Chemotherapy Drug May Improve Appearance Of Sun Damaged Skin, Study

Researchers in the US found that the chemotherapy drug fluorouracil appeared to reduce the appearance of sun-damaged and aging skin as well as the number of potentially pre-cancerous skin patches.

The study was the work of Dr Dana L Sachs, associate professor in the Department of Dermatology at the University of Michigan, Ann Arbor, and colleagues, and is published in the 6 June issue of Archives of Dermatology, one of the Journal of the American Medical Association/Archives journals.

Fluorouracil, which is used in chemotherapy treatment of cancers of the colon, head and neck, pancreas and other organs, stops the body being able to make thymine, a building block of DNA. Researchers studying cancer patients having treatments with fluorouracil have noticed changes in skin appearance and as a result of this the drug was developed as a skin cream to treat potentially pre-cancerous skin patches.

For this study, Sachs and colleagues asked 21 healthy volunteers with sun-damaged skin and lesions to apply 5 per cent fluorouracil cream to the face twice a day for two weeks and regularly examined their skin for molecular and clinical changes during this time and also for another 22 weeks afterwards.

This included taking biopsies, taking photographs and doing clinical evaluations at the start and then at intervals during the treatment period.

19 of the volunteers completed all parts of the study and 20 filled in questionnaires at week 10.

Three dermatologists who were not part of the research team who examined the volunteers during the study were invited to evaluate the photographs which were taken at the end of week 1, 2, 4, 6, 10 and 24 of the study.

The results showed that:

* The number of lesions at the end of treatment was significantly lower than the number at the start of treatment.

* This went down from an average of 11.6 lesions per volunteer to an average of 1.5.

* The clinical evaluation identified overall improvements in aging-related damage.

* This included reductions in wrinkling, dark skin spots, skin that has become darker (hyperpigmentation) and sallowness (when the skin tone goes yellow).

* Skin biopsies taken just after the end of treatment showed an increase in the compounds that are produced when skin is injured and inflamed and when the non-living tissue that acts like a "scaffold" for living skin cells, the extracellular matrix, breaks down.

* After this stage, levels of a collagen precursor called procollagen, appeared to increase (collagen is the main protein in skin and tends to lessen when skin is photo-damaged, also it fragments and degrades as skin ages).

* The treatment was well tolerated and according to the questionnaire they filled in during week 10, 95 per cent of the volunteers rated their skin as improved while 89 per cent said they would be willing to have the treatment again.

The authors concluded that:

"Topical fluorouracil causes epidermal injury, which stimulates wound healing and dermal remodeling resulting in improved appearance. The mechanism of topical fluorouracil in photoaged skin follows a predictable wound healing pattern of events reminiscent of that seen with laser treatment of photoaging."

They noted that patients who receive fluorouracil treatment for skin lesions are likely also to benefit from a reduction in sun-damage, a side-effect that may motivate them to persevere with the "rigorous" treatment. It is also possible that for some patients the drug could have an important role against photo-aging, they commented.

But some patients may not be prepared to endure two or three weeks with the cream on their face or other part of their skin, and then the rather unsightly after effects for several more weeks, while others may be prepared to do it if the cost proves to be much lower than ablative laser resurfacing. For the typical patient the skin gets dry, it itches and peels for several weeks before it recovers and gets softer.

The study was sponsored by Valeant Pharmaceuticals International who make Efudex, the cream that was used.

"Topical Fluorouracil for Actinic Keratoses and Photoaging: A Clinical and Molecular Analysis."
Dana L. Sachs; Sewon Kang; Craig Hammerberg; Yolanda Helfrich; Darius Karimipour; Jeffrey Orringer; Timothy Johnson; Ted A. Hamilton; Gary Fisher; John J. Voorhees.