Post-transplant premalignant skin disease tx explored

September 1, 2007

Effective treatment of premalignant epidermal dysplasia can be very challenging, especially in immunocompromised solid organ transplant recipients. A recent study comparing the effects of topical 5% Fluorouracil (5-FU) cream and topical methylaminolaevulinate photodynamic therapy (MAL PDT) showed that MAL PDT is more effective in treating pre-malignant skin lesions in this group of

Key Points

London - Topical methyl aminolaevulinate (MAL) photodynamic therapy (PDT) proves to be extremely effective as well as cosmetically acceptable in the treatment of premalignant epidermal dysplasia in organ transplant recipients (OTR) compared with topical 5 percent fluorouracil (5-FU) cream, according to a leading specialist.

Topical PDT involves activation of a photosensitizer by light to produce reactive oxygen species (ROS) that selectively destroy target precancerous and cancerous cells.

"Organ transplant patients tend to develop many premalignant skin lesions due to their immunocompromised state. Effective treatment of these lesions in OTRs presents a challenge because (treatments) are often extensive and may become confluent, forming large areas of precancerous field change. Although PDT can be painful, it is, nonetheless, a convenient, practical and effective way of treating these areas of dysplasia in this patient group," according to Conal M. Perrett, M.D., department of dermatology and center for cutaneous research, Institute of Cell and Molecular Science at Barts and the London School of Medicine and Dentistry, London.

Dr. Perrett conducted an open-label, single-center, randomized, intra-patient study comparing the effects of 5-FU and MAL-PDT in eight OTRs with widespread epidermal dysplasia, including carcinoma in situ (Bowen's disease) and actinic keratoses.

The study design randomly assigned one area of epidermal dysplasia with a treatment consisting of two cycles of topical MAL-PDT, spaced one week apart. The 5-FU cream was applied twice daily for three weeks to a clinically and histologically comparable area. Patients were reviewed one, three and six months following treatments.

The results showed that at each follow-up, PDT was more effective than 5-FU in achieving complete resolution of the pre-malignant skin lesions. Eight of nine lesional areas cleared with the MAL-PDT treatment (89 percent complete resolution rate), compared with one of nine lesional areas with 5-FU cream (11 percent complete resolution rate). Dr. Perrett also observed that the mean lesional area reduction was proportionately greater with MAL-PDT (100 percent) than with 5-FU (79 percent).

Dr. Perrett says he still continues to use 5-FU cream, particularly in the small number of patients who find PDT too painful. However, many patients find the inflammation associated with 5-FU treatment unacceptable, especially when large areas are treated.

Key benefits

Each MAL-PDT illumination lasts seven minutes and 42 seconds, and patients perceive the pain as moderate to severe.

Dr. Perrett says despite the pain, all study patients expressed an overall preference for PDT over 5-FU.

He adds that the key benefits of PDT are that physicians can treat large areas in one or two visits (one or two treatments) spaced approximately seven days to 10 days apart.

However, there remain some outstanding issues regarding PDT in OTRs. Because the host immune response is important in PDT, it follows that the long- term efficacy of PDT in OTRs may be reduced because they are immunocompromised. Also, as with any new treatment, long-term safety data on the use of PDT in OTRs is not yet available.