ice r Sc nce ce a n n a d C R f Journal of Cancer Science and e o s l e a a n r r c Moustafa et al., J Can Sci Res 2017, 2:1 h u o J Research DOI: 10.4172/2576-1447.1000107 ISSN: 2576-1447 Research Article Open Access Efficacy and Safety of Aprepitant in Combination with Dexamethasone, Granisetron and Metoclopramide as a Prophylaxis of Chemotherapy- Induced Nausea and Vomiting in a Cute and Delayed Emesis in Arab Cancer Patient Iman Moustafa1*, Frasia Oosthuizen2, Essam M Badwey2 and Abdulkarim Cara2 1King Abdulaziz Medical City, Alhasa, Saudi Arabia 2School of Health Sciences, University of KwaZulu-Natal, South Africa *Corresponding author: Iman Moustafa, King Abdulaziz Medical City, Alhasa, Saudi Arabia, Tel: +966118011111; E-mail: [email protected] Received date: May 8, 2017; Accepted date: May 17, 2017; Published date: May 20, 2017 Copyright: © 2017 Moustafa I, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Abstract Background: Chemotherapy Induced Nausea and Vomiting (CINV) is one of the greatest sources of distress for patients. Severe CINV may force interruption of chemotherapy, it is important to control CINV to achieve successful chemotherapy. Objective: This study to evaluate the efficacy and safety of aprepitant in a regimen containing aprepitant in combination with dexamethasone, granisetron and metoclopramide (APRDGM) versus a regimen dexamethasone, granisetron and metoclopramide (DGM) only, as a prophylaxis in (CINV) in highly emetogenic chemotherapy(HEC) in Arabic cancer patients. Setting: This study was conducted at King Abdul-Aziz Medical city (Eastern Region, AlHasa, Saudi Arabia). Methods: 309 patients all Arab population, treated with HEC, were enrolled in a retrospective, cohort study to investigate the efficacy and safety of (APR-DGM) compared to (DGM) regimen. Main outcome measure: The primary efficacy endpoint was the complete response (CR) for acute emesis and determines the adverse drug events. Secondary endpoint was the CR for delayed emesis. Results: The APR-DGM regimen showed a significantly improved control in the management of CINV in patients treated with HEC in acute emesis compared to the DGM regimen (P=0.0021). No significant difference was observed between the two regimens regards to delayed emesis (P=0.145). Both regimens were well tolerated, and the rates of adverse events were not significantly different between the regimens. Conclusion: The addition of aprepitant to the standard regimen of dexamethasone, granisetron and metoclopramide was found to be significantly better than dexamethasone, granisetron and metoclopramide alone, but only in the control of acute emesis, with no significant change in delayed emesis in Arab population. Keywords: Aprepitant; CINV; Nausea; Vomiting; Safety; Efficacy The incidence of acute and delayed nausea and vomiting (N&V) was investigated in highly and moderately emetogenic chemotherapy Introduction treatment regimens. Patients were recruited from 14 oncology practices in six countries. More than 35% of patients experienced acute According to the world statistics, 14.1 million adults in the world nausea and 13% experienced acute emesis. In patients treated with were diagnosed with cancer in 2012. There were 8.2 million deaths highly emetogenic chemotherapy, 60% experienced delayed nausea, from cancer in the world in 2012 [1]. Therefore a lot of research is and 50% experienced delayed emesis. In patients treated with directed towards the treatment of cancer and the management of moderately emetogenic chemotherapy, 52% experienced delayed related side effects of chemotherapy. There are many side effects nausea, and 28% experienced delayed emesis [2]. associated with chemotherapy but chemotherapy-induced nausea and vomiting (CINV) is considered an extreme side effect that affects the At the 2009 MASCC/ESMO Consensus Conference, an expert panel quality of life of the patient. CINV is a common adverse event in used data to establish rankings of emetogenicity for chemotherapy cancer therapy. Because CINV has a strong negative influence on agents [3,4]. Oral chemotherapy agents are now ranked separately patient quality of life (QOL), CINV management is highly important. from IV agents as there are intrinsic differences in emetogenicity as The most problematic effects caused by CINV are dehydration, well as different schedules of administration [4,5]. malnutrition, metabolic imbalances, and potential withdrawal from Emesis is classified according to the two following major types: future cycles of chemotherapy. J Can Sci Res, an open access journal Volume 2 • Issue 1 • 1000107 ISSN:2576-1447 Citation: Moustafa I, Oosthuizen F, Badwey EM, Cara A (2017) Efficacy and Safety of Aprepitant in Combination with Dexamethasone, Granisetron and Metoclopramide as a Prophylaxis of Chemotherapy-Induced Nausea and Vomiting in a Cute and Delayed Emesis in Arab Cancer Patient. J Can Sci Res 2: 107. doi:10.4172/2576-1447.1000107 Page 2 of 6 Acute emesis is vomiting that occurs during the first 18-24 hours administration of chemotherapy in delayed (24-20 hours) phase of after chemotherapy administration with peak occurring at 4-6 hours emesis. depending on the agent given. Evaluate the incidence of delayed emesis (25-120 hours) in regimen Delayed emesis with vomiting occurring >18-24 hours after 1 (DGM) 25-120 hours after administration of chemotherapy chemotherapy administration, but may occur up to 5 days after compared to regimen 2 (APR-DGM) 25-120 hours after chemotherapy with the peak in 2 to 3 days [6]. CINV can range from administration of chemotherapy. mild, to moderate and severe [7]. Chemotherapeutic agents are generally classified by their Ethics Approval emetogenic effects, namely, “highly emetogenic chemotherapy” (HEC), This study received approval from the Investigational Review Board “moderately emetogenic chemotherapy” (MEC), and “lower-minimal KAIMRC Research Office - King Abdullah International Medical emetogenic chemotherapy”, according to the frequency and strength of Research Center under Subject RA15/002/A-"Efficacy and safety of vomit-inducing effects [8,9]. Aprepitant as a prophylaxis of CINV in highly emetogenic level of The triple antiemetic therapy, using a 5-HT3 receptor antagonist, chemotherapy in combination with Dexamethasone, Granisetron and dexamethasone, and a neurokinin-1 (NK1) receptor antagonist, is the Metoclopramide (DGM)". Full ethical approval for the study was established and recommended treatment for HEC regimens. This triple obtained from the Biomedical Research Ethics Committee of the antiemetic therapy prevents vomiting, and, to a lesser extent, nausea in University of KwaZulu-Natal (BE050/1). the majority of patients [6,10,11]. The study was conducted in accordance with the principles of the While the majority of trials in literature have studied triple Declaration of Helsinki and its amendments and in compliance with medication including dexamethasone, granisetron and aprepitant for International Conference on Harmonization, Good Clinical Practices, prophylaxis of CINV, the aim of this study was to compare aprepitant and all applicable regulatory guidelines. in combination with DGM as a prophylaxis of CINV to the DGM regimen (without aprepitant) as prophylaxis of CINV in highly Methods emetogenic chemotherapy. Study design Aim and Objectives This study was designed as a retrospective medical chart review, The aim of this study is to determine if aprepitant is safe and single-center study, conducted at the National Guard Hospital in King effective by comparing aprepitant in combination with DGM as a Abdul-Aziz Medical city (Eastern Region, Saudi Arabia). This study is prophylaxis of CINV to the DGM regimen (without aprepitant) as a cross sectional study for the period 2010-2014. The study population prophylaxis of CINV in highly emetogenic chemotherapy in Arabic consisted of cancer patients treated with a highly emetogenic regimen cancer patient. as treatment for either breast cancer, lymphoma NHL (Non Hodgkin Lymphoma) or HL (Hodgkin Lymphoma), in the period from April Objectives of the Study 2010 till the end of 2014. The HEC protocols included: Primary objectives • Breast cancer protocols Efficacy of aprepitant: The primary end point is to evaluate the acute AC: Intravenous doxorubicin 60 mg/m2 and cyclophosphamide 600 emesis within 24 hours after administration of chemotherapy (0-24 mg/m2, hours) by using complete response (CR): no emesis, no admission because of emesis and no rescue therapy needed. CAF: Intravenous doxorubicin 50 mg/m2, cyclophosphamide 500 mg/m2, and fluorouracil 500 mg/m2, Efficacy of aprepitant will be determined by comparing the incidence of acute emesis (0-24 hours) in regimen 1 (DGM) vs. CEF: Intravenous epirubicin 100 mg/m2, cyclophosphamide 500 regimen 2 (APR-DGM) via the following: mg/m2, and fluorouracil 500 mg/m2 [12]. a) Cases with emesis. • Lymphomas protocols b) Administration of antiemetic rescue medication including RCHOP (rituximab 375 mg/m2 doxorubicin 50 mg/m2 metoclopramide, lorazepam, granisetron or dexamethasone. cyclophosphamide 750 mg/m2 vincristine 1.4 mg/m2, prednisone 45 mg/m2 PO or methylprednisolone 125 mg IV) [13], c) Hospital admissions due to CINV. ABVD (doxorubicin 25 mg/m2 vinblastine 6 mg/m2 bleomycin 10 Safety of the aprepitant mg/m2 dacarbazine 375 mg/m2) [14]. Determine the observed