Effect of topically applied T4 endonuclease V in liposomes on skin cancer in xeroderma pigmentosum: a randomised study

Background In patients with xeroderma pigmentosum the frequency of all form s of skin cancer is higher than in the general population, owing to a genet ic defect in DNA repair. The bacterial DNA repair enzyme, T4 endonuclease V , delivered intracellularly, increases the rate of repair of sunlight-induc ed DNA damage in human cells. We tested the ability of this enzyme in a lip osomal delivery vehicle applied topically (T4N5 liposome lotion) to lower t he 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 plac ebo liposome lotion, to be applied daily for 1 year. At 3-monthly visits, n ew actinic keratoses and basal-cell carcinomas were identified and removed. Analyses were by intention to treat. Findings 20 patients were assigned T4N5 liposome lotion and ten placebo lot ion; one placebo-group patient withdrew before treatment and one withdrew w ith progressive disease at 9 months. The annualised rate of new actinic ker atoses was 8.2 among the patients assigned T4N5 liposome lotion and 25.9 am ong 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 l esions were 3.8 in the treatment group and 5.4 in the placebo group (differ ence 1.6 [0.38-2.82]). No significant adverse effects were found among any of the patients. Interpretation 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 shin of patients with xeroderma pigmentosum lowered the rate of development of two forms of these lesions during a year of tre atment.