minimal systemic exposure of a new topical triazole antifungal, efinaconazole 10% solution, in...

P6446Incidence of alopecia from endocrine therapies in cancer

Vishal Saggar, New York University School of Medicine, New York, NY, UnitedStates; Mario E. Lacouture, MD, Memorial Sloan-Kettering Cancer Center, NewYork, NY, United States; Maura Dickler, MD, Memorial Sloan-Kettering CancerCenter, New York, NY, United States; Shenhong Wu, MD, PhD, Stony BrookUniversity, Stony Brook, NY, United States

Background: Whereas alopecia to cytotoxic chemotherapies is a well describedevent, hair loss in patients treated with endocrine therapies (antiestrogens,aromatase inhibitors) has not been systematically investigated. These agents arewidely used in the treatment and prevention of many types of solid tumors,including breast and prostate cancers. We performed a systematic analysis of theliterature in order to determine the frequency of alopecia for each of these drugs, inorder to provide information that is critical for counseling and interventions againstalopecia, a major quality of life issue for many patients.

Methods: Relevant publications were identified from a PubMed search confined tophase II and III clinical trials, from 1966-2012. Keywords used in the search were‘‘fulvestrant, octreotide, fluoxymesterone, nilutamide, flutamide, bicalutamide,estradiol, medroxyprogesterone, megestrol, leuprolide, anastrozole, letrozole,exemestane, tamoxifen, toremifene, and raloxifene.’’

Results: Of 1384 search results, 35 (2.5%) trials were found that included rates ofalopecia, without confounding variables such as concurrent treatment with addi-tional biologic therapy or chemotherapy. Data from a total of 14,769 patients wereanalyzed. Alopecia was reported with the use of the aromatase inhibitorsanastrozole, letrozole, and exemestane, ranging from 0 to 9.4%, the LHRH agonistleuprolide, in 9.5% of patients, fulvestrant, ranging from 0% to 8%, megestrol,ranging from 0.5% to 11%, and tamoxifen, ranging from 0% to 17%. The types ofcancer in which agents were reported to cause alopecia were breast (74%),hepatocellular (5.7%), ovarian (5.7%), prostate (5.7%), endometrial (2.8%), renal(2.8%), and meningioma (2.8%).

Conclusion: Alopecia is a common, yet underreported side effect secondary toendocrine agents used against cancer, especially those of the breast and prostate.The long-term use of these agents heightens the importance of this adverse event onpatients’ quality of life. Knowledge of the incidence of alopecia represents the firststep towards the understanding and management of this frequently occurringuntoward event that may affect many people receiving these therapies.

APRIL 20

cial support: None identified.

P6603Insulin resistance and hair disorders, idiopathic hirsutism, and andro-genic alopecia

Gita Meshkat Razavi, MD, Gita Meshkat Razavi, Palo Alto, CA, United States; GityMeshkat Razavi, MD, Gity Meshkat Razavi, Palo Alto, CA, United States

Background: Insulin resistance is becoming a focused cause in hair disorder such asidiopathic hirsutism that is characterized by hirsutism with normal ovulatoryfunction in females and androgenic alopecia which is known to be androgendependent in males since insulin has found in hair follicles and may play a role inregulation of hair growth cycle.

Objective: To evaluate the accuracy of this hypothesis we conduct a case controlstudy to evaluate the relation between metabolic syndrome factors and androgenicalopecia (AGA) in a male group and idiopathic hirsutism (IH) in a female group andcontrol groups.

Methods: This study conducted as a case control assay with 33 females with IH and35 nonobese female control group and 97 males with AGA and 87 males as a controlgroup.

Results: Serum fasting insulin level, FBG, serum total cholesterol, triglyceride, HDLshow no significant difference between cases and controls in male group, mean-while fasting insulin level, HOMA, free androgen in IH group were higher thancontrol subjects but it still it was not meaningful.

Conclusion: Our study shows no significant relation between insulin resistanceneither with idiopathic hirsutism nor with androgenic alopecia. However, it mightbe recommendable to consider this relationship more cautiously.

cial support: None identified.

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P6548Minimal systemic exposure of a new topical triazole antifungal, efinaco-nazole 10% solution, in patients with severe onychomycosis following 28-day treatment

Christopher Crean, MS, Valeant Pharmaceuticals North America LLC, Durham,NC, United States; Akinori Aoyama, MS, Kaken Pharmaceutical Co Ltd, Shizuoka,Japan; Alexander Oh, PhD, Valeant Pharmaceuticals North America LLC,Bridgewater, NJ, United States; Robert Kang, MS, Valeant PharmaceuticalsNorth America LLC, Durham, NC, United States

Background: Onychomycosis is a common fungal infection of toenails with oralmedication preferred as first line therapy. However this approach may be limited insome patients by potential drugedrug interactions, systemic safety concerns (eg,liver toxicity), and by the potential need for laboratory monitoring. A topicaltreatment may be preferable, but the cure rates reported are much lower than thoseobserved with systemic treatments and to date no topical treatment has beenapproved as monotherapy in the United States.

Objective: To evaluate the safety and systemic exposure of once daily topicallyapplied efinaconazole 10% solution in subjects with severe onychomycosis of thetoenails.

Methods: Single center, open-label study in 19 subjects (21-70 years old) with severeonychomycosis (approximately 90% of the toenail affected with a positive KOH).Efinaconazole 10% solution (0.42 mL) was applied once daily for 28 days undermaximal exposure conditions (to all 10 toenails), with a 2-week posttreatmentfollow-up. Pharmacokinetic evaluations of efinaconazole and its metabolites (H3 andH4) were conducted during 3 separate periods: day 1-2, day 14-15, and day 28-29.Evaluations of safety were conducted throughout the study.

Results: Efinaconazole Cmax increased slightly at each assessment period from 0.23ng/mL on day 1, to 0.67 ng/mL on day 29. H3 metabolite Cmax increased from 0.09ng/mL on day 1, to 2.36 ng/mL on day 28. The H4metabolite was not quantifiable onday 1 and Cmax was 0.045 ng/mL on day 28. Plasma concentrations versus timecurves were generally flat for efinaconazole and H3. Mean total exposure levels(AUCt) of efinaconazole, H3, and H4 were very low at 12, 46, and 2.0 ngh/mL,respectively, on day 28. A total of 4 adverse events (AEs) were reported; none wereserious, related to study drug or resulted in study discontinuation. There were noclinically meaningful changes in laboratory parameters and no reports of swelling orvesiculation. One subject reported mild redness on day 7 following application ofeffinaconazole and there were a few (10%) reports of burning and/or itching, butthese were not considered AEs.

Conclusion: Efinaconazole 10% solution provided low systemic exposures toefinaconazole and its metabolites when applied once daily for 28 days to all 10toenails. Efinaconazole was safe and well tolerated in adult subjects with severedistal lateral subungual onychomycosis affecting both great toenails.

nsored by Valeant Dermatology a division of Valeant Pharmacerica LLC.

100% spo euticalsNorth Am

P6362Onychomatricoma with classic features: Case report and review of theliterature

John Kelly, MD, PhD, University of Connecticut Health Center, Farmington, CT,United States; Adrienne Berke, MD, University of Connecticut Health Center,Farmington, CT, United States; Arni Kristjansson, MD, University of ConnecticutHealth Center, Farmington, CT, United States; Douglas Leone, MD, Great LakesDermatology, Racine, WI, United States; Siobhan Collins, MD, DermatologySurgical Associates, Farmington, CT, United States

A 63-year-old white man presented to the dermatology clinic for the evaluation ofnail dystrophy of the left pollex. It initially appeared 7 years earlier, with nopreceding trauma, and had been consistently asymptomatic. Physical examinationrevealed a nontender, ill-defined subungal mass distorting the distal left pollex.There was partial onychodystrophy with splitting, longitudinal ridging, thickening,splinter hemorrhages, increased transverse curvature, and yellow discoloration ofthe nail plate. Radiographic studies revealed only minor degenerative changes of theIP joint. Diagnostic surgical biopsy revealed a very firm, exophytic, white, 5-mmnodule of the nail matrix with multiple soft filiform extensions projecting distallyover the nail bed. Hematoxylineeosin staining showed a polypoid lesion. Thematrix epitheliumhad deepprojection into the underlying dermis and stroma,whichwas organized into two layers: (1) a superficial, highly-cellular layer with prominentfibrillary collagen, fibroblasts and mast cells and (2) a deeper, less-cellular layer withthicker collagen fibers. In addition, there were small nail plate extensions formingglove-like projections at the end of proximal nail plate. Immunohistochemistryrevealed staining of stromal cells with CD34 and factor XIIIA and no staining withS100, Mart-1, EMA, and CD56. This analysis and clinical picture were consistent withthe definitive diagnosis of onychomatricoma, a rare, benign, subungual tumor thatproduces deformity through autonomous production of nail plate keratin. Thepatient was successfully treated via elective surgical excision and has remained freefrom recurrence. As of 2012 approximately 70 cases of definitive onychomatricomahave been identified worldwide, with nearly 2/3 of patients being European andsporadic reports fromNorth and South America. The female:male ratio is;1:1.8, andnearly every digit has been reported affected at least once. Age at presentation varieswidely, from 24 to 70 years old (excluding a single pediatric report), and mostpatients have had an indolent tumor for several years before seeking medicalattention.While there is some histologic variation suggesting potential for malignanttransformation, there are no reports of malignancy arising from an onychomatri-coma, though there are a handful of cases that have relapsed following surgicalresection.

cial support: None identified.

J AM ACAD DERMATOL AB107