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Off-label aprepitant quells refractory pruritus.

WAIKOLOA, HAWAII - Oral aprepitant has shown considerable promise as a novel therapy in patients with refractory pruritus, including those with severe itching induced by biologic therapies for cancer.

"It's a tool we should consider using in patients with pruritus who do not respond to the usual measures," Dr. Mario E. Lacouture said at the annual seminar sponsored by Skin Disease Education Foundation (SDEF).

Aprepitant (Emend) is approved as an antiemetic agent for cancer patients on chemotherapy. But a growing body of data, including two proof-of-concept studies, has shown a high response rate in patients with itching resistant to standard treatment, including steroids, UV therapy, and antihistamines, noted Dr. Lacouture, a dermatologist at Memorial Sloan-Kettering Cancer Center, New York.

Severe itching is increasingly recognized as a side effect of targeted biologic agents for cancer, including erlotinib (Tarceva) and cetuximab (Erbitux). At last year's meeting of the American Society of Clinical Oncology Dr. Daniele Santini and coworkers at the Universita "Campus Bio-Medico" di Roma presented a study of 22 patients with severe pruritus treated with aprepitant using a regimen of 125 mg on day 1 and 80 mg on days 3 and 5.

After the single three-dose cycle of aprepitant, the patients' median pruritus intensity plummeted from a baseline of 8 down to 1 on a 0-10 visual analog scale (VAS). Twenty of 22 patients had more than a 50% reduction in pruritus. The median duration of benefit following a three-dose cycle given over 5 days was 25 days.

In the second proof-of-concept study, dermatologists at the Westfalische Wil-helms-Universitat Mi.inster (Germany) reported on 20 patients with refractory chronic pruritus from nonmalignant underlying disorders placed on aprepitant at 80 mg/day for 1 week. Sixteen of the 20 patients had a marked reduction in itch intensity. From a baseline mean of 8.4 points on the VAS, the group averaged a 42% improvement to a score of 4.3.

A significant reduction in itching was observed as early as 2 days after initiating aprepitant in the study population (PLoS One 2010;5:el0968). Patients with itching related to prurigo nodularis or atopic disease responded better than those without the conditions, and patients under age 60 obtained greater improvement than older patients. However, patients with chronic kidney disease as the underlying cause of their itching achieved only minimal benefit.

Side effects were confined to mild, non-treatment-limiting nausea, dizziness, and drowsiness in three patients.

Between the two proof-of-concept studies and smaller published case series, Dr. Lacouture said that he is aware of 63 patients with severe refractory pruritus who were treated with aprepitant. The result was an improvement from a mean baseline VAS of 8.4 to 2.3.

Dr. Lacouture has served as a consultant to more than a dozen pharmaceutical companies, although Merck, which markets aprepitant, is not among them.

SDEF and this news organization are owned by Elsevier.

BY BRUCE JANCIN

EXPERT ANALYSIS FROM THE SDEF HAWAII DERMATOLOGY SEMINAR
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Title Annotation:DERMATOLOGY
Author:Jancin, Bruce
Publication:Internal Medicine News
Date:Mar 15, 2012
Words:488
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