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

• Published in: The Lancet (British edition) Vol. 357; no. 9260; pp. 926 - 929
• Main Authors: Yarosh, Daniel, Klein, Jonathan, O'Connor, Adrienne, Hawk, John, Rafal, Elyse, Wolf, Peter
• Format: Journal Article
• Language: English
• Published: London Elsevier Ltd 24.03.2001; Lancet; Elsevier Limited
• Subjects: Biological and medical sciences; Clinical trials; Deoxyribonucleic acid; Dermatology; DNA; Enzymes; Immune system; Infertility; Lesions; Medical sciences; Pharmacology. Drug treatments; Pigmentary diseases of the skin; Skin cancer; Skin, nail, hair, dermoskeleton; United States; North America; Europe; America; Human; Photosensitivity; Chemoprophylaxis; Skin disease; Pigmentation disorder; Enzyme; Treatment efficiency; Multicenter study; Xeroderma pigmentosum; Malignant tumor; Genetic disease; Percutaneous route; Prevention; Photodermatosis; Concomitant disease; Chemotherapy; Treatment; Follow up study; Double blind study; Adult; Skin; Public health
• ISSN: 0140-6736; 1474-547X
• DOI: 10.1016/S0140-6736(00)04214-8

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. 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. 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. 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.