Successful treatment of actinic keratosis with imiquimod cream 5%: a report of six cases

BACKGROUND: Actinic keratoses (AK) are premalignant lesions, which are routinely treated by destructive procedures such as cryotherapy, electrodessication or topical 5-fluorouracil. OBJECTIVES: The aim of this study is to report six cases of AK treated with a potential new topical therapy, imiquimod. METHODS: Subjects included in this study had suffered with recurrent AK for between 5 and 16 years. All six men were treated with imiquimod 5% cream three times a week for 6-8 weeks. In the event of a local skin reaction treatment was modified to two times per week. RESULTS: All the AK lesions were successfully cleared after treatment with imiquimod cream 5% for 6-8 weeks. Histologically, no apparent signs of persisting AK could be detected, and no recurrences were reported during follow up. CONCLUSIONS: This study suggests that imiquimod may be useful as a new therapy for the treatment of actinic keratoses.     

Vehicle-controlled, randomized, double-blind study to assess safety and efficacy of imiquimod 5% cream applied once daily 3 days per week in one or two courses of treatment of actinic keratoses on the head

BACKGROUND: Imiquimod has been investigated as a safe and effective therapeutic option for the treatment of actinic keratosis (AK). OBJECTIVES: To evaluate imiquimod vs. vehicle applied three times a week for 4 weeks in one or two courses of treatment for AK on the face or balding scalp. PATIENTS AND METHODS: Patients diagnosed with AK were enrolled in this multicentre, vehicle-controlled, double-blind study conducted in Europe. Twenty study centres enrolled a total of 259 patients in this study. Patients applied the study drug for 4 weeks, entered a 4-week rest period and if they did not have complete clearance, they then entered a second course of treatment. RESULTS: Patients in the imiquimod group had an overall complete clearance rate of 55.0% (71/129) vs. a rate of 2.3% (3/130) for the vehicle group. There was a high rate of agreement between the clinical assessment and histological findings with respect to AK lesion clearance. At both 8-week post-treatment visits, the negative predictive value of the investigator assessment was 92.2% for clinical assessments vs. histological results. CONCLUSIONS: A 4-week course of treatment with three times weekly dosing of imiquimod 5% cream, with a repeated course of treatment for those patients who fail to clear after the first course of treatment, is a safe and effective treatment for AK. The overall complete clearance rate (complete clearance after either course 1 or course 2) is comparable to the 16-week treatment regimen, while decreasing drug exposure to the patient and decreasing the overall treatment time.     

Short-course therapy with imiquimod 5% cream for solar keratoses: a randomized controlled trial

A dual-centre, randomized, double-blind, vehicle-controlled study was conducted to evaluate the safety and efficacy of short courses of therapy with imiquimod 5% cream in clearing >/=75% of baseline solar keratoses (SK) within a field of treatment. Subjects with 5-15 baseline SK within one treatment area (scalp, forehead and temples, or both cheeks) were randomized to apply imiquimod or vehicle cream to the entire treatment area three times a week for 3 weeks. Subjects were assessed 4 weeks after completing the first course for clearance of lesions. Subjects with <75% clearance were commenced on a second 3-week course of study cream. Subjects with >/=75% clearance were followed up until study completion without further therapy. All subjects were evaluated at the study endpoint of 14 weeks after initiating therapy for assessment of the primary outcome (>/=75% clearance of baseline solar keratoses). Twenty-one out of 29 (72%) imiquimod-treated subjects cleared >/=75% of baseline lesions compared with 3/10 (30%) subjects using the vehicle cream (Fisher's exact test, P = 0.027). Imiquimod was well tolerated. The present study has a short follow-up endpoint, but suggests that imiquimod is a potential therapeutic alternative in patients with SK.     

A randomized trial of topical 5% 5-fluorouracil (Efudix cream) in the treatment of actinic keratoses comparing daily with weekly treatment

BACKGROUND: Topical 5-fluorouracil (5-FU) cream is widely used in the treatment of actinic keratoses (AKs) but the optimum treatment regimen that provides efficacy while minimizing side-effects remains unclear. OBJECTIVES: A randomized trial to compare the efficacy and side-effects of daily vs. weekly application of 5% 5-FU in the treatment of AKs of the scalp and face. PATIENTS/METHODS: Twenty patients were recruited and randomized to two groups. Group 1 (13 patients) applied 5% 5-FU twice daily for 3 weeks, group 2 (seven patients) applied 5% 5-FU twice daily for 1 day per week for 12 weeks. Patients were reviewed at weeks 3, 12, 24 and 52. At each review a lesion count and lesion map were completed and patients were asked to score efficacy and inflammation. RESULTS: At week 0 the median lesion count was the same in both groups, 17.5 lesions. At 12 weeks the median lesion count in group 1 had fallen to 0 where it remained for the duration of follow-up. In group 2 the median lesion count fell to 6 at 12 weeks, 5.5 at 24 weeks and was 3 at 52 weeks. The difference in the lesion count was significant at all time points after week 0: P < 0.05 at weeks 12 and 52, and P < 0.01 at week 24. The mean inflammation score was higher in patients clear of AKs at 12 weeks compared with those who had not cleared, 3.8 compared with 1.9. This difference was statistically significant (P < 0.05) suggesting that inflammation is necessary for efficacy. CONCLUSIONS: We conclude that daily application of 5% 5-FU cream is more effective than weekly application at clearing AKs from the scalp and face. Our results also suggest that inflammation is likely to be required to achieve a therapeutic effect.     

The efficacy and safety of topical 5% 5‐fluorouracil in renal transplant recipients for the treatment of actinic keratoses

Actinic keratoses (AK) occur more commonly and behave more aggressively in renal transplant recipients (RTR). Topical 5% 5‐fluorouracil (5‐FU) cream is a commonly used agent whose efficacy and safety have never been exclusively studied in the RTR population before. Eight RTR were enrolled and 5% 5‐FU cream applied to AK lesions on their face twice daily for 3 weeks. They were reviewed at 2 and 8 weeks, and 12 months post‐commencement of treatment. Their AK were counted and their cumulative surface areas measured. Patients completed surveys monitoring adverse effects and tolerability. Complete (100%) and partial clearance (≥ 75%) rates were measured, as well as mean percentages of the reduction in AK surface area. Patients had complete clearance rates of 63 and 0% at 8 weeks and 12 months, respectively. All (100%) patients had partial clearance at week 8 and 71% had partial clearance at 12 months. Patients had on average 15 AK at week 0 and 1 and 3 at 8 weeks and 12 months, respectively. The mean AK clearance rate was 98% at week 8 and 79% at 12 months. Common side‐effects were erythema, itch and flaking or scaling, mostly mild in severity. 5‐FU appears to be an efficacious and safe treatment for AK in RTR.     

Two cases of squamous cell carcinoma treated with topical imiquimod 5%

We report the first two cases of squamous cell carcinoma successfully treated with imiquimod 5% cream as a monotherapy. Imiquimod is a new immunomodulating drug that is registered for genital HPV infection but has also shown good efficacy in several cutaneous malignancies.     

Intraindividual, right–left comparison of topical 5-aminolevulinic acid photodynamic therapy vs. 5% imiquimod cream for actinic keratoses on the upper extremities

Backround  Actinic keratoses (AKs) are considered as in situ squamous cell carcinoma. Early and effective treatment is 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.

Conflicts of interest

None declared.     

咪喹莫特乳膏治疗光化性角化病Meta分析

目的:以循证医学的方法对5%咪喹莫特乳膏治疗光化性角化病的疗效与安全性进行系统评价。方法:检索PubMed、Ovid、Web of Science、UMI、elsevier,以及Cochrane图书馆,纳入比较5%咪喹莫特乳膏与安慰剂的随机对照试验,由两名评价者独立提取资料并进行方法学质量评估。试验数据的统计分析采用RevMan 4.2.8软件进行。结果:最终纳入5个RCT,对其治疗光化性角化病进行了Me-ta分析,显示其与对照组相比,差异具有统计学意义,合并后RR=5.82(95%CI,3.44~9.83),没有报道与5%咪喹莫特乳膏临床应用相关的严重系统性不良反应。结论:现有临床证据表明,5%咪喹莫特乳膏治疗光化性角化病有确切的疗效与较好的安全性。     

Earliest stage treatment of actinic keratosis with imiquimod 3.75% cream: Two case reports—Perspective for non melanoma skin cancer prevention

Imiquimod 3.75% cream is licensed for the treatment of actinic keratosis (AK). Two case reports on the treatment of facial UV‐exposed skin shall open the discussion if subclinical AKs can be detected by the use of imiquimod cream in UV‐exposed areas even if no lesions can be found clinically. A 87‐year old female showing small scaly AK lesions on her right cheek was treated with imiquimod 3.75% cream. A 59‐year old female without obvious clinical signs of UV‐damage on the face experimentally applied imiquimod 3.75% cream twice daily on the entire face for 2 weeks. In the 87‐year old, inflammatory reaction developed from day 3 onward and showed field cancerization, the lesions healed without scarring. In the 59‐year old at the end of the treatment phase, distinct signs of inflammation appeared, then taking 2 weeks for healing without sequalae. These results open the discussion if the use of imiquimod 3.75% cream could be recommended preventively in UV‐exposed skin areas to obviate a later development of AKs/squamous cell carcinoma/nonmelanoma skin cancer.     

Treatment of actinic keratoses with a novel betulin‐based oleogel. A prospective,randomized, comparative pilot study

Background: Actinic keratoses (AK) are squamous cell carcinomas in situ and require treatment. Betulin‐based oleogel prepared from a standardized triter‐pene dry extract from birch bark represents a new topical agent with anti‐inflammatory and anti‐tumor potential. Patients and Methods: In the prospective, randomized, monocentric phase 2a study 45 patients with < 10 AK were included and randomly assigned to one of the three treatment groups. Intervention consisted of topical betulin‐based oleogel twice daily versus cryotherapy with liquid nitrogen versus the combination of cryotherapy with topical betulin‐based oleogel.Treatment response was assessed clinically after three months. The clinical response was graded into complete clearing (100 %), therapy responders (> 75 % clearing of the lesions) and non‐responders (< 75 % clearing). Additionally, punch biopsies were obtained from some patients before and at the end of treatment. Results: Therapy with betulin‐based oleogel was well tolerated.Three patients discontinued therapy because of personal reasons. After three months, the 100% (and > 75%) clearing rates of the lesions were as follows: 64% (86%) with betulin‐based oleogel (n = 14),79% (93%) with cryotherapy (n = 14),and 71% (71%) with the combined therapy (n = 14). Histological analysis of biopsies taken before and after treatment (n = 8) showed a reduced degree of dys‐plasia in the epidermis in all study arms. Conclusions: Betulin‐based oleogel seems to be an effective novel approach in the topical treatment of actinic keratoses. However,the clinical and histological findings of the present pilot study have to be verified against placebo with larger case numbers.     

The impact of different fluence rates on pain and clinical outcome in patients with actinic keratoses treated with photodynamic therapy

Background/purpose: Literature data suggest that lower fluence rates are preferable in terms of clinical response and tolerability for treating patients with actinic keratoses (AKs). We aimed to clarify the impact of different fluence rates on pain during photodynamic therapy (PDT) for AKs, as well as on treatment outcome. Methods: Individuals with at least three discrete AKs were recruited. Each lesion was randomly allocated to 25, 50 or 75 mW/cm² of topical 5‐aminolevulinic acid (5‐ALA) PDT, using non‐coherent light source. Primary end point was pain during illumination, evaluated using a visual analogue scale (VAS). Secondary end points were clinical outcome and adverse events. Results: Fifty adults, with 150 AKs lesions were recruited in the study. Mean VAS score did not significantly differ between the groups of 25 and 50 mW/cm² (P=0.714). However, mean VAS was significantly higher at the group of 75 mW/cm² in comparison to the former ones (P=0.000). With respect to the clinical outcome and adverse events during the first year of follow‐up, no differences were observed between the three groups. Comparison between the 25 and the 50 mW/cm² (P=0.749), as well as between the former and the 75 mW/cm², did not show a dependence of complete response rate on fluence (P=0.749 and P=1.000, respectively). Conclusions: According to our observations a fluence rate between 25 and 50 mW/cm² is effective and better tolerated by patients treated with topical 5‐ALA PDT for AKs.     

Peeling with 70% glicolic acid followed by 5% 5‐fluorouracil as well as 5% 5‐fluorouracil cream are effective methods for the treatment of actinic keratoses on upper limbs: A randomized clinical trial

The 5% 5‐fluorouracil (5‐FU) cream, considered the gold standard topical treatment, and peeling using 70% glycolic acid (GA) followed by 5% 5‐FU are methods for the treatment of actinic keratoses (AKs). However, the comparison of these two treatments had not yet been described and therefore was the objective of this study. A randomized clinical trial, intrapatient study in which 17 patients received a type of treatment in the right and left upper limb with 5% 5‐FU cream (twice daily) or a peeling application of 70% GA (every 15 days) followed by 5% 5‐FU cream. There was a significant reduction of 75% and 85.71% in the mean number of AK lesions and of 74.5% and 85.71% in the size of lesions on the upper limbs of patients treated with peeling and 5% 5‐FU cream (P‐value ≤.001), respectively. Neither treatment was superior to the other since there was no significant difference (P‐value ≥.05) between the treatments, both at the post‐intervention period as well as when comparing the difference between the pre and post‐intervention periods. The peeling with 70% GA followed by 5% 5‐FU as well as 5% 5‐FU cream are effective methods for the treatment of AKs on upper limbs.     

Use of topical immunomodulators in organ transplant recipients

Solid organ transplant recipients are a growing population at increased risk for the development of cutaneous premalignant and malignant lesions, resulting in significant morbidity and mortality. Topical immunomodulators, in particular imiquimod, have shown efficacy in the management of multiple malignant, precancerous, and viral conditions. The ability to locally induce an immune response, presumably against tumor and viral antigens, and induce apoptosis makes topical immunomodulators a promising therapeutic option in organ transplant recipients. Although limited, data have begun to accumulate on the use of imiquimod in transplant patients for the management of superficial, nodular, and infiltrative basal cell carcinomas; in situ and invasive squamous cell carcinomas; condyloma acuminata; and common warts. As more experience is gathered, the role of imiquimod and other topical immunomodulators in the care of OTRs will be clarified. The authors reviewed the existing data on the use of topical imiquimod in OTRs with mention of its presumed mechanisms of action and other immunomodulators with potential efficacy against cancerous and precancerous lesions.