Clinical efficacy of methyl aminolevulinate (Metvix) photodynamic therapy

Several studies have reported the efficacy of photodynamic therapy (PDT) in the treatment of non-melanoma skin cancer (NMSC) and pre-cursor lesions, such as actinic keratosis (AK). Recent studies investigating the use of methyl aminolevulinate (MAL, Metvix PDT have made comparisons to existing standard treatments for basal cell carcinoma (BCC) and AK in terms of efficacy, adverse events and cosmetic outcome. This review considers these studies as a body of evidence that supports the use of MAL PDT over traditional therapies in these conditions. The data thus far show PDT to be superior to cryotherapy, 5-fluorouracil (5FU) and excisional surgery in terms of cosmetic outcome, and equivalent in efficacy to other treatment modalities in managing AK and BCC. The studies also show an advantage in the treatment of extensive lesions.     

A clinical study comparing methyl aminolevulinate photodynamic therapy and surgery in small superficial basal cell carcinoma (8–20 mm), with a 12‐month follow‐up.

Objective To compare the efficacy and cosmetic outcome (CO) of photodynamic therapy with topical methyl aminolevulinate (MAL‐PDT) with simple excision surgery for superficial basal cell carcinoma (sBCC) over a 1‐year period. Methods In this multicentre, randomised, controlled, open study, patients were treated at baseline either with MAL‐PDT (two sessions, 7 days apart, repeated 3 months later if incomplete clinical response) or surgery (at baseline). Primary endpoints were clinical lesion response (CR) 3 months after last treatment and CO assessed by the investigator 12 months after last treatment. Secondary endpoints were CR at 12 months (i.e. recurrence) and CO assessed by the investigator at 3 and 6 months and by the patient at 3, 6 and 12 months. Results Overall, 196 patients were enrolled with 1.4 sBCC lesions on average per patient. Mean lesion count reduction at 3 months was 92.2% with MAL‐PDT vs. 99.2% with surgery [per protocol (PP) population] confirming the non‐inferiority hypothesis (95% confidence interval, –12.1, –1.9). A total of 92.2% lesions showed CR at 3 months with MAL‐PDT vs. 99.2% with surgery (PP population). At 12 months, 9.3% lesions recurred with MAL‐PDT and none with surgery. CO was statistically superior for MAL‐PDT at all time points. At 12 months, 94.1% lesions treated with MAL‐PDT had an excellent or good CO according to the investigator compared with 59.8% with surgery. This difference was confirmed with the patients’ assessment. The proportion of excellent CO markedly improved with time with MAL‐PDT unlike surgery. Conclusions MAL‐PDT offers a similarly high efficacy and a much better CO than simple excision surgery in the treatment of sBCC.     

Allergic contact dermatitis to methyl aminolevulinate (Metvix) cream used in photodynamic therapy

Topical photodynamic therapy (PDT) is increasingly used in the treatment of superficial skin malignancies including actinic keratosis, Bowen's disease and superficial basal cell carcinoma. Contact allergy to the prodrug is rarely reported. We report a case of allergic contact dermatitis to methyl aminolevulinate cream used in PDT.     

Real-life practice study of the clinical outcome and cost-effectiveness of photodynamic therapy using methyl aminolevulinate (MAL-PDT) in the management of actinic keratosis and basal cell carcinoma

Clinical trials have shown that photodynamic therapy using methyl aminolevulinate (MAL-PDT) is an effective treatment for actinic keratosis (AK), and nodular and superficial basal cell carcinoma (nBCC and sBCC) unsuitable for other available therapies. Economic evaluation models have shown that it is a cost effective intervention as well. The objectives of this prospective, observational, one arm study were (i) to verify in a real-life practice study the results obtained in previous clinical trials with MAL-PDT in the treatment of AK, nBCC and sBCC; (ii) to calculate the real-life cost of treatment and validate predictions from an economic evaluation model. Patients with AK and/or BCC were selected according to Belgian reimbursement criteria for treatment with MAL-PDT. Clinical response, cosmetic outcome and tolerability were assessed. MAL-PDT cost was calculated and compared to published model cost data. Data were collected from 247 patients (117 AK, 130 BCC). A complete clinical response was obtained for 83% of AK (85/102) and BCC (97/116) patients. A good or excellent cosmetic outcome was obtained for 95% of AK patients and 93% of BCC patients. Tolerability was good: only 2 patients withdrew for adverse events. Clinical results were similar to previous studies. Total cost of care per patient was euro381 for AK, euro318 for nBCC, and euro298 for sBCC. Total cost per lesion was euro58 for AK (identical to model prediction), euro316 for nBCC and euro178 for sBCC (both within 20% of model prediction). The clinical results of MAL-PDT in this real-life practice study confirm those demonstrated in previous clinical trials. Costs calculated from this study confirm predicted cost-effectiveness in the original model for MAL-PDT in the management of AK and BCC.     

Long‐term follow‐up of photodynamic therapy with a self‐adhesive 5‐aminolaevulinic acid patch: 12 months data

Background Photodynamic therapy with a self‐adhesive 5‐aminolaevulinic acid (5‐ALA) patch shows high efficacy rates in the treatment of mild to moderate actinic keratosis (AK) in short term trials. Objectives The purpose of the trial was to follow up patients after successful 5‐ALA patch‐PDT at 3 month intervals over a total period of 12 months. Patients who had received placebo‐PDT or cryosurgery served for comparison. Patients/methods Three months after therapy, 360 patients from two separate randomized parallel group phase III studies (one superiority trial vs. placebo‐PDT, one noninferiority trial vs. cryosurgery) were suitable for the follow‐up study. Patients had to show at least one successfully treated AK lesion after initial therapy. A total of 316 patients completed the follow‐up. Results Twelve months after a single treatment, 5‐ALA patch‐PDT still proved superior to placebo‐PDT and cryosurgery (P < 0·001 for all tests). On a lesion basis, efficacy rates were 63% and 79% for PDT, 63% for cryosurgery and 9% and 25% for placebo‐PDT. Recurrence rates of patch‐PDT proved superior to those of cryosurgery (per protocol set: P = 0·011, full analysis set: P = 0·049). While 31% of cryosurgery lesions were still hypopigmented after 1 year, the 5‐ALA patch‐PDT groups showed hypopigmentation in 0% (superiority trial) and 3% (noninferiority trial) of the treated lesions. Conclusion Twelve months after a single 5‐ALA patch‐PDT the majority of lesions were still cleared with an excellent cosmetic outcome. 5‐ALA patch‐PDT proved to be superior to cryosurgery in the noninferiority study setting.     

Long‐term (6 and 12 months) follow‐up of two prospective,randomized, controlled phase III trials of photodynamic therapy with BF‐200 ALA and methyl aminolaevulinate for the treatment of actinic keratosis

Summary Background Two phase III trials of photodynamic therapy (PDT) with BF‐200 ALA, a recently approved nanoemulsion formulation of 5‐aminolaevulinic acid (ALA) demonstrated high clearance rates in mild‐to‐moderate actinic keratosis (AK). The comparison to a registered methyl aminolaevulinate (MAL) cream demonstrated significantly superior total patient clearance rates. Objectives To evaluate long‐term efficacy and safety of PDT for AK 6 and 12 months after the last PDT with BF‐200 ALA, MAL or placebo. Methods The follow‐up phase (FUP) was performed with patients of two phase III studies. Both studies compared BF‐200 ALA with placebo, one of the studies additionally with MAL. Overall recurrence rates and various subgroups (light source, lesion severity, lesion location, complete responders after first PDT) were assessed 6 and 12 months after the last PDT. Results Recurrence rates were similar for BF‐200 ALA and MAL, with a tendency to lower recurrence rates for BF‐200 ALA. The proportion of patients who were fully cleared during PDT and remained completely clear for at least 12 months after PDT were 47% for BF‐200 ALA (both studies) and 36% for MAL treatment. The subgroup that was illuminated with narrow wavelength LED lamps reached 69% and 53% for BF‐200 ALA (both studies, respectively) and 41% for MAL. No safety concerns were reported. Conclusions The FUP data confirmed the high efficacy and safety of PDT with BF‐200 ALA. The slightly lower recurrence rates after BF‐200 ALA treatment compared with MAL treatment enhanced the better treatment outcome due to the significantly superior efficacy.     

Daylight photodynamic therapy with 1.5% 3‐butenyl 5‐aminolevulinate gel as a convenient,effective and safe therapy in acne treatment: A double‐blind randomized controlled trial

While daylight photodynamic therapy (PDT) is a simpler and more tolerable treatment procedure for both clinicians and patients, it has never been applied for acne treatment. In this study, we evaluated efficacy, safety and histological changes of facial acne after application of the novel variant of 5‐aminolevulinate (ALA)‐ester, 1.5% 3‐butenyl ALA‐bu gel, using daylight only as the potential visible light source. Forty‐six acne patients were randomly assigned to either ALA‐bu or vehicle application group in a double‐blind fashion. Both groups applied the allocated gel to facial acne lesions every other day for 12 weeks. At the final 12 week, both inflammatory and non‐inflammatory acne lesions had decreased significantly by 58.0% and 34.1% in the ALA‐bu group, respectively. Only a few patients expressed mild adverse effects. In the histopathological analysis, attenuated inflammatory cell infiltrations were observed and immunostaining intensities for interleukin‐8, interleukin‐1β, matrix metalloproteinase‐9 and phosphorylated nuclear factor‐κB were reduced concomitantly. Changes of their mRNA expression demonstrated comparable patterns. In conclusion, this ambulatory PDT was effective, very well tolerated and convenient for treating inflammatory acne lesions. Experimental results correlated well with clinical results. This novel regimen would provide a viable option for acne therapy.