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      Differential clinical pharmacology of rolapitant in delayed chemotherapy-induced nausea and vomiting (CINV)

      1 , 2

      Drug Design, Development and Therapy

      Dove Medical Press

      nausea, vomiting, chemotherapy, rolapitant, CINV

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          Abstract

          Rolapitant is a highly selective neurokinin-1 receptor antagonist, orally administered for a single dose of 180 mg before chemotherapy with granisetron D1, dexamethasone 8 mg BID on day 2–4. It has a unique pharmacological characteristic of a long plasma half-life (between 163 and 183 hours); this long half-life makes a single use sufficient to cover the delayed emesis risk period. No major drug–drug interactions between rolapitant and dexamethasone or other cytochrome P450 inducers or inhibitors were observed. The clinical efficacy of rolapitant was studied in two phase III trials in highly emetogenic chemotherapy and in one clinical trial in moderately emetogenic chemotherapy. The primary endpoint was the proportion of patients achieving a complete response (defined as no emesis or use of rescue medication) in the delayed phase (>24–120 hours after chemotherapy). In comparison to granisetron (10 μg/kg intravenously) and dexamethasone (20 mg orally) on day 1, and dexamethasone (8 mg orally) twice daily on days 2–4 and placebo, rolapitant showed superior efficacy in the control of delayed and overall emesis. This review aims at revising the pharmacological characteristics of rolapitant, offering an updated review of the available clinical efficacy and safety data of rolapitant in different clinical settings, highlighting the place of rolapitant in the management of chemotherapy-induced nausea and vomiting (CINV) among currently available guidelines, and exploring the future directions of CINV management.

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          Most cited references 54

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          Antiemetics: American Society of Clinical Oncology clinical practice guideline update.

          To update the American Society of Clinical Oncology (ASCO) guideline for antiemetics in oncology. A systematic review of the medical literature was completed to inform this update. MEDLINE, the Cochrane Collaboration Library, and meeting materials from ASCO and the Multinational Association for Supportive Care in Cancer were all searched. Primary outcomes of interest were complete response and rates of any vomiting or nausea. Thirty-seven trials met prespecified inclusion and exclusion criteria for this systematic review. Two systematic reviews from the Cochrane Collaboration were identified; one surveyed the pediatric literature. The other compared the relative efficacy of the 5-hydroxytryptamine-3 (5-HT(3)) receptor antagonists. Combined anthracycline and cyclophosphamide regimens were reclassified as highly emetic. Patients who receive this combination or any highly emetic agents should receive a 5-HT(3) receptor antagonist, dexamethasone, and a neurokinin 1 (NK(1)) receptor antagonist. A large trial validated the equivalency of fosaprepitant, a single-day intravenous formulation, with aprepitant; either therapy is appropriate. Preferential use of palonosetron is recommended for moderate emetic risk regimens, combined with dexamethasone. For low-risk agents, patients can be offered dexamethasone before the first dose of chemotherapy. Patients undergoing high emetic risk radiation therapy should receive a 5-HT(3) receptor antagonist before each fraction and for 24 hours after treatment and may receive a 5-day course of dexamethasone during fractions 1 to 5. The Update Committee noted the importance of continued symptom monitoring throughout therapy. Clinicians underestimate the incidence of nausea, which is not as well controlled as emesis.
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            Chemotherapy-induced nausea and vomiting.

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              On the receiving end--patient perception of the side-effects of cancer chemotherapy.

              We conducted a survey to identify and rank side-effects perceived by 99 patients receiving cancer chemotherapy. Non-physical side-effects constituted 54% of the 15 most severe symptoms, and included the thought of coming for treatment, the length of time taken by treatment and having to have a needle. Major physical side-effects were vomiting, nausea and hair loss. Differences in ranking of severity of side-effects were evident when patient groups were divided by sex, age, marital status and domestic situation, as well as by diagnosis, treatment and response. Evaluation of patient perception of the severity of side-effects is an aid to striking the cost benefit balance when deciding whether to use cancer chemotherapy.
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                Author and article information

                Journal
                Drug Des Devel Ther
                Drug Des Devel Ther
                Drug Design, Development and Therapy
                Drug Design, Development and Therapy
                Dove Medical Press
                1177-8881
                2017
                24 March 2017
                : 11
                : 947-954
                Affiliations
                [1 ]Medical Oncology Department, Maadi Armed Forces Hospital
                [2 ]Clinical Oncology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt
                Author notes
                Correspondence: Omar Abdel-Rahman, Clinical Oncology Department, Faculty of Medicine, Ain Shams University, PO Box 11331, Cairo, Egypt, Tel +20 100 854 1806, Fax +20 2 685 8397, Email omar.abdelrhman@ 123456med.asu.edu.eg
                Article
                dddt-11-947
                10.2147/DDDT.S108872
                5373840
                © 2017 Rashad and Abdel-Rahman. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                Categories
                Review

                Pharmacology & Pharmaceutical medicine

                cinv, rolapitant, chemotherapy, vomiting, nausea

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