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

Lancet. 2001 Mar 24;357(9260):926-9. doi: 10.1016/s0140-6736(00)04214-8.


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.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

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


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