pep005 and Carcinoma--Basal-Cell

Skin cancer is a broad term used to describe a number of different malignant indications of the skin. Skin cancers mostly comprise of the keratinocyte cancers [Basal Cell Carcinoma (BCC) and cutaneous Squamous Cell Carcinoma (SCC)], and melanoma. Surgical excision of these malignancies has been the preferred treatment of patients for decades. However, the decision to perform surgery can be affected by various considerations, including co-morbidities of the patient, the anatomical site of the lesion and potential intolerance for repeated excisions. Topical treatment of skin cancer may therefore be more appropriate in certain instances. Topical treatment potentially allows for higher drug levels at the tumor site, and may result in less overall toxicity than systemic agents. This review will specifically address the current agents used in topical treatment of skin cancers, and introduce emerging treatments from the natural product field that may also find utility in these indications.

Topics: Administration, Cutaneous; Antineoplastic Agents; Carcinoma, Basal Cell; Clinical Trials as Topic; Diterpenes; Drug Delivery Systems; Fluorouracil; Humans; Hutchinson's Melanotic Freckle; Imiquimod; Keratosis, Actinic; Melanoma; Neoplasms, Squamous Cell; Photochemotherapy; Retinoids; Skin; Skin Neoplasms; Ultraviolet Rays

Although surgical intervention remains the standard of care for nonmelanoma skin cancer, other treatment modalities have been studied and used. Nonsurgical treatment methods include cryotherapy, topical medications, photodynamic therapy, radiation therapy, Hedgehog pathway inhibitors, programmed cell death protein 1 inhibitors, and active nonintervention. Despite the favorable efficacy of surgical treatment methods, many factors, including but not limited to patient age, preference, and severity of disease, must be taken into consideration when choosing the most appropriate, patient-centered treatment approach.

Topics: Administration, Cutaneous; Anilides; Antineoplastic Agents; Antineoplastic Agents, Immunological; Biphenyl Compounds; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Cryosurgery; Cyclooxygenase Inhibitors; Diclofenac; Diterpenes; Fluorouracil; Humans; Imiquimod; Photochemotherapy; Programmed Cell Death 1 Receptor; Pyridines; Radiotherapy; Skin Neoplasms; Watchful Waiting

Chemoprevention of nonmelanoma skin cancer should be considered in patients likely to develop numerous, invasive, or metastatic nonmelanoma skin cancers. This article reviews the various topical and systemic substances studied as chemopreventive agents.

Topics: Administration, Cutaneous; Administration, Oral; Antineoplastic Agents; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Chemoprevention; Cyclooxygenase Inhibitors; Diclofenac; Diterpenes; Fluorouracil; Humans; Imiquimod; Niacinamide; Photochemotherapy; Retinoids; Skin Neoplasms

Actinic keratosis (AK) is a common premalignant skin lesion that is frequently treated by cryosurgery. Basal cell carcinoma is the most common malignancy of man, and early-stage lesions are usually cured via surgery. Advanced basal cell carcinoma may require more extensive surgery resulting in deformity, and many advanced lesions cannot be treated surgically. Several recent developments have improved therapeutic options for both conditions. Cryosurgery is still a mainstay of treatment for AK, but the introduction of effective topical agents, imiquimod cream and ingenol mebutate, has provided alternatives to cryosurgery. For advanced basal cell carcinoma, the small-molecule inhibitor vismodegib has proven to be an effective therapy for lesions that are not amenable to surgery and has demonstrated ability to achieve dramatic improvement in advanced, potentially disfiguring cancer.

Topics: Aminoquinolines; Anilides; Antineoplastic Agents; Carcinoma, Basal Cell; Cryosurgery; Diterpenes; Humans; Imiquimod; Keratosis, Actinic; Mutation; Patched Receptors; Pyridines; Receptors, Cell Surface; Skin Neoplasms; Treatment Outcome

To present a brief review of periorbital cutaneous tumorogenesis, highlighting the steps which might be amenable to topical treatments and then discuss the use of topical agents in the management of periorbital skin malignancy.. A rapid expansion in the understanding of the pathogenesis of melanoma and nonmelanoma skin cancer has allowed the development of a number of topical agents targeting specific tumor-forming processes. Topical agents have been shown to be effective in the management of periorbital skin malignancy.. 5-Fluorouracil and imiquimod have established roles in the management of periorbital skin malignancy. Newer agents such as ingenol mebutate, tazarotene, and diclofenac gel probably have evolving roles that require further research but show promise.

Topics: Administration, Topical; Aminoquinolines; Antineoplastic Agents; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Diterpenes; Fluorouracil; Humans; Imiquimod; Mitomycin; Orbital Neoplasms; Skin Neoplasms

Ingenol mebutate gel is approved for actinic keratosis field therapy, but little has been published as a treatment of basal cell carcinoma (BCC). Our objective is to characterise the histopathological changes and the infiltrating cell populations to better understand its mechanism of action.. Sixteen patients with various BCC subtypes were prospectively evaluated and treated once daily for two consecutive days with ingenol mebutate gel 0.05% under occlusion. Patients were randomised to two arms: the first arm was biopsied between the third and the tenth day after treatment initiation ('early immune response'), and the second arm was biopsied at day 30 after treatment initiation ('late immune response'). The immunopathology was evaluated by immunohistochemistry: anti-CD3, anti-CD4, anti-CD8, anti-CD20, anti-CD56, anti-CD68, anti-Bcl-2, anti-CASP3, anti-FoxP3, anti-GrzB and anti-TIA-1.. Ten BCCs were in complete remission after 2 years of follow-up. The early immune response was characterised by a quick recruitment of T lymphocytes, macrophages and natural killer cells. At later time-points, T-regulatory cells and some pro-apoptotic markers were detected. Treatment-related adverse events were described.. Ingenol mebutate gel produces a transient immuno-inflammatory response and an important necrosis reaction in BCCs. Larger studies will be required to determine the maximum effective tolerated dose of ingenol mebutate gel for BCC.

Topics: Administration, Cutaneous; Aged; Antineoplastic Agents; Carcinoma, Basal Cell; Diterpenes; Female; Humans; Inflammation; Male; Middle Aged; Prospective Studies; Skin Neoplasms; Treatment Outcome

To evaluate the safety of two applications of PEP005 (ingenol mebutate) gel in superficial basal cell carcinoma. Efficacy was a secondary end-point.. Randomized, vehicle-controlled, phase IIa study conducted at eight private dermatology clinics in Australia. A total of 60 patients with histologically confirmed superficial basal cell carcinoma (lesion size, 4-15 mm) were randomized to treatment on days 1 and 2 (Arm A) or days 1 and 8 (Arm B) and, within each arm, to ingenol mebutate gel, 0.0025%, 0.01% or 0.05%, or vehicle gel. The main outcome measures were the incidence and severity of adverse events and local skin responses in Arms A and B; lesion clearance at day 85 was a secondary measure.. The incidence of adverse events was low. One patient treated with ingenol mebutate gel, 0.05% in Arm A experienced severe flaking/scaling/dryness extending beyond the application site. Non-severe, potentially treatment-related events included erythema extending beyond the application site, application-site pain and headache in two patients each. Six patients in Arm A had one or more severe local skin responses. Efficacy appeared to be dose-related and there was a trend towards higher clinical and histological lesion clearance rates in Arm A compared with Arm B. Histological clearance occurred in five of eight patients (63%) randomized to ingenol mebutate gel, 0.05% in Arm A.. Two applications of ingenol mebutate gel, 0.05%, are safe and have efficacy in patients with superficial basal cell carcinoma.

Topics: Administration, Topical; Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Carcinoma, Basal Cell; Diterpenes; Dose-Response Relationship, Drug; Female; Gels; Headache; Humans; Male; Middle Aged; Pain; Remission Induction; Skin Diseases; Skin Neoplasms; Treatment Outcome

The incidence of nonmelanoma skin cancer continues to increase. Surgical excision remains the best choice of treatment but the demand of patients is to have tissue-sparing approaches with good cosmetic results; these aims led to the development of novel therapeutic agents such as topical ingenol mebutate gel. We report the successful treatment with ingenol mebutate gel 0.05% of three pigmented basal cell carcinomas. Lesions were evaluated by dermoscopy and confocal microscopy before, during and after the treatment.

Topics: Antineoplastic Agents; Carcinoma, Basal Cell; Dermoscopy; Diterpenes; Female; Humans; Male; Microscopy, Confocal; Middle Aged; Skin Neoplasms; Treatment Outcome

Topics: Administration, Cutaneous; Aged; Aminoquinolines; Antineoplastic Agents; Carcinoma, Basal Cell; Cryotherapy; Diterpenes; Female; Gels; Humans; Imiquimod; Neoplasms, Multiple Primary; Nevus, Sebaceous of Jadassohn; Skin Neoplasms; Treatment Outcome

Topics: Aged, 80 and over; Carcinoma, Basal Cell; Diterpenes; Drug Monitoring; Hamartoma Syndrome, Multiple; Humans; Male; Microscopy; Microscopy, Confocal; Skin Neoplasms; Time Factors

Basal cell carcinoma is the most common non-melanoma skin cancer, and its incidence continues to raise. Although surgery can be considered the mainstay of therapy, new current pharmacological options are available and focus on tumor eradication, maximizing cosmetic results, and functional capacity. Several studies have recently reported on safety and efficacy of topical ingenol mebutate gel, a derivative of the plant Euphorbia Peplus, used to treat actinic keratosis and superficial basal cell carcinoma. In our knowledge, we report for the first time the dermoscopic evaluation of outcome and monitoring of superficial pigmented and non-pigmented basal cell carcinomas in four patients treated by this novel non-ablative agent. Ingenol mebutate gel therapy has showed to be effective and without important side-effects for pigmented and non-pigmented superficial basal cell carcinomas. We emphasize the usefulness of dermoscopy in supporting the clinical diagnosis and excluding the presence of tumor residue or recurrence. In a future scenario, we hope it will be soon possible to follow-up the lesions, after treatment, avoiding post-control biopsy punch.

Topics: Aged, 80 and over; Antineoplastic Agents; Biopsy; Carcinoma, Basal Cell; Dermoscopy; Diterpenes; Female; Humans; Male; Middle Aged; Nevus, Pigmented; Skin Neoplasms; Time Factors; Treatment Outcome

Epidermodysplasia verruciformis (EV) is a rare genetic disorder characterized by widespread human papillomavirus (HPV) associated lesions and an increase susceptibility to cutaneous malignancies. A host of medications traditionally used to treat warty lesions have been used with variable results and limited success. To our knowledge, we describe the first reported case of a patient with Imiquimod resistant EV successfully treated with topical ingenol mebutate (Picato).. A patient with a 5 year history of EV failed to respond to a 6 week course of 5% imiquimod on the forehead and was subsequently treated with a 3 day course of 0.015% Picato gel which resulted in significant clinical improvement. A one month follow-up examination showed no reoccurrence of the lesions with the patient reporting continued satisfaction of the outcome.. Our case provides insight into the potential use of ingenol mebutate for EV patients unresponsive to traditional medical treatments.

Topics: Acitretin; Adult; Aminoquinolines; Antineoplastic Agents; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Diterpenes; Drug Resistance; Epidermodysplasia Verruciformis; Female; Gels; Humans; Imiquimod; Keratolytic Agents; Rare Diseases; Skin Neoplasms; Treatment Outcome; Tretinoin

We present the case of a 73-year-old male patient who had received a first renal transplant at 36 years and a second one at the age of 55 years. He is currently under immunosuppression with everolimus 2.5 mg/day and prednisone 5 mg/day. The patient presented with multiple actinic keratoses on both cheeks and the forehead and received treatment by ingenol mebutate 150 µg/g gel daily on 3 consecutive days on his right cheek and methyl aminolevulinate (MAL) photodynamic therapy activated by daylight (MAL-dPDT) on the forehead and the left cheek. MAL-dPDT treatment proved a feasible, repeatable, physician-directed method of treating field cancerization with limited morbidity for a period of 6 days. Treatment with ingenol mebutate gel was a feasible, possibly self-directed method of treating field cancerization with limited morbidity for 10 days in this immunosuppressed patient. Both treatments showed similar efficacy. At the time of treatment, the MAL daylight PDT ran at 3 times the cost of ingenol mebutate gel.

Topics: Aged; Aminolevulinic Acid; Antineoplastic Agents; Carcinogenesis; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Diterpenes; Face; Humans; Keratosis, Actinic; Kidney Transplantation; Male; Photochemotherapy; Photosensitizing Agents; Skin Neoplasms; Transplant Recipients

Patients suffering from chronic lymphocytic leukemia often develop actinic keratosis (AK) and squamous cell carcinoma in sun-exposed areas. In these particular patients, who have a suboptimal immune function, AK treatment can be particularly challenging. We report the case of a patient who failed to respond to most AK treatments, including 5-FU, imiquimod and photodynamic therapy, but responded to ingenol mebutate. We started with 3 applications of 150 μg/g (registered treatment of the scalp) and also 2 applications of 500 μg/g (registered in for trunk and extremities). Both treatments were well tolerated, but only the latter led to significant clinical success. This suggests that 500 μg/g of ingenol mebutate may represent an interesting therapeutic option in patients with mild immunosuppression.

Topics: Aged; Antineoplastic Agents; Carcinogenesis; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Diterpenes; Humans; Keratosis, Actinic; Leukemia, Lymphocytic, Chronic, B-Cell; Male; Scalp; Skin Neoplasms

Surgery is the therapy of choice in the guidelines to treat basal cell carcinomas (BCCs) but a variety of non-surgical options are available. The objective of this study is to evaluate the efficacy and safety of ingenol mebutate 0.05% gel for the treatment of superficial BCCs. We accepted twenty patients with superficial BCCs on the body and we treated them once daily for two consecutive days with ingenol mebutate 0.05% gel. We examined the lesions at the screening visit and after four days from the gel application to describe the local skin reaction due to the therapy. Then we followed the patients after two and six months from the first visit. All the lesions were clinically and dermoscopically documented with a digital camera and we used the LSR (local skin reaction) grading scale based on a 0-4 numerical index of severity with specific clinical parameters and a characteristic photographic image for each rating, to assess the local side effects related to the therapy.

Topics: Administration, Cutaneous; Aged; Aged, 80 and over; Antineoplastic Agents; Carcinoma, Basal Cell; Dermoscopy; Diterpenes; Female; Gels; Humans; Male; Middle Aged; Photography; Skin Neoplasms; Time Factors; Treatment Outcome

The incidence of nonmelanoma skin cancer continues to increase. While surgical excision remains the mainstay of treatment, growing demand from patients for effective, tissue-sparing approaches with good cosmetic results has led to the development of novel therapeutic agents. Several studies have reported on the safety and efficacy of topical ingenol mebutate gel, a derivative of the plant Euphorbia peplus, in the treatment of actinic keratosis and superficial basal cell carcinoma. An understanding of the history, mechanism of action, and recent trial evidence for this emerging therapy can assist physicians in counseling patients on available treatment options and in selecting appropriate therapy.

Topics: Administration, Cutaneous; Antineoplastic Agents, Phytogenic; Carcinoma, Basal Cell; Diterpenes; Euphorbia; Humans; Keratosis, Actinic; Skin Neoplasms