This study evaluated the efficacy and safety of short incubation methyl aminolevulinate photodynamic therapy without occlusion for the treatment of actinic keratoses. Twenty patients with actinic keratoses on the face received methyl aminolevulinate application followed by red light 90 minutes later without occlusion. At 12 weeks, there was a significant reduction in the number of actinic keratoses and improvement in photoaging, with a 69% complete lesion response rate. Treatment was well tolerated with few adverse events reported.

1. POSTER P2361
SHORT INCUBATION METHYL AMINOLEVULINATE
PHOTODYNAMIC THERAPY WITHOUT OCCLUSION
FOR THE TREATMENT OF ACTINIC KERATOSES
Robert Bissonnette, MD, FRCPC
Simon Nigen, MD, FRCPC
Chantal Bolduc, MD, FRCPC
Catherine Maari, MD, FRCPC
Innovaderm Research, Montreal, Canada
The authors of this poster have received grants and/or honoraria from DUSA Pharmaceuticals, Galderma Canada, Graceway and
Photocure ASA.
This study was funded by a grant from and study medication was provided by Galderma Canada Inc.

2. Introduction
• Actinic keratoses (AK) are precursors of squamous cell
carcinoma frequently found in fair skin individuals1
• Photodynamic therapy with methyl aminolevulinate (MAL-
PDT) is approved for the treatment of AKs:
• MAL forms photoactive porphyrins;
• Photoactivation of porphyrins induces cytotoxic effects in
malignant cells;
• Complete lesional response rates of 83-93%2-6
.
– Approved treatment protocol7
:
• MAL application to individual lesions plus 5 mm adjacent
border;
• Occlusion for 3 hours after MAL application;

3. Introduction
• Rationale for the current study:
– Application of MAL with occlusion is difficult for patients
with numerous and widespread AKs
– Strong phototoxic reactions are sometimes observed
after 3-hour incubation which is problematic if large
surfaces are treated
– A 3-hour incubation implies a fairly long waiting period
between MAL application and light exposure for
patients and clinicians

4. Introduction
• Primary Objective:
– Study the efficacy of MAL-PDT performed without occlusion when red light
exposure takes place 90 minutes after the application of MAL.
• Secondary Objectives:
– Study the safety of MAL-PDT performed without occlusion when red light
exposure takes place 90 minutes after the application of MAL.
– Study the effect of MAL-PDT on photoaging/photodamage when MAL-
PDT is performed without occlusion when red light exposure takes place
90 minutes after the application of MAL

5. • Phase IIIb, open-label study;
• 20 patients, 18 years of age or older;
• Treatment procedure (Day 0 and Week 4):
- Mapping of AKs on a transparent template;
- Application of MAL (2-4 g) on entire face, except the nose,
without occlusion;
- Incubation time: 90 minutes followed by
- Exposure to 37 J/cm2
of 630 nm red light (Aktilite)
• Patients were seen at Day 0 and Weeks 4, 12 and 24
Study Design

6. • Main inclusion / exclusion criteria:
– At least 5 non-hypertrophic AKs on the face
– Absence of malignant skin lesions on the face
– Absence of excessive facial hair (beard)
– Fitzpatrick phototype of I, II or III;
– No clinically significant sensitivity to visible light or porphyrin;
– Absence of porphyria
– No photodynamic therapy for 8 weeks before Day 0
– No exposure to UV radiation, cryotherapy, surgery to face or
topical treatment for AKs for 4 weeks before Day 0
Study Design

7. • Day 0:
– AK mapping;
– Clinical Photography
– MAL application and red light exposure.
• Weeks 4 and 12:
– AKs response evaluation;
– Photoaging assessed with Griffiths photonumeric scale8
and a descriptive scale8
;
– Safety evaluated by collecting adverse events.
– Treatment procedure repeated if incomplete response to first treatment
(Week 4 only)
– Clinical photography (Week 12 only)
• Week 24:
– AKs recurrence evaluation
– SAE evaluation
Study Procedures

8. Endpoints
• Primary Endpoint:
– Mean number of facial AK at Week 12 as compared to Day 0.
• Secondary Endpoints:
– Proportion of patients with complete clinical response of all AKs at Week 12;
– Proportion of lesions with complete clinical response at Week 12;
– Mean Griffiths photonumeric scale for photodamage score at Week 12 as
compared to Day 0;
– Mean fine wrinkling score at Week 12 as compared to Day 0;
– Mean coarse wrinkling score at Week 12 as compared to Day 0;
– Mean sallowness score at Week 12 as compared to Day 0;
– Mean mottled hyperpigmentation at Week 12 as compared to Day 0.

9. Methods – Efficacy Evaluations
• Evaluation of Mapped Actinic Keratoses
– Efficacy evaluated by noting the presence or absence of each AK mapped at
baseline
– Patients examined in a well lit room without the aid of magnification
– Care taken to have the same assessor for all visits for each subject.
• Photonumeric and Descriptive Scales for Photodamage
– Effect of MAL-PDT on photodamage evaluated by using the Griffiths photonumeric
scale8
and a descriptive scale8
for photodamage.
• Griffiths scale was evaluated on a scale from 0 to 8 where zero means little or no
photodammage.
• The following descriptive scale parameters ( fine wrinkling, coarse wrinkling, and mottled
hyperpigmentation) were assessed individually from 0-9 (where zero means little or no
photodamage). Sallowness represents a visual assessment of color tone from very pink
or rosy (0) to very sallow or pale (9).

10. Results - Demographics
Demographic values
N 20
Male - n (%) 16 (80)
Age (mean ± SD) 65.3 ± 10.7
Caucasian - n (%) 20 (100)
Phototype I - n (%) 3 (15)
Phototype II - n (%) 11 (55)
Phototype III - n (%) 6 (30)

11. Proportion of complete clinical responsesMean number of facial AK lesions per patient
All patients received a second MAL-PDT treatment at Week 4.
*Significant difference between Day 0 and Week 12 (p=0.001)
*
Complete lesional response at Week 4 = 58.7% (95% CI 50.0
– 68.4) and at Week 12 = 69.1% (95% CI 57.1 – 81.2).
Results – Efficacy
Primary and Secondary Endpoints

12. Results – Efficacy
Secondary Endpoints
* **
***
*P=0.002 , **P=0.012 and *** P<0.001.
(As compared to Day 0).

13. Results – Efficacy
Day 0 Week 12
Patient received 2 treatments 4 weeks apart.

14. Results – Efficacy
Day 0 Week 12
Patient received 2 treatments 4 weeks apart.

15. Safety
• No patients withdrew from the study;
• One serious adverse event reported:
– (pneumonia – not related to study treatment);
• Treatment was generally well tolerated.

16. Safety
Adverse Events Number of patients
Application site crusting* 1 (5%)
Application site burning sensation*,
** 1 (5%)
Application site erythema* 1 (5%)
Common cold 3 (15%)
Erythema of the chin* 1 (5%)
Pneumonia 1 (5%)
Squamous cell carcinoma on face 1 (5%)
Sore Throat 1 (5%)
Vitreous detachment left eye 1 (5%)
* Treatment related adverse events **Burning caused interruption of treatment.

17. Conclusion
• PDT with MAL applied on the entire face without occlusion and with a 90 minutes incubation was:
– Effective for treatment of actinic keratoses
• Significant difference between mean number of AK at Day 0 and Week 12 (p=0.001).
• Complete lesional response at Week 12 was 69.1% (95% CI 57.1 – 81.2)
• Complete patient response at Week 12 was 15.0% (95% CI 5.2 – 36.0)
– Resulted in improvement in photo-aging
• Significant improvement in overall photo-aging (Griffiths scale) according to time (p=0.002)
• Reduction in fine wrinkling at week 12 (p<0.001)
– Well tolerated
• The current study did not directly compare the 90 minutes no-occlusion no-lesion preparation
regimen to the approved 3-hour under occlusion MAL-PDT treatment. However the 69%
observed complete lesional response with 90-min no-occlusion is only slightly inferior to the 86%2
and 83%6
lesion response previously reported for MAL under occlusion for 3 hours.
• This treatment strategy should be further explored for patients with numerous and widespread
facial AK;

18. References
1. Touma D, Yaar M, Whitehead S, et al. A trial of short incubation, broad-area photodynamic therapy for facial actinic
keratoses and diffuse photodamage. Arch Dermatol. 2004;140:33-40.
2. Pariser D, Loss R, Jarratt M, et al. Topical methyl-aminolevulinate photodynamic therapy using red light-emitting diode light
for treatment of multiple actinic keratoses: A randomized, double-blind, placebo-controlled study. J Am Acad Dermatol. 2008;
59:569-76.
3. Pariser DM, Lowe NJ, Stewart DM et al. Photodynamic therapy with topical methyl aminolevulinate for actinic keratosis:
results of a prospective randomized multicenter trial. J Am Acad Dermatol. 2003; 48: 227-32.
4. Tarstedt M, Rosdahl I, Berne B, Svanberg K. Wennberg AMA randomized multicenter study to compare two treatment
regimens of topical methyl aminolevulinate (Metvix)-PDT in actinic keratosis of the face and scalp. Acta Derm Venereol.
2005; 85: 424-8.
5. Freeman M, Vinciullo C, Francis D et al. A comparison of photodynamic therapy using topical methylaminolevulinate (Metvix)
with single cycle cryotherapy in patients with actinic keratosis: a prospective, randomized study. J Dermatolog Treat. 2003;
14:99-106.
6. Szeimies RM, Matheson RT, Davis SA, et al. Topical Methyl Aminolevulinate Photodynamic Therapy Using Red Light-
Emitting Diode Light for Multiple Actinic Keratoses: A Randomized Study. Dermtol Surg 2009;35:586-92.
7. Galderma Canada Inc. Methyl aminolevulinate topical cream – Product Monograph. 2009. Retrieved Feb 23, 2011 from
http://webprod.hc-sc.gc.ca/dpd-bdpp/info.do?lang=eng&code=80876.
8. Griffiths CE, Wang TS, Hamilton TA, et al. A photonumeric scale for the assessment of cutaneous photodamage. Arch
Dermatol. 1992;128:347-51.