Effect of topically applied T4 endonuclease V in liposomes on skin cancer in xeroderma pigmentosum: a randomised study. Xeroderma Pigmentosum Study Group.
BACKGROUND
In patients with xeroderma pigmentosum the frequency of all forms of skin cancer is higher than in the general population, owing to a genetic defect in DNA repair. The bacterial DNA repair enzyme, T4 endonuclease V, delivered intracellularly, increases the rate of repair of sunlight-induced DNA damage in human cells. We tested the ability of this enzyme in a liposomal delivery vehicle applied topically (T4N5 liposome lotion) to lower the rate of new skin cancers in patients with xeroderma pigmentosum.


METHODS
30 patients were enrolled in this prospective, multicentre, double-blind study. Patients were randomly assigned T4N5 liposome lotion or a placebo liposome lotion, to be applied daily for 1 year. At 3-monthly visits, new actinic keratoses and basal-cell carcinomas were identified and removed. Analyses were by intention to treat.


RESULTS
20 patients were assigned T4N5 liposome lotion and ten placebo lotion; one placebo-group patient withdrew before treatment and one withdrew with progressive disease at 9 months. The annualised rate of new actinic keratoses was 8.2 among the patients assigned T4N5 liposome lotion and 25.9 among those assigned placebo (difference 17.7 [95% CI 11.8-26.5]; p=0.004 by Poisson modelling). For basal-cell carcinoma, the annualised rates of new lesions were 3.8 in the treatment group and 5.4 in the placebo group (difference 1.6 [0.38-2.82]). No significant adverse effects were found among any of the patients.


CONCLUSIONS
DNA damage has an important role in the development of skin cancer and precancerous skin lesions. The topical application of DNA repair enzymes to sun-damaged skin of patients with xeroderma pigmentosum lowered the rate of development of two forms of these lesions during a year of treatment.
Yarosh
D
D
Applied Genetics Incorporated Dermatics, Freeport, NY 11520, USA. danyarosh@agiderm.com
Klein
J
J
O'Connor
A
A
Hawk
J
J
Rafal
E
E
Wolf
P
P
D000287:Administration, Topical; D000293:Adolescent; D000328:Adult; D002280:Basal Cell Carcinoma / Q000453:epidemiology / Q000517:prevention & control; D002648:Child; D002675:Child, Preschool; D004260:DNA Repair / Q000187:drug effects*; D043224:Deoxyribonuclease (Pyrimidine Dimer); D004311:Double-Blind Method; D004706:Endodeoxyribonucleases / Q000008:administration & dosage*; D005060:Europe / Q000453:epidemiology; D005260:Female; D006801:Humans; D007642:Keratosis / Q000453:epidemiology / Q000517:prevention & control; D008081:Liposomes; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010787:Photosensitivity Disorders / Q000453:epidemiology / Q000517:prevention & control; D011446:Prospective Studies; D012044:Regression Analysis; D012878:Skin Neoplasms / Q000453:epidemiology / Q000517:prevention & control*; D014481:United States / Q000453:epidemiology; D014764:Viral Proteins; D014983:Xeroderma Pigmentosum / Q000188:drug therapy*
D008081:Liposomes; D014764:Viral Proteins; D004706:Endodeoxyribonucleases; C470698:endonuclease V, phage T4; D043224:Deoxyribonuclease (Pyrimidine Dimer)