pep005 and Skin-Diseases

Topical antineoplastic agents have a well-established role in the treatment of several dermatological conditions. Their use in the treatment of mucosal skin disease also has gained increasing recognition. Topical 5-fluorouracil (5-FU), an antimetabolite, and imiquimod, an immunomodulatory agent with antitumor properties, are the two principal topical antineoplastic agents used in the treatment of mucocutaneous diseases. Although the vast majority of their mucosal uses are currently not approved by the Federal Drug Administration, there are numerous case series, open-label studies and randomized controlled trials supporting their uses in the treatment of mucocutaneous diseases. Both topical 5-FU and imiquimod have been successfully utilized in the treatment of a wide range of mucosal diseases, including actinic cheilitis, Bowen's disease of the anal and vulvar mucosa, and genital and perianal condyloma. Reports of their uses in the treatment of mucocutaneous diseases indicate that these agents can be safely administered, though adverse effects such as local inflammation may be augmented when these agents are applied to mucosal surfaces. Additionally, locally acting intralesional chemotherapeutic agents, such as bleomycin and interferon, have well-defined applications in the treatment of mucosal skin diseases such as condyloma acuminata. As further studies are conducted, these topical and intralesional neoplastic agents, in addition to emerging agents that are in various stages of development, such as Toll-like receptor 9 agonists and ingenol mebutate, may play an increasingly important role in the future treatment of mucocutaneous diseases.

Topics: Administration, Topical; Aminoquinolines; Antineoplastic Agents; Diterpenes; Fluorouracil; Humans; Imiquimod; Keratosis, Actinic; Mucositis; Mucous Membrane; Skin Diseases; Skin Neoplasms

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

Topics: Aged, 80 and over; Carcinoma, Squamous Cell; Diterpenes; Granulation Tissue; Humans; Male; Scalp; Skin Diseases; Skin Neoplasms; Treatment Outcome

Topics: Aged; Diterpenes; Humans; Male; Middle Aged; Scalp; Skin Diseases

'Hydroxyurea-induced Squamous Dysplasia' (HISD) is a cutaneous side-effect related to chronic oral treatment with Hydroxyurea. Ingenol mebutate gel is a topical drug approved for the treatment of multiple, non-hypertrophic actinic keratoses (AK) localized within a limited cancerization field. Since HISD may be considered as a drug-induced variant of classic AK, ingenol mebutate is likely to have therapeutic effects.. The aim of this study was to evaluate efficacy and safety of ingenol mebutate 150 mcg/g and 500 mcg/g, as a treatment of HISD lesions on face/scalp and trunk/extremities respectively.. Seven areas with a mean of lesions of 5.9 ± 1.7 in five patients with HISD were treated. Patients with lesions on face/scalp self-treated a 25 cm(2) skin affected area with ingenol mebutate gel 150 mcg/g, one tube daily for 3 days. Patients with lesions localized on trunk/extremities treated the same size affected area with ingenol mebutate gel 500 mcg/g, one tube daily for 2 days. Clinical assessment and count of HISD lesions has been performed by an experienced dermatologist at day 0, at day 57, and at time of last feasible follow-up visit (median 337 days). Safety assessment included the report of all SAEs.. At 57-day follow-up, we observed an overall response rate (ORR) - the sum of Complete Responses (CR) + Partial Responses (PR) - of 87.5%, with a 57.1% CR, and a 78.0% total lesions' reduction compared to time 0 (P < 0.01). On a median follow-up of 337 days, we observed a long-term ORR of 71.4%, a 57.1% CR ratio and a 65.9% total lesions' reduction compared to time 0 (P = 0.01). No severe (grade 3-4) adverse events have been reported.. Although obtained in a small case series, these encouraging data lead us to propose ingenol mebutate gel as a possible treatment for HISD.

Topics: Aged; Diterpenes; Female; Humans; Hydroxyurea; Male; Middle Aged; Skin; Skin Diseases