Gene Expression in Renal Transplant Patients With Field Actinic Keratosis Undergoing Metvix® Photodynamic Therapy (PDT)

The aim of this study is to determine possible molecular changes on large scale gene expression profiling after treatment with Metvix photodynamic therapy (PDT) of actinic keratoses (AK) and cancerised field in renal transplant recipients.

Transplant recipients have an increased propensity to develop multiple areas field of cancerisation and subsequently to develop multiple actinic keratoses, which demonstrate an increased transformation rate into invasive squamous cell carcinoma (SCC). The incidence of cutaneous premalignant epithelial lesions such as actinic keratosis (AK) is increased compared with the immunocompetent population with a mean occurrence of 38% after 5 years of immunosuppression, compared with <5% in the immunocompetent patients. Since the development of multiple AKs may portend further possibility extensive cutaneous carcinogenesis, early and aggressive treatment is essential to prevent the progression to invasive SCC.

Although they may occur as single lesion, multiple actinic keratoses (AKs) are commonly present in areas of chronic actinic damage (field of AKs or field of cancerisation). The concept of "field cancerisation" suggests that the clinically normal appearing skin around AKs provides the basis for clonal expansion of genetically altered neoplastic cells. This is called sub-clinical AK lesions.

In this study, the whole target area defined by the investigator will be treated by Metvix PDT: this means that both lesions and sub-clinical lesions will be exposed to Metvix PDT. Biopsies will be performed in both regions: lesional and peri-lesional ones. This will allow us to compare pre and post treatment molecular changes that occurred in these regions and so to evaluate if Metvix PDT acts on the sub-clinical lesions.

Inclusion Criteria:

• Renal transplant with an history of immunosuppression from 5 to 15 years,
• Presenting at least 4 discrete AK lesions, mild or moderate, either on the face, the scalp, forearms or the chest.

Exclusion Criteria:

• At risk in terms of precautions, warnings, and contra-indication referred in the package insert of Metvix®,
• AK lesions clinically atypical or suspicious for malignancy on the target field,

• Any of the following topical treatments within the specified washout period at Screening:

  • 5-FU, Imiquimod, Diclofenac sodium: 3 months,
  • Cryotherapy: 3 months,
  • PDT: 3 months,
  • Other less common AK treatments: 3 months.
• Systemic retinoids within the last month prior to Screening visit.