The oral NK1 antagonist, aprepitant, given with standard antiemetics provides protection against nausea and vomiting over multiple cycles of cisplatin-based chemotherapy

Wit, Ronald de; Herrstedt, Jørn; Rapoport, Bernardo; Carides, Alexandra D.; Guoguang-Ma, J.; Elmer, M.; Schmidt, Cristhiane Martins; Evans, Judith K.; Horgan, Kevin J.

doi:10.1016/j.ejca.2003.08.028

Cited by 124 publications

(57 citation statements)

References 11 publications

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“…Furthermore, there appears to be a close association between the neuropharmacology of toxicosisinduced pica and emesis. Like emesis in cancer patients receiving chemotherapy (Tsukada et al, 2001;Hesketh et al, 2003;de Wit et al, 2004), cisplatin-induced pica in the rat can be characterized into acute and delayed phases that are most sensitive to 5-HT3 and NK1 receptor antagonists, respectively (Saeki et al, 2001;Rudd et al, 2002). However, the relation between emesis and pica is not always so clear.…”

Section: Kaolin Ingestion (Pica)-mentioning

confidence: 99%

Signals for nausea and emesis: Implications for models of upper gastrointestinal diseases

Andrews

Horn

2006

Autonomic Neuroscience

218

206

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Nausea and vomiting are amongst the most common symptoms encountered in medicine as either symptoms of diseases or side effects of treatments. In a more biological setting they are also important components of an organism's defences against ingested toxins. Identification of treatments for nausea and vomiting and reduction of emetic liability of new therapies has largely relied on the use of animal models, and although such models have proven invaluable in identification of the anti-emetic effects of both 5-hydroxytryptamine3 and neurokinin1 receptor antagonists selection of appropriate models is still a matter of debate. The present paper focuses on a number of controversial issues and gaps in our knowledge in the study of the physiology of nausea and vomiting including: The choice of species for the study of emesis and the underlying behavioural (e.g. neophobia), anatomical (e.g. elongated, narrow abdominal oesophagus with reduced ability to shorten) and physiological (e.g. brainstem circuitry) mechanisms that explain the lack of a vomiting reflex in certain species (e.g. rats); The choice of response to measure (emesis[retching and vomiting], conditioned flavour avoidance or aversion, ingestion of clay [pica], plasma hormone levels[e.g. vasopressin], gastric dysrhythmias) and the relationship of these responses to those observed in humans and especially to the sensation of nausea; The stimulus coding of nausea and emesis by abdominal visceral afferents and especially the vagus-how do the afferents encode information for normal postprandial sensations, nausea and finally vomiting?; Understanding the central processing of signals for nausea and vomiting is particularly problematic in the light of observations that vomiting is more readily amenable to pharmacological treatment than is nausea, despite the assumption that nausea represents "low" intensity activation of pathways that can evoke vomiting when stimulated more intensely.

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Section: Kaolin Ingestion (Pica)-mentioning

confidence: 99%

Signals for nausea and emesis: Implications for models of upper gastrointestinal diseases

Andrews

Horn

2006

Autonomic Neuroscience

218

206

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“…Both these results were evaluated in a metanalysis by De Wit et al (9) and the authors stated that aprepitant was useful in then prevention of emesis for patients receiving moderately emetogenic chemotherapy plus high-dose cisplatin.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the Efficacy of Aprepitant on the Prevention of Chemotherapy-Induced Nausea and Vomiting and Quality of Life with Functional Living Index Emesis

Aksu¹,

Dolasik²,

Ensaroğlu³

et al. 2013

Balkan Med J

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IntroductionApproxiamately 70-80% of patients receiving chemotherapy experience nausea and/or vomiting. However, emesis, nausea and vomiting significantly affect patients quality of life and can lead to poor compliance with further treatment. They can also cause metabolic imbalances, nutrient depletion, anorexia, decline of the patient's performance status and even withdrawal from curative anticancer treatment. There are several factors affecting the severity and incidence of emesis and vomiting, including type of chemotherapy, dosage, schedule and even individual patient variability (1-3).Vomiting is triggered by impulses to the vomiting center from the chemoreceptor trigger zone, pharynx, gastrointestinal tract and cerebral kortex. The principal neuroreceptors involved in emetic response are dopamine and the seratonin receptors. The others are, corticosteroid, histamine, cannabinoid, acetylcholine and neurokinin-1 (NK-1) receptors. Antiemetics can block different neuronal pathways and exert their effects at different points during emesis course (4).Aprepitant (AP) is a selective NK-1 receptor blocker that blocks the binding of substance -P at the NK-1 receptor in the central nervous system. It differs from the other antiemetics by augmenting the antiemetic activity of the 5-HT3-receptor anatagonists and dexamethasone to inhibit both acute and delayed cisplatin-induced emesis. However, most of the studies, including two phase III studies evaluated the efficieny of aprepitant by self-diary reports and reported only the incidence and severity of emesis. It is also commonly claimed that the nausea and vomiting accompanying cytotoxic chemotherapy have a negative impact on quality of life but there is little empirical data demonstrating that the failure to control postchemotherapy emesis affects aspects of quality of life other than directly related physical symptoms (5, 6). ABSTRACTObjective: Functional Living Index Emesis (FLIE) is developed to evaluate the relationship between emesis and it's effects on patient's daily life and is far more relevant to detect the effectiveness of antiemetic treatment compared with self-diary reports. In this study, the efficacy of oral neurokinin-1 antagonist aprepitant on the prevention of chemotherapy-induced nausea and vomiting and quality of life is evaluated with FLIE.Study Design: Cross sectional study. Material and Methods:Sixty patients with Non-Small Cell Lung Cancer (NSCLC) receiving a chemotherapy regimen consisting of Cisplatin and Docetaxel were evaluated. The patients were prospectively randomized to two groups before the first cycle of chemotherapy. Patients in Group A (31 patients) received 3 daily doses of aprepitant along with oral ondansetron and dexamethasone. The patients in group B (29 patients) received only ondansetron and dexamathasone. The efficacy of both regimens was evaluated by a modified Turkish version of FLIE scale consisting of 18 questions. Results:The number of patients with complete response was 31 in the whole group. Of these 18 patients (58%...

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“…Chemotherapy-induced nausea and vomiting (CINV) development after standard premedication (palonosetron and dexamethasone) and after the addition of aprepitant. genic chemotherapy [24,[33][34][35][36][37][38][39]. Moreover, a single oral dose of aprepitant administered prior to abdominal surgery was found to be effective in the prevention of postoperative nausea and vomiting [40].…”

Section: Discussionmentioning

confidence: 99%

Aprepitant plus palonosetron as salvage therapy for CINV induced by moderately emetogenic chemotherapy in cancer patients

Vincenzi

Frezza

Silletta

et al. 2016

CBN

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Background Despite the efficacy of prophylaxis with serotonin type 3 (5-HT 3 ) receptor antagonists, nausea and vomiting are still among the most common chemotherapy-induced toxicities. The aim of this study was to evaluate the efficacy of adding aprepitant in patients with chemotherapy-induced nausea and vomiting (CINV) refractory to prophylaxis with 5-HT 3 receptor antagonists and dexamethasone. Patients and Methods Between January 2008 and November 2010, 51 patients (median age 59 years) with a variety of malignancies (breast cancer: 23; lung cancer: 12; sarcoma: 6; ovarian cancer: 3; other: 7) were enrolled. All patients were refractory to antiemetic therapy according to ASCO guidelines and developed at least grade 2 nausea and/or vomiting after the first chemotherapy course. Aprepitant was given at 125 mg on day 1 and 80 mg on days 2-3. Patients also received a single dose of palonosetron 250 µg on day 1 plus dexamethasone 12-20 mg at a constant dose. Results After addition of aprepitant, the number of patients with grade 3/4 nausea decreased from 31 (61%) to 4 (8%), and those with grade 2 nausea from 20 (39%) to 6 (12%) [both p<0.0001]. All patients received aprepitant for more then two courses (range 3-8) and efficacy was maintained during all chemotherapy cycles. Conclusions This study showed that aprepitant was effective as salvage therapy in patients with CINV refractory to prophylaxis with 5-HT 3 receptor antagonists and dexamethasone following platinum-or nonplatinum-based chemotherapy, and that the efficacy of aprepitant persists over multiple cycles.

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The oral NK1 antagonist, aprepitant, given with standard antiemetics provides protection against nausea and vomiting over multiple cycles of cisplatin-based chemotherapy

Cited by 124 publications

References 11 publications

Signals for nausea and emesis: Implications for models of upper gastrointestinal diseases

Signals for nausea and emesis: Implications for models of upper gastrointestinal diseases

Evaluation of the Efficacy of Aprepitant on the Prevention of Chemotherapy-Induced Nausea and Vomiting and Quality of Life with Functional Living Index Emesis

Aprepitant plus palonosetron as salvage therapy for CINV induced by moderately emetogenic chemotherapy in cancer patients

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