aprepitant and Acute-Disease

In this work, data from two phase III studies were pooled to further evaluate the NK(1) antagonist aprepitant for prevention of cisplatin induced nausea and vomiting. One thousand and forty three patients receiving cisplatin (> or = 70 mg/m2) were randomised to receive either a control regimen (32 mg intravenous ondansetron [O] and 20 mg oral dexamethasone [D] on day 1; 8 mg D twice daily on days 2-4) or an aprepitant (A) regimen (125 mg A plus 32 mg O and 12 mg D on day 1, 80 mg A and 8 mg D once daily on days 2-3, and 8 mg D on day 4). The primary endpoint was no emesis and no rescue therapy. Potential correlations between acute and delayed emesis were assessed, as were frequency of emetic episodes by time interval and effects on nausea and quality of life as measured by the functional living index emesis (FLIE) questionnaire. In the aprepitant group, there was statistically significantly less nausea over the study period as well as higher functioning on the FLIE questionnaire in both the nausea and vomiting domains. Patients without acute emesis were more likely to have no emesis in the delayed phase. Compared with control, the aprepitant regimen improved prevention of delayed emesis by 16% points in patients without acute emesis, and by 17% points in patients with acute emesis. Among patients who did not have complete response, the frequency of emesis at various intervals over 5 days was consistently lower in patients receiving aprepitant. Analyses of this combined Phase III population further characterized the clinical profile of the aprepitant regimen, showing that delayed emesis is correlated with, but not entirely dependent on, the presence of acute emesis, and that aprepitant has a favorable effect against nausea throughout 5 days postchemotherapy. In addition, even among patients who had emesis or needed rescue therapy, aprepitant was associated with a lower frequency of these events compared with the control regimen.

Topics: Acute Disease; Adolescent; Adult; Aged; Aged, 80 and over; Antiemetics; Antineoplastic Agents; Aprepitant; Chronic Disease; Cisplatin; Clinical Trials, Phase III as Topic; Double-Blind Method; Female; Humans; Male; Middle Aged; Morpholines; Multicenter Studies as Topic; Nausea; Randomized Controlled Trials as Topic; Treatment Outcome; Vomiting

More than 50% patients develop emesis during induction therapy for acute myeloid leukaemia (AML). The addition of aprepitant for emesis control in children receiving induction for AML have not been explored.. A single-institutional randomised, open-label trial (NCT02979548) was conducted where children between 5 and 18 years with the diagnosis of AML being planned for 3+7 induction regimen were included. All study participants received ondansetron (0.15 mg/kg) every 8 hours for 8 days starting 30 min prior to chemotherapy. Children belonging to aprepitant group additionally received aprepitant capsules (15-40 kg=days 1-3, 80 mg; >40 kg=day 1, 125 mg and days 2-3, 80 mg) starting from 1 hour prior to chemotherapy. The proportion of patients with complete response (CR) in chemotherapy induced vomiting (CIV) in acute phase (day 1-8), delayed phase (day 9-13), overall and initial 96 hours were recorded along with severity of vomiting and adverse effects.. Total 78 children were randomised (Aprepitant group: 37 and control group: 41). The proportion of patients with CR in CIV was significantly higher in Aprepitant group in acute phase (p=0.007), overall phase (p=0.007) and in initial 96 hours (p<0.001) but it was not different in delayed phase (p=0.07). The first episode of vomiting was also significantly delayed in aprepitant group (p=0.02). Adverse effect profile was similar in two groups.. Aprepitant significantly improves emesis control in children receiving induction therapy for AML, especially in acute phase and should be routinely incorporated as part of antiemetic prophylaxis.. The study was registered at ClinicalTrials.gov (NCT02979548).

Topics: Acute Disease; Adolescent; Antiemetics; Antineoplastic Agents; Aprepitant; Child; Dexamethasone; Drug-Related Side Effects and Adverse Reactions; Humans; Induction Chemotherapy; Leukemia, Myeloid, Acute; Morpholines; Nausea; Vomiting

The combination of palonosetron and aprepitant is safe and effective in the prevention of chemotherapy-induced emesis (CIE). The purpose of this pilot study was to ascertain the effectiveness of 1-day versus 3-day aprepitant in the prevention of acute and delayed nausea and vomiting in patients who were receiving highly emetogenic chemotherapy.. This study was institutional review board-approved and informed consent was obtained before this study was begun. This was a pilot, single-institution, randomized, double-blind, placebo-controlled trial that evaluated 3 different treatment arms. All groups received palonosetron 0.25 mg intravenously on Day 1 and dexamethasone on Days 1-4. Arm A received aprepitant 125 mg orally on Day 1 followed by 80 mg on Days 2-3. Arm B received aprepitant 125 mg orally on Day 1 and placebo on Days 2-3. Arm C received placebos on Days 1-3. The primary endpoint was to evaluate the proportion of patients with acute and delayed emesis within each group.. Seventy-five patients were included in the analysis. The study commenced with 3 groups; however, an interim analysis displayed unacceptable emesis events in Arm C, and this group was terminated. There were no significant differences between Arms A and B for emesis, nausea, or the use of breakthrough antiemetics. In Arms A and B, 93% of patients were emesis-free from Days 1-5 compared with only 50% in Arm C.. From this pilot study of patients who were receiving palonosetron, aprepitant, and dexamethasone for highly emetogenic chemotherapy, a single dose of aprepitant displayed similar effectiveness compared with 3-day aprepitant.

Topics: Acute Disease; Antiemetics; Antineoplastic Agents; Aprepitant; Dexamethasone; Double-Blind Method; Drug Therapy, Combination; Humans; Isoquinolines; Morpholines; Nausea; Palonosetron; Pilot Projects; Quinuclidines; Vomiting

Topics: Acute Disease; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Humans; Morpholines; Nausea; Sensitivity and Specificity; Vomiting

The anti-emetic profile of the novel brain penetrant tachykinin NK1 receptor antagonist MK-0869 (L-754,030) 2-(R)-(1-(R)-(3,5-bis(trifluoromethyl)phenylethoxy)-3-(S)-(4-fluor o)phenyl-4-(3-oxo-1,2,4-triazol-5-yl)methylmorpholine and its water soluble prodrug, L-758,298, has been examined against emesis induced by cisplatin in ferrets. In a 4 h observation period, MK-0869 and L-758,298 (3 mg/kg i.v. or p.o.) inhibited the emetic response to cisplatin (10 mg/kg i.v.). The anti-emetic protection afforded by MK-0869 (0.1 mg/kg i.v.) was enhanced by combined treatment with either dexamethasone (20 mg/kg i.v.) or the 5-HT3 receptor antagonist ondansetron (0.1 mg/kg i.v.). In a model of acute and delayed emesis, ferrets were dosed with cisplatin (5 mg/kg i.p.) and the retching and vomiting response recorded for 72 h. Pretreatment with MK-0869 (4-16 mg/kg p.o.) dose-dependently inhibited the emetic response to cisplatin. Once daily treatment with MK-0869 (2 and 4 mg/kg p.o.) completely prevented retching and vomiting in all ferrets tested. Further when daily dosing began at 24 h after cisplatin injection, when the acute phase of emesis had already become established, MK-0869 (4 mg/kg p.o. at 24 and 48 h after cisplatin) prevented retching and vomiting in three out of four ferrets. These data show that MK-0869 and its prodrug, L-758,298, have good activity against cisplatin-induced emesis in ferrets and provided a basis for the clinical testing of these agents for the treatment of emesis associated with cancer chemotherapy.

Topics: Acetals; Acute Disease; Animals; Antiemetics; Antineoplastic Agents; Aprepitant; CHO Cells; Cisplatin; COS Cells; Cricetinae; Dose-Response Relationship, Drug; Ferrets; Humans; Male; Morpholines; Neurokinin-1 Receptor Antagonists; Prodrugs; Rats; Receptors, Neurokinin-1; Solubility; Vomiting