Aprepitant against pruritus in patients with solid tumours

ArticleinSupportive Care in Cancer 18(9):1229-30 · September 2010with25 Reads
DOI: 10.1007/s00520-010-0895-9 · Source: PubMed
    • "Lesional skin from patients with AD and prurigo nodularis is characterized by increased SP-positive sensory neurons [178, 179]. In an uncontrolled case series study, aprepitant, an antiemetic with NK1-receptor antagonist properties , effectively reduced pruritus due to various cutaneous and systemic causes180181182183. "
    [Show abstract] [Hide abstract] ABSTRACT: For centuries, itch was categorized as a submodality of pain. Recent research over the last decade has led to the realization that itch is in fact a separate and distinct, albeit closely related, sensation. Chronic itch is a common complaint and has numerous etiologies. Various receptors (TRPA1, TRPV1, PAR2, gastrin-releasing peptide receptor (GRPR), Mas-related G proteins), secreted molecules (histamine, nerve growth factor (NGF), substance P (SP), proteases), and cytokines/chemokines (thymic stromal lymphopoietin (TSLP), IL-2, IL-4, IL-13, and IL-31) are implicated as mediators of chronic pruritus. While much remains unknown regarding the mechanisms of chronic itch, this much is certain: there is no singular cause of itch. Rather, itch is caused by a complex interface between skin, keratinocytes, cutaneous nerve fibers, pruritogenic molecules, and the peripheral and central nervous systems. Atopic dermatitis is one of the most itchy skin dermatoses and affects millions worldwide. The sensation of atopic itch is mediated by the interplay between epidermal barrier dysfunction, upregulated immune cascades, and the activation of structures in the central nervous system. Clinicians are in possession of an arsenal of different treatment options ranging from moisturizers, topical immunomodulators, topical anesthetic ion channel inhibitors, systemic immunomodulators, as well as oral drugs capable of reducing neural hypersensitization. Emerging targeted therapies on the horizon, such as dupilumab, promise to usher in a new era of highly specific and efficacious treatments. Alternative medicine, stress reduction techniques, and patient education are also important treatment modalities. This review will focus on the mediators of chronic pruritus mainly associated with atopic dermatitis (atopic itch), as well as numerous different therapeutic options.
    Full-text · Article · May 2015
    • "One drug that appears to be effective in this respect is off-label aprepitant, a neurokinin 1 (NK-1) receptor antagonist that was approved in 2003 for the prevention of chemotherapy-induced nausea and vomiting, both acute and delayed. The main ligand of the NK-1 receptor , substance P, has emerged as an important mediator of the induction and maintenance of pruritus [5] . Furthermore , increased levels of NK-1 have been reported in the keratinocytes of patients with chronic pruritus [6]. "
    [Show abstract] [Hide abstract] ABSTRACT: Introduction: Paraneoplastic pruritus is defined as pruritus that occurs before or during the natural evolution of a hematologic disease. The reported prevalence is 30% in patients with Hodgkin's lymphoma. The severity of this pruritus has a very negative impact on patients' quality of life. Very few studies have been made to examine the efficacy of pharmacological treatments for this type of pruritus. One drug that appears to be effective in this respect is off-label aprepitant, a neurokinin 1 receptor antagonist. Case presentation: A 20-year-old Caucasian woman presented with lateral neck nodes, sweating, and pruritus and was diagnosed with stage IIB nodular sclerosis Hodgkin's lymphoma. Throughout this period during the disease the pruritus was ever-present. Improvement was achieved with some of the chemotherapy treatments, but the symptom returned when the various treatments were withdrawn due to disease progression or poor tolerance. In the middle of the seventh year, she was admitted to our hospital with uncontrolled pruritus that resulted in severe lesions due to scratching. In response, aprepitant (off-label) 80 mg/day was added to the chemotherapic treatment of the pruritus, after studying the various treatment options. She reported a score of 9 on a visual analogue scale for the pruritus, and a score of 3 on the Eastern Cooperative Oncology Group performance status scale of performance status. After two weeks of treatment with aprepitant, she reported a score of 5 on the visual analogue scale for the pruritus, and this improved to a score of 4 in a month, which allowed her to lead a better quality of life, with an Eastern Cooperative Oncology Group performance status score between 1 and 2. Conclusions: Several cases and case series have been reported on the use of aprepitant for paraneoplastic pruritus, but none have referred to its use for Hodgkin's lymphoma. A prospective study was carried out to evaluate the efficacy of this drug in refractory pruritus secondary to Sezary syndrome, and other authors have studied the effectiveness of aprepitant against pruritus, secondary to biological therapy with erlotinib. In our case report, treatment was started with daily doses of aprepitant 80 mg. Pruritus improvement appeared to be attributable exclusively to the administration of aprepitant.
    Full-text · Article · Sep 2014
    • "Moreover, lesional skin of patients with atopic dermatitis and prurigo nodularis is characterized by increased substance P positive sensory neurons [90,91] . Recently, the antiemetic NK1-receptor antagonist aprepitant was shown in uncontrolled case series to effectively reduce pruritus in patients with various dermatological and some systemic disorders [92], Sézary syndrome [93], solid tumours [94], and pruritus due to the epidermal growth factor inhibitor erlotinib [95]. These very promising results warrant confirmation in randomized, placebo-controlled trials. "
    [Show abstract] [Hide abstract] ABSTRACT: Pruritus is a sensory phenomenon accompanying a broad range of systemic disorders including hematologic and lymphoproliferative disorders, metabolic and endocrine diseases, solid tumours, and infectious diseases. The molecular mechanisms involved in itch sensation remain enigmatic in most of these diseases. However, from studies in patients and animal models a large number of mediators and receptors responsible for scratching behaviour have been identified in recent years. New insights into the interplay between neuronal and non-neuronal cells in the initiation, modulation and sensitization of itch sensation have been acquired. This review highlights the current knowledge of the molecular mechanism involved in pruritus of systemic disorders and summarizes the signalling pathways of biogenic amines, neuropeptides, proteases, eicosanoids, cytokines, opioids, endocannabinoids, neurotrophins, phospholipids and other signalling molecules participating in pruritus.
    Full-text · Article · Jul 2014
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