case example are reproduced as Figure 1.
Tschen et al, conducted a phase 4 open-label study of 110 patients with 6 to 12 AKs on the face or scalp.20 Patients were treated with ALA-PDT and followed with monthly visits for 12 months. Any treated lesions that remained at month 2 were retreated with ALA-PDT; 66% of these patients received a second treatment at month 2. Lesions that did not respond to treatment were biopsied at month 3.20 Seventy-six percent (76%) of target lesions were completely cleared at month 1 and 72% at month 2; complete clearance peaked at month 4 at 86% of lesions and then declined gradually to 78% of all lesions at month 12. The percent of patients with complete clearance (100% of target lesions) was 67% at month 3 and declined to 40% at month 12. Beginning at month 6, clearance rates were slightly higher in patients with skin types I and II compared with skin types III and IV.20 The percentage of lesions that cleared was similar for grade 1 and grade 2 lesions.
Jiang et al, investigated treatment with ALA-PDT or vehicle-PDT in patients with 4 to 15 grade 1 or 2 AKs on one upper extremity.15 Among patients who received a second treatment, the mean AK lesion clearance rate in patients who received ALA was 69.1% at week 12, compared with 29.9% in vehicle-treated patients (P <0.0001).15 The number of patients who experienced complete clearance was also significantly greater in those who received ALA vs vehicle (P=0.0001).15
In a post hoc analysis of a phase 3 study of 269 patients with 4–15 grade 1–2 AKs on an upper extremity, patients were treated with ALA-PDT or vehicle-PDT, applied twice. Treatment was also applied at week 8 if lesions were present in the treatment area.1 At weeks 8 and 12, AK clearance rates were significantly greater in patients who received ALA-PDT vs vehicle-PDT. At week 12, the clearance rates were 80.6% in those receiving ALA-PDT and 45.5% in those receiving vehicle-PDT. Cumulative disease area cleared was also greater in those who received ALA-PDT. Results were similar across all baseline lesion sizes.1
Efficacy in High-Risk Patients
Piacquadio conducted a phase 2 trial in patients at high risk for progression to NMSC. Patients had 4–15 facial AKs grade 1–3 and had been previously been treated for NMSC in a sunexposed area.21 A total of 166 patients underwent cryotherapy at screening and then were randomized to treatment with ALA-PDT or vehicle-PDT applied 2 times (baseline and week 4) or 3 times (baseline, week 4, and week 24).21 Compared with vehicle-PDT treatment, ALA-PDT treatment performed 3 times significantly reduced the rate of new and recurrent AKs at 52 weeks.21 Complete clearance rates at week 52 were 36% for ALA 2x, 37.5% for ALA 3x, and 18.9% for vehicle (P ≤0.01 for each ALA treatment vs vehicle).21
Clinical Safety
The safety profile of ALA-PDT includes consideration of the immediate and short-term effects of PDT, ALA, and ALA-PDT as well as potential long-term effects of treatment, particularly the development of NMSC. However, long-term NMSC rates have only been reported in more recent trials.
Early-Onset Side Effects
Common early-onset side effects of PDT include pain and local skin reactions (erythema, edema, desquamation, and pustules). These effects often occur within hours or days of exposure to PDT and can negatively impact patient satisfaction.17
In the trial of patients with AK on the face or scalp by Piacquadio et al, adverse events (AEs) were similar in patients treated with either ALA or vehicle.19 The overwhelming majority of AEs (92%) were mild or moderate; 97% of AEs were considered unrelated to ALA treatment. The most common AEs related to treatment were headache, dry skin, and conjunctivitis.19 Patient discomfort due to PDT (eg, stinging and burning during PDT treatment) was reported by >90% of patients receiving ALA-PDT; only 28% reported any discomfort after 24 hours. Other common local responses included erythema, edema, crusting, pruritis, and scaling.19 Rates of SCC or BCC diagnosis following treatment were not reported.
In the open-label study reported by Tschen et al, AEs associated with PDT were common immediately after treatment; 95% of
