins E and C. Trial results of the chemoprevention effect of vitamin E and vitamin C have not been positive. However, a recent trial of both vitamins together reported that the combination provided significant UV protection, increasing the minimal erythema dose by an average of about 50% in just a single week, Dr. Spencer said.