Effect of topically applied T4 endonuclease V in liposomes on skin cancer in xeroderma pigmentosum: a randomised study. Xeroderma Pigmentosum Study Group.

Abstract

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.

FINDINGS:

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.

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 skin of patients with xeroderma pigmentosum lowered the rate of development of two forms of these lesions during a year of treatment.

• Authors: D Yarosh, J Klein, A O'Connor, J Hawk, E Rafal, P Wolf
• Journal: Lancet (London, England) (Lancet) Vol. 357 Issue 9260 Pg. 926-9 (Mar 24 2001) ISSN: 0140-6736 [Print] England
• PMID: 11289350 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Liposomes
• Viral Proteins
• Endodeoxyribonucleases
• endonuclease V, phage T4
• Deoxyribonuclease (Pyrimidine Dimer)

Topics

• Administration, Topical
• Adolescent
• Adult
• Carcinoma, Basal Cell (epidemiology, prevention & control)
• Child
• Child, Preschool
• DNA Repair (drug effects)
• Deoxyribonuclease (Pyrimidine Dimer)
• Double-Blind Method
• Endodeoxyribonucleases (administration & dosage)
• Europe (epidemiology)
• Female
• Humans
• Keratosis (epidemiology, prevention & control)
• Liposomes
• Male
• Middle Aged
• Multivariate Analysis
• Photosensitivity Disorders (epidemiology, prevention & control)
• Prospective Studies
• Regression Analysis
• Skin Neoplasms (epidemiology, prevention & control)
• United States (epidemiology)
• Viral Proteins
• Xeroderma Pigmentosum (drug therapy)