-
Advanced Biomedical Research 2023In order to improve the complete recovery of nausea and vomiting, we conducted a study with the aim of preventing acute and delayed nausea and vomiting in children...
BACKGROUND
In order to improve the complete recovery of nausea and vomiting, we conducted a study with the aim of preventing acute and delayed nausea and vomiting in children undergoing moderate emetogenic chemotherapy.
MATERIALS AND METHODS
A clinical trial study was done on 130 children received chemotherapy. Patients received olanzapine and placebo. All groups received granisetron along with dexamethasone (DEX). The severity of chemotherapy-induced nausea and vomiting (CINV) induced by chemotherapy was compared in two groups.
RESULTS
The severity of nausea on the first, second, third, and fourth days was not significantly different ( > .05) in two groups. The number of patients without vomiting was significantly different during the first 24 hours after chemotherapy between patients in the two groups (82.3% vs 64.5%; = .016).
CONCLUSION
This study showed that olanzapine, which acts as an inhibitor of neurotransmitters, had a favorable efficacy in controlling acute and delayed CINV. More studies with large sample size are needed to compare the effect of olanzapine with other agents including aprepitant and palonosetron in the prevention of CINV.
PubMed: 37564446
DOI: 10.4103/abr.abr_356_22 -
Cancer Medicine Aug 2023Non-inferiority of NEPA (fixed combination of NK receptor antagonist (RA), netupitant, and 5-HT RA, palonosetron) versus an aprepitant regimen was previously shown in a... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Non-inferiority of NEPA (fixed combination of NK receptor antagonist (RA), netupitant, and 5-HT RA, palonosetron) versus an aprepitant regimen was previously shown in a pragmatic study in patients receiving anthracycline cyclophosphamide (AC) and non-AC moderately emetogenic chemotherapy (MEC). In the MEC group a numerically higher complete response (CR: no emesis, no rescue) rate was seen for NEPA during the overall 0-120 h phase (NEPA 76.1% vs. 63.1% aprepitant). As NEPA exhibits long-lasting efficacy, this study evaluated a prolonged period up to 144 h, beyond the traditional 120 h post-chemotherapy. In this post-hoc analysis we explore the comparative efficacy of NEPA versus the aprepitant regimen in the MEC group up to 144 h, while also assessing the impact of risk factors on CINV prevention.
METHODS
This was a pragmatic, multicenter, randomized, prospective study. Oral NEPA was administered as a single dose on day 1, while aprepitant was given on days 1-3 + ondansetron on day 1; all patients were to receive dexamethasone on days 1-4. Patients were chemotherapy-naïve and receiving MEC, with a subset evaluation of those with a risk factor for developing CINV (i.e., female, male <60 years, male ≥60 years who received carboplatin, or male ≥60 years with anxiety). CR rates were compared during the extended overall (0-144 h) phase.
RESULTS
The MEC group included 211 patients; of these 181 were in the risk factor subset. Significantly higher CR rates were seen for NEPA than aprepitant during the extended overall phase for the total MEC group (NEPA 77.1%, aprepitant 57.8%, p = 0.003) and also in the subset of patients with CINV risk factors (NEPA 73.9%, aprepitant 56.2%, p = 0.012).
CONCLUSION
A single dose of NEPA, administered on day 1 only, was more effective than a 3-day aprepitant regimen in preventing CINV for an extended duration in patients receiving MEC and in those with emetic risk factors.
Topics: Humans; Male; Female; Aprepitant; Antiemetics; Vomiting; Prospective Studies; Isoquinolines; Quinuclidines; Drug Combinations; Nausea; Cyclophosphamide; Anthracyclines; Antineoplastic Agents; Dexamethasone
PubMed: 37537943
DOI: 10.1002/cam4.6121 -
The efficacy of aprepitant for the prevention of postoperative nausea and vomiting: A meta-analysis.Medicine Jul 2023Postoperative nausea and vomiting (PONV) is one of the common adverse reactions after surgery. Recent randomized controlled trials (RCTs) investigating antiemetic drugs... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Postoperative nausea and vomiting (PONV) is one of the common adverse reactions after surgery. Recent randomized controlled trials (RCTs) investigating antiemetic drugs suggest that aprepitant has the strongest antiemetic effect of any single drug. This meta-analysis aimed to explore the efficacy of aprepitant for preventing PONV based on the existing literature.
METHODS
To identify RCTs investigating the use of aprepitant for PONV prevention, we searched PubMed, Embase, and Cochrane Library databases for articles published prior to March 20, 2022. Seventeen RCTs were identified, with 3299 patients, meeting the inclusion criteria. PONV incidence, complete response, 80 mg aprepitant combined with dexamethasone and ondansetron, vomiting, nausea, and analgesic dose-response were the main outcomes measured.
RESULTS
Compared with the control group, PONV incidence was significantly reduced among those receiving aprepitant (odds ratio [OR]: 0.34; 95% confidence interval [CI]: 0.26, 0.44; P < .0001), with a more complete response (OR: 1.35; 95% CI: 1.14, 1.59; P = .0004). Supplementation of 80 mg aprepitant in combination with dexamethasone and ondansetron substantially improved the effects of PONV (OR: 0.36; 95% CI: 0.16, 0.82; P = .01). Further, administration of 80 mg aprepitant was better at preventing vomiting than nausea (OR: 8.6; 95% CI: 3.84, 19. 29; P < .00001). No statistically significant difference between the dose-response of analgesics was identified (mean difference: -1.09; 95% CI: -6.48, 4.30; P = .69). The risk of bias was assessed independently by paired evaluators.
CONCLUSION
Aprepitant effectively reduces the incidence of PONV; however, the effects of postoperative analgesia require further exploration.
Topics: Humans; Aprepitant; Postoperative Nausea and Vomiting; Ondansetron; Morpholines; Antiemetics; Vomiting; Dexamethasone
PubMed: 37478247
DOI: 10.1097/MD.0000000000034385 -
Frontiers in Genetics 2023Almost all patients treated with androgen deprivation therapy (ADT) eventually develop castration-resistant prostate cancer (CRPC). Our research aims to elucidate the...
Almost all patients treated with androgen deprivation therapy (ADT) eventually develop castration-resistant prostate cancer (CRPC). Our research aims to elucidate the potential biomarkers and molecular mechanisms that underlie the transformation of primary prostate cancer into CRPC. We collected three microarray datasets (GSE32269, GSE74367, and GSE66187) from the Gene Expression Omnibus (GEO) database for CRPC. Differentially expressed genes (DEGs) in CRPC were identified for further analyses, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA). Weighted gene coexpression network analysis (WGCNA) and two machine learning algorithms were employed to identify potential biomarkers for CRPC. The diagnostic efficiency of the selected biomarkers was evaluated based on gene expression level and receiver operating characteristic (ROC) curve analyses. We conducted virtual screening of drugs using AutoDock Vina. experiments were performed using the Cell Counting Kit-8 (CCK-8) assay to evaluate the inhibitory effects of the drugs on CRPC cell viability. Scratch and transwell invasion assays were employed to assess the effects of the drugs on the migration and invasion abilities of prostate cancer cells. Overall, a total of 719 DEGs, consisting of 513 upregulated and 206 downregulated genes, were identified. The biological functional enrichment analysis indicated that DEGs were mainly enriched in pathways related to the cell cycle and metabolism. CCNA2 and CKS2 were identified as promising biomarkers using a combination of WGCNA, LASSO logistic regression, SVM-RFE, and Venn diagram analyses. These potential biomarkers were further validated and exhibited a strong predictive ability. The results of the virtual screening revealed Aprepitant and Dolutegravir as the optimal targeted drugs for CCNA2 and CKS2, respectively. experiments demonstrated that both Aprepitant and Dolutegravir exerted significant inhibitory effects on CRPC cells ( < 0.05), with Aprepitant displaying a superior inhibitory effect compared to Dolutegravir. The expression of CCNA2 and CKS2 increases with the progression of prostate cancer, which may be one of the driving factors for the progression of prostate cancer and can serve as diagnostic biomarkers and therapeutic targets for CRPC. Additionally, Aprepitant and Dolutegravir show potential as anti-tumor drugs for CRPC.
PubMed: 37476415
DOI: 10.3389/fgene.2023.1184704 -
Yakugaku Zasshi : Journal of the... 2023
Topics: Humans; Aprepitant; Ifosfamide; Antiemetics; Brain Diseases; Drug Interactions
PubMed: 37394457
DOI: 10.1248/yakushi.143.621 -
European Journal of Pharmacology Sep 2023Capsaicin and allyl isothiocyanate (AITC) activate transient receptor potential (TRP) vanilloid-1 (TRPV1) and TRP ankyrin-1 (TRPA1), respectively. TRPV1 and TRPA1...
Capsaicin and allyl isothiocyanate (AITC) activate transient receptor potential (TRP) vanilloid-1 (TRPV1) and TRP ankyrin-1 (TRPA1), respectively. TRPV1 and TRPA1 expression have been identified in the gastrointestinal (GI) tract. GI mucosal functions remain largely undefined for TRPV1 and TRPA1 with side-dependence and regional differences in signalling unclear. Here we investigated TRPV1- and TRPA1-induced vectorial ion transport as changes in short-circuit current (ΔI), in defined segments of mouse colon mucosa (ascending, transverse and descending) under voltage-clamp conditions in Ussing chambers. Drugs were applied basolaterally (bl) or apically (ap). Capsaicin responses were biphasic, with primary secretory and secondary anti-secretory phases, observed with bl application only, which predominated in descending colon. AITC responses were monophasic and secretory, with ΔI dependent on colonic region (ascending vs. descending) and sidedness (bl vs. ap). Aprepitant (neurokinin-1 (NK1) antagonist, bl) and tetrodotoxin (Na channel blocker, bl) significantly inhibited capsaicin primary responses in descending colon, while GW627368 (EP4 receptor antagonist, bl) and piroxicam (cyclooxygenase inhibitor, bl) inhibited AITC responses in ascending and descending colonic mucosae. Antagonism of the calcitonin gene-related peptide (CGRP) receptor had no effect on mucosal TRPV1 signalling, while tetrodotoxin and antagonists of the 5-hydroxytryptamine-3 and 4 receptors, CGRP receptor, and EP1/2/3 receptors had no effect on mucosal TRPA1 signalling. Our data demonstrates the regional-specificity and side-dependence of colonic TRPV1 and TRPA1 signalling, with involvement of submucosal neurons and mediation by epithelial NK1 receptor activation for TRPV1, and endogenous prostaglandins and EP4 receptor activation for TRPA1 mucosal responses.
Topics: Mice; Animals; Transient Receptor Potential Channels; TRPA1 Cation Channel; Capsaicin; Tetrodotoxin; Colon; Mucous Membrane; TRPV Cation Channels
PubMed: 37394028
DOI: 10.1016/j.ejphar.2023.175897 -
The Oncologist Aug 2023A protocol was developed to evaluate the value of an NK-1 receptor antagonist for preventing nausea and vomiting resulting from highly emetogenic chemotherapy when an... (Randomized Controlled Trial)
Randomized Controlled Trial
Olanzapine With or Without Fosaprepitant for Preventing Chemotherapy Induced Nausea and Vomiting in Patients Receiving Highly Emetogenic Chemotherapy: A Phase III Randomized, Double-Blind, Placebo-Controlled Trial (ALLIANCE A221602).
PURPOSE
A protocol was developed to evaluate the value of an NK-1 receptor antagonist for preventing nausea and vomiting resulting from highly emetogenic chemotherapy when an olanzapine-based antiemetogenic regimen was used.
MATERIALS AND METHODS
A221602, a prospective double-blind, placebo-controlled clinical trial, was developed to compare 2 -olanzapine-containing antiemetic regimens, one with an NK-1 receptor antagonist (aprepitant or fosaprepitant) and one without. Trial patients had a malignant disease for which they received intravenous highly emetogenic chemotherapy (single day cisplatin ≥ 70 mg/m2 or doxorubicin plus cyclophosphamide on 1 day). Patients on both arms received commonly administered doses of a 5-HT3 receptor antagonist, dexamethasone, and olanzapine. Additionally, patients were randomized to receive an NK-1 receptor antagonist (fosaprepitant 150 mg IV or aprepitant 130 mg IV) or a corresponding placebo. The primary objective was to compare the proportion of patients with no nausea for 5 days following chemotherapy between the 2 study arms. This trial was designed to test for the noninferiority of deleting the NK-1 receptor antagonist, with noninferiority defined as a decrease in freedom from nausea by less than 10%.
RESULTS
A total of 690 patients were entered on this trial, 50% on each arm. The proportion of patients without nausea for the complete 5-day study period was 7.4% lower (upper limit of the one-sided 95% confidence interval was 13.5%) in the arm without an NK-1 receptor antagonist compared with the arm with an NK-1 receptor antagonist.
CONCLUSION
This trial did not provide sufficient evidence to support that deletion of the NK-1 receptor antagonist was as good as keeping it, as a part of a 4-drug antiemetic regimen for highly emetogenic chemotherapy (ClinicalTrials.gov Identifier: NCT03578081).
Topics: Humans; Antiemetics; Olanzapine; Aprepitant; Prospective Studies; Receptors, Neurokinin-1; Vomiting; Nausea; Antineoplastic Agents; Double-Blind Method; Dexamethasone
PubMed: 37284847
DOI: 10.1093/oncolo/oyad140 -
Yakugaku Zasshi : Journal of the... 2023A 72-year-old man with a malignant retroperitoneal soft tissue tumor was treated with ifosfamide (IFO) for 5 consecutive days (1.8 g/m/d×5 d, expected dose...
A 72-year-old man with a malignant retroperitoneal soft tissue tumor was treated with ifosfamide (IFO) for 5 consecutive days (1.8 g/m/d×5 d, expected dose 9 g/m). The patient developed neurological symptoms such as mild somnolence, seizures, and inability to write from Day 1, and became delirious on Day 3, so IFO was discontinued on Day 4 (dose: 7.2 g/m). Since there are reports of drug interactions that increase the frequency of encephalopathy when combined with aprepitant (Apr), Dexamethasone was increased and IFO was administered without the use of Apr after the second course, and there was no recurrence of encephalopathy in the second and third courses. IFO-induced encephalopathy is considered to occur due to an increase in blood concentration of IFOs caused by high dosage, decreased renal function, or other factors. In this case, encephalopathy was observed even though the dose of IFO was reduced due to the patient's advanced age and impaired renal function. The combination use of Apr with IFO should be considered with caution for the occurrence of adverse events, including encephalopathy, and if possible, control of gastrointestinal toxicity with other antiemetic agents should be considered.
Topics: Male; Humans; Aged; Ifosfamide; Aprepitant; Brain Diseases; Antiemetics; Drug Interactions
PubMed: 37258187
DOI: 10.1248/yakushi.22-00186 -
Pharmaceutics May 2023Aprepitant is the first member of a relatively new antiemetic drug class called NK receptor antagonists. It is commonly prescribed to prevent chemotherapy-induced nausea...
Aprepitant is the first member of a relatively new antiemetic drug class called NK receptor antagonists. It is commonly prescribed to prevent chemotherapy-induced nausea and vomiting. Although it is included in many treatment guidelines, its poor solubility causes bioavailability issues. A particle size reduction technique was used in the commercial formulation to overcome low bioavailability. Production with this method consists of many successive steps that cause the cost of the drug to increase. This study aims to develop an alternative, cost-effective formulation to the existing nanocrystal form. We designed a self-emulsifying formulation that can be filled into capsules in a melted state and then solidified at room temperature. Solidification was achieved by using surfactants with a melting temperature above room temperature. Various polymers have also been tested to maintain the supersaturated state of the drug. The optimized formulation consists of Capryol 90, Kolliphor CS20, Transcutol P, and Soluplus; it was characterized by DLS, FTIR, DSC, and XRPD techniques. A lipolysis test was conducted to predict the digestion performance of formulations in the gastrointestinal system. Dissolution studies showed an increased dissolution rate of the drug. Finally, the cytotoxicity of the formulation was tested in the Caco-2 cell line. According to the results, a formulation with improved solubility and low toxicity was obtained.
PubMed: 37242751
DOI: 10.3390/pharmaceutics15051509 -
Daru : Journal of Faculty of Pharmacy,... Dec 2023Chemotherapy-induced nausea and vomiting are commonly experienced side effects in breast cancer (BCa) patients. Antiemetic drugs used in BCa treatment are either...
BACKGROUND
Chemotherapy-induced nausea and vomiting are commonly experienced side effects in breast cancer (BCa) patients. Antiemetic drugs used in BCa treatment are either inhibitors or inducers of cytochrome P450 (CYP) enzymes, while anticancer drugs are metabolized by CYPs.
OBJECTIVES
The purpose of the present work was to evaluate in silico drug-drug interaction (DDI) potential between BCa chemotherapeutic drugs and antiemetic agents.
METHODS
The Drug-Drug Interaction™ module of GastroPlus™ was employed to assess CYP-related interactions between antiemetic and anticancer therapy combinations. The CYP inhibitory or inducing parameters (IC, K, EC) used in simulations were obtained from the literature.
RESULTS
Analyses of twenty-three BCa drugs indicated that 22% of the chemotherapeutic drugs do not need an antiemetic agent due to their low emetogenicity, whereas 30% of the anticancer drugs are not metabolized by CYPs. The remaining eleven anticancer drugs metabolized by CYPs generated ninety-nine combinations with nine antiemetics. Simulation of DDIs suggest that about half of the pairs did not demonstrate any potential for DDI, whereas 30%, 10%, and 9% of the pairs showed weak, moderate, and strong interaction potential, respectively. In the present study, netupitant was the only antiemetic that showed strong inhibitory interactions (predicted AUC ratio > 5) with CYP3A4-metabolzied anticancer therapies (e.g., docetaxel, ribociclib, olaparib). Moderate to no interactions were observed with ondansetron, aprepitant, rolapitant, and dexamethasone in combination with anticancer agents.
CONCLUSION
It is critical to recognize that these interactions can get amplified in cancer patients because of the severity of the disease and chemotherapy toxicities. Clinicians need to be aware of the DDI likelihood of the drug combinations used in BCa treatment.
Topics: Humans; Female; Antiemetics; Breast Neoplasms; Antineoplastic Agents; Aprepitant; Drug Interactions
PubMed: 37223851
DOI: 10.1007/s40199-023-00463-1