PHILADELPHIA — High-dose topical tretinoin is generally well tolerated for chemoprevention of basal and squamous cell carcinomas, Dr. Amy Geng said at the annual meeting of the Society for Investigative Dermatology.
Daily application of 0.1% tretinoin causes some irritation, but it is generally mild, and tolerability tends to improve over time.
“Dermatologists tend to use 0.05% concentrations or lower, in an attempt to reduce the chances of irritation or other side effects. This is especially true for young patients with acne,” said Dr. Geng of the department of dermatology at Veterans Affairs Medical Center, Providence, R.I., and Brown University in Providence. But when using retinoids for long-term prevention of skin cancers, the lower concentrations may not give the full benefit. The challenge is always to balance optimal clinical outcomes against the potential for adverse effects.
Dr. Geng presented tolerability data from the VA Topical Tretinoin Chemoprevention Trial (VATTC), a large-scale, long-term study involving 736 elderly men with histories of keratinocyte skin cancers (BCC or SCCD). The patients were randomized to treatment with a vehicle cream or a 0.1% tretinoin cream on an ongoing basis. All of the study participants, who had an average age of 71 years, had had two or more keratinocyte skin cancers in the 6 months prior to enrollment.
The patients were instructed to apply the assigned treatment once daily for the first 3 weeks and twice daily thereafter. At any time during the study they could step back down to once-daily application if the twice-daily dosing proved to be too irritating. They could also apply sunscreens and moisturizers whenever they felt the need.
Investigators at the four participating centers saw the patients for follow-up visits every 6 months. To date, the patients have been on the protocol for a range of 1.5 to 5.5 years.
There is no question that the tretinoin produced more irritation than did the placebo. At 6 months, 61% of the tretinoin-treated patients reported some sort of retinoid-associated symptoms such as burning, itching, tingling, or other localized reactions, compared with 42% of those using the vehicle alone. Burning sensations, the most common reason people discontinue retinoid therapy, were reported by 39% of the tretinoin group but only 17% of the placebo group during the first 6 months.
The prevalence of all side effects tended to drop off steadily as the patients continued with treatment. By 30 months, there was no longer any statistically significant difference between the two groups in terms of frequency or severity of burning.
Overall, the side effects were mild, and there was no difference in severity of burning sensations between the patients in the two treatment groups.
There were more treatment cessations or dosing step-downs in the tretinoin group than in the placebo group. In all, 30% of those on the retinoid maintained their twice-daily dosing schedules, compared with 42% of those on placebo. Of the tretinoin patients, 15% had stopped using the medication, compared with 9% in the placebo group.
“By 6 months, the patients in the tretinoin group were less likely than were the controls to apply the treatment twice daily, but they were more likely to be using it twice daily than not at all,” Dr. Geng said. “Overall, 0.1% tretinoin is well tolerated, even with twice-daily application. It may be better tolerated in older people who have had keratinocyte cancers than in younger acne patients.”
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