Pilot study using topical imiquimod 5% cream in the treatment of nodular basal cell carcinoma after initial treatment with curettage

BACKGROUND: Nodular basal cell carcinoma (nBCC) is the most common cutaneous malignancy and studies assessing the use of topical imiquimod 5% cream as a monotherapy in the treatment of nBCC have resulted in less than optimal clearance rates. OBJECTIVE: This pilot study was designed to evaluate the efficacy of imiquimod 5% cream on nodular basal cell carcinoma lesions after initial treatment with curettage. METHODS: After obtaining informed consent, 17 nBCCs on 15 patients were included in this institutional review board-approved, open-label study with initial treatment using curettage without electrodesiccation followed by once-daily application of imiquimod 5% cream 5 times per week for 6 weeks. The area was excised and examined histologically 6 weeks after cessation of imiquimod cream. RESULTS: All 17 lesions (100%) showed no histologic evidence of residual tumor on the post-treatment excision. Local site reactions necessitating a rest period from medication application were experienced by most patients (67%), but the majority of patients stated that they would choose this treatment modality over excision if they developed a subsequent tumor. CONCLUSION: Imiquimod 5% cream appears to be an effective treatment method for nodular basal cell carcinoma if combined with curettage prior to application.     

One-week treatment with 0.5% fluorouracil cream prior to cryosurgery in patients with actinic keratoses: a double-blind, vehicle-controlled, long-term study

Topical fluorouracil is currently approved for the treatment of actinic keratosis (AK) and is often used prior to or following cryosurgery as interval therapy in patients with severe AK lesions. No randomized, controlled studies are available to confirm anecdotal evidence suggesting pretreatment with fluorouracil is beneficial. This prospective, randomized, double-blind, vehicle-controlled study evaluated the effect of pretreatment with 0.5% fluorouracil cream (FC; Carac) or a vehicle cream (VC) once daily for 7 days to the face plus scalp, ears, neck, and/or lips in patients with > or = 5 visible or palpable AKs on the face prior to cryosurgery. Efficacy was determined by evaluating AK reduction and clearance (complete lack of AK lesions in the treatment area) at 4 weeks follow-up. Statistically significant decreases from baseline number of AKs were observed on all treatment areas in both groups. However, the mean number of facial AKs was significantly lower in the FC group at each treatment cycle (p = .011). No serious adverse events were considered related to treatment.     

The treatment of actinic keratoses with a combination of 5-fluorouracil and imiquimod creams

BACKGROUND: 5-fluorouracil (5-FU) and imiquimod creams are accepted topical therapies for actinic keratosis (AK). Both are associated with a prolonged course of treatment with an inflammatory response that may preclude the treatment process. OBJECTIVES: To describe the treatment regimen and the extent of side effects in the use of the combined application of 5-FU and imiquimod creams in patients presenting with AKs and to demonstrate the convenience and ease of the methodology of this regimen. METHODS: The patients applied 5-FU and imiquimod creams to their lesions daily for one week each month over the course of 3 months. The patients were seen after the completion of each one-week course to evaluate their progress and side effects. RESULTS: There were 64 patients in the study, 48 of whom completed the study and demonstrated a clearing of their AKs by the end of the third course of treatment. All of the patients developed an inflammatory response at the sites of their AKs as well as at subclinical sites with no apparent AKs. Nearly all of these inflammatory reactions were confined to localized sites without involvement of the surrounding skin. CONCLUSIONS: Therapy with the combined application of 5-FU and imiquimod creams is a relatively rapid and convenient form of therapy as compared to the separate use of each medication.     

Pharmacoeconomic analysis of the treatment of multiple actinic keratoses

Actinic keratosis (AK) is common and lesions may progress to squamous cell carcinoma. The choice of therapy depends mainly on 2 factors: the efficacy of therapeutic options and the number of lesions present. Cryotherapy alone is suitable for treating a few lesions, whereas topical medications, photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA), or either in combination with cryotherapy are appropriate for treating multiple (>15) lesions. When combinations are necessary, the total cost to treat multiple AKs to 100% clearance becomes important. This report provides a simple pharmacoeconomic analysis of 4 FDA-cleared therapies (imiquimod, diclofenac, 5-fluorouacil [5-FU], and ALA PDT) for AK given in combination with cryotherapy. This analysis assumes standard costs of procedures and office visits (based on April 2007 reimbursement data) and 2 treatment courses (medications: imiquimod, diclofenac, 5-FU) or sessions (ALA PDT) of each modality followed by cryotherapy to 100% clearance. The total cost of each combination is $725.17 for ALA PDT, $845.07 for diclofenac, $942.13 for 5-FU, and $1,473.39 for imiquimod. When phase III trial efficacies of the 4 modalities are considered, the actual cost of using imiquimod or diclofenac increases because additional treatments may be required. Among these 4 FDA-cleared therapies for multiple AK lesions, ALA PDT is the least expensive treatment and imiquimod is the most expensive treatment under the stated assumptions.     

Imiquimod 3.75% cream (Zyclara) for the treatment of actinic keratoses

INTRODUCTION: actinic keratosis is a premalignant disease with a high incidence and is a strong predictor for the development of squamous cell carcinoma. Various treatment options have been established over recent years, including topical treatment with imiquimod, 5-fluorouracil, diclofenac or photodynamic therapy, cryotherapy and surgical procedures. AREAS COVERED: this review covers basic and clinical experiences with imiquimod 3.75% for topical treatment of actinic keratosis of the face and balding scalp and its comparators with special focus on imiquimod 5%. It also covers pharmacology of imiquimod 3.5% and its contribution to the current treatment options of actinic keratoses. EXPERT OPINION: imiquimod 3.75% is an interesting, safe and well-tolerated treatment option for actinic keratoses of the face or balding scalp especially in respect of compliance, as it is indicated for daily use for a shorter time period (2 times, 2-week cycles) and approved for use on larger areas compared with imiquimod 5%. Data from current trials indicate lower efficacy compared with imiquimod 5% cream when applied three times a week for 16 weeks or for two 4-week cycles with a 4-week no-treatment interval, but indicate similar efficacy when compared with a twice-weekly schedule for 16 weeks. An additive effect was observed when combining cryosurgery followed by imiquimod 3.75%.     

Topical imiquimod: a review of its use in genital warts.

Imiquimod is a topically active immunomodulatory agent that is formulated as a 5% cream for application by the patient. It is the first agent of its class, the immune response modifiers, to be used in the treatment of genital warts. In immunocompetent patients with genital warts, imiquimod stimulates the production of interferon-alpha and various other cytokines, and has indirect antiviral activity. In randomised, double-blind, vehicle-controlled clinical trials, complete clearance of warts occurred in 37 to 50% of immunocompetent patients with genital warts treated with imiquimod 5% cream 3 times a week for up to 16 weeks; partial clearance of warts (defined as a reduction in wart area of > or = 50%) was observed in 76% of recipients of imiquimod 5% cream. Rates of complete or partial clearance of warts were significantly higher in patients who applied imiquimod 5% cream 3 times a week than in recipients of imiquimod 1% or vehicle cream, each applied 3 times a week. A between-gender difference in clinical response to imiquimod 5% cream has been reported, with female patients experiencing higher rates of complete clearance of warts than males. Recurrence(s) of > or = 1 wart occurred in 13 to 19% of immunocompetent patients in whom complete clearance of warts had been achieved with imiquimod 5% cream. Imiquimod 5% cream also shows some clearance of warts in immunosuppressed HIV-infected patients with genital warts. Preliminary results of a vehicle-controlled study showed that the rate of partial clearance of warts (defined as a reduction in baseline wart area of >50%) [38%] was significantly higher with imiquimod 5% cream than with vehicle cream; however, the rate of complete clearance was not significantly higher than with vehicle cream. Imiquimod 5% cream is generally well tolerated by immunocompetent and HIV-infected patients. Local skin reactions (mainly mild or moderate), including erythema, itching and burning, are the most commonly reported adverse events, occurring in < or = 67% of patients applying imiquimod 5% cream 3 times a week. The incidence of adverse events is lower in patients applying the cream 3 times a week than with daily application. The incidence of systemic adverse events with imiquimod 5% cream (applied daily or 3 times a week) is similar to that of vehicle cream. The tolerability profile of imiquimod cream appears favourable compared with that of podophyllotoxin. CONCLUSION: Imiquimod 5% cream is a new therapeutic option for patients with genital warts. It produces clearance rates broadly similar to those of other treatment approaches and rates of wart recurrence compare favourably with those reported for established treatments. In contrast to most alternative treatment strategies. which are administered in the physician's office, imiquimod cream is a self-administered therapy for outpatient use.     

Treatment of genital herpes in males with imiquimod 1% cream: a randomised, double-blind, placebo-controlled study

OBJECTIVE: The aim of this randomised, double-blind, placebo-controlled study was to examine the clinical significance, efficacy and tolerability of imiquimod 1% cream to manage patients exposed to first episodes of genital herpes. PATIENTS: Male patients (n = 60), ranging in age between 18 and 50 years (mean 25.7 years), presenting for <6 days (mean 4.4 days) with culture-confirmed diagnosis of genital herpes, and bearing a total of 696 lesions (mean 11.6 lesions/ patient), entered the study and were randomised to receive a precoded 40g tube and instructions on how to apply the trial medication to their lesions twice for 5 consecutive days per week. RESULTS: A marked clinical benefit from self-application of imiquimod 1% cream was demonstrated, resulting in both significantly shorter mean duration of healing than with the placebo (5.2 vs 14 days; p < 0.001) and more healed patients [23 of 30 (76.7%) vs 2 of 30 (6.7%); p < 0.0001]. Of the 60 patients, 54 (90%) reported no drug-related adverse effects. Two patients in the imiquimod group reported non-objective mild burning sensation and four experienced a transitory increase in their body temperature (>38 degrees C) accompanied by mild headache and malaise; however, such indications were not severe enough to cause discontinuation of the treatment, and resolved within 24 hours. Treatment was well tolerated by all the patients, with no dropouts. Among 25 healed patients, four had a relapse after 9 months. CONCLUSION: Although the analogue of imiquimod 1% cream demonstrated mild to moderate subjective adverse effects, it was significantly more effective than placebo in treating patients with a first episode of genital herpes. Further clinical studies appear warranted.     

Nonsyndromic multiple basal cell carcinomas successfully treated with imiquimod 5% cream

This report describes the case of a 60-year-old man with nonsyndromic multiple basal cell carcinomas that responded to imiquimod 5% cream. The patient had no additional anomalies suggesting any syndromes associated with multiple basal cell carcinomas. By applying the agent 5 times a week for 20 weeks, we obtained good clinical results, and we confirmed the improvement with histopathologic examination. We suggest that patients with multiple basal cell carcinomas should be interviewed about and tested for the associated syndromes, and topical imiquimod should be kept in mind as an alternative therapy choice in these patients.     

Pharmacokinetics of daily self-application of imiquimod 3.75% cream in adult patients with external anogenital warts

Imiquimod 3.75% cream is a new formulation intended for daily self-application. The objective of this study was to characterize serum imiquimod pharmacokinetics under maximal use conditions. Adults with ≥8 warts or total wart area ≥100 mm2 applied up to 1 packet of imiquimod 3.75% cream (250 mg cream, 9.375 mg imiquimod) once daily for 3 weeks. Blood was obtained prior to doses 1, 7, 14, and 21 and at selected time points after doses 1 and 21. Eighteen patients (13 men and 5 women) with a median wart count of 16 and total wart area of 60 mm2 were enrolled. Day 21 mean (SD) serum C(max) was 0.49 (0.37) ng/mL, AUC???? 6.80 (3.59) ng·h/mL, and t(1/2) 24.1 (12.4) hours. Steady state was achieved by day 7 with ~2-fold increase in C(max) and AUC after multiple dosing. Overall, C(max) was higher and t(max) shorter in women, with comparable AUC????. Imiquimod metabolites were sporadically quantifiable. No patients discontinued for adverse events; 1 interrupted dosing for an application site ulcer. Treatment-related adverse events occurred in 16.7% of the patients. In conclusion, serum imiquimod concentrations were low after daily self-application to external anogenital warts of up to 1 packet of imiquimod 3.75% cream for 21 days.     

Treatment of lentigo maligna with imiquimod 5% cream

Lentigo maligna (LM) is an in situ melanoma that occurs in sun-damaged skin on the head and neck of elderly patients. Surgical excision is the treatment of choice for LM. However, surgical options may be limited by the location of LM in cosmetically sensitive areas. We present a woman with a history of skin cancer with a large, asymmetrically pigmented lesion on her right superior cheek below her eyelid. The lesion had been present for approximately 15 years. Histologic analysis confirmed that the lesion was an LM. Imiquimod 5% cream was applied topically once daily. Approximately 5 months later, the previous LM had healed well and no new lesions were observed. Histologic clearance of the lentigo maligna was evident in skin biopsies. Imiquimod 5% cream appears effective in the treatment of lentigo maligna. We describe the treatment of a patient with facial LM with imiquimod 5% cream.     

Treatment of all basal cell carcinoma variants including large and high-risk lesions with 5% imiquimod cream: histological and clinical changes, outcome, and follow-up

Forty-one patients with 47 basal cell carcinomas (BCCs; 15 superficial, 26 nodular, and 6 sclerodermiform) were treated with 5% imiquimod cream once daily 5 times a week for 6 weeks in an open-label clinical trial. The overall response rate was 95.7%. Local side effects occurred in 68% of the patients as mild to moderate reactions with a clear association to the histological BCC subtype. Follow-up examinations for up to 17 months (median 10 months) showed scars in 14.9% of the patients and a recurrence rate of 6.6%. Overall, imiquimod represents a safe and effective treatment option for a selected cohort of BCC patients. Notably, by the second week of treatment 72.7% of BCC biopsies were histologically tumor-free, which correlated with a substantial decrease of the inflammatory infiltrate by up to 58% between weeks 3 to 6. This early imiquimod response might have important implications for the final definition of potentially shorter imiquimod treatment periods.     

Bilateral comparison of the efficacy and tolerability of 3% diclofenac sodium gel and 5% 5-fluorouracil cream in the treatment of actinic keratoses of the face and scalp

Actinic keratoses (AKs) are a common precancerous condition and are said to account for 14% of visits to dermatologists in the US each year. Along with cryotherapy, topical treatments are a mainstay of therapy for these lesions. One of the potential benefits of topical therapy is less pain and irritation as compared to cryotherapy. Additionally, topical therapies have a perceived benefit of treating subclinical lesions along with clinically evident keratoses. We conducted a bilateral comparison study of the efficacy and tolerability of diclofenac 3% gel used for 90 days and 5% fluorouracil cream used for 28 days in thirty patients with AK of the face and scalp. The diclofenac gel and 5-fluorouracil cream each demonstrated substantial efficacy in the number of lesions cleared and the proportion of patients with significant lesion clearing. In most patients, diclofenac induced only mild signs of inflammation compared to 5-fluoruracil, despite a longer treatment period. A greater number of patients expressed significant satisfaction with diclofenac gel compared to the 5-fluorouracil cream.     

5％咪喹莫特乳膏治疗浅表型婴儿血管瘤的临床疗效研究

目的：5％咪喹莫特乳膏（明欣利迪,四川明欣药业提供,批号：10091）作为一种新的免疫调节剂在国内已开始用于多种疾病的治疗,本研究旨在观察咪喹莫特治疗浅表型婴儿血管瘤的疗效。方法：60例浅表型婴幼儿血管瘤,平均年龄在17周,每周三次外用5％咪喹莫特乳膏,至一岁时,观察用药前后对比疗效和不良反应发生情况。治疗的消退程度以百分数计算,并比较IH各临床表型间有效率的统计学差异,用爿。检验。结果：60浅表型婴儿血管瘤（IH）的有效率为75％,使用前后疗效有统计学差异。不良反应主要为轻微皮肤红斑。结论：外用5％咪喹莫特乳膏对浅表型婴儿血管瘤有明显的疗效且使用安全,不良反应轻微。     

0.25% Prednicarbate cream and the corresponding vehicle induce less skin atrophy than 0.1% betamethasone-17-valerate cream and 0.05% clobetasol-17-propionate cream

Summary The atrophogenic potential of medium-potent topical glucocorticoids is still controversial. In a double-blind controlled trial 24 healthy volunteers either applied 0.25% prednicarbate cream or the corresponding vehicle to one and 0.1% betamethasone-17-valerate cream or 0.05% clobetasol-17-propionate cream to the other forearm twice daily. Skin thickness was regularly assessed during the six week period of application and for further three weeks thereafter, using both the B- and A-mode of a 20 MHz ultrasound scanner.Both betamethasone-17-valerate and clobetasol-17-propionate cream significantly reduced skin thickness as compared to cream base while prednicarbate cream did not.Given that 0.1% betamethasone-17-valerate- and 0.25% prednicarbate cream are reported to be about equipotent in the treatment of atopic eczema the latter preparation shows an increased ratio between its desired anti-inflammatory and its unwanted atrophogenic effect.     

Prospective, case-based assessment of sequential therapy with topical Fluorouracil cream 0.5% and ALA-PDT for the treatment of actinic keratosis

The sequential use of topical therapies and short-incubation photodynamic therapy for actinic keratosis (AK) has not been extensively studied. The author reports on treatment with sequential 5-fluorouracil (5-FU) cream 0.5% and 5-aminolevulinic acid?photodynamic therapy (ALA-PDT) in three older men with photodamaged skin and a history of AK. These findings suggest that this combination therapy, when compared with short-contact (1 hour) ALA-PDT alone, is more effective, minimizes the recurrence of areas of field cancerization and improves the appearance of the skin. The use of 5-FU cream 0.5% before and after photodynamic therapy is effective in revealing the presence of both clinical and subclinical AK lesions.     

艾拉光动力联合咪喹莫特乳膏治疗扁平疣的疗效

目的 观察艾拉光动力联合5%咪喹莫特乳膏治疗扁平疣的临床疗效。 方法 选取2010年5月至2014年10月收治的81例扁平疣患者,随机分为观察组41例与对照组40例。对照组患者仅给予5-氨基酮戊酸光动力疗法,而观察组患者在光动力治疗基础上再于患处涂抹5%咪喹莫特乳膏8周。治疗结束后连续3个月观察两组患者的临床疗效与复发情况并比较分析。 结果 观察组患者的总有效率为100.00%,高于对照组的92.50%,两组差异无统计学意义(P >0.05);②观察组患者复发率为5.26%,而对照组患者复发率为28.57%,两组比较差异有统计学意义(P <0.05)。结论 艾拉光动力联合5%咪喹莫特乳膏治疗扁平疣可以有效提高临床疗效,降低复发率。     

Safety studies of topical imiquimod 5% cream on normal skin exposed to ultraviolet radiation

BACKGROUND: Imiquimod 5% topical cream is an immune response modifier that induces interferon alpha and interleukin-12, and exhibits antiviral and tumor-inhibiting properties. It is currently available for treatment of genital and perianal warts. Three randomized, open-label or assessor-blinded, placebo-controlled studies were carried out to assess its safety on normal white skin exposed to ultraviolet radiation (UVR). METHODS: Healthy white volunteer adult subjects between the ages of 18 and 60 years with skin types I, II or III (Fitzpatrick Scale, US Federal Register 43:38260, 1978) were invited to participate. Imiquimod 5% cream (each dose approximately 0.1-0.2 ml) was compared with placebo cream. Two preliminary studies assessed the potential photosensitizing properties of the drug, and the third study added measurement of sunburn cell counts (SBC) and deoxyribonucleic acid (DNA) pyrimidine dimer (PD) formation. The three studies were: a 6-week standard photocontact allergenicity bioassay; a 4-day standard phototoxicity bioassay; and a 4-week photodamage study using biopsy sample analyses to determine SBC or PD frequency. RESULTS: Imiquimod had no detectable potential for inducing either photocontact allergy (n=115) or phototoxicity (n=20). The final study further assessing photodamage potential of imiquimod included 44 subjects. There were no significant differences between imiquimod vs. the control (no drug+UVB) for SBC counts (mean 0.88 vs. 0.93), or PD frequency (mean 60.86 vs. 70.03). CONCLUSIONS: Results from the two preliminary safety studies suggest that imiquimod 5% cream does not possess a detectable photosensitizing potential in humans. Furthermore, topical imiquimod did not enhance UVR-induced damage to epidermal cells or DNA.     

Treatment of Zoon's balanitis with imiquimod 5% cream

We report a case of a 43-year-old uncircumcised Caucasian, diabetic man with a 4-year history of Zoon's balanitis unresponsive to topical steroids, in whom control of the disease was achieved with topical imiquimod. A histopathological examination of a biopsy specimen was performed before and after treatment with imiquimod 5% cream applied 3 times a week. A moderate to marked increased local skin reaction occurred several times throughout the treatment period, necessitating multiple rest periods of several days' duration. Clinical but not histological resolution was obtained after 4 months of treatment, with no relapses at an 18-month follow-up. This positive treatment outcome indicates that imiquimod may have a role in the management of Zoon's balanitis. However, the dose and duration of therapy required to achieve complete clinical response still needs to be established. Also, the question of whether normalization of histology can be achieved with topical imiquimod has yet to be answered.     

Topical 5% 5-fluorouracil cream in the treatment of plantar warts: a prospective, randomized, and controlled clinical study

Topical 5-fluorouracil (5-FU) is an antineoplastic antimetabolite that inhibits DNA and RNA synthesis, thereby preventing cell replication and proliferation. This mechanism of action may allow topical 5-FU to be utilized in the treatment of human papilloma virus (HPV). We conducted a study comparing 5% 5-FU cream under tape occlusion versus tape occlusion alone in 40 patients presenting with plantar warts. Nineteen out of 20 patients (95%) randomized to 5% 5-FU with tape occlusion had complete eradication of all plantar warts within 12 weeks of treatment. The average time to cure occurred at 9 weeks of treatment. Three patients (15%) had a recurrence at the 6-month follow-up visit; accordingly, an 85% sustained cure rate was observed. It is concluded that use of topical 5% 5-fluorouracil cream for plantar warts is safe, efficacious, and accepted by the patient.