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Chinese Clinical Oncology Oct 2020The goal of this study was to evaluate aprepitant usage in the context of routine clinical practice with dose/regimens at the discretion of prescribers for...
Safety and efficacy of aprepitant as mono and combination therapy for the prevention of emetogenic chemotherapy-induced nausea and vomiting: post-marketing surveillance in China.
BACKGROUND
The goal of this study was to evaluate aprepitant usage in the context of routine clinical practice with dose/regimens at the discretion of prescribers for chemotherapy-induced nausea and vomiting (CINV) treatments.
METHODS
In this single arm, multicenter prospective study 1,000 patients with solid malignancies were enrolled across 21 centers in China. The primary endpoint was the rate of adverse events (AEs), including drug related AEs and serious AEs (SAEs). Secondary efficacy endpoints included the proportion of patients achieving complete response (CR; no vomiting, no nausea, and no use of rescue medication) within 120 h after highly emetogenic chemotherapy, the rates of no nausea and no vomiting, as well as quality of life (QoL). Multivariable logistic regression analysis was carried out to determine factors associated with the overall (0-120 h), acute (0-24 h) and delayed (25-120 h) CR.
RESULTS
Of the 1,000 highly emetogenic chemotherapy treated patients enrolled in the study ≥1 AE, ≥1 drug related AE, ≥1 SAE and drug related SAE rates in 998 patients were 45.9%, 2.5%, 4.0% and 0.1%, respectively. Approximately half of the patients (455/990, 46.0%) received aprepitant as part of a 3-drug anti-CINV regimen consistent with prescribing guidelines. The overall CR (0 to 120 h) for anti-emetic drug use was 41.0%, with an acute CR of 66.0% and a delayed CR of 46.5%. The rates of no vomiting and no nausea after solely aprepitant anti-emetic therapy from 0 to 120 h were 70.9% and 43.0%, for dual anti-emetic therapy 86.9% and 64.6%, and for triple therapy 86.4% and 69.5%, respectively. Multivariate regression analysis revealed that triple anti-emetic therapy (P=0.038), male gender (P<0.001) and a history of chemotherapy (P=0.016) were significantly associated with the overall acute CR.
CONCLUSIONS
Especially as a combination treatment, aprepitant is safe and efficient for preventing CINV in patients receiving highly emetogenic chemotherapy.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antiemetics; Aprepitant; China; Female; Humans; Male; Middle Aged; Nausea; Product Surveillance, Postmarketing; Vomiting; Young Adult
PubMed: 33161724
DOI: 10.21037/cco-20-160 -
Drug Design, Development and Therapy 2021The stability of aprepitant injectable emulsion is evaluated in various admixture bags and solutions, under different storage conditions, and when combined with other...
PURPOSE
The stability of aprepitant injectable emulsion is evaluated in various admixture bags and solutions, under different storage conditions, and when combined with other antiemetics.
METHODS
A volume of 18 mL aprepitant injectable emulsion was added to infusion bags (either non-di-(2-ethylhexyl) phthalate [DEHP], polyvinyl chloride [PVC]-containing bags or non-DEHP, non-PVC bags) containing 100, 130, or 250 mL of 0.9% normal saline solution (NSS) or 5% dextrose in water (D5W). Bags were stored at controlled room temperature (20-25°C) for up to 12 hours or refrigerated (2-8°C) for up to 72 hours. Compatibility/stability was also assessed in admixtures combined with either dexamethasone or palonosetron. At specified time points, bags were tested for appearance, pH, assay for aprepitant (ie, percent label claim of aprepitant) and aprepitant-related substances, Z-average particle size, globule size distribution, particulate matter, and DEHP content (PVC bags). In separate analyses to assess microbial burden, bags containing aprepitant were inoculated with seven different organisms and assessed for microbial growth.
RESULTS
There was no detectable impact on the physicochemical properties or potential to promote microbial growth of aprepitant when diluted with various amounts of either NSS or D5W and when admixed with either dexamethasone or palonosetron at room temperature for at least 6 hours or during refrigeration for up to 72 hours in either PVC- or non-PVC-containing bags.
CONCLUSION
Aprepitant-containing admixtures are stable under these conditions, a finding that may improve patient and provider convenience and reduce medication wastage.
Topics: Antiemetics; Aprepitant; Dexamethasone; Diethylhexyl Phthalate; Drug Combinations; Drug Incompatibility; Drug Packaging; Drug Stability; Drug Storage; Emulsions; Hydrogen-Ion Concentration; Palonosetron; Polyvinyl Chloride; Refrigeration; Temperature; Time Factors
PubMed: 34163138
DOI: 10.2147/DDDT.S282058 -
Saudi Journal of Gastroenterology :... 2016Gastrointestinal (GI) cancer is the term for a group of cancers affecting the digestive system. After binding to the neurokinin-1 (NK-1) receptor, the undecapeptide... (Review)
Review
Gastrointestinal (GI) cancer is the term for a group of cancers affecting the digestive system. After binding to the neurokinin-1 (NK-1) receptor, the undecapeptide substance P (SP) regulates GI cancer cell proliferation and migration for invasion and metastasis, and controls endothelial cell proliferation for angiogenesis. SP also exerts an antiapoptotic effect. Both SP and the NK-1 receptor are located in GI tumor cells, the NK-1 receptor being overexpressed. By contrast, after binding to the NK-1 receptor, NK-1 receptor antagonists elicit the inhibition (epidermal growth factor receptor inhibition) of the proliferation of GI cancer cells in a concentration-dependent manner, induce the death of GI cancer cells by apoptosis, counteract the Warburg effect, inhibit cancer cell migration (counteracting invasion and metastasis), and inhibit angiogenesis (vascular endothelial growth factor inhibition). NK-1 receptor antagonists are safe and well tolerated. Thus, the NK-1 receptor could be considered as a new target in GI cancer and NK-1 receptor antagonists (eg, aprepitant) could be a new promising approach for the treatment of GI cancer.
Topics: Animals; Antineoplastic Agents; Cell Proliferation; Cell Survival; Gastrointestinal Neoplasms; Humans; Neoplasm Invasiveness; Neurokinin-1 Receptor Antagonists
PubMed: 27488320
DOI: 10.4103/1319-3767.187601 -
Molecules (Basel, Switzerland) Jun 2015Solid dispersions are a useful approach to improve the dissolution rate and bioavailability of poorly water-soluble active pharmaceutical ingredients (APIs). The aim of...
Solid dispersions are a useful approach to improve the dissolution rate and bioavailability of poorly water-soluble active pharmaceutical ingredients (APIs). The aim of this study was to improve the physicochemical properties and bioavailability of a poorly water-soluble aprepitant by preparation of solid dispersions. The solid dispersions were characterized by dissolution, FTIR, XRPD, DSC, SEM and pharmacokinetic studies in rats. The dissolution rate of the aprepitant was significantly increased by solid dispersions, and XRD, DSC, and SEM analysis indicated that the aprepitant existed in an amorphous form within the solid dispersions. The result of dissolution study showed that the dissolution rate of SDs was nearly five-fold faster than aprepitant. FTIR spectrometry suggested the presence of intermolecular hydrogen bonds between the aprepitant and polymer. Pharmacokinetic studies in rats indicated that the degree drug absorption was comparable with that of Emend®. Aprepitant exists in an amorphous state in solid dispersions and the solid dispersions can markedly improve the dissolution and oral bioavailability of the aprepitant. The AUC0-t of the SDs was 2.4-fold that of the aprepitant. In addition, the method and its associated techniques are very easy to carry out.
Topics: Administration, Oral; Animals; Aprepitant; Biological Availability; Chemistry, Pharmaceutical; Morpholines; Polyethylene Glycols; Polyvinyls; Rats; Solubility; Water
PubMed: 26102068
DOI: 10.3390/molecules200611345 -
Current Problems in Cancer Dec 2019To assess the safety and efficacy of combined neurokinin-1 antagonist aprepitant treatment for multiple-day anthracycline chemotherapy-induced nausea and vomiting. (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To assess the safety and efficacy of combined neurokinin-1 antagonist aprepitant treatment for multiple-day anthracycline chemotherapy-induced nausea and vomiting.
METHODS
One hundred patients with breast cancer from department of Medical Oncology of Ordos Central Hospital from June 2015 to February 2018 were selected and randomize subdivided into 2 groups. All cases received anthracycline (30 mg/m/d for pirarubicin or 45 mg/m/d for epirubicin) and cyclophosphamide adjuvant chemotherapy, along with either the standard therapy (dexamethasone and tropisetron) or the combined aprepitant therapy (aprepitant plus dexamethasone and tropisetron). The results of the observation between groups were presented by complete response in the overall phase (OP, 0-120 hours), acute phase (AP, 0-24 hours) and delay phase (DP, 25-120 hours). The Kaplan-Meier curves were plotted to exhibit the first time of vomiting, Functional Living Index-Emesis of patients' quality of life, and therapy-related adverse effects (AEs).
RESULTS
The complete response of OP, AP, and DP were statistically different between aprepitant group and standard group (80.0% vs 48%, P = 0.001; 92.0% vs 74%, P = 0.017; 80.0% vs 48%, P = 0.001). The aprepitant group held a longer time reaching the first emesis after the relevant treatment than the standard group. The Functional Living Index-Emesis increased significantly in the aprepitant group compared with the standard group (24% vs 8.3%, P = 0.029). Fatigue and constipation were the only AEs of aprepitant, since no significant differences were observed in fatigue between the 2 groups (72% vs 70%, P = 0.826), while the incidence of constipation of aprepitant group was higher than the standard group (48% vs 28%, P = 0.039).
CONCLUSION
Combined aprepitant therapy is efficient and safe in the multiple-day anthracycline chemotherapy-induced nausea and vomiting control and is recommended for the clinical use.
Topics: Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Breast Neoplasms; Case-Control Studies; Doxorubicin; Epirubicin; Female; Follow-Up Studies; Humans; Middle Aged; Nausea; Neurokinin-1 Receptor Antagonists; Prognosis; Prospective Studies; Survival Rate; Vomiting
PubMed: 30709557
DOI: 10.1016/j.currproblcancer.2019.01.003 -
Cell Death & Disease Jan 2024Transient receptor potential melastatin 8 (TRPM8) is a cold sensory receptor in primary sensory neurons that regulates various neuronal functions. Substance P (SP) is a...
Transient receptor potential melastatin 8 (TRPM8) is a cold sensory receptor in primary sensory neurons that regulates various neuronal functions. Substance P (SP) is a pro-inflammatory neuropeptide secreted by the neurons, and it aggravates colitis. However, the regulatory role of TRPM8 in SP release is still unclear. Our study aimed to investigate TRPM8's role in SP release from primary sensory neurons during colitis and clarify the effect of SP on colonic epithelium. We analyzed inflammatory bowel disease patients' data from the Gene Expression Omnibus dataset. Dextran sulfate sodium (DSS, 2.5%)-induced colitis in mice, mouse dorsal root ganglion (DRG) neurons, ND7/23 cell line, and mouse or human colonic organoids were used for this experiment. Our study found that TRPM8, TAC1 and WNT3A expression were significantly correlated with the severity of ulcerative colitis in patients and DSS-induced colitis in mice. The TRPM8 agonist (menthol) and the SP receptor antagonist (Aprepitant) can attenuate colitis in mice, but the effects were not additive. Menthol promoted calcium ion influx in mouse DRG neurons and inhibited the combination and phosphorylation of PKAca from the cAMP signaling pathway and GSK-3β from the Wnt/β-catenin signaling pathway, thereby inhibiting the effect of Wnt3a-driven β-catenin on promoting SP release in ND7/23 cells. Long-term stimulation with SP inhibited proliferation and enhanced apoptosis in both mouse and human colonic organoids. Conclusively, TRPM8 inhibits SP release from primary sensory neurons by inhibiting the interaction between PKAca and GSK-3β, thereby inhibiting the role of SP in promoting colonic epithelial apoptosis and relieving colitis.
Topics: Humans; Mice; Animals; Substance P; Glycogen Synthase Kinase 3 beta; Menthol; Colitis; Sensory Receptor Cells; Epithelium; TRPM Cation Channels; Dextran Sulfate; Mice, Inbred C57BL; Ganglia, Spinal; Membrane Proteins
PubMed: 38280896
DOI: 10.1038/s41419-024-06480-5 -
Current Oncology Reports Aug 2019Chemotherapy-induced nausea and vomiting (CINV) is a common cause of acute morbidity that impacts quality of life in children receiving cancer treatment. Here, we review... (Review)
Review
PURPOSE OF REVIEW
Chemotherapy-induced nausea and vomiting (CINV) is a common cause of acute morbidity that impacts quality of life in children receiving cancer treatment. Here, we review the evolution of CINV prophylaxis guidelines in children, with an emphasis on the literature published in the last 5 years, to bring the reader up to date.
RECENT FINDINGS
Recent studies have led to the adoption of the "triple therapy" regimen of antiemetic prophylaxis (a 5-HT3 antagonist, dexamethasone, and a neurokinin-1 antagonist) as the backbone of recommendations for the prevention of CINV in children. Areas of new data include the addition of aprepitant and inclusion of palonosetron as a non-inferior 5-HT3 antagonist. In addition, there are emerging pediatric data informing patient-derived risk factors associated with CINV risk and classification of antineoplastic drugs based on emetogenicity. Several recent pediatric studies have shaped published guidelines for CINV prophylaxis in children.
Topics: Antiemetics; Antineoplastic Agents; Child; Humans; Nausea; Neoplasms; Prognosis; Quality of Life; Randomized Controlled Trials as Topic; Serotonin 5-HT3 Receptor Antagonists; Vomiting
PubMed: 31418119
DOI: 10.1007/s11912-019-0840-0 -
British Journal of Clinical Pharmacology Jul 2017The aim of the present study was to evaluate the efficacy of olanzapine for the prevention of chemotherapy-induced nausea and vomiting (CINV). (Meta-Analysis)
Meta-Analysis Review
AIM
The aim of the present study was to evaluate the efficacy of olanzapine for the prevention of chemotherapy-induced nausea and vomiting (CINV).
METHODS
The literature was searched for randomized controlled trials (RCTs) evaluating the efficacy of olanzapine for the prophylaxis of CINV using PubMed, Embase, Central, as well as clinicaltrials.gov for unpublished studies. The endpoints of the study were the number of patients who achieved a complete response (CR; no emesis and no rescue) and no nausea in the acute, delayed and overall phases. Two authors independently selected studies, assessed the risk of bias and extracted data. The included RCTs were analysed using RevMan 5.3 provided by the Cochrane Collaboration.
RESULTS
Ten RCTs were identified for the meta-analysis. Compared with other antiemetic agents, olanzapine significantly improved the CR in the delayed and overall phases, but did not enhance the CR in the acute phase. For the control of CINV, olanzapine was better than and comparable with aprepitant in the acute phase and delayed phase, respectively. Compared with placebo, treatment with 5 mg and 10 mg olanzapine exhibited similar efficacy in terms of the CR in the delayed and overall phases.
CONCLUSIONS
Olanzapine is an excellent alternative for the prophylaxis of CINV. Olanzapine 5 mg per day should be recommended as the initial dose because of equivalent efficacy to a 10 mg dose but a lower potential risk of side effects. Further studies are needed to explore the optimal combination of medicines.
Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Benzodiazepines; Dose-Response Relationship, Drug; Drug-Related Side Effects and Adverse Reactions; Humans; Morpholines; Nausea; Neoplasms; Olanzapine; Randomized Controlled Trials as Topic; Treatment Outcome; Vomiting
PubMed: 28112422
DOI: 10.1111/bcp.13242 -
JAMA Network Open Apr 2021The prevention of chemotherapy-induced nausea and vomiting has an important role in the overall management of cancer treatment. (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
The prevention of chemotherapy-induced nausea and vomiting has an important role in the overall management of cancer treatment.
OBJECTIVE
To evaluate whether adding aprepitant to palonosetron and dexamethasone can further prevent the incidence and severity of nausea and vomiting caused by FOLFIRI (fluorouracil, leucovorin, and irinotecan) or FOLFOX (fluorouracil, leucovorin, and oxaliplatin) chemotherapy regimens among women with gastrointestinal cancer at higher risk.
DESIGN, SETTING, AND PARTICIPANTS
This phase 3, double-blind, placebo-controlled randomized clinical trial recruited young women (age ≤50 years) who drank little or no alcohol and had gastrointestinal cancer for which they received FOLFOX or FOLFIRI chemotherapy. A total of 248 women were enrolled and assigned in the ratio 1:1 to intervention and control groups from August 4, 2015, to March 31, 2020. Intention-to-treat analysis was used to evaluate patient baseline characteristics and efficacy. The analysis was conducted on October 30, 2020.
INTERVENTIONS
Patients were randomly assigned to the aprepitant group (aprepitant, 125 mg, orally 60 minutes before initiation of chemotherapy on day 1 and 80 mg orally each morning of days 2 and 3; palonosetron, 0.25 mg, intravenously; and dexamethasone, 6 mg, orally 30 minutes before chemotherapy initiation on day 1) or the placebo group (placebo, 125 mg, orally 60 minutes before initiation of chemotherapy on day 1 and 80 mg orally on each morning of days 2 and 3; palonosetron, 0.25 mg, intravenously; and dexamethasone, 12 mg, orally 30 minutes before chemotherapy initiation on day 1).
MAIN OUTCOMES AND MEASURES
The primary end point was the complete response (CR) rate, defined as the proportion of patients without emesis episodes or rescue medication use during the overall phase of the first cycle. Other efficacy indicators, such as no vomiting and no nausea, were measured as the secondary and exploratory end points.
RESULTS
A total of 248 women from 4 clinical centers in China entered this study, and 243 patients (aprepitant regimen, 125 patients [51.4%]; placebo regimen, 118 patients [48.5%]) were evaluable for efficacy and safety; mean (SD) age of the total population was 40.1 (7.3) years. The CR rate was significantly higher in the aprepitant group vs the control group overall (107 [87.0%] vs 80 [66.7%]; P < .001) and in the acute (114 [92.7%] vs 91 [75.8%]; P = .001) and delayed (109 [88.6%] vs 84 [70.0%]; P = .001) phases of the trial. The incidence of adverse events was similar between the 2 groups (100 [80.0%] vs 96 [81.3%]; P = .79), and no grade 3 or 4 aprepitant treatment-related adverse events were observed. Multivariable analysis revealed that aprepitant use was the only independent factor associated with CR during the overall phase.
CONCLUSIONS AND RELEVANCE
The combination of aprepitant with palonosetron and dexamethasone provided increased antiemetic efficacy in the FOLFOX or FOLFIRI chemotherapy regimen and was well tolerated by younger women with gastrointestinal cancer who have a history of little or no alcohol consumption.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT03674294.
Topics: Adult; Antiemetics; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Camptothecin; China; Double-Blind Method; Female; Fluorouracil; Humans; Leucovorin; Middle Aged; Nausea; Organoplatinum Compounds; Stomach Neoplasms; Vomiting
PubMed: 33835174
DOI: 10.1001/jamanetworkopen.2021.5250