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.
"I think it’s a tool we should consider using in our patients with pruritus who do not respond to the usual measures," Dr. Mario E. Lacouture said at the annual Hawaii Dermatology Seminar sponsored by Skin Disease Education Foundation (SDEF).
BRUCE JANCIN/Elsevier Global Medical News
Dr. Mario E. Lacouture discusses the side effects of biologic agents used for treating cancer.
Aprepitant (Emend) is approved as an antiemetic agent for cancer patients undergoing chemotherapy. But a growing body of data, including two single-arm proof-of-concept studies, has shown a high response rate in patients with itching resistant to standard treatment, including corticosteroids, UV therapy, and antihistamines, noted Dr. Lacouture, a dermatologist at Memorial Sloan-Kettering Cancer Center, New York.
Severe itching is increasingly recognized as an important 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 Università "Campus Bio-Medico" di Roma presented a study involving 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 3-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 experienced a greater than 50% reduction in pruritus. The median duration of benefit following a 3-dose cycle given over 5 days was 25 days.
In the second proof-of-concept study, dermatologists at the Westfälische Wilhelms-Universität Münster (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 experienced a marked reduction in itch intensity. From a baseline mean of 8.4 points on the VAS, the group as a whole averaged a 42% improvement to a post-treatment 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:e10968).
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 reported patients with severe refractory pruritus, including 6 with Sézary syndrome and 2 with mycosis fungoides, who were treated with aprepitant on various dosing regimens. The result was an improvement from a mean baseline VAS of 8.4 to 2.3.
Aprepitant’s mechanism of benefit in cases of severe pruritus is believed to lie in the drug’s high affinity as an antagonist of neurokinin receptor 1, which is expressed in the skin and CNS, he explained. Substance P, an important mediator in the initiation and maintenance of pruritus, binds to this receptor.
Dry skin due to radiation therapy, chemotherapy, or cachexia is the most common cause of pruritus in oncology. But he added that pruritus is intrinsically often a prominent feature of a variety of paraneoplastic diseases and malignancies, and aprepitant is worthy of study in refractory cases.
Pruritic paraneoplastic dermatoses in which the skin findings are an indication of potential concurrent underlying malignancy include dermatomyositis, erythroderma, generalized granuloma annulare, and acrokeratosis paraneoplastica.
Hematologic malignancies where itch often figures prominently include Hodgkin’s disease, polycythemia vera, and Waldenström macroglobulinemia. The solid cancers most frequently accompanied by severe itching include malignancies of the brain, prostate, rectum, and vulva.
Dr. Lacouture reported serving 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.