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`DOI: 10.1111/j.1468-3083.2009.03259.x
`
`JEADV
`
`Blackwell Publishing Ltd
`
`ORIGINAL ARTICLE
`Intraindividual, right–left comparison of topical 5-aminolevulinic
`acid photodynamic therapy vs. 5% imiquimod cream for actinic
`keratoses on the upper extremities
`
`E Sotiriou,* Z Apalla, F Maliamani, N Zaparas, D Panagiotidou, D Ioannides
`
`1st Dermatology Department, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece
` E Sotiriou.
` elenasotiriou@yahoo.gr
`*Correspondence:
`E-mail:
`
`
`
`Actinic keratoses (AKs) are considered as in situ squamous cell carcinoma. Early and effective treatment is
`
`
`
`Abstract
`Backround
`important.
`Objective
`To compare the efficacy, cosmetic outcome and patient preference of 5-aminolevulinic acid photodynamic
`therapy (ALA-PDT) with that of 5% imiquimod (IMIQ) cream in patients with AKs on the dorsa of hands and forearms.
`Methods
`Subjects received two ALA-PDT treatment sessions and one or two courses of imiquimod (three times per
`week for 4 weeks each). Treatments were randomly allocated to alternate upper extremities. Assessments included lesion
`response one and six months after treatment, cosmetic outcome evaluated by the investigators and patients’ preference
`6 months after treatment. Efficacy end point included the individual AK lesion clearance rate.
`Results
`Thirty patients with 256 lesions were included in the study. At the first follow-up, treatment with ALA-PDT
`resulted in significantly larger rate of cured lesions relative to 5% IMIQ cream (70.16% vs. 18.26%). At the second
`follow-up both treatments showed a high rate of cured lesions (65.32% for PDT vs. 55.65% for IMIQ cream). Response
`rates obtained in grade I lesions were higher for both treatments (71.64% for PDT vs. 72.13% for IMIQ), while treatment
`with PDT resulted in a significant larger rate of cured grade II lesions (57.89% for PDT vs. 37.03 for IMIQ).
`Difference in cosmetic outcome was not statistically significant. Results for subject preference favoured ALA-PDT.
`Conclusions
`Our study shows that ALA-PDT and 5% IMIQ cream are both attractive treatment options for upper
`extremities AKs with comparable efficacy and cosmetic outcomes.
`Received: 28 November 2008; Accepted 13 February 2009
`
`Keywords
`actinic keratosis, extremities, imiquimod, photodynamic therapy, treatment
`
`Conflicts of interest
`.
`None declared
`
`The term actinic keratosis refers to a sun-induced clinical
`erythematous lesion covered with scale. Histologically, it represents
`an intraepidermal malignant neoplasm with proliferation of
` Epidemiological data show a significant
`atypical keratinocytes.
`1
`prevalence of actinic keratoses among the Caucasian population.
`In Europe, a prevalence of 15% in men and 6% in women has been
`documented.
` Rates of malignant transformation of actinic
`2
`keratoses are considerable: approximately 10% of actinic keratoses
`in immunocompetent patients progress into invasive squamous
`cell carcinoma (SCC), while progression rates raise to 40% in
`immunocompromized patients.
` Early identification and treatment
`3
`are therefore advisable as it is impossible to predict which lesions
`may become invasive and develop into metastatic SCC. Moreover,
`
`an effective treatment that leads to good cosmesis is important
`because of the cosmetically sensitive sites of actinic keratoses’
`development.
`Therapies established for the treatment of actinic keratoses
`include both ablative procedures (surgery, laser ablation,
`curettage, cryotherapy) and topical treatments [photodynamic
`therapy (PDT), 5-fluorouracil, diclofenac 3% gel, 5% imiquimod
`cream].
`PDT is a non-invasive and precisely directed treatment. The
`procedure involves activation of a photosensitizing agent by
`visible light, with subsequent release of reactive oxygen species,
`which in turn produce local tissue destruction. PDT has the ability
`to treat large skin areas, while previous clinical studies showed
`
`JEADV
` 2009,
`, 1061–1065
`23
`
`© 2009 The Authors
`Journal compilation © 2009 European Academy of Dermatology and Venereology
`
`

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`DOI: 10.1111/j.1468-3083.2009.03259.x
`
`JEADV
`
`Blackwell Publishing Ltd
`
`ORIGINAL ARTICLE
`Intraindividual, right–left comparison of topical 5-aminolevulinic
`acid photodynamic therapy vs. 5% imiquimod cream for actinic
`keratoses on the upper extremities
`
`E Sotiriou,* Z Apalla, F Maliamani, N Zaparas, D Panagiotidou, D Ioannides
`
`1st Dermatology Department, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece
` E Sotiriou.
` elenasotiriou@yahoo.gr
`*Correspondence:
`E-mail:
`
`
`
`Actinic keratoses (AKs) are considered as in situ squamous cell carcinoma. Early and effective treatment is
`
`
`
`Abstract
`Backround
`important.
`Objective
`To compare the efficacy, cosmetic outcome and patient preference of 5-aminolevulinic acid photodynamic
`therapy (ALA-PDT) with that of 5% imiquimod (IMIQ) cream in patients with AKs on the dorsa of hands and forearms.
`Methods
`Subjects received two ALA-PDT treatment sessions and one or two courses of imiquimod (three times per
`week for 4 weeks each). Treatments were randomly allocated to alternate upper extremities. Assessments included lesion
`response one and six months after treatment, cosmetic outcome evaluated by the investigators and patients’ preference
`6 months after treatment. Efficacy end point included the individual AK lesion clearance rate.
`Results
`Thirty patients with 256 lesions were included in the study. At the first follow-up, treatment with ALA-PDT
`resulted in significantly larger rate of cured lesions relative to 5% IMIQ cream (70.16% vs. 18.26%). At the second
`follow-up both treatments showed a high rate of cured lesions (65.32% for PDT vs. 55.65% for IMIQ cream). Response
`rates obtained in grade I lesions were higher for both treatments (71.64% for PDT vs. 72.13% for IMIQ), while treatment
`with PDT resulted in a significant larger rate of cured grade II lesions (57.89% for PDT vs. 37.03 for IMIQ).
`Difference in cosmetic outcome was not statistically significant. Results for subject preference favoured ALA-PDT.
`Conclusions
`Our study shows that ALA-PDT and 5% IMIQ cream are both attractive treatment options for upper
`extremities AKs with comparable efficacy and cosmetic outcomes.
`Received: 28 November 2008; Accepted 13 February 2009
`
`Keywords
`actinic keratosis, extremities, imiquimod, photodynamic therapy, treatment
`
`Conflicts of interest
`.
`None declared
`
`The term actinic keratosis refers to a sun-induced clinical
`erythematous lesion covered with scale. Histologically, it represents
`an intraepidermal malignant neoplasm with proliferation of
` Epidemiological data show a significant
`atypical keratinocytes.
`1
`prevalence of actinic keratoses among the Caucasian population.
`In Europe, a prevalence of 15% in men and 6% in women has been
`documented.
` Rates of malignant transformation of actinic
`2
`keratoses are considerable: approximately 10% of actinic keratoses
`in immunocompetent patients progress into invasive squamous
`cell carcinoma (SCC), while progression rates raise to 40% in
`immunocompromized patients.
` Early identification and treatment
`3
`are therefore advisable as it is impossible to predict which lesions
`may become invasive and develop into metastatic SCC. Moreover,
`
`an effective treatment that leads to good cosmesis is important
`because of the cosmetically sensitive sites of actinic keratoses’
`development.
`Therapies established for the treatment of actinic keratoses
`include both ablative procedures (surgery, laser ablation,
`curettage, cryotherapy) and topical treatments [photodynamic
`therapy (PDT), 5-fluorouracil, diclofenac 3% gel, 5% imiquimod
`cream].
`PDT is a non-invasive and precisely directed treatment. The
`procedure involves activation of a photosensitizing agent by
`visible light, with subsequent release of reactive oxygen species,
`which in turn produce local tissue destruction. PDT has the ability
`to treat large skin areas, while previous clinical studies showed
`
`JEADV
` 2009,
`, 1061–1065
`23
`
`© 2009 The Authors
`Journal compilation © 2009 European Academy of Dermatology and Venereology
`
`

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`1062
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`
`Sotiriou et al.
`
`that it provides high response rates and superior cosmetic
`outcome compared with conventional therapies.
` Moreover, it
`4,5
`has recently been recommended as first-line therapy in the
`international PDT guidelines for non-melanoma skin cancer.
`6
`Imiquimod is a representative of a new class of Toll-like receptor
`7 agonists which serve as immune response modifiers. It stimulates
`the immune response by induction, synthesis and release of
`cytokines that increases immunity at the cellular level inducing
`the indirect antiviral and anticancerous activity.
` Several studies
`7
`have shown that imiquimod is effective at treating clinical and
`subclinical actinic keratoses.
`8,9
`The aim of our intraindividual (right–left) study was to
`compare the efficacy, tolerability, safety and cosmetic outcome of
`topical 5-aminolevulinic acid (5-ALA) PDT with that of 5%
`imiquimod cream in patients with actinic keratoses on the dorsa
`of hands and forearms, and to evaluate patient preference.
`
`lower third of the forearm and one illuminating the upper two
`thirds of the forearm. Each patient received two ALA-PDT
`sessions 15 days apart.
`Treatment with imiquimod was based on the approved dosage
`regimen for the treatment of multiple actinic keratoses on the
`head.
` At baseline visit, patients were instructed to apply imiquimod
`10
`5% cream once daily 3 days per week, just prior to their sleeping
`hours. Cream was left on the skin for at least 8 h. Patients applied
`500 mg (two sachets) of cream, amount needed because of the size
`of the treatment area. Treatment started at the day of baseline
`visit, continued for 4 weeks (course 1) followed by a 4-week
`post-treatment period. Patients who had not cleared all their
`actinic keratosis lesions in the treatment area participated in a
`second 4-week treatment cycle (course 2).
`After end of treatment and during follow-up period, no
`additional actinic keratosis treatment was allowed.
`
`Patients and methods
`Thirty patients (25 male, 5 female) with clinical diagnosis of
`non-hyperkeratotic grade I (mild) and grade II (moderate) actinic
`keratoses on the dorsa of hands and forearms were enrolled in this
`intraindividual (right–left) comparison study. The study was
`conducted between September 2007 and July 2008. Each patient
`had to have at least six comparable lesions of similar severity on
`both sides (at least three lesions on each side). Precise location of
`each lesion was recorded on an anatomical diagram and
`documented with digital photographs. Exclusion criteria were
`other dermatological diseases or conditions in the treatment or
`surrounding (3 cm distance) area, topical treatments for actinic
`keratoses on hands and forearms within the past 2 months,
`invasive tumours within the treated area. All patients gave written
`consent to participate after having received detailed information
`on the purpose and design of the study. The study was approved
`by the local ethics committee and was conducted in accordance
`with the latest revision of the Declaration of Helsinki.
`
`Treatment protocol
`Eligible patients received PDT treatment and treatment with
`imiquimod 5% cream randomly allocated to alternate upper
`extremities.
`At baseline, all patients were treated with ALA-PDT. Lesions
`were prepared by gently removing crusts and by roughening
`their surface with a small curette. 20% 5-ALA (MEDAC Gmbh,
`Hamburg, Germany) was applied on the lesions as well as on
`5 mm of normal surrounding skin and left under occlusion for
`4 h. Immediately after removal of the dressing and the cream
`remnants, treatment area was illuminated with red light (570–
`670 nm) by a non-coherent light source (Waldmann PDT 1200,
`Waldmann-Medizin-Technik, Villingen-Schwenningen, Germany)
`at a light dose of 75 J/cm
` and a fluence rate of 75 mW/cm
`.
`2
`2
`Because of the great size of the treatment area, two PDT sessions
`were performed on the same day; one illuminating the hand and
`
`Response evaluation
`All patients were evaluated at baseline and at 1 and 6 months after
`treatment. Patients who had not completely cleared all their
`actinic keratosis lesions after the course 1 post-treatment period
`with imiquimod cream underwent a second treatment cycle and
`returned for a final assessment 6 months after treatment. The
`same examiners counted and recorded the number and performed
`the clinical evaluation of lesions at baseline and at follow-up visits.
`Efficacy end point included the individual actinic keratosis
`lesion clearance rate.
`Clinical lesion response was defined as complete response (CR;
`complete disappearance of the lesion) or as non-complete response
`(non-CR; incomplete disappearance of the lesion).
`Cosmetic outcome was assessed by investigators at month
`6 after treatment and was based on the amount of scarring,
`atrophy, induration, erythema and pigment change within the
`treated area in comparison with adjacent, untreated skin. It was
`graded as excellent (no erythema, change in pigmentation,
`scarring, atrophy or induration), good (slight to moderate erythema
`or change in pigmentation but no scarring, atrophy or induration),
`fair (slight scarring, atrophy or induration) and poor (moderate to
`extensive scarring, atrophy or induration).
`At month 6, patients completed a questionnaire regarding their
`preference in treatment procedure, efficacy and treatment choice
`in case of new lesions.
`Adverse events were noted at each visit, together with their
`severity, duration and need for additional therapy.
`
`Statistical analysis
`Lesion complete response was compared between the treatment
`t
`-test and 95% confidence intervals (95% CI),
`groups using
`assuming independency between lesions within patients. The
`number of lesions with excellent, good, fair or poor cosmetic
`outcome was compared between the two groups by means of the
`Mann-Whitney test.
`
`JEADV
` 2009,
`, 1061–1065
`23
`
`© 2009 The Authors
`Journal compilation © 2009 European Academy of Dermatology and Venereology
`
`

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`PDT vs. imiquimod for actinic keratoses
`
`1063
`
`Table 1 Patient demographics and lesion characteristics at baseline
`
`Table 3 Overall cosmetic outcome
`
`25 (83.33)
`5 (16.66)
`
`ALA-PDT
`
`Imiquimod
`
`Excellent
`Good
`Fair
`Poor
`
`ALA-PDT (n = 124)
`105 (85%)
`17 (14%)
`1 (1%)
`0 (0%)
`
`Imiquimod (n = 115)
`86 (75%)
`23 (20%)
`6 (5%)
`0 (0%)
`
`PDT and between 22.5 and 46.3 for imiquimod. No grade II
`lesions treated with imiquimod cream achieved clearance, while
`complete clearance rate achieved with PDT was 64.91% with 95%
`CI between 52.5 and 77.3.
`At month 6, both treatments showed a significant reduction
`from baseline in lesion count. The overall lesion complete
`response was 65.32% for PDT (95% CI, 56.9–73.7%) vs. 55.65%
`for imiquimod cream (95% CI, 46.6–64.7%), difference that was
`P
`not statistically significant (
`> 0.05) The observed treatment
`difference was not similar for mild and moderate thickness
`lesions. Response rates obtained in grade I lesions were 71.6%
`(95% CI, 60.8–82.4%) and 72.13% (95% CI, 60.9–83.4%) for PDT
`P
`and imiquimod cream respectively (
`> 0.05). On the contrary,
`around 20% difference between treatments was observed in grade
`II lesions with response rates at 57.8% (95% CI, 45.15–70.7%) for
`PDT and 37% (95% CI, 24.15–49.9%) for imiquimod cream, a
`P
`difference that was statistically significant (
`< 0.05). Overall and
`by-grade lesion response is summarized in Table 2.
`
`Cosmetic outcome
`At month 6, the investigator-assessed cosmetic outcome showed
`no significant difference between the two groups. In the PDT
`group, 80% of the lesions had an excellent cosmetic outcome
`compared with 75% of those treated with imiquimod cream.
`Good, fair and poor outcome was observed in 19, 1% and 0%
`lesions treated with PDT and in 20, 5% and 0% lesions treated with
`imiquimod cream, respectively. Difference in cosmetic outcome
`P
` =
`between the two groups was not statistically significant (
`0.065).
`Cosmetic outcome assessed by the investigators can be seen in
`Table 3.
`
`Patient preference
`Results from patient questionnaire showed that patients preferred
`PDT regarding the procedure (69% vs. 31%). Despite response
`
`Sex, n (%)
`Male
`Female
`Age (years)
`Mean ± SD (range)
`Total lesions, n (%)
`Severity, n (%)
`Grade I
`Grade II
`
`63.8 ± 9.5 (49–79)
`256 (100)
`
`133 (52)
`
`123 (48)
`
`72 (54.1)
`61 (45.9)
`
`66 (53.7)
`57 (46.3)
`
`Results
`In total, 30 patients were enrolled in the study. Patients were all
`white-skinned, while 83.33% (25 of 30) were male and 16.66%
`were (5 of 30) female. Their ages ranged from 49 to 78 years
`(mean ± SD, 63.8 ± 9.5). Distribution according to Fitzpatrick
`skin types was as follows: II, 30% (9 of 30); III, 56.6% (17 of 30);
`IV, 13.3% (4 of 30).
`The 30 patients had a total of 256 lesions. Baseline lesion
`characteristics were similar between the two treatment groups
`with 133 lesions on the ALA-PDT side and 123 lesions on the 5%
`imiquimod cream side. Both sides were well balanced in terms of
`number and severity of lesions. Overall, 84.96% (113 of 133) of
`lesions treated with ALA-PDT were prepared at baseline. Lesions
`not prepared were all grade I lesions.
`Patient demographics and baseline lesion characteristics are
`summarized in Table 1.
`Overall, 28 patients (93.33%) with 239 lesions completed the
`study. Two patients were lost to follow-up and were not included
`in the analysis. Of the 239 lesions included in the analysis, 124
`were treated with PDT and 115 with imiquimod.
`
`Clinical evaluation
`At 1 month after PDT treatment cycle and at course 1 4-week
`post-treatment period with imiquimod, the overall lesion
`complete response rate was 70.16% for PDT and 18.26% for
`P
`imiquimod cream (
`< 0.05). When looking at lesion response for
`the subgroups based on lesion grade, higher response rate was
`achieved in grade I lesions treated with PDT (75% for PDT
`vs. 34.42% for imiquimod). The difference was statistically
`P
`significant (
`< 0.05) with a 95% CI between 64.6 and 85.3 for
`
`Table 2 Overall and by grade lesion response 1 and 6 months after treatment
`
`Overall lesion response
`Grade I lesion response
`Grade II lesion response
`
`1 month
`ALA-PDT
`87/124 (70.16%)
`50/67 (75%)
`37/57 (64.91%)
`
`Imiquimod
`21/115 (18.26%)
`21/61 (34.42%)
`0/54 (0%)
`
`6 months
`ALA-PDT
`81/124 (65.32%)
`48/67 (71.64%)
`33/57 (57.89%)
`
`Imiquimod
`64/115 (55.65%)
`44/61 (72.13%)
`20/54 (37.03%)
`
`JEADV
` 2009,
`, 1061–1065
`23
`
`© 2009 The Authors
`Journal compilation © 2009 European Academy of Dermatology and Venereology
`
`

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`1064
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`Sotiriou et al.
`
`rates, only 55% of the patients favoured PDT in terms of efficacy
`vs. 45% who favoured imiquimod cream. Finally, if they had to be
`treated again, 70% of them would prefer PDT vs. 30% of them who
`would prefer imiquimod cream.
`
`Adverse events
`No unexpected safety issues occurred in the study population
`until end of the follow-up period. The most commonly reported
`adverse events were expected, were specifically related to the type
`of therapeutic procedure and were mild to moderate and transient
`in nature. No patient discontinued the study due to adverse events.
`PDT reactions recorded during light treatment were stinging
`(83.3%), burning (100%) and pain (100%). Pain management
`included the use of a fan or of cooling sprays in patients who felt
`intense pain and discomfort. Local phototoxic reactions included
`moderate erythema (100%), oedema (66.6%) and blistering
`(26.6%). These reactions were well tolerated, did not demand
`additional treatment and resolved within 7–15 days without
`further complications.
`The most frequently reported adverse events in the imiquimod
`cream group were application site reactions. Application site
`itching, burning and pain were reported by 21.4%, 10.7% and
`3.5% of the patients accordingly.
`Local skin reactions in the treatment area were mild to moderate
`and were well tolerated. They were more intense during course 1
`than during course 2 and included erythema (92.8%), crusting
`(10.7%), scaling (10.7%), erosions/ulcerations (7.1%), and oedema
`(7.1%).
`Infections in the treatment area were not observed.
`
`Discussion
`Actinic keratoses are among the most common cutaneous
`in situ
`malignancies and are classified as an early
` squamous cell
`carcinoma with reported progression rates of up to 20% over
`10 years.
` It is therefore recommended that all actinic keratoses
`1
`are treated to prevent possible invasion.
`There are numerous previous studies demonstrating the effi-
`cacy of PDT and imiquimod 5% cream in treating non-hyperkeratotic
`actinic keratoses.
` However, we believe this is the first study
`11–18
`comparing the efficacy of ALA-PDT vs. imiquimod 5% cream on
`multiple actinic keratoses located on sites other than the face and
`scalp (i.e. the upper extremities).
`Based on the clinical assessment, ALA-PDT treatment provided
`6 months after treatment resulted in a complete clearance rate
`of 65.32%. Response was best in grade I lesions with a complete
`clearance rate at 71.6%, while grade II lesions achieved a complete
`clearance rate of 57.8%.
`Previous studies have shown complete response rates of
`71–91% for lesions on the face or scalp given a single PDT with
`topical ALA.
` With repeated PDT treatment – as was the case
`11,12
`in our study – higher response rates can be achieved. actinic
`keratoses of the extremities may be more resistant than that of
`
`the face and scalp. One possible explanation for this increased
`resistance could be the lack of pilosebaceous units in these areas,
`as the presence of pilosebaceous units could lead to a better
`absorption of the prodrug and to a better response. Compared
`with studies with topical MAL-PDT in AK of extremities, our
`study demonstrated lower complete clearance rates. In a previous
`prospective randomized study, the authors demonstrated that
`two MAL-PDT sessions lead to complete response in 76% of
`actinic keratoses on the extremities 3 months after the initial
`treatment.
` In a more recent multicentre intraindividual study for
`4
`multiple actinic keratoses of the extremities, MAL-PDT provided
`6 months after treatment resulted in a mean percentage reduction
`of 78% in lesion count, while 72% of the cured lesions had been
`treated only once.
` In both studies, response was best in thin
`15
`non-hyperkeratotic lesions, which is consistent with our results.
`However, in a study with 110 patients and a total of 968 lesions on
`the face and scalp treated with ALA-PDT, the percentage of
`lesions clearing completely was similar in grade I and grade II
`actinic keratoses.
`16
`The drop in response rate from 70.16% to 65.32% at 1- and 6-
`month follow-up examination can be interpreted as an apparent
`rather then real complete resolution of some actinic keratoses.
`Residual malignant cells that are still in the epidermis, but not
`apparent by visual inspection, will continue to proliferate and
`result in a clinical recurrence at a later follow-up examination.
`14
`Clearance rates obtained with imiquimod 5% cream in our
`study after the first course of treatment were lower compared with
`previous studies conducted on multiple actinic keratoses of the
`face and scalp.
` However, the overall complete clearance rate
`17,18
`raised from 18.26% to 34.42% when only grade I lesions’ response
`was estimated. Clearance rates for individual actinic keratosis
`lesions on the head after one treatment course were 64.6% in a
`previous multicentre study;
` however, baseline numbers of grade
`18
`I and grade II lesions are not mentioned. A further increase in
`efficacy was demonstrated in our study after the second course
`of treatment, resulting in an overall complete clearance rate of
`55.65%. This percentage rose to 72.13% after clinical assessment
`of grade I lesions only. In the above-mentioned study,
` individual
`18
`lesion clearance rates after a second course treatment reached
`
` et
`al
`85.4%, while in a study conducted by Jorizo
`
`., the individual
`17
`lesion clearance rate after two treatment courses was 74.4%.
`Again, clearance rates are not mentioned separately for grade I
`and grade II lesions.
`Possible explanations for the higher response rates observed in
`treatment of actinic keratoses on the face and scalp with imiquimod
`cream might be the greater number of pilosebaceous units as well
`as the increased area vasculature that promote drug absorption
`and lead to a better result.
`The excellent cosmetic outcome of both therapies is consistent
`with previous findings and may favour the use of PDT or imiquimod
`5% cream over larger areas, which is useful considering the
`widespread nature of actinic keratoses in many patients.
`15,19
`
`JEADV
` 2009,
`, 1061–1065
`23
`
`© 2009 The Authors
`Journal compilation © 2009 European Academy of Dermatology and Venereology
`
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`PDT vs. imiquimod for actinic keratoses
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`1065
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`Both therapies were safe and well tolerated. No unexpected
`safety issues were observed in the study population. The most
`commonly reported adverse events were mild to moderate and
`transient in nature.
`Patients confirmed their preference for PDT as a therapeutic
`option, and more patients would prefer new lesions to be treated
`with ALA-PDT than with imiquimod cream.
`In conclusion, the present study demonstrated that ALA-
`PDT provided a significantly better therapeutic response than
`one 4-week course with imiquimod 5% cream for both grade
`I and II actinic keratoses of the extremities. ALA-PDT was
`shown to be superior to two 4-week courses with imiquimod
`5% cream in terms of efficacy for grade II actinic keratoses, while
`both treatments were comparable for grade I actinic keratoses.
`ALA-PDT should be considered as a first-line therapy both for
`grade I and grade II actinic keratoses of the extremities. For treat-
`ing patients with dominating grade II lesions, repetitive schemes
`of at least two ALA-PDT sessions are advisable, while follow-up
`visits are recommended.
`As imiquimod cream is a topical, patient-applied product, an
`8-week treatment scheme could be seen as one of the first thera-
`peutic options in patients with dominating grade I lesions.
`Long-term safety and recurrence rates need to be evaluated
`in a long-term follow-up study. Future clinical studies will be
`necessary to evaluate further the comparative clinical benefits of
`these therapies.
`
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`JEADV
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`, 1061–1065
`23
`
`© 2009 The Authors
`Journal compilation © 2009 European Academy of Dermatology and Venereology
`
`

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