Prolonged adverse events following photodynamic therapy: regulatory implications.

Objective: To determine whether field photodynamic therapy (PDT) of actinic keratoses (AKs) using a novel preparation of 5-aminolevulonic acid (ALA) would result in fewer subsequent invasive skin cancers developing on the face.
Design: A prospective multi-center randomized controlled trial. The protocol was approved by the Bond University Human Research Ethics Committee in accord with the TGA's Clinical Trial Notification Scheme. The trial was registered (12609000025235) on the Australian New Zealand Clinical Trials Registry.
Setting: Six centers in four states in Australia.
Protocol: Two treatments of ALA PDT, 2 weeks apart for each patient. Controls were observed. Patients were followed up with biopsies of any suspicious lesions every 6 months for 2 years.
Main Outcome Measure(s): Development of new skin cancers.
Results: The trial was suspended after 3 months and closed after 6 months after ethics committee approval was withdrawn on the basis of a breakdown in trial governance. Over the following 2 years, some investigators noted and formally reported the continued occurrence of serious adverse events in excess of those described with other approved cutaneous PDT treatments. USA dermatologists with experience managing AKs with FDA approved ALA products subsequently confirmed prolonged and severe adverse events in 6 of the former trial intervention patients.
Discussion and Conclusions: Adverse effects experienced by patients using the investigational ALA PDT appeared more severe than those experienced when an FDA-approved ALA product is used. We believe the former should be further evaluated for safety. It is of concern that this ALA product and lamp could be promoted and used widely in Australia following these reports of significant adverse events and continued lack of TGA approval.