aprepitant and Nausea

Most cancer patients suffer from the pain of chemotherapy-induced nausea and vomiting (CINV). This meta-analysis was performed to evaluate the efficacy and safety of a regimen consisting of aprepitant, dexamethasone, and 5-HT3 receptor antagonists in the prevention and treatment of CINV.. A systematic literature search was conducted across multiple databases, including PubMed, EMbase, Cochrane Library, MEDLINE, CENTRAL, HEED, CNKI, Wanfang, and VIP, to identify randomized controlled trials (RCTs) investigating the use of triple therapy (aprepitant, 5-HT3 receptor antagonist, and dexamethasone) to prevent and treat CINV. Meta-analysis was performed using RevMan 5.4 and Stata17 software, employing either a fixed-effect or random-effect model based on statistical heterogeneity.. A meta-analysis of 23 randomized controlled trials (RCTs) involving 7956 patients was conducted. Efficacy: Results showed significantly improved complete responses (CRs) for CINV in the test group versus the control group in the overall, acute, and delayed phases. Furthermore, in the test group, substantial alleviation of nausea symptoms was observed in the delayed and overall phases but not in the acute phase. Safety: There was no statistically significant difference in the incidence of febrile neutropenia, diarrhea, anorexia, and headache between the 2 groups. The incidence of fatigue and hiccups in the test group was higher than that in the control group; however, the incidence of constipation was significantly lower.. Aprepitant-containing triple therapy is highly effective in the prevention and treatment of CINV, with reliable medication safety.

Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Dexamethasone; Humans; Morpholines; Nausea; Receptors, Serotonin, 5-HT3; Vomiting

Topics: Antineoplastic Agents; Aprepitant; Cost-Benefit Analysis; Humans; Nausea; Vomiting

Researchers have not clearly determined whether adding aprepitant (ADH) to dexamethasone and one 5-HT3 receptor antagonist (DH) is clinically effective at preventing chemotherapy-induced nausea and vomiting (CINV) among patients with lung cancer (LC) treated with platinum-based chemotherapy (PBC). Therefore, we conducted a meta-analysis to examine the efficacy and safety of ADH and DH.. We searched the PubMed, ScienceDirect, Cochrane Library, and Scopus databases, among others, for relevant studies. The primary outcomes were the complete response (CR) and the no nausea rate (NNR). The secondary endpoints were the number of patients who needed rescue antiemetic treatment (RAT), adverse events (AEs), and the Functional Living Index Emesis (FLIE) score.. We initially screened 2,118 articles; ultimately, four randomized controlled trials (RCTs) with 518 patients were included. The ADH group had a superior overall CR [risk ratio (RR): 1.16 (1.06, 1.27), P=0.002] and a lower number of patients who needed RAT [RR: 0.44 (0.29, 0.65), P<0.0001]. The ADH group also had a better overall NNR [RR: 1.11 (0.97, 1.26), P=0.12] and delayed CR [RR: 1.12 (0.97, 1.31), P=0.13]. No significant differences were observed in acute CR, acute NNR, or delayed NNR. In the subgroup analysis of the overall CR and NNR, ADH was superior in certain clinical characteristics (China, cisplatin-based chemotherapy, 2nd-generation 5-HT3 receptor antagonist, ADC <50%, and Eastern Cooperative Oncology Group (ECOG) score of 0-2). No significant differences in the AEs characterized as hematological or nonhematological toxicity were observed between the groups.. Compared with DH, ADH appears to be superior at preventing CINV and achieving a better CR among patients with LC treated with PBC.

Topics: Antiemetics; Antineoplastic Agents; Aprepitant; China; Dexamethasone; Humans; Lung Neoplasms; Morpholines; Nausea; Platinum; Randomized Controlled Trials as Topic; Receptors, Serotonin, 5-HT3; Vomiting

To systematically evaluate the efficacy and safety of antiemetic regimen with aprepitant in the prevention of chemotherapy-induced nausea and vomiting (CINV) and provide updated information for clinical practice.. Pubmed, Embase, the Cochrane Library, and 3 Chinese literature databases were systematically searched. Randomized controlled trials comparing standard regimen (5-hydroxytryptamine-3 receptor antagonist and glucocorticoid) with aprepitant triple regimen (aprepitant plus the standard regimen) for preventing CINV were screened. Literature selection, data extraction, and quality evaluation were performed by 2 reviewers independently. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated in the meta-analysis using RevMan 5.3 software.. A total of 51 randomized controlled trials were finally included in the systematic review. Compared with the standard regimen, the aprepitant triple regimen significantly improved the complete response in the overall (OR 1.88, 95% CI 1.71-2.07), acute (OR 1.96, 95% CI 1.65-2.32) and delayed (OR 1.96, 95% CI 1.70-2.27) phases, regardless of emetogenic risk of chemotherapy. Aprepitant could also significantly enhance the proportions of patients who have no emesis, nausea, or use of rescue medication respectively in the overall, acute and/or delayed phases. Aprepitant was found to be associated with decreased risk of constipation (OR 0.85, 95% CI 0.74-0.97), but increased the incidence of hiccup (OR 1.26, 95% CI 1.05, 1.51). There were no statistically significant differences between the 2 groups on other safety outcomes.. The aprepitant triple regimen is effective for the prevention of CINV in patients being treated with moderately or highly emetogenic chemotherapy, and has a significant tendency to reduce the risk of constipation and increase the incidence of hiccup.

Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Humans; Nausea; Randomized Controlled Trials as Topic; Vomiting

It is important to control chemotherapy-induced nausea and vomiting (CINV) to maintain dose intensity and patients' quality of life. The National Comprehensive Cancer Network guidelines suggest combination therapy of antiemetic agents. The growing number of antiemetic regimens, and in particular the growing use of regimens containing antagonists to the Nk-1 receptor (NK1RAs) and the antipsychotic drug olanzapine (OLZ), call for the re-evaluation of the optimal regimen for CINV. This study assessed the efficacy and safety of antiemetic regimens for highly emetogenic chemotherapy, using Bayesian network meta-analysis.. Randomized trials that compared different antiemetic regimens were included. We strictly followed Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. The main outcomes were the odds ratio (OR) for overall complete response (absence of vomiting). We conducted network meta-analysis within a Bayesian model to combine the direct and indirect evidence. Safety was assessed from the trial description. All statistical tests were two-sided.. We systematically reviewed 27 randomized control trials (13,356 participants), which compared 12 different antiemetic regimens: serotonin-3 receptor antagonist (5HT3), 5HT3 + dexamethasone (Dex), palonosetron (PAL), PAL + Dex, PAL at 0.75 mg (PAL0.75), PAL0.75 + Dex, NK1RA + 5HT3 + Dex, NK1RA + PAL + Dex, an oral combination of netupitant and palonosetron (NEPA) + Dex, OLZ + 5HT3 + Dex, OLZ + PAL + Dex, and OLZ + NK1RA + 5HT3 + Dex. An NK1RA + 5HT3 + Dex regimen and an NK1RA + palonosetron + Dex regimen gave a higher complete response (CR) rate than the reference regimen, 5HT3 + Dex (OR, 1.75; 95% credibility interval [95% CrI], 1.56-1.97, and OR, 2.25; 95% CrI, 1.66-3.03, respectively). A regimen containing NEPA was more effective in producing CR than conventional regimens without NEPA or olanzapine. Further analysis, based on the surface under the cumulative ranking probability curve, indicated that olanzapine-containing regimens were the most effective in producing CR.. Our meta-analysis supports the conclusion that olanzapine-containing regimens are the most effective for CINV of highly emetogenic chemotherapy. We confirmed that NK1RA + PAL + Dex is the most effective of conventional regimens. Substituting olanzapine for an Nk-1 receptor antagonist may offer a less costly and more effective alternative for patients.. Nausea and vomiting during chemotherapy often pose difficulties for patients and doctors, making it hard to continue the proper therapy and to maintain the quality of life. This article gives insights into the optimal choice of medicine to treat nausea during chemotherapy. The findings reported here provide readers with a robust efficacy ranking of antinausea medicine, which can be used as a reference for the best possible treatment. Furthermore, the 70% less costly drug, olanzapine, is suggested to be equally effective to aprepitant in reducing nausea and vomiting. The possibility of offering a cost-effective treatment to a wider range of the population is discussed.

Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Cost-Benefit Analysis; Drug Costs; Humans; Nausea; Neoplasms; Network Meta-Analysis; Olanzapine; Practice Guidelines as Topic; Quality of Life; Randomized Controlled Trials as Topic; Vomiting

High-dose melphalan (HDMel) is the most common conditioning chemotherapy regimen for autologous stem cell transplantation (SCT) in patients affected by multiple myeloma (MM). No consensus exists for the emetogenicity or prophylaxis of chemotherapy-induced nausea and vomiting (CINV) in this regimen.. Data on the incidence and efficacy/safety of CINV prophylaxis among patients affected by MM undergoing autologous SCT with the HDMel regimen was extracted from electronic databases and analyzed.. Eleven studies involving multiple CINV prophylaxis regimens were identified and included. No consensus on HDMel emetogenicity was reached, but most studies summarized the emetogenicity as moderate-high risk. An aprepitant-based three-drug regimen (aprepitant + serotonin receptor antagonist (5HT3RA) + dexamethasone) showed better efficacy than a two-drug regimen (5HT3RA + dexamethasone) for CINV prevention without increasing the frequency in adverse events.. The aprepitant-based three-drug regimen should be the regimen of choice for CINV prophylaxis for MM patients undergoing autologous SCT with HDMel conditioning.

Topics: Adult; Antiemetics; Antineoplastic Agents, Alkylating; Aprepitant; Dexamethasone; Female; Hematopoietic Stem Cell Transplantation; Humans; Induction Chemotherapy; Male; Melphalan; Multiple Myeloma; Nausea; Quality of Life; Serotonin Antagonists; Transplantation Conditioning; Transplantation, Autologous; Vomiting

Cancer chemotherapy has progressed remarkably with conventional and molecular-targeted anticancer drugs as well as immune checkpoint inhibitors. However, adverse drug reaction (ADR) management remains a challenge in cancer chemotherapy. Therefore, improving the quality of medical care through clinical pharmacology research is warranted. Intravenous injection of bendamustine in patients with follicular or mantle cell lymphoma frequently causes venous irritation. Because the underlying mechanisms are not clear, we investigated the factors responsible for bendamustine-induced venous irritation. Based on the results of our analysis, we altered the administration regimen and observed that the incidence of venous irritation, which manifested in a concentration-dependent manner following conventional approaches, significantly decreased when following the modified regimen. Guidelines on the management of chemotherapy-induced nausea and vomiting recommend aprepitant, a selective neurokinin-1 (NK-1) receptor antagonist, 5-hydroxytryptamine 3 (5-HT

Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Bendamustine Hydrochloride; Dose-Response Relationship, Drug; Humans; Injections, Intravenous; Nausea; Neoplasms; Pharmacology, Clinical; Precision Medicine; Quality of Health Care; Research

Aprepitant and fosaprepitant, commonly used for the prevention of chemotherapy-induced nausea and vomiting, alter cytochrome P450 activity. This systematic review evaluates clinically significant pharmacokinetic drug interactions with aprepitant and fosaprepitant and describes adverse events ascribed to drug interactions with aprepitant or fosaprepitant.. We systematically reviewed the literature to September 11, 2016, to identify articles evaluating drug interactions involving aprepitant/fosaprepitant. The clinical significance of each reported pharmacokinetic drug interaction was evaluated based on the United States Food and Drug Administration guidance document on conducting drug interaction studies. The probability of an adverse event reported in case reports being due to a drug interaction with aprepitant/fosaprepitant was determined using the Drug Interaction Probability Scale.. A total of 4377 publications were identified. Of these, 64 met inclusion eligibility criteria: 34 described pharmacokinetic drug interactions and 30 described adverse events ascribed to a drug interaction. Clinically significant pharmacokinetic interactions between aprepitant/fosaprepitant and bosutinib PO, cabazitaxel IV, cyclophosphamide IV, dexamethasone PO, methylprednisolone IV, midazolam PO/IV, oxycodone PO and tolbutamide PO were identified, as were adverse events resulting from an interaction between aprepitant/fosaprepitant and alcohol, anthracyclines, ifosfamide, oxycodone, quetiapine, selective serotonin reuptake inhibitors/serotonin-norepinephrine reuptake inhibitors and warfarin.. The potential for a drug interaction with aprepitant and fosaprepitant should be considered when selecting antiemetic therapy.

Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Cytochrome P-450 CYP2C9 Inducers; Cytochrome P-450 CYP3A Inhibitors; Drug Interactions; Ethanol; Humans; Injection Site Reaction; Morpholines; Nausea; Oxycodone; Quetiapine Fumarate; Selective Serotonin Reuptake Inhibitors; Serotonin and Noradrenaline Reuptake Inhibitors; Vomiting

Neurokinin-1 receptor antagonists (NK-1RAs) are widely used for chemotherapy-induced nausea and vomiting (CINV) control in patients with highly emetogenic chemotherapy (HEC) and/or moderately emetogenic chemotherapy (MEC). Whether the efficacy and toxicity of antiemesis are different among various NK-1RA-based triple regimens is unknown.. Data of complete responses (CRs) in the acute, delayed, and overall phases and treatment-related adverse events (TRAEs) were extracted from electronic databases. Efficacy and toxicity were integrated by pairwise and network meta-analyses.. Thirty-six trials involving 18 889 patients using triple regimens (NK-1RA+serotonin receptor antagonists [5HT3RA] + dexamethasone) or duplex regimen (5HT3RA+dexamethasone) to control CINV were included in the analysis. Different NK-1RA-based triple regimens shared equivalent effect on CRs. In patients with HEC, almost all triple regimens showed statistically significantly higher CRs than duplex regimen (odds ratio [OR]. Different NK-1RAs-based triple regimens shared equivalent effect on CINV control. Various triple regimens had superior antiemetic effect than duplex regimen in patients with HEC. Only aprepitant-based triple regimen showed better CINV control compared with duplex regimen in patients receiving MEC. Palonosetron and first-generation 5HT3RAs might share equivalent CINV control in the combination of NK-1RAs and dexamethasone. Lower doses of dexamethasone might be applied when used with NK-1RAs and 5HT3RAs.

Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Dexamethasone; Drug Therapy, Combination; Humans; Isoquinolines; Morpholines; Nausea; Network Meta-Analysis; Neurokinin-1 Receptor Antagonists; Palonosetron; Quinuclidines; Serotonin Antagonists; Vomiting

To review the efficacy and safety of aprepitant in combination with ondansetron and dexamethasone (triple therapy) in children and adolescents on moderate to highly emetogenic chemotherapy.. Medline, Embase, Scielo, Lilacs, Cochrane and congress abstracts published until September 2016 were used as data sources. Two reviewers independently selected manuscripts and extracted data. A third reviewer solved discrepancies in study selection and data extraction. The primary outcome was overall complete response (no vomiting from 0 to 120 h). Secondary outcomes were: response in acute phase, delayed phase and reported toxicities. Each study was considered a unit of analysis. Summarized relative risks were recalculated based on reported data. All meta-analyses used a random-effects model and heterogeneity was reported using the I. From 1004 studies, we screened 288 titles and abstracts and included three trials for data extraction. The population comprised 451 patients. Most patients were males, ranging from 6 months to 19 years of age, and weighing from 6 to 134 kg. Bone cancer was the most incident (≥50%) neoplasm, followed by rhabdomyosarcoma and Hodgkin's lymphoma. Triple therapy was associated with a reduced risk of developing chemotherapy-induced vomiting (CIV) (RR = 0.48; 95% CI 0.34-0.67). There were no differences in incidence of febrile neutropenia between groups (RR = 1.02; 95% CI 0.66-1.58).. Triple therapy decreased CIV risk, without increasing the occurrence of febrile neutropenia. However, this review could not address which subpopulations would most benefit from using this strategy. Future studies should focus on assessing risk factors for nausea and vomiting, as many patients did not achieve a complete antiemetic response.

Topics: Adolescent; Antiemetics; Antineoplastic Agents; Aprepitant; Child; Child, Preschool; Dexamethasone; Drug Therapy, Combination; Humans; Infant; Morpholines; Nausea; Neoplasms; Ondansetron; Randomized Controlled Trials as Topic; Risk Factors; Vomiting; Young Adult

The aim of the present study was to evaluate the efficacy of olanzapine for the prevention of chemotherapy-induced nausea and vomiting (CINV).. 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.. 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.. 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

A variety of triple antiemetic regimens are being used to prevent cisplatin-based chemotherapy induced delayed emesis and nausea in cancer patients. We performed a network meta-analysis to compare the efficacies of the different regimens. Electronic searches of the PubMed, Cochrane Library and MEDLINE databases were performed to identify randomized controlled trials, and data were analyzed using JAGS, Stata 14.0 and R project. The primary outcome was a complete response (CR). The secondary outcomes were no vomiting (NV) and no nausea (NN). Among the 398 studies identified, 10 were eligible and included, providing data on nine regimens. In the CR analysis, the absolute rank of netupitant + palonosetron + dexamethasone (NEPA) was 0.8579. In the NV and NN analyses, NEPA's absolute ranks were 0.8631 and 0.7902, respectively. The compliance of patients treated with rolapitant + granisetron + dexamethasone (RGD) was the best due to a low incidence of adverse events, and good compliance was also observed with NEPA. It was difficult to achieve good compliance with aprepitant + granisetron + dexamethasone (AGD). Overall, NEPA was the best regimen, and aprepitant + ondansetron + dexamethasone (AOD) is also worthy of recommendation because of its low cost and good effect. For patients with severe constipation, hiccups, asthenia and/or delayed nausea, RGD is worthy of consideration.

Topics: Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Cisplatin; Dexamethasone; Drug Therapy, Combination; Granisetron; Humans; Isoquinolines; Morpholines; Nausea; Neoplasms; Network Meta-Analysis; Ondansetron; Palonosetron; Quinuclidines; Randomized Controlled Trials as Topic; Spiro Compounds; Treatment Outcome; Vomiting

Chemotherapy-induced nausea and vomiting (CINV) is a common adverse event associated with anticancer treatment that can have a significant adverse impact on patient health-related quality of life and that can potentially undermine the effectiveness of chemotherapy. Traditional regimens to prevent CINV generally involved a combination of a corticosteroid plus a 5-hydroxytryptamine (5HT3) receptor antagonist (RA). In the past 10 years, antiemetic treatment has greatly advanced with the availability of the neurokinin-1 receptor antagonist (NK1 RA) aprepitant and its prodrug fosaprepitant. NK1 RAs have a different mechanism of action in CINV than corticosteroids and 5HT3 RAs, thus their use can complement traditional antiemetic drugs and can enhance control of CINV. This review examined accumulated data regarding the safety and efficacy of aprepitant and fosaprepitant over the decade since the first regulatory approval. Data from key studies of aprepitant and fosaprepitant in the prevention of CINV in patients receiving moderately and highly emetogenic chemotherapy were explored, as were recommendations in currently available guidelines for their use. In addition, their use as antiemetic therapy in special patient populations was highlighted. Future perspectives on potential uses of aprepitant and fosaprepitant for indications other than CINV are presented.

Topics: Administration, Intravenous; Administration, Oral; Antiemetics; Antineoplastic Agents; Aprepitant; Drug Interactions; Guidelines as Topic; Humans; Morpholines; Nausea; Stem Cell Transplantation; Vomiting

Nausea and vomiting are common adverse events in chemotherapy. In spite of the serious effects on the quality of life and further treatment, they remain overlooked by physicians, and no standard treatment has been developed. Neurokinin-1 (NK-1) receptor antagonists and palonosetron are the major agents in the standard regimen for treating moderately and highly emetogenic chemotherapy-induced nausea and vomiting (CINV). However, NK-1 receptor antagonists first became commercially available at the end of 2013 and palonosetron has not been extensively applied in China. Olanzapine was recommended as a therapy for moderate and severe CINV in antiemesis-clinical practice guidelines in oncology in 2014 for the first time. It is an atypical antipsychotic agent, which can block multiple receptors on neurotransmitters. During more than 10 years, olanzapine has demonstrated significant effects in preventing CINV and treating breakthrough and refractor CINV, which was observed in case reports, precise retrospective studies, and phase I, II and III clinical trials, with no grade 3 to 4 adverse events. In particular, it is superior to aprepitant and dexamethasone in delayed nausea and vomiting. Therefore, this compound is worthy of further investigation.

Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Benzodiazepines; Dexamethasone; Emetics; Humans; Isoquinolines; Morpholines; Nausea; Neoplasms; Neurokinin-1 Receptor Antagonists; Olanzapine; Palonosetron; Quinuclidines; Vomiting

Chemotherapy is a major therapeutic approach for malignant neoplasms; however, due to the most common adverse events of nausea and vomiting, scheduled chemotherapeutic programs may be impeded or even interrupted, which severely impairs the efficacy. Aprepitants, 5-HT3 antagonists and dexamethasone are primary drugs used to prevent chemotherapy-induced nausea and vomiting (CINV). These drugs have excellent efficacy for control of acute vomiting but are relatively ineffective for delayed vomiting. Aprepitant may remedy this deficiency. Substance P was discovered in the 1930s and its association with vomiting was confirmed in the 1950s. This was followed by a period of non-peptide neurokinin-1 (NK-1) receptor antagonist synthesis and investigation in preclinical studies and clinical trials (phases I, II and III). The FDA granted permission for the clinical chemotherapeutic use of aprepitant in 2003. At present, the combined use of aprepitant, 5-HT3 antagonists and dexamethasone satisfactorily controls vomiting but not nausea. Therefore, new therapeutic approaches and drugs are still needed.

Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Dexamethasone; Humans; Morpholines; Nausea; Serotonin 5-HT3 Receptor Agonists; Vomiting

Various antiemetic agents are commonly administered during and after chemotherapy to prevent nausea and vomiting depending on the emetogenic risk. Data specific for patients older than 65 are rarely discussed and it is often assumed that such patients have less risk of nausea and vomiting and might not need the same prevention.. To determine whether response to antiemetic regimens incorporating aprepitant varies with patient age, we combined previously unpublished subgroup analyses from four previously published studies.. Risk ratios were combined using standard meta-analytic techniques to determine whether antiemetic regimens including aprepitant lead to more complete responses to antiemetic therapy than regimens without aprepitant, among patients aged 65 and over.. Patients aged 65 and over have a significantly greater chance of experiencing a complete response (no vomiting or use of rescue therapy) to antiemetic treatment when aprepitant is included in the antiemetic regimen (Risk Ratio 1.25, 95% Confidence Interval 1.11 to 1.40, p=0.0002) than when it is not. This risk ratio is not significantly different (Q=0.281, p=0.596) from the risk ratio calculated for patients under age 65 (1.30, 95% Confidence Interval 1.19 to 1.42), from the same set of studies.. This meta-analysis combines studies utilizing different antiemetic regimens and different patient populations. Only a single efficacy outcome is included, and safety is not assessed.. We conclude that for both the under 65years and the age 65 and over populations, antiemetic regimens including aprepitant, along with a 5-HT3 antagonist and a corticosteroid, are more effective in reducing chemotherapy-induced nausea and vomiting than regimens that do not include aprepitant.

Topics: Aged; Antiemetics; Antineoplastic Agents; Aprepitant; Double-Blind Method; Female; Humans; Male; Morpholines; Nausea; Neoplasms; Randomized Controlled Trials as Topic; Vomiting

Chemotherapy regimens differ according to the tumor type being treated and are associated with varying degrees of emetogenic potential. Since the distribution of risk factors for chemotherapy-induced nausea and vomiting differs across tumor types, it is important to understand the efficacy of antiemetic regimens in multiple patient populations. To characterize treatment response in patients with various malignancies (e.g., breast, gastrointestinal, genitourinary, and lung) treated with either highly emetogenic chemotherapy (HEC) or moderately emetogenic chemotherapy (MEC) regimens, a pooled analysis of patient-level data from 4 large randomized trials was performed (N=2813). Patients receiving an antiemetic regimen containing aprepitant, ondansetron, and dexamethasone were compared with patients receiving an active-control antiemetic regimen containing ondansetron plus dexamethasone. In all tumor types analyzed, complete responses were observed in a higher proportion of HEC-treated patients receiving aprepitant compared with active-control patients (genitourinary [61.5% vs 40.6%, P<0.001], gastrointestinal [68.2% vs 44.7%, P=0.013], and lung cancers [73.5% vs 52.8%, P<0.001]). For MEC-treated patients, complete response rates were also higher for aprepitant patients than active-control patients for all tumor types, with a significant difference noted among patients with breast cancer (54.9% vs 43.9%, P<0.0001). The proportion of patients with no vomiting was higher in both HEC- and MEC-treated patients. While results of previous studies provide support for the use of antiemetic regimens that include aprepitant, a selective 5-hydroxytryptamine-3 receptor antagonist, and dexamethasone, this analysis demonstrates the consistent efficacy of aprepitant as part of an antiemetic regimen across different tumor types and chemotherapy regimens.

Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Clinical Trials, Phase III as Topic; Humans; Morpholines; Nausea; Neoplasms; Randomized Controlled Trials as Topic; Vomiting

Chemotherapy-induced nausea and vomiting (CINV) and nephrotoxicity are adverse events induced by cisplatin administration. These effects can be reduced by treatment regimens with low-dose cisplatin, but high-dose cisplatin is still used. In Japan, high-dose cisplatin is usually administered in an inpatient setting to permit management of CINV. However, with use of new-generation antiemetic agents such as aprepitant, CINV and nephrotoxicity are controllable in an outpatient setting. Here, we discuss issues related to the management of high-dose cisplatin administration in outpatients. Grade 2 or worse CINV induced by high-dose cisplatin occurs in more than 40% of patients without treatment with aprepitant, but is controllable by administration of a 5-HT3 receptor antagonist, steroids and aprepitant. Moreover, prevention of CINV using these drugs is cost-effective, since outpatient settings have advantages with regard to health economics and patient quality of life. These findings suggest that shifting high-dose cisplatin administration to the outpatient setting may be achieved with co-administration of aprepitant. Available facilities and the status of the patient should be considered when selecting whether an outpatient setting is suitable for administration of cisplatin, but the use of aprepitant and adequate oral hydration should allow use of cisplatin in this setting.

Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Cisplatin; Fluid Therapy; Humans; Kidney; Kidney Diseases; Morpholines; Nausea; Neoplasms; Vomiting

A number of studies have reported that aprepitant has been used to prevent chemotherapy-induced nausea and vomiting. In this study, we aimed to analyze the efficacy and safety of aprepitant, which can provide evidence for aprepitant administration.. Fifteen trials involving patients who received moderately or highly emetogenic chemotherapy were included in this pooled analysis. Antiemetic drugs in these studies included aprepitant, dexamethasone, and 5-HT3 receptor antagonists.. A total of 4,798 cases were investigated in these clinical trials. Compared with placebo or the standard antiemetic therapy, the cumulative incidence of emesis was significantly reduced in the patients treated with aprepitant-based (125 mg/80 mg) therapy on the first day [relative risk (RR) = 1.13, 95% confidence interval (CI) 1.10-1.16], from 2 to 5 days (RR = 1.35, 95% CI 1.22-1.48) and in the overall 5 days (RR = 1.30, 95% CI 1.22-1.39). In terms of drug safety, there was no significant difference between aprepitant-based regimens and non-aprepitant regimens.. Results from the analysis suggest that aprepitant with 5-HT3 receptor antagonists and dexamethasone is highly effective in preventing nausea and vomiting in the days after administration of moderately or highly emetogenic chemotherapy (MEC or HEC) agents.

Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Dexamethasone; Humans; Morpholines; Nausea; Serotonin 5-HT3 Receptor Antagonists; Treatment Outcome; Vomiting

For patients receiving cancer chemotherapy, the ongoing development of antiemetic treatment is of significant importance. Patients consider nausea and vomiting among the most distressing symptoms of chemotherapy, and as new antiemetics have been very successful in prevention of vomiting, agents effective against nausea have become one of the major unmet needs. The neurokinin (NK)(1) receptor antagonist aprepitant potentiates the antiemetic efficacy of the combination of a serotonin receptor antagonist and a corticosteroid. Fosaprepitant (intravenous prodrug of aprepitant) given as a single intravenous dose of 150 mg can replace the aprepitant 3-day oral regimen. This article focuses on the development and clinical application of fosaprepitant.

Topics: Animals; Antiemetics; Antineoplastic Agents; Aprepitant; Clinical Trials as Topic; Humans; Morpholines; Nausea; Neurokinin-1 Receptor Antagonists; Receptors, Neurokinin-1; Treatment Outcome; Vomiting

The addition of neurokinin-1 receptor (NK1R) antagonists to antiemetic regimens has substantially reduced chemotherapy-induced nausea and vomiting (CINV). We sought to systematically review the overall impact of NK1R antagonists on CINV prevention.. We systematically searched the MEDLINE, EMBASE, and CENTRAL databases, and meeting proceedings for randomized controlled trials (RCTs) that evaluated NK1R antagonists plus standard antiemetic therapy for CINV prevention. Complete response (CR) to therapy was defined as the absence of emesis and the absence of rescue therapy. The endpoints were defined as CR in the overall phase (during the first 120 hours of chemotherapy), CR in the acute phase (first 24 hours), and the delayed phase (24-120 hours) after chemotherapy, nausea, and toxicity. Subgroup analyses evaluated the type of NK1R antagonist used, the emetogenic potential of the chemotherapy regimen, and prolonged use of 5-HT3 (serotonin) receptor antagonists, a class of standard antiemetic agents. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random-effects model. Statistical tests for heterogeneity were one-sided; statistical tests for effect estimates and publication bias were two-sided.. Seventeen trials (8740 patients) were included in this analysis. NK1R antagonists increased the CR rate in the overall phase from 54% to 72% (OR = 0.51, 95% CI = 0.46 to 0.57, P < .001). CR and nausea were improved in all phases and subgroups. The expected side effects from NK1R antagonists did not statistically significantly differ from previous reports; however, this analysis suggests that the incidence of severe infection increased from 2% to 6% in the NK1R antagonist group (three RCTs with a total of 1480 patients; OR = 3.10; 95% CI = 1.69 to 5.67, P < .001).. NK1R antagonists increased CINV control in the acute, delayed, and overall phases. They are effective for both moderately and highly emetogenic chemotherapy regimens. Their use might be associated with increased infection rates; however, additional appraisal of specific data from RCTs is needed.

Topics: Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Confidence Intervals; Humans; Infections; Morpholines; Nausea; Neoplasms; Neurokinin-1 Receptor Antagonists; Odds Ratio; Piperazines; Piperidines; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Serotonin 5-HT3 Receptor Antagonists; Vomiting

Aprepitant is the only neurokinin (NK(1)) receptor antagonist (RA) approved for prevention of chemotherapy-induced nausea and vomiting (CINV). Aprepitant is co-administered with a 5-HT(3) RA and a corticosteroid. Although aprepitant is safe, in most clinical settings potential drug-drug interactions need to be considered before prescription.. This article thoroughly reviews aprepitant and, in particular, clinically relevant safety aspects of the drug. The literature review was performed using Medline with the following search terms: adverse events, aprepitant, chemotherapy, CYP3A4, MK-0869, neurokinin(1) receptor antagonist, safety and tolerability.. The recommended antiemetic regimen of aprepitant, a 5-HT(3) RA and a corticosteroid is safe. The combination of aprepitant, a 5-HT(3) RA and dexamethasone is now the gold standard of antiemetic treatment in prevention of CINV induced by HEC, or by the combination of an anthracycline and cyclophosphamide. The intravenous formulation of aprepitant used as a single dose is expected to be of benefit to cancer patients.

Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Clinical Trials as Topic; Drug Interactions; Humans; Morpholines; Nausea; Vomiting

Chemotherapy can be a life-prolonging treatment for many cancer patients, but it is often associated with profound nausea and vomiting that is so distressing that patients may delay or decline treatment to avoid these side effects. EMEND (aprepitant) is the first and only neurokinin-1 (NK-1) receptor antagonist available on the market for the prevention of acute and delayed chemotherapy-induced nausea and vomiting (CINV). Aprepitant acts centrally at NK-1 receptors in vomiting centers within the central nervous system to block their activation by substance P released as an unwanted consequence of chemotherapy. By controlling nausea and vomiting, EMEND helps improve patients' daily living and their ability to complete multiple cycles of chemotherapy. The development of aprepitant included a novel nanoparticle formulation to optimize oral absorption and innovative chemistry to discover a prodrug form suitable for intravenous administration to improve compliance and convenience for healthcare professionals and cancer patients.

Topics: Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Drug Discovery; History, 20th Century; History, 21st Century; Humans; Models, Biological; Morpholines; Nausea; Neoplasms; Neurokinin-1 Receptor Antagonists; Vomiting

To update the American Society of Clinical Oncology (ASCO) guideline for antiemetics in oncology.. A systematic review of the medical literature was completed to inform this update. MEDLINE, the Cochrane Collaboration Library, and meeting materials from ASCO and the Multinational Association for Supportive Care in Cancer were all searched. Primary outcomes of interest were complete response and rates of any vomiting or nausea.. Thirty-seven trials met prespecified inclusion and exclusion criteria for this systematic review. Two systematic reviews from the Cochrane Collaboration were identified; one surveyed the pediatric literature. The other compared the relative efficacy of the 5-hydroxytryptamine-3 (5-HT(3)) receptor antagonists.. Combined anthracycline and cyclophosphamide regimens were reclassified as highly emetic. Patients who receive this combination or any highly emetic agents should receive a 5-HT(3) receptor antagonist, dexamethasone, and a neurokinin 1 (NK(1)) receptor antagonist. A large trial validated the equivalency of fosaprepitant, a single-day intravenous formulation, with aprepitant; either therapy is appropriate. Preferential use of palonosetron is recommended for moderate emetic risk regimens, combined with dexamethasone. For low-risk agents, patients can be offered dexamethasone before the first dose of chemotherapy. Patients undergoing high emetic risk radiation therapy should receive a 5-HT(3) receptor antagonist before each fraction and for 24 hours after treatment and may receive a 5-day course of dexamethasone during fractions 1 to 5. The Update Committee noted the importance of continued symptom monitoring throughout therapy. Clinicians underestimate the incidence of nausea, which is not as well controlled as emesis.

Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Dexamethasone; Drug Administration Schedule; Humans; Infusions, Intravenous; Isoquinolines; Morpholines; Nausea; Neurokinin-1 Receptor Antagonists; Palonosetron; Quinuclidines; Radiotherapy; Serotonin Antagonists; Surveys and Questionnaires; Vomiting

Chemotherapy induced nausea and vomiting (CINV) is a common complication in the treatment of patients with cancer. The introduction of the first in class neurokinin-1 receptor antagonist aprepitant provided additive control on CINV in combination to existing antiemetics. Due to formulation issues, aprepitant is only available for oral administration. Fosaprepitant, a prodrug of aprepitant, was introduced to the market in 2008 as an intravenous bioequivalent to aprepitant.. This review examines the chemical development of fosaprepitant, its pharmacokinetic properties, approved uses and potential applications.. The reader will get up-to-date information on the pharmacology and clinical uses of fosaprepitant. Clinical studies have demonstrated pharmacokinetic bioequivalence of aprepitant 125 mg to fosaprepitant 115 mg, as well as comparable efficacy in prevention of acute and delayed emesis following the first day of chemotherapy regimens.. Fosaprepitant is an intravenous prodrug of aprepitant that offers a new alternative to patients with CINV. Currently, fosaprepitant can substitute oral aprepitant in day 1 of a 3-day regimen. Current studies show that a single-day fosaprepitant regimen is also bioequivalent to the 3-day aprepitant regimen; this could significantly simplify the care for CINV patients in the future.

Topics: Animals; Antiemetics; Antineoplastic Agents; Aprepitant; Humans; Morpholines; Nausea; Neoplasms; Neurokinin-1 Receptor Antagonists; Prodrugs; Therapeutic Equivalency; Vomiting

To assess the efficacy and safety of aprepitant for the prevention of chemotherapy-induced nausea and vomiting (CINV) after moderately or highly emetogenic chemotherapy.. Studies were identified by searching PubMed (1980 to March, 2010), EMbase (1980 to March, 2010), Cochrane Libraries (Issue 2, 2010), CNKI (1980 to March, 2010), CBMdisc (1980 to March, 2010), and WanFang Data (1982 to March, 2010). Randomized controlled trials of aprepitant for the prevention of CINV were included. The quality of included studies was assessed and meta-analysis was performed for the results of homogeneous studies by RevMan 5.0.23 software.. Ten studies involving 4 376 oncology patients were included. They were all high quality studies, with Jadad scores more than 5. The results of meta-analysis were as follows: (1) Acute CINV: The overall complete response rate was improved by 14.21% when aprepitant was combined with ondansetron and dexamethasone (83.33% vs 72.96%; P<0.001). Subgroup analysis showed the patients receiving AC (anthracycline/cyclophosphamide) regimen benefited less than the patients receiving cisplatin chemotherapy. The rate of no significant nausea was only improved by 3.92% (P=0.04). (2) Delayed CINV: Compared with ondansetron, aprepitant could improve vomiting by 14.98% (P=0.004). When aprepitant was added with dexamethasone, the response rate of vomiting and nausea was improved by 37.72% (P<0.001) and 11.24% (P=0.008) respectively. (3) Adverse reactions: The incidence of fatigue/asthenia was higher in the aprepitant regimen (P=0.001), while the incidence of constipation was lower (P=0.002).. Aprepitant can improve the control of vomiting, but has slight effect on nausea. Patients receiving AC regimen benefit less than patients receiving cisplatin chemotherapy. In view of its high cost, pharmacoeconomics researches of aprepitant should be considered.

Topics: Adult; Antiemetics; Antineoplastic Agents; Aprepitant; Female; Humans; Male; Morpholines; Nausea; Randomized Controlled Trials as Topic; Vomiting

Chemotherapy-induced nausea and vomiting (CINV) is associated with a significant deterioration in quality of life. The emetogenicity of the chemotherapeutic agents, repeated chemotherapy cycles, and patient risk factors significantly influence CINV. 5-hydroxytryptamine-3 (5-HT(3)) receptor antagonists plus dexamethasone have significantly improved the control of acute CINV, but delayed CINV remains a significant clinical problem. Two new agents, palonosetron and aprepitant, have been approved for the prevention of both acute and delayed CINV. Palonosetron is a second-generation 5-HT(3) receptor antagonist with a longer half-life and a higher binding affinity than first-generation 5-HT(3) receptor antagonists. Aprepitant is the first agent available in the new drug class of neurokinin-1 (NK-1) receptor antagonists. Casopitant is another NK-1 receptor antagonist that is under review by the FDA after recent completion of Phase III clinical trials. The introduction of these new agents has generated revised antiemetic guidelines for the prevention of CINV. Future studies may consider the use of palonosetron, aprepitant and casopitant with other antiemetic agents (olanzapine, gabapentin, cannabinoids) in moderately and highly emetogenic chemotherapy, as well as in the clinical settings of multiple-day chemotherapy and bone marrow transplantation.

Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Clinical Trials, Phase III as Topic; Humans; Isoquinolines; Morpholines; Nausea; Palonosetron; Piperazines; Piperidines; Quinuclidines; Serotonin Antagonists; Vomiting

Even today, nausea and vomiting are two of the most distressing adverse effects associated with tumor therapy. The authors give an overview of the mechanism and the trigger factors (emetogenic potential of the chemotherapies, the patient risk factors, and the used antiemetic drugs) of nausea and vomiting. A short summary will describe the antiemetic drugs focusing on metoclopramide, steroid and the currently widely used setron therapy which is effective only during the acute phase of chemotherapy-induced nausea and vomiting (CINV). In the treatment of CINV the latest improvement was the introduction of the neurokinin (NK1) receptor antagonist class. Currently the only available agent is aprepitant which is indicated to treat CINV in case of highly and moderately emetogenic chemotherapies. The pivotal phase III trials defined that aprepitant is the first drug that is able to protect against the delayed phase of CINV plus can improve the antiemetic therapy during the acute phase. Currently aprepitant is reimbursed in Hungary only after the failure of setron therapy in case of high dose (\\>50 mg/m2) cisplatin protocols. The authors give a recommendation how to treat CINV based on the latest international antiemetic guidelines.The mechanism and the trigger factors of radiotherapy-induced nausea and vomiting (RINV) are different from CINV. For treatment of RINV metoclopramide (due to reimbursement regulation) and ondansetron can be used. In case of radio-chemotherapy the antiemetic treatment should follow the CINV guidelines.

Topics: Anti-Anxiety Agents; Antiemetics; Antineoplastic Agents; Aprepitant; Drug Therapy, Combination; Humans; Methylprednisolone; Metoclopramide; Morpholines; Nausea; Neoplasms; Ondansetron; Practice Guidelines as Topic; Selective Serotonin Reuptake Inhibitors; Vomiting

Aprepitant (Emend) is a neurokinin-1 (NK(1)) receptor antagonist that is able to alleviate the emetic effects of substance P. When combined with a standard regimen of a corticosteroid (dexamethasone) and a serotonin 5-HT(3) receptor antagonist (ondansetron), oral aprepitant (125 mg on day 1 then 80 mg once daily on days 2 and 3) was effective in the prevention of acute and delayed chemotherapy-induced nausea and vomiting (CINV) associated with single or multiple cycles of highly emetogenic chemotherapy (HEC). This aprepitant regimen was also effective in the prevention of CINV in patients treated with single or multiple cycles of moderately emetogenic chemotherapy (MEC). A single oral dose of aprepitant 40 mg administered prior to patients undergoing abdominal surgery was also effective in the prevention of postoperative nausea and vomiting (PONV). Aprepitant was generally well tolerated. Aprepitant is a recommended option for the treatment of PONV, and when combined with a corticosteroid and 5-HT(3) receptor antagonist is a recommended regimen for the treatment of CINV.

Topics: Animals; Antiemetics; Aprepitant; Clinical Trials as Topic; Humans; Morpholines; Nausea; Vomiting

Nausea and vomiting is one of the most feared side effects of chemotherapy; however, in the past 20 years, a better understanding of the pathophysiology of chemotherapy-induced nausea and vomiting (CINV) has led to the introduction of newer antiemetics, which have improved the management of this side effect.. This article reviews the prevention of CINV and the role of aprepitant, the first of the newest class of antiemetics, the neurokinin-1 inhibitors. A brief description of the pathophysiology of CINV and the background on the prevention of CINV using the 5-HT(3) antagonists is outlined. The pharmacology, pharmacokinetics, drug interactions and various clinical studies with aprepitant are reviewed.. The literature about aprepitant is reviewed focusing on the role of aprepitant in the management of CINV in relationship to other commonly used antiemetics. The literature was searched regarding aprepitant and its pharmacological characteristics, pharmacokinetics, drug interactions and various clinical studies.. Aprepitant has a significant role in the management of CINV, as it allows the majority of patients to complete their chemotherapies without significant morbidity. Its use in a variety of clinical settings in cancer patients needs to be further explored.

Topics: Animals; Antiemetics; Antineoplastic Agents; Aprepitant; Clinical Trials as Topic; Humans; Morpholines; Nausea; Neurokinin-1 Receptor Antagonists; Vomiting

Topics: Animals; Antiemetics; Antineoplastic Agents; Aprepitant; Dexamethasone; Drug Therapy, Combination; Female; Humans; Male; Morpholines; Nausea; Neoplasms; Neurokinin-1 Receptor Antagonists; Risk Factors; Serotonin 5-HT3 Receptor Antagonists; Serotonin Antagonists; Vomiting

Only a few studies have investigated the effect of antiemetic therapy in patients treated with multiple-day or multiple cycles of chemotherapy. The present review will assess the available data, highlight the current recommendations and draw attention towards the remaining problems in this field of antiemetic treatment.. Evidence-based guidelines recommend a combination of a 5-HT3-receptor antagonist and dexamethasone in the prophylaxis of nausea and vomiting in multiple-day cisplatin-based chemotherapy. In patients treated with multiple cycles of chemotherapy the addition of a NK1-receptor antagonist aprepitant to standard antiemetic therapy has increased the antiemetic effect, and multiple cycle extension studies have demonstrated that this increment in effect is sustained during multiple cycles of chemotherapy. A recent study indicated that the dopamine D2-receptor antagonist metopimazine has some additive effect on delayed symptoms induced by multiple-day chemotherapy.. The development of the NK1-receptor antagonist aprepitant has significantly improved the antiemetic control in patients treated with multiple cycles of chemotherapy. Far too many patients still experience considerable emetic side effects. The effect of aprepitant in multiple-day chemotherapy has yet to be defined. The effect of new antiemetic agents such as palonosetron and olanzapine also needs to be investigated in randomized trials.

Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Benzodiazepines; Cisplatin; Dexamethasone; Dopamine D2 Receptor Antagonists; Drug Administration Schedule; Humans; Isonipecotic Acids; Isoquinolines; Morpholines; Nausea; Neurokinin-1 Receptor Antagonists; Olanzapine; Palonosetron; Quinuclidines; Serotonin 5-HT3 Receptor Antagonists; Serotonin Antagonists; Vomiting

The experience of patients living with cancer and being treated with chemotherapy often includes the symptoms of nausea and vomiting. To provide a framework for high-quality management of these symptoms, we developed a set of key targeted evidence-based standards through an iterative process of targeted systematic review, development, and refinement of topic areas and standards and consensus ratings by a multidisciplinary expert panel as part of the RAND Cancer Quality-Assessing Symptoms Side Effects and Indicators of Supportive Treatment Project. For nausea and vomiting, key clinical standards included screening at the initial outpatient and inpatient visit, prophylaxis for acute and delayed emesis in patients receiving moderate to highly emetic chemotherapy, and follow-up after treatment for nausea and vomiting symptoms. In addition, patients with cancer and small bowel obstruction were examined as a special subset of patients who present with nausea and vomiting. The standards presented here for preventing and managing nausea and vomiting in cancer care should be incorporated into care pathways and should become the expectation rather than the exception.

Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Dexamethasone; Electroacupuncture; Evidence-Based Medicine; Humans; Intestinal Obstruction; Morpholines; Nausea; Neoplasms; Quality Assurance, Health Care; Randomized Controlled Trials as Topic; Risk Factors; Serotonin 5-HT3 Receptor Antagonists; Vomiting

Chemotherapy-induced nausea and vomiting (CINV) is a distressing and common adverse event associated with cancer treatment. Updated antiemetic guidelines were published in 2008 by the National Comprehensive Cancer Network and, in 2006, by the American Society of Clinical Oncology, which have included the use of the new and more effective antiemetic agents 5-hydroxytryptamine-3 (5-HT(3)) receptor antagonist and neurokinin (NK)-1 receptor antagonist. Aprepitant is a selective NK-1 receptor antagonist approved as part of combination therapy with a corticosteroid and a 5-HT(3) receptor antagonist for the prevention of acute and delayed CINV in patients receiving moderately and highly emetogenic chemotherapy. Fosaprepitant (also known as MK-0517 and L-758,298) is a water-soluble phosphoryl prodrug for aprepitant, which, when administered intravenously, is converted to aprepitant within 30 min of intravenous administration via the action of ubiquitous phosphatases. Owing to the rapid conversion of fosaprepitant to the active form (aprepitant), fosaprepitant 115 mg provided the same aprepitant exposure in terms of AUC as aprepitant 12 mg orally, and fosaprepitant is expected to provide a correspondingly similar antiemetic effect as aprepitant. Clinical studies have suggested that fosaprepitant could be appropriate as an intravenous alternative to the aprepitant oral capsule. In a study in healthy subjects, fosaprepitant 115 mg was generally well tolerated at a final drug concentration of 1 mg/ml, and fosaprepitant 115 mg was AUC bioequivalent to aprepitant 125 mg. Fosaprepitant in the dose of 115 mg has been approved by the US FDA, the EU and the Australian authorities on day 1 of a 3-day oral aprepitant regimen, with oral aprepitant administered on days 2 and 3. Fosaprepitant may be a useful parenteral alternative to oral aprepitant. Further study is needed to clarify the utility of fosaprepitant in the prevention of CINV and to clarify optimal dosing regimens that may be appropriate substitutes for oral aprepitant.

Topics: Animals; Antineoplastic Agents; Aprepitant; Clinical Trials as Topic; Humans; Morpholines; Nausea; Neurokinin-1 Receptor Antagonists; Receptors, Neurokinin-1; Vomiting

This paper reviews the existing literature on fosaprepitant, an intravenous neurokinin-1 anatgonist for the prevention of chemotherapy induced nausea and vomiting.. To describe the development of fosaprepitant and to situate the intravenous form of aprepitant in the current market of available antiemetics.. Literature was screened and selected in order to compare the intravenous form of the already commonly used NK-1 receptor antagonist aprepitant.. Aprepitant is the first and still the only marketed neurokinin-1 (NK-1) antagonist. Interestingly, the first studies were performed with fosaprepitant dimeglumine (MK-0517 or L-785,298), the water-soluble prodrug of aprepitant. Fosaprepitant is converted into aprepitant within 30 min after intravenous administration. Based on equivalence studies, 115 mg fosaprepitant seems to be the substitute for 125 mg orally administrated aprepitant. Tolerability of the prodrug is no different from the active drug. The number of efficacy studies with fosaprepitant is very limited and most data are derived from existing aprepitant results. Fosaprepitant has recently been approved by FDA and EMEA as an intravenous substitute for oral aprepitant on day 1 of the standard 3-day CINV prevention regimen, which also includes dexamethasone and a 5-HT3 antagonist.

Topics: Antiemetics; Aprepitant; Humans; Injections, Intravenous; Molecular Structure; Morpholines; Nausea; Neurokinin-1 Receptor Antagonists; Prodrugs; Treatment Outcome; Vomiting

Chemotherapy-induced vomiting and nausea is the most common adverse event of anticancer therapy. In different guide-lines (MASCC, NCCN, ESMO and ASCO) antiemetic prophylaxis is directed toward the emetogenic potential of the chemotherapy and the type of vomiting and nausea. Chemotherapeutic agents are classified into four emetic risk groups: high, moderate, low, and minimal. Steroids, dexamethasone, metoclopramide, cannabinoids, benzodiazepines, 5-HT3 receptor antagonists (ondansetron, granisetron, tropisetron) and a new group of antiemetics, the neurokinin1 receptor antagonists are used to prevent anticipatory, acute and delayed vomiting and nausea. This paper examines evidence-based recommendations for optimal use of antiemetics.

Topics: Adrenal Cortex Hormones; Antiemetics; Antineoplastic Agents; Aprepitant; Granisetron; Humans; Morpholines; Nausea; Neurokinin-1 Receptor Antagonists; Ondansetron; Primary Prevention; Serotonin 5-HT3 Receptor Antagonists; Time Factors; Vomiting

This review highlights recent updates in cytotoxic treatment-induced gastrointestinal symptoms and complications, outlines the development of new diagnostic tools, and offers an up-to-date overview on management.. The neurokinin-1 receptor antagonist, aprepitant, has consolidated its attributive role in the prevention of acute phase chemotherapy-induced nausea and vomiting. Delayed gastrointestinal symptomatology related to the process of cytotoxic treatment-induced mucosal damage needs to be better understood in order to enable the clinician to assess gastrointestinal mucosal damage properly by documenting symptomatology, testing functionality and visualizing anatomical changes. By contrast to the proven beneficial effects of new drugs, such as palifermin (a trophic epidermal growth factor) or amifostine (free radical scavenger), in the management of oral mucositis, efficacy still needs to be determined regarding its gastrointestinal counterpart.. Gastrointestinal symptoms originating from cytotoxic treatment-induced mucosal barrier injury are the clinical features of a complex, dynamic pathobiological process that diminishes the quality of life but, more importantly, places the patient at risk for serious complications, like neutropenic enterocolitis. It is crucial, therefore, to adequately detect mucosal barrier injury using a complementary approach that will allow new therapeutic options to be tested thoroughly and improve supportive care.

Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Enterocolitis, Neutropenic; Humans; Morpholines; Mucositis; Nausea; Neoplasms; Neurokinin-1 Receptor Antagonists; Receptors, Neurokinin-1; Risk Factors; Vomiting

Chemotherapy-induced nausea and vomiting (CINV) remains a major adverse effect of cancer therapy. We aimed to determine outcomes associated with use of aprepitant in outpatients undergoing highly emetogenic chemotherapy in Germany from a patient's and payer's perspective.. A decision-analytic model compared an aprepitant regimen (aprepitant/ondansetron/dexamethasone) to a control regimen (ondansetron/dexamethasone) over a five days period. Clinical results and resource utilisation observed in aprepitant phase III clinical trials were assigned German unit cost data.. Complete response over one chemotherapy cycle was observed in 68% of patients in the aprepitant group (N=514) compared to 48% of patients in the control group (N=518). Patients were estimated to have gained an equivalent of 15 additional hours of perfect health per cycle (0.63 quality-adjusted life days) with aprepitant-based regimen compared to control regimen. Cost per quality-adjusted life year gained with aprepitant was estimated at euro28,891.. Aprepitant substantially improved CINV-related health outcomes in patients undergoing highly emetogenic chemotherapy. Incremental benefits materialised in a cost-effective fashion.

Topics: Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Cisplatin; Clinical Trials, Phase III as Topic; Cost-Benefit Analysis; Dexamethasone; Double-Blind Method; Drug Therapy, Combination; Health Resources; Humans; Morpholines; Multicenter Studies as Topic; Nausea; Neoplasms; Ondansetron; Randomized Controlled Trials as Topic; Treatment Outcome; Vomiting

Patients consider nausea and vomiting among the worst side effects of chemotherapy. This paper reviews the development of antiemetics during the past 12 years, focusing on the neurokinin (NK)1-receptor antagonist, aprepitant, and the new 5-HT3-receptor antagonist palonosetron. Evidence-based recommendations for prophylaxis of chemotherapy-induced nausea and vomiting are given. Antiemetics are effective in prevention of vomiting, but less effective against nausea. Therefore studies with potential new antiemetics, such as olanzapine and ghrelin are awaited with suspense.

Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Benzodiazepines; Dexamethasone; Drug Interactions; Drug Therapy, Combination; Evidence-Based Medicine; Ghrelin; Glucocorticoids; Granisetron; Humans; Isoquinolines; Morpholines; Nausea; Neurokinin-1 Receptor Antagonists; Olanzapine; Palonosetron; Peptide Hormones; Practice Guidelines as Topic; Quinuclidines; Serotonin Antagonists; Vomiting

Topics: Animals; Antiemetics; Antineoplastic Agents; Aprepitant; Humans; Morpholines; Nausea; Neurokinin-1 Receptor Antagonists; Substance P; Vomiting

Chemotherapy-induced nausea and vomiting (CINV) is a distressing and common adverse event associated with cancer treatment. Updated anti-emetic guidelines were published in 2007 by the National Comprehensive Cancer Network and in 2006 by the American Society of Clinical Oncology, which have included the use of the new and more effective anti-emetic agents (5-hydroxytryptamine-3 [5-HT(3)] receptor antagonists and neurokinin-1 [NK-1] receptor antagonists). Aprepitant is a selective NK-1 receptor antagonist approved as part of combination therapy with a corticosteroid and a 5-HT(3) receptor antagonist for the prevention of acute and delayed CINV. Fosaprepitant (also known as MK-0517 and L-758,298) is a water-soluble phosphoryl prodrug for aprepitant, which, when administered intravenously, is converted to aprepitant within 30 min after intravenous administration via the action of ubiquitous phosphatases. Because fosaprepitant is rapidly converted to the active form (aprepitant), it is expected to provide the same aprepitant exposure in terms of AUC, and a correspondingly similar anti-emetic effect. Clinical studies have suggested that fosaprepitant could be appropriate as an intravenous alternative to the aprepitant oral capsule. In a study in healthy subjects, fosaprepitant was well tolerated up to 150 mg (1 mg/ml), and fosaprepitant 115 mg was bioequivalent in its AUC to aprepitant 125 mg. Fosaprepitant 115 mg has been submitted for FDA approval as an alternative on day 1 of a 3-day oral aprepitant regimen, with oral aprepitant administered on days 2 and 3. Fosaprepitant may be a useful parenteral alternative to oral aprepitant. Further study is needed to clarify the use of fosaprepitant for the prevention of CINV, and to clarify optimal dosing regimens that may be appropriate substitutes for oral aprepitant.

Topics: Animals; Antineoplastic Agents; Aprepitant; Humans; Morpholines; Nausea; Neurokinin-1 Receptor Antagonists; Receptors, Neurokinin-1; Vomiting

Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Diarrhea; Humans; Isoquinolines; Morpholines; Nausea; Palonosetron; Quinuclidines; Risk; Serotonin Antagonists; Stomatitis; Vomiting

Chemotherapy-induced nausea and vomiting (CINV) remains a significant detriment to patient quality of life and a major impediment to successful delivery of chemotherapy. CINV is generally categorized in three phases: acute (0-24 hours post treatment), delayed (24-120 hours post treatment), and anticipatory. Two agents represents an important step forward in the clinician's ability to control CINV. Palonosetron, a serotonin-receptor antagonist, and aprepitant, a neurokinin-1 receptor antagonist, have both shown efficacy in combating emesis in the acute and delayed phases; since these two agents are of different drug classes, there is the potential for augmented antiemetic efficacy when the two are used together, as shown in a recent phase III trial. Challenges remain in the prevention of CINV, such as improved detection, the development of clinically useful assessment tools, and the revision of treatment guidelines.

Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Humans; Isoquinolines; Medical Oncology; Morpholines; Nausea; Neoplasms; Palonosetron; Quality of Life; Quinuclidines; Vomiting

Chemotherapy-induced nausea and vomiting (CINV) is associated with a significant deterioration in quality of life. The emetogenicity of the chemotherapeutic agents, repeated chemotherapy cycles and patient risk factors (female gender, younger age, no alcohol consumption, history of motion sickness) are the major risk factors for CINV. The use of 5-hydroxytryptamine-3 (5-HT3) receptor antagonists plus dexamethasone has significantly improved the control of acute CINV, but delayed nausea and vomiting remains a significant clinical problem. Two new agents, palonosetron and aprepitant, have recently been approved for the prevention of both acute and delayed CINV. Palonosetron is a 5-HT3 receptor antagonist with a longer half-life and a higher binding affinity than first-generation 5-HT3 receptor antagonists. Aprepitant is the first agent available in the new drug class of neurokinin-1 receptor (NK-1) antagonists. There are a number of 5-HT3 receptor antagonists and NK-1 receptor antagonists currently in Phase II and III clinical trials. Revised antiemetic guidelines for the prevention of CINV are reviewed. Future studies may consider the use of palonosetron and aprepitant with current and other new agents (olanzapine, gabapentin) in moderately and highly emetogenic chemotherapy, as well as in the clinical settings of multiple-day chemotherapy and bone marrow transplantation.

Topics: Antiemetics; Antineoplastic Agents; Antipsychotic Agents; Aprepitant; Benzodiazepines; Brain; Dexamethasone; Drug Therapy, Combination; Gastrointestinal Tract; Humans; Isoquinolines; Morpholines; Nausea; Neurokinin-1 Receptor Antagonists; Olanzapine; Palonosetron; Quinuclidines; Randomized Controlled Trials as Topic; Receptors, Neurokinin-1; Receptors, Serotonin, 5-HT3; Serotonin 5-HT3 Receptor Antagonists; Serotonin Antagonists; Vagus Nerve; Vomiting

Aprepitant (Emend), the first neurokinin-1-receptor antagonist (NK-1-RA), represents a new class of antiemetics. Aprepitant has been approved for the prevention and treatment of acute (0-24 h after chemotherapy) and delayed (1-5 days after chemotherapy) emesis resulting from cisplatin-based chemotherapy and moderately emetogenic chemotherapy. The addition of aprepitant to standard antiemetic therapy in cisplatin-based chemotherapy significantly improves emesis protection in general and, in particular, in the delayed phase by approximately 20%. Results from a recently published study in patients receiving moderately emetogenic chemotherapy suggest a benefit of aprepitant when combined with dexamethasone and a 5-HT(3) receptor antagonist for the prevention of acute emesis, followed by aprepitant as a single agent in the prevention of delayed emesis. Altogether, the addition of aprepitant to the standard antiemetic regimen (5-HT(3) receptor antagonist and dexamethasone) significantly improves the protection against vomiting in the acute as well as in the delayed phase in highly and moderately emetogenic chemotherapies. Therefore, the combination of a 5-HT(3) receptor antagonist, dexamethasone and aprepitant should be considered as a new standard antiemetic therapy.

Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Clinical Trials as Topic; Humans; Morpholines; Nausea; Neoplasms; Neurokinin-1 Receptor Antagonists; Practice Guidelines as Topic; Practice Patterns, Physicians'; Treatment Outcome; Vomiting

Important progress in the prophylaxis of chemotherapy-induced acute and delayed emesis has been achieved but some fundamental needs still remain that requires new, efficacious antiemetic drugs.. A critical review of the results of published studies of aprepitant, a new NK1 receptor antagonist, and of palonosetron, a 5-HT3 receptor antagonist with a longer half-life.. Aprepitant combined with dexamethasone and a 5-HT3 antagonist significantly increased the control of acute emesis with respect to dexamethasone and a 5-HT3 antagonist alone after cisplatin and moderately emetogenic chemotherapy. For cisplatin nausea, aprepitant combined with dexamethasone significantly increased the control of delayed emesis with respect to dexamethasone alone, while for moderately emetogenic chemotherapy aprepitant is superior to a 5-HT3 antagonist in the control of delayed emesis. Palonosetron showed superior or similar efficacy to ondansetron and dolasetron in patients submitted to moderately emetogenic chemotherapy and similar efficacy to ondansetron in patients submitted to cisplatin.. More studies are necessary comparing aprepitant alone or combined with dexamethasone with respect to the recommended antiemetic drugs for the prevention of delayed emesis induced by cisplatin and moderately emetogenic chemotherapy as well as for palonosetron combined with dexamethasone with respect to other 5-HT3 antagonists combined with dexamethasone.

Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Dexamethasone; Drug Therapy, Combination; Humans; Isoquinolines; Medical Oncology; Morpholines; Nausea; Neoplasms; Palonosetron; Quinuclidines; Receptors, Serotonin, 5-HT3; Serotonin Antagonists; Vomiting

To evaluate the safety and efficacy of aprepitant in the prevention of acute and delayed chemotherapy-induced nausea and vomiting (CINV).. MEDLINE and PubMed database searches were conducted from 1966 to May 2004 using the following search terms: aprepitant, Emend, substance P, neurokinin-1, chemotherapy, nausea, vomiting, L-754,030, and MK-869.. Large, randomized Phase II and III clinical trials examining the use of aprepitant for CINV, as well as all published drug interaction studies with aprepitant, were included and reviewed. Data lacking in published trials were supplemented with the manufacturer product information.. The pharmacokinetics of aprepitant are favorable for once-daily oral dosing. Based on the results of published clinical trials, aprepitant appears to augment the effects of corticosteroids and 5-HT3 antagonists when given prior to highly emetogenic chemotherapy, including cisplatin. Aprepitant appears to have the most benefit in the prevention of delayed CINV and in preventing emesis rather than nausea. Data in pediatric patients, patients undergoing stem-cell transplantation, and those receiving multiple-day or moderately emetogenic chemotherapy are lacking. Common adverse effects are limited to hiccups, asthenia, and diarrhea. More serious but rare adverse effects include neutropenia. Because aprepitant is a CYP3A4 substrate, a 3A4 inhibitor and inducer, and a 2C9 inducer, close monitoring for drug interactions is warranted.. Triple antiemetic therapy with aprepitant, a corticosteroid, and a 5-HT3 antagonist appears to provide improved efficacy in the prevention of emesis in patients receiving highly emetogenic chemotherapy. Due to its novel mechanism of action and demonstrated efficacy in this combination, aprepitant should be considered for formulary addition.

Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Drug Interactions; Humans; Morpholines; Nausea; Patient Education as Topic; Vomiting

Chemotherapy-induced nausea and vomiting (CINV) are among the most feared side effects of cancer treatment. With increasingly more complex chemotherapy treatments, CINV plays an important role in determining patients' quality of life, as well as when to halt potentially lifesaving therapy. Although significant progress has been made in the treatment of CINV, patients undergoing chemotherapy continue to report that this side effect is persistent and distressing. In 2003, two new agents were added to the armamentarium of antiemetic therapy. The U.S. Food and Drug Administration approved palonosetron, a longer-acting serotonin antagonist, and aprepitant, a neurokinin-1 antagonist and the first in a new class of antiemetics, for the treatment of CINV. Although the indications for both agents are similar, they have distinct differences. Decisions regarding placement of these agents into existing antiemetic protocols can be based on national guidelines, review of the literature, and clinical experience. This article will review current antiemetic therapy with an emphasis on the new additions to the treatment of CINV. Aprepitant and palonosetron represent significant changes in the treatment of CINV. Oncology nurses need to know current approaches to maximize effective antiemetic therapy.

Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Humans; Isoquinolines; Morpholines; Nausea; Palonosetron; Practice Guidelines as Topic; Quinuclidines; Vomiting

Systemic treatment options in gastrointestinal malignancies have increased markedly. At the same time, the need for supportive measures has become more complex. Nausea and vomiting continue to impair the patients' quality of life and to jeopardise the goals of chemotherapy. Antiemetic strategies as proposed by treatment guidelines should be employed consistently in daily clinical practice. Deficits in cancer care exist in this area. In addition, newly available antiemetic drugs should be considered. Aprepitant is the first approved representative of a new drug class. Aprepitant inhibits substance P binding to the neurokinin-1-receptor. Given orally on the first three days of a cisplatin-based chemotherapy in combination with a standard antiemetic regimen, aprepitant proved to be significantly more effective in the prevention of nausea and vomiting compared to the standard regimen without aprepitant. Recently presented results for chemotherapy with moderate emetogenic risks indicate that aprepitant shows superior effectiveness even in this setting. Palonosetron is a new drug in the class of 5-HT (3) (serotonin) receptor antagonists. Compared to older setrones, palonosetron exhibits a higher receptor binding activity, a longer half life, and a slightly improved activity in the prevention of nausea and vomiting after chemotherapy with moderate emetogenic risks. The implementation of standardised treatment guidelines into clinical practice will contribute to a higher patient satisfaction and a more effective utilisation of economic resources.

Topics: Administration, Oral; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Drug Therapy, Combination; Gastrointestinal Neoplasms; Humans; Isoquinolines; Morpholines; Nausea; Palonosetron; Premedication; Quinuclidines; Treatment Outcome; Vomiting

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

Aprepitant (EMEND) is the first commercially available drug from a new class of agents, the Substance P/neurokinin NK-1 receptor antagonists. Aprepitant is indicated for prevention of acute and delayed chemotherapy-induced nausea and vomiting (CINV) associated with highly emetogenic chemotherapy in adults. Its ability to antagonize the effects of Substance P has lead to greater understanding of the pathophysiology of nausea and vomiting. Its broad range of activity against a wide variety of central and peripheral emetogenic stimuli make it potentially useful in non-chemotherapy related nausea and vomiting.

Topics: Animals; Antiemetics; Antineoplastic Agents; Aprepitant; Cisplatin; Clinical Trials as Topic; Cytochrome P-450 Enzyme System; Drug Interactions; Humans; Liver; Morpholines; Nausea; Neurokinin-1 Receptor Antagonists; Receptors, Neurokinin-1; Substance P; Vomiting

Aprepitant (Emend) is the first commercially available drug from a new class of agents, the neurokinin NK(1) receptor antagonists. Oral aprepitant, in combination with other agents, is indicated for the prevention of acute and delayed chemotherapy-induced nausea and vomiting (CINV) associated with highly emetogenic chemotherapy in adults. In three randomised, double-blind, placebo-controlled trials comparing aprepitant (125 mg day 1, 80mg once daily on days 2 and 3 or 2-5) plus standard therapy (intravenous ondansetron and oral dexamethasone) with standard therapy plus placebo, overall complete responses (primary endpoint, defined as no emesis and no rescue therapy) were seen in significantly more patients in the aprepitant arms (63-73% versus 43-52%, p < 0.01 for all comparisons). Complete responses and complete protection during the acute and delayed phase, and overall complete protection were also observed in significantly more patients in the aprepitant arms. The difference between treatment groups was more marked in the overall and delayed phases than in the acute phase. The antiemetic efficacy of aprepitant plus standard therapy in the prevention of CINV was maintained for up to six cycles of chemotherapy. Where assessed, more patients in the aprepitant plus standard therapy arms than the standard therapy plus placebo arms reported no impact of CINV on daily life, as assessed by the Functional Living Index-Emesis. Aprepitant is generally well tolerated. The most common adverse events in randomised trials were asthenia or fatigue. Other adverse events experienced by aprepitant recipients include anorexia, constipation, diarrhoea, nausea (after day 5 of the study) and hiccups. In addition to being a substrate for cytochrome P450 (CYP) 3A4, aprepitant is also a moderate inhibitor and inducer of this isoenzyme as well as an inducer of CYP2C9. Thus, aprepitant has the potential to interact with other agents metabolised by hepatic CYP isoenzymes. In one trial, there was a higher incidence of serious infection or febrile neutropenia in the aprepitant plus standard therapy arm than the standard therapy plus placebo arm; this was attributed to a pharmacokinetic interaction between aprepitant and dexamethasone. In subsequent trials, a modified dexamethasone regimen was used. In conclusion, when added to standard therapy (a serotonin 5-HT(3) receptor antagonist and a corticosteroid), aprepitant is effective and generally well tolerated in the prevention of CIN

Topics: Animals; Aprepitant; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Double-Blind Method; Drug-Related Side Effects and Adverse Reactions; Humans; Morpholines; Multicenter Studies as Topic; Nausea; Neurokinin-1 Receptor Antagonists; Randomized Controlled Trials as Topic; Receptors, Neurokinin-1; Vomiting

Although the development of serotonin receptor antagonists has greatly improved treatment for chemotherapy-induced nausea and vomiting, patients receiving chemotherapy continue to experience this troublesome side effect. On March 26, 2003, the U.S. Food and Drug Administration approved aprepitant (Emend, Merck & Co., Inc., Whitehouse Station, NJ) for use in combination with standard antiemetic agents for acute and delayed nausea and vomiting with initial and repeat courses of highly emetogenic therapy. Aprepitant appears to provide superior control of acute and delayed emesis compared to standard antiemetic therapy. Aprepitant was well tolerated in phase III studies, with side effects similar to standard therapy. Healthcare providers need to be aware of potential drug interactions with aprepitant. Oncology nurses continue to play a key role in helping patients adhere to their antiemetic schedules, stressing the importance of prevention of nausea and vomiting.

Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Male; Morpholines; Nausea; Oncology Nursing; Randomized Controlled Trials as Topic; Treatment Outcome; Vomiting

Chemotherapy-induced nausea and vomiting (CINV) is associated with a significant deterioration in quality of life, and although the use of 5-hydroxytryptamine-3 (5-HT3) receptor antagonists plus dexamethasone has significantly improved the control of acute CINV, delayed nausea and vomiting remain a significant clinical problem. Aprepitant (Emend), Merck) is the first agent available in the new drug class of neurokinin-1 receptor antagonists. When added to a standard regimen of a 5-HT3 receptor antagonist and dexamethasone in patients receiving highly emetogenic chemotherapy, it improves the complete response rate of acute CINV. Aprepitant also improves the complete response of delayed CINV when used in combination with dexamethasone compared with dexamethasone alone. Based on these studies, new guidelines for the prevention of CINV have been developed for patients receiving highly emetogenic chemotherapy. The use of aprepitant in patients receiving moderately emetogenic chemotherapy will await the review and analysis of recently completed Phase III trials. Aprepitant is a substrate, a moderate inhibitor and an inducer of cytochrome P450 (CYP)3A4 and CYP2C9. Drug interactions should be monitored when aprepitant is coadministered with agents affected by CYP3A4 and CYP2C9 isoenzymes. The safety and efficacy of aprepitant has not been established in pediatric or adolescent patients, and aprepitant has not been evaluated in the treatment of patients with established nausea and vomiting. Future studies may consider the use of aprepitant with current and other new agents in moderately and highly emetogenic chemotherapy, as well in the clinical settings of multiple-day chemotherapy and bone marrow transplantation.

Topics: Adolescent; Adult; Aged; Antiemetics; Antineoplastic Agents; Aprepitant; Clinical Trials as Topic; Female; Humans; Male; Middle Aged; Morpholines; Nausea; Risk Factors; Vomiting

This paper reviews the clinical profile of aprepitant, the first neurokinin-1 (NK(1)) receptor antagonist to be approved for use in the prevention of chemotherapy-induced nausea and vomiting. When given to patients receiving highly emetogenic chemotherapy, aprepitant in combination with a 5-hydroxytryptamine type-3 (5HT(3)) receptor antagonist and a corticosteroid provides significantly improved protection from chemotherapy-induced nausea and vomiting over that which has been previously achievable with current antiemetics.

Topics: Administration, Oral; Antiemetics; Aprepitant; Clinical Trials as Topic; Drug-Related Side Effects and Adverse Reactions; Humans; Morpholines; Nausea; Neurokinin-1 Receptor Antagonists; Receptors, Neurokinin-1; Vomiting

Recently, a new class of agents, the substance P antagonists, has heralded a novel approach for the control of emesis. Aprepitant (Emend, Merck & Co., Inc.), the first of this class, was recently approved by the FDA for the prevention of both acute and delayed chemotherapy-induced nausea and vomiting (CINV). Of interest is the vast array of processes in which substance P is involved such as pain, anxiety, depression and inflammation and the potential wide applicability of substance P antagonists to a number of medical conditions outside of the nausea and vomiting realm. The following review provides an overview of aprepitant including pharmacokinetics, pharmacology and clinical evidence for its use in CINV. A brief discussion of other possible indications for aprepitant will also be presented.

Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Clinical Trials as Topic; Drug Interactions; Humans; Morpholines; Nausea; Neurokinin-1 Receptor Antagonists; Vomiting

Highly emetogenic chemotherapy induces emesis in cancer patients without prophylaxis. The purpose of this study was to evaluate the efficacy and safety of a fosaprepitant-based triple antiemetic regimen for the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients with solid malignant tumors, determine risk factors and externally validate different personalized risk models for CINV.. This phase III trial was designed to test the non-inferiority of fosaprepitant toward aprepitant in cancer patients who were to receive the first cycle of single-day cisplatin chemotherapy. The primary endpoint was complete response (CR) during the overall phase (OP) with a non-inferiority margin of 10.0%. Logistic regression models were used to assess the risk factors of CR and no nausea. To validate the personalized risk models, the accuracy of the risk scoring systems was determined by measuring the specificity, sensitivity and area under the receiver operating characteristic (ROC) curve (AUC), while the predictive accuracy of the nomogram was measured using concordance index (C-index).. A total of 720 patients were randomly assigned. CR during the OP in the fosaprepitant group was not inferior to that in the aprepitant group (78.1% vs. 77.7%, P = 0.765) with a between-group difference of 0.4% (95% CI, -5.7% to 6.6%). Female sex, higher cisplatin dose (≥ 70 mg/m. Fosaprepitant-based triple prophylaxis demonstrated non-inferior control for preventing CINV in patients treated with cisplatin-base chemotherapy. Female cancer patients without a history of alcohol consumption, with larger BSA and received high-dose cisplatin might be more vulnerable to CINV. Three personalized prediction models were well-validated and could be used to optimize antiemetic therapy for individual patients.

Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Cisplatin; Female; Humans; Nausea; Neoplasms; Vomiting

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.. 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%.. 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.. 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: Antiemetics; Antineoplastic Agents; Aprepitant; Dexamethasone; Double-Blind Method; Humans; Nausea; Olanzapine; Prospective Studies; Receptors, Neurokinin-1; Vomiting

Non-inferiority of NEPA (fixed combination of NK. 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.. 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).. 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: Anthracyclines; Antiemetics; Antineoplastic Agents; Aprepitant; Cyclophosphamide; Dexamethasone; Drug Combinations; Female; Humans; Isoquinolines; Male; Nausea; Prospective Studies; Quinuclidines; Vomiting

We aim to investigate the correlation between gene polymorphisms and cisplatin chemotherapy-induced nausea and vomiting (CINV), which was prevented by olanzapine or aprepitant triple antiemetic regimen.. Before chemotherapy, the blood samples of 89 malignant tumor patients who received multi-day chemotherapy with cisplatin were collected for sequencing and typing. As there were duplicate patients enrolled in different chemotherapy cycles, there were a total of 190 cases. The patients were divided into two groups randomly, who received the triple antiemetic regimen of olanzapine or aprepitant combined with 5-HT3RA and dexamethasone. The main evaluation indicators were the total protection (TP) rate in the acute phase (0-24 h), the delayed phase (25-120 h) and the overall phase (0-120 h).. Univariate analysis was performed on genetic loci that reached H-W balance with TP. In the olanzapine group, increased TP in the acute phase was associated with HTR3A rs1176719 non-GG (P < 0.05) genotype etc. Increased TP in the delayed phase was associated with HTR3A rs1176719 non-GG (P < 0.05) genotype etc. In the aprepitant group, increased TP in the acute phase was associated with the MTHFR rs1801131 TT (P < 0.05) genotype etc. Increased TP in the delayed phase was associated with HTR3A rs1062613 CC (P < 0.05) genetype ect. Multivariate Logistic regression analysis showed that HTR3B rs7943062GG (P < 0.05) genotype etc. were correlated with increased TP in the delayed phase. MTHFR rs1801131TT genotype was associated with increased TP in the acute phase (P < 0.05) and delayed phase (P < 0.05).. This study found that gene polymorphisms, including HTR3B (rs1062613, rs1176719, rs2276303), HTR3B (rs45460698, rs7943062), HTR3C (rs6766410), ERCC1 (rs3212986), ERCC4 (rs744154) and MTHFR(rs1801131), may be independent prognostic factors for CINV.

Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Cisplatin; Humans; Nausea; Olanzapine; Polymorphism, Genetic; 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

A prospective randomized controlled trial was conducted to compare 5 mg olanzapine plus standard triple antiemetic therapy for the prevention of nausea and vomiting induced by multiple-day cisplatin chemotherapy.. (1) The primary endpoint CR during OP was 76.0% (45/59) vs 67.0% (41/61) between the quadruple group and triplet group (P = 0.271). The secondary endpoint CR during the AP was significantly higher in the quadruple group than in the triplet group, which was 100.0% (59/59) vs 93.0% (57/61) (P = 0.045). The difference of CR during delayed phase between the groups was especially higher in the quadruple group compared to the triplet group (76.0% (45/59) vs 67.0% (41/61) (P = 0.271)). The rate of patients who achieved total protection in the overall phase was also higher in the quadruple group than the triplet group (28.8% (17/59) vs 23.0% (14/61) (P = 0.463)). During the OP, the incidence of no vomiting in the quadruple group and the triplet group was 93.2% (55/59) vs 80.3% (49/61) (P = 0.038), respectively. (2) Kaplan-Meier curves of time to first emesis were obviously longer in the quadruple group compared with the triplet group (P = 0.031). According to FLIE, no impact of CINV on daily life was defined as total score of questionnaire > 108; this study exhibited identical life quality between two groups. (3) The most common aprepitant- or olanzapine-related AEs included sedation, fatigue, and constipation. The occurrences between two groups were identical.. It may been recommended that 5 mg olanzapine plus tropisetron and dexamethasone, omitting aprepitant triplet regimen as an alternative therapy in prevention CINV induced by multiple-day cisplatin chemotherapy due to the excellent CINV control rate and safety.

Topics: Antiemetics; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Cisplatin; Dexamethasone; Humans; Nausea; Olanzapine; Prospective Studies; Quality of Life; Tropisetron; Vomiting

The aim of this study was to determine the effectiveness of a 6-day aprepitant schedule in patients receiving a multiple-day highly emetogenic chemotherapy drug (cisplatin). Aprepitant is an important medication used to prevent chemotherapy-induced nausea and vomiting (CINV). The patients willing to use aprepitant were randomly divided into two groups: prolonged use of aprepitant (PA; 6-day aprepitant) and standard use of aprepitant (SA; 3-day aprepitant). The patients who rejected aprepitant were recruited into the control group. The results showed that cases of CINV in group PA ended more quickly. Group PA also had more days with no vomiting and no nausea than the other two groups. The results of this study propose 6-day aprepitant use as more effective to prevent CINV in patients receiving 3-day cisplatin-based chemotherapy.  Clinical trial registration: ChiCTR-IPR-15005933 (http://www.chictr.org.cn).

Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Cisplatin; Dexamethasone; Humans; Nausea; Vomiting

The triplet antiemetic regimen is administered to prevent chemotherapy-induced nausea and vomiting (CINV) after moderately emetogenic chemotherapy (MEC). However, the superiority of palonosetron over first-generation 5-hydroxytryptamine-3 receptor antagonists in triplet antiemetic therapy remains unclear. In this study, we evaluated the efficacy of palonosetron (PALO) and granisetron (GRA) in triplet antiemetic therapy for CINV. This study included 267 patients who received MEC at our hospital between April 2017 and September 2020. Patients were pretreated with antiemetic therapy comprising PALO or GRA and dexamethasone on day 1 and aprepitant on days 1-3. We evaluated the rate of complete response (CR) (i.e., no vomiting and no use of rescue medication) in the acute phase (0-24 h), delayed phase (24-120 h), and overall phase (0-120 h) after first-cycle chemotherapy. Furthermore, multivariate analysis was conducted to identify risk factors for non-CR. The rate of CR in the overall and delayed phases was significantly higher in the PALO group (91.9 and 91.9%, respectively) than in the GRA group (74.1 and 75.5%, respectively). In the acute phase, the incidence was not different between the GRA and PALO groups (96.5 and 99.2%, respectively). Multivariate analysis revealed that female sex and the use of GRA were risk factors for non-CR. Subgroup analysis revealed the superiority of PALO over GRA in female patients, but not in male patients. In conclusion, PALO was more effective than GRA in triplet antiemetic therapy in preventing CINV during MEC, especially for female patients.

Topics: Aged; Antiemetics; Antineoplastic Agents; Aprepitant; Drug Therapy, Combination; Female; Granisetron; Humans; Incidence; Male; Middle Aged; Nausea; Neoplasms; Palonosetron; Retrospective Studies; Treatment Outcome; Vomiting

Delayed chemotherapy-induced nausea and vomiting (CINV) is not well controlled in colorectal cancer (CRC) patients undergoing oxaliplatin (L-OHP)-based chemotherapy. Whether neurokinin-1 receptor antagonist addition to a first-generation 5HT

Topics: Aged; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Colorectal Neoplasms; Dexamethasone; Female; Humans; Incidence; Male; Middle Aged; Nausea; Oxaliplatin; Palonosetron; Serotonin 5-HT3 Receptor Antagonists; Vomiting

The prevention of chemotherapy-induced nausea and vomiting has an important role in the overall management of cancer treatment.. 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.. 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.. 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).. 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.. 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.. 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.. 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

Chemotherapy-induced nausea and vomiting (CINV) is considered one of the most serious adverse events affecting chemotherapy-receiving cancer patients. It dramatically affects their food intake, nutritional status and more importantly their quality of life. We can observe CINV in highly emetogenic chemotherapy (HEC) such as adriamycin-cyclophosphamide combination (AC) in breast cancer patients and cisplatin-based regimens in other cancer types. This study aimed to evaluate the antiemetic efficacy of palonosetron (PALO) over granisetron (GRA) in combination with dexamethasone for multiple highly emetogenic chemotherapy drugs (HEC), especially in chemotherapy regimens in Egyptian breast cancer patients and cisplatin-based regimens in other diseases.. An open-label randomized trial was carried out, including 115 patients receiving at least four cycles of highly emetogenic chemotherapy regimens. All patients received dexamethasone in combination with the 5-HT3 receptor antagonist. We recorded patients' clinical and biochemical characteristics and withdraw blood samples to monitor serum substance P and serotonin in correlation with chemotherapy-induced nausea and vomiting (CINV). We use the MASCC antiemetic tool in the acute phase (0-24 hr) and delayed phase (24-120 h) to evaluate patient outcomes in both stages after each chemotherapy cycle.. In (PALO) group, only 7.84% of patients showed acute vomiting, and 11.76% showed acute nausea, whereas 43.75% of patients showed acute vomiting and 89.06% showed acute nausea in (GRA) group (P < 0.0001). For delayed CINV, 23.53% of patients showed delayed vomiting, and 47.06% showed delayed nausea in the (PALO) group, while 82.81% of patients showed delayed emesis, and 92.19% showed delayed nausea in (GRA) group (P < 0.0001). The study showed that PALO is a cost-effective choice when compared to GRA in CINV prevention as 45.10% of patients in (PALO) required additional rescue medications (Domperidone 10 mg orally three times per day plus Trimebutine 200 mg orally three times per week both for 5 days), while 95.24% in the (GRA) group used the same medications. Adverse events of both antiemetic drugs (PALO and GRA) include headaches and constipation and QTc prolongation reports, mostly mild to moderate, with relatively low rates among the two groups.. Palonosetron, combined with dexamethasone, is more effective than granisetron and dexamethasone combination against both acute and delayed emesis induced by highly emetogenic chemotherapy (HEC) cisplatin-based protocols and the combination of cyclophosphamide and anthracyclines (AC). Medical team members should make more efforts, especially clinical pharmacy personnel, to monitor medications' effectiveness and help the medical team achieve a suitable and reliable care plan.

Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Cisplatin; Cyclophosphamide; Dexamethasone; Doxorubicin; Drug Therapy, Combination; Egypt; Female; Granisetron; Humans; Male; Middle Aged; Nausea; Palonosetron; Quality of Life; Vomiting

Neurokinin (NK) 1 receptor antagonists (RAs), administered in combination with a 5-hydroxytryptamine-3 (5-HT. This was a pragmatic, multicenter, randomized, single-cycle, open-label, prospective study designed to demonstrate noninferiority of single-dose NEPA to a 3-day aprepitant regimen in preventing CINV in chemotherapy-naive patients receiving AC/non-AC MEC in a real-life setting. The primary efficacy endpoint was complete response (no emesis/no rescue) during the overall (0-120 hour) phase. Noninferiority was achieved if the lower limit of the 95% confidence interval (CI) of the difference between NEPA and the aprepitant group was greater than the noninferiority margin set at -10%.. Noninferiority of NEPA versus aprepitant was demonstrated (risk difference 9.2%; 95% CI, -2.3% to 20.7%); the overall complete response rate was numerically higher for NEPA (64.9%) than aprepitant (54.1%). Secondary endpoints also revealed numerically higher rates for NEPA than aprepitant.. This pragmatic study in patients with cancer receiving AC and non-AC MEC revealed that a single dose of oral NEPA plus DEX was at least as effective as a 3-day aprepitant regimen, with indication of a potential efficacy benefit for NEPA.

Topics: Antibiotics, Antineoplastic; Antiemetics; Antineoplastic Agents; Aprepitant; Double-Blind Method; Humans; Isoquinolines; Nausea; Palonosetron; Prospective Studies; Quinuclidines; Vomiting

CINV remains a distressing side effect experienced by glioma patients receiving multi-day temozolomide therapy, in spite of guideline-based antiemetic therapy with selective serotonin-receptor-antagonists. Antiemetic research with aprepitant has routinely excluded glioma patients. In this randomized open-label phase II study, use of a nonstandard 5-day regimen of aprepitant for glioma patients was investigated.. Patients were 61% male, 97% white, 48% with KPS > 90%, 60% non-smokers, mean age 54, 92% with low alcohol use, and 46% with a CINV history. The CC was 58.6% (Arm-A) and 54.5% (Arm-B). Acute-complete response (CR) rates, defined as CC on day 1 in Arm-A and -B, were 97.1% and 87.9%, respectively (p = 0.056). Treatment-related toxicities were mild or moderate in severity.. Aprepitant plus ondansetron may increase acute-CR, may have benefit regarding CINV's effect on QoL, and is safe for 5-day temozolomide compared to ondansetron. This study provides no evidence that aprepitant increases CC rate over ondansetron alone.

Topics: Adult; Aged; Antiemetics; Antineoplastic Agents; Aprepitant; Brain Neoplasms; Female; Glioma; Humans; Male; Middle Aged; Nausea; Ondansetron; Quality of Life; Temozolomide; Vomiting

Compared with older 5-HT. Patients were randomized to palonosetron (0.25 mg) every other day until the last dose of chemotherapy alone or with aprepitant on days 1-3. Patients mainly received an anthracycline on days 1-3 plus cytarabine administered for 5-10 days. The primary end point was complete response (CR; no emesis and no rescue medication) over the whole study period (days of chemotherapy plus two additional days). Unplanned analysis of time to anti-emetic treatment failure (TTF) was also performed.. Of the 134 patients enrolled in the study, 130 were evaluable: 68 subjects received palonosetron plus aprepitant and 62 received palonosetron alone. Although the primary end point of CR was similar between the treatment arms (72% vs 69%; P = .55), a higher proportion of patients treated with palonosetron plus aprepitant were free from nausea during the whole study period (43% vs 27%; P = .03). There was also a significant difference in favor of the two-drug regimens in TTF (median: 5 days vs 3 days; P = .03).. The study suggests that every-other-day palonosetron plus 3-day aprepitant can add clinical benefit to the control of CINV caused by multiple-day, corticosteroid-free chemotherapy for AML. In this challenging setting of CINV, further investigations of palonosetron in combination with aprepitant administered with an expanded schedule are warranted. ClinicalTrial.gov identifier: NCT02205164.

Topics: Adult; Aged; Aged, 80 and over; Anthracyclines; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Cytarabine; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Induction Chemotherapy; Leukemia, Myeloid, Acute; Male; Middle Aged; Nausea; Palonosetron; Treatment Failure; Vomiting; Young Adult

The aim of this study was to investigate the efficacy and safety of prophylactic administration of 5 mg olanzapine (OLZ) combined with neurokinin 1 receptor antagonist (NK. We conducted a single-arm, multi-institution, phase II study. Gynecological cancer patients scheduled to receive AUC ≥4 mg/mL/min CBDCA were enrolled. All patients received 5 mg OLZ (once daily after supper on days 1-4) combined with NK. Between May 2018 and June 2019, 60 patients were enrolled from 3 institutions in Japan. A total of 57 patients who met the criteria were included in the efficacy and safety analysis. The CR rate for the overall phase was 78.9%. Acute (0-24 h) and delayed phases (24-120 h) were 96.5% and 80.7%, respectively. Somnolence was observed in 73.7% patients. However, somnolence of grade 2 or higher was observed in only 3.5% of cases. There were no grade 3 or 4 toxicities associated with OLZ.. Preventive use of OLZ combined with standard triplet therapy had promising activity with manageable safety, suggesting that this combination could be an effective standard treatment option for patients with AUC ≥4 mg/mL/min CBDCA combination therapy.

Topics: Adult; Aged; Antiemetics; Aprepitant; Carboplatin; Dexamethasone; Female; Genital Neoplasms, Female; Granisetron; Humans; Middle Aged; Nausea; Olanzapine; Vomiting

Chemotherapy-induced nausea and vomiting (CINV) are distressing symptoms. This randomized study evaluated the antiemetic efficacies of standard antiemetic regimen with/without olanzapine.. Eligible patients were chemotherapy-naive Chinese breast cancer patients who were planned for (neo)adjuvant doxorubicin/cyclophosphamide. Antiemetic regimen for all studied population included aprepitant, ondansetron and dexamethasone; patients were randomized to Olanzapine (with olanzapine) or Standard arms (without olanzapine). Patients filled in self-reported diaries and completed visual analogue scales for nausea, as well as Functional Living Index-Emesis questionnaires. Blood profiles including fasting glucose and lipids were monitored.. 120 patients were randomized. In Cycle 1 doxorubicin/cyclophosphamide, the Olanzapine arm had significantly higher rates of "Complete Response" than the Standard arm: 65.0% vs 38.3% in the overall period (p = 0.0035), 70.0% vs 51.7% in the acute period (p = 0.0397) and 92.9% vs 74.2% in the delayed period (p = 0.0254). Olanzapine arm also had significantly higher rates of "No significant nausea" and "No nausea" during all 3 time-frames and better QOL. Similar findings were also revealed throughout multiple cycles. Pre-study abnormalities in glucose and lipids occurred in 39.7% and 34.2% of the studied population respectively; there were no differences in these parameters between the two arms at end-of-study assessment.. The addition of olanzapine to standard aprepitant-based antiemetic regimen provides clinically meaningful improvement in controlling CINV. This was associated with a positive impact on QOL and tolerable toxicity profiles among Chinese breast cancer patients receiving doxorubicin/cyclophosphamide chemotherapy. Further studies on metabolic profiles of breast cancer patients are warranted.

Topics: Adult; Aged; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Breast Neoplasms; China; Cyclophosphamide; Dexamethasone; Doxorubicin; Female; Humans; Middle Aged; Nausea; Olanzapine; Ondansetron; Vomiting

Background We examined the efficacy of mirtazapine in preventing delayed nausea and vomiting following highly emetogenic chemotherapy (HEC). Patients and methods Patients who had experienced delayed emesis and would be subsequently scheduled for at least three more cycles of the same chemotherapy were randomly assigned to either a mirtazapine (15 mg daily on days 2-4) or a control group. In addition, both groups received a standard triplet regimen comprising aprepitant, a 5-HT3 receptor antagonist, and dexamethasone (7.5 mg on days 2-4). The chemotherapy regimens were either an epirubicin plus cyclophosphamide regimen or cisplatin-containing regimens. The primary end point was a complete response (no emesis and no rescue treatment) to the delayed phase (25-120 h post-chemotherapy) during Cycle 1. The impact on quality of life (QOL) was assessed using the Functional Living Index-Emesis (FLIE) questionnaire. Results Of 95 enrolled patients, 46 were assigned to the mirtazapine group and 49 to the control group. The complete response rate in the delayed phase during Cycle 1 was significantly higher with mirtazapine than in the control group (78.3% versus 49.0%, P = 0.003). The main adverse effects of mirtazapine were mild to moderate somnolence and weight gain. Mean total FLIE scores were similar between the two arms. Conclusions This is the first randomized prospective study to show that adding mirtazapine has a substantial and statistically significant benefit with good tolerance in patients with breast cancer who have experienced delayed emesis following the same prior HEC. (Trial registration: ClinicalTrials.gov NCT02336750).

Topics: Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Breast Neoplasms; Cisplatin; Cyclophosphamide; Dexamethasone; Dopamine Antagonists; Epirubicin; Female; Humans; Middle Aged; Mirtazapine; Nausea; Quality of Life; Serotonin 5-HT3 Receptor Antagonists; Treatment Outcome; Vomiting

We assessed the efficacy of aprepitant (APR) or 10 or 5 mg OLN (OLN10 or OLN5) plus ondansetron and dexamethasone for chemotherapy-induced nausea/vomiting (CINV) prophylaxis in patients receiving high-emetogenic chemotherapy (HEC).. Patients who received doxorubicin + cyclophosphamide or cisplatin were given intravenous ondansetron and dexamethasone prior to chemotherapy and oral dexamethasone on days 2-4 and randomized 1:1:1 to receive APR125 on day 1 and APR80 on days 2-3 or OLN10 or OLN5 on days 1-4. Matched placebo controls were used. The primary endpoint was no nausea in ≤ 120 h. Secondary endpoints included CINV severity, complete response (CR) rate, adverse effects (AE), and quality of life.. Of 141 patients, 104 received AC and 37 received cisplatin. The no-nausea rates were 33% (APR), 43.2% (OLN10; p = 0.24), and 37% (OLN5; p = 0.87). Grades 2-4 nausea were experienced by fewer patients for OLN10 than for APR (24-120 h, 8.7% vs. 27.7%, respectively; p = 0.02; overall period, 19.6% vs. 40.4%, respectively; p = 0.03). The median visual analog scale nausea score from 24 to 120 h was significantly lower for OLN10 (2.3) than for APR (1.2, p = 0.03). The degrees of vomiting, CR, and AE were similar between the APR and OLN10 groups. CINV was similar between the OLN5 and APR groups.. Nausea was less severe for OLN10 than for APR in patients receiving HEC, but other measures were similar. CINV prevention efficacy was comparable between OLN5 and APR.

Topics: Adult; Aged; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Chemoprevention; Cisplatin; Cyclophosphamide; Dexamethasone; Dose-Response Relationship, Drug; Double-Blind Method; Doxorubicin; Drug Therapy, Combination; Emetics; Female; Humans; Induction Chemotherapy; Male; Middle Aged; Nausea; Neoplasms; Olanzapine; Ondansetron; Placebos; Quality of Life; Treatment Outcome; Vomiting; Young Adult

The purpose of this study was to compare ramosetron (RAM), aprepitant (APR), and dexamethasone (DEX) [RAD] with palonosetron (PAL), APR, and DEX [PAD] in controlling highly-emetogenic chemotherapy (HEC)-induced nausea and vomiting.. Patients were randomly assigned (1:1) to receive RAD or PAD:RAM (0.3 mg intravenously) or PAL (0.25 mg intravenously) D1, combined with APR (125 mg orally, D1 and 80 mg orally, D2-3) and DEX (12 mg orally or intravenously, D1 and 8 mg orally, D2-4). Patients were stratified by sex, cisplatin-based chemotherapy, and administration schedule. The primary endpoint was overall complete response (CR), defined as no emesis and no rescue regimen during 5 days of HEC. Secondary endpoints were overall complete protection (CP; CR+nausea score < 25 mm) and total control (TC; CR+nausea score < 5 mm). Quality of life was assessed by Functional Living Index Emesis (FLIE) questionnaire on D0 and D6.. A total of 279 patients receiving RAD (n=137) or PAD (n=142) were evaluated. Overall CR rates in RAD and PAD recipients were 81.8% and 79.6% (risk difference [RD], 2.2%; 95% confidence interval [CI], -7.1 to 11.4), respectively. Overall CP and TC rates for RAD and PAD were 56.2% and 58.5% (RD, -2.3%; 95% CI, -13.9 to 9.4) and 47.5% vs. 43.7% (RD, 3.8%; 95% CI, -7.9 to 15.5), respectively. FLIE total score ≥ 108 (no impact on daily life) was comparable between RAD and PAD (73.9% vs. 73.4%, respectively). Adverse events were similar between the two groups.. In all aspects of efficacy, safety and QOL, RAD is non-inferior to PAD for the control of CINV in cancer patients receiving HEC.

Topics: Adult; Aged; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Benzimidazoles; Dexamethasone; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Male; Middle Aged; Nausea; Neoplasms; Palonosetron; Prognosis; Prospective Studies; Quality of Life; Surveys and Questionnaires; Vomiting; Young Adult

The triplet antiemetic regimen is recommended for cisplatin-based highly emetogenic chemotherapy, in the current guidelines for antiemetic prophylaxis. Although risk factors related to chemotherapy-induced nausea and vomiting (CINV) have been identified by several prior studies, there are only few studies evaluating risk factors associated with the prophylactic triplet antiemetic therapy, particularly in palonosetron use. The present study aimed to reveal the risk factors related to CINV development in patients receiving cisplatin and to compare CINV risk factors between palonosetron and granisetron use.. In total, 825 patients in a phase III trial receiving palonosetron with graniestron were evaluated. Multivariate logistic regression models were used to predict risk factors associated with CINV development. Additionally, risk factors associated with CINV development were separately evaluated in each treatment group.. Multivariate analysis of the entire study group revealed that sex, age, cisplatin dose, and granisetron use were significant and independent factors affecting CINV development in the overall phase. Similarly, sex and age were risk factors for CINV in both treatment groups. Kaplan-Meier curves classified by each treatment group showed no significant difference between the groups among patients without any risk factors for CINV (P = 0.353). Conversely, complete response rates for patients with at least one risk factor were higher in patients receiving palonosetron (P = 0.049).. This analysis revealed the importance of previously reported CINV risk factors when using triplet antiemetics. Palonosetron might be preferred for patients with at least one risk factor.

Topics: Adult; Aged; Aged, 80 and over; Antiemetics; Antineoplastic Agents; Aprepitant; Cisplatin; Double-Blind Method; Drug Therapy, Combination; Female; Granisetron; Humans; Japan; Logistic Models; Male; Middle Aged; Multivariate Analysis; Nausea; Palonosetron; Risk Factors; Vomiting

HTX-019 (CINVANTI. Study comprised Part A, a pilot Phase I, single-center, randomized, pharmacokinetic, safety and tolerability, open-label study, followed by Part B, a two-sequence crossover study of HTX-019 130 mg in healthy adults, via injection and infusion. Blood samples were evaluated for aprepitant pharmacokinetics and bioequivalence. Safety evaluations included treatment-emergent adverse events (TEAEs), vital signs, clinical laboratory testing and electrocardiograms.. In Part A, 24 subjects were randomly assigned to three cohorts (n = 8 per cohort) and received HTX-019 130 mg, administered intravenously over 15 min (cohort 1), 5 min (cohort 2) or 2 min (cohort 3). Progression to Part B occurred after acceptable tolerability was established in cohorts 2 and 3. In Part B, 50 randomized subjects received a 2-min injection (9 ml/min) and 30-min infusion (296 ml/h) of HTX-019 130 mg. Bioequivalence was demonstrated for HTX-019 injection and infusion. Both administration methods via a peripheral line were well tolerated; eight subjects experienced 11 TEAEs (six related) following injection and nine experienced 14 TEAEs (nine related) following infusion. Headache and fatigue were the most prevalent treatment-related TEAEs; one subject per group experienced feeling hot ≤30 min after drug administration.. Pharmacokinetic and tolerability profiles of 2-min HTX-019 injection support this potential alternative administration method for CINV prevention.

Topics: Adult; Antineoplastic Agents; Aprepitant; Cross-Over Studies; Fatigue; Female; Headache; Healthy Volunteers; Humans; Infusions, Intravenous; Injections, Intravenous; Male; Middle Aged; Nausea; Neurokinin-1 Receptor Antagonists; Pilot Projects; Time Factors; Treatment Outcome; Vomiting; Young Adult

This trial is an open-label, single-arm, multicentre phase II trial. Patients who receive CBDCA (AUC ≥4)-based therapy and have never been administered moderate to high emetogenic chemotherapy will be enrolled. All patients will receive OLZ (5 mg oral administration on days 1-4, after supper) in combination with 5-HT. The study protocol was approved by the institutional review board at each of the participating centres. Data will be presented at international conferences and published in peer-reviewed journals.. UMIN000031646.

Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Carboplatin; Dexamethasone; Drug Therapy, Combination; Female; Genital Neoplasms, Female; Granisetron; Humans; Morpholines; Nausea; Neurokinin-1 Receptor Antagonists; Olanzapine; Serotonin 5-HT3 Receptor Antagonists; Treatment Outcome; Vomiting

Chemotherapy-induced nausea and vomiting (CINV) is a distressing treatment side-effect that could negatively affect children's quality of life (QoL). Different scoring systems for CINV were applied and different antiemetic drugs were used; however, few studies have been performed in children undergoing chemotherapy with Aprepitant. Herein, we report a pediatric experience on efficacy and safety of Aprepitant as part of triple antiemetic prophylaxis, in a cohort of thirty-two children and adolescents with Hodgkin Lymphoma (HL), treated with moderate/highly emetogenic chemotherapy (MEC/HEC) regimens in a single Hemato-Oncology Institution. The triple therapy was compared to standard antiemetic therapy in a cohort of twenty-three HL patients (control group). Aprepitant therapy was associated to a significant decrease of chemotherapy-induced vomiting (p = 0.0001), while no impact on the reduction of nausea was observed; these observations were also confirmed by multivariate analysis (p = 0.0040). Aprepitant was well tolerated and the most commonly reported adverse events were neutropenia and hypertransaminasemia. No significant differences on the toxicity were observed between the two compared groups. Our experience on Aprepitant efficacy and safety, associated with feasibility of orally administration, suggests a possible widespread use of the drug to prevent pediatric CINV.

Topics: Adolescent; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Chemoprevention; Child; Female; Hodgkin Disease; Humans; Male; Nausea; Retrospective Studies; Safety; Vomiting

There remains an unmet clinical need for the control of chemotherapy-induced nausea and vomiting (CINV), particularly in the prevention of nausea and the delayed phase control. We evaluated the efficacy and safety of antiemetic therapy with olanzapine, a neurokinin-1 receptor antagonist, a 5-hydroxytryptamine-3 (5-HT. Chemotherapy-naïve patients with lung cancer who received carboplatin-containing chemotherapy were enrolled in this phase-II study. Patients received olanzapine, aprepitant, a 5-HT. Thirty-three patients received olanzapine-containing antiemetic therapy. The overall complete response rate was 93.3% (95% confidence interval, 80.4-98.3%). The frequency of nausea was 15.2% in the delayed phase and 18.2% in the overall phase. Somnolence was observed in 16 patients.. Adding olanzapine to antiemetic therapy with aprepitant, a 5-HT

Topics: Aged; Aged, 80 and over; Antiemetics; Antineoplastic Agents; Aprepitant; Carboplatin; Dexamethasone; Drug Therapy, Combination; Female; Humans; Lung Neoplasms; Male; Middle Aged; Nausea; Olanzapine; Prospective Studies; Vomiting

Chemotherapy-induced nausea and vomiting (CINV) causes significant morbidity among colorectal cancer patients, receiving fluorouracil, oxaliplatin, and leucovorin (FOLFOX) chemotherapy even with standard antiemetic prophylaxis. The purpose of this study is to determine if the addition of aprepitant to standard antiemetic therapy improves CINV in these patients.. Patients receiving FOLFOX for colorectal cancer were given antiemetic prophylaxis with aprepitant 125 mg orally on day 1 and 80 mg on days 2 and 3. Palonosetron 0.25 mg was given IV push on day 1 only. Dexamethasone 12 mg was administered orally on day 1 and 8 mg each morning on days 2 through 4. Assessments including emetic events, rescue doses, nutritional intake, and appetite were recorded in a patient diary which was returned to study personnel in the following cycle.. Of the 53 patients screened, 50 were evaluable and had a complete dataset for cycle 1. For the first cycle, 74% of patients achieved a complete response (CR), 22% achieved a major response and 4% experienced treatment failure. The percentage of patients achieving a CR remained high throughout each cycle at 83, 83, and 86% for cycles 2, 3, and 4, respectively. Appetite and nutritional status remained largely unchanged throughout treatment. Adverse events occurring in more than 10% of patients included diarrhea (13.6%), fatigue (12.6%), and neutropenia (11%).. Aprepitant added to standard antiemetic therapy appears to be an effective and safe regimen for prevention of CINV in patients receiving FOLFOX.

Topics: Adult; Aged; Aged, 80 and over; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Colorectal Neoplasms; Dexamethasone; Female; Fluorouracil; Humans; Induction Chemotherapy; Leucovorin; Male; Middle Aged; Morpholines; Nausea; Organoplatinum Compounds; Palonosetron; Pilot Projects; Vomiting

Co-administration of multiple antiemetics that inhibit several molecular pathways involved in emesis is required to optimize chemotherapy-induced nausea and vomiting (CINV) control in patients receiving highly emetogenic chemotherapy (HEC). NEPA, a fixed combination of a highly selective NK1 receptor antagonist, netupitant (300 mg), and the pharmacologically distinct 5-HT3RA, palonosetron (PALO 0.50 mg), has shown superior CINV prevention compared with PALO in cisplatin and anthracycline/cyclophosphamide-based settings. This study is the first head-to-head comparison of NEPA versus an aprepitant (APR)/granisetron (GRAN) regimen.. This randomized, double-blind phase III study conducted in Asia was designed with the primary objective to demonstrate non-inferiority of a single oral dose of NEPA compared with a 3-day oral APR/GRAN regimen in chemotherapy-naïve patients receiving cisplatin-based HEC. All patients also received oral dexamethasone (DEX) on days 1-4. The primary efficacy endpoint was complete response (CR: no emesis/no rescue medication) during the overall (0-120 h) phase. Non-inferiority was defined as a lower 95% CI greater than the non-inferiority margin set at - 10%. Secondary efficacy endpoints included no emesis, no rescue medication, and no significant nausea (NSN).. Treatment groups were comparable for the 828 patients analyzed: predominantly male (71%); mean age 54.5 years; ECOG 0-1 (98%); lung cancer (58%). NEPA demonstrated non-inferiority to APR/GRAN for overall CR [NEPA 73.8% versus APR/GRAN 72.4%, 95% CI (-4.5%, 7.5%)]. No emesis [NEPA 75.0% versus APR/GRAN 74.0%, 95% CI (-4.8%, 6.9%)] and NSN rates [NEPA 75.7% versus APR/GRAN 70.4%, 95% CI (-0.6%, 11.4%)] were similar between groups, but significantly more NEPA patients did not take rescue medication [NEPA 96.6% versus APR/GRAN 93.5%, 95% CI (0.2%, 6.1%)]. NEPA was well tolerated with a similar safety profile to APR/GRAN.. In this first study comparing NK1RA regimens and DEX, NEPA administered only on day 1 was non-inferior to a 3-day oral APR/GRAN regimen in preventing CINV associated with HEC.

Topics: Adult; Aged; Antiemetics; Antineoplastic Agents; Aprepitant; Asia; Cisplatin; Dexamethasone; Double-Blind Method; Drug Combinations; Female; Humans; Isoquinolines; Male; Middle Aged; Nausea; Neoplasms; Pyridines; Quinuclidines; Vomiting

There are few effective treatments for nausea and other symptoms in patients with gastroparesis and related syndromes. We performed a randomized trial of the ability of the neurokinin-1 receptor antagonist aprepitant to reduce symptoms in patients with chronic nausea and vomiting caused by gastroparesis or gastroparesis-like syndrome.. We conducted a 4-week multicenter, double-masked trial of 126 patients with at least moderate symptoms of chronic nausea and vomiting of presumed gastric origin for a minimum of 6 months. Patients were randomly assigned to groups given oral aprepitant (125 mg/day, n = 63) or placebo (n = 63). The primary outcome from the intention-to-treat analysis was reduction in nausea, defined as a decrease of 25 mm or more, or absolute level below 25 mm, on a daily patient-reported 0-to-100 visual analog scale (VAS) of nausea severity. We calculated relative risks of nausea improvement using stratified Cochran-Mental-Haenszel analysis.. Aprepitant did not reduce symptoms of nausea, based on the primary outcome measure (46% reduction in the VAS score in the aprepitant group vs 40% reduction in the placebo group; relative risk, 1.2; 95% CI, 0.8-1.7) (P = .43). However, patients in the aprepitant group had significant changes in secondary outcomes such as reduction in symptom severity (measured by the 0-5 Gastroparesis Clinical Symptom Index) for nausea (1.8 vs 1.0; P = .005), vomiting (1.6 vs 0.5; P = .001), and overall symptoms (1.3 vs 0.7; P = .001). Adverse events, predominantly mild or moderate in severity grade, were more common in aprepitant (22 of 63 patients, 35% vs 11 of 63, 17% in the placebo group) (P = .04).. In a randomized trial of patients with chronic nausea and vomiting caused by gastroparesis or gastroparesis-like syndrome, aprepitant did not reduce the severity of nausea when reduction in VAS score was used as the primary outcome. However, aprepitant had varying effects on secondary outcomes of symptom improvement. These findings support the need to identify appropriate patient outcomes for trials of therapies for gastroparesis, including potential additional trials for aprepitant. ClinicalTrials.gov no: NCT01149369.

Topics: Adult; Antiemetics; Aprepitant; Chronic Disease; Double-Blind Method; Female; Gastroparesis; Humans; Male; Middle Aged; Morpholines; Nausea; Treatment Outcome; Vomiting

This study aimed to determine the antiemetic efficacy and safety of palonosetron, aprepitant and dexamethasone in patients with testicular germ cell tumours (TGCTs) receiving 5-day cisplatin-based combination chemotherapy.. In this open-label, single-arm, single-centre study, the antiemetic therapy consisted of palonosetron 0.75 mg on day 1, aprepitant 125 mg on day 1 and 80 mg on days 2-7 and dexamethasone 6.6 mg on days 1-7. The primary endpoint was complete response (CR; no vomiting/retching or rescue medication) in the overall period (0-240 h), and secondary endpoints included complete protection (CP; defined as CR and no more than mild nausea) and total control (TC; defined as CR and no nausea). The incidence and severity of nausea were assessed on the basis of the Common Terminology Criteria for Adverse Events v4.0 and a subjective rating scale completed by patients.. Twenty-five patients were enrolled and evaluated for safety, and 24 patients were evaluated for efficacy. CR was achieved in 62.5% of patients (95% confidence interval [CI] = 40.6-81.2, p = 0.043) in the overall period. CP and TC were achieved in 62.5% (95% CI = 40.6-81.2) and 25.0% of patients (95% CI = 9.8-46.7), respectively, in the overall period. The primary adverse drug reaction was hiccups (48.0%). The events were expected, and none was grade 3 or 4.. The examined combination antiemetic therapy was effective and well-tolerated in patients with TGCTs receiving 5-day cisplatin-based combination chemotherapy.

Topics: Adult; Antiemetics; Aprepitant; Dexamethasone; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Nausea; Palonosetron; Vomiting; Young Adult

The aim of this study was to evaluate the safety and efficacy of aprepitant when used prophylactically to prevent nausea and vomiting during cyclophosphamide-based conditioning regimens. The primary objective of this study was to determine if there was a difference in the number of emesis-free days in patients who received aprepitant as compared to those who received placebo. This prospective, randomized, double blind, placebo-controlled study was performed in 40 adult patients who received a cyclophosphamide-containing HSCT conditioning regimen. Twenty patients were randomized to receive aprepitant, ondansetron, and dexamethasone, and 20 were randomized to receive placebo, ondansetron, and dexamethasone. Complete response (CR) was defined as the absence of emesis and the absence of mild to moderate nausea. The average number of emesis-free days was 14.25 (standard deviation 1.48 days) in the aprepitant group compared to 12.45 days (standard deviation 2.16 days) for patients in the placebo group. Eight patients (40%) in the aprepitant group achieved CR as compared to four patients (20%) in the placebo group. In the setting of cyclophosphamide-containing conditioning regimens, the addition of aprepitant to a standard antiemetic regimen decreased the incidence of emesis as compared to placebo. Aprepitant was well tolerated.

Topics: Adult; Antiemetics; Aprepitant; Cyclophosphamide; Female; Hematopoietic Stem Cell Transplantation; Humans; Male; Middle Aged; Nausea; Pilot Projects; Prospective Studies; Transplantation Conditioning; Vomiting; Young Adult

Background The role of olanzapine in the treatment of chemotherapy-induced nausea and vomiting (CINV) in addition to the antiemetic therapeutic combination with aprepitant, setrons, and corticosteroids has not been well defined. Objective To investigate the effectiveness of the addition of olanzapine to a standard triplet therapy for the prevention of CINV in patients who experienced CINV during their first chemotherapy course, despite receiving a well-managed prevention protocol. Setting One comprehensive cancer centre in France. Method In a retrospective study with comparator, patients with a high risk of emesis were assigned to two groups during two different 6-month periods, before and after the introduction of olanzapine in clinical practice, respectively. In the olanzapine group, the antiemetic protocol for the second course of chemotherapy was reinforced by the addition of olanzapine at 5 mg/day from day 1 to 5 in contrast with the control group. Main outcome measure The proportion of patients who experienced neither nausea nor emesis during the delayed phase (24-120 h). Results The 25 patients in each group exhibited comparable characteristics and emetic chemotherapy level. During the first course, no significant difference was observed. During the second course, nausea and vomiting were ameliorated in 12 patients in the olanzapine group and 4 patients in the control group (p < 0.05). Nausea (12 vs. 4, p < 0.05) and vomiting (18 vs. 11, p < 0.05) also significantly improved. In the OLZ group, no adverse event was linked to olanzapine use. Conclusion The addition of olanzapine was observed to effectively restore CINV prevention in patients who did not respond to standard antiemetic therapy.

Topics: Adrenal Cortex Hormones; Adult; Aged; Aged, 80 and over; Antiemetics; Antineoplastic Agents; Aprepitant; Drug Resistance; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Nausea; Olanzapine; Retrospective Studies; Serotonin Antagonists; Vomiting; Young Adult

Evaluate safety of HTX-019, a novel polysorbate 80- and synthetic surfactant-free intravenous formulation of neurokinin 1 receptor antagonist aprepitant for chemotherapy-induced nausea and vomiting.. Two open-label, randomized, two-way crossover studies evaluated treatment-emergent adverse events (TEAEs) in 200 healthy subjects. Subjects received HTX-019 130 mg (30-min infusion) and fosaprepitant 150 mg (20- or 30-min infusion), with ≥7-day washout between doses.. Less than or equal to 30 min after start of infusion, TEAEs occurred in 5 (3%) HTX-019 and 30 (15%) fosaprepitant recipients. No HTX-019 recipients had infusion-site adverse events, versus 15 (8%) fosaprepitant recipients. Treatment-related dyspnea occurred in one HTX-019 and six fosaprepitant recipients. No severe/serious TEAEs occurred; all TEAEs resolved.. HTX-019 may provide a safer aprepitant formulation than fosaprepitant for chemotherapy-induced nausea and vomiting prevention.

Topics: Adult; Antiemetics; Antineoplastic Agents; Aprepitant; Cross-Over Studies; Dyspnea; Female; Healthy Volunteers; Humans; Infusions, Intravenous; Male; Middle Aged; Morpholines; Nausea; Neoplasms; Neurokinin-1 Receptor Antagonists; Treatment Outcome; Vomiting; Young Adult

This was a subgroup analysis of age group, dexamethasone use, and very highly emetogenic chemotherapy (VHEC) use from a randomised, multicentre, double-blind, Phase 3 study of oral aprepitant in paediatric subjects.. Subjects aged 6 months to 17 years scheduled to receive chemotherapeutic agents associated with at least moderate risk for emesis were randomly assigned to receive either aprepitant plus ondansetron (aprepitant regimen) or placebo plus ondansetron (control regimen); both could be administered with or without dexamethasone. This secondary analysis evaluated subjects stratified by pre-specified age groups, dexamethasone use, and VHEC use. The primary endpoint of this analysis was the proportion of subjects who experienced complete response (CR) during the delayed phase.. CR rates in the delayed phase were numerically higher with the aprepitant than the control regimen across all age categories, and reached significance for subjects aged 12-17 years (51% vs. 10%; P < 0.0001). In subjects receiving dexamethasone, CR was twice as high for the aprepitant versus control regimen in the 6 months to <2 year group (50% vs. 25%) and significantly higher in the 12-17 year group (40% vs. 7%, P < 0.05). CR was also significantly higher with aprepitant in the 6 months to <2 year and 12-17 year age groups who received VHEC. Similar proportions of subjects experiencing at least one adverse event were seen in both regimens across age categories.. A 3 day aprepitant regimen seemed effective and safe for prevention of chemotherapy-induced nausea and vomiting in paediatric subjects across subgroups (ClinicalTrials.gov NCT01362530).

Topics: Adolescent; Age Factors; Antiemetics; Antineoplastic Agents; Aprepitant; Child; Child, Preschool; Double-Blind Method; Female; Humans; Infant; Male; Nausea; Neoplasms; Ondansetron; Vomiting

The prevention of chemotherapy-induced nausea and vomiting was one of the most challenging supportive care issues in oncology, especially to highly emetogenic chemotherapy (HEC). A total of 645 patients were randomized into fosaprepitant group (fosaprepitant/placebo 150 mg d1 in combination with granisetron and dexamethasone) or aprepitant group (aprepitant/placebo 125 mg d1; 80 mg d2-d3 plus granisetron and dexamethasone).The primary endpoint was the percentage of patients who had a complete response (CR) over the entire treatment course (0-120 hr, overall phase [OP]). It was assessed by using a non-inferiority model, with a non-inferiority margin of 10%. The difference of the CR rate was compared between two groups with chi-square analysis. Six hundred and twenty-six patients were included in the per protocol analysis. The percentage of patients with a CR in the fosaprepitant group was not inferior to that in the aprepitant group (90.85% versus 94.17%, p = .1302) during OP. Whether the cisplatin-based chemotherapy or not, the CR rate of the fosaprepitant group was not inferior to that of the aprepitant group. Both regimens were well tolerated. The most common adverse event was constipation. Fosaprepitant provided effective and well-tolerated control of nausea and vomiting associated with HEC in Chinese patients.

Topics: Adult; Aged; Antiemetics; Antineoplastic Agents; Aprepitant; Asian People; China; Cisplatin; Dexamethasone; Double-Blind Method; Drug Therapy, Combination; Female; Granisetron; Humans; Male; Middle Aged; Morpholines; Nausea; Treatment Outcome; Vomiting; Young Adult

The three-drug combination of a 5-hydroxytryptamine type 3 receptor antagonist, a neurokinin 1 receptor antagonist and dexamethasone is recommended for patients receiving highly emetogenic chemotherapy. However, standard antiemetic therapy is not completely effective in all patients.. We conducted an open-label, single-center, single-arm Phase II study to evaluate the efficacy of olanzapine in combination with standard antiemetic therapy in preventing chemotherapy-induced nausea and vomiting in patients with thoracic malignancy receiving their first cycle of cisplatin-based chemotherapy. Patients received 5 mg oral olanzapine on Days 1-5 in combination with standard antiemetic therapy. The primary endpoint was complete response (no vomiting and no use of rescue therapy) during the overall Phase (0-120 h post-chemotherapy).. Twenty-three men and seven women were enrolled between May and October 2015. The median age was 64 years (range: 36-75 years). The most common chemotherapy regimen was 75 mg/m2 cisplatin and 500 mg/m2 pemetrexed, which was administered to 14 patients. Complete response rates in acute (0-24 h post-chemotherapy), delayed (24-120 h post-chemotherapy) and overall phases were 100%, 83% and 83% (90% confidence interval: 70-92%; 95% confidence interval: 66-93%), respectively. There were no Grade 3 or Grade 4 adverse events. Although four patients (13%) experienced Grade 1 somnolence, no patients discontinued olanzapine.. The addition of 5 mg oral olanzapine to standard antiemetic therapy demonstrates promising efficacy in preventing cisplatin-based chemotherapy-induced nausea and vomiting and an acceptable safety profile in patients with thoracic malignancy.

Topics: Adult; Aged; Antiemetics; Antineoplastic Agents; Aprepitant; Benzodiazepines; Cisplatin; Dexamethasone; Female; Humans; Isoquinolines; Male; Middle Aged; Morpholines; Nausea; Olanzapine; Palonosetron; Quinuclidines; Thoracic Neoplasms; Vomiting

Aprepitant, an NK1 receptor antagonist, is approved for the treatment of chemotherapy-induced or postoperative emesis by blocking NK1 receptors in the brain stem vomiting center. The effects of NK1 receptors on gastric functions and postprandial symptoms in humans are unclear; a single, crossover study did not show a significant effect of aprepitant on gastrointestinal transit. Our aim was to compare, in a randomized, double-blind, placebo-controlled, parallel-group study (12 healthy volunteers per group), the effects of aprepitant vs. placebo on gastric emptying of solids (by scintigraphy) with a 320-kcal meal, gastric volumes (GVs; fasting and accommodation by single photon emission-computed tomography ), satiation [maximum tolerated volume (MTV)], and symptoms after a dyspeptogenic meal of Ensure. Aprepitant (125 mg on

Topics: Abdominal Pain; Adolescent; Adult; Aged; Aprepitant; Cross-Over Studies; Double-Blind Method; Female; Gastrointestinal Motility; Humans; Male; Maximum Tolerated Dose; Middle Aged; Morpholines; Nausea; Neurokinin-1 Receptor Antagonists; Postprandial Period; Receptors, Neurokinin-1; Satiety Response; Stomach; Young Adult

Neurokinin-1 receptor antagonists, such as aprepitant are currently emerging as powerful prophylactic agents for chemotherapy-induced nausea and vomiting (CINV). Therefore, it is important to adjust the anti-emetic regimens based on personal risk factors of the patient, duration of the chemotherapy regimen and cost-effectiveness.. To determine the efficacy of the 3-day aprepitant along with ondansetron and dexamethasone in controlling CINV in patients with large B cell lymphoma receiving multiday-cisplatin regimen chemotherapy.. This is a pilot prospective cross-over trial. Patients were allocated to either aprepitant 125mg on day 1 and 80mg on days 2 & 3 or placebo in the first 2 cycles, with crossover to the opposite treatment in the 3rd and 4th cycles. The primary end point was complete response (CR) of both acute (days 1-5) and delayed (days 6-8) CINV. CR means neither to develop emetic episodes nor to use rescue anti-emetics medication.. Twelve of the 15 patients recruited for the study were fully evaluable and completed 4 cycles of ESHAP regimen with a total of 48 cycles given. In the cycles with aprepitant and those without the CR were 83.3% and 0% respectively (p<0.05). Patients receiving aprepitant in the first 2 cycles recorded less nausea in subsequent cycles that were given without aprepitant. This was not statistically significant.. This triple anti-emetic regimen showed efficacy in controlling the multi-day cisplatin-induced nausea and vomiting. Further randomized controlled trials are needed to compare between 3-day and 7-day aprepitant for multi-day cisplatin regimens.

Topics: Adult; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Chemoprevention; Cisplatin; Dexamethasone; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Lymphoma, Large B-Cell, Diffuse; Male; Middle Aged; Morpholines; Nausea; Ondansetron; Pilot Projects; Time Factors; Treatment Outcome; Vomiting

Chemotherapy-induced nausea and vomiting (CINV) is one of the most frequently encountered side effects of cancer treatment. Severe CINV can lead patients to refuse chemotherapy, which ultimately affects cancer outcomes. The development of fairly new antiemetic agents, 5-hydroxytryptamine-3 receptor antagonists, palonosetron and neurokinin-1 receptor antagonists and aprepitant has reduced the risk and incidence of CINV. In this study, we assessed the efficacy of aprepitant plus palonosetron against palonosetron for CINV in patients receiving moderately emetic cancer chemotherapy (paclitaxel and carboplatin combination [TC] therapy).. Between November 2010 and March 2014, 78 patients with gynecological cancer treated with TC therapy were randomized into two groups: an aprepitant group (administered aprepitant, dexamethasone and palonosetron) and a control group (administered dexamethasone and palonosetron). The primary study endpoint was complete response, defined as the complete absence of emetic events in the delayed phase.. The complete response rate in the delayed phase differed significantly between the two groups, with 82% in the aprepitant group and 97% in the control group (P = 0.025).. The combination of aprepitant and palonosetron appears to be of greater efficacy than palonosetron alone for the prevention of delayed-phase CINV induced by TC therapy.

Topics: Adult; Aged; Antiemetics; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Carboplatin; Drug Therapy, Combination; Female; Genital Neoplasms, Female; Humans; Isoquinolines; Middle Aged; Morpholines; Nausea; Outcome Assessment, Health Care; Paclitaxel; Palonosetron; Quinuclidines; Serotonin 5-HT3 Receptor Antagonists; Vomiting

Chemotherapy-induced nausea-vomiting (CINV) compromises the quality of life of patients with cancer. We present data on the effectiveness of olanzapine after failure of aprepitant in patients receiving highly emetogenic chemotherapy (HEC). A single-center prospective study was conducted, where patients ≥ 18 years who failed aprepitant, palonosetron, dexamethasone (APD) received olanzapine, palonosetron and dexamethasone (OPD) in the subsequent cycle of HEC. Failure of APD was defined as occurrence of ≥ grade 2 acute and/or delayed nausea ± vomiting. Response rates were compared with what was achieved in their previous cycle with the use of APD in the acute (0-24 h), delayed (24-120 h) and overall (0-120 h) periods after the start of HEC. Impact on life was assessed using the MD Anderson Symptom Inventory (MDASI). Fifty-five patients failed APD and received OPD in the subsequent cycle; 54 were evaluable for response. Complete response rate for OPD versus APD is 80 versus 20% (acute period), 90 versus 18% (delayed period) and 74 versus 5% (overall period), and no nausea rate for OPD versus APD is 57 versus 13% (acute), 59 versus 15% (delayed) and 48 versus 0% (overall period), p < 0.001 for all comparisons. MDASI scores showed significant improvement after switching to OPD. A mild increase in drowsiness noted in patients receiving OPD did not affect daily life in most patients. In patients receiving HEC and failing CINV prophylaxis with APD, switching to OPD regimen in the subsequent cycle greatly improves control of vomiting, increases "no nausea" rates and significantly reduces symptom severity scores.

Topics: Adolescent; Aged; Antiemetics; Antineoplastic Agents; Aprepitant; Benzodiazepines; Humans; Middle Aged; Morpholines; Nausea; Olanzapine; Prospective Studies; Treatment Failure; Vomiting; Young Adult

We previously reported in the SENRI trial on the usefulness of aprepitant for the prevention of chemotherapy-induced nausea and vomiting (CINV) in colorectal cancer patients receiving an oxaliplatin-based regimen which is classified as moderately emetogenic cancer chemotherapy. In the present subgroup analysis of the SENRI trial, we assessed the risk factors for CINV in colorectal cancer patients who received oxaliplatin-based chemotherapy.. Multivariate logistic regression models were used to assess the impact of aprepitant use and patient characteristics on vomiting and nausea. We also assessed the proportion of CINV in patients by gender.. Female gender and aprepitant use were associated with the incidence of vomiting and no significant nausea. Significantly more men achieved no vomiting than women (92.9 vs 84.5 % in men and women, respectively; P = 0.0001). The rate of no nausea, complete response, complete protection, and total control was also higher in men. The rate rescue therapy use was significantly higher in women than men. We compared the rate of CINV between aprepitant and control groups and found a significant difference in male patients who achieved no vomiting and complete protection in the overall phase. In women, the rate of no nausea, no vomiting, and total control was higher in the aprepitant group than in the control group.. Gender and aprepitant use were risk factors for CINV in colorectal patients who received oxaliplatin-based chemotherapy. Aprepitant therapy was more effective for women than for men in the prevention of CINV in colorectal cancer patients receiving an oxaliplatin-based regimen.

Topics: Adult; Aged; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Colorectal Neoplasms; Female; Humans; Logistic Models; Male; Middle Aged; Morpholines; Nausea; Organoplatinum Compounds; Oxaliplatin; Risk Factors; Vomiting

We performed a prospective study to investigate the efficacy and safety of triple therapy with aprepitant, ondansetron, and prednisone in non-Hodgkin lymphoma patients receiving R-CEOP or CEOP chemotherapy regimen. All patients were randomly assigned to either an aprepitant regimen (aprepitant plus ondansetron and prednisone), or a control regimen (ondansetron and prednisone) treatment group. For the complete response, the aprepitant group was statistically superior to the control group in the overall study period (76.5% vs. 56.0%; p = .03), as well as in separate analyses of the acute phase (92.2% vs. 78.0%; p = .045), and even more notably in the delayed phase (82.4% vs. 64.0%; p = .037). The overall incidence of adverse events was similar between the two treatment groups (p > .05). The aprepitant regimen was more effective than the control regimen for the prevention of CINV in patients receiving R-CEOP or CEOP regimen and was generally well tolerated.

Topics: Activities of Daily Living; Adult; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Drug Therapy, Combination; Female; Humans; Lymphoma, Non-Hodgkin; Male; Middle Aged; Morpholines; Nausea; Ondansetron; Prednisone; Quality of Life; Treatment Outcome; Vomiting

This study evaluated the efficacy and safety of a 3-day aprepitant regimen for the prevention of chemotherapy-induced nausea and vomiting (CINV) during the first cycle of non-anthracycline plus cyclophosphamide (AC)-based moderately emetogenic chemotherapy (MEC) based on government guidelines in Korean patients.. This multicenter, randomized, double-blind, phase IV trial (NCT01636947) enrolled adult South Korean patients with a broad range of tumor types who were scheduled to receive a single dose of ≥1 MEC agent. Patients were randomized to a 3-day regimen of aprepitant (aprepitant regimen) or placebo (control regimen) on top of ondansetron plus dexamethasone. The primary and key secondary efficacy endpoints were the proportions of subjects who achieved no vomiting and complete response (CR) during the overall phase.. Of the 494 randomized subjects, 480 were included in the modified intent-to-treat population. Response rates for no vomiting and CR in the overall phase were numerically higher for the aprepitant regimen compared with the control regimen groups, but failed to reach statistical significance (no vomiting 77.2 vs 72.0%; p = 0.191; CR 73.4 vs 70.4%; p = 0.458). Both the aprepitant and control regimens were generally well tolerated.. A 3-day aprepitant regimen was numerically better but not statistically superior to a control regimen with respect to the achievement of no vomiting or CR during the overall phase in a non-AC MEC Korean population based on government reimbursement guidelines.. ClinicalTrials.gov NCT01636947 ( https://clinicaltrials.Gov/ct2/show/NCT01636947 ).

Topics: Adult; Aged; Aged, 80 and over; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Cyclophosphamide; Dexamethasone; Double-Blind Method; Female; Humans; Male; Middle Aged; Morpholines; Nausea; Neoplasms; Ondansetron; Vomiting; Young Adult

Despite a lower risk of nausea and vomiting in patients receiving radiotherapy to the upper abdomen (UA-RINV) with prophylactic 5-HT3 antagonist therapy, patients can still experience UA-RINV. The aim of this multicenter phase II study was to assess effectiveness, safety, and tolerability of protracted dual NK1-receptor and 5-HT3 antagonist prophylaxis against UA-RINV.. Patients receiving fractionated radiotherapy with radiosensitizing chemotherapy received oral ondansetron 8 mg po q12 h and aprepitant 125/80/80 mg on a Monday, Wednesday, Friday schedules throughout radiotherapy. The primary outcome was complete response (CR) defined as no vomiting or rescue therapy during the entire observation period of radiotherapy (OP). Nausea, vomiting, and use of rescue medication were recorded in a modified version of the MASCC antiemesis tool completed twice weekly.. Fifty-five patients were enrolled at 5 sites, 52 of whom were evaluable. 57.7% of patients (30/52, 95% CI 43.2-71.3%) achieved CR on study, with 73.1% (38/52, 95% CI 59.0-84.4%) who did not vomit, and 71.2% (37/52, 95% CI 56.9-82.9%) who did not use rescue medication during the OP. Overall, participants vomited or experienced significant nausea (SN) for an average of 6.8% (95% CI 11.4-21.0) and 8.4% (95% CI 4.2-12.7%) of time on study, respectively. Nausea was common with 32 (61.5%) reporting SN at any time during the OP.. UA-RINV remains an important morbidity despite the advent of modern radiotherapy. Aprepitant and ondansetron as dosed in this trial was not superior to standard ondansetron monotherapy.

Topics: Abdomen; Aged; Antiemetics; Aprepitant; Dose Fractionation, Radiation; Female; Humans; Male; Middle Aged; Morpholines; Nausea; Ondansetron; Radiotherapy; Vomiting

Our aim was to evaluate the efficacy of oral aprepitant in rescue treatment after the primary rescue for breakthrough chemotherapy-induced nausea and vomiting (CINV) in chemotherapy-naive patients receiving moderately emetogenic chemotherapy (MEC).. This was a single-institutional phase 2 study. Patients who had received MEC regimens and developed breakthrough CINV despite antiemetic prophylaxis without aprepitant were treated with primary rescue antiemetic treatments chosen by physicians. When the primary rescue (1st rescue) failed, patients received oral aprepitant as the second rescue (2nd rescue). The primary endpoint of this study was the proportion of patients requiring aprepitant as the 2nd rescue and experiencing successful rescue (SR). SR was defined as no vomiting and no need for additional rescue therapy, with nausea up to grade 1 on Common Terminology Criteria for Adverse Events and a Visual Analog Scale score of 25 mm, for 48 h after initiation of aprepitant.. Eighty patients were eligible for this analysis. Thirty-eight (47.5%) developed breakthrough emesis and received 1st rescue. The 1st rescue was ineffective in 29 (76.3%) patients, and they received the 2nd rescue with aprepitant. Thirteen of these 29 patients (16.3% of the total patients) satisfied the criteria for SR. The primary endpoint, SR rate, in patients treated with aprepitant, was 44.8% (95% confidence interval 26.4-64.4).. Since the lower end of the 95% confidence interval of SR is 26.4%, the SR in our study did not meet the predefined primary endpoint threshold. However, aprepitant was estimated to be useful in suppressing breakthrough CINV in 16% of the patients treated with MEC.

Topics: Administration, Oral; Adult; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Female; Humans; Lung Neoplasms; Male; Middle Aged; Morpholines; Nausea; Treatment Outcome; Vomiting

BACKGROUND The aim of this study was to evaluate the antiemetic effect of aprepitant and to determine how to provide triple combination therapy (aprepitant/azasetron/dexamethasone) to women receiving paclitaxel/carboplatin moderately emetogenic chemotherapy (MEC). MATERIAL AND METHODS The current study was a prospective study of 163 women with gynecologic cancers. We compared the digestive symptoms scores (nausea, vomiting, appetite loss, and dietary intake) of 37 women with ovarian cancers before and after aprepitant administration. We also compared these symptoms in women who underwent 193 cycles of triple combination therapy with symptoms of women who underwent 226 cycles of double combination therapy. For triple combination therapy, azasetron, dexamethasone (reduced dose: 40% of 20 mg), and aprepitant (125 mg) were administered on Day 1, followed by only aprepitant (80 mg) administration on Days 2 and Day 3. RESULTS In 37 women with ovarian cancer, three symptoms, nausea, appetite loss, and dietary intake, were significantly improved by primarily adding aprepitant to double combination therapy in the delayed phase of MEC. Upon comparing their digestive symptoms in all cycles, however, these three symptoms were not significantly different in the delayed phase. Furthermore, all four symptoms in all cycles were worse following triple combination therapy than following double combination therapy in the acute phase (p<0.02). The control of digestive symptoms was generally insufficient without the administration of dexamethasone. CONCLUSIONS Primary aprepitant as an addition to MEC demonstrated efficacy in improving digestive symptoms in the delayed phase. However, its effect may decrease with repeated use. To improve the antiemetic effect, the dose reduction of dexamethasone should be restricted on Day 1 and dexamethasone should be used throughout the delayed phase as well.

Topics: Adult; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Bridged Bicyclo Compounds, Heterocyclic; Carboplatin; Dexamethasone; Female; Humans; Middle Aged; Morpholines; Nausea; Ovarian Neoplasms; Oxazines; Paclitaxel; Pre-Exposure Prophylaxis; Prospective Studies; Vomiting

Olanzapine is effective in chemotherapy-induced nausea and vomiting (CINV). In patients receiving highly emetogenic chemotherapy (HEC), its efficacy was reported as rescue therapy for breakthrough emesis refractory to triplet therapy (palonosetron, aprepitant, and dexamethasone). However, its preventive effects with triplet therapy for CINV are unknown. This study aimed to investigate efficacy and safety of preventive use of olanzapine with triplet therapy for CINV of HEC.. This study is a prospective multicenter study conducted by Kansai Clinical Oncology Group. Forty chemo-naïve gynecological cancer patients receiving HEC with cisplatin (≥50 mg/m(2)) were enrolled. Oral olanzapine (5 mg) was administered with triplet therapy a day prior to cisplatin administration and on days 1-5. The primary endpoint was complete response (no vomiting and no rescue) rate for the overall phase (0-120 h post-chemotherapy). Secondary endpoints were complete response rate for acute phase (0-24 h post-chemotherapy) and delayed phase (24-120 h post-chemotherapy) and complete control (no vomiting, no rescue, and no significant nausea) rate and total control (no vomiting, no rescue, and no nausea) rate for each phase. These endpoints were evaluated during the first cycle of chemotherapy.. Complete response rates for acute, delayed, and overall phases were 97.5, 95.0, and 92.5 %, respectively. Complete control rates were 92.5, 87.5, and 82.5 %, respectively. Total control rates were 87.5, 67.5, and 67.5 %, respectively. There were no grade 3 or 4 adverse events.. Preventive use of olanzapine combined with triplet therapy gives better results than those from previously reported studies of triplet therapy.

Topics: Adult; Aged; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Benzodiazepines; Cisplatin; Dexamethasone; Female; Genital Neoplasms, Female; Humans; Isoquinolines; Male; Middle Aged; Morpholines; Nausea; Olanzapine; Palonosetron; Prospective Studies; Quinuclidines; Serotonin Antagonists; Vomiting

We aimed to compare the preventive effect of 5-day administration of aprepitant with single administration of fosaprepitant meglumine against nausea and vomiting symptoms due to highly emetogenic chemotherapy regimens comprising cisplatin (CDDP).. Subjects were inpatients who underwent chemotherapy for gastric cancer, esophageal cancer, lung cancer, or head and neck cancer with a regimen comprising 60 mg/m(2) or higher dose of CDDP. In this randomised, open-label, controlled study, the subjects were assigned to a group given aprepitant for 5 days or a group given a single administration of fosaprepitant meglumine. The nausea and vomiting symptoms that emerged within 7 days after the first CDDP administration were investigated with a questionnaire form; the results were compared between the two groups. Risk factors affecting nausea and vomiting symptoms were also investigated.. Of the 101 patients enrolled, 93 patients were included (48 in the 5-day aprepitant group and 45 in the single fosaprepitant meglumine group). No significant intergroup differences in the complete response rate or the complete control rate were found over the entire period. The nausea score tended to increase from day 3 in both groups, but no significant intergroup difference was observed. Furthermore, the investigation of risk factors affecting moderate or severe nausea symptoms indicated that the fosaprepitant meglumine administration was not a risk factor.. Single administration of fosaprepitant meglumine was not inferior to 5-day administration of aprepitant for preventing acute and delayed nausea and vomiting symptoms occurring after administration of CDDP (60 mg/m(2) or higher).

Topics: Aged; Antiemetics; Aprepitant; Cisplatin; Esophageal Neoplasms; Female; Head and Neck Neoplasms; Humans; Lung Neoplasms; Male; Meglumine; Middle Aged; Morpholines; Nausea; Risk Factors; Stomach Neoplasms; Surveys and Questionnaires; Treatment Outcome; Vomiting

Dexamethasone, plus a 5-HT3 receptor antagonist and an NK-1 receptor antagonist are recommended for controlling the chemotherapy-induced nausea and vomiting (CINV) of highly emetogenic chemotherapy. Several days of dexamethasone are effective for CINV; however, dexamethasone also has side effects. The purpose of this trial was to investigate whether the use of a second-generation 5-HT3 receptor antagonist and an NK-1 receptor antagonist could allow a reduced dose of dexamethasone for breast cancer patients receiving highly emetogenic chemotherapy.. Eighty breast cancer patients who received an anthracycline-cyclophosphamide combination regimen were enrolled. The patients were randomized to arm A (dexamethasone days 1-3) and arm B (dexamethasone day 1). The primary endpoint was complete response (CR) (no emetic episodes and no rescue medication) during the overall phase (days 1-5). The secondary endpoints were the CR during the delayed phase (days 2-5), complete control (CC) (no emetic episodes, no rescue medication, and no more than mild nausea) during the overall phase, and the safety of this antiemetic therapy.. There were no significant differences in the rates of CR and CC between arm A and B as follows: CR overall phase--arm A: 82.9%, 90% confidence interval [CI] 71.3-90.5% vs arm B: 82.1%, 90% CI 70.0-90.0%; p = 1.00; CR delayed phase--arm A: 87.8%, 90% CI 77.0-93.9% vs arm B: 94.9%, 90% CI 85.6-98.3%; p = 0.43; CC overall phase--arm A: 48.8%, 90% CI 36.4-61.3% vs arm B: 61.5%, 90% CI 48.4-73.2%; p = 0.27. There were very few adverse events and no severe adverse events associated with this antiemetic therapy.. The results suggest that the antiemetic effect provided by dexamethasone administered for 3 days can be obtained by dexamethasone administered for 1 day.

Topics: Adult; Aged; Anthracyclines; Antiemetics; Antineoplastic Agents; Aprepitant; Breast Neoplasms; Dexamethasone; Female; Humans; Isoquinolines; Japan; Middle Aged; Morpholines; Nausea; Palonosetron; Quinuclidines; Vomiting

The objective of this exploratory analysis was to determine if individual patient risk factors could be used to optimize chemotherapy-induced nausea and vomiting (CINV).. Through validated risk prediction models which quantify patient risk factors, 152 patients with early-stage breast cancer scheduled to received adjuvant anthracycline-based chemotherapy were categorized as being at low (level 0) or high-risk (level 1) for CINV. Prior to the first cycle of chemotherapy, low-risk patients received ondansetron and dexamethasone, while high-risk level 1 patients also received aprepitant. For subsequent cycles, patients who experienced CINV had their antiemetics changed in a stepwise manner to level 2 (extended-duration dexamethasone) or level 3 (extended-duration dexamethasone and low-dose olanzapine).. The study enrolled 152 patients who received 484 cycles of chemotherapy. Forty patient cycles were classified as low risk (level 0) compared to 201, 162 and 81 that were classified as high-risk levels 1, 2 and 3, respectively. Complete control of acute and delayed vomiting was comparable and was achieved in over 85 % of patients across all risk levels (p = 0.56 and p = 0.99). In contrast, complete control of acute and delayed nausea was reduced in risk levels 1 to 3 compared to level 0 (acute = 51.2, 58.0, 45.7 vs. 70.0 %; p = 0.013)-(delayed = 32.8, 45.7, 34.6 vs. 62.5 %; p < 0.001).. Despite the addition of aprepitant, extended-duration dexamethasone and olanzapine, patients at high risk for CINV due to personal risk factors failed to achieve good nausea control.

Topics: Adult; Aged; Antiemetics; Antineoplastic Agents; Aprepitant; Breast Neoplasms; Dexamethasone; Female; Humans; Middle Aged; Morpholines; Nausea; Ondansetron; Outcome Assessment, Health Care; Practice Guidelines as Topic; Risk Factors; Vomiting

The purpose of this pilot study was to compare the response rates and daily living activities of patients with newly diagnosed gynecologic cancer treated with fosaprepitant or aprepitant in the management of chemotherapy-induced nausea and vomiting.. Eligible participants were randomized to either intravenous fosaprepitant (150 mg, day 1) or oral aprepitant (125 mg on day 1 and 80 mg on days 2-3) before undergoing weekly paclitaxel (80 mg/2)(2) and monthly carboplatin (AUC 6)-based chemotherapy. In addition, standard premedications (eg, ranitidine, dexamethasone, and diphenhydramine) were administered intravenously on day 1. Response evaluation and impact on daily life were measured throughout the acute phase (0-24 hours), delayed period (days 2-4), and overall phase (0-120 hours) of the patients' initial chemotherapy cycle via the Functional Living Index-Emesis.. In the current investigation, 20 gynecologic cancer subjects were treated with either fosaprepitant (n = 10) or aprepitant (n = 10) before their first chemotherapy cycle. We observed 7 overall complete responses (70%, no emetic episodes or rescue medications) in the aprepitant group and 6 (60%) in the fosaprepitant cohort (P = 0.660). In addition, both treatment groups reported similarly, favorable rates of daily living activities throughout the acute (P = 0.626) and delayed (P = 0.648) phases of cycle 1 chemotherapy.. The findings from the current analysis suggest that intravenous fosaprepitant and oral aprepitant confer beneficial antiemetic prevention. Moreover, the 2 medications theoretically afford a favorable impact on daily living, thereby potentially facilitating the completion of a patient's clinically prescribed chemotherapy regimen.

Topics: Adult; Aged; Antiemetics; Antineoplastic Agents; Aprepitant; Female; Genital Neoplasms, Female; Humans; Middle Aged; Morpholines; Nausea; Pilot Projects; Vomiting

Substance P contributes to the hypersensitivity reaction (HSR) to paclitaxel in a rat model. Aprepitant acts as an inhibitor of the binding of substance P to the neurokinin-1 receptor and, consequently, may reduce the frequency of paclitaxel-induced HSR. While aprepitant has a prophylactic effect against vomiting caused by high-dose cisplatin, the benefits of aprepitant have not been clearly demonstrated in patients receiving paclitaxel and carboplatin (TC) combination chemotherapy.. We conducted a multicenter, placebo-controlled, double-blind, randomized study in Japanese patients with gynecologic cancer who received TC combination chemotherapy. Patients received aprepitant or placebo together with both a 5-HT3 receptor antagonist and dexamethasone prior to chemotherapy. The primary endpoint was the proportion of patients with HSR, and the secondary endpoints were the proportion of patients with "no vomiting", "no significant nausea", and complete response, respectively.. Of the 324 randomized patients, 297 (151 in the aprepitant group; 146 in the placebo group) were evaluated. The percentage of patients with HSR (9.2 vs. 7.5 %, respectively; P = 0.339) was not significantly different between the groups. The percentage of "no vomiting" patients (78.2 vs. 54.8 %; P < 0.0001), "no significant nausea" patients (85.4 vs. 74.7 %; P = 0.014), and patients showing complete response (61.6 vs. 47.3 %, P = 0.0073) was significantly higher in the aprepitant group than in the placebo group.. The administration of aprepitant did not have a prophylactic effect on the HSR but was effective in reducing nausea and vomiting in gynecologic cancer patients receiving TC combination chemotherapy.

Topics: Adult; Aged; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Carboplatin; Dexamethasone; Double-Blind Method; Drug Hypersensitivity; Drug Therapy, Combination; Female; Genital Neoplasms, Female; Humans; Middle Aged; Morpholines; Nausea; Paclitaxel; Remission Induction; Serotonin 5-HT3 Receptor Antagonists; Vomiting; Young Adult

Docetaxel-cyclophosphamide (TC) has become a common regimen in moderate-high-risk early breast cancer (EBC), but the incidence of chemotherapy-induced nausea and vomiting (CINV) with this regimen is not well established. This trial investigates the effect of guideline-consistent prophylaxis on CINV related to TC regimen and explores the efficacy of aprepitant among resistant patients.. This prospective multicentre study enrolled 212 chemotherapy-naïve EBC patients receiving T-75 mg/m(2) and C-600 mg/m(2). Antiemetic therapy on the first cycle consisted of dexamethasone for 3 d plus 5-hydroxytryptamine (5-HT3) antagonists on day 1, according to Multinational Association of Supportive Care in Cancer guidelines. The primary end-point was complete response (CR) (no emesis and no need of rescue treatment within the initial 120 h). Patients failing CR on cycle 1 entered in a single-arm study exploring the efficacy of aprepitant on the second cycle. Patients' diaries and Functional Living Index-Emesis (FLIE) questionnaires were collected in cycles 1 and 2.. Among the 185 evaluable patients on cycle 1, 161 (87%, 95% confidence interval [CI]: 82.2-91.8) achieved a CR. Twenty-three patients received aprepitant on cycle 2, and 12 reached a CR (52.2%, 95% CI: 31.8-72.6). The absence of CR had a very substantial impact on quality of life on cycles 1 (FLIE before and after: 23.8-38.1, p = 0.0124) and 2 (18.3-42.9, p = 0.0059).. Guideline-consistent antiemetic prophylaxis for the TC regimen is associated with a low incidence of CINV. Aprepitant is effective as secondary prevention of CINV and should be considered as rescue therapy in patients treated with moderate emetogenic chemotherapy.

Topics: Adult; Aged; Aged, 80 and over; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Breast Neoplasms; Cyclophosphamide; Dexamethasone; Docetaxel; Female; Humans; Middle Aged; Morpholines; Nausea; Neoplasm Staging; Prospective Studies; Quality of Life; Salvage Therapy; Secondary Prevention; Serotonin 5-HT3 Receptor Antagonists; Spain; Surveys and Questionnaires; Taxoids; Time Factors; Treatment Outcome; Vomiting

Chemotherapy-induced nausea and vomiting is a challenging issue. Although aprepitant is sometimes used as a therapeutic option in patients receiving moderately emetogenic chemotherapy, the potential benefit of sequential addition of aprepitant to dexamethasone and a 5-hydroxytryptamine-3 (5-HT3) receptor antagonist during the second cycle of carboplatin-based chemotherapy remains unclear. Chemo-naïve patients with advanced non-small cell lung cancer (NSCLC) who received carboplatin-based chemotherapy were treated with doublet antiemetic therapy with dexamethasone and a 5-HT3 receptor antagonist during the first cycle of chemotherapy. Aprepitant was then added during the second cycle of chemotherapy. The primary endpoint was overall complete response rate, defined as no vomiting and no rescue therapy during the 120 h after administration of chemotherapy. Sixty-seven patients were enrolled, 63 of whom were eligible after two cycles of chemotherapy. The overall complete response rate was significantly improved in the second cycle [87.3 %, 95 % confidence interval (CI) 76.5-94.4 %] compared with the first cycle (65.1 %, 95 % CI 52.0-76.7 %; p < 0.001). Improvement was observed in the delayed phase, but not in the acute phase. Subsequent addition of aprepitant significantly improved the overall complete response rate in NSCLC patients receiving a second cycle of carboplatin-based chemotherapy.

Topics: Adult; Aged; Aged, 80 and over; Antiemetics; Antineoplastic Agents; Aprepitant; Bevacizumab; Carboplatin; Carcinoma, Non-Small-Cell Lung; Dexamethasone; Female; Granisetron; Humans; Lung Neoplasms; Male; Middle Aged; Morpholines; Nausea; Ondansetron; Paclitaxel; Pemetrexed; Vomiting

We conducted a randomized trial to compare the safety and effectiveness of aprepitant, granisetron, and dexamethasone (AGD) with those of palonosetron and dexamethasone (PD) in patients who received highly emetogenic chemotherapy (HEC). Patients with esophageal or gastric cancer who were scheduled to receive HEC including at least 60 mg/m of cisplatin as the first-line treatment were randomly assigned to receive AGD (oral aprepitant 125 mg on day 1 and 80 mg on days 2-3; intravenous granisetron 3 mg on day 1; intravenous dexamethasone 6.6 mg on day 1 and oral dexamethasone 4 mg on days 2-3) or PD (intravenous palonosetron 0.75 mg on day 1; intravenous dexamethasone 13.2 mg on day 1 and oral dexamethasone 8 mg on days 2-3). The primary endpoint was a complete response during the overall study period (0-120 h after the start of chemotherapy) in the first cycle. Eighty-five patients were enrolled, and 84 were eligible. The complete response rate did not differ between the treatment groups, but the proportion of patients with no vomiting was significantly higher in the AGD group than in the PD group (81.4 vs. 58.5%; P=0.031). The results of a quality-of-life survey indicated that the proportion of patients with no or minimal impact on daily life in the vomiting domain was significantly higher in the AGD group (79.1 vs. 53.7%; P=0.020). The primary endpoint of complete response was not achieved, but AGD seems to be more effective than PD for the prevention of HEC-induced vomiting.

Topics: Adult; Aged; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Cisplatin; Cross-Over Studies; Dexamethasone; Esophageal Neoplasms; Female; Granisetron; Humans; Isoquinolines; Male; Middle Aged; Morpholines; Nausea; Palonosetron; Quinuclidines; Serotonin Antagonists; Stomach Neoplasms; Vomiting

Antiemetic recommendations during concurrent chemoradiotherapy (cisplatin-based concurrent chemoradiotherapy (CCRT)) have not been established yet. The aim of this study was to investigate whether the combination of palonosetron plus aprepitant, without routine use of dexamethasone, could alleviate chemoradiotherapy-induced nausea and vomiting (CRINV).. This was a non-randomized, prospective, single-center, open phase II study. Patients with cervical cancer, who were treated with daily low-dose cisplatin (8 mg/m(2)/day) and concurrent radiation (2 Gy/day, 25 fractions, five times a week), were enrolled in this study. All patients received intravenous palonosetron (0.75 mg on day 1 of each week) and oral aprepitant (125 mg on day 1 and 80 mg on days 2 and 3 of each week). The primary endpoint was the percentage of patients with a complete response, defined as no emetic episodes and no use of antiemetic rescue medication during the treatment.. Twenty-seven patients (median age, 50 years; range, 33-72 years) were enrolled in this study between June 2013 and April 2014. A total of 13 (48 %) patients showed a complete response to the antiemetic regimen, while 8 patients (30 %) had emetic episodes and 6 patients (22 %) used rescue medication without emetic episodes. No severe adverse effects caused by palonosetron plus aprepitant were observed.. The combination of palonosetron plus aprepitant was permissive for the prevention of CRINV. This regimen should be considered for patients in whom dexamethasone is contraindicated or not well tolerated.

Topics: Adult; Aged; Aprepitant; Chemoradiotherapy; Cisplatin; Drug Therapy, Combination; Female; Humans; Isoquinolines; Middle Aged; Morpholines; Nausea; Palonosetron; Prospective Studies; Quinuclidines; Uterine Cervical Neoplasms; Vomiting

We examined the efficacy of olanzapine for the prevention of nausea and vomiting in patients receiving highly emetogenic chemotherapy.. In a randomized, double-blind, phase 3 trial, we compared olanzapine with placebo, in combination with dexamethasone, aprepitant or fosaprepitant, and a 5-hydroxytryptamine type 3-receptor antagonist, in patients with no previous chemotherapy who were receiving cisplatin (≥70 mg per square meter of body-surface area) or cyclophosphamide-doxorubicin. The doses of the three concomitant drugs administered before and after chemotherapy were similar in the two groups. The two groups received either 10 mg of olanzapine orally or matching placebo daily on days 1 through 4. Nausea prevention was the primary end point; a complete response (no emesis and no use of rescue medication) was a secondary end point.. In the analysis, we included 380 patients who could be evaluated (192 assigned to olanzapine, and 188 to placebo). The proportion of patients with no chemotherapy-induced nausea was significantly greater with olanzapine than with placebo in the first 24 hours after chemotherapy (74% vs. 45%, P=0.002), the period from 25 to 120 hours after chemotherapy (42% vs. 25%, P=0.002), and the overall 120-hour period (37% vs. 22%, P=0.002). The complete-response rate was also significantly increased with olanzapine during the three periods: 86% versus 65% (P<0.001), 67% versus 52% (P=0.007), and 64% versus 41% (P<0.001), respectively. Although there were no grade 5 toxic effects, some patients receiving olanzapine had increased sedation (severe in 5%) on day 2.. Olanzapine, as compared with placebo, significantly improved nausea prevention, as well as the complete-response rate, among previously untreated patients who were receiving highly emetogenic chemotherapy. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT02116530.).

Topics: Adult; Aged; Aged, 80 and over; Antiemetics; Antineoplastic Agents; Aprepitant; Benzodiazepines; Dexamethasone; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Intention to Treat Analysis; Male; Middle Aged; Morpholines; Nausea; Olanzapine; Vomiting

The purpose of the study is to investigate the usefulness of the triplet regimen comprising aprepitant, palonosetron, and dexamethasone in patients treated with highly emetogenic chemotherapy (HEC) and moderately emetogenic chemotherapy (MEC).. Patients with lung cancer (aged 65.8 ± 8.4 years) who received carboplatin-based MEC and those treated with cisplatin-based HEC were enrolled. The antiemetic regimen for both types of chemotherapy consisted of aprepitant, palonosetron, and dexamethasone based on the May 2010 guidelines prepared by the Japan Society of Clinical Oncology. The incidence of chemotherapy-induced nausea and vomiting (CINV) and the use of salvage treatment were assessed. The primary endpoints were the percentage of patients with a complete response (CR: no nausea and no salvage treatment) during the entire study period (5 days) after chemotherapy, during the acute phase (day 1), and during the delayed phase (days 2-5).. CR rates for the entire period were 86 and 71% in patients receiving carboplatin-based and cisplatin-based chemotherapy, respectively. CR rates were respectively 98 and 100% in the acute phase versus 87 and 71% in the delayed phase. Most of the patients could ingest food throughout the entire period after chemotherapy. Assessment of various risk factors for acute and delayed CINV (gender, age, prior vomiting due to antineoplastic therapy, prior experience of motion sickness, and history of drinking) revealed no significant influence of these factors on the CR rate for the entire period in patients receiving either carboplatin-based or cisplatin-based chemotherapy.. The present triple therapy can be recommended for supporting both carboplatin-based and cisplatin-based chemotherapy regimens.

Topics: Aged; Antiemetics; Antineoplastic Agents; Aprepitant; Carboplatin; Cisplatin; Dexamethasone; Drug Therapy, Combination; Female; Humans; Isoquinolines; Japan; Lung Neoplasms; Male; Middle Aged; Morpholines; Nausea; Palonosetron; Quinuclidines; Salvage Therapy; Surveys and Questionnaires; Treatment Outcome; Vomiting

A randomized Phase II dose-finding trial comparing olanzapine 10 mg with olanzapine 5 mg for patients receiving highly emetogenic chemotherapy with cisplatin was started in June 2014. The purpose of the trial is to evaluate the efficacy and safety of the two olanzapine doses and to determine which is more promising as a test arm for comparison with the current standard antiemetic care (a combination of aprepitant, a 5-HT3 receptor antagonist and dexamethasone) in a subsequent Phase III trial. Patients receiving cisplatin-containing regimens will be randomized to the olanzapine 10 or 5 mg arm. A total of 150 patients will be accumulated from nine institutions over 2 years. The primary endpoint is complete response defined as no emetic episodes and no use of rescue medications in the delayed (24-120 h) phase. This trial has been registered at the UMIN Clinical Trials Registry as UMIN000014214.

Topics: Adult; Aged; Antiemetics; Antineoplastic Agents; Aprepitant; Benzodiazepines; Cisplatin; Dexamethasone; Double-Blind Method; Drug Administration Schedule; Emetics; Female; Humans; Male; Middle Aged; Morpholines; Nausea; Olanzapine; Patient Selection; Research Design; Treatment Outcome; Vomiting

The first aim of this study was to evaluate combination antiemetic therapy consisting of 5-HT3 receptor antagonists, neurokinin-1 receptor antagonists (NK-1RAs), and dexamethasone for multiple high emetogenic risk (HER) anticancer agents in bone and soft tissue sarcoma. The second aim was to compare the effectiveness of single-shot palonosetron and consecutive-day granisetron in a randomized, single-blinded crossover study. A single randomization method was used to assign eligible patients to the palonosetron or granisetron arm. Patients in the palonosetron arm received a palonosetron regimen during the first and third chemotherapy courses and a granisetron regimen during the second and fourth courses. All patients received NK-1RA and dexamethasone. Patients receiving the palonosetron regimen were administered 0.75 mg palonosetron on day 1, and patients receiving the granisetron regimen were administered 3 mg granisetron twice daily on days 1 through 5. All 24 patients in this study received at least 4 chemotherapy courses. A total of 96 courses of antiemetic therapy were evaluated. Overall, the complete response CR rate (no emetic episodes and no rescue medication use) was 34%, while the total control rate (a CR plus no nausea) was 7%. No significant differences were observed between single-shot palonosetron and consecutive-day granisetron. Antiemetic therapy with a 3-drug combination was not sufficient to control chemotherapy-induced nausea and vomiting (CINV) during chemotherapy with multiple HER agents for bone and soft tissue sarcoma. This study also demonstrated that consecutive-day granisetron was not inferior to single-shot palonosetron for treating CINV.

Topics: Adolescent; Adult; Aged; Antiemetics; Antineoplastic Agents; Aprepitant; Bone Neoplasms; Cross-Over Studies; Dexamethasone; Drug Administration Schedule; Drug Therapy, Combination; Female; Granisetron; Humans; Isoquinolines; Male; Middle Aged; Morpholines; Nausea; Neurokinin-1 Receptor Antagonists; Palonosetron; Quinuclidines; Sarcoma; Serotonin 5-HT3 Receptor Antagonists; Treatment Outcome; Vomiting; Young Adult

Chemotherapy-induced nausea and vomiting (CINV) is a serious complication of treatments of hematological malignancies. Although aprepitant, an NK1 receptor antagonist, has been shown to control CINV in highly emetogenic therapies for solid tumors, the antiemetic effect of this agent in hematological chemotherapies is not well established. In this randomized controlled trial, we examined the additional effect of aprepitant in combination with conventional 5HT3 blocker-based prophylaxis for CINV in highly or moderately emetic chemotherapies for hematological malignancies (n = 41). The complete response rate, defined as no emetic episodes and no salvage treatments, was significantly higher in the aprepitant arm than the control arm (82 versus 47 %, p = 0.026), with no increase in severe adverse effects. However, the difference of nausea, measured with visual analog scale, and of oral intake impairment was moderate, which suggests insufficiency of blocking NK receptor for these events. Furthermore, sub-group analysis revealed that merit of aprepitant addition depends on treatment regimens. Our results indicate the overall advantage of applying aprepitant in the control of CINV in hematological malignancies and the need for further refinement of anti-CINV strategies, including stratification according to regimen.

Topics: Adult; Aged; Antiemetics; Antineoplastic Agents; Aprepitant; Female; Hematologic Neoplasms; Humans; Male; Middle Aged; Morpholines; Nausea; Neurokinin-1 Receptor Antagonists; Vomiting

Background. Aprepitant is a P/neurokinin-1 receptor antagonist approved for the prevention of CINV in moderate emetic risk chemotherapy. We explored its effectiveness in patients with leukemia receiving cytarabine-based chemotherapy. Methods. Patients were randomized to ondansetron (OND) 8 mg IV 30 minutes before cytarabine followed by 24 mg IV continuous infusion daily until 6-12 hours after the last dose of chemotherapy alone or with aprepitant (APREP) oral 125 mg 6-12 hrs before chemotherapy and 80 mg daily until 1 day after the last dose of chemotherapy. Results. Forty-nine patients were enrolled in each arm; 42 in OND and 41 in OND + APREP arm were evaluable for efficacy. The ORR with OND + APREP was 80% compared to 67% with OND alone (P = 0.11). On days 6 and 7, higher proportion of patients treated with OND + APREP were free from nausea (74%, 74% versus 68%, 67%; P = 0.27 and 0.18, resp.). Requirement of rescue medications on days 2 and 3 was fewer in OND + APREP arm 7% and 5% compared to 21% and 16% in the OND arm, respectively (P = 0.06 and P = 0.07). Conclusions. There was a trend for overall improvement in emesis with ondansetron plus aprepitant. The potential benefit of this approach with specific chemotherapy combinations remains to be determined.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Cytarabine; Dose-Response Relationship, Drug; Female; Hematologic Neoplasms; Humans; Male; Middle Aged; Morpholines; Nausea; Ondansetron; Treatment Outcome; Vomiting

Chemotherapy-induced nausea/vomiting (CINV) is a major problem for patients treated with high-dose chemotherapy (HDCT) conditioning before stem cell transplantation (SCT), both during chemotherapy and afterwards (delayed nausea/vomiting). The standard of care (5-HT3 antagonist and dexamethasone) appears to be ineffective against delayed nausea and vomiting. The objective of this study was to compare standard antiemetic treatment with standard treatment plus prolonged treatment with aprepitant (Emend®) until 7 days after the end of chemotherapy in patients treated with HDCT before autologous SCT. Ninety-six patients were randomized to the experiment (EXP) group receiving Emend in addition to standard antiemetics or to the control (CTR) group receiving placebo. Emend or placebo treatment started 1 h before the first HDCT dose for SCT and ended 7 days after HDCT. Thirty-eight patients in the EXP group experienced complete response (no vomiting) compared to 16 patients in the CTR group. There was a significant difference between the EXP (0.63 ± 2.71) and the CTR (3.72 ± 4.91) group during 10 days after the end of HDCT (p = 0.001) with regard to the number of vomiting episodes. No difference with regard to days of nausea or in the use of antiemetic rescue was noted between the groups. We conclude that standard antiemetic treatment can be improved by addition of aprepitant continued for 7 days after the end of chemotherapy.

Topics: Adult; Aged; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Dexamethasone; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Lymphoma; Male; Middle Aged; Morpholines; Multiple Myeloma; Nausea; Serotonin 5-HT3 Receptor Antagonists; Stem Cell Transplantation; Treatment Outcome; Vomiting

The aim of our study was to evaluate the efficacy and safety of a three-drug antiemetic prophylaxis in a single-center series treated with anthracyclines and cyclophosphamide-based regimen for BC. We collected data from 92 consecutive patients treated with routine antiemetic prophylaxis consisted of aprepitant (oral 125 mg, on day 1; oral 80 mg, on days 2 and 3), a 5-HT3 receptor antagonist (palonosetron iv 0.25 mg, on day 1), and dexamethasone (iv 12 mg, on day 1). Acute and delayed phases were defined as the first 24 h and days 2-5 after treatment, respectively. Therapy outcomes were defined as complete response (CR), in case of no vomiting, no rescue treatment; complete protection (CP), in case of no vomiting, no rescue treatment, no significant nausea; and total control (TC), in case of no vomiting, no rescue treatment, no nausea. Overall, 89.1 and 81.5% of patients showed CR in acute and delayed phase, respectively; 67.4 and 62% showed CP in acute and delayed phase, respectively; and 52.2 and 48.9% of patients showed TC in acute and delayed phase, respectively. 4.3% complained an episode of emesis during the first 24 h from treatment, while in delayed phase, only 2.2% of patients had vomiting. Our analysis confirmed that a three-drug prophylaxis is safe, effective, and consequently highly recommended in patients who undergo anthracyclines and cyclophosphamide-based regimens, though still not classified as highly emetogenic chemotherapy by all the international guidelines.

Topics: Adult; Aged; Anthracyclines; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Breast Neoplasms; Chemotherapy, Adjuvant; Cyclophosphamide; Dexamethasone; Female; Humans; Isoquinolines; Middle Aged; Morpholines; Nausea; Palonosetron; Quinuclidines; Treatment Outcome; Vomiting

A combination of aprepitant, a 5-HT3 receptor antagonist (r.a.), and dexamethasone is recommended for the prophylaxis of cisplatin-induced nausea and vomiting in the acute phase, and aprepitant + dexamethasone (A + D) in the delayed phase. The aim of this study was to verify if A + D is superior to metoclopramide plus dexamethasone (M + D) in preventing delayed emesis in cancer patients receiving the same prophylaxis for acute emesis.. A randomized double-blind study comparing A + D versus M + D was completed in previously untreated cancer patients. Before chemotherapy, all patients were treated with intravenous palonosetron 0.25 mg and dexamethasone 12 mg, and oral aprepitant 125 mg. On day 2-4, patients randomly received oral dexamethasone 8 mg plus aprepitant 80 mg once daily (days 2-3) or metoclopramide 20 mg four times daily plus dexamethasone 8 mg bid. Primary endpoint was rate of complete response (no vomiting, no rescue treatment) in day 2-5 after chemotherapy.. Due to difficulty in the accrual of patients, 303 of the 480 planned patients were enrolled, 284 were fully evaluable, 147 receiving A + D, 137 M + D. Day 1 results were similar in both arms. On day 2-5, complete response rate was not significantly different (80.3% with A + D versus 82.5% with M + D, P < 0.38, respectively), and all secondary endpoints were also similar (complete protection, total control, no vomiting, no nausea, and score of Functional Living Index-Emesis; P < 0.24). Adverse events incidence was not significantly different between the two treatments.. In cancer patients submitted to cisplatin-based chemotherapy, receiving the same antiemetic prophylaxis for acute emesis, A + D is not superior to M + D in preventing delayed emesis, and both treatments present similar toxicity.. NCT00869310.

Topics: Activities of Daily Living; Administration, Intravenous; Administration, Oral; Adolescent; Adult; Aged; Antiemetics; Antineoplastic Agents; Aprepitant; Cisplatin; Dexamethasone; Double-Blind Method; Drug Administration Schedule; Drug Combinations; Female; Humans; Isoquinolines; Italy; Male; Metoclopramide; Middle Aged; Morpholines; Nausea; Palonosetron; Quality of Life; Quinuclidines; Risk Factors; Time Factors; Treatment Outcome; Vomiting; Young Adult

Oral aprepitant, a neurokinin-1 receptor antagonist, is recommended in combination with other anti-emetic agents for the prevention of nausea and vomiting associated with moderately or highly emetogenic chemotherapy in adults, but its efficacy and safety in paediatric patients are unknown. We did this phase 3 trial to examine the safety and efficacy of such treatment in children.. In this final analysis of a phase 3, randomised, multicentre, double-blind study, patients aged 6 months to 17 years with a documented malignancy who were scheduled to receive either moderately or highly emetogenic chemotherapy were randomly assigned with an interactive voice response system to an age-based and weight-based blinded regimen of aprepitant (125 mg for ages 12-17 years; 3·0 mg/kg up to 125 mg for ages 6 months to <12 years) plus ondansetron on day 1, followed by aprepitant (80 mg for ages 12-17 years; 2·0 mg/kg up to 80 mg for ages 6 months to <12 years) on days 2 and 3, or placebo plus ondansetron on day 1 followed by placebo on days 2 and 3; addition of dexamethasone was allowed. Randomisation was stratified according to patient age, planned use of chemotherapy associated with very high risk of emetogenicity, and planned use of dexamethasone as an anti-emetic. Ondansetron was dosed per the product label for paediatric use or local standard of care. The primary efficacy endpoint was the proportion of patients who achieved complete response (defined as no vomiting, no retching, and no use of rescue medication) during the 25-120 h (delayed phase) after initiation of emetogenic chemotherapy. Efficacy and safety analyses were done with all randomly assigned patients who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, number NCT01362530.. Between Sept 22, 2011, and Aug 16, 2013, 307 patients were randomly assigned at 49 sites in 24 countries to either the aprepitant group (155 patients) or to the control group (152 patients). Three patients in the aprepitant group and two in the control group did not receive study medication, and thus were excluded from analyses. 77 (51%) of 152 patients in the aprepitant group and 39 (26%) of 150 in the control group achieved a complete response in the delayed phase (p<0·0001). The most common grade 3-4 adverse events were febrile neutropenia (23 [15%] of 152 in the aprepitant group vs 21 [14%] of 150 in the control group), anaemia (14 [9%] vs 26 [17%]), and decreased neutrophil count (11 [7%] vs 17 [11%]). The most common serious adverse event was febrile neutropenia (23 [15%] patients in the aprepitant group vs 22 [15%] in the control group).. Addition of aprepitant to ondansetron with or without dexamethasone is effective for the prevention of chemotherapy-induced nausea and vomiting in paediatric patients being treated with moderately or highly emetogenic chemotherapy.. Merck & Co., Inc.

Topics: Adolescent; Adult; Aprepitant; Child; Child, Preschool; Dexamethasone; Double-Blind Method; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Induction Chemotherapy; Infant; Male; Morpholines; Nausea; Neoplasms; Vomiting

Aprepitant, a neurokinin-1 receptor antagonist, in combination with 5 HT-3 antagonist and dexamethasone is recommended in adults receiving moderately and highly emetogenic chemotherapy to reduce chemotherapy-induced vomiting (CIV). Data for use of aprepitant in children is limited and hence aprepitant is not recommended by Pediatric Oncology Group of Ontario guidelines for prevention of CIV in children <12 years.. A randomized, double-blind, placebo-controlled trial was conducted at a single center in chemotherapy naïve children (5-18 years) receiving highly emetogenic chemotherapy. All patients received intravenous ondansetron (0.15 mg/kg) and dexamethasone (0.15 mg/kg) prior to chemotherapy followed by oral ondansetron and dexamethasone. Patients randomly assigned to aprepitant arm received oral aprepitant (15-40 kg = days 1-3, 80 mg; 41-65 kg = day 1, 125 mg and days 2-3, 80 mg) 1 h before chemotherapy. Control group received placebo as add-on therapy. Primary outcome measure was the incidence of acute moderate to severe vomiting, which was defined as more than two vomiting episodes within 24 h after the administration of the first chemotherapy dose until 24 h after the last chemotherapy dose in the block. Complete response (CR) was defined as absence of vomiting and retching during the specified phase.. Of the 96 randomized patients, three were excluded from analysis; 93 patients were analyzed (50 in aprepitant arm and 43 in placebo arm). Acute moderate and severe vomiting was reported in 72 % patients receiving placebo and 38 % patients receiving aprepitant (p = 0.001). Complete response rates during acute phase were significantly higher in aprepitant arm (48 vs. 12 %, p < 0.001). No major adverse effects were reported by patients/guardians.. This double-blind, randomized, placebo-controlled trial shows that aprepitant significantly decreases the incidence of CIV during acute phase when used as an add-on drug with ondansetron and dexamethasone in children receiving highly emetogenic chemotherapy.

Topics: Administration, Intravenous; Adolescent; Anti-Inflammatory Agents; Antiemetics; Aprepitant; Child; Child, Preschool; Dexamethasone; Double-Blind Method; Female; Humans; Induction Chemotherapy; Male; Morpholines; Nausea; Neoplasms; Neurokinin-1 Receptor Antagonists; Ondansetron; Ontario; Remission Induction; Serotonin 5-HT3 Receptor Antagonists; Vomiting

The oral neurokinin-1 antagonist aprepitant is recommended in several guidelines for preventing chemotherapy-induced nausea & vomiting (CINV) due to highly emetogenic cancer chemotherapy. Little is known about the feasibility and safety of aprepitant in patients treated with oxaliplatin.. In this multicentre, open label, randomised, phase 3 trial, we recruited patients with colorectal cancer who underwent an oxaliplatin-based chemotherapy. Patients were centrally randomised in a 1:1 ratio to the control group (5-HT3-receptor antagonist+dexamethasone) or aprepitant group (5-HT3-receptor antagonist+dexamethasone+aprepitant or fosaprepitant) in the first course. All patients were treated with aprepitant/fosaprepitant therapy in the second course. The primary end-point was the proportion of patients with no emesis.. A total of 413 patients entered this clinical trial from 25 centres in Japan. Significantly more patients in the aprepitant group achieved no vomiting overall and delayed phase than those in the control group (95.7% versus 83.6%, and 95.7% versus 84.7%, respectively). The aprepitant group also had statistically significantly higher percentages of no significant nausea, complete response and complete protection than the control group overall. In the control group, the percentages of no vomiting were higher in the second cycle than in the first cycle. The incidence of vomiting occurred day 7 or later was significantly higher in the control group compared with the aprepitant group. Other adverse events were not significant between the groups.. The aprepitant therapy was more effective than the control therapy for prevention of CINV in colorectal cancer patients receiving an oxaliplatin-based regimen.

Topics: Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Capecitabine; Colorectal Neoplasms; Deoxycytidine; Drug Therapy, Combination; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Morpholines; Nausea; Organoplatinum Compounds; Oxaliplatin; Oxaloacetates; Vomiting

To assess, in a prospective, observational study, the safety and efficacy of the addition of the neurokinin-1-receptor antagonist (NK1-RA) aprepitant to concomitant radiochemotherapy, for the prophylaxis of radiation therapy-induced nausea and vomiting.. This prospective observational study compared the antiemetic efficacy of an NK1-RA (aprepitant), a 5-hydroxytryptamine-RA, and dexamethasone (aprepitant regimen) versus a 5-hydroxytryptamine-RA and dexamethasone (control regimen) in patients receiving concomitant radiochemotherapy with cisplatin at the Department of Radiation Oncology, University Hospital Halle (Saale), Germany. The primary endpoint was complete response in the overall phase, defined as no vomiting and no use of rescue therapy in this period.. Fifty-nine patients treated with concomitant radiochemotherapy with cisplatin were included in this study. Thirty-one patients received the aprepitant regimen and 29 the control regimen. The overall complete response rates for cycles 1 and 2 were 75.9% and 64.5% for the aprepitant group and 60.7% and 54.2% for the control group, respectively. Although a 15.2% absolute difference was reached in cycle 1, a statistical significance was not detected (P=.22). Furthermore maximum nausea was 1.58 ± 1.91 in the control group and 0.73 ± 1.79 in the aprepitant group (P=.084); for the head-and-neck subset, 2.23 ± 2.13 in the control group and 0.64 ± 1.77 in the aprepitant group, respectively (P=.03).. This is the first study of an NK1-RA-containing antiemetic prophylaxis regimen in patients receiving concomitant radiochemotherapy. Although the primary endpoint was not obtained, the absolute difference of 10% in efficacy was reached, which is defined as clinically meaningful for patients by international guidelines groups. Randomized phase 3 studies are necessary to further define the potential role of an NK1-RA in this setting.

Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Chemoradiotherapy; Cisplatin; Dexamethasone; Drug Therapy, Combination; Esophageal Neoplasms; Female; Head and Neck Neoplasms; Humans; Indoles; Lung Neoplasms; Male; Middle Aged; Morpholines; Nausea; Neurokinin-1 Receptor Antagonists; Ondansetron; Prospective Studies; Serotonin Antagonists; Tropisetron; Uterine Cervical Neoplasms; Vomiting

This study aimed to evaluate the efficacy of aprepitant, a neurokinin (NK)1 receptor antagonist, on chemotherapy-induced nausea and vomiting (CINV).. A randomized, open-labeled, parallel-design study was undertaken in gynecologic-cancer (GC) patients at the Fukuoka University Hospital. Twenty-three patients were divided into without (group A) or with aprepitant (Group B) in the first cycle of paclitaxel and carboplatin (TC) therapy. From the second cycle onwards, all patients used aprepitant. Statistical significance was assessed using McNemar and Chi-square tests.. In the first cycle, the prevalence of a complete response, no episodes of nausea or food intake in group B was significantly increased compared to group A. No significant difference in the prevalence of a complete response or food intake situation was found from the second cycle onwards.. Combination of aprepitant with standard anti-emetic therapy may contribute to prevention of CINV in TC therapy for GC patients.

Topics: Adult; Antiemetics; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Carboplatin; Female; Genital Neoplasms, Female; Humans; Middle Aged; Morpholines; Nausea; Neurokinin-1 Receptor Antagonists; Paclitaxel; Treatment Outcome; Vomiting

There is no research regarding the appropriate antiemetic agents for female patients, especially those receiving moderately emetogenic chemotherapy (MEC). We evaluated the antiemetic efficacy of a combination of 5-HT₃ receptor with/without aprepitant in patients with gynecological cancer treated with the TC (paclitaxel and carboplatin) regimen of MEC.. We enrolled 38 patients diagnosed with gynecologic cancer and scheduled to receive the TC regimen. The patients were randomly assigned to receive a 5-HT₃ receptor antagonist, either palonosetron in the first cycle followed by granisetron in the second cycle or vice versa. In the third cycle, all patients received a combination of the 5-HT₃ receptor and dexamethasone with/without aprepitant.. When three drugs were administered, palonosetron consistently produced an equivalent complete response (CR) rate to granisetron in the acute phase (89.5% vs. 86.8%, p=0.87) and delayed phase (60.5% vs. 65.8%, p=0.79). With regard to the change in dietary intake, palonosetron exhibited similar efficacy to granisetron in the acute phase (92.1% vs. 89.4%, p=0.19) and delayed phase (65.7% vs. 68.4%, p=0.14). However, in the delayed phase, the addition of aprepitant therapy with a 5-HT₃ receptor antagonist and dexamethasone produced a higher CR rate than a 5-HT₃ receptor antagonist with dexamethasone (93.3% vs. 47.8%, p<0.001) and allowed the patients to maintain a higher level of dietary intake (93.3% vs. 56.5%, p<0.001).. The addition of aprepitant therapy was more effective than the control therapy of a 5-HT₃ receptor antagonist, and dexamethasone in gynecological cancer patients treated with the TC regimen.

Topics: Adult; Aged; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Carboplatin; Cross-Over Studies; Diet; Drug Administration Schedule; Female; Genital Neoplasms, Female; Granisetron; Humans; Isoquinolines; Middle Aged; Morpholines; Nausea; Paclitaxel; Palonosetron; Quinuclidines; Serotonin 5-HT3 Receptor Antagonists; Vomiting

Topics: Antiemetics; Aprepitant; Chemoradiotherapy; Female; Humans; Morpholines; Nausea; Pilot Projects; Prospective Studies; Uterine Cervical Neoplasms; Vomiting

A combination of serotonin receptor (5-hydroxytryptamine receptor type 3) antagonists, NK-1 receptor antagonist, and steroid improves the complete response (CR) of chemotherapy-induced nausea and vomiting (CINV) in cancer patients. Ramosetron's efficacy in this triple combination regimen has not been investigated. This prospective, multicenter, single-blind, randomized, phase III study compares a combination of ramosetron, aprepitant, and dexamethasone (RAD) with a combination of ondansetron, aprepitant, and dexamethasone (OAD) to prove the noninferiority of RAD in controlling highly emetogenic CINV.. Aprepitant and dexamethasone were orally administered for both arms. Ramosetron and ondansetron were intravenously given to the RAD and OAD groups. The primary endpoint was no vomiting and retching and no need for rescue medication during the acute period (day 1); the noninferiority margin was -15%.. A total of 299 modified intention-to-treat cancer patients who received RAD (144 patients) and OAD (155 patients) were eligible for the efficacy analysis. The CR rates of RAD versus OAD were 97.2% versus 93.6% during the acute period, 77.8% versus 73.6% during the delayed period (day 2-5), and 77.1% versus 71.6% during the overall period. Furthermore, RAD was noninferior to OAD in subgroups stratified by age, cancer type, chemotherapeutic agents, and schedule. Repeated measures analysis showed that in male patients, RAD was superior to OAD. Profiles of adverse events were similar in both groups.. RAD is as effective and tolerable as OAD for CINV prevention in patients receiving highly emetogenic chemotherapy. Ramosetron could be considered one of the best partners for aprepitant.

Topics: Aged; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Benzimidazoles; Dexamethasone; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Morpholines; Nausea; Neoplasms; Ondansetron; Prospective Studies; Single-Blind Method; Treatment Outcome; Vomiting

Aprepitant, an oral neurokinin-1 receptor antagonist, has demonstrated improved control of chemotherapy-induced nausea and vomiting (CINV) in previous studies. This is the first phase III study to evaluate the efficacy and tolerability of aprepitant in patients receiving highly emetogenic chemotherapy (HEC) in Asian countries.. This multicenter, double-blind, placebo-controlled trial assessed the prevention of CINV during the acute phase (AP), delayed phase (DP), and overall phase (OP). Patients receiving HEC were randomized to either an aprepitant group (day 1, aprepitant 125 mg; days 2-3, aprepitant 80 mg) or a standard therapy group (days 1-3, placebo). Both groups received intravenous granisetron and oral dexamethasone. The primary end point was complete response (CR; no emesis and no use of rescue therapy) during the OP.. Of the 421 randomized patients, 411 (98%) were assessable for efficacy; 69.6% (142/204) and 57.0% (118/207) of patients reported CR during the OP in the aprepitant and standard therapy groups, respectively (P = 0.007). CR rates in the aprepitant group were higher during the DP (74.0% vs. 59.4%, P = 0.001) but were similar during the AP (79.4% vs. 79.3%, P = 0.942). Toxicity and adverse events were comparable in both groups.. The addition of aprepitant to standard antiemetic treatment regimens for Chinese patients undergoing HEC provided superior CINV prevention and was well tolerated.

Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Asian People; Cisplatin; Double-Blind Method; Female; Humans; Male; Middle Aged; Morpholines; Nausea; Vomiting

A combination of aprepitant, a 5-HT3 receptor antagonist, and dexamethasone is recommended for the prophylaxis of acute or delayed emesis induced by chemotherapy containing anthracyclines plus cyclophosphamide in patients with breast cancer. The aim of this study was to verify whether dexamethasone is superior to aprepitant in preventing delayed emesis in patients receiving the same prophylaxis for acute emesis.. A randomized double-blind study comparing aprepitant versus dexamethasone was completed in chemotherapy-naive patients with breast cancer treated with anthracyclines plus cyclophosphamide. Before chemotherapy, all patients were treated with intravenous palonosetron 0.25 mg, dexamethasone 8 mg, and oral aprepitant 125 mg. On days 2 and 3, patients randomly received oral dexamethasone 4 mg twice per day or aprepitant 80 mg once per day. Primary end point was rate of complete response (ie, no vomiting or rescue treatment) from days 2 to 5 after chemotherapy.. Of 580 enrolled patients, 551 were evaluable: 273 received dexamethasone, and 278 received aprepitant. Day 1 complete response rates were similar: 87.6% for dexamethasone and 84.9% for aprepitant (P < .39). From days 2 to 5, complete response rates were the same with both antiemetic prophylaxes (79.5%; P < 1.00), as were results of secondary end points (ie, complete protection, total control, no vomiting, no nausea, score of Functional Living Index-Emesis; P < .24). Incidences of insomnia (2.9% v 0.4%; P < .02) and heartburn (8.1% v 3.6%; P < .03) were significantly greater with dexamethasone on days 2 to 5.. In patients with breast cancer treated with anthracycline plus cyclophosphamide chemotherapy and receiving the same antiemetic prophylaxis for acute emesis, dexamethasone was not superior to aprepitant but instead had similar efficacy and toxicity in preventing delayed emesis.

Topics: Adult; Aged; Aged, 80 and over; Anthracyclines; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Breast Neoplasms; Cyclophosphamide; Dexamethasone; Double-Blind Method; Drug Administration Schedule; Female; Heartburn; Humans; Male; Middle Aged; Morpholines; Nausea; Sleep Initiation and Maintenance Disorders; Time Factors; Treatment Outcome; Vomiting

Women with ovarian carcinoma that are treated with paclitaxel/carboplatin are particularly susceptible to chemotherapy-induced nausea and vomiting (CINV). The current study evaluated the new combination (aprepitant/ramosetron/dexamethasone, 20 mg) in ovarian cancer patients receiving multiple cycles of paclitaxel/carboplatin.. This is a prospective non-randomized single site study. Patients received the following regimen for the prevention of CINV-day 1, 125 mg aprepitant, 0.6 mg ramosetron, and 20 mg dexamethasone before chemotherapy; and days 2-3, 80 mg aprepitant each day. The primary end point was the proportion of patients with complete response (CR) during the 120 h following the first chemotherapy cycle. Toxicity assessments were conducted using the NCI-CTC investigator guide (version 3.0).. Of the 89 patients enrolled, 85 patients were evaluable for efficacy and toxicity, and 68 (80 %) completed all 6 cycles. In cycle 1, the percentage of patients who achieved CR in the acute, delayed, and overall phases was 98.8 %, 89.4 %, and 89.4 %, respectively. Of the 460 cycles, adverse events, drug-related adverse events, and serious adverse events occurred in 179 (38.9 %), 35 (7.6 %), and 10 cycles (2.2 %), respectively. The most common adverse event was constipation (12.4 %) and headache (11.1 %). None of the patients discontinued the study because of adverse events.. The combination of aprepitant, ramosetron, and high-dose dexamethasone demonstrated efficacy for CINV prevention in ovarian cancer patients receiving paclitaxel and carboplatin.

Topics: Adult; Aged; Aged, 80 and over; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Benzimidazoles; Carboplatin; Dexamethasone; Fallopian Tube Neoplasms; Female; Humans; Middle Aged; Morpholines; Nausea; Ovarian Neoplasms; Paclitaxel; Prospective Studies; Vomiting; Young Adult

Pediatric patients between the ages of 12 months and 17 years with a confirmed malignancy who were scheduled to receive aprepitant as part of triple therapy antiemetic prophylaxis for a cycle of moderately- or highly emetogenic chemotherapy were eligible for enrollment. Patients were evaluated for the incidence of nausea, episodes of emesis, interference with activities of daily living (ADLs), and appetite through utilization of a patient survey. Eleven patients were enrolled for a total of 20 patient encounters, mean age 9.55 ± 4.85 (range, 12 months-17 years). Aprepitant was well-tolerated and complete response (CR) rate was 38.9%.

Topics: Adolescent; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Body Weight; Child; Child, Preschool; Dexamethasone; Drug Therapy, Combination; Female; Humans; Incidence; Infant; Male; Morpholines; Nausea; Neoplasms; Ondansetron; Prospective Studies; Remission Induction; Severity of Illness Index; Treatment Outcome; Vomiting

This study aimed to determine the antiemetic efficacy and safety of a combination of palonosetron, aprepitant, and dexamethasone in patients with testicular germ cell tumor (TGCT) receiving 5-day cisplatin-based combination chemotherapy.. An open-label, single-arm, multicenter study was performed in patients with TGCT who were scheduled to receive 5-day cisplatin-based combination chemotherapy. The antiemetic therapy consisted of palonosetron 0.75 mg on day 1, aprepitant 125 mg on day 1 and 80 mg on days 2 to 5, and dexamethasone 9.9 mg on day 1 and 6.6 mg on days 2 to 8. The primary endpoint was complete response (CR) rate, which was defined as no vomiting and no rescue medication, in the overall period (0 to 216 h) in the first chemotherapy course. Incidence and severity of nausea were assessed based on the Common Terminology Criteria for Adverse Events (CTCAE) and a subjective rating scale completed by patients.. Thirty patients were included in the analysis. CR was achieved in 90.0% of the patients in the first chemotherapy course, and high CR rates were also observed in the second and third courses (82.1 and 78.3%, respectively). The incidence of nausea peaked on days 4 to 6 in about 50% of the patients. The reported adverse drug reactions were hiccups (13.3%), anorexia (3.3%), and stomach pain (3.3%). None of these were unexpected and none were grade 3 or 4.. The combination antiemetic therapy examined in this study was highly effective and well-tolerated in patients with TGCT receiving 5-day cisplatin-based combination chemotherapy.

Topics: Adult; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Cisplatin; Dexamethasone; Female; Humans; Isoquinolines; Male; Morpholines; Nausea; Neoplasms, Germ Cell and Embryonal; Palonosetron; Quinuclidines; Testicular Neoplasms; Vomiting

Chemotherapy-induced nausea and vomiting (CINV) is an unanswered problem in cancer therapy. We evaluated the efficacy and safety of triple antiemetic therapy with aprepitant, a 5-hydroxytryptamine-3 (5-HT(3)) receptor antagonist, and dexamethasone in patients with advanced non-small-cell lung cancer (NSCLC) who received carboplatin-based first-line chemotherapy.. Chemotherapy-naïve patients with NSCLC were enrolled in this randomized phase-II study. Patients were randomized to standard antiemetic therapy with a 5-HT(3) receptor antagonist and dexamethasone, and aprepitant add-on triple antiemetic therapy. The primary endpoint was the complete response rate (no vomiting and no rescue therapy) during the 120 h post-chemotherapy.. A total of 134 patients were assigned randomly to the aprepitant group or the control group. The aprepitant group and the control group showed an overall complete response rate of 80.3% (95% confidence interval (CI), 69.2-88.1%) and 67.2% (95% CI, 55.3-77.2%; odds ratio (OR), 0.50; 95% CI, 0.22-1.10; p = 0.085), respectively. Among patients taking carboplatin and pemetrexed, adding aprepitant significantly improved the complete response rate in the overall phase (83.8% in the aprepitant group and 56.8% in the control group; OR, 0.26; 95% CI, 0.08-0.70; p < 0.01) and the delayed phase (86.5% in the aprepitant group and 59.1% in the control group; OR, 0.23; 95% CI, 0.07-0.65; p < 0.01).. Carboplatin-based chemotherapy has considerable emetic potential. Triple antiemetic therapy with aprepitant, a 5-HT(3) receptor antagonist, and dexamethasone improved the control of CINV prevention in patients receiving carboplatin and pemetrexed chemotherapy.

Topics: Adult; Aged; Aged, 80 and over; Antiemetics; Antineoplastic Agents; Aprepitant; Carboplatin; Carcinoma, Non-Small-Cell Lung; Dexamethasone; Drug Therapy, Combination; Female; Glutamates; Guanine; Humans; Lung Neoplasms; Male; Middle Aged; Morpholines; Nausea; Pemetrexed; Serotonin; Vomiting

We investigated whether aprepitant, a neurokinin-1 antagonist, could decrease chemotherapy-induced nausea and vomiting (CINV) following cisplatin, when a conventional anti-emetic regimen had failed.. This was a prospective study (April 2011-April 2012) of patients with lung cancer, treated with cisplatin at the Beijing Cancer Hospital, and initially receiving granisetron, dexamethasone, and metoclopramide as anti-emetics. If patients experienced vomiting of grade ≥2 and required rescue anti-emetic medications during the first cycle, oral aprepitant was added in subsequent cycles (day 1: 125 mg; days 2-3: 80 mg once daily). Acute (day 1) and delayed (days 2-5) nausea and vomiting, use of rescue medications, and occurrence of adverse reactions were monitored after the start of chemotherapy.. Twenty-five of 132 patients (18.9 %) were administered aprepitant for secondary prophylaxis against emesis during the second cycle of chemotherapy. The incidences of acute and delayed nausea were 52 and 100 % in the first cycle, but 8 and 72 % in the second cycle. The incidences of acute and delayed vomiting were 20 and 100 % in the first cycle, but 0 and 36 % in the second cycle. No patients required rescue medications or intravenous rehydration during the second cycle. Aprepitant was not associated with additional adverse events.. In patients with lung cancer receiving cisplatin-based chemotherapy, the addition of aprepitant to a 5-HT3 antagonist, dexamethasone, and metoclopramide improves protection against CINV when the conventional anti-emetic regimen fails.

Topics: Adult; Aged; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Cisplatin; Female; Humans; Lung Neoplasms; Male; Middle Aged; Morpholines; Nausea; Prospective Studies; Treatment Outcome

Prevention of chemotherapy-induced nausea and vomiting (CINV) is crucial for maintaining the quality of life of cancer patients. Female patients have been underrepresented in previous clinical studies of aprepitant or palonosetron. We performed a prospective multicenter study to investigate the efficacy and safety of triple therapy comprising these two agents and dexamethasone in female cancer patients receiving chemotherapy that included cisplatin (≥ 50 mg/m(2)).. Aprepitant was administered at a dose of 125 mg before chemotherapy on day 1 and at 80 mg on days 2 and 3. Palonosetron (0.75 mg) was given before chemotherapy on day 1. Dexamethasone was administered at a dose of 9.9 mg before chemotherapy on day 1 and at 6.6 mg on days 2-4. The primary endpoint was the the proportion of patients with a complete response (CR no vomiting and no use of rescue medication) throughout the overall period (0-120 h post-chemotherapy).. Ninety-six women (median age 55 years) were enrolled. The overall CR rate was 54.2 %. CR was obtained during the acute phase (0-24 h post-chemotherapy) and the delayed phase (24-120 h post-chemotherapy) in 87.5 and 56.3 % of the patients, respectively. The most common adverse reactions were constipation and fatigue (reported by three patients each).. Exhibition of a favorable overall CR rate over existing two-drug combinations suggests that the triple therapy regimen used in the present study is effective and tolerable in patients with gynecological malignancies receiving cisplatin-based chemotherapy. Female patients may have a higher risk of developing CINV.

Topics: Adult; Aged; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Cisplatin; Dexamethasone; Drug Therapy, Combination; Female; Genital Neoplasms, Female; Humans; Isoquinolines; Middle Aged; Morpholines; Nausea; Neoplasms; Palonosetron; Prospective Studies; Quality of Life; Quinuclidines; Vomiting

The aim of this study is to evaluate the efficacy of aprepitant as part of the antiemetic regimen for high-dose melphalan conditioning in multiple myeloma patients.. This is a prospective, single-arm study.. The study was conducted at an Academic Medical Facility.. Twenty-six patients receiving high-dose melphalan with autologous stem cell support were included in this study.. Eligible patients were >18 years with a diagnosis of MM undergoing high-dose melphalan followed by autologous peripheral blood stem cell transplantation (PBSCT). All patients had serum aminotransferases and total bilirubin less than 2× upper limit of normal. Treatment consisted of aprepitant 125 mg orally on day 1, followed by 80 mg orally 24 and 48 h after the initial dose; ondansetron 16 mg orally day 1; dexamethasone 12 mg orally day 1, and 8 mg orally days 2-4 with breakthrough medications as needed.. Patients were evaluated for the frequency of emetic episodes, the need for breakthrough antiemetic medication, and the mean nausea score in 24-h increments beginning 24 h after chemotherapy and continuing until 120 h. Nausea score was determined using a linear analog scale (0-10). Complete response (CR) was defined as no more than one (1) emetic episode during the evaluation period. A total of 26 patients (17 male, 9 female) were enrolled in the study. Of these, 25 (96 %) were complete responders and 24 (92 %) had no documented emetic episodes during the study period. One patient (4 %) had 1 emetic episode and one patient (4 %) had 2 emetic episodes. Some degree of nausea was reported by 23/26 patients, and the mean nausea score for the entire group over the study period was 0.7 (range 0-10).. Addition of aprepitant to standard antiemetics resulted in low rates of delayed nausea/vomiting associated with high-dose melphalan and PBSCT, and has now become standard practice in this patient population at our institution.

Topics: Antiemetics; Aprepitant; Female; Humans; Male; Melphalan; Middle Aged; Morpholines; Multiple Myeloma; Nausea; Peripheral Blood Stem Cell Transplantation; Prospective Studies; Transplantation Conditioning; Vomiting

To determine the variability in treatment responses to antiemetic therapy (ondansetron and dexamethasone vs ondansetron and dexamethasone plus aprepitant) given with moderately emetogenic chemotherapy.. Post hoc subgroup analysis of data from a phase III, randomized, double-blind clinical trial evaluated whether the efficacy of aprepitant triple therapy (ondansetron and dexamethasone plus aprepitant) versus control (ondansetron and dexamethasone) varies by gender, age, or region in 848 men and women ≥18 years old with histologically confirmed malignancies and who were naïve to moderately or highly emetogenic chemotherapeutic agents. Endpoints compared were the incidences of no vomiting, complete response, and no use of rescue therapy, all during the overall period (0-120 h).. Regardless of age, gender, or region, the aprepitant regimen provided better control for the no-vomiting and complete-response (no vomiting, no rescue therapy) endpoints.. The aprepitant regimen provided better control for the no-vomiting and complete-response (no vomiting, no rescue therapy) endpoints. Overall response rates were higher in men and in older (≥55 y) patients, but treatment differences were greater among women and younger patients, known to be at increased chemotherapy-induced nausea and vomiting (CINV) risk. Aprepitant showed a benefit versus control across regions, although the between-treatment difference appeared to be smaller for patients in Central/South America versus North America or international regions.. Although we acknowledge that subset numbers in this post hoc analysis may be too small to allow definitive conclusions, the data suggest that aprepitant triple therapy provides a benefit over control therapy for the prevention of CINV in patients receiving anthracycline and cyclophosphamide (AC)- or non-AC-based moderately emetogenic chemotherapy across age, gender, and region. (Original trial results available at ClinicalTrials.gov: NCT00337727.).

Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Antiemetics; Antineoplastic Agents; Aprepitant; Dexamethasone; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Morpholines; Nausea; Ondansetron; Prospective Studies; Sex Factors; Treatment Outcome; Vomiting; Young Adult

The optimal regimen to prevent chemotherapy-induced nausea and vomiting (CINV) for patients undergoing high-dose chemotherapy and autologous stem-cell transplantation (ASCT) is unclear. To evaluate the effect of aprepitant in addition to a standard regimen, we conducted this randomized, placebo-controlled phase III trial.. Patients with multiple myeloma were randomly assigned at a one-to-one ratio to receive either aprepitant (125 mg orally on day 1 and 80 mg orally on days 2 to 4), granisetron (2 mg orally on days 1 to 4), and dexamethasone (4 mg orally on day 1 and 2 mg orally on days 2 to 3) or matching placebo, granisetron (2 mg orally on days 1 to 4), and dexamethasone (8 mg orally on day 1 and 4 mg orally on days 2 to 3). Melphalan 100 mg/m(2) was administered intravenously on days 1 to 2. ASCT was performed on day 4. The primary end point (complete response) was defined as no emesis and no rescue therapy within 120 hours of melphalan administration. Quality of life was assessed by modified Functional Living Index-Emesis (FLIE) questionnaire on days -1 and 6.. Overall, 362 patients were available for the efficacy analysis (181 in each treatment arm). Significantly more patients receiving aprepitant reached the primary end point (58% v 41%; odds ratio [OR], 1.92; 95% CI, 1.23 to 3.00; P = .0042). Absence of major nausea (94% v 88%; OR, 2.37; 95% CI, 1.09 to 5.15; P = .026) and emesis (78% v 65%; OR, 1.99; 95% CI, 1.25 to 3.18; P = .0036) within 120 hours was increased by aprepitant. Mean total FLIE score (± standard deviation) was 114 ± 18 for aprepitant and 106 ± 26 for placebo (P < .001).. The addition of aprepitant resulted in significantly less CINV and had a positive effect on quality of life.

Topics: Aprepitant; Dexamethasone; Double-Blind Method; Granisetron; Hematopoietic Stem Cell Transplantation; Humans; Melphalan; Morpholines; Multiple Myeloma; Nausea; Prospective Studies; Quality of Life; Transplantation, Autologous; Vomiting

Chemotherapy-induced nausea and vomiting (CINV) are some of the most problematic symptoms for cancer patients. Triplet therapy consisting of a 5HT3 receptor antagonist, aprepitant, and dexamethasone is a guideline-recommended antiemetic prophylaxis for highly emetogenic chemotherapy (HEC). The efficacy and safety of triplet therapy using a 0.75-mg dose of palonosetron have not yet been investigated. We performed a prospective phase II study using triplet antiemetic therapy with 0.75 mg of palonosetron.. Chemotherapy-naïve lung cancer patients scheduled to receive HEC were enrolled. The eligible patients were pretreated with antiemetic therapy consisting of the intravenous administration of 0.75 mg of palonosetron, and 9.9 mg of dexamethasone and the oral administration of 125 mg of aprepitant on day 1, followed by the oral administration of 80 mg of aprepitant on days 2-3 and the oral administration of 8 mg of dexamethasone on days 2-4. The primary endpoint was the complete response rate (the CR rate; no vomiting and no rescue medication) during the overall phase (0-120 h).. The efficacy analysis was performed in 63 patients. The CR rates during the overall, acute and delayed phases were 81.0, 96.8, and 81.0%, respectively. The no nausea and no significant nausea rate during the overall phase were 54.0 and 66.7%, respectively. The most common adverse event was grade 1 or 2 constipation.. Triplet antiemetic therapy using a 0.75-mg dose of palonosetron shows a promising antiemetic effect in preventing CINV in lung cancer patients receiving HEC.

Topics: Adult; Aged; Antiemetics; Antineoplastic Agents; Aprepitant; Cisplatin; Dexamethasone; Drug Therapy, Combination; Female; Humans; Isoquinolines; Lung Neoplasms; Male; Middle Aged; Morpholines; Nausea; Palonosetron; Prospective Studies; Quinuclidines; Serotonin 5-HT3 Receptor Antagonists; Serotonin Antagonists; Treatment Outcome; Vomiting

Nausea and vomiting are among the most feared complications of chemotherapy reported by patients. The objective of this study was to establish the overall complete response (CR; no emesis or use of rescue medication 0-120 h after chemotherapy) with either ondansetron- or palonosetron-containing antiemetic regimens in patients receiving highly emetogenic chemotherapy (HEC).. This was a prospective, open-label, randomized, single-center, pilot study that enrolled patients receiving their first cycle of HEC. Patients were randomized to receive either palonosetron 0.25 mg IV (PAD) or ondansetron 24 mg orally (OAD) on day 1 prior to HEC. All patients received oral aprepitant 125 mg on day 1, then 80 mg on days 2 and 3, and oral dexamethasone 12 mg on day 1, then 8 mg on days 2, 3, and 4. Descriptive statistics were used to summarize the data.. A total of 40 patients were enrolled, 20 in each arm. All patients were female, and 39 received doxorubicin/cyclophosphamide chemotherapy for breast cancer. For the primary endpoint, 65 % (95 % CI, 40.8-84.6 %) of patients in the PAD arm and 40 % (95 % CI, 19.1-63.9 %) of patients in the OAD arm achieved an overall CR.. While CR rates for aprepitant and dexamethasone plus palonosetron or ondansetron-containing regimens have been published previously, this is the first documentation of CR rates with these regimens in the same patient population. These results may be used to design a larger, adequately powered, prospective study comparing these regimens.

Topics: Adult; Aged; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Breast Neoplasms; Cyclophosphamide; Dexamethasone; Doxorubicin; Female; Humans; Isoquinolines; Middle Aged; Morpholines; Nausea; Ondansetron; Palonosetron; Pilot Projects; Prospective Studies; Quinuclidines; Vomiting

Topics: Aged; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Benztropine; Camptothecin; Dexamethasone; Drug Combinations; Female; Fluorouracil; Haloperidol; Humans; Leucovorin; Male; Metoclopramide; Morpholines; Nausea; Organoplatinum Compounds; Pancreatic Neoplasms; Vomiting

Chemotherapy-induced nausea and vomiting remain among the most feared adverse effects for cancer patients.. The aim of this study was to evaluate the efficacy and safety of a combination of aprepitant, palonosetron and dexamethasone as antiemetic prophylaxis in patients receiving multiple-day cisplatin-based chemotherapy.. Forty-one solid cancer patients received aprepitant, palonosetron and dexamethasone during a 3-day cisplatin-based chemotherapy. Primary end-point was complete response in the overall phase (day 1 until 5 days after the end of chemotherapy).. Aprepitant in combination with palonosetron and dexamethasone was safe, with hiccups (31.7%), fatigue (17.1%), headache (14.6%) and constipation (12.2%) the most common treatment-related adverse events, mostly mild. Complete response was seen in 58.5% of patients in the overall phase. In 23 patients receiving aprepitant in combination with palonosetron and dexamethasone more than one cycle (range: 2-5 cycles), the cumulative emetic protection rate after five cycles was 0.82.. This study shows aprepitant in combination with palonosetron and dexamethasone is safe and effectively controls chemotherapy-induced nausea and vomiting in patients undergoing 3-day cisplatin-based chemotherapy, moreover, the efficacy is maintained during multiple cycles.

Topics: Adult; Aged; Antiemetics; Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Cisplatin; Constipation; Dexamethasone; Drug Administration Schedule; Drug Therapy, Combination; Fatigue; Female; Headache; Hiccup; Humans; Isoquinolines; Male; Middle Aged; Morpholines; Nausea; Neoplasms; Neurokinin-1 Receptor Antagonists; Palonosetron; Prospective Studies; Quinuclidines; Serotonin 5-HT3 Receptor Antagonists; Vomiting; Young Adult

We evaluated the efficacy and safety of single-dose fosaprepitant in combination with intravenous granisetron and dexamethasone.. Patients receiving chemotherapy including cisplatin (≥70 mg/m(2)) were eligible. A total of 347 patients (21% had received cisplatin with vomiting) were enrolled in this trial to receive the fosaprepitant regimen (fosaprepitant 150 mg, intravenous, on day 1 in combination with granisetron, 40 μg/kg, intravenous, on day 1 and dexamethasone, intravenous, on days 1-3) or the control regimen (placebo plus intravenous granisetron and dexamethasone). The primary end point was the percentage of patients who had a complete response (no emesis and no rescue therapy) over the entire treatment course (0-120 h).. The percentage of patients with a complete response was significantly higher in the fosaprepitant group than in the control group (64% versus 47%, P = 0.0015). The fosaprepitant regimen was more effective than the control regimen in both the acute (0-24 h postchemotherapy) phase (94% versus 81%, P = 0.0006) and the delayed (24-120 h postchemotherapy) phase (65% versus 49%, P = 0.0025).. Single-dose fosaprepitant used in combination with granisetron and dexamethasone was well-tolerated and effective in preventing chemotherapy-induced nausea and vomiting in patients receiving highly emetogenic cancer chemotherapy, including high-dose cisplatin.

Topics: Adult; Aged; Aprepitant; Cisplatin; Dexamethasone; Double-Blind Method; Drug-Related Side Effects and Adverse Reactions; Female; Granisetron; Humans; Male; Middle Aged; Morpholines; Nausea; Neoplasms; Vomiting

The purpose of this study was to determine the efficacy of adding a 7-day aprepitant schedule to a 5HT3 receptor antagonist and dexamethasone for patients with germ cell tumors receiving first-line 5-day cisplatin-based chemotherapy.. In a single-arm, open-label, multi-center, phase 2 trial, chemo-naive patients received aprepitant 125 mg PO (per oral) on day 1 and 80 mg PO on days 2 to 7, a 5HT3 receptor antagonist on days 1 to 5, and dexamethasone 8 mg on days 1 to 8. The primary endpoint was no emesis (vomiting or dry retching) during days 1 to 7 of cycle 1.. Fifty patients were recruited. For cycle 1, proportions reporting no emesis on day 1, no emesis on days 1 to 7, no nausea on day 1, and no nausea on days 1 to 7 were 96, 82, 71, and 27%, respectively. The efficacy was maintained in all cycles with over 80% of patients reporting no emesis on any given day of any given cycle. Emesis was more common on days 4 to 7 (68% episodes) than on days 1 to 3 (32% episodes). Over any 24-h period, 49% of patients with emesis reported no more than two episodes, and 62% of patients with nausea reported intensity as 3 or less on a scale from 0 to 10. There were no unexpected or serious adverse events reported.. Adding 7 days of aprepitant to a 5HT3 receptor antagonist and dexamethasone effectively controlled acute and delayed emesis with 5-day cisplatin regimens. Days of nausea were more common than days of vomiting.

Topics: Administration, Oral; Adult; Antiemetics; Antineoplastic Agents; Aprepitant; Cisplatin; Dexamethasone; Drug Therapy, Combination; Female; Humans; Male; Mediastinal Neoplasms; Middle Aged; Morpholines; Nausea; Neoplasms, Germ Cell and Embryonal; Ovarian Neoplasms; Retroperitoneal Neoplasms; Serotonin 5-HT3 Receptor Antagonists; Testicular Neoplasms; Treatment Outcome; Vomiting; Young Adult

Olanzapine has been shown to be a safe and effective agent for the prevention of chemotherapy-induced nausea and vomiting (CINV). Olanzapine may also be an effective rescue medication for patients who develop breakthrough CINV despite having received guideline-directed CINV prophylaxis.. A double-blind, randomized phase III trial was performed for the treatment of breakthrough CINV in chemotherapy-naive patients receiving highly emetogenic chemotherapy (cisplatin, ≥ 70 mg/m2 or doxorubicin, ≥ 50 mg/m2 and cyclophosphamide, ≥ 600 mg/m2), comparing olanzapine to metoclopramide. Patients who developed breakthrough emesis or nausea despite prophylactic dexamethasone (12 mg IV), palonosetron (0.25 mg IV), and fosaprepitant (150 mg IV) pre-chemotherapy and dexamethasone (8 mg p.o. daily, days 2-4) post-chemotherapy were randomized to receive olanzapine, 10 mg orally daily for 3 days or metoclopramide, 10 mg orally TID for 3 days. Patients were monitored for emesis and nausea for 72 h after taking olanzapine or metoclopramide. Two hundred seventy-six patients (median age 62 years, range 38-79; 43% women; Eastern Cooperative Oncology Group (ECOG) PS 0,1) consented to the protocol. One hundred twelve patients developed breakthrough CINV and 108 were evaluable.. During the 72-h observation period, 39 out of 56 (70%) patients receiving olanzapine had no emesis compared to 16 out of 52 (31%) patients with no emesis for patients receiving metoclopramide (p < 0.01). Patients without nausea (0, scale 0-10, M.D. Anderson Symptom Inventory) during the 72-h observation period were those who took olanzapine, 68% (38 of 56), and metoclopramide, 23% (12 of 52) (p < 0.01). There were no grade 3 or 4 toxicities.. Olanzapine was significantly better than metoclopramide in the control of breakthrough emesis and nausea in patients receiving highly emetogenic chemotherapy.

Topics: Adult; Aged; Aged, 80 and over; Antiemetics; Antineoplastic Agents; Aprepitant; Benzodiazepines; Cisplatin; Cyclophosphamide; Dexamethasone; Double-Blind Method; Doxorubicin; Female; Humans; Isoquinolines; Male; Metoclopramide; Middle Aged; Morpholines; Nausea; Neoplasms; Olanzapine; Palonosetron; Quinuclidines; Vomiting

Aprepitant, a neurokinin antagonist, is an effective antiemetic agent in chemotherapy for delayed nausea and vomiting. The study objective was to evaluate the pharmacokinetics of aprepitant and concurrent cyclophosphamide (CY), often a component of hematopoietic stem cell transplant (HSCT) conditioning regimen, in cancer patients undergoing HSCT. Forty subjects were randomized to either aprepitant or placebo in addition to standard antiemetics. Aprepitant or placebo was started 1 hour before the first chemotherapy or radiation dose for HSCT conditioning and administered daily until 4 days after infusion of the hematopoietic cell graft (for a total of 10-12 days). Serial blood samples were collected for aprepitant and CY plus 2 important CY metabolites. The results indicate that aprepitant is well absorbed and does not auto-induce its metabolism. No significant drug interaction was observed with CY or its metabolites. A significant portion of the patients had subtherapeutic aprepitant concentrations; however, chemotherapy-induced nausea and vomiting were effectively managed. No dosage adjustment was necessary, and administration of aprepitant in HSCT at the prescribed dosage of 125 mg orally on day 1 and 80 mg orally on each consecutive day through day +4 after HSCT was well tolerated with no significant changes in CY pharmacokinetic parameters.

Topics: Adult; Antiemetics; Antineoplastic Agents, Alkylating; Aprepitant; Cyclophosphamide; Double-Blind Method; Drug Interactions; Female; Hematopoietic Stem Cell Transplantation; Humans; Male; Middle Aged; Morpholines; Nausea; Neoplasms; Vomiting; Young Adult

This study evaluated the efficacy and tolerability of aprepitant, dexamethasone, and palonosetron in the prevention of nausea and vomiting in breast cancer patients receiving their initial cycle of doxorubicin and cyclophosphamide (AC).. Patients with breast cancer, ≥ age 18, with a performance status of ≤ 2, receiving doxorubicin (≥ 60 mg/m(2)) and cyclophosphamide (≥ 500 mg/m(2)) for the first time were eligible. Prior to chemotherapy patients received aprepitant 125 mg orally (PO), dexamethasone 8-10 mg PO/intravenously (IV), and palonosetron 0.25 mg IV. On days 2-3, dexamethasone 4 mg PO and aprepitant 80 mg PO were given. Outcomes were recorded in patient diaries for the 120-h study period following chemotherapy. Primary endpoint was the proportion of patients achieving complete response (no emesis or rescue) for the 120-h study period.. Thirty-six patients were enrolled and all are evaluable. The median age was 53 (33-75) and 36 are females. Eighteen patients (50%) achieved a complete response during the 120-h study period. Acute (≤ 24 h) and delayed (24-120 h) complete response rates were 81% (27/36) and 61% (22/36), respectively. No emesis rates for the acute, delayed, and overall study periods were 97% (35/36), 94% (34/36), and 92% (33/36), respectively. Treatment was well tolerated.. The combination of aprepitant, dexamethasone, and palonosetron prevented emesis in more than 90% of breast cancer patients receiving their initial cycle of AC chemotherapy. Nausea was less well controlled. Overall complete response was achieved in one half of the study patients. Further improvement in the prevention of AC-induced chemotherapy-induced nausea and vomiting will require more effective antinausea treatments.

Topics: Adult; Aged; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Breast Neoplasms; Cyclophosphamide; Dexamethasone; Doxorubicin; Female; Humans; Isoquinolines; Middle Aged; Morpholines; Nausea; Palonosetron; Pilot Projects; Quinuclidines; Vomiting

This is a phase II trial evaluating efficacy and safety of aprepitant (AP) in combination with 5-HT3 antagonist and adjusted dose dexamethasone in patients receiving high-dose cyclophosphamide (CY) and filgrastim for stem cell mobilization. We used Simon's optimal two-stage design constrained to fewer than 40 patients with 10% type I error and 85% statistical power. The first stage of the study required accrual of 18 response-evaluable patients. The primary endpoint was the control of vomiting without the use of any rescue anti-emetics at 24 h after the administration of high dose CY (4 g/m(2)). If emesis was controlled in ≥9 patients, an additional cohort of 17 patients would be enrolled. The null hypothesis would be rejected if there were ≥20 responses among 35 patients. Forty patients were enrolled, five of whom were not evaluable for response. Eighteen evaluable patients were enrolled in the first stage. Acute emesis was controlled in 10 patients; therefore, enrollment proceeded to stage 2. An additional 17 patients were enrolled; 20/35 response-evaluable patients (57%) did not develop acute vomiting or require rescue anti-emetics, thus achieving the goal of the study. A total of 22/35 response-evaluable patients (63%) met the secondary endpoint of delayed emesis control (days 2-5). Thirty-three out of 35 patients underwent successful stem cell mobilization. No ≥ grade 3 AP-related adverse events were noted. The AP regimen can effectively control acute and delayed emesis in the majority patients receiving high-dose CY.

Topics: Adult; Antiemetics; Antineoplastic Agents; Aprepitant; Cyclophosphamide; Dexamethasone; Female; Filgrastim; Granulocyte Colony-Stimulating Factor; Humans; Male; Middle Aged; Morpholines; Nausea; Recombinant Proteins; Stem Cell Transplantation; Vomiting; Young Adult

The efficacy and safety of aprepitant(APR)were examined in cancer patients who received chemotherapy including cisplatin(CDDP)at a dose of ≥ 50mg/m2.APR was administered concomitantly with conventional antiemetic therapy to 20 patients(APR group)in a prospective study performed from May to July 2010. In addition, a retrospective study based on medical records of 20 patients(conventional therapy group)from February to April 2010 was performed.These patients received antiemetic therapy with a serotonin receptor antagonist and dexamethasone. Significantly more patients did not vomit in the 5-day study period(days 1-5).Also, severity of vomiting was significantly improved over the 5-day period and in the late phase(days 2-5)in the APR group, compared to the conventional therapy group. Loss of appetite was significantly improved over the 5-day period and the acute(day 1)and late phases, leading to increased food intake during the 5-day period and late phase. There were no adverse events with suspected involvement of APR, and the tolerability was favorable. These results suggest that APR is useful for nausea, vomiting, and appetite loss caused by CDDP, which is a highly emetic drug, and that such guideline-based antiemetic therapy might improve the quality of life of patients.

Topics: Adult; Aged; Aged, 80 and over; Antiemetics; Antineoplastic Agents; Aprepitant; Cisplatin; Feeding and Eating Disorders; Female; Humans; Male; Middle Aged; Morpholines; Nausea; Neoplasms; Retrospective Studies; Vomiting

Aprepitant, a 5-HT3 receptor antagonist (5HT3-RA), and dexamethasone are standard antiemetic therapy for prevention of single-day, cisplatin-induced nausea and vomiting. We conducted a double-blind, placebo-controlled phase III cross-over study that compared aprepitant to placebo combined with standard antiemetic prophylaxis (a 5HT3-RA and dexamethasone) in patients receiving 5 days of cisplatin combination chemotherapy for testicular cancer.. Patients receiving two consecutive identical courses of a 5-day cisplatin-based chemotherapy were randomly assigned to aprepitant 125 mg on day 3 and 80 mg per day on days 4 through 7 or to placebo with the initial course and crossover to the opposite treatment with the second course. The primary objective was complete response (CR). Secondary end points were emetic episodes (acute and delayed), nausea measurement based on a visual analog scale (VAS), and patient-stated preference after the second study cycle.. In all, 71 patients were screened for the study and 69 were evaluable. Thirty-five patients were randomly assigned to receive aprepitant and 34 to receive placebo for the first course. Forty-two percent achieved CR with aprepitant compared with 13% with placebo (P < .001). Eleven patients (16.2%) had at least one emetic episode during the aprepitant cycle versus 32 patients (47.1%) with placebo. Thirty-eight patients preferred the aprepitant cycle whereas 11 preferred placebo (P < .001). There was no statistical difference in VAS for nausea, but it was numerically superior with aprepitant. There was no toxicity with aprepitant compared with placebo.. There was a significant improvement in CR rate with aprepitant combined with a 5HT3-RA and dexamethasone. Patient preference strongly favored the aprepitant cycle.

Topics: Administration, Oral; Adolescent; Adult; Aged; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Cisplatin; Cross-Over Studies; Dexamethasone; Double-Blind Method; Drug Therapy, Combination; Humans; Male; Middle Aged; Morpholines; Nausea; Neoplasms, Germ Cell and Embryonal; Serotonin 5-HT3 Receptor Antagonists; Treatment Outcome; Vomiting

We conducted a double-blind randomized clinical trial of the following four regimens for controlling delayed nausea (DN): group 1: palonosetron + dexamethasone on day 1 with prochlorperazine on days 2 and 3; group 2: granisetron + dexamethasone on day 1 with prochlorperazine on days 2 and 3; group 3: aprepitant + palonosetron + dexamethasone on day 1 with aprepitant + dexamethasone on days 2 and 3; and group 4: palonosetron + dexamethasone on day 1 with prochlorperazine + dexamethasone on days 2 and 3.. Chemotherapy-naive patients received doxorubicin, epirubicin, cisplatin, carboplatin, or oxaliplatin. The primary end point was average nausea assessed four times daily on days 2 and 3. Primary analyses were whether nausea control would be improved by using palonosetron versus granisetron on day 1 (group 1 v group 2); by adding dexamethasone on days 2 and 3 (group 1 v group 4); and by using aprepitant versus prochlorperazine (group 3 v group 4). Statistical significance was set at P = .017.. Two hundred thirty-four, 234, 241, and 235 evaluable patients were accrued to groups 1, 2, 3, and 4, respectively. Adjusted mean differences for the three planned analyses were as follows: palonosetron versus granisetron: -0.01 (95% CI, -0.23 to 0.20; P = .72); adding dexamethasone on days 2 and 3: 0.20 (95% CI, -0.02 to 0.41; P = .01); and using aprepitant versus prochlorperazine: -0.03 (95% CI, -0.24 to 0.19; P = .56).. The addition of dexamethasone on days 2 and 3 reduced DN. Palonosetron and granisetron have similar effects on DN. The beneficial effect of adding aprepitant for control of DN was the same as adding prochlorperazine.

Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Dexamethasone; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Granisetron; Humans; Intention to Treat Analysis; Isoquinolines; Male; Middle Aged; Morpholines; Nausea; Neurokinin-1 Receptor Antagonists; Palonosetron; Prochlorperazine; Quinuclidines; Serotonin Antagonists

Dinaciclib, a selective inhibitor of cyclin-dependent kinase (CDK) 1, CDK2, CDK5, and CDK9, is metabolized via CYP3A4. Aprepitant, a neurokinin-1 receptor antagonist for the prevention of chemotherapy-induced nausea and vomiting, is an inhibitor and inducer of CYP3A4. We conducted a randomized, crossover study to investigate the effects of single oral doses of aprepitant when coadministered with dinaciclib.. As part of a phase 1 dose-escalation trial, subjects with advanced malignancies were randomized into a 2-period, multi-cycle, crossover study to investigate the effect of single doses of oral aprepitant on the pharmacokinetics of 29.6 mg/m(2) dinaciclib administered by 2-h intravenous infusion. During cycle 1 and cycle 2, subjects received dinaciclib with aprepitant in one cycle and dinaciclib without aprepitant in the other cycle; aprepitant was administered at a dose of 125 mg orally on day 1 and 80 mg orally on days 2 and 3, along with standard dosing regimens of ondansetron and dexamethasone.. Twelve patients completed the study; T (max) occurred approximately 2 h after the initiation of the infusion. The percent geometric mean ratio (dinaciclib + aprepitant vs. dinaciclib alone) was 106 % (90 % confidence interval [CI] 89-126 %) and 111 % (90 % CI 93-132 %) for dinaciclib C(max) and AUC([I]), respectively. The half-life and clearance of dinaciclib were similar, with or without aprepitant.. Coadministration of dinaciclib with aprepitant resulted in no clinically significant effect on the pharmacokinetics and did not alter the safety profile of dinaciclib in patients with advanced malignancies.

Topics: Administration, Oral; Adult; Aged; Analysis of Variance; Antiemetics; Antineoplastic Agents; Aprepitant; Area Under Curve; Bridged Bicyclo Compounds, Heterocyclic; Cross-Over Studies; Cyclic N-Oxides; Cyclin-Dependent Kinases; Dexamethasone; Drug Administration Schedule; Female; Half-Life; Humans; Indolizines; Infusions, Intravenous; Linear Models; Male; Middle Aged; Morpholines; Nausea; Neoplasms; Ondansetron; Pyridinium Compounds; Treatment Failure; Vomiting

A number of prognostic factors have been identified as risk factors for chemotherapy-induced emesis. This post-hoc analysis addressed whether: (1) these prognostic factors can identify a low-risk group for whom ondansetron plus dexamethasone alone provide a high level of protection (≥80% no emesis); (2) the NK1 receptor antagonist aprepitant improves antiemetic outcome regardless of emetic risk.. Breast cancer patients in a phase III double-blind, placebo-controlled trial were randomized to antiemetic regimens including ondansetron and dexamethasone, or aprepitant, ondansetron, and dexamethasone. Multivariate logistic regression models were used to assess the impact on emesis (but not nausea) of the regimen with aprepitant, and previously reported risk factors, including age (<55 and ≥55 years), ethanol use (0-4 or ≥5 drinks/week), history of pregnancy-related morning sickness, and history of motion sickness, using a modified intent-to-treat approach.. Treatment with aprepitant (P < 0.0001), older age (P = 0.006), ethanol use (P = 0.0048), and no history of morning sickness (P = 0.0007) were all significantly associated with reduced likelihood of emesis. The proportion of patients with one, two, or three risk factors who remained emesis free was significantly higher with the aprepitant-containing regimen than with the active control (70.2-82.8% vs. 38.6-66.4%, respectively).. Aprepitant markedly improved control of emesis in patients with one or more risk factors. This analysis did not support using risk factors for modifying the antiemetic approach. A low-risk group with zero risk factors for whom aprepitant provided little benefit was of questionable clinical utility, since they comprised less than 3% of patients.

Topics: Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Breast Neoplasms; Breast Neoplasms, Male; Cyclophosphamide; Dexamethasone; Double-Blind Method; Doxorubicin; Drug Therapy, Combination; Female; Humans; Logistic Models; Male; Middle Aged; Morpholines; Multivariate Analysis; Nausea; Neurokinin-1 Receptor Antagonists; Ondansetron; Prognosis; Risk Factors; Vomiting

Cisplatin-based highly emetogenic chemotherapy (HEC) displays a biphasic pattern of emesis with both an early and delayed period. In contrast, moderately emetogenic chemotherapy (MEC) has a monophasic pattern. The objective of this analysis was to further investigate the impact of the NK1-receptor antagonist aprepitant on these patterns.. Three phase III HEC (patients scheduled to receive cisplatin-based chemotherapy) and one phase III MEC (breast cancer patients scheduled to receive anthracycline plus cyclophosphamide (AC)) trials of aprepitant were included. In all studies, patients were randomized in a 1:1 ratio to an aprepitant regimen (aprepitant plus ondansetron plus dexamethasone) or the standard regimen (ondansetron plus dexamethasone). The exact dosing regimen for ondansetron and dexamethasone was different in each study. In a post hoc analysis, multivariate logistic regression models were used to assess the impact on first emesis at different time intervals after chemotherapy.. One thousand five hundred twenty-seven patients and 856 patients were randomized and assessed for efficacy in the HEC and MEC trials, respectively. For HEC, aprepitant reduced the risk of first emesis by 38-77% vs. standard regimen, beginning 15-18 h after cisplatin and extending to 60 h. For MEC, aprepitant reduced the risk of first emesis by 38-61% vs. active control, beginning 3 h after AC and for up to 12 h.. Time of onset and duration of enhanced control of emesis with the addition of aprepitant differed between HEC and MEC. This suggests that the pattern of NK1-sensitive mechanisms may vary for different chemotherapy regimens.

Topics: Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Cisplatin; Dexamethasone; Double-Blind Method; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Logistic Models; Male; Middle Aged; Morpholines; Multivariate Analysis; Nausea; Neoplasms; Neurokinin-1 Receptor Antagonists; Ondansetron; Serotonin 5-HT3 Receptor Antagonists; Time Factors; Vomiting

Complete protection from nausea/vomiting is currently achieved in a minority of patients receiving high-dose chemotherapy (HDC). Currently the use of 5-HT3-antagonists and dexamethasone (DEX) represents the standard of care. The role of the NK-1-antagonist aprepitant in HDC remains to be better defined. A total of 64 patients undergoing multiple days of HDC received granisetron, DEX plus aprepitant during chemotherapy. After the end of chemotherapy aprepitant plus DEX was given for a further 2 days. Primary end point was CR defined as no vomiting and no use of rescue medication in the overall phase (day 1 until 5 days after end of chemotherapy). Acute/delayed and overall CR were achieved in 83%/70% and 63%, respectively. Acute and delayed nausea were observed in 20 and 38% of the patients. The tolerability of the aprepitant regimen over 4-5 days was comparable with the 3-day antiemetic regimen. In our study, aprepitant demonstrated good tolerability. Taking into account the methodological constraints of comparing our results with those from the available literature, the addition of aprepitant to the antiemetic treatment regimen may provide improved prevention of chemotherapy-induced nausea and vomiting during HDC.

Topics: Adult; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Carboplatin; Drug Combinations; Drug-Related Side Effects and Adverse Reactions; Etoposide; Female; Granisetron; Humans; Ifosfamide; Male; Melphalan; Middle Aged; Morpholines; Nausea; Neurokinin-1 Receptor Antagonists; Paclitaxel; Treatment Outcome; Vomiting; Young Adult

This study was conducted to determine the pharmacokinetics of aprepitant and dexamethasone as well as the relationship between the plasma concentration of substance P and nausea/vomiting in Japanese cancer patients.. After administration of aprepitant (125/80 mg group [10 patients]: 125 mg on day 1 and 80 mg on days 2-5; 40/25 mg group [10 patients]: 40 mg on day 1 and 25 mg on days 2-5) and dexamethasone (6 mg on day 1 and 4 mg on days 2 and 3 in the 125/80 mg group, and 8 mg on day 1 and 6 mg on days 2 and 3 in the 40/25 mg group) to Japanese cancer patients receiving at least moderately emetogenic antitumor agents, the plasma concentrations of aprepitant, dexamethasone, and substance P were measured.. All of 20 patients were treated with the highly emetogenic agent cisplatin (≥70 mg/m(2)). The C(max) and AUC(0-24 h) of aprepitant in Japanese cancer patients were similar with those in non-Japanese patients. The clearance of dexamethasone in the 125/80 mg group was approximately one-half of that previously determined in the absence of aprepitant. The substance P concentration in plasma significantly increased only in patients with delayed nausea/vomiting.. This study demonstrated similar plasma pharmacokinetics of aprepitant in Japanese and non-Japanese, the validity of reducing dexamethasone dose, and the existence of increased plasma substance P concentration in patients receiving highly emetogenic cisplatin-based chemotherapy.

Topics: Adult; Aged; Anti-Inflammatory Agents; Antiemetics; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Area Under Curve; Carcinoma, Non-Small-Cell Lung; Dexamethasone; Drug Therapy, Combination; Female; Granisetron; Humans; Immunoenzyme Techniques; Japan; Lung Neoplasms; Male; Mesothelioma; Middle Aged; Morpholines; Nausea; Small Cell Lung Carcinoma; Substance P; Vomiting; Young Adult

Addition of aprepitant, a neurokinin-1 receptor antagonist (NK1RA), to an ondansetron and dexamethasone regimen improves prevention of chemotherapy-induced nausea/vomiting (CINV), particularly during the delayed phase (DP; 25 to 120 hours). Therefore, recommended antiemetic regimens include multiple-day NK1RA administration. Preliminary data suggested that single-dose aprepitant before chemotherapy could provide CINV protection throughout the overall risk phase (OP; 0 to 120 hours). This study compared a 3-day oral aprepitant schedule to a regimen containing a single dose of the intravenous NK1RA fosaprepitant.. A randomized, double-blind, active-control design was used to test whether fosaprepitant is noninferior to aprepitant. Patients receiving cisplatin ≥ 70 mg/m(2) for the first time received ondansetron and dexamethasone with a standard aprepitant regimen (125 mg on day 1, 80 mg on day 2, 80 mg on day 3) or a single-dose fosaprepitant regimen (150 mg on day 1). The primary end point was complete response (CR; no vomiting, no rescue medication) during OP. Secondary end points were CR during DP and no vomiting during OP. Accrual of 1,113 evaluable patients per treatment arm was planned to confirm noninferiority with expected CR of 67.7% and noninferiority margin of minus 7 percentage points.. A total of 2,322 patients were randomly assigned, and 2,247 were evaluable for efficacy. Antiemetic protection with aprepitant and fosaprepitant was equivalent within predefined bounds for noninferiority. Both regimens were well tolerated, although more frequent infusion site pain/erythema/thrombophlebitis was seen with fosaprepitant relative to aprepitant (2.7% v 0.3%, respectively).. Given with ondansetron and dexamethasone, single-dose intravenous fosaprepitant (150 mg) was noninferior to standard 3-day oral aprepitant in preventing CINV during OP and DP.

Topics: Adult; Aged; Aged, 80 and over; Antiemetics; Antineoplastic Agents; Aprepitant; Cisplatin; Dexamethasone; Double-Blind Method; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Morpholines; Nausea; Ondansetron; Treatment Outcome; Vomiting

A standard therapeutic regimen of a 5-HT₃ receptor antagonist antiemetic agent+dexamethasone was administered as antiemetic therapy for 29 patients who received chemotherapy for colorectal cancer in the Department of Surgery at Gunma Saiseikai Maebashi Hospital, from January to March 2010. For 13 patients with delayed nausea, the therapy was changed to an aprepitant regimen (aprepitant+5-HT₃ receptor antagonist antiemetic agent+dexamethasone)to evaluate the preventive effect of aprepitant on acute and delayed nausea and vomiting. This aprepitant regimen produced a significant improvement in the primary endpoint, based on a complete response (CR) of no vomiting and no rescue treatment throughout the administration period, and in the secondary endpoint of CR in the delayed phase, with no delayed nausea. In addition, a tendency for improvement was found in other secondary endpoints: complete protection (CP) based on no vomiting, no rescue treatment, and no significant nausea throughout the observation period; no vomiting; and no significant nausea. These findings suggest that using aprepitant as an antiemetic therapy during chemotherapy for colorectal cancer may be effective for patients with nausea and vomiting that are intractable to standard therapeutic regimens.

Topics: Administration, Oral; Aged; Antineoplastic Agents; Aprepitant; Colorectal Neoplasms; Female; Humans; Male; Morpholines; Nausea; Neurokinin-1 Receptor Antagonists; Vomiting

We performed a clinical study of a triple-drug combination to evaluate its efficacy to prevent both acute and delayed emesis after high-dose chemotherapy with BEAM (BCNU [carmustine]+etoposide+ARA-C [cytarabine]+melphalan) before hematopoietic stem cell transplantation (HSCT) by comparison with a historical control group of patients treated with dexamethasone (dex) and ondansetron or palonosetron.. We evaluated 96 patients non-Hodgkin's lymphomas (n=54), and Hodgkin's disease (n=42). Evaluated patients received: aprepitant+palonosetron and dex. The observation period started with the initiation of chemotherapy (0 hours) and continued for 24 hours after the completion of the chemotherapy for the acute phase, and during 5 days after finishing chemotherapy for the delayed phase. The response rate to study drugs was evaluated using a four-grade scale based on the degree of control of nausea and vomiting: high, modrate, slightly effective, or not effective.. Patients treated with the three-drug combination showed a significantly higher response rate than those receiving palonosetron or ondasetron (+dex) during the both the acute and the delayed phases: highly effective early+late phases, 82% versus 70% versus 35%; highly effective early phase, 94% versus 70% versus 35%; highly effective late phase, 85% versus 85% versus 50%; highly+moderately effective early phase, 97% versus 70% versus 40%; highly+moderately effective late phase, 97% versus 90% versus 60%, for triple combination, palonosctron with dexamethasone and ondasetron+dex, respectively. All antiemetic regimens were well tolerated. The three-drug combination showed a similar safety profile; adverse events were generally mild and transient.. The triple-drug combination was more effective than ondansetron or palonosetron (+dex) treatments to prevent acute (especially) and delayed nausea and vomiting following BEAM before HSCT.

Topics: Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Carmustine; Cytarabine; Dexamethasone; Drug Therapy, Combination; Etoposide; Female; Hematopoietic Stem Cell Transplantation; Hodgkin Disease; Humans; Isoquinolines; Lymphoma, Non-Hodgkin; Male; Melphalan; Morpholines; Nausea; Ondansetron; Palonosetron; Quinuclidines; Transplantation, Autologous; Treatment Outcome; Vomiting

This study describes the efficacy of aprepitant in preventing nausea and vomiting associated with high-dose chemotherapy in hematopoietic stem cell transplant (HSCT) patients. Our hypothesis is the addition of aprepitant to 5-HT3 antagonists and dexamethasone would result in a 20% increase in complete response (CR) rates compared to CR rates from published studies evaluating antiemetic regimens without aprepitant.. Adult HSCT patients receiving high-dose chemotherapy and aprepitant as part of their antiemetic regimen were included following written informed consent. CR was defined as no emesis, none to mild nausea, and no breakthrough antiemetic use. Daily patient diaries were used on days 1 through 7 following high-dose chemotherapy to collect severity of nausea, emetic episodes, breakthrough antiemetic use, and any antiemetic related side effects.. We accrued a total of 42 patients. CR rates ranged from 42.9% to 73.8% for the 7 days. The average CR rate for days 1 through 7 was 54%. Fourteen patients (33%) maintained a complete emetic response on each of the 7 days. The average CR rate for published studies in HSCT patients receiving an antiemetic regimen without aprepitant is 57%. Most common adverse effects reported by patients receiving aprepitant were hiccups (33%) and drowsiness (33%).. The addition of aprepitant failed to meet our primary endpoint of increasing CR rates by 20%. The lower than expected CR rate was attributed to use of breakthrough antiemetics. Aprepitant did result in preventing emesis in the majority of patients and was associated with minimal side effects.

Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Dexamethasone; Drug Therapy, Combination; Female; Hematopoietic Stem Cell Transplantation; Hiccup; Humans; Male; Middle Aged; Morpholines; Nausea; Serotonin Antagonists; Severity of Illness Index; Sleep Stages; Time Factors; Treatment Outcome; Vomiting

Aprepitant was shown previously to be effective for prevention of chemotherapy-induced nausea and vomiting (CINV) with moderately emetogenic chemotherapy (MEC) in breast cancer patients receiving an anthracycline and cyclophosphamide (AC)-based regimen. This study assessed aprepitant in patients receiving a broad range of MEC regimens with a variety of tumor types.. This phase III, randomized, gender-stratified, double-blind trial enrolled patients with confirmed malignancies, naïve to MEC or highly emetogenic chemotherapy, who were scheduled to receive a single dose of at least one MEC agent. Patients received an aprepitant triple-therapy regimen (aprepitant, ondansetron, and dexamethasone) or a control regimen (ondansetron and dexamethasone) administered orally. Primary and key secondary efficacy endpoints were proportions of patients with no vomiting and complete response (no vomiting and no rescue medication), respectively, during the 120 h post-chemotherapy.. Of 848 randomized patients, 77% were female, and 52% received non-AC-based antineoplastic regimens. Significantly, more patients in the aprepitant group achieved no vomiting and complete response, regardless of whether they received AC or non-AC regimens, in the 120 h after chemotherapy. Overall, the incidences of adverse events were generally similar in the aprepitant (62.8%) and control groups (67.2%).. The aprepitant regimen provided superior efficacy in the treatment of CINV in a broad range of patients receiving MEC (non-AC or AC) in both no vomiting and complete response endpoints. Aprepitant was generally well tolerated. These results show the benefit of including aprepitant as part of the standard antiemetic regimen for cancer patients receiving MEC.

Topics: Adult; Aged; Antiemetics; Antineoplastic Agents; Aprepitant; Dexamethasone; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Morpholines; Nausea; Neoplasms; Ondansetron; Prospective Studies; Treatment Outcome; Vomiting

Certain patient and treatment characteristics are predictive of chemotherapy-induced nausea and vomiting (CINV). Objectives of this analysis were: (1) confirm the importance of several previously reported adverse risk factors for CINV in patients receiving chemotherapy, (2) assess the impact of the NK(1) receptor antagonist aprepitant according to these risk factors, and (3) assess the impact of age on antiemetic outcome.. Patients from two double-blind, placebo-controlled trials were randomized to an active-control group (ondansetron 32 mg IV, dexamethasone 20 mg PO day 1; dexamethasone 8 mg bid days 2-4) or an aprepitant group (aprepitant 125 mg PO, ondansetron 32 mg IV, dexamethasone 12 mg day 1; aprepitant 80 mg days 2-3; dexamethasone 8 mg qd days 2-4). The primary endpoint was complete response (no emesis or rescue therapy use). In a post-hoc analysis, multivariate logistic regression models were used to assess the impact of treatment with aprepitant and previously reported risk factors, using a modified intent-to-treat approach.. Treatment with aprepitant (p < 0.0001), male gender (p = 0.023), cisplatin dose <80 mg/m(2) (p = 0.001), age >or=65 years (p = 0.021), and five or more alcoholic drinks per week (p = 0.027) were all significantly associated with improved complete response. Aprepitant improved complete response regardless of risk for all factors and neutralized the risk associated with female gender.. This analysis confirmed the relevance of several previously reported risk factors for CINV in patients receiving chemotherapy. Aprepitant improved complete response regardless of risk and eliminated the increased risk of CINV associated with the female gender.

Topics: Aged; Antiemetics; Antineoplastic Agents; Aprepitant; Cisplatin; Clinical Protocols; Double-Blind Method; Female; Humans; Male; Middle Aged; Morpholines; Nausea; Predictive Value of Tests; Risk Factors; Vomiting

Aprepitant is a new neurokinin-1 (NK(1) ) receptor antagonist developed as a treatment for chemotherapy-induced nausea and vomiting (CINV). To evaluate the efficacy and safety of aprepitant used in combination with standard therapy (granisetron and dexamethasone), we conducted a multicenter, phase II, placebo-controlled, double-blind, randomized study in Japanese cancer patients who received cancer chemotherapy including cisplatin (≥70mg/m(2) ). Aprepitant was administered for 5days. A total of 453 patients were enrolled. In the three study groups, (i) standard therapy, (ii) aprepitant 40/25mg (40mg on day 1 and 25mg on days 2-5) and (iii) aprepitant 125/80mg (125mg on day 1 and 80mg on days 2-5), the percentage of patients with complete response (no emesis and no rescue therapy) was 50.3% (75/149 subjects), 66.4% (95/143 subjects) and 70.5% (103/146 subjects), respectively. This shows that efficacy was significantly higher in the aprepitant 40/25mg and 125/80mg groups than in the standard therapy group (χ(2) test [closed testing procedure]: P=0.0053 and P=0.0004, respectively) and highest in the aprepitant 125/80mg group. The delayed phase efficacy (days 2-5) was similar to the overall phase efficacy (days 1-5), indicating that aprepitant is effective in the delayed phase when standard therapy is not very effective. In terms of safety, aprepitant was generally well tolerated in Japanese cancer patients. (ClinicalTrials.gov number, NCT00212602.)

Topics: Aged; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Asian People; Cisplatin; Constipation; Dexamethasone; Double-Blind Method; Drug Administration Schedule; Female; Granisetron; Hiccup; Humans; Japan; Male; Middle Aged; Morpholines; Nausea; Neoplasms; Placebos; Treatment Outcome

The neurokinin-1 receptor antagonist aprepitant, plus a 5HT3 antagonist and corticosteroid is well-tolerated and effective in preventing chemotherapy-induced nausea and vomiting in adults but has not been formally assessed in adolescents.. Patients age 11-19 years old receiving emetogenic chemotherapy were randomized 2:1 to aprepitant triple therapy (aprepitant [A] 125 mg p.o., dexamethasone [D] 8 mg p.o., and ondansetron [O] 0.15 mg/kg i.v. t.i.d. day 1; A 80 mg, D 4 mg, and O 0.15 mg/kg t.i.d. day 2; A 80 mg and D 4 mg day 3; and D 4 mg day 4) or a control regimen (D 16 mg and O 0.15 mg/kg t.i.d. day 1; D 8 mg and O 0.15 mg/kg t.i.d. day 2; and D 8 mg days 3 and 4). The primary endpoint was the difference in drug-related adverse events during and for 14 days following treatment. Efficacy and aprepitant pharmacokinetics were assessed.. Baseline characteristics were similar between aprepitant (N = 28) and control (N = 18) groups. Febrile neutropenia was more frequent in the aprepitant group (25% vs. 11.1%). Complete response (CR) rates were 35.7% for aprepitant triple therapy versus 5.6% for the control group. Mean plasma aprepitant AUC(0-24 hr) and C(max) on day 1 and mean trough concentrations on days 2 and 3 were consistently lower compared to historical data obtained from healthy adults; however, the differences were not clinically significant.. Aprepitant triple therapy was generally well tolerated; CR were greater with aprepitant, although not statistically significant. Pharmacokinetics suggest that the adult dosing regimen is appropriate for adolescents.

Topics: Adolescent; Antineoplastic Agents; Aprepitant; Area Under Curve; Child; Dexamethasone; Double-Blind Method; Drug-Related Side Effects and Adverse Reactions; Humans; Metabolic Clearance Rate; Morpholines; Nausea; Neutropenia; Ondansetron; Placebos; Treatment Outcome; Vomiting; Young Adult

Ginger has been used to treat numerous types of nausea and vomiting. Ginger has also been studied for its efficacy for acute chemotherapy-induced nausea and vomiting (CINV). However, its efficacy for delayed CINV in a diverse oncology population is unknown.. We performed a randomized, double-blind, placebo-controlled trial in 162 patients with cancer who were receiving chemotherapy and had experienced CINV during at least one previous round of chemotherapy. All participants were receiving a 5-HT3 receptor antagonists and/or aprepitant. Participants were randomized to receive either 1.0 g ginger, 2.0 g ginger daily, or matching placebo for 3 days. The primary outcome was change in the prevalence of delayed CINV. Secondary outcomes included acute prevalence of CINV, acute and delayed severity of CINV, and assessment of blinding.. There were no differences between groups in the prevalence of delayed nausea or vomiting, prevalence of acute CINV, or severity of delayed vomiting or acute nausea and vomiting. Participants who took both ginger and aprepitant had more severe acute nausea than participants who took only aprepitant. Participants were able to accurately guess which treatment they had received. Ginger appeared well tolerated, with no difference in all adverse events (AEs) and significantly less fatigue and miscellaneous AEs in the ginger group.. Ginger provides no additional benefit for reduction of the prevalence or severity of acute or delayed CINV when given with 5-HT3 receptor antagonists and/or aprepitant.

Topics: Adult; Aged; Antiemetics; Antineoplastic Agents; Aprepitant; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Morpholines; Nausea; Prevalence; Serotonin 5-HT3 Receptor Antagonists; Serotonin Antagonists; Severity of Illness Index; Vomiting; Zingiber officinale

Chemotherapy-induced nausea and vomiting includes both Acute (0-24 h) and Delayed (24-120 h) components with different physiologic mechanisms. A combination of a serotonin antagonist, a corticosteroid, and an NK-1 antagonist has proven effective against this problem. However, standard antiemetic regimens require administration over 3-4 days after chemotherapy. The present study evaluated a more convenient single-day three-drug antiemetic regimen for patients receiving moderately emetogenic chemotherapy.. Chemotherapy-naïve patients with solid tumors receiving cyclophosphamide and/or doxorubicin were eligible. Patients could not have pre-existing etiologies for vomiting. Prior to chemotherapy, patients received a single dose of aprepitant 285 mg p.o., dexamethasone 20 mg p.o., and palonosetron 0.25 mg i.v. A daily patient diary recording episodes of emesis and severity of nausea was then kept for 5 days. Any further antiemetics were considered rescue medication.. Forty-one eligible and evaluable patients (40 women, one man) with breast cancer were entered on study. Most were receiving adjuvant chemotherapy. Complete Response (no vomiting, no rescue medication) was seen in 51% of patients, including 76% with Complete Response for the Acute period and 66% for the Delayed period. No emesis was reported for 100% of patients in the Acute period and 95% in the Delayed period. No Nausea was seen in 32% of patients. No untoward toxicities were seen.. A single-day three-drug antiemetic regimen is feasible and effective for protection against both Acute and Delayed vomiting after moderately emetogenic chemotherapy. Formal comparison to a standard multi-day antiemetic regimen is warranted.

Topics: Adult; Aged; Antiemetics; Antineoplastic Agents; Aprepitant; Breast Neoplasms; Breast Neoplasms, Male; Chemotherapy, Adjuvant; Cyclophosphamide; Dexamethasone; Doxorubicin; Drug Administration Schedule; Drug Therapy, Combination; Female; Humans; Isoquinolines; Male; Middle Aged; Morpholines; Nausea; Palonosetron; Quinuclidines; Time Factors; Vomiting

To assess the efficacy of adding aprepitant to a 5-HT(3) antagonist and dexamethasone as salvage antiemetic therapy for breast cancer patients receiving their initial cycle of an anthracycline and cyclophosphamide (AC) and failing to achieve complete control of emesis.. Eligibility: breast cancer patients receiving their first cycle of AC.. standard dose of a 5-HT(3) antagonist and dexamethasone 8-10 mg IV/PO on day 1 prior to cycle 1 of AC and dexamethasone 4 mg bid on days 2 and 3. Patients without complete control (no emesis, no nausea, or rescue antiemetics) during cycle 1 could proceed to cycle 2. During cycle 2, patients received AC and identical antiemetics (except dexamethasone 4 mg qd on days 2 and 3) plus aprepitant 125 mg PO day 1 and 80 mg PO days 2 and 3. Primary endpoint: complete control, 0-120 h after chemotherapy.. Sixty-two patients received cycle 1 of AC. Complete control cycle 1: 13 patients (21%; 95%CI, 12-33%). Of the 49 patients eligible for cycle 2, four elected not to continue on study. Of the 45 patients receiving cycle 2, 44 were evaluable. Complete control and complete response (no emesis, no rescue) for the 5-day study period improved from 0% to 18% (p = 0.14) and 7% to 36% (p = 0.02) on cycles 1 and 2, respectively.. In breast cancer patients receiving AC, the addition of aprepitant to a 5-HT(3) antagonist and dexamethasone during cycle 2 of treatment improved antiemetic outcome. Although the improvement in the primary endpoint of complete control during cycle 2 was not significant, all secondary endpoints such as complete response and no emesis rates were significantly better during cycle 2. The extent of antiemetic control during cycle 2 was numerically inferior to the results achieved in a phase III trial employing aprepitant with cycle 1 of AC chemotherapy, suggesting that the preferred approach is to include aprepitant with the initial cycle of AC chemotherapy.

Topics: Adult; Aged; Aged, 80 and over; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Breast Neoplasms; Cyclophosphamide; Dexamethasone; Dose-Response Relationship, Drug; Doxorubicin; Drug Therapy, Combination; Female; Humans; Middle Aged; Morpholines; Nausea; Prospective Studies; Salvage Therapy; Time Factors; Treatment Outcome; Vomiting

This is a single center, randomized, double-blind placebo-controlled study to evaluate the NK(1)-receptor antagonist, aprepitant, in Chinese breast cancer patients. The primary objective was to compare the efficacy of aprepitant-based antiemetic regimen and standard antiemetic regimen for the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients who received moderately emetogenic chemotherapy. The secondary objective was to compare the patient-reported quality of life in these two groups of patients.. Eligible breast cancer patients were chemotherapy-naive and treated with adjuvant AC chemotherapy (i.e. doxorubicin 60 mg/m(2) and cyclophosphamide 600 mg/m(2)). Patients were randomly assigned to either an aprepitant-based regimen (day 1, aprepitant 125 mg, ondansetron 8 mg, and dexamethasone 12 mg before chemotherapy and ondansetron 8 mg 8 h later; days 2 through 3, aprepitant 80 qd) or a control arm which consisted of standard regimen (day 1, ondansetron 8 mg and dexamethasone 20 mg before chemotherapy and ondansetron 8 mg 8 h later; days 2 through 3, ondansetron 8 mg bid). Data on nausea, vomiting, and use of rescue medication were collected with a self-report diary, patients quality of life were assessed by self-administered Functional Living Index-Emesis (FLIE).. Of 127 patients randomized, 124 were assessable. For CINV in Cycle 1 AC, there was no significant difference in the proportion of patients with reported complete response, complete protection, total control, 'no vomiting', 'no significant nausea' and 'no nausea'. The requirement of rescue medication appears to be lesser in patients treated with the aprepitant-based regimen compared to those with the standard regimen (11% vs. 20%; P = 0.06). Assessment of FLIE revealed that while there was no difference in the nausea domain and the total score between the two groups; however, patients receiving standard antiemetic regimen had significantly worse quality of life in the vomiting domain (mean score [SD] = 23.99 [30.79]) when compared with those who received the aprepitant-based regimen (mean score [SD] = 3.40 [13.18]) (P = 0.0002). Both treatments were generally well tolerated. Patients treated with the aprepitant-based regimen had a significantly lower incidence of neutropenia (53.2% vs. 35.5%, P = 0.0468), grade >or= 3 neutropenia (21.0% vs. 45.2, P = 0.0042) and delay in subsequent cycle of chemotherapy (8.1% vs. 27.4%, P = 0.0048).. The aprepitant regimen appears to reduce the requirement of rescue medication when compared with the control regimen for prevention of CINV in patients receiving both an anthracycline and cyclophosphamide, and is associated with a better quality of life during adjuvant AC chemotherapy.

Topics: Adult; Aged; Antiemetics; Antineoplastic Agents; Aprepitant; Breast Neoplasms; Carcinoma, Ductal, Breast; China; Dexamethasone; Double-Blind Method; Female; Humans; Middle Aged; Morpholines; Nausea; Ondansetron; Quality of Life; Vomiting

To develop a population pharmacokinetic model of aprepitant and dexamethasone in Japanese patients with cancer, explore the factors that affect the pharmacokinetics of aprepitant, and evaluate the effect of aprepitant on the clearance of intravenous dexamethasone.. A total of 897 aprepitant concentration measurements were obtained from 290 cancer patients and 25 healthy volunteers. For dexamethasone, a total of 847 measurements were obtained from 440 patients who were co-administered aprepitant (40, 125 mg, or placebo). Plasma concentration of aprepitant and dexamethasone were determined by liquid chromatography connected with a tandem mass spectrometer and analyzed by a population approach using NONMEM software.. The plasma concentration time course of aprepitant was described using a one-compartment model with first-order absorption and lag time. Oral clearance (CL/F) of aprepitant was changed by aprepitant dose at doses of 40 or 125 mg. Body weight was the most influential intrinsic factor to CL/F of aprepitant. Age, ALT, and BUN also had mild effects on the CL/F. Typical population estimates of CL/F, apparent distribution volume (V(d)/F), absorption constant (K(a)) and absorption lag time were 1.54 L/h, 72.1 L, 0.893/h and 0.295 h, respectively. Inter-individual variability in CL/F, V(d)/F and K(a) were 53.9, 21.0, and 141%, respectively; intra-individual variability was 27.7%. The plasma concentration time course of intravenous dexamethasone was also described using a one-compartment model. Clearance of dexamethasone was decreased 24.7 and 47.5% by co-administration of aprepitant 40 and 125 mg. All final model estimates of aprepitant and dexamethasone fell within 10% of the bootstrapped mean.. A pharmacokinetic model for aprepitant has been developed that incorporates body weight, age, ALT, BUN and aprepitant dose to predict the CL/F. The results of population pharmacokinetic analysis of dexamethasone support dose adjustment of dexamethasone in the case of co-administration with aprepitant.

Topics: Administration, Oral; Adult; Aged; Aged, 80 and over; Antiemetics; Antineoplastic Agents; Aprepitant; Biological Availability; Dexamethasone; Drug Therapy, Combination; Female; Granisetron; Humans; Infusions, Intravenous; Male; Middle Aged; Models, Biological; 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

Prevention of chemotherapy-induced nausea and vomiting (CINV) with standard antiemetics has been more difficult to achieve in female patients. Data from two phase III trials of the NK1 antagonist aprepitant were assessed for potential effect of gender on treatment response.. 1,044 patients receiving cisplatin (> or = 70 mg/m2) were randomly assigned to control regimen [ondansetron (O) 32 mg i.v. and dexamethasone (D) 20 mg p.o. on day 1; D 8 mg twice daily on days 2-4] or aprepitant (A) regimen (A 125 mg p.o. plus O 32 mg and D 12 mg on day 1; A 80 mg and D 8 mg once daily on days 2-3; and D 8 mg on day 4). The primary endpoint was overall complete response (no emesis and no rescue therapy over days 1-5). Data were analyzed by a modified intent-to-treat approach. Between-treatment comparisons for each gender were made using logistic regression.. Women comprised 42 and 43% of the aprepitant and control groups, respectively. In the control group, 41% of women had overall complete response compared with 53% of men. In the aprepitant group, 66% of women had overall complete response compared with 69% of men.. The addition of aprepitant may negate the adverse prognostic effect of female gender on the prevention of CINV in patients receiving highly emetogenic chemotherapy.

Topics: Adrenal Cortex Hormones; Antiemetics; Aprepitant; Clinical Trials, Phase III as Topic; Drug Therapy, Combination; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Male; Morpholines; Nausea; Placebos; Receptors, Serotonin, 5-HT3; Sex Factors; United States; Vomiting

The objective of this multicenter, phase II, open-label study was to evaluate the safety and efficacy of the newest 5-hydroxytryptamine3 (5-HT3) receptor antagonist, palonosetron, plus dexamethasone and aprepitant in preventing nausea and vomiting in patients receiving moderately emetogenic chemotherapy. Eligible patients received a single intravenous dose of palonosetron (0.25 mg on day 1 of chemotherapy), along with 3 daily oral doses of aprepitant (125 mg on day 1,80 mg on days 2 and 3) and dexamethasone (12 mg on day 1,8 mg on days 2 and 3). Efficacy and safety data were obtained from patient diaries and adverse event reporting. Fifty-eight patients were evaluable; 47% were women with breast cancer and 52% received cyclophosphamide-based chemotherapy. The proportion of patients with complete response (no emesis and no rescue medication) was 88% during the acute (0-24 hours) interval, 78% during the delayed (> 24-120 hours) interval, and 78% during the overall (0-120 hours post chemotherapy) interval. More than 90% of patients during all time intervals had no emetic episodes, and between 57% and 71% of patients reported no nausea during each of the 5 days post chemotherapy. Treatment was well tolerated, with no unexpected adverse events. These data demonstrate that palonosetron in combination with dexamethasone and aprepitant is safe and highly effective in preventing chemotherapy-induced nausea and vomiting in the days following administration of moderately emetogenic chemotherapy.

Topics: Adult; Aged; Aged, 80 and over; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Dexamethasone; Female; Humans; Isoquinolines; Male; Middle Aged; Morpholines; Nausea; Neoplasms; Palonosetron; Quinuclidines; Serotonin Antagonists; Vomiting

Despite prophylaxis with 5-HT(3) antagonists and dexamethasone, nausea/emesis are common chemotherapy- induced toxicities. The aim of this trial was to evaluate the efficacy of adding the NK1 antagonist aprepitant in patients refractory to standard prophylaxis.. Patients with significant nausea/vomiting despite prophylaxis with 5-HT(3) antagonists and dexamethasone were eligible. Aprepitant was added to the same antiemetic regimen used during previous cycles.. 34 patients received 92 cycles of chemotherapy with aprepitant which was applied orally at 125 mg on day 1 and 80 mg on days 2 and 3. All patients were refractory to standard antiemetic prophylaxis during cisplatin-based (n = 12) or other chemotherapy (n = 22). With the addition of aprepitant, all patients reported subjective improvement. The number of patients with nausea for >4 days decreased from 24 (71%) to 4 (12%) (p < 0.001), and the number of those with emesis for >2 days decreased from 26 (77%) to 0 (0%) (p < 0.001). In 12 patients receiving aprepitant for >2 cycles (3-8) the efficacy was maintained. No toxicity possibly related to aprepitant was observed.. Aprepitant demonstrated significant activity in patients with nausea/vomiting refractory to prophylaxis with 5-HT(3) antagonists and dexamethasone.

Topics: Administration, Topical; Adult; Aged; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Dexamethasone; Female; Humans; Male; Middle Aged; Morpholines; Nausea; Neoplasms; Salvage Therapy; Serotonin 5-HT3 Receptor Antagonists; Serotonin Antagonists; Treatment Outcome; Vomiting

Aprepitant is a selective neurokinin-1 receptor antagonist that is effective for the prevention of nausea and vomiting caused by highly emetogenic chemotherapy. In vitro, aprepitant is a moderate inhibitor of the CYP3A4 enzyme, which is involved in the clearance of several chemotherapeutic agents. In this study we examined the potential for aprepitant to affect the pharmacokinetics and toxicity of intravenously administered docetaxel, a chemotherapeutic agent that is primarily metabolized by CYP3A4.. A total of 11 cancer patients (4 male, 7 female, aged 50-68 years) were enrolled in this multicenter, randomized, open-label, two-period, crossover study. Patients received a single infusion of docetaxel monotherapy, 60-100 mg/m(2), on two occasions at least 3 weeks apart. During one of the cycles (treatment A), patients received docetaxel alone. During the alternate cycle (treatment B), they also received aprepitant 125 mg orally 1 h prior to docetaxel infusion (day 1), and a single oral dose of aprepitant 80 mg on days 2 and 3. The pharmacokinetic profile of docetaxel was assessed over 30 h following docetaxel infusion. Blood counts were monitored on days 1, 4, 7, and 14.. Ten patients completed the study. Concomitant administration of aprepitant did not cause any statistically or clinically significant changes in docetaxel pharmacokinetics. Values for docetaxel alone (treatment A) versus docetaxel with aprepitant (treatment B) were as follows: geometric mean AUC(0-last) was 3.26 vs 3.17 microg h/ml (P>0.25; ratio B/A 0.97); geometric mean AUC(0-infinity) 3.51 vs 3.39 microg h/ml (P>0.25; ratio B/A 0.96); geometric mean C(max) was 3.53 vs 3.37 microg/ml (P>0.25; ratio B/A 0.95); and geometric mean plasma clearance was 23.3 vs 24.2 l/h/m(2) (P>0.25; ratio B/A 1.04). The corresponding harmonic mean half-life values were 10.1 and 8.5 h. The two treatment regimens had similar tolerability profiles; the median absolute neutrophil count nadirs were 681/mm(3) during treatment with docetaxel alone and 975/mm(3) during aprepitant coadministration.. Aprepitant had no clinically significant effect on either the pharmacokinetics or toxicity of standard doses of docetaxel in cancer patients. Aprepitant at clinically recommended doses may have a low potential to affect the pharmacokinetics of intravenous chemotherapeutic agents metabolized by CYP3A4.

Topics: Administration, Oral; Aged; Antiemetics; Antineoplastic Agents, Phytogenic; Aprepitant; Cross-Over Studies; Docetaxel; Female; Humans; Infusions, Intravenous; Male; Metabolic Clearance Rate; Middle Aged; Morpholines; Nausea; Neoplasms; Taxoids

This is the first study in which the NK(1)-receptor antagonist, aprepitant (APR), was evaluated for the prevention of chemotherapy-induced nausea and vomiting (CINV) with moderately emetogenic chemotherapy.. Eligible breast cancer patients were naive to emetogenic chemotherapy and treated with cyclophosphamide +/- doxorubicin or epirubicin. Patients were randomly assigned to either an aprepitant regimen (day 1, APR 125 mg, ondansetron (OND) 8 mg, and dexamethasone 12 mg before chemotherapy and OND 8 mg 8 hours later; days 2 through 3, APR 80 qd) [DOSAGE ERROR CORRECTED] or a control regimen (day 1, OND 8 mg and dexamethasone 20 mg before chemotherapy and OND 8 mg 8 hours later; days 2 through 3, OND 8 mg bid). Data on nausea, vomiting, and use of rescue medication were collected with a self-report diary. The primary efficacy end point was the proportion of patients with complete response, defined as no vomiting and no use of rescue therapy, during 120 hours after initiation of chemotherapy in cycle 1. The secondary end point was the proportion of patients with an average item score higher than 6 of 7 on the Functional Living Index-Emesis questionnaire.. Of 866 patients randomized, 857 patients (99%) were assessable. Overall complete response was greater with the aprepitant regimen than with the control regimen (50.8% v 42.5%; P = .015). More patients in the aprepitant group reported minimal or no impact of CINV on daily life (63.5% v 55.6%; P = .019). Both treatments were generally well tolerated.. The aprepitant regimen was more effective than the control regimen for prevention of CINV in patients receiving both an anthracycline and cyclophosphamide.

Topics: Adult; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Breast Neoplasms; Cyclophosphamide; Dexamethasone; Double-Blind Method; Doxorubicin; Epirubicin; Female; Humans; Middle Aged; Morpholines; Nausea; Ondansetron; Vomiting

Patients receiving the highly emetogenic high-dose chemotherapy regimen with cyclophosphamide, thiotepa and carboplatin (CTC) may benefit from the neurokin-1 receptor antagonist aprepitant in addition to standard anti-emetic therapy. As aprepitant has been shown to be a moderate inhibitor of the cytochrome P450 (CYP) 3A4 isoenzyme, its effect on the pharmacokinetics and metabolism of cyclophosphamide and thiotepa was evaluated. Moreover, preliminary results on the clinical efficacy of aprepitant in the CTC regimen are reported.. Six patients were enrolled in a protocol that employed a 4-day course of CTC high-dose chemotherapy with cyclophosphamide (1,500 mg/m2/day), thiotepa (120 mg/m2/day) and carboplatin (AUC 5 mg min/ml/day). Two patients received the tCTC protocol, which comprises two-third of the dose of CTC. In addition to standard anti-emetic therapy, the patients received aprepitant from one day before the start of their course until 3 days after chemotherapy. Blood samples were collected on days one and three of the course and analyzed for cyclophosphamide and its activated metabolite 4-hydroxycyclophosphamide, thiotepa and its main active metabolite tepa. The influence of aprepitant on the pharmacokinetics of cyclophosphamide and thiotepa was analyzed using a population pharmacokinetic analysis including a reference population of 49 patients receiving the same chemotherapy regimen without aprepitant and sampled under the same conditions. The frequency of nausea and vomiting in the six patients receiving CTC was compared with those of the last 22 consecutive patients receiving CTC chemotherapy without aprepitant. Inhibitory activity of aprepitant on cyclophosphamide and thiotepa metabolism was also tested in human liver microsomes.. In our patient population, the rate of autoinduction of cyclophosphamide (P=0.040) and the formation clearance of tepa (P<0.001) were reduced with 23% and 33% when aprepitant was co-administered, respectively. Exposures to the active metabolite 4-hydroxycyclophosphamide and tepa were therefore reduced (5% and 20%, respectively) in the presence of aprepitant. In human liver microsomes, the 50% inhibitory concentrations (IC50) of aprepitant for inhibition of cyclophosphamide (IC50=1.3 microg/ml) and thiotepa (IC50=0.27 microg/ml) metabolism were within the therapeutic range. Patients receiving aprepitant experienced less frequently CINV both during and after the CTC course compared with the reference population (nausea 3.7 days vs. 5.8 days, P=0.052; vomiting 0.5 days vs. 4.8 days, P<0.001).. Aprepitant inhibited both cyclophosphamide and thiotepa metabolism, most probably due to inhibition of the CYP 3A4 and/or 2B6 isoenzymes. The effects of this interaction are, however, small compared to the total variability. Addition of aprepitant may provide superior protection against vomiting in patients receiving the highly emetogenic high-dose CTC chemotherapy.

Topics: Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Breast Neoplasms; Carboplatin; Cyclophosphamide; Cytochrome P-450 Enzyme Inhibitors; Drug Interactions; Female; Humans; Male; Microsomes, Liver; Morpholines; Nausea; Neoplasms, Germ Cell and Embryonal; Thiotepa

The tendency of chemotherapeutic regimens to cause vomiting is dependent on the individual drugs in the regimen. The authors analyzed data combined from 2 Phase III trials to assess the effect of the neurokinin-1 (NK(1)) antagonist aprepitant combined with a 5HT(3) antagonist plus a corticosteroid in a subpopulation receiving > 1 emetogenic chemotherapeutic agent.. In the current study, 1043 cisplatin-naive patients (42% were women) receiving cisplatin-based (> or = 70 mg/m(2)) chemotherapy were assigned randomly to a control regimen (ondansetron [O] 32 mg intravenously and dexamethasone [D] 20 mg orally on Day 1; D 8 mg twice daily on Days 2-4) or an aprepitant (A) regimen (A 125 mg orally plus O 32 mg and D 12 mg on Day 1; A 80 mg and D 8 mg once daily on Days 2-3; and D 8 mg on Day 4). Randomization was stratified for use of concomitant chemotherapy and female gender. The primary end point was complete response (no vomiting and no rescue therapy) on Days 1-5 (0-120 hours). Data were analyzed by a modified intent-to-treat approach, and logistic regression was used to make treatment comparisons among patients receiving the most frequently coadministered emetogenic concomitant chemotherapy (Hesketh level > or = 3).. Among the approximately 13% of patients (n = 81 for A; n = 80 for control) who received additional emetogenic chemotherapy (doxorubicin or cyclophosphamide), the aprepitant regimen provided a 33 percentage-point improvement in the complete response rate compared with the control regimen. Among the general population, the advantage with aprepitant was 20 percentage points.. The current analysis of > 1000 patients from 2 large randomized trials showed that in the subpopulation at increased risk of chemotherapy-induced nausea and vomiting due to concomitant emetogenic chemotherapy, the addition of aprepitant to standard antiemetics improved protection to an even greater extent than in the general study population.

Topics: Adrenal Cortex Hormones; Anthracyclines; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Cisplatin; Cyclophosphamide; Dexamethasone; Female; Humans; Male; Morpholines; Nausea; Neoplasms; Neurokinin-1 Receptor Antagonists; Ondansetron; Serotonin 5-HT3 Receptor Antagonists; Vomiting

An aprepitant (APR) regimen was evaluated for prevention of nausea and emesis due to moderately emetogenic chemotherapy (MEC) over multiple cycles.. The authors performed a randomized, double-blind study. Eligible patients with breast carcinoma were naïve to emetogenic chemotherapy and treated with cyclophosphamide alone or with doxorubicin or epirubicin. Patients were randomized to receive either an APR regimen (Day 1: APR 125 mg, ondansetron [OND] 8 mg, and dexamethasone [DEX] 12 mg before chemotherapy and OND 8 mg 8 hrs later; Days 2-3: APR 80 mg every day) or a control regimen (Day 1: OND 8 mg and DEX 20 mg before chemotherapy and OND 8 mg 8 hrs later; Days 2-3: OND 8 mg twice per day). Data on nausea, emesis, and use of rescue medication were collected. The primary end point was the proportion of patients with a complete response (CR; no emesis or use of rescue therapy) in Cycle 1. Efficacy end points for the multiple-cycle extension were the probabilities of a CR in Cycles 2-4 and a sustained CR rate across multiple cycles.. Of 866 patients randomized, 744 (85.9%) entered the multiple-cycle extension, and 650 (75.1%) completed all 4 cycles. Overall, the CR was greater with the APR regimen over the 4 cycles: 53.8% versus 39.4% for Cycle 2, 54.1% versus 39.3% for Cycle 3, and 55.0% versus 38.4% for Cycle 4. The cumulative percentage of patients with a sustained CR over all 4 cycles was greater with the APR regimen (P = 0.017).. The APR regimen was more effective than a control regimen for the prevention of nausea and emesis induced by MEC over multiple chemotherapy cycles.

Topics: Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Cross-Over Studies; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Male; Maximum Tolerated Dose; Morpholines; Nausea; Neoplasms; Probability; Prospective Studies; Reference Values; Risk Assessment; Treatment Outcome; Vomiting

In early clinical trials, the NK(1) receptor antagonist, aprepitant (EMEND(R)) was shown to improve the protection provided by the best available therapy (hereafter referred to as 'standard therapy': a 5-HT(3) receptor antagonist and dexamethasone) against chemotherapy-induced nausea and vomiting over multiple cycles of cisplatin-based chemotherapy. To further study the sustainment of antiemetic efficacy of aprepitant plus standard therapy over more than one cycle of chemotherapy, we examined combined data from the multiple cycles extensions of two phase III clinical trials of oral aprepitant plus standard therapy for the prevention of chemotherapy-induced nausea and vomiting. Data were pooled from two multicentre, randomised, double-blind, placebo-controlled studies with identical design and treatment regimens. Cancer patients receiving a first cycle of cisplatin-based (>or=70 mg/m(2)) chemotherapy were randomised to one of two treatment groups as follows: the standard therapy group received ondansetron 32 mg intravenously (i.v.) and dexamethasone 20 mg on day 1 and dexamethasone 8 mg twice daily (b.i.d.) on days 2-4. The aprepitant group received aprepitant 125 mg, ondansetron 32 mg i.v., and dexamethasone 12 mg on day 1, aprepitant 80 mg and dexamethasone 8 mg on days 2-3, and dexamethasone 8 mg on day 4. Patients had the option to receive the same blinded treatment for up to five additional cycles. The analysis used a combined exploratory endpoint of no emesis and no significant nausea (i.e. nausea which interfered with a patient's normal activities) over the 5 days following cisplatin, for up to six cycles of chemotherapy. A cumulative probabilities approach incorporating a model for transitional probabilities was used to analyse the data. Tolerability was assessed by reported adverse events and physical and laboratory assessments. Baseline characteristics, reasons for discontinuation, and drop-out rates were similar between groups. In every cycle, the estimated probabilities (rates) of no emesis and no significant nausea were significantly higher (P<0.006) in the aprepitant group: in the first cycle, rates were 61% in the aprepitant group (N=516) and 46% in the standard therapy group (N=522), and thereafter, rates for the aprepitant regimen remained higher throughout (59% (N=89) versus 40% (N=78) for the standard therapy, by cycle 6). Repeated dosing with aprepitant over multiple cycles was generally well tolerated. Compared with patients who receiv

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antiemetics; Antineoplastic Agents; Aprepitant; Cisplatin; Female; Humans; Male; Middle Aged; Morpholines; Nausea; Neoplasms; Neurokinin-1 Receptor Antagonists; Treatment Outcome; Vomiting

The neurokinin-1 antagonist aprepitant (EMEND; Merck Research Laboratories, West Point, PA) has been shown to reduce chemotherapy-induced nausea and vomiting when it is given with a 5-hydroxytryptamine-3 receptor antagonist and dexamethasone. The current study sought to define the most appropriate dose regimen of oral aprepitant.. This multicenter, randomized, double-blind, placebo-controlled study was conducted in patients with cancer who were receiving initial cisplatin (> or = 70 mg/m(2)) and standard antiemetic therapy (intravenous ondansetron plus oral dexamethasone). Patients were randomized to receive standard therapy plus either aprepitant 375 mg on Day 1 and 250 mg on Days 2-5, aprepitant 125 mg on Day 1 and 80 mg on Days 2-5, or placebo. Due to an apparent interaction with dexamethasone suggested by pharmacokinetic data obtained while the study was ongoing, the aprepitant 375/250 mg dose was discontinued and replaced with aprepitant 40 mg on Day 1 and 25 mg on Days 2-5, and a new randomization schedule was generated. Patients recorded nausea and emesis in a diary. The primary endpoint was complete response (no emesis and no rescue therapy), which was analyzed using an intent-to-treat approach with data obtained after the dose adjustment. Treatment comparisons were made using logistic regression models. Tolerability was assessed by reported adverse events and physical and laboratory assessments, and included all available data.. The percentages of patients who achieved a complete response in the overall study period were 71.0% for the aprepitant 125/80-mg group (n = 131 patients), 58.8% for the aprepitant 40/25-mg group (n = 119 patients), and 43.7% for the standard therapy group (n = 126 patients; P < 0.05 for either aprepitant regimen vs. standard therapy). Rates for Day 1 were 83.2% for the aprepitant 125/80-mg group, 75.6% for aprepitant 40/25-mg group, and 71.4% for the standard therapy group (P < 0.05 for aprepitant 125/80 mg vs. standard therapy), and rates on Days 2-5 were 72.7% for the aprepitant 125/80-mg group, 63.9% for the aprepitant 40/25-mg group, and 45.2% for the standard therapy group (P < 0.01 for either aprepitant group vs. standard therapy). The efficacy of the aprepitant 375/250-mg regimen was similar to that of the aprepitant 125/80-mg regimen. The overall incidence of adverse events was generally similar across treatment groups: 85% in the aprepitant 375/250-mg group (n = 34 patients), 76% in the aprepitant 125/80-mg group (n = 214 patients), 71% in the aprepitant 40/25-mg group (n = 120 patients), and 72% in the standard therapy group (n = 212 patients), with the exception of a higher incidence of infection in the aprepitant 125/80-mg group (13%) compared with the standard therapy group (4%).. When it was added to a standard regimen of intravenous ondansetron and oral dexamethasone in the current study, aprepitant reduced chemotherapy-induced nausea and vomiting and was generally well tolerated, although increases in infection were noted that were assumed to be due to elevated dexamethasone levels as a result of the pharmacokinetic interaction. The aprepitant 125/80-mg regimen had the most favorable benefit:risk profile.

Topics: Administration, Oral; Antiemetics; Antineoplastic Agents; Aprepitant; Cisplatin; Dexamethasone; Double-Blind Method; Female; Humans; Injections, Intravenous; Male; Middle Aged; Morpholines; Nausea; Neoplasms; Neurokinin-1 Receptor Antagonists; Ondansetron; Treatment Outcome; Vomiting

Aprepitant is a novel neurokinin 1 (NK(1)) antagonist that has been shown to improve control of chemotherapy-induced nausea and vomiting (CINV) when added to a standard antiemetic regimen of a 5-hydroxytriptamine-3 antagonist plus a corticosteroid. The authors sought to evaluate further the efficacy and tolerability of aprepitant plus standard therapy in a large clinical trial.. This was a multicenter, randomized, double-blind, placebo-controlled, parallel-groups, Phase III study. Patients with cancer who were scheduled to receive treatment with high-dose cisplatin chemotherapy were randomized to receive 1 of 2 treatment regimens; the standard therapy group received intravenous ondansetron 32 mg and oral dexamethasone 20 mg on Day 1, and oral dexamethasone 8 mg twice daily on Days 2-4. The aprepitant group received oral aprepitant 125 mg, intravenous ondansetron 32 mg, and oral dexamethasone 12 mg on Day 1; oral aprepitant 80 mg and oral dexamethasone 8 mg once daily on Days 2-3; and oral dexamethasone 8 mg on Day 4. Patients recorded episodes of emesis, use of rescue therapy, and severity of nausea in a diary. A modified intent-to-treat approach was used to analyze the efficacy data. The primary endpoint was complete response (no emesis and no rescue therapy) during the 5-day period postcisplatin. Treatment comparisons were made using logistic regression models, and reported adverse events and physical and laboratory assessments were used to assess tolerability.. A total of 523 patients were evaluated for efficacy, and 568 patients were evaluated for safety. During the 5 days after chemotherapy, the percentages of patients who achieved a complete response were 62.7% in the aprepitant group (163 of 260 patients) versus 43.3% in the standard therapy group (114 of 263 patients; P < 0.001). For Day 1, the complete response rates were 82.8% for the aprepitant group and 68.4% for the standard therapy group (P < 0.001); for Days 2-5, the complete response rates were 67.7% in the aprepitant group and 46.8% in the standard therapy group (P < 0.001). The overall incidence of adverse events was similar between the 2 treatment groups (72.8% in the aprepitant group [206 of 283 patients] and 72.6% in the standard therapy group [207 of 285 patients]) as were rates of serious adverse events, discontinuations due to adverse events, and deaths.. In patients with cancer who are receiving high-dose cisplatin-based chemotherapy, therapy consisting of aprepitant (125 mg on Day 1 and 80 mg on Days 2-3) plus a standard regimen of ondansetron and dexamethasone provided superior antiemetic protection compared with standard therapy alone and was generally well tolerated.

Topics: Adolescent; Adult; Aged; Antiemetics; Antineoplastic Agents; Aprepitant; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Latin America; Male; Middle Aged; Morpholines; Nausea; Neurokinin-1 Receptor Antagonists; Placebos; Vomiting

Little information exists on the functional impact of effective antiemetic protection. In the present study, the Functional Living Index-Emesis (FLIE), was used to assess patient-reported impact of chemotherapy-induced nausea and vomiting (CINV) after administration of a new NK-1 receptor antagonist (aprepitant). Cisplatin-treated patients in a double-blind randomised trial received either aprepitant+dexamethasone+ondansetron on day 1 and aprepitant+dexamethasone on days 2-5 or standard antiemetic therapy (dexamethasone and ondansetron on day 1 and dexamethasone on days 2-5). Emetic events, nausea ratings and rescue medications were recorded in a 5-day diary and the FLIE was completed on day 6. Compared with standard therapy, significantly more patients treated with the high dose aprepitant regimen achieved a Complete Response (71 vs 44%, P<0.001) and also reported no impact on daily life as indicated by the FLIE total score (84 vs 66%, P<0.01). Use of the FLIE demonstrated that improved control of emesis was highly effective in reducing the impact of CINV on patients' daily lives.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antiemetics; Antineoplastic Agents; Aprepitant; Cisplatin; Dexamethasone; Double-Blind Method; Female; Humans; Male; Middle Aged; Morpholines; Nausea; Neoplasms; Ondansetron; Receptors, Neurokinin-1; Surveys and Questionnaires; Vomiting

In early clinical trials with patients receiving highly emetogenic chemotherapy, the neurokinin antagonist aprepitant significantly enhanced the efficacy of a standard antiemetic regimen consisting of a type-three 5-hydroxytryptamine antagonist and a corticosteroid. This multicenter, randomized, double-blind, placebo-controlled phase III study was performed to establish definitively the superiority of the aprepitant regimen versus standard therapy in the prevention of chemotherapy-induced nausea and vomiting (CINV).. Patients receiving cisplatin > or = 70 mg/m2 for the first time were given either standard therapy (ondansetron and dexamethasone on day 1; dexamethasone on days 2 to 4) or an aprepitant regimen (aprepitant plus ondansetron and dexamethasone on day 1; aprepitant and dexamethasone on days 2 to 3; dexamethasone on day 4). Patients recorded nausea and vomiting episodes in a diary. The primary end point was complete response (no emesis and no rescue therapy) on days 1 to 5 postcisplatin, analyzed by a modified intent-to-treat approach. Treatment comparisons were made using logistic regression models. Tolerability was assessed by reported adverse events and physical and laboratory assessments.. The percentage of patients with complete response on days 1 to 5 was significantly higher in the aprepitant group (72.7% [n = 260] v 52.3% in the standard therapy group [n = 260]), as were the percentages on day 1, and especially on days 2 to 5 (P <.001 for all three comparisons).. Compared with standard dual therapy, addition of aprepitant was generally well tolerated and provided consistently superior protection against CINV in patients receiving highly emetogenic cisplatin-based chemotherapy.

Topics: Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Antiemetics; Antineoplastic Agents; Aprepitant; Cisplatin; Dexamethasone; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Injections, Intravenous; Male; Middle Aged; Morpholines; Nausea; Neoplasms; Neurokinin-1 Receptor Antagonists; Ondansetron; Placebos; Treatment Outcome; Vomiting

This analysis evaluated whether the antiemetic efficacy of the NK1 receptor antagonist aprepitant (EMEND trade mark, Merck, Whitehouse Station, NJ) plus standard antiemetics could be sustained for up to six cycles of cisplatin-based chemotherapy.. Patients receiving cisplatin > or = 70 mg/m2 were blindly assigned to receive one of the following three regimens: (1) aprepitant 375 mg 1 hour before cisplatin on day 1 and aprepitant 250 mg on days 2 to 5 (n = 35); (2) aprepitant 125 mg before cisplatin and aprepitant 80 mg on days 2 to 5 (n = 81); or (3) placebo before cisplatin on days 2 to 5 (n = 86). All groups received ondansetron 32 mg and dexamethasone 20 mg before cisplatin, and dexamethasone 8 mg on days 2 to 5. The primary end point was complete response (no emesis and no rescue therapy) over 5 days following cisplatin in up to six cycles. A cumulative probability analysis using a model for transitional probabilities was used to analyze the data. The aprepitant 375/250-mg regimen was discontinued early in light of new pharmacokinetic data.. In the first cycle, 64% of patients in the aprepitant group and 49% in the standard therapy group had a complete response. Thereafter, complete response rates for the aprepitant group were still 59% by cycle 6, but decreased to 34% by cycle 6 for the standard therapy group. Reasons for discontinuation were similar across treatment groups.. Compared with patients who received standard therapy, those who received only the aprepitant regimen had better and more sustained protection against chemotherapy-induced nausea and vomiting over multiple cycles.

Topics: Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Antiemetics; Antineoplastic Agents; Aprepitant; Cisplatin; Dexamethasone; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Morpholines; Nausea; Neoplasms; Neurokinin-1 Receptor Antagonists; Treatment Outcome; Vomiting

Substance P is localised in brainstem regions associated with emesis. Based on studies in the ferret, it was postulated that a neurokinin-1 (NK1) receptor antagonist would have antiemetic activity as monotherapy in humans receiving chemotherapy. L-758,298 is a water-soluble, intravenous (i.v.) prodrug for L-754,030, a potent and selective NK1 receptor antagonist. This double-blind, randomised, active-agent (ondansetron)-controlled study enrolled 53 cisplatin-naïve patients and evaluated the prevention of both acute (0-24 h) and delayed (days 2-7) emesis after cisplatin treatment (50-100 mg/m(2)). All patients received i.v. L-758,298 (60 or 100 mg) (n=30) or ondansetron (32 mg) (n=23) before cisplatin and efficacy was evaluated up to day 7 post-cisplatin. Nausea was assessed by means of a four-point ordinal scale at intervals over the 7 day period. In the acute period, the proportion of patients without emesis in the L-758,298 and ondansetron groups was 37 and 52%, respectively (no significant difference between the groups). Comparing the distribution of average nausea scores over the entire first 24 h revealed no significant difference between the groups. In the delayed period, the proportion of patients without emesis in the L-758,298 and ondansetron treatment groups was 72 and 30%, respectively (P=0.005). The distribution of average nausea scores in the delayed period was lower in the L-758,298 group compared with the ondansetron group (P=0.15 for the entire delayed period and P=0.043 for day 2 only). No serious adverse events were attributed to L-758,298. A single dose of L-758,298 substantially suppressed the delayed nausea and vomiting characteristic of high dose cisplatin and also appeared to reduce acute emesis post-cisplatin. The data also support the proposition that the underlying mechanism(s) of acute and delayed emesis are different.

Topics: Acetals; Adult; Aged; Antiemetics; Antineoplastic Agents; Aprepitant; Cisplatin; Double-Blind Method; Female; Humans; Male; Middle Aged; Morpholines; Nausea; Ondansetron; Patient Satisfaction; Prodrugs; Vomiting

Aprepitant is used for the treatment of chemotherapy induced nausea and vomiting. A liquid formulation is needed for treatment of young children. However, the commercial (powder for) suspension was not available worldwide for a prolonged period of time and, therefore, a 10 mg/mL aprepitant oral suspension was extemporarily prepared to prevent suboptimal antiemetic treatment. The current pharmacokinetic study was developed to investigate whether this extemporaneous oral suspension offers an appropriate treatment option.. From 49 pediatric patients (0.7-17.9 years) 235 plasma concentrations were collected. Patients were either treated with our extemporaneous oral suspension (n = 26; 53%), commercially available capsules (n = 18; 37%), or the intravenous prodrug formulation of aprepitant (fosaprepitant, n = 5; 10%). Pharmacokinetic analyses were performed using nonlinear mixed effects modelling.. A one-compartment model adequately described the pharmacokinetics of aprepitant in children. The bioavailability of the extemporaneous oral suspension was not significantly different to that of the capsules (P = 0.26). The observed bioavailability throughout the total population was 83% (95% CI 69%-97%). The absorption of the extemporaneous oral suspension was 39.4% (95%CI 19.5-57.4%) faster than that of capsules (mean absorption time of 1.78 h (95%CI 1.32-2.35), but was comparable to that of the commercial oral suspension. The median area under the curve after (fos)aprepitant was 22.2 mg/L*h (range 8.9-50.3 mg/L*h) on day 1.. Our extemporaneous oral suspension is an adequate alternative for the commercially (un)available oral suspension in young children. An adequate exposure to aprepitant in children was yielded and the bioavailability of the extemporaneous suspension was comparable to capsules.

Topics: Antiemetics; Aprepitant; Capsules; Child; Child, Preschool; Humans; Nausea; Suspensions; Vomiting

Oral aprepitant has a large interindividual variation in clinical responses in advanced cancer. This study aimed to characterize plasma aprepitant and its N-dealkylated metabolite (ND-AP) based on the cachexia status and clinical responses in head and neck cancer patients.. Fifty-three head and neck cancer patients receiving cisplatin-based chemotherapy with oral aprepitant were enrolled. Plasma concentrations of total and free aprepitant and ND-AP were determined at 24 h after a 3-day aprepitant treatment. The clinical responses to aprepitant and degrees of cachexia status were assessed using a questionnaire and Glasgow Prognostic Score (GPS).. Serum albumin level was negatively correlated with the plasma concentrations of total and free aprepitant but not ND-AP. The serum albumin level had a negative correlation with the metabolic ratio of aprepitant. The patients with GPS 1 or 2 had higher plasma concentrations of total and free aprepitant than those with GPS 0. No difference was observed in the plasma concentration of ND-AP between the GPS classifications. The plasma interleukin-6 level was higher in patients with GPS 1 or 2 than 0. The absolute plasma concentration of free ND-AP was higher in patients without the delayed nausea, and its concentration to determine the occurrence was 18.9 ng/mL. The occurrence of delayed nausea had no relation with absolute plasma aprepitant.. Cancer patients with a lower serum albumin and progressive cachectic condition had a higher plasma aprepitant level. In contrast, plasma free ND-AP but not aprepitant was related to the antiemetic efficacy of oral aprepitant.

Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Cachexia; Cisplatin; Dexamethasone; Head and Neck Neoplasms; Humans; Morpholines; Nausea; Vomiting

Dexamethasone (DEX)-sparing strategy with 5-hydroxytryptamine-3 receptor antagonist (5HT3RA) and aprepitant (APR), as triplet antiemetic prophylaxis, is associated with poor control of delayed chemotherapy-induced nausea and vomiting (CINV) in patients receiving carboplatin (CBDCA)-based chemotherapy. This study aimed to evaluate whether using palonosetron (PALO) as a 5HT3RA provides superior control with CINV than first-generation (1st) 5HT3RA in triplet antiemetic prophylaxis with a DEX-sparing strategy.. Pooled patient-level data from a nationwide, multicenter, and prospective observational study were analyzed to compare the incidence of CINV between patients administered PALO and 1st 5HT3RA in combination with 1-day DEX and APR.. No significant differences were observed in the incidence of CINV, pattern of CINV, or severity of nausea by type of 5HT3RA in triplet antiemetic prophylaxis with DEX-sparing strategy. In both groups, the incidence of nausea gradually increased from day 3, peaked on day 4 or 5, and then declined slowly. The visual analog scale scores in the delayed phase remained high throughout the 7-day observation period.. Careful patient selection and symptom monitoring are needed when implementing the DEX-sparing strategy in triplet antiemetic prophylaxis for patients undergoing CBDCA-based chemotherapy. Furthermore, additional strategies may be needed to achieve better control of delayed CINV.

Topics: Antiemetics; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Carboplatin; Dexamethasone; Humans; Isoquinolines; Nausea; Palonosetron; Quinuclidines; Vomiting

Chemotherapy-induced nausea and vomiting (CINV) is a very common side effect of pediatric cancer therapy. High-quality, evidence-based, pediatric-specific guidelines for prophylaxis and treatment of CINV are available. At many centers, guideline-concordant care is uncommon. We formed a multidisciplinary quality improvement team to implement guideline-concordant care for CINV prophylaxis at our center. We present the results following the first year of our interventions.. We planned and implemented a multipronged approach in three key phases: (1) developing and publishing an acute CINV prophylaxis pathway, (2) education of providers, and (3) updating the computerized provider order entry system. We used iterative, sequential Plan-Do-Study-Act cycles and behavioral economic strategies to improve adherence to guideline-concordant CINV prophylaxis. We focused on aprepitant usage as a key area for improvement.. At the beginning of the study period, < 50% of patients were receiving guideline-concordant CINV prophylaxis and < 15% of eligible patients were receiving aprepitant. After 1 year, more than 60% of patients were receiving guideline-concordant care and 50% of eligible patients were receiving aprepitant.. We describe the development and implementation of a standardized pathway for prevention of acute CINV in pediatric oncology patients. With a multidisciplinary, multifaceted approach, we demonstrate significant improvements to guideline-congruent CINV prophylaxis.

Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Child; Humans; Nausea; Neoplasms; Vomiting

Aprepitant, a substance P neurokinin-1 receptor antagonist, is licenced for the prevention of acute and delayed nausea and vomiting associated with highly and moderately emetogenic cancer chemotherapy.. A 33 year-old male with metastatic gastro-oesophageal cancer had multiple admissions for refractory nausea and vomiting following insertion of an oesophageal stent.. Mechanical issues with the stent, stent removal and central causes were excluded. Multiple anti-emetic agents were trialled in combination and with varying routes of administration without significant symptomatic improvement.. A trial of aprepitant was proposed as an off-licence therapy.. One hundred sixty-five milligrammes of aprepitant was given orally every 3 days and then up titrated to once daily with significant symptomatic improvement enabling the patient to tolerate an oral diet. The patient remained stable at 12 weeks and has been accepted into two clinical trials for potential further cancer treatment.. Aprepitant can be effective in refractory nausea and vomiting outside of emetogenic chemotherapy and safely used as a chronic treatment. The prevalence of refractory nausea and vomiting as a rare adverse outcome post-oesophageal stent insertion should be studied.. Further research of neurokinin-1 inhibitors for indications other than chemotherapy-induced nausea and vomiting is indicated.

Topics: Adult; Antineoplastic Agents; Aprepitant; Humans; Male; Morpholines; Nausea; Stents; Vomiting

Aprepitant (Apr) is an effective antiemetic agent for chemotherapy-induced nausea and vomiting (CINV). Current CINV guidelines recommend the antiemetic combination of a 5-HT3 receptor antagonist, Apr, and dexamethasone (Dex) for highly emetogenic chemotherapies. Apr inhibits CYP3A4 dose-dependently. Since Dex is metabolized by CYP3A4, the combined use of Apr and Dex inhibits Dex metabolism. CINV guidelines therefore recommend dose-reduction of Dex when Apr and Dex are used together. However, there is some controversy over whether or not Dex should be reduced when administered as an antitumor agent for lymphoid malignancies. We retrospectively compared the antitumor effect of Dex-containing chemotherapy in which Dex is administered at the usual dose without Apr (group A) or administered at a half-dose in combination with Apr (group B). We analyzed 62 consecutive patients with refractory or relapsed CD20 + B cell lymphoma who received R-DHAP therapy in our hospital, including 29 and 33 cases in groups A and B, respectively. The response rate at the end of the first course of R-DHAP was 62.1% and 54.5%, respectively (P = 0.61). As another endpoint to evaluate the effect of Dex, group B tended to show greater suppression of the lymphocyte count (P = 0.05). Therefore, decreasing the dose of Dex by half appeared to be reasonable when combined with Apr.

Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Cytochrome P-450 CYP3A; Dexamethasone; Humans; Lymphoma; Nausea; Retrospective Studies; Vomiting

Three different injectable neurokinin-1 (NK-1) receptor antagonist formulations (CINVANTI® [C] vs. intravenous Emend® [E] vs. generic formulations of fosaprepitant [GFF]) were compared with respect to nausea and vomiting control, use of rescue therapy, and the development of infusion reactions over multiple cycles of chemotherapy.. A retrospective analysis from 17 community oncology practices across the USA was conducted on patients who received moderately or highly emetogenic chemotherapy. The co-primary endpoints were the control of chemotherapy-induced nausea and vomiting (CINV) from days 1 to 5 over all cycles and the frequency of infusion-related reactions. Propensity score weighted multivariable logistic regression analysis was used to compare complete CINV control, the use of rescue therapy, and the risk of infusion reactions between groups.. The study enrolled 294 patients (C = 101, E = 101, GFF = 92) who received 1432 cycles of chemotherapy. Using CINVANTI® as the reference group, comparative effectiveness was suggested in CINV control over all chemotherapy cycles (odds ratio (OR): E vs. C = 1.00 [0.54 to 1.86] and GFF vs. C = 1.12 [0.54 to 2.32]). However, use of rescue therapy was significantly higher in the EMEND® group relative to CINVANTI® (OR = 2.69; 95%CI: 1.06 to 6.84). Infusion reactions were also numerically higher in the EMEND® group, but the difference did not reach statistical significance (OR = 4.35; 95%CI: 0.83 to 22.8).. In this real-world analysis, patients receiving CINVANTI® had a reduced need for CINV rescue therapy and a numerically lower incidence of infusion reactions.

Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Humans; Nausea; Neoplasms; Neurokinin-1 Receptor Antagonists; Retrospective Studies; Vomiting

A triple antiemetic therapy combining aprepitant (APR) with conventional double antiemetic therapy, including 5-hydroxytryptamine 3 receptor antagonist (5-HT₃-RA) and dexamethasone (DEX), is recommended for preventing chemotherapy-induced nausea and vomiting induced by a carboplatin (CBDCA) regimen. However, consensus on the additive effects of APR for gynecological patients on a combined regimen of paclitaxel and CBDCA (TC regimen) has yet to be reached. This retrospective study investigated the antiemetic effects of palonosetron and DEX (PD therapy) and granisetron and DEX with APR (GDA therapy) in patients with gynecologic cancer and who underwent their first TC regimen cycle between April 2017 and March 2020 at the Gunma University Hospital Outpatient Chemotherapy Center. The results showed that the complete response rate of the 92 patients who underwent PD therapy (PD group) and the 46 patients who underwent GDA therapy (GDA group) were both 80.4% (p = 1.000), and the complete control rates of the PD and GDA groups were 78.3% and 80.4%, respectively (p = 0.828), resulting in no significant difference. Furthermore, we observed no significant difference between the PD and GDA groups in the incidence of grade ≥2 nausea, vomiting, and anorexia (nausea: 7.6% vs. 0%, p = 0.095; vomiting: 4.3% vs. 0%, p = 0.301; and anorexia: 9.8% vs. 2.2%, p = 0.164). Concerning adverse events, compared to the PD group, the GDA group showed significantly higher incidence of grade ≥2 malaise (7.6% vs. 19.6%, p = 0.039). Given the lack of difference in the antiemetic effects of PD and GDA therapies, antiemetic therapy should be selected carefully for individual patients by accounting for the incidence of adverse reactions and interactions with APR.

Topics: Anorexia; Antiemetics; Aprepitant; Carboplatin; Dexamethasone; Female; Granisetron; Humans; Nausea; Neoplasms; Paclitaxel; Palonosetron; Retrospective Studies; Vomiting

The aim of this study was to assess the cost-effectiveness of NEPA, a fixed-dose combination of oral netupitant (300 mg) and palonosetron (0.5 mg), compared to available treatments in Spain after aprepitant generic introduction in the market, and to discuss results in previously performed analyses in different wordwide settings.. A Markov model including three health states, complete protection, complete response at best and incomplete response, was used to evaluate the cost-effectiveness of NEPA versus common treatment options in Spain during 5 days after chemotherapy. Incremental costs including treatment costs and treatment failure management cost as well as incremental effects including quality adjusted life days (QALDs) and emesis-free days were compared between NEPA and the comparator arms. The primary outcomes were cost per avoided emetic event and cost per QALDs gained.. NEPA was dominant (more effective and less costly) against aprepitant combined with palonosetron, and fosaprepitant combined with granisetron, while, compared to generic aprepitant plus ondansetron, NEPA showed an incremental cost per avoided emetic event of €33 and cost per QALD gained of €125.. By most evaluations, NEPA is a dominant or cost-effective treatment alternative to current antiemetic standards of care in Spain during the first 5 days of chemotherapy treatment in cancer patients, despite the introduction of generics. These results are in line with previously reported analyses throughout different international settings.

Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Cost-Benefit Analysis; Emetics; Humans; Internationality; Nausea; Palonosetron; Quinuclidines; Vomiting

Combination therapy using multiple antiemetic drugs is recommended for intravenous administration of cisplatin, a highly emetogenic agent, whereas a 5-HT3 receptor antagonist alone is commonly used in hepatic arterial infusion chemotherapy using cisplatin for hepatocellular carcinoma owing to its less toxicity than that in the intravenous administration. Given that optimal antiemetic therapy is not yet established, we retrospectively investigated the efficacy of antiemetic drugs for hepatic arterial infusion chemotherapy using cisplatin. This study enrolled 72 patients with hepatocellular carcinoma who received hepatic arterial infusion chemotherapy using cisplatin at Kurashiki Central Hospital between January 2011 and May 2019. A 5-HT3 receptor antagonist was used in all cases, while aprepitant and/or dexamethasone were used concomitantly in 6 cases. After chemotherapy, a complete response rate for 5 days was achieved in 73.6% of the patients; however, complete control could be achieved only in 29.2%. During these 5 days, both rates were lower on days 2-5 than on day 1. In addition, younger age was associated with worse control rates. Our findings suggest that more effective antiemetic therapy is needed for hepatic arterial infusion chemotherapy using cisplatin, especially in non-elderly patients.

Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Carcinoma, Hepatocellular; Cisplatin; Dexamethasone; Drug Therapy, Combination; Humans; Liver Neoplasms; Middle Aged; Morpholines; Nausea; Palonosetron; Receptors, Serotonin, 5-HT3; Retrospective Studies; Vomiting

Chemotherapy-induced nausea and vomiting (CINV) are common side effects in pediatric oncology treatment. Besides 5-HT. In total, 65 children (0.6-17.9 years), receiving intravenous or oral antiemetic therapy (dexamethasone ± aprepitant) as standard of care, were included. 305 dexamethasone plasma concentrations were determined using LC-MS/MS. An integrated dexamethasone and aprepitant pharmacokinetic model was developed using non-linear mixed effects modelling in order to investigate the effect of aprepitant administration on dexamethasone CL.. In this population, dexamethasone CL in patients with concomitant administration of aprepitant was reduced by approximately 30% of the uninhibited CL (23.3 L/h (95% confidence interval 20.4-26.0)). This result is not consistent with the results of adult studies (50% reduction). This difference was not age dependent, but might be related to the route of administration of dexamethasone. Future studies are needed to assess the difference in oral/intravenous dexamethasone.. When dexamethasone is given intravenously as a component of triple therapy to prevent CINV in children, we advise to reduce the dexamethasone dose by 30% instead of 50%.

Topics: Adult; Antiemetics; Antineoplastic Agents; Aprepitant; Child; Chromatography, Liquid; Dexamethasone; Drug Therapy, Combination; Humans; Morpholines; Nausea; Tandem Mass Spectrometry; Vomiting

Nausea and vomiting is a common symptom in children through their end of life journey. Aprepitant, a NK-1 antagonist, has become a potent weapon in the fight against chemo-induced nausea and vomiting. However, its use in palliative care for refractory nausea and vomiting has been limited due to limited experience or evidence of continuous use. Emerging evidence suggests that continuous use is not only safe, but also effective in patients with nausea and vomiting refractory to multiple lines of antiemetic therapy.. We conducted a single centre retrospective chart review of children receiving care from a specialist palliative care team who were given continuous daily aprepitant for nausea and vomiting and were unresponsive to at least two prior lines of antiemetic therapy. Parental reports of the impact of nausea on mobility and feeding were used as proxy efficacy markers. Duration of effect and toxicity was also evaluated.. Ten children (eight with cancer as a primary diagnosis and two with noncancer diagnoses) received continuous aprepitant and all showed resolution of nausea and vomiting and an increased ability to mobilize and tolerate feeds. No adverse events noted.. Our review suggests a role for aprepitant in management of refractory nausea and vomiting, demonstrating safety and efficacy. This case series is the first report of aprepitant use in this manner in the paediatric palliative care setting.

Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Child; Humans; Morpholines; Nausea; Retrospective Studies; Vomiting

This study developed a novel Aprepitant micells (APPT-Ms) formulation that uses a mixture of 15-hydroxystearate (HS15) as surfactant to solubilize AAPT. This article determines the content of APPT by HPLC. The in vitro test results show that the optimized APPT-Ms has small particle size, excellent stability and long-lasting release. At a test dose of 20mg/kg, the pharmacokinetic study of APPT-Ms showed that it accorded with first-order kinetics in mice, and its AUC value was higher than the pure AAPT about 6 times. The tissue distribution study of mice showed that the APPT-Ms had higher tissue binding ability than pure AAPT. The APPT-Ms could be rapidly distributed to various tissues and it was easier to pass through the blood-brain barrier than APPT. In this study, the APPT-Ms has high antiemetic activity and improves the compliance of patient. The pharmacokinetics and tissue distribution of APPT-Ms after injection administration were studied, which may be of guiding significance for further research.

Topics: Animals; Antiemetics; Antineoplastic Agents; Aprepitant; Blood-Brain Barrier; Drug Delivery Systems; In Vitro Techniques; Mice; Micelles; Nausea; Rats; Stearic Acids; Surface-Active Agents; Tissue Distribution; Vomiting

Topics: Adult; Aged; Aged, 80 and over; Antiemetics; Antineoplastic Agents; Aprepitant; Dexamethasone; Drug Therapy, Combination; Female; Humans; Infusions, Intravenous; Injections, Intravenous; Male; Middle Aged; Nausea; Neoplasms; Neurokinin-1 Receptor Antagonists; Ondansetron; Palonosetron; Retrospective Studies; Vomiting

Chemotherapy-induced nausea and vomiting (CINV) is a common treatment-related adverse event that negatively impacts the quality of life of cancer patients. During pediatric drug development, extrapolation of efficacy from adult to pediatric populations is a pathway that can minimize the exposure of children to unnecessary clinical trials, improve efficiency, and increase the likelihood of success in obtaining a pediatric indication. The acceptability of the use of extrapolation depends on a series of evidence-based assumptions regarding the similarity of disease, response to intervention, and exposure-response relationships between adult and pediatric patients. This study evaluated publicly available summaries of data submitted to the US Food and Drug Administration for drugs approved for CINV to assess the feasibility of extrapolation for future development programs. Extracted data included trial design, emetogenic potential of chemotherapy, primary end points, participant enrollment criteria, and antiemetic pharmacokinetics. Adult and pediatric clinical trial designs for assessment of efficacy and safety shared key design elements. Antiemetic drugs found to be efficacious in adults were also efficacious in pediatric patients. Systemic drug concentrations at approved doses were similar for ondansetron, granisetron, and aprepitant, but an exposure-response analysis of palonosetron in children suggested that higher palonosetron systemic exposure is necessary for the prevention of CINV in the pediatric population. For 5-hydroxytryptamine-3 and neurokinin-1 receptor antagonist antiemetic drugs, efficacy in adults predicts efficacy in children, supporting the extrapolation of effectiveness of an antiemetic product in children from adequate and well-controlled studies in adult patients with CINV.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antiemetics; Antineoplastic Agents; Aprepitant; Child; Child, Preschool; Clinical Trials as Topic; Data Interpretation, Statistical; Dose-Response Relationship, Drug; Drug Dosage Calculations; Female; Granisetron; Humans; Infant; Male; Middle Aged; Nausea; Neurokinin-1 Receptor Antagonists; Ondansetron; Palonosetron; Treatment Outcome; United States; United States Food and Drug Administration; Vomiting; Young Adult

To evaluate the impact on cost, time, resource use, and clinic workflow of converting the route of drug administration from a neurokinin-1 receptor antagonist (NK-1 RA) 30-min intravenous (IV) infusion to aprepitant IV, and more specifically to IV push, within a multicenter community oncology practice.. This was a retrospective, multicenter time, motion, and resource/cost evaluation study. Conversion to aprepitant IV was determined by calculating number of doses of aprepitant IV versus fosaprepitant administered in patients receiving moderately or highly emetogenic chemotherapy regimens. Operational advantages (i.e., supply costs, time saved) of switching from fosaprepitant IV infusion to aprepitant administered as a 2-min IV push were assessed.. A total of 12,908 doses of aprepitant IV 130 mg were administered at 13 Rocky Mountain Cancer Centers clinics over an 18-month period. Conversion from fosaprepitant to aprepitant IV reached 90% after 9 months of aprepitant IV initiation. Supply costs per administration were reduced ($2.51 to $0.52) when aprepitant was prepared as an IV push versus an NK-1 RA infusion. The overall time savings per administration of aprepitant was reduced by 90% (from 36.5 to 3.5 min, 33 min saved) as an IV push rather than an infusion. Most of the time saved per administration (30 min) pertained to the infusion nurse, and 3 min was saved by the pharmacy technician.. Successful conversion to aprepitant, and specifically to a 2-min IV push, provides time, cost, and resource savings, improves operational efficiency, and avoids the negative impact of potential future IV fluid shortages.. Chemotherapy-induced nausea and vomiting (CINV) can have a major impact on quality of life for patients receiving chemotherapy. Intravenous (IV) aprepitant is an approved neurokinin-1 receptor antagonist (NK-1 RA) that has been effective and safe when administered as part of a guideline-recommended regimen in patients receiving chemotherapy. In addition to being approved as a 30-min infusion, aprepitant IV is the only NK-1 RA approved for administration as a 2-min injection. These factors contributed to Rocky Mountain Cancer Centers (RMCC), which is a physician-owned community oncology practice, evaluating the impact on cost, time, and resource use of converting from a 30-min infusion of fosaprepitant to aprepitant IV, and more specifically a 2-min injection. Within 9 months of implementing aprepitant IV at RMCC, the percent utilization compared to fosaprepitant reached over 90%, signifying a successful conversion within the practice. Furthermore, a 2-min injection of aprepitant IV resulted in several operational advantages compared to a 30-min infusion. When accounting for all 13 clinics within RMCC, total monthly time savings to the practice would be over 28,000 min, or approximately 60 workdays per month of saved time. This new workflow is more efficient and allows for pharmacy technicians to complete other necessary tasks in the pharmacy such as cleaning, organizing, managing inventory, drug ordering, and charge/documentation corrections. Time saved by the nurses could be used for enhanced patient care, thoroughly reviewing chemotherapy or other orders, and assisting other nurses.

Topics: Administration, Intravenous; Adult; Aged; Aged, 80 and over; Antiemetics; Antineoplastic Agents; Aprepitant; Female; Humans; Infusions, Intravenous; Injections, Intravenous; Male; Middle Aged; Morpholines; Nausea; Neoplasms; Retrospective Studies; Vomiting

Topics: Antineoplastic Agents; Aprepitant; Glioma; Humans; Nausea; Ondansetron; Temozolomide; Vomiting

Chemotherapy-induced nausea and vomiting (CINV) is one of the scariest chemotherapy-induced adverse effects. We evaluated the adherence to the 2017 American Society of Clinical Oncology (ASCO), the latest guideline recommendations, for the management of acute CINV at our institute.. During a 6-months cross-sectional study on outpatient's cancer patients, we collected data from the prescription documents during temporary hospitalization and compared the results with ASCO guideline recommendations.. The most prescribed prophylactic regimens for the management of CINV were combination of aprepitant, granisetron, and dexamethasone and metoclopramide (51.8%). Regarding prescription compatibility in our center with ASCO guideline recommnedations, selection of different regimens for prophylaxis of acute CINV in our institute was compliant in 0 %, 22%, 4%, and 40% of high, moderate, low, and minimal emetogenic potential of chemotherapy regimen groupss, respectively.. Although our hospital is a referral and university-affiliated center, adherence to the ASCO guideline recommendations for prophylaxis of CINV was poor.

Topics: Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Drug-Related Side Effects and Adverse Reactions; Female; Follow-Up Studies; Granisetron; Guideline Adherence; Humans; Induction Chemotherapy; Male; Middle Aged; Nausea; Neoplasms; Prognosis; Vomiting

Aprepitant is a selective SP/NK-1 receptor antagonist and used in postoperative and chemotherapeutics induced emesis and vomiting. The aim of our study is to show aprepitant may have beneficial effects on gastrointestinal complaints in cancer patients undergoing chemotherapeutics by indomethacin-induced gastric ulcer model. A total of 48 rats were fasted 24 h for ulcer experiment. Aprepitant doses of 5, 10, 20, and 40 mg/kg were evaluated for their antiulcer activity. Omeprazole (20 mg/kg) was used as a positive control group. Six hours after 25 mg/kg indomethacin administration, all stomachs were dissected out. After macroscopic analyses, tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), COX-1, and COX-2 mRNA levels and SOD activity, and GSH and MDA levels of stomachs were determined. Histopathological examinations were evaluated. Aprepitant administration exerted 48.14%, 49.62%, 65.92%, and 76.77% ulcer inhibition effects at 5, 10, 20, and 40 mg/kg, respectively. Aprepitant administration decreased oxidative stress and inflammatory parameters in stomach tissues dose dependently. Aprepitant administration increased stomach COX-2 mRNA levels at 20 and 40 mg/kg doses. Although aprepitant appears to be disadvantageous in terms of treating gastric ulcer due to COX enzyme inhibition according to the previous studies, aprepitant has been shown to have ulcer healing effect in our study. When aprepitant is given as an anti-nausea and vomiting drug to cancer patients undergoing chemotherapy, we can argue that it will not be necessary to add a new gastric protective agent as it also shows beneficial effects in gastrointestinal complaints.

Topics: Animals; Antiemetics; Aprepitant; Gastric Mucosa; Inflammation Mediators; Male; Nausea; Rats; Rats, Wistar; Stomach Ulcer; Vomiting

Topics: Antineoplastic Agents; Aprepitant; Glioma; Humans; Nausea; Ondansetron; Temozolomide; Vomiting

Cisplatin is classified as a drug with high emetic risk; thus, the use of aprepitant or fosaprepitant in addition to a 5-hydroxytryptamine-3 (5-HT

Topics: Aged; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Cisplatin; Dexamethasone; Drug Therapy, Combination; Esophageal Neoplasms; Female; Humans; Infusions, Intravenous; Magnesium Sulfate; Male; Middle Aged; Morpholines; Nausea; Premedication; Quality of Life; Retrospective Studies; Serotonin 5-HT3 Receptor Antagonists; Solutions; Treatment Outcome; Vomiting

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.. 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.. 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.. 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

To assess, from a United States (US) perspective, the cost-effectiveness of chemotherapy-induced nausea and vomiting (CINV) prophylaxis using a single dose of netupitant and palonosetron in a fixed combination (NEPA) versus aprepitant plus granisetron (APR + GRAN), each in combination with dexamethasone, in chemotherapy-naïve patients receiving highly emetogenic chemotherapy (HEC).. We analyzed patient-level outcomes over a 5-day post-HEC period from a randomized, double-blind, phase 3 clinical trial of NEPA (n = 412) versus APR + GRAN (n = 416). Costs and CINV-related utilities were assigned to each subject using published sources. Parameter uncertainty was addressed via multivariate probabilistic sensitivity analyses (PSA).. Compared to APR + GRAN, NEPA resulted in a gain of 0.09 quality-adjusted life-days (QALDs) (4.04 vs 3.95; 95% CI -0.06 to 0.25) and a significant total per-patient cost reduction of $309 ($943 vs $1252; 95% CI $4-$626), due principally to $258 in lower medical costs of CINV-related events ($409 vs $668; 95% CI -$46 to $572) and $45 in lower study drug costs ($531 vs $577). In the PSA, NEPA resulted in lower costs and higher QALD in 86.5% of cases and cost ≤ $25,000 per quality-adjusted life-year gained in 97.8% of cases.. This first-ever economic analysis using patient-level data from a phase 3 trial comparing neurokinin-1 receptor antagonist (NK1 RA) antiemetic regimens suggests that NEPA is highly cost-effective (and in fact cost-saving) versus an aprepitant-based regimen in post-HEC CINV prevention. Actual savings may be higher, as we focused only on the first chemotherapy cycle and omitted the impact of CINV-related chemotherapy discontinuation.

Topics: Antiemetics; Aprepitant; Cost-Benefit Analysis; Drug Therapy, Combination; Female; Granisetron; Humans; Male; Middle Aged; Nausea; Palonosetron; Pyridines; Vomiting

Recent studies suggested that olanzapine, together with dexamethasone and serotonin-3 receptor antagonist (5HT3RA), is effective in preventing chemotherapy-induced nausea and vomiting (CINV) following highly emetogenic chemotherapy (HEC). This regimen is particularly useful in Southeast Asia (SEA) countries where resources are limited. We aimed to evaluate the cost-effectiveness of incorporating olanzapine into standard antiemetic regimens for the prevention of CINV in patients receiving HEC among SEA countries.. Using a decision tree model, clinical and economic outcomes associated with olanzapine-containing regimen and standard antiemetic regimen (doublet antiemetic regimen: dexamethasone+first generation 5HT3RA) in most SEA countries except in Singapore (triplet antiemetic regimen: dexamethasone+first generation 5HT3RA + aprepitant) for CINV prevention following HEC were evaluated. This analysis was performed in Thailand, Malaysia, Indonesia, and Singapore, using societal perspective method with 5-day time horizon. Input parameters were derived from literature, network meta-analysis, government documents, and hospital databases. Outcomes were incremental cost-effectiveness ratio (ICER) in USD/quality-adjusted life year (QALY) gained. A series of sensitivity analyses including probabilistic sensitivity analysis were also performed.. Compared to doublet antiemetic regimen, addition of olanzapine resulted in incremental QALY of 0.0022-0.0026 with cost saving of USD 2.98, USD 27.71, and USD 52.20 in Thailand, Malaysia, and Indonesia, respectively. Compared to triplet antiemetic regimen, switching aprepitant to olanzapine yields additional 0.0005 QALY with cost saving of USD 60.91 in Singapore. The probability of being cost-effective at a cost-effectiveness threshold of 1 GDP/capita varies from 14.7 to 85.2% across countries.. The use of olanzapine as part of standard antiemetic regimen is cost-effective for the prevention of CINV in patients receiving HEC in multiple SEA countries.

Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Asia, Southeastern; Cost-Benefit Analysis; Dexamethasone; Drug Therapy, Combination; Emetics; Humans; Indonesia; Malaysia; Nausea; Olanzapine; Quality-Adjusted Life Years; Serotonin 5-HT3 Receptor Antagonists; Singapore; Vomiting

Fosaprepitant, an intravenous neurokinin-1 receptor antagonist for chemotherapy-induced nausea and vomiting, contains polysorbate 80, which is associated with infusion-site adverse events (ISAEs) and hypersensitivity systemic reactions (HSRs). This study investigated ISAEs/HSRs following fosaprepitant with anthracycline-containing chemotherapy.. This retrospective chart review noted ISAEs/HSRs following the anthracycline doxorubicin+cyclophosphamide and a three-drug fosaprepitant regimen, via peripheral line.. 35/127 patients (28%) developed ISAEs/HSRs with chemotherapy and antiemetic therapy: 32 developed 137 individual ISAEs, primarily erythema, pain and catheter-site swelling; 16 developed 50 individual HSRs, primarily edema/swelling, erythema or dermatitis (no anaphylaxis).. Fosaprepitant is associated with a significant ISAE/HSR rate following anthracycline-containing chemotherapy via peripheral line. Polysorbate 80-free intravenous neurokinin-1 receptor antagonist may provide a safer chemotherapy-induced nausea and vomiting prophylaxis option.

Topics: Administration, Intravenous; Adult; Aged; Anthracyclines; Antiemetics; Aprepitant; Cyclophosphamide; Doxorubicin; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Male; Middle Aged; Morpholines; Nausea; Neurokinin-1 Receptor Antagonists; Polysorbates; Vomiting

Chemotherapy-induced nausea and vomiting (CINV) may occur during the acute (0-24 h) or delayed (25-120 h) phase following chemotherapy administration. The addition of a neurokinin 1 receptor antagonist to antiemetic regimens containing a 5-hydroxytryptamine type 3 receptor antagonist and dexamethasone has resulted in improved CINV prophylaxis. Due to numerous adverse events and hypersensitivity reactions associated with fosaprepitant, a commonly used neurokinin 1 receptor antagonist, there remains an unmet need for better-tolerated formulations. HTX-019, the US FDA-approved polysorbate 80- and synthetic surfactant-free aprepitant injectable emulsion, is bioequivalent to and better tolerated (fewer treatment-emergent adverse events) than fosaprepitant. HTX-019 represents a valuable alternative to fosaprepitant for CINV prophylaxis.

Topics: Aprepitant; Clinical Trials as Topic; Drug-Related Side Effects and Adverse Reactions; Humans; Induction Chemotherapy; Morpholines; Nausea; Neurokinin-1 Receptor Antagonists; Polysorbates; Receptors, Neurokinin-1; Vomiting

Polypharmacy of elderly oncology patients and fragmented medication management are well-known risk factors for drug-drug interactions (DDIs). These interactions can occur among antineoplastic, ongoing chronic treatment(s) and chemotherapy-associated treatments, like antiemetics. Clinically relevant interactions based on enzyme- or transporter-inhibition phenomena of active drugs can increase the frequency of their DDIs. We describe a strongly suspected elderly cancer patient's DDI between aprepitant and opium powder in the context of an irinotecan-based regimen manifested by nightmares and visual hallucinations. We discuss this DDI's hypothetical pharmacological mechanisms and management.

Topics: Adenocarcinoma; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Arthralgia; Camptothecin; Dreams; Drug Interactions; Fluorouracil; Hallucinations; Humans; Leucovorin; Male; Nausea; Opium; Polypharmacy; Powders; Sigmoid Neoplasms

Nausea is more difficult to control than vomiting in chemotherapy. We therefore analyzed the efficacy of a strong supportive treatment with aprepitant, palonosetron, and dexamethasone against nausea for various moderately emetogenic chemotherapy (MEC).. A total of 312 cases treated by palonosetron with or without aprepitant receiving MEC regimens using oxaliplatin, carboplatin, and irinotecan from 2014 to 2016 in our outpatient center for digestive organ cancers, lung cancers, and gynecological cancers were analyzed. Through propensity score matching analysis, cases were divided into 97 cases receiving 2 drugs (palonosetron+dexamethasone) and 97 receiving 3 drugs (aprepitant+palonosetron+dexamethasone). We examined the control rates of nausea for the first two consecutive courses in the both groups. Additionally, risk factors for acute and delayed nausea were analyzed using a multivariate analysis among overall 312 cases.. The control rates of nausea in the two- and the three-drug groups were as follows: acute, 92.8 and 95.9% (p = 0.35); and delayed, 83.5 and 81.4% (p = 0.85), although the control rates of vomiting exceeded 95% in both groups. A multivariate analysis showed that significant risk factors for acute nausea (odds ratio, 95% confidence interval) were elevation of serum creatinine (12.601, 2.437-65.157), general fatigue (3.728, 1.098-12.661), and performance status (PS) 2 (19.829, 3.200-122.865). The significant risk factors for delayed nausea were elevation of alanine aminotransferase (2.397, 1.153-4.984), general fatigue (2.652, 1.380-5.097), and PS 2 (5.748, 1.392-23.740).. The control for nausea in MEC was insufficient even with palonosetron and aprepitant, and we should pay attention to risk factors for preventing nausea.

Topics: Aged; Antiemetics; Antineoplastic Agents; Aprepitant; Dexamethasone; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Nausea; Neoplasms; Palonosetron; Treatment Outcome

HTX-019 [CINVANTI. This retrospective review involved six sites in Alabama, USA. Analyzed patients were 18-94 years old with an Eastern Cooperative Oncology Group performance status ranging from 0 to 4. Seventy-six chemotherapy regimens were utilized (emetogenicity high, n = 35; moderate, n = 35; low, n = 6) and patients received HTX-019 130 mg only or switched from fosaprepitant 150 mg to HTX-019 130 mg within a three-drug antiemetic regimen with a 5-hydroxytryptamine type 3 RA and dexamethasone. HTX-019 was administered via IV push. Electronic medical records of patients receiving HTX-019 were queried for nursing and medical documentation associated with infusion-site adverse events (ISAEs). The detailed notes were also reviewed for any discontinuation of HTX-019 or substitution of HTX-019 with another NK-1 RA.. The HTX-019 safety profile was analyzed on the basis of 2066 IV push administrations in 591 cancer patients (most common diagnoses: lung, n = 107; breast, n = 100; colon, n = 92). No clinically significant ISAEs or adverse events associated with HTX-019 were reported. Also, no patients discontinued HTX-019 treatment, and none switched from HTX-019 to another NK-1 RA.. This is the first study to demonstrate that HTX-019 can be safely administered via IV push in patients with cancer receiving emetogenic chemotherapy while negating the need for fluid bags, which are scarce.. Heron Therapeutics, Inc., San Diego, CA, USA. Plain language summary available for this article.

Topics: Administration, Intravenous; Adolescent; Adult; Aged; Aged, 80 and over; Antiemetics; Antineoplastic Agents; Aprepitant; Female; Humans; Male; Middle Aged; Morpholines; Nausea; Neoplasms; Neurokinin-1 Receptor Antagonists; Retrospective Studies; Vomiting; Young Adult

Neurokinin-1 receptor antagonist (NK. A decision-analytic model was developed according to the necessity of aprepitant and CINV responses in both acute and delayed phases of chemotherapy. Probabilities of health states and medical costs were derived from the results of the abovementioned trial.. In patients who received HEC and needed aprepitant, the incremental cost-effectiveness ratio (ICER) with aprepitant, relative to the regimen with no aprepitant, was 7912 US dollars (USD) per quality-adjusted life year (QALY) gained, which was far below the commonly accepted threshold of 50,000 USD/QALY. The ICER was 27,457 USD/QALY in patients who received MEC and needed aprepitant. In contrast, in patients who received HEC or MEC but did not need aprepitant, the ICER was 175,959 or 478,844 USD/QALY, respectively.. Regardless of whether a patient received HEC or MEC, aprepitant use was highly cost-effective for patients who truly needed it. These results warrant further research to predict the necessity of NK

Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Cost-Benefit Analysis; Emetics; Humans; Japan; Middle Aged; Nausea; Neurokinin-1 Receptor Antagonists; Quality-Adjusted Life Years; Vomiting

We aimed to investigate the efficacy of 0.25 mg dose of palonosetron and granisetron in triplet antiemetic prophylaxis in breast cancer patients receiving HEC.. Patients with nonmetastatic breast cancer who received HEC [doxorubicin or epirubicin plus cyclophosphamide (AC/EC)] were enrolled in the study. The prophylactic triplet antiemetic regimens were used according to the doctor's preference during the first cycle of HEC as intravenous dexamethasone and palonosetron 0.25 mg or granisetron 3 mg on day 1 as well as oral aprepitant (125 mg on day 1 and 80 mg on days 2 and 3).The primary endpoint was complete response rate (CR) on acute and delayed chemotherapy-induced nausea and vomiting (CINV), separately.. A total of 118 female patients were included in the study. Patients received AC (83%), EC (3%), and dose-dense AC (14%) as adjuvant (88%) or neoadjuvant (12%). The majority of patients received palonosetron (59%) containing antiemetic treatment. The CR rate on acute and delayed vomiting was very high and not statistically different in both of the arms (acute 87% vs. 96%, p = 0.089; delayed 90% vs. 92%, p = 0.489), respectively. Nevertheless, the CR rate on either acute or delayed nausea was lower than vomiting (acute 51% vs. 51%; delayed 38% vs. 29%, p = 0.203; respectively).. This is the second study that compared a 0.25 mg dose of palonosetron with first-generation setron in triplet antiemetic prophylaxis in cancer patients receiving HEC. We could not find meaningful statistical differences between two arms, regarding CR rate on acute and delayed CINV.

Topics: Adult; Aged; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Breast Neoplasms; Cyclophosphamide; Dexamethasone; Doxorubicin; Drug Therapy, Combination; Epirubicin; Female; Granisetron; Humans; Middle Aged; Nausea; Palonosetron; Prospective Studies; Vomiting

Clinical trials have shown that the addition of aprepitant (APR) or a phosphorylated prodrug of aprepitant, fosaprepitant (FosAPR) as prophylactic antiemetic therapy consisting of a 5-hydrotryptamine-3 receptor antagonist and dexamethasone is effective in patients receiving highly emetogenic chemotherapy. These combination therapies have been commonly used in Japan. In the present study, we performed a cost-utility analysis of APR and FosAPR in the context of the Japanese medical insurance system, and economic efficiency was compared.. Data from randomized controlled trials that examined the efficacy of APR and FosAPR in the Japanese population were used. A decision tree was constructed to estimate the effectiveness of chemotherapy for 5 days from the day of the treatment and the cost associated with outpatient chemotherapy from the perspective of a payer. Health outcome was expressed in quality-adjusted life-years (QALYs), and costs were estimated based on medical fees and drug prices from 2018. An incremental cost-effectiveness ratio (ICER) was calculated for each regimen containing either APR or FosAPR. The robustness of the model was assessed using 1-way and probabilistic sensitivity analysis.. The base-case analysis estimated that the addition of APR or FosAPR would have incremental effects of 0.00166 and 0.00143 QALY and incremental costs of 8305 and 11,348 JPY (74 and 101 USD [1 USD = 112.17 JPY]), resulting in ICERs of 4,992,172 and 7,955,560 JPY/QALY (44,505 and 70,924 USD/QALY), respectively. Sensitivity analysis revealed that the probability of a complete response for delayed chemotherapy-induced nausea and vomiting had the most influence on the ICERs. Reductions in the drug costs of APR and FosAPR also had an effect on the ICERs. According to the probabilistic sensitivity analysis, APR and FosAPR were dominant in terms of cost-effectiveness in 48.7% and 8.55% of cases, respectively.. The ICER of outpatient prophylactic antiemetic therapy in patients receiving highly emetogenic chemotherapy was calculated in the context of the Japanese medical insurance system. Assuming the willingness-to-pay of 5,000,000 JPY/QALY based on the calculated ICER, our findings suggest that although the addition of APR is cost-effective, FosAPR is not cost-effective.

Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Cost-Benefit Analysis; Dexamethasone; Drug Costs; Female; Humans; Japan; Male; Morpholines; Nausea; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; Vomiting

Scleroderma is a disease characterized by excessive deposition of collagen and extracellular matrix proteins in affected organ systems, which results in tissue fibrosis and organ dysfunction. It is estimated that 90% of patients with systemic sclerosis have gastrointestinal involvement, with approximately 50% being symptomatic. Clinical manifestations of gastrointestinal scleroderma manifestations relate to impaired motility and absorption and ultimately malnutrition. Treatments for these symptoms often fail and are limited. The objective of this case report is to highlight the potential use of a substance P antagonist in the treatment of scleroderma associated nausea.. A 56-year-old woman presented with GI complications of her underlying systemic sclerosis. The majority of her stay was marked by severe nausea and vomiting, resistant to numerous therapies. Obstructive causes for her symptoms were ruled out with a gastroscopy. A motility study revealed completely absent peristalsis in her esophagus, likely due to complete fibrosis of smooth muscle fibres. For the first time, off-label use of aprepitant 80 mg once daily was trialed with success in hospital. With this medication, she was able to maintain an adequate oral intake and ultimately achieve discharge from hospital.. Despite the wide array of medications for gastrointestinal scleroderma, their effect is very limited. In this article, we report to the best of our knowledge the first successful use of the substance P antagonist aprepitant to treat refractory nausea and vomiting in a patient with gastrointestinal scleroderma. Not only does this medication carry promise in treating the GI symptoms of scleroderma, but it may also prove cost effective as compared to PEG insertions or TPN. This case study is congruent with recent evidence of the utility of aprepitant in other infiltrative disease conditions. This may spur interest randomized control trials for expanding the role of this medication.

Topics: Aged; Antiemetics; Aprepitant; Female; Humans; Nausea; Off-Label Use; Scleroderma, Systemic; Vomiting

Breast cancer patients often receive anthracycline-based chemotherapy, and chemotherapy-induced nausea and vomiting (CINV) remains one of the most uncomfortable and distressing adverse reactions. Poor control of CINV reduces the relative dose intensity of chemotherapy agents, which has been associated with poor clinical outcomes and shorter survival. The aim of the present study was to identify genetic risk factors associated with anthracycline-based CINV.. We evaluated CINV attributable to anthracycline-based chemotherapy in Japanese breast cancer patients treated with an antiemetic regimen that included palonosetron, aprepitant, and dexamethasone. Furthermore, we investigated the associations between CINV and single nucleotide polymorphisms in 6 candidate genes.. Emesis episodes were rarely observed in the 125 patients included in the present survey (7.2%; n = 9); however, significant nausea occurred in more than one half of the patients (52.8%; n = 66). In particular, acute significant nausea was not effectively controlled. Multivariate logistic regression analysis revealed that the ABCG2 (rs2231142) AA genotype is significantly associated with acute significant nausea (odds ratio, 4.87; 95% confidence interval, 1.01-23.60; P = .049).. The findings of the present study provide significant insights for developing personalized antiemetic strategies for breast cancer patients receiving anthracycline-based chemotherapy.

Topics: Adult; Anthracyclines; Antibiotics, Antineoplastic; Antiemetics; Aprepitant; ATP Binding Cassette Transporter, Subfamily G, Member 2; Breast Neoplasms; Dexamethasone; Female; Genetic Predisposition to Disease; Humans; Middle Aged; Nausea; Neoplasm Proteins; Odds Ratio; Palonosetron; Polymorphism, Single Nucleotide; Prospective Studies; Risk Factors; Treatment Outcome; Vomiting

Chemotherapy-induced nausea and vomiting (CINV) remains a challenge in cancer care. Improved understanding of CINV pathophysiology has triggered the development of new antiemetic therapeutic options, such as selective neurokinin-1 (NK

Topics: Antiemetics; Aprepitant; Dexamethasone; Humans; Morpholines; Nausea; Neoplasms; Neurokinin-1 Receptor Antagonists; Receptors, Neurokinin-1; Risk Factors; Serotonin 5-HT3 Receptor Antagonists; Sex Characteristics; Treatment Outcome; Vomiting

Topics: Antiemetics; Aprepitant; Humans; Nausea; Palonosetron; Pyridines; Vomiting

Topics: Aprepitant; Contraceptive Agents; Humans; Morpholines; Nausea

Topics: Aprepitant; Contraceptive Agents; Humans; Morpholines; Nausea

Topics: Antineoplastic Agents; Aprepitant; Hematopoietic Stem Cell Transplantation; Humans; Melphalan; Nausea; Olanzapine; Retrospective Studies; Transplantation, Autologous; Vomiting

The antiemetic effects and safety of granisetron and palonosetron against chemotherapy-induced nausea and vomiting (CINV) were retrospectively evaluated in patients with non-Hodgkin lymphoma receiving bendamustine-based chemotherapy. A total of 61 patients were eligible for this study. Before starting the bendamustine-based chemotherapy, granisetron or palonosetron were intravenously administered with or without aprepitant and/or dexamethasone. The proportions of patients with complete control (CC) during the overall (during the 6 days after the start of the chemotherapy), acute (up to 2 days), and delayed (3 to 6 days) phases were assessed. CC was defined as complete response with only grade 0-1 nausea, no vomiting, and no use of antiemetic rescue medication. Granisetron or palonosetron alone were administered to 9 and 19 patients, respectively. Aprepitant and/or dexamethasone were combined with granisetron and palonosetron in 28 and 5 patients, respectively. Acute CINV was completely controlled in all patients. Both granisetron monotherapy and palonosetron combination therapy could provide good control of delayed CINV, although the CC rates during the delayed and overall phases were not significantly different among mono- and combination therapy of the antiemetics. There was no significant difference in the frequencies of adverse drug events between the granisetron and palonosetron treatment groups. The present study showed that the antiemetic efficacy and safety of granisetron-based therapy were non-inferior to those of palonosetron-based therapy. Taken together with treatment costs, granisetron monotherapy would be adequate to prevent CINV in patients with non-Hodgkin lymphoma receiving bendamustine-based chemotherapy.

Topics: Aged; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Bendamustine Hydrochloride; Dexamethasone; Female; Granisetron; Humans; Lymphoma, Non-Hodgkin; Male; Middle Aged; Nausea; Palonosetron; Retrospective Studies; Vomiting

Topics: Alemtuzumab; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Busulfan; Cyclosporine; Gastroparesis; Hematopoietic Stem Cell Transplantation; Humans; Infant; Lymphohistiocytosis, Hemophagocytic; Male; Methotrexate; Nausea; Unrelated Donors; Vidarabine; Vomiting

Aprepitant prevents chemotherapy-induced nausea and vomiting (CINV) in carboplatin-containing chemotherapy. However, it is unknown whether aprepitant salvage therapy after the development of emesis is as effective as adding prophylactic aprepitant to doublet therapy with dexamethasone and a 5-HT

Topics: Adult; Aged; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Carboplatin; Carcinoma, Non-Small-Cell Lung; Female; Humans; Lung Neoplasms; Male; Middle Aged; Nausea; Pre-Exposure Prophylaxis; Propensity Score; Prospective Studies; Salvage Therapy; Vomiting

Chemotherapy is the most important method for cancer treatment. However, chemotherapy induced nausea and vomiting (CINV) has a profound effect on patients. In recent years, there have been new antiemetic drugs, such as aprepitant. We review the curative effect of aprepitant with tropisetron and dexamethasone for prevention of nausea and vomiting in patients receiving Cisplatin chemotherapy.. Observation is divided into three stages. Whole study phase (0-120 h after chemotherapy administration), acute phases (0-24 h), and delayed phase (24 h-120 h). The primary endpoints were complete response (CR) and complete prevention (CP) during the three different study phase.. In the whole study phase, 86.02% of patients achieved CR; in acute phases and delayed phases were 89.25%, 87.1%, respectively. CP were 46.22%, 83.87%, 45.16%, respectively. Anti-CINV effect was significantly associated with age distribution (P=0.008).. Aprepitant with tropisetron and dexamethasone prevented effectively CNIV for patients receiving Cisplatin chemotherapy. This combination could improve the quality of life and the compliance of patient with chemotherapy.. 【中文题目：阿瑞匹坦预防化疗诱导恶心呕吐
的疗效分析】 【中文摘要：背景与目的 化疗是治疗恶性肿瘤最重要的手段，然而化疗诱导的恶心呕吐对患者影响深远。近些年来，不断有新的止吐药物问世，如阿瑞匹坦。我们回顾性分析了2014年8月-2016年12月使用含高度致吐药顺铂化疗方案的肿瘤患者中，阿瑞匹坦联合托烷司琼、地塞米松预防化疗诱导呕吐（chemotherapy-induced nausea and vomiting, CINV）的效果。方法 在使用含高度致吐药顺铂化疗方案的肿瘤患者中，应用阿瑞匹坦联合托烷司琼、地塞米松的止吐方案，观察期分为整体观察期：化疗后0 h-120 h；急性呕吐观察期：化疗0 h-24 h；延迟性呕吐观察期：化疗后24 h-120 h。观察目标包括完全应答（complete response, CR）和完全预防（complete protection, CP）。结果 整体观察期的CR为86.02%，急性呕吐观察期和延迟性呕吐观察期分别为89.25%、87.1%；CP分别为46.22%、83.87%、45.16%。止吐效果与年龄分布关系具有显著性（P=0.008）。结论 阿瑞匹坦联合托烷司琼、地塞米松的方案可有效预防使用含高度致吐药顺铂化疗方案的肿瘤患者中CINV的发生，提高患者的生活质量和化疗的依从性。
】 【中文关键词：阿瑞匹坦；癌症；化疗诱导的恶心呕吐；顺铂】.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Aprepitant; Cisplatin; Female; Humans; Male; Middle Aged; Morpholines; Nausea; Quality of Life; Vomiting

This study aimed to compare the antiemetic efficacy and safety of a four-drug combination with those of a standard three-drug combination in Japanese patients with breast cancer treated with anthracycline. We retrospectively analyzed data from Japanese patients with breast cancer, who had received their first cycle of anthracycline and were treated with aprepitant, palonosetron, and dexamethasone with or without olanzapine. This retrospective observational study was performed at Ehime University Hospital using the electronic medical records. Multivariable and propensity score-adjusted analyses were performed to compare the onset of complete response (CR) failure between the groups. One-hundred and thirty patients were included in this study and the four- and three-drug group had 22 and 108 patients, respectively. Similar to multivariable logistic regression analysis, propensity-adjusted logistic regression analysis revealed that the four-drug group was markedly associated with a decreased odds of CR failure in the overall, acute, and delayed phases (odds ratio [OR]: 0.27, 95% confidence interval [CI]: 0.10-0.73; OR: 0.28, 95% CI: 0.10-0.76; and OR: 0.15, 95% CI: 0.04-0.57, respectively). Additionally, treatment-related adverse events were well tolerated in both the groups. These findings suggest that the antiemetic efficacy of the four-drug combination is superior to that of the standard three-drug combination.

Topics: Anthracyclines; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Breast Neoplasms; Dexamethasone; Drug Therapy, Combination; Female; Humans; Incidence; Middle Aged; Nausea; Olanzapine; Palonosetron; Retrospective Studies; Sleep Initiation and Maintenance Disorders; Sleepiness; Treatment Outcome; Vomiting

The aim of this study was to identify a high-risk or low-risk population for chemotherapy-induced nausea and vomiting among patients with breast cancer treated with a current standard 3-drug antiemetic regimen and receiving anthracycline.. We analyzed data from chemotherapy-naive Japanese patients with breast cancer, who had received the first cycle of anthracycline-based regimen and were treated with a 3-drug combination of aprepitant, palonosetron, and dexamethasone. This study was carried out at Ehime University Hospital (Toon, Japan) using electronic medical records from May 2011 to June 2017. The primary end point was complete response (CR), which was defined as no emesis and no use of rescue medication.. A total of 103 patients were included in this study. The percentages of patients who had a CR in the overall, acute, and delayed phases were 35.0%, 40.8%, and 50.5%, respectively. Multivariate logistic regression analysis revealed that age <55 years and body mass index <27.5 kg/m. The present findings suggest that, among patients with breast cancer receiving anthracycline and treated with aprepitant, palonosetron, and dexamethasone, patients younger than 55 years and having a body mass index <27.5 kg/m

Topics: Anthracyclines; Antiemetics; Antineoplastic Agents; Aprepitant; Breast Neoplasms; Dexamethasone; Female; Humans; Middle Aged; Nausea; Palonosetron; Retrospective Studies; Risk Factors; Vomiting

Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Drug Interactions; Humans; Infusions, Intravenous; Nausea; Neurokinin-1 Receptor Antagonists; Treatment Outcome; Vomiting

This study was conducted to evaluate the efficacy and the difference in effects of the oral neurokinin-1(NK-1) receptor antagonist aprepitant for chemotherapy-induced nausea/vomiting (CINV) in Japanese patients with gynecological cancer receiving highly emetogenic (cisplatin) and moderately emetogenic (carboplatin) chemotherapy.. Aprepitant was added during the second course of chemotherapy in Japanese patients with grade ≥ 2 (Common Terminology Criteria for Adverse Events, version 3.0) nausea and vomiting during the first course despite receiving antiemetic therapy (a first-generation 5-hydroxytryptamine 3 receptor antagonist + dexamethasone), and in patients who requested stronger antiemetic therapy despite only having grade 1 nausea and vomiting. The incidence of nausea and vomiting was compared between the first and second courses in each group.. Ninety-six (55.5%) out of 173 patients received add-on therapy with aprepitant. There was a significant increase in the complete response (CR: no vomiting or salvage therapy) rate in the patients receiving aprepitant, with marked improvement being confirmed for delayed CINV. Stratified analysis showed that patients with delayed CINV treated with carboplatin had a significantly higher CR rate, while patients with both acute and delayed CINV treated with cisplatin had significantly higher CR rates. There was a positive correlation between the incidence of nausea and the incidence of vomiting in the patients treated with aprepitant.. The oral NK-1 receptor antagonist aprepitant could be effective for both acute and delayed CINV with cisplatin and for delayed CINV with carboplatin in Japanese gynecological cancer patients.

Topics: Adult; Aged; Antineoplastic Agents; Aprepitant; Carboplatin; Cisplatin; Female; Genital Neoplasms, Female; Humans; Japan; Middle Aged; Morpholines; Nausea; Neurokinin-1 Receptor Antagonists; Outcome Assessment, Health Care; Vomiting

Acute and delayed chemotherapy-induced nausea and vomiting (CINV) occurs in most patients who receive high-dose melphalan and significantly affects patients' quality of life during autologous stem cell transplantation. Faced with unsatisfactory results using an aprepitant-based regimen, an olanzapine-based regimen was initiated, with the hope of improving the incidence of acute and delayed CINV. A retrospective study was conducted to compare the effectiveness of olanzapine- versus aprepitant-based regimens for CINV prevention in adult hematopoietic stem cell recipients who received high-dose melphalan.. We compared olanzapine (n = 43) to aprepitant (n = 54) and fosaprepitant (n = 20). Olanzapine was given orally at 5 mg twice daily for 5 days, aprepitant was given at 125 mg on day -1 and 80 mg on days 0 and 1, and fosaprepitant was given at 150 mg on day -1. The dose of 2 concomitant drugs (dexamethasone and 5-hydroxytryptamine type 3 receptor antagonist) was similar in the 2 groups. Nausea prevention was the primary endpoint. A complete response using a composite index of no emesis and no use of rescue medications was the secondary endpoint.. The results showed that olanzapine significantly reduced the number of patients who experienced acute (P < .0001) or delayed (P < .004) nausea and significantly reduced the use of rescue medications for acute-onset (P < .0046) and delayed-onset (P < .0001) CINV compared with aprepitant.. Compared with fosaprepitant, olanzapine reduced the number of patients with acute (P < .0318) and delayed (P < .1519) nausea and reduced the need for rescue medications for acute-onset (P < .0643) and delayed-onset (P < .0024) CINV.

Topics: Adult; Aged; Algorithms; Antiemetics; Aprepitant; Benzodiazepines; Disease Management; Female; Hematopoietic Stem Cell Transplantation; Humans; Induction Chemotherapy; Male; Melphalan; Middle Aged; Morpholines; Multiple Myeloma; Myeloablative Agonists; Nausea; Olanzapine; Transplantation Conditioning; Treatment Outcome; Vomiting

The objective of this study was to determine the effect of aprepitant(from days 1 to 3, po)and fosaprepitant(day 1, iv) for nausea in patients with oral cancer receiving combination chemotherapy with docetaxel, nedaplatin, or cisplatin(divided doses for 5 days), and 5-fluorouracil(TPF).The incidence rate of nausea in the aprepitant group was 60%(6/10), and that in the fosaprepitant group was 90%(9/10).The incidence rate of continuous nausea for more than 2 days was significantly lower in the aprepitant group than in the fosaprepitant group(40%[4/10]vs 90%[9/10], p=0.02; c 2 test).In addition, the mean area under the curve of the chronological changes in the grade of nausea tended to be lower in the aprepitant group than in the fosaprepitant group.In both groups, 3 cases(30%)of vomiting were observed.However, the incidence of continued daily vomiting tended to be lower in the aprepitant group than in the fosaprepitant group.These results suggest that aprepitant is more effective than fosaprepitant for nausea induced by TPF.

Topics: Aged; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Cisplatin; Docetaxel; Female; Fluorouracil; Humans; Male; Morpholines; Nausea; Organoplatinum Compounds; Taxoids

To evaluate the clinical and cost benefits of the administration of aprepitant for the prophylaxis of chemotherapy-induced nausea and vomiting (CINV) during high-dose chemotherapy (HDCT).. We retrospectively reviewed the charts of patients who received HDCT at our institution between January 2009 and December 2013. Cost-effectiveness was analyzed using direct medical costs.. We identified a total of 38 patients (27 with non-Hodgkin lymphoma and 11 with multiple myeloma). Thirteen patients received aprepitant and granisetron (aprepitant group) for CINV prophylaxis, whereas 25 patients received granisetron only (non-aprepitant group). The incidence of severe nausea (≥grade 3) was significantly lower in the aprepitant group than in the non-aprepitant group (p = 0.039). The total mean cost per patient during hospitalization, excluding the cost of HDCT and transplantation, was USD 10,941.8 in the aprepitant group and USD 14,577.2 in the non-aprepitant group (p = 0.041). This cost benefit reflected reductions in the costs of hospitalization, transfusion, and infection treatment.. Our data indicated that the addition of aprepitant for CINV prophylaxis during HDCT reduced the incidence of severe nausea and might also provide economic benefit in the overall management of HDCT prior to autologous peripheral blood stem cell transplantation.

Topics: Adult; Aged; Antineoplastic Agents; Aprepitant; Cost-Benefit Analysis; Female; Granisetron; Humans; Lymphoma, Non-Hodgkin; Male; Middle Aged; Morpholines; Multiple Myeloma; Nausea; Peripheral Blood Stem Cell Transplantation; Retrospective Studies; Vomiting

There is no positive evidence for the efficacy of antiemetic triplet therapy with aprepitant (APR), palonosetron (PALO), and dexamethasone (DEX) for moderate emetogenic chemotherapy, especially for gynecologic malignancies. Thus, the present study evaluated the efficacy of this triplet therapy in patients receiving carboplatin and paclitaxel (CP) for gynecologic malignancy.. Seventy patients with gynecologic cancer receiving CP were enrolled into a prospective single-arm study with APR (125 mg on day 1, 80 mg on days 2-3), PALO (0.75 mg), and DEX (20 mg) before initiating chemotherapy. The primary endpoint was delayed complete response (CR) rate, i.e., no vomiting and no rescue, at 24-120 h after chemotherapy administration.. Seventy patients were enrolled. The delayed CR rate was 97.1% (68/70). No serious adverse events were observed. Younger patient age (≤50 years) tended to be associated with a poor delayed CR rate.. This study demonstrated a notable efficacy of antiemetic triplet therapy with APR, PALO, and DEX in female patients receiving CP. Further evaluation with a larger phase III trial is warranted.

Topics: Adult; Antiemetics; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Carboplatin; Dexamethasone; Female; Genital Neoplasms, Female; Humans; Isoquinolines; Morpholines; Nausea; Paclitaxel; Palonosetron; Prospective Studies; Quinuclidines; Vomiting; Young Adult

The purpose of our study was to evaluate the efficacy of a new combination antiemetic therapy consisting of palonosetron, aprepitant, and dexamethasone in gastric cancer patients undergoing chemotherapy with S-1 plus cisplatin.. This prospective, multi-institutional observational study assessed patient-reported nausea, vomiting, use of rescue therapy, change of dietary intake, and Functional Living Index-Emesis (FLIE) questionnaire results. The percentages of patients showing complete response (CR; no emesis and non-use of any rescue antiemetics) and complete protection (CP; no significant nausea and non-use of any rescue antiemetics), change of dietary intake, and impact of chemotherapy-induced nausea and vomiting on daily life during the overall (0-120 h after cisplatin administration), acute (0-24 h), and delayed (24-120 h) phases were examined. These findings were compared with our previous study, which used granisetron, aprepitant, and dexamethasone, to assess the relative effectiveness of palonosetron versus granisetron in combination antiemetic therapy.. Of the 72 included patients, 66 (91.6 %), 70 (97.2 %), and 50 (69.1 %) achieved CR, and 48 (66.7 %), 61 (84.7 %) and 49 (68.1 %) achieved CP during in the overall, acute, and delayed phases of cisplatin administration, respectively. Approximately half of the patients had some degree of anorexia. FLIE results indicated that 78.6 % of patients maintained their quality of life. Palonosetron was not superior to granisetron in combination antiemetic therapy.. Three-drug combination antiemetic therapy with palonosetron, aprepitant, and dexamethasone was tolerable in gastric cancer patients undergoing treatment with S-1 plus cisplatin. The predominance of palonosetron to granisetron was not demonstrated in this study.

Topics: Aged; Aged, 80 and over; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Cisplatin; Dexamethasone; Drug Combinations; Drug Therapy, Combination; Female; Granisetron; Humans; Isoquinolines; Male; Middle Aged; Morpholines; Nausea; Oxonic Acid; Palonosetron; Prospective Studies; Quality of Life; Quinuclidines; Stomach Neoplasms; Surveys and Questionnaires; Tegafur; Vomiting

Antiemetic prophylaxis with aprepitant, a 5-hydroxytryptamine3 (5-HT3) receptor antagonist and dexamethasone is recommended for patients receiving intravenous cisplatin chemotherapy. Whether the same antiemetic regime is superior for hepatic transcatheter arterial infusion chemotherapy with cisplatin (CDDP-TAI) is unknown. We conducted a retrospective study of antiemetic prophylaxis protection against chemotherapy-induced nausea and vomiting (CINV) in CDDP-TAI at Nagasaki University Hospital. The rate of complete response (CR) to antiemetics in the acute (<24 h) and delayed phases (24-120 h) was measured. Twenty-four patients were treated with a 5-HT3 receptor antagonist (granisetron or azasetron) and dexamethasone on the day of chemotherapy (day 1 only). There was a significant difference between the CR rates in the acute and delayed phases, 91.6, and 69.7%, respectively. Combination of a 5-HT3 antagonist and dexamethasone on day 1 is effective against acute CINV, but not delayed CINV during CDDP-TAI. These results may help guide the management of nausea and vomiting during CDDP-TAI to achieve better tolerance and compliance for fewer interventions and increased favorable therapeutic outcomes.

Topics: Adult; Aged; Aged, 80 and over; Antiemetics; Antineoplastic Agents; Aprepitant; Bridged Bicyclo Compounds, Heterocyclic; Catheterization, Peripheral; Cisplatin; Dexamethasone; Drug Therapy, Combination; Female; Granisetron; Humans; Isoquinolines; Liver; Liver Neoplasms; Male; Middle Aged; Morpholines; Nausea; Oxazines; Palonosetron; Quinuclidines; Serotonin 5-HT3 Receptor Antagonists; Vomiting

This study investigated the prevalence of chemotherapy-induced nausea and vomiting (CINV) in patients with hepatobiliary-pancreatic (HBP) cancer in a prospective nationwide survey.. One hundred patients with HBP cancer (biliary tract cancer; n=70, hepatocellular carcinoma; n=20, and pancreatic cancer; n=10) who received chemotherapy for the first time were analyzed. Medical personnel were surveyed to examine the accuracy of their predicted frequency of CINV.. The compliance rate with the Japanese guideline with highly emetogenic chemotherapy was 36/89 (40%). Although the prevalence of CINV in patients with HBP cancer was significantly lower than that of the total 1,910 patients with cancer, the prevalence of delayed CINV in patients with HBP cancer was as high as 28%. The survey results suggested that the medical staff tended to overestimate the incidence of CINV.. CINV appears to be controlled under management according to the guidelines, but delayed nausea remains prevalent and requires further investigation.

Topics: Adult; Aged; Aged, 80 and over; Antiemetics; Antineoplastic Agents; Aprepitant; Biliary Tract Neoplasms; Carcinoma, Hepatocellular; Dexamethasone; Female; Humans; Liver Neoplasms; Male; Middle Aged; Morpholines; Nausea; Pancreatic Neoplasms; Serotonin 5-HT3 Receptor Antagonists; Vomiting

The purpose of this study was to evaluate the efficacy of combined treatment with the long-acting 5-hydroxytryptamine receptor-3 antagonist, palonosetron, the neurokinin-1 receptor antagonist, oral aprepitant, and dexamethasone as primary antiemetic prophylaxis for cancer patients receiving highly emetogenic cisplatin-based chemotherapy.. Chemotherapy-naïve patients received the triple combination of palonosetron (0.25 mg), aprepitant (125 mg on day 1 and 80 mg on days 2 and 3), and dexamethasone (20 mg) from the beginning of highly emetogenic chemotherapy with cisplatin-based (≥50 mg/m(2)) regimens. The primary endpoint was a complete response (no emetic episodes and no rescue antiemetics) during the days 1-6.. Sixty-nine hospitalized patients receiving chemotherapy from September 2012 to October 2014 were analyzed. Complete response of vomiting and nausea-free was achieved in 97.1% and 85.5% of patients in the first cycle, respectively, and 96.7% and 83.6% of patients in the second cycle, respectively. Common adverse events in all 69 patients included constipation (43%), hiccup (26%), and headache (4%).. The combination of palonosetron, aprepitant, and dexamethasone as primary antiemetic prophylaxis for cancer patients with highly emetogenic cisplatin-based chemotherapy is effective.

Topics: Adult; Aged; Aged, 80 and over; Antiemetics; Antineoplastic Agents; Aprepitant; Cisplatin; Dexamethasone; Drug Therapy, Combination; Female; Humans; Isoquinolines; Male; Middle Aged; Morpholines; Nausea; Neoplasms; Palonosetron; Quinuclidines; Treatment Outcome; Vomiting

Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Benzodiazepines; Dexamethasone; Drug Therapy, Combination; Female; Humans; Middle Aged; Morpholines; Nausea; Olanzapine; Ondansetron; Vomiting

To assess the efficacy and tolerability of oral aprepitant, a substance P/neurokinin A receptor antagonist, in controlling nausea associated with IV dihydroergotamine (DHE) administered for medically refractory migrainous headache in patients not responding to standard antiemetics or with a history of uncontrolled nausea with DHE.. This was a retrospective chart review of prospectively collected hourly diary data and clinical notes of patients hospitalized between 2011 and 2015 for inpatient treatment with DHE. Patients were classified using the International Classification of Headache Disorders, 3rd edition (beta version). Peak and average daily nausea scores from hourly diaries, or daily entries of notes, and concurrent antiemetic use were collected and tabulated.. Seventy-four patients, of whom 24 had daily diaries, with chronic migraine with or without aura, with or without medication overuse, or new daily persistent headache of a migrainous type, were identified. In 36 of 57 cases in which aprepitant was administered during hospitalization, there was a 50% reduction in the average daily number of as-needed antinausea medications. Of 57 patients, 52 reported that the addition of aprepitant improved nausea. Among 21 of 24 patients with hourly diary data, nausea scores were reduced and in all 12 with vomiting there was cessation of emesis after aprepitant was added. Aprepitant was well tolerated with no treatment emergent adverse events.. Aprepitant can be effective in the treatment of refractory DHE-induced nausea and emesis. Given the broader issue of troublesome nausea and vomiting in acute presentations of migraine, general neurologists may consider what place aprepitant has in the management of such patients.. This study provides Class IV evidence that for patients with medically refractory migraine receiving IV DHE, oral aprepitant reduces nausea.

Topics: Administration, Intravenous; Administration, Oral; Analgesics, Non-Narcotic; Antiemetics; Aprepitant; Dihydroergotamine; Humans; Inpatients; Migraine Disorders; Morpholines; Nausea; Prospective Studies; Retrospective Studies; Treatment Outcome

Concomitant use of temozolomide (TMZ) and radiotherapy, which is the standard therapy for patients with high-grade glioma, involves a unique regimen with multiple-day, long-term administration. In a previous study, we showed not only higher incidence rates of chemotherapy-induced nausea and vomiting (CINV) during the overall study period, but also substantially higher incidence rates of moderate/severe nausea and particularly severe appetite suppression during the late phase of the treatment. Here, we prospectively evaluated the efficacy of a combination of palonosetron, aprepitant, and dexamethasone for CINV in patients treated with concomitant TMZ and radiotherapy. Twenty-one consecutive patients with newly diagnosed high-grade glioma were enrolled. CINV was recorded using a daily diary and included nausea assessment, emetic episodes, degree of appetite suppression, and use of antiemetic medication. The percentage of patients with a complete response in the overall period was 76.2%. The percentages of patients with no moderate/severe nausea were 90.5, 100, and 90.5% in the early phase, late phase, and overall period, respectively. Severe appetite suppression throughout the overall period completely disappeared. The combination of palonosetron, aprepitant, and dexamethasone was highly effective and well tolerated in patients treated with concomitant TMZ and radiotherapy. This combination of antiemetic therapy focused on delayed as well as acute CINV and may have the potential to overcome CINV associated with a multiple-day, long-term chemotherapy regimen.

Topics: Adult; Aged; Antiemetics; Antineoplastic Agents, Alkylating; Aprepitant; Brain Neoplasms; Dacarbazine; Dexamethasone; Drug Therapy, Combination; Female; Glioma; Humans; Isoquinolines; Male; Middle Aged; Morpholines; Nausea; Palonosetron; Prospective Studies; Quinuclidines; Serotonin Antagonists; Temozolomide; Vomiting

Radiation-induced nausea and vomiting (RINV) is one of the most distressing symptoms that adversely affects quality of life (QOL) as well as the ongoing management plan of cancer patients. Although there are protocols for management of chemotherapy induced nausea and vomiting (CINV) but such guidelines are still lacking for RINV. Various agents like 5-hydroxy tryptophan 3 (5-HT3) antagonist, dexamethasone, metoclopramide and haloperidol are used in clinical practice for RINV but the results are not very encouraging. Because of proposed similarity in the mechanism of nausea and vomiting following chemotherapy and radiotherapy, aprepitant, a substance P neurokinin 1 receptor antagonist can be an optimal agent for RINV on account of its unique pharmacological property. We report a case of metastatic carcinoma breast with bilateral cerebellar metastasis. She presented with complaints of headache and intractable nausea and vomiting. A single fraction whole brain radiotherapy (WBRT) was given for bilateral cerebellum metastasis which further precipitated her symptoms. The prophylactic and therapeutic efficacy of antiemetic used for RINV may be enhanced by adding aprepitant before starting radiotherapy in high risk cases as in ours.

Topics: Antiemetics; Aprepitant; Brain Neoplasms; Female; Humans; Middle Aged; Morpholines; Nausea; Palliative Care; Tomography, X-Ray Computed; Vomiting

The objective of this study was to evaluate five commercial ready-to-use transdermal vehicles (Phytobase

Topics: Administration, Cutaneous; Animals; Antiemetics; Antineoplastic Agents; Aprepitant; Chemistry, Pharmaceutical; Dexamethasone; Drug Carriers; Humans; Lecithins; Morpholines; Nausea; Ondansetron; Pharmaceutical Vehicles; Swine; Vomiting

Appropriate antiemetic prophylaxis for moderately emetogenic chemotherapy in patients with non-round cell soft-tissue sarcomas (NRC-STS) remains unclear. We retrospectively investigated efficacy and safety of aprepitant-combined antiemetic prophylaxis in patients with NRC-STS receiving adriamycin plus ifosfamide (AI) therapy. Forty NRC-STS patients were enrolled, their median age was 50 years (range 18-74), and 13 (32.5%) were female. Median cycle number of AI therapy was 4. Twenty patients received the doublet antiemetic prophylaxis (5-hydroxytryptamine-3 receptor antagonist and dexamethasone), and 20 received triplet (5-hydroxytryptamine-3 receptor antagonist, dexamethasone, and aprepitant). In the overall period, complete response rate for nausea and emesis in the triplet group was significantly higher than that in the doublet group (70% vs 35%; P = 0.027). Patients with no-emesis in the overall period were more frequently observed in the triplet group than in the doublet group (90% vs 65%; P = 0.058). All toxicities other than emesis were almost equivalent in both the groups. These results suggest that a triplet antiemetic prophylaxis may be optimal in the treatment with AI therapy for NRC-STS.

Topics: Adolescent; Adult; Aged; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Doxorubicin; Female; Humans; Ifosfamide; Male; Middle Aged; Morpholines; Nausea; Retrospective Studies; Sarcoma; Treatment Outcome; Young Adult

Fosaprepitant is an antiemetic used for chemotherapy-induced nausea and vomiting. We recently reported increased infusion site adverse events (ISAE) in a cohort of breast cancer patients receiving chemotherapy with doxorubicin and cyclophosphamide (AC). In this current study, we evaluated the venous toxicity of fosaprepitant use with non-anthracycline platinum-based antineoplastic regimens.. A retrospective review was conducted of the first 81 patients initiated on fosaprepitant among patients receiving highly emetogenic chemotherapy, on or after January 1, 2011 at Mayo Clinic Rochester. None of these regimens included an anthracycline. Data collected included baseline demographics, chemotherapy regimen, type of intravenous access and type, and severity of ISAE. Data from these patients were compared to previously collected data from patients who had received AC. Statistical analysis using χ 2 and univariate logistic regression was used to evaluate the association between treatment regimen, fosaprepitant, and risk of ISAE.. Among these 81 patients, the incidence of ISAE was 7.4% in the non-anthracycline platinum group. The most commonly reported ISAE were swelling (3%), extravasation (3%), and phlebitis (3%). When stratified by regimen, fosaprepitant was associated with a statistically significant increased risk of ISAE in the anthracycline group (OR 8.1; 95% CI 2.0-31.9) compared to the platinum group.. Fosaprepitant antiemetic therapy causes significant ISAE that are appreciably higher than previous reports. Patients receiving platinum-based chemotherapy appear to have less significant ISAE than do patients who receive anthracycline-based regimens.

Topics: Adult; Aged; Anthracyclines; Antiemetics; Antineoplastic Agents; Aprepitant; Cyclophosphamide; Doxorubicin; Female; Humans; Infusions, Intravenous; Male; Middle Aged; Morpholines; Nausea; Neoplasms; Phlebitis; Retrospective Studies; Vomiting; Young Adult

Chemotherapy-induced nausea and vomiting (CINV) are significant problems in cancer patients, but a correlation between plasma aprepitant concentration and antiemetic effect has not been reported. This study aimed to characterize the correlation between plasma aprepitant concentration and clinical antiemetic effect in a limited group of Japanese gastric or esophageal cancer patients.. Thirty-three Japanese cancer patients receiving cisplatin-based chemotherapy for the first time following oral aprepitant (125 mg on day 1 and 80 mg on days 2 and 3) were enrolled. The plasma aprepitant concentrations 48 h after the first administration were determined using liquid chromatography-mass spectrometry. Patients were allocated to the high-concentration group (plasma aprepitant concentration was >331.1 ng/ml) or the low-concentration group (plasma aprepitant concentration was ≤ 331.1 ng/ml) to investigate the relationship between plasma aprepitant concentration and antiemetic effects.. No significant differences were found between the two groups in terms of percentage of CINV prevention. Of 13 patients who experienced CINV [MASCC Antiemesis Tool (MAT) score >3], those in the high-concentration group showed a significant improvement in CINV following aprepitant administration (days 1-3).. The present study suggests that the antiemetic effect of aprepitant is associated with plasma aprepitant concentration. A plasma aprepitant concentration of 331.1 ng/ml may be a valid threshold for identifying its optimal antiemetic effects in Japanese gastric or esophageal cancer patients.

Topics: Aged; Antiemetics; Antineoplastic Agents; Aprepitant; Cisplatin; Drug Monitoring; Esophageal Neoplasms; Female; Gastrointestinal Neoplasms; Humans; Male; Middle Aged; Morpholines; Nausea; Stomach Neoplasms; Vomiting

Neurokinin-1 (NK-1) receptor antagonist is recommended for chemotherapy-induced nausea and vomiting (CINV) in highly emetogenic chemotherapy (HEC) and has recently been introduced to oncology practice in Japan. However, whether all patients undergoing HEC truly need NK-1 receptor antagonist remains unknown, and increasing medical costs due to uniform use of NK-1 receptor antagonist are a concern. This study was conducted to examine the prevalence of patients who needed aprepitant at the time of its introduction in Japan, and therapeutic and preventive effects of aprepitant on HEC or moderately emetogenic chemotherapy (MEC).. Eligible patients with thoracic malignancies who were to undergo HEC or MEC received 5-hydroxytryptamine receptor antagonists and dexamethasone to prevent CINV. Aprepitant was administered to treat CINV occurring in the first course, or to prevent CINV in the second course. Frequency of vomiting, degree of nausea, and quality of life with respect to CINV were assessed.. In total, 96 patients were enrolled. Aprepitant was not administered in 57 and 88 % of patients who received HEC and MEC, respectively. In patients treated with aprepitant (n = 18), therapeutic use of aprepitant after occurrence of CINV (n = 9) decreased average scores in numerical rating scale for nausea from 7.44 to 5.44 (p = 0.10), and average frequency of vomiting per day from 2.11 to 0.11 (p = 0.03). Prophylactic use of aprepitant in the second course (n = 18) increased the proportion of patients with no significant nausea from 6 % (first course) to 50 % (second course; p = 0.007), and those with no vomiting from 33 to 89 % (p = 0.002). Aprepitant use also significantly improved quality of life with respect to CINV in the second course.. More than half of patients receiving HEC and 88 % of patients receiving MEC did not use aprepitant. Aprepitant showed significant therapeutic and preventive effects on CINV in patients who truly needed it.

Topics: Aged; Antiemetics; Antineoplastic Agents; Aprepitant; Female; Humans; Japan; Male; Middle Aged; Morpholines; Nausea; Neurokinin-1 Receptor Antagonists; Quality of Life; Thoracic Neoplasms; Vomiting

Radiotherapy-induced nausea and vomiting (RINV) is a toxicity that can occur in 40-80% of individuals who receive radiation treatment. Current guidelines recommend 5-hydroxytryptamine3 receptor antagonists (5-HT3 RAs) for prophylaxis of RINV for moderate and highly emetogenic radiotherapy; however, certain patients may suffer from RINV despite prophylaxis.. This report details the case of a 47-year-old female with extensive bony involvement to the spine from breast cancer presenting with lower back pain.. To palliate her symptoms, the patient underwent a course of irradiation to the lumbar spine and was prescribed ondansetron as an antiemetic. However, the patient experienced severe nausea and emesis and was subsequently switched to granisetron and aprepitant.. The patient completed the remainder of the radiation treatment with no further emesis and minimal nausea, representing the first documented success of granisetron and aprepitant for RINV after failure on ondansetron.. In chemotherapy, switching 5-HT3 RAs after failure on the first is successful in preventing chemotherapy-induced nausea and vomiting (CINV), yet this has not been previously reported in radiation. In this patient, granisetron and aprepitant were successful in substantially reducing nausea and preventing further emesis, and may represent an alternative antiemetic regimen for RINV prophylaxis and salvage.

Topics: Antiemetics; Aprepitant; Bone Neoplasms; Breast Neoplasms; Female; Granisetron; Humans; Middle Aged; Morpholines; Nausea; Neoplasm Metastasis; Ondansetron

To evaluate the appearance of chemotherapy-induced nausea and vomiting, and to compare the antiemetic efficacy of the triple combination of palonosetron, aprepitant and dexamethasone with that of our old regimen using first-generation 5-hydroxytryptamine 3-receptor antagonists and dexamethasone during gemcitabine and cisplatin chemotherapy in patients with advanced urothelial cancer.. We carried out a multi-institutional study including 122 patients who received gemcitabine and cisplatin for advanced urothelial cancer between February 2005 and January 2012. Uncontrolled chemotherapy-induced nausea and vomiting events were identified through records of nausea and vomiting, additional infusion, rescue medications, and/or records of food intake.. First-generation 5-hydroxytryptamine 3-receptor antagonists (ondansetron or granisetron) plus dexamethasone were used for 75 patients (cohort 1), and palonosetron with dexamethasone plus aprepitant for 47 patients (cohort 2). Patients in cohort 2 had significantly higher complete response (defined as no emetic episodes and no rescue medication use) rates than those in cohort 1 during the overall phase in the first cycle (85.7% vs 65.3%, P = 0.012), and all cycles (78.7% vs 50.7%, P = 0.0019) of gemcitabine and cisplatin. Patients in cohort 2 were more likely to achieve more favorable chemotherapy-induced nausea and vomiting control; that is, a lower grade of nausea, vomiting or anorexia, lower incidence of rescue therapy required, and shorter time to become chemotherapy-induced nausea- and vomiting-free than patients in cohort 1.. The present results show that palonosetron in combination with aprepitant and dexamethasone is more effective to prevent chemotherapy-induced nausea and vomiting in urothelial cancer patients treated with gemcitabine and cisplatin than first-generation 5-hydroxytryptamine 3-receptor antagonists plus dexamethasone.

Topics: Adult; Aged; Aged, 80 and over; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Carcinoma, Transitional Cell; Cisplatin; Deoxycytidine; Dexamethasone; Drug Therapy, Combination; Female; Gemcitabine; Granisetron; Humans; Isoquinolines; Kidney Neoplasms; Male; Middle Aged; Morpholines; Nausea; Ondansetron; Palonosetron; Quinuclidines; Retrospective Studies; Serotonin 5-HT3 Receptor Antagonists; Serotonin Antagonists; Ureteral Neoplasms; Urinary Bladder Neoplasms; Urologic Neoplasms; Vomiting

Guidelines for antiemetic therapy, such as the American Society of Clinical Oncology (ASCO) guidelines, recommend that aprepitant, an NK1 receptor antagonist, should be used in addition to conventional antiemetic therapy for acute and delayed nausea/vomiting caused by highly emetogenic chemotherapy. However, only few studies have been conducted to evaluate the efficacy of aprepitant in patients receiving moderately emetogenic chemotherapy. Therefore, we examined the antiemetic effects of additional doses of aprepitant in the next course in patients with lung cancer who were undergoing chemotherapy with carboplatin and who developed chemotherapy-induced nausea and vomiting (CINV) despite the preventive administration of a 5-HT3 receptor antagonist and dexamethasone. Consequently, the incidences of vomiting and nausea significantly decreased from 59% to 0% and from 91% to 64%, respectively, during the entire study period. Furthermore, a significant improvement in dietary intake during the entire study period was confirmed. These results suggest that the additional administration of aprepitant has high antiemetic effects in patients with lung cancer who are undergoing chemotherapy with carbo- platin and who show insufficient control of nausea/vomiting.

Topics: Aged; Aged, 80 and over; Antiemetics; Antineoplastic Agents; Aprepitant; Carboplatin; Female; Humans; Lung Neoplasms; Male; Middle Aged; Morpholines; Nausea; Vomiting

Chemotherapy-induced nausea and vomiting is a significant clinical issue which affects patient's quality of life and treatment decisions. Significant improvements in the control of chemotherapy-induced nausea and vomiting have occurred in the past 15 years with the introduction of new antiemetic agents 5-HT3, receptor antagonists, neurokinin-1 (NK-1) receptor antagonists, and olanzapine. Aprepitant was the first NK-1 receptor antagonist introduced (2003) for the prevention of chemotherapy-induced nausea and vomiting in combination with a 5-HT3 receptor antagonist and dexamethasone. A second NK-1 receptor antagonist netupitant was approved for use in October 2014. Phase III clinical trials of an additional NK-1 receptor antagonist rolapitant have been completed, and the data have been submitted for regulatory approval. A description of rolapitant and its role in chemotherapy-induced nausea and vomiting will be presented, along with a comparison of the other neurolinin-1 receptor antagonists aprepitant and netupitant.

Topics: Animals; Antiemetics; Antineoplastic Agents; Aprepitant; Humans; Morpholines; Nausea; Neurokinin-1 Receptor Antagonists; Pyridines; Quality of Life; Spiro Compounds; Vomiting

The objective of this study was to determine the appropriate timing of aprepitant administration in patients with oral cancer by comparing the antiemetic effect of aprepitant administered on the first day (first-day group) and third day (third-day group) of combination chemotherapy with docetaxel, nedaplatin (divided doses for 5 days), and 5-fluorouracil. 1. In both groups, very few cases of vomiting were observed. Therefore, we could not compare the incidence of vomiting. 2. The mean highest grade of nausea in the third-day group was significantly higher than that in the first-day group (2.33±0.71 vs 0.78±0.22, p=0.002; U-test). 3. In addition, the mean area under the curve of the chronological changes in the grade of nausea in the third-day group was significantly higher than that in the first-day group (13.44±9.58 vs 3.11±3.59, p=0.019; U-test). 4. The incidence of nausea of grade 2 or higher in the first-day group was significantly lower than that in the third-day group (11.1% [1/9] vs 88.9% [8/9], p<0.001; c 2 test). These results indicate that initiation of aprepitant administration on the first day of combination chemotherapy with docetaxel, nedaplatin, and 5-fluorouracil successfully prevented the development of nausea in patients with oral cancer.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Docetaxel; Female; Fluorouracil; Head and Neck Neoplasms; Humans; Male; Morpholines; Nausea; Organoplatinum Compounds; Taxoids; Time Factors

The current standard for prevention of chemotherapy-induced nausea/vomiting in autologous stem cell transplant only achieves 4-20% emetic control.. To assess emetic responses to multiday palonosetron, aprepitant, and low-dose dexamethasone among patients with myeloma and lymphoma undergoing autologous hematopoietic stem cell transplant.. Oral aprepitant 125/80/80 mg was administered with intravenous dexamethasone 4 mg and palonosetron 0.25 mg on days -3, -2, -1 for multiple myeloma and days -7 through -3 for lymphoma. Palonosetron was repeated day +3 in both groups.. A total of 20 patients were enrolled and 18 analyzed. None experienced emetic failure with complete control achieved in 78, 33, and 17% in the acute, delayed, and extended phases, respectively. Nausea occurred in 78% although not significant in 61%, with median Nausea Visual Score of 4.5. Quality of life correlated with emetic and nausea control. Eight patients developed grade 2-3 nonhematologic toxicities with only one event attributed to the study medications.. This triplet regimen was feasible with acceptable safety profile in the autologous hematopoietic stem cell transplant setting. Emetic control was best achieved in the acute phase. Lesser degree of emetic and nausea control in the delayed and extended phases impacted quality of life. Our results warrant further evaluation in a larger autologous hematopoietic stem cell transplant population.

Topics: Adult; Aged; Antiemetics; Aprepitant; Dexamethasone; Female; Hematopoietic Stem Cell Transplantation; Humans; Isoquinolines; Lymphoma; Male; Middle Aged; Morpholines; Multiple Myeloma; Nausea; Palonosetron; Pilot Projects; Quality of Life; Quinuclidines; Transplantation, Autologous; Vomiting

Topics: Antibodies, Monoclonal, Murine-Derived; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Cyclophosphamide; Doxorubicin; Drug Interactions; Humans; Lymphoma, Non-Hodgkin; Morpholines; Nausea; Prednisolone; Rituximab; Vincristine

The purpose of this study was to investigate the incidence of fosaprepitant-associated infusion site adverse events (ISAEs) among a cohort of breast cancer patients receiving doxorubicin/cyclophosphamide (AC) chemotherapy.. A retrospective review of electronic medical record (EMR) data was performed for all patients who were initiated on AC from January 2011 to April 2012. Data collected included baseline demographics, antiemetic regimen, documentation of ISAEs, and type of intravenous (IV) access. Descriptive statistics (mean and standard deviation or percentages) were summarized overall, by type of IV access and initial antiemetic given.. Among the 148 patients included in this analysis, 98 initially received fosaprepitant and 44 received aprepitant. The incidence of ISAEs associated with fosaprepitant administration was 34.7 % (n=34), while the incidence of aprepitant-associated ISAEs was 2.3 % (n=1). All ISAEs were associated with peripheral IV access. The most commonly reported ISAEs were infusion site pain (n=26), erythema (n=22), swelling (n=12), superficial thrombosis (n=8), infusion site hives (n=5), and phlebitis/thrombophlebitis (n=5). Twenty-six patients experienced more than one type of ISAE.. The incidence and severity of ISAEs associated with fosaprepitant administration among a group of patients receiving AC chemotherapy are significant and appreciably higher than what has been previously reported.

Topics: Adult; Aged; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Breast Neoplasms; Cyclophosphamide; Doxorubicin; Female; Humans; Infusions, Intravenous; Middle Aged; Morpholines; Nausea; Phlebitis; Retrospective Studies; Vomiting

We aim to evaluate the cost effectiveness of aprepitant-containing regimens for the prevention of chemotherapy-induced nausea and vomiting (CINV) among patients receiving high emetogenic chemotherapy (HEC) in Hong Kong.. Both cost-effectiveness and cost-utility analyses were conducted utilizing a decision-analytic model to measure the economic costs and clinical outcomes associated with the aprepitant-containing regimen versus a standard regimen in the prevention of CINV. Analyses were conducted on the basis of four published double-blind randomized clinical trials involving different usages of serotonin receptor antagonists.. The use of aprepitant-containing regimens is associated with an improvement in quality-adjusted life years (QALYs) compared with non-aprepitant regimens. For cisplatin-based chemotherapy, the incremental cost per QALY gained is HKD 239,644 (1 USD approximates HKD 7.8) when ondansetron is administered on day 1 only. The incremental cost per QALY is HKD 440,950 when ondansetron is used on day 1 to 4. For anthracycline and cyclophosphamide chemotherapy, the aprepitant-containing regimen is associated with incremental cost of HKD 195,442 per QALY gained. Similar results were obtained when other 5HT3 receptor antagonists are used. The use of aprepitant was associated with higher cost of drug but lower costs of emesis-related management. With the cost-effectiveness threshold set at the World Health Organization endorsed criteria of three times gross domestic product (GDP) per capita (three times GDP per capita in Hong Kong in 2011 is HKD 798,078), the current analyses showed that the aprepitant-containing regimen was cost-effective.. In patients undergoing HEC, the use of aprepitant as the anti-emetic is cost-effective in Hong Kong.

Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Cost-Benefit Analysis; Hong Kong; Humans; Morpholines; Nausea; Neoplasms; Quality-Adjusted Life Years; Vomiting

High-dose melphalan has been gaining recognition as a highly emetogenic agent used in hematopoietic stem cell transplantation (HSCT). The aim of this retrospective study was to elucidate the efficacy of aprepitant in preventing high-dose melphalan-induced emesis. Sixty patients who received melphalan (70 mg/m(2)/day, 2 days) and fludarabine (125 mg/m(2)/day, 5 days) as conditioning for allogeneic HSCT for hematological malignancies, and who received ondansetron and methylprednisolone as an antiemetic prophylaxis, were eligible. Twenty of these 60 patients also received aprepitant for 5 days (aprepitant group); the remaining 40 patients served as a control. The rates of complete response (CR), defined as no emesis without rescue medications, and complete protection (CP), defined as no emesis with or without rescue medications, were assessed between the two groups. The observation period was 12 days from the first day of melphalan administration. The CR and CP rates were significantly higher in the aprepitant group than in the control group during the observation period (35 % versus 10 %, P < 0.05; 85 % versus 33 %, P < 0.001; respectively). These results suggest that aprepitant in combination with ondansetron and steroid effectively ameliorates nausea and vomiting caused by the high-dose melphalan-based conditioning for allogeneic HSCT.

Topics: Adult; Aged; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Female; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Male; Melphalan; Middle Aged; Morpholines; Myeloablative Agonists; Nausea; Retrospective Studies; Transplantation Conditioning; Transplantation, Homologous; Vomiting

Although substance P (SP) and neurokinin NK1 receptors have been reported to be involved in cisplatin-induced acute and delayed emesis, their precise roles remain unclear. Pica, the consumption of non-nutrient materials such as kaolin in rats, can be used as a model of nausea in humans. We investigated the time-dependent changes in cisplatin-induced pica and the involvement of SP and NK1 receptors in this behaviour.. Rats were administered cisplatin with or without a daily injection of a 5-HT3 receptor antagonist (granisetron) or an NK1 receptor antagonist (aprepitant), and kaolin intake was then monitored for 5 days. The effects of granisetron on the cisplatin-induced expression of preprotachykinin-A (PPT-A) mRNA, which encodes mainly for SP, and on SP release in the medulla, measured by in vivo brain microdialysis, were also investigated.. Cisplatin induced pica within 8 h of its administration that continued for 5 days. Granisetron inhibited the acute phase (day 1), but not the delayed phase (days 2-5), of pica, whereas aprepitant abolished both phases. Within 24 h of the injection of cisplatin, PPT-A mRNA expression and SP release in the medulla were significantly increased; these findings lasted during the observation period and were inhibited by granisetron for up to 24 h.. The profiles of cisplatin-induced pica in rats are similar to clinical findings for cisplatin-induced emesis in humans, and we showed that SP production in the medulla and activation of NK1 receptors are involved in this cisplatin-induced pica.

Topics: Animals; Antiemetics; Antineoplastic Agents; Aprepitant; Cisplatin; Eating; Granisetron; Kaolin; Male; Medulla Oblongata; Morpholines; Nausea; Neurokinin-1 Receptor Antagonists; Pica; Protein Precursors; Rats, Wistar; Receptors, Neurokinin-1; Receptors, Serotonin, 5-HT3; RNA, Messenger; Serotonin Antagonists; Solitary Nucleus; Substance P; Tachykinins

In the present study, we evaluated the antiemetic effect of aprepitant in combination with 5-hydroxytryptophan(5-HT3) receptor antagonist and dexamethasone for chemotherapy-induced emesis and nausea in lung cancer patients treated with carboplatin-based systemic chemotherapy using the Functional Living Index-Emesis, an emesis- and nausea-specific quality of life(QOL)questionnaire. Patients experiencing emesis and/or nausea during and/or after previous courses of carboplatin-based chemotherapy received aprepitant in the following treatment cycle with the same anti-cancer agent. Emesis- and nausea-specific QOL aspects were significantly improved with the addition of aprepitant to the existing regimen containing dexamethasone and 5-HT3 receptor antagonist. Our result suggests that combined antiemetic treatment with aprepitant, dexamethasone, and 5-HT3 receptor antagonist is more effective in lung cancer patients receiving carboplatin-based systemic chemotherapy than dexamethasone and 5-HT3 receptor antagonist alone.

Topics: Aged; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Carboplatin; Dexamethasone; Female; Humans; Lung Neoplasms; Male; Middle Aged; Morpholines; Nausea; Surveys and Questionnaires; Vomiting

Nausea and vomiting are common distressing symptoms with multiple etiologies. Serotonin and substance P can induce nausea and vomiting by binding to specific receptors (5-hydroxytryptamine3 [5HT3] and neurokinin-1 [NK-1] receptors respectively). Carcinoid tumors, which originate from enterochromaffin cells of the neuroendocrine system, secrete several biologically active amines and peptides, including serotonin and substance P, that are responsible for the distant effects of this tumor. The authors present an 88-year-old lady with metastatic carcinoid tumor, with evidence of carcinoid syndrome. She had nausea and vomiting that became unresponsive to 5HT3 receptor antagonists and other antiemetics. As substance P is released from carcinoid tumors and has a role in the pathogenesis of emesis, the NK-1 receptor antagonist aprepitant was trialed. This provided complete and sustained improvement of the nausea and vomiting until her death 2 months later. This case demonstrates the potential role and rationale of NK-1 receptor antagonists in the management of resistant emesis in patients with carcinoid tumors. Clinical trials are needed to evaluate the efficacy and toxicity of these drugs in the management of emesis in patients with carcinoid syndrome.

Topics: Aged, 80 and over; Antiemetics; Aprepitant; Carcinoid Tumor; Female; Humans; Intestinal Neoplasms; Morpholines; Nausea; Neurokinin-1 Receptor Antagonists; Serotonin; Serotonin 5-HT3 Receptor Antagonists; Substance P; Treatment Outcome; Vomiting

The cisplatin split regimen has not been sufficiently well investigated to validate the use of aprepitant as a prophylactic antiemetic. This study aimed to retrospectively evaluate the efficacy of repeated administrations of 3-day courses of aprepitant according to the cisplatin split regimen (20mg/m² day, days 1-4, 22-25, 43-46) in combination with radiation. We compared the worst Grade of nausea between 23 patients with head and neck cancer who had been administered with aprepitant (group A: between January 2010 and June 2010) and 34-patients who were not administered with aprepitant (group B: between July 2011 and December 2012). In group A, the median age was 60 years (range, 35-73 years), the male/ female ratio was 18: 5, and the Eastern Cooperative Oncology Group (ECOG) performance status (PS) was 0 in 20 patients and 1 in 3 patients. In group B, the median age was 62 years (range, 31-71 years), the male/female ratio was 30: 4, and the ECOG PS was 0 in 31 patients and 1 in 3 patients. The worst nausea grade was 0, 1, and 2 in 21, 2, and 0 patients in group A and in 19, 9, and 6 patients in group B, respectively. The proportion of patients who developed nausea was significantly lower in group A than in group B (8% vs 44%, p<0.01). Of 6 patients who experienced Grade 2 nausea, 5 patients were administered with aprepitant during the next course of chemotherapy, and 60% of them had a lower severity of nausea. Thus, aprepitant could be effectively used as a prophylactic antiemetic in the cisplatin split regimen.

Topics: Adult; Aged; Antiemetics; Aprepitant; Chemoradiotherapy; Cisplatin; Female; Head and Neck Neoplasms; Humans; Male; Middle Aged; Morpholines; Nausea; Retrospective Studies; Vomiting

Although efficacy of aprepitant for suppressing emesis associated with single-dose cisplatin has been demonstrated, there are limited data on the antiemetic effect of this oral neurokinin-1 receptor antagonist during daily administration of cisplatin. Accordingly, we investigated the efficacy and safety of aprepitant in patients with head and neck cancer (HNC) receiving combination therapy with cisplatin and 5-FU (FP therapy).. Twenty patients with HNC were prospectively studied who received a triple antiemetic regimen comprising granisetron (40 μg/kg on Days 1-4), dexamethasone (8 mg on Days 1-4), and aprepitant (125 mg on day 1 and 80 mg on days 2-5) with FP therapy (cisplatin 20 mg/m2 on days 1-4; 5-FU 400 mg/m2 on days 1-5) (aprepitant group). We also retrospectively studied another 20 HNC patients who received the same regimen except for aprepitant (control group).. For efficacy endpoints based on nausea, the aprepitant group showed significantly better results, including a higher rate of complete response (no vomiting and no salvage therapy) for the acute phase (p=0.0342), although there was no marked difference between the two groups with regard to percentage of patients in whom vomiting was suppressed. There were no clinically relevant adverse reactions to aprepitant.. This study suggested that a triple antiemetic regimen containing aprepitant is safe and effective for HNC patients receiving daily cisplatin therapy.

Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Cisplatin; Dexamethasone; Drug Therapy, Combination; Fluorouracil; Granisetron; Head and Neck Neoplasms; Humans; Morpholines; Nausea; Neurokinin-1 Receptor Antagonists; Prospective Studies; Treatment Outcome; Vomiting

For patients receiving high-dose chemotherapy, a 5-hydroxytryptamine 3 receptor antagonist combined with dexamethasone is a standard antiemetic therapy. Despite this prophylactic anti-emetic treatment, many patients still suffer from uncontrollable emesis. In this study, we retrospectively evaluated the antiemetic effectiveness and safety of aprepitant (a neurokinin-1 receptor antagonist) in addition to 5-HT3 antagonist in Japanese patients with hematologic malignancy receiving high-dose chemotherapy prior to autologous peripheral blood stem cell transplantation (auto-PBSCT). Twenty-six patients received aprepitant and granisetron (the aprepitant group), whereas, 22 patients received granisetron alone (the control group). All patients received 3 mg of granisetron intravenously 30 min before chemotherapy administration. Patients in the aprepitant group additionally received 125 mg of aprepitant 60-90 min before administration of the first moderately to highly emetogenic chemotherapy. On the next day or thereafter, 80 mg of aprepitant was administered in the morning until the last administration of moderately to highly emetogenic anticancer drugs. The percentage of patients who achieved complete response (CR), defined as no emesis with only grade 1-2 nausea, in the aprepitant group was significantly higher than that in the control group (42% vs. 5%, p=0.003). Logistic regression analysis showed that non-prophylactic use of aprepitant was significantly associated with non-CR. The frequencies of adverse drug events (ADEs) were not significantly different between two groups. In conclusion, the results of this study suggest that the addition of aprepitant to granisetron can improve the antiemetic effect without increasing ADEs in patients receiving high-dose chemotherapy prior to auto-PBSCT.

Topics: Adult; Aged; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Asian People; Female; Granisetron; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Male; Middle Aged; Morpholines; Nausea; Neurokinin-1 Receptor Antagonists; Retrospective Studies; Treatment Outcome; Vomiting; Young Adult

To evaluate the efficacy and safety of aprepitant added to standard antiemetic regimens used in high-dose chemotherapy for allogeneic hematopoietic stem cell transplantation (allo-HSCT).. Retrospective medical record review.. Hematology ward of a university hospital in Japan.. Of 88 patients treated with high-dose chemotherapy followed by allo-HSCT, 46 received aprepitant and granisetron as antiemetic therapy (between April 1, 2010, and December 31, 2011), and 42 received granisetron alone (between April 1, 2008, and March 31, 2010).. Patients in both groups received 3 mg of granisetron intravenously 30 minutes before the administration of anticancer drugs. In the aprepitant group, 125 mg of aprepitant was administered orally 60-90 minutes before the administration of the first moderately to highly emetogenic anticancer drug. On the following days, 80 mg of aprepitant was administered orally every morning. The mean administration duration of aprepitant was 3.3 days (range 3-6 days).. The primary objective was to evaluate the percentage of patients who achieved complete response (CR; no vomiting and none to mild nausea). The CR rate in the aprepitant group was significantly higher than that in the control group (48% vs 24%, p=0.02). Multivariate analysis showed that nonprophylactic use of aprepitant was associated with failure to achieve CR (odds ratio [OR] 2.92; 95% confidence interval [CI] 1.13-7.99, p=0.03). The frequency of abdominal pain was lower in the aprepitant group (9% vs 25%, p=0.03). Rates of other frequently observed adverse drug events were similar between groups. There was no significant difference in neutrophil engraftment (median 18 vs 17 days), platelet engraftment (median 32 vs 32 days), the incidence of acute graft-versus-host-disease (63% vs 55%, p=0.52), viral infection (74% vs 67%, p=0.49), or 1-year overall survival (63% vs 62%, p=0.90) between the two groups.. The addition of aprepitant to granisetron increases the antiemetic effect without influencing transplantation-related toxicities in allo-HSCT.

Topics: Adult; Aged; Antiemetics; Antineoplastic Agents; Aprepitant; Drug Therapy, Combination; Female; Granisetron; Hematopoietic Stem Cell Transplantation; Humans; Male; Middle Aged; Morpholines; Nausea; Retrospective Studies; Transplantation, Homologous; Vomiting

Nausea and vomiting are among the most problematic symptoms experienced by patients with cancer who are receiving chemotherapy. 5-hydroxytryptamine 3(5-HT3)-receptor antagonists, NK1 receptor antagonists(aprepitant)and dexamethasone are now the standard therapies for preventing chemotherapy-induced nausea and vomiting(CINV)that follow highly emetogenic chemotherapy, such as cisplatin and anthracycline. However, since it is not cleared which 5-HT3-recepter antagonist is a proper treatment for combined use with aprepitant and dexamethasone, we conducted a questionnaire survey, which used the numerical rating scale(NRS), for comparing palonosetron with granisetron in the same patient. Palonosetron showed a significant improvement of nausea for both acute(within 24 hours)and delayed phase(24-120 hours later), regardless of the type of chemotherapy(cisplatin or anthracycline-based regimen). Furthermore, palonosetron had a tolerable safety profile. Our study suggests that palonosetron-based antiemetic treatment will be a preferred choice for preventing CINV following highly emetogenic chemotherapy.

Topics: Aged; Antiemetics; Antineoplastic Agents; Aprepitant; Dexamethasone; Drug Combinations; Female; Granisetron; Humans; Isoquinolines; Male; Middle Aged; Morpholines; Nausea; Neoplasms; Palonosetron; Quinuclidines; Retrospective Studies; Risk; Vomiting

This study aimed to determine how aprepitant affects the impact of chemotherapy-induced nausea and vomiting (CINV) on daily activities during highly emetogenic chemotherapy (HEC) or moderately emetogenic chemotherapy (MEC).. Patients received aprepitant plus standard antiemetic therapy (ondansetron plus dexamethasone) or standard antiemetic therapy alone. Data were analyzed from pooled data of two Phase III randomized, double-blind HEC trials and one MEC trial. Patients completed the Functional Living Index-Emesis questionnaire.. A significantly greater percentage of patients receiving aprepitant reported no or minimal CINV impact on daily life (overall total Functional Living Index-Emesis score >6) compared with those receiving standard therapy alone (HEC: 74.4 vs 63.9%, respectively; p < 0.01; MEC: 73.4 vs 66.3%; p < 0.05). In HEC, favorable responses to aprepitant treatment persisted in nausea (70.2 vs 60.9%) and vomiting domains (84.6 vs 68.7%; both p < 0.01). Similar results were seen in MEC.. Addition of aprepitant reduced CINV impact on daily life compared with standard antiemetic therapy.

Topics: Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Humans; Morpholines; Nausea; Neoplasms; Treatment Outcome; Vomiting

Chemotherapy-induced nausea and vomiting (CINV) is a feared adverse reaction during cancer treatment. Aprepitant has shown to be effective for CINV in adults, but little is known on its effect in pediatrics. So far, the drug is not licensed in this population.. To investigate efficacy of aprepitant in children and young adolescents with high or moderate emetogenic courses, with uncontrollable emesis in previous cycles.. Retrospective, observational study in children and adolescents treated with aprepitant at Ghent University Hospital, Belgium. Antiemetic regimens and emesis control were analyzed.. Twenty patient charts representing 104 chemotherapy cycles were reviewed. Complete vomiting control was observed in 10 patients (50 %), representing 89/104 (85.6 %) episodes. Incomplete vomiting control was observed in 10 patients (50 %), representing only 15 episodes (14.4 %). Of these episodes with incomplete vomiting control, 6 were in acute phase (40 %), 7 in delayed phase (46.7 %) and 2 in both acute and delayed phase (13.3 %).. Aprepitant might be effective in preventing or reducing vomiting in children. When combined with standard antiemetics, aprepitant was well tolerated. In attendance of results of on-going international clinical trials, our results encourage us to continue the use of aprepitant after failure of emesis control in previous cycles.

Topics: Adolescent; Antiemetics; Antineoplastic Agents; Aprepitant; Belgium; Child; Drug Therapy, Combination; Female; Hospitals, University; Humans; Male; Morpholines; Nausea; Neoplasms; Retrospective Studies; Treatment Outcome; Vomiting

We aimed to evaluate the efficacy of a new combination antiemetic therapy comprising aprepitant, granisetron, and dexamethasone in gastric cancer patients undergoing chemotherapy with cisplatin and S-1.. Gastric cancer patients scheduled to receive their first course of chemotherapy with cisplatin (60 mg/m(2)) and S-1 (80 mg/m(2)) were treated with a new combination antiemetic therapy aprepitant, granisetron, and dexamethasone on day 1; aprepitant and dexamethasone on days 2 and 3; and dexamethasone on day 4. The patients reported vomiting, nausea, use of rescue therapy, and change in the amount of diet intake, and completed the Functional Living Index-Emesis (FLIE) questionnaire. The primary endpoint was complete response (CR; no emesis and use of no rescue antiemetics) during the overall study phase (0-120 h after cisplatin administration). The secondary endpoints included complete protection (CP; CR plus no significant nausea); change in the amount of diet intake; and the impact of chemotherapy-induced nausea and vomiting (CINV) on daily life during the overall, acute (0-24 h), and delayed (24-120 h) phases.. Fifty-three patients were included. CR was achieved in 88.7, 98.1, and 88.7% of patients in the overall, acute, and delayed phases, respectively. The corresponding rates of CP were 67.9, 96.2, and 67.9%. Approximately half of the patients had some degree of anorexia. FLIE results indicated that 79.5% of patients reported "minimal or no impact of CINV on daily life".. Addition of aprepitant to standard antiemetic therapy was effective in gastric cancer patients undergoing treatment with cisplatin and S-1.

Topics: Aged; Aged, 80 and over; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Cisplatin; Dexamethasone; Drug Combinations; Drug Therapy, Combination; Female; Granisetron; Humans; Male; Middle Aged; Morpholines; Nausea; Neoplasm Staging; Oxonic Acid; Prospective Studies; Psychometrics; Quality of Life; Stomach Neoplasms; Tegafur; Treatment Outcome; Vomiting

Antiemetic effectiveness and safety of aprepitant in patients with hematologic malignancy receiving multiday chemotherapy were evaluated.. All data were retrospectively collected from the Kyushu University Hospital's electronic medical record system. Patients age 20 years or older with hematologic malignancies who received multiday chemotherapy were included in the study. All patients received 3 mg of granisetron i.v. 30 minutes before chemotherapy administration. Patients in the aprepitant group received 125 mg of aprepitant orally 60-90 minutes before administration of the first moderately to highly emetogenic chemotherapy (day 1). On day 2 or thereafter, an 80-mg oral dose of aprepitant was administered in the morning for up to five days. The primary endpoint was the percentage of patients who achieved complete response (CR).. A total of 42 patients were treated with aprepitant and granisetron as antiemetic prophylaxis between April and December 2010 (aprepitant group), and 40 patients were treated with only granisetron between March 1, 2009, and March 31, 2010, before the introduction of aprepitant. The percentage of patients who achieved CR in the aprepitant group was significantly higher than that in the control group (p = 0.01). Factors that were significantly associated with non-CR included the prophylactic use of aprepitant and chemotherapies containing ≥4 g/m(2)/day of cytarabine. The rates of adverse drug events (ADEs) did not significantly differ between groups.. The addition of aprepitant to granisetron increased the antiemetic effect without influencing ADEs in patients treated with moderately to highly emetogenic multiday chemotherapy for hematologic malignancies.

Topics: Administration, Oral; Adult; Aged; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Drug Therapy, Combination; Female; Granisetron; Hematologic Neoplasms; Hospitals, University; Humans; Male; Middle Aged; Morpholines; Nausea; Retrospective Studies; Treatment Outcome; Vomiting; Young Adult

While aprepitant is actually recommended for the prevention of nausea and vomiting induced by a single cisplatin administration, it is still unclear whether it has a clinical benefit when administered along with daily administrations of low- dose cisplatin(20mg/m2 days 1-5). This study was conducted to evaluate the efficacy of aprepitant in patients receiving daily administration of low-dose cisplatin.. Our study focused on 25 patients who received cancer therapy including cisplatin, with or without aprepitant (days 1-5). We performed a retrospective study to identify any significant positive effect of aprepitant in the prevention of nausea and vomiting for 10 days(days 1-10). Because cisplatin has a long half-life, we assessed the delayed phase nausea and vomiting(days 6-10).. Multiple-day dosing of aprepitant was effective for prevention of nausea(Odds ratio: 0. 30, p= 0. 0012)and vomiting(Odds ratio: 0. 04, p=0. 0001)throughout the observation. Furthermore, we observed a significant positive effect of aprepitant in the prevention of delayed nausea(Odds ratio: 0. 19, p=0. 0083)and vomiting(Odds ratio: 0. 07, p=0. 0040). These findings suggest that multiple-day dosing of aprepitant is useful for the inhibition of acute delayed nausea and vomiting caused by chemotherapy including daily administration of low-dose cisplatin.

Topics: Adult; Aprepitant; Cisplatin; Female; Humans; Male; Morpholines; Nausea; Retrospective Studies; Vomiting

Previous reports suggested that selective serotonin reuptake inhibitors (SSRI) could decrease the activity of 5-hydroxytryptamine type 3 (5-HT3) antagonists against acute chemotherapy-induced nausea and vomiting (CINV), possibly through serotonin accumulation for 5-HT3 receptors.. Chemonaive cancer patients receiving SSRI and antiemetic agents, including the 5-HT3 antagonist ondansetron and the neurokinin 1 (NK1) antagonist aprepitant for highly emetogenic chemotherapy (etoposide-platinum), were matched to control patients for the following variables: age, gender, primary tumor, past history of gestational emesis, chronic intake of benzodiazepines and/or corticosteroids, chronic alcohol intake, and aprepitant use. The primary evaluation criterion was the occurrence of acute vomiting during the first two cycles of treatment.. Forty-four patients were eligible for this analysis. The proportion of patients, who experienced at least one episode of grade ≥ 1 acute vomiting in patients receiving SSRI, compared to patients who did not, was significantly higher (59.1 vs. 22.7%, respectively, p = 0.03, odds ratio 4.72, 95% confidence interval 1.13-22.88). Grade ≥ 2 acute vomiting was also significantly more frequent in patients receiving SSRI, even after the implementation of aprepitant to antiemetic prophylaxis (41.2 vs. 5.9%, p = 0.04).. Our findings reinforce the hypothesis that SSRI decrease the antiemetic activity of the 5-HT3 serotonin antagonist ondansetron, resulting in higher rates of acute vomiting in cancer patients despite adequate antiemetic prophylaxis. Adding the NK1 antagonist aprepitant do not counterbalance the deleterious effect of SSRI, probably due to the synergistic effects of SSRI and NK1 antagonists on serotonin transmission.

Topics: Adult; Aged; Antiemetics; Antineoplastic Agents, Phytogenic; Aprepitant; Case-Control Studies; Drug Interactions; Drug Therapy, Combination; Etoposide; Female; Humans; Male; Middle Aged; Morpholines; Nausea; Neoplasms; Platinum; Selective Serotonin Reuptake Inhibitors; Serotonin Antagonists; Vomiting

We examined the antiemetic effect and impact of aprepitant on the quality of life (QOL) of outpatients receiving moderately emetogenic chemotherapy (MEC). Data were compared between patients who received aprepitant (aprepitant group, n=30, treated May to September 2010) and those who did not (control group, n=14, treated February to April 2010). Controls received antiemetic treatment with a serotonin receptor antagonist and dexamethasone on Day 1. The aprepitant group received oral aprepitant (125 mg) concomitantly with these drugs on Day 1, and aprepitant (80 mg) on Days 2 and 3. The percentages of subjects without vomiting and nausea during the overall phase (0-96 h), acute phase (0-24 h), and delayed phase (24-96 h), and without loss of appetite during the entire period and delayed phase, were significantly higher in the aprepitant group. A QOL evaluation using the Functional Living Index-Emesis (FLIE) questionnaire showed a significantly higher percentage of subjects without the impact of nausea and vomiting disturbing their daily lives during the overall phase, and a significant decrease in QOL disturbance in the aprepitant group. Our results suggest that nausea, vomiting, loss of appetite, and QOL disturbance occur in many outpatients undergoing MEC, and that concomitant therapy with 3 drugs including aprepitant can improve symptoms and QOL of these patients.

Topics: Antiemetics; Antineoplastic Agents; Appetite; Aprepitant; Female; Humans; Male; Middle Aged; Morpholines; Nausea; Neoplasms; Outpatients; Quality of Life; Vomiting

The type 1 neurokinin receptor (NK1R) antagonist aprepitant and its i.v. prodrug fosaprepitant have been approved for prevention of acute and delayed nausea and vomiting associated with chemotherapy. This study evaluated the magnitude and duration of brain NK1R occupancy over a period of 5 days after single-dose i.v. infusion of 150-mg fosaprepitant and single-dose oral administration of 165-mg aprepitant, using serial [(18)F]MK-0999 positron emission tomography (PET) in 16 healthy subjects. Each subject underwent three scans. Brain NK1R occupancy rates after i.v. fosaprepitant at time to peak concentration (T(max); ~30 min), 24, 48, and 120 h after the dose were 100, 100, ≥97, and 41-75%, respectively. After aprepitant, NK1R occupancy rates at these time points (T(max) ~4 h) were ≥99, ≥99, ≥97, and 37-76%, respectively. Aprepitant plasma concentration profiles were comparable for the two dosage forms. The study illustrates the utility of PET imaging in determining central bioequivalence in a limited number of subjects.

Topics: Adult; Antiemetics; Antineoplastic Agents; Aprepitant; Brain; Dose-Response Relationship, Drug; Female; Humans; Male; Morpholines; Nausea; Neurokinin-1 Receptor Antagonists; Positron-Emission Tomography; Prodrugs; Receptors, Neurokinin-1; Therapeutic Equivalency; Vomiting; Young Adult

To evaluate the efficacy of a combination of aprepitant and conventional antiemetic therapy in patients with advanced or recurrent lung cancer receiving moderately emetogenic chemotherapy (MEC).. Patients with advanced or recurrent lung cancer who were treated with MEC regimens at the Department of Respiratory Medicine, Fukuoka University Hospital, were included and classified into the following groups: control group (treatment: 5-HT3 receptor antagonists + dexamethasone) and aprepitant group (treatment: 5-HT3 receptor antagonists + dexamethasone + aprepitant). The presence or absence of chemotherapy-induced nausea and vomiting (CINV) was evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE) v4.0; patients with grade 1 or above were considered positive for CINV. Food intake per day, completion of planned chemotherapy, and progression-free survival (PFS) achieved by chemotherapy were investigated.. The complete suppression rate of nausea in the aprepitant group was significantly higher than that in the control group (p = 0.0043). Throughout the study, the food intake in the aprepitant group was greater than that in the control group, with the rate being significantly higher, in particular, on day 5 (p = 0.003). The completion rate of planned chemotherapy was also higher in the aprepitant group (p = 0.042). PFS did not differ significantly, but tended to be improved in the aprepitant group.. The aprepitant group showed significantly higher complete suppression of nausea, food intake on day 5, and completion of planned chemotherapy than the control group.

Topics: Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Case-Control Studies; Dexamethasone; Drug Therapy, Combination; Female; Humans; Lung Neoplasms; Male; Middle Aged; Morpholines; Nausea; Neoplasm Recurrence, Local; Neoplasm Staging; Prognosis; Retrospective Studies; Serotonin 5-HT3 Receptor Antagonists; Survival Rate; Vomiting

To report a case of refractory nausea in a patient with idiopathic gastroparesis successfully treated with aprepitant.. A 41-year-old female with idiopathic gastroparesis demonstrated by a delayed gastric emptying time experienced significant nausea, vomiting, and abdominal pain. This resulted in numerous hospital admissions and regular outpatient intravenous fluid administration. Over a 3-year period the patient had been treated with numerous agents for nausea and vomiting, including metoclopramide 10 mg 3 times daily, ondansetron 8 mg 2 times daily, and promethazine (various doses from 12.5 to 25 mg orally up to 3 times daily). No treatment tried was either tolerated or effective. As a last option before considering gastric pacing the patient was started on aprepitant 40 mg daily. The patient had a dramatic response to aprepitant and reported that her nausea had decreased significantly after 48 hours of starting the medication (2 doses). She was able to tolerate oral feeding and her need for outpatient intravenous hydration abated. Over the course of 2 months while using aprepitant her gastroparesis symptoms continued to improve. She reported no adverse effects attributable to aprepitant. After the first 2 months of aprepitant treatment, the patient was unable to continue the medication due to cost. Although her symptoms did worsen after discontinuation, they did not return to their initial severity. At 4 months after the trial of aprepitant, she continued to have improved symptoms. She claimed not to have daily nausea or vomiting, but still required high-dose promethazine and occasional outpatient intravenous fluids. At that point, she had gained 7.2 kg from the time that she had started aprepitant.. Aprepitant, a neurokinin-1 receptor antagonist, is approved in the US for nausea and vomiting associated with surgery and cancer chemotherapy. To our knowledge, this is the second reported case of its use in gastroparesis-induced nausea. Our patient reported relief of nausea and vomiting despite existing evidence showing that aprepitant has no significant effect on accelerating gastric emptying. Despite its acquisition cost, our patient avoided hospital admission and the administration of intravenous hydration, suggesting aprepitant may be cost-effective in this case.. Aprepitant may have some utility in treating refractory nausea caused by gastroparesis. This case suggests that the drug's antiemetic effect may be successfully used in areas not approved by the Food and Drug Administration. A controlled trial examining aprepitant in patients with such challenging clinical conditions may be warranted.

Topics: Abdominal Pain; Adult; Antiemetics; Aprepitant; Female; Follow-Up Studies; Gastroparesis; Humans; Morpholines; Nausea; Neurokinin-1 Receptor Antagonists; Promethazine; Treatment Outcome; Vomiting

The combination of a neurokinin-1 receptor antagonist, dexamethasone, and a 5-HT(3) receptor antagonist is currently the standard antiemetic treatment in patients receiving cisplatin-based high emetogenic chemotherapy (HEC). The aim of this study was to evaluate the efficacy of a combination of palonosetron, a unique second-generation 5-HT(3) receptor antagonist, aprepitant, the only approved neurokinin-1 receptor antagonist, and dexamethasone as antiemetic prophylaxis in patients receiving HEC (cisplatin ≥50 mg/mq).. Chemotherapy-naïve adult patients, receiving cisplatin-based HEC, were treated with palonosetron 0.25 mg/i.v., dexamethasone 20 mg/i.v., and aprepitant 125 mg/p.o., 1-h before chemotherapy. Aprepitant 80 mg/p.o. and dexamethasone 4 mg p.o. were administered on days 2-3. Primary end point was complete response (CR; no vomiting and no use of rescue medication), during the overall study period (0-120 h). Secondary end points were complete control (CR and no more than mild nausea), emesis-free rate, and nausea-free rate during the acute (0-24 h), delayed (24-120 h), and overall (0-120 h) periods. Safety was also evaluated.. A total of 222 patients were included in the study. Median age was 62 years, 76.6% were male and 23.4% female, and most common tumors were lung (66.7%) and head and neck (15.8%); 70.3% of patients achieved CR during the overall study period. Complete control, emesis-free rate, and nausea-free rate were 70.3%, 92.8%, and 59.9%, respectively, during the overall phase. The most commonly reported side effects were constipation (39% of patients) and headache (5%).. This study shows that palonosetron in combination with aprepitant and dexamethasone is effective to prevent chemotherapy-induced nausea and vomiting in patients treated with cisplatin-based HEC.

Topics: Adult; Aged; Aged, 80 and over; Antiemetics; Antineoplastic Agents; Aprepitant; Cisplatin; Dexamethasone; Drug Therapy, Combination; Female; Health Status Indicators; Humans; Isoquinolines; Male; Middle Aged; Morpholines; Nausea; Palonosetron; Prospective Studies; Quality of Life; Quinuclidines; Serotonin Antagonists; Surveys and Questionnaires; Vomiting; Young Adult

Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Asian People; Humans; Morpholines; Nausea; Randomized Controlled Trials as Topic; Vomiting

It is recommended that patients initiate triple antiemetic therapy with one of the 5-hydroxytryptamine receptor antagonists (5-HT(3) RAs), aprepitant (or its intravenous prodrug fosaprepitant) and dexamethasone prior to the start of highly emetogenic chemotherapy (HEC). However, the impact of 5-HT(3) RA selection within triple antiemetic regimens on the risk of uncontrolled chemotherapy-induced nausea and vomiting (CINV) with HEC has not been well studied.. To assess the likelihood of an uncontrolled CINV event following antiemetic prophylaxis with the 5-HT(3) RA palonosetron + aprepitant/fosaprepitant + dexamethasone (palonosetron cohort) versus any of the other 5-HT(3) RAs + aprepitant/fosaprepitant + dexamethasone (other 5-HT(3) RA cohort) among single-day HEC cycles.. Single-day HEC cycles (a gap of at least 5 days between two administrations) among patients with a cancer diagnosis and receiving antiemetic prophylaxis with the aforementioned regimens between 1/1/2006 and 6/30/2010 were identified from the IMS LifeLink claims database. Uncontrolled CINV events were identified through ICD-9-CM codes (nausea and vomiting), Current Procedural Terminology codes (hydration), rescue medications and/or use of antiemetic therapy from days 2-5 following HEC administration. Risks for an uncontrolled CINV event among all patients, and within breast cancer and multiple cancer subpopulations, were analyzed at cycle level using logistic multivariate regression models.. A total of 8018 cycles for the palonosetron cohort and 1926 cycles for the other 5-HT(3) RA cohort (3574 and 978 patients, respectively) were analyzed. Single-day HEC cycles received by the palonosetron cohort had a significantly lower unadjusted risk of an uncontrolled CINV event (17.5 vs 20.7% for the other 5-HT(3) RA cohort; p = 0.0010), with a 17% lower adjusted risk for palonosetron-administered cycles (odds ratio: 0.83; 95% CI: 0.73-0.94; p = 0.0042). Results in the breast cancer and multiple cancer subgroups were consistent with those for the overall population.. In this retrospective claims data analysis, single-day HEC cycles administered with palonosetron + aprepitant/fosaprepitant + dexamethasone had a lower risk for an uncontrolled CINV event versus other 5-HT(3) RAs + aprepitant/fosaprepitant + dexamethasone.

Topics: Adult; Antiemetics; Antineoplastic Agents; Aprepitant; Databases, Factual; Dexamethasone; Drug Therapy, Combination; Female; Humans; Isoquinolines; Logistic Models; Male; Middle Aged; Morpholines; Multivariate Analysis; Nausea; Palonosetron; Quinuclidines; Retrospective Studies; Serotonin 5-HT3 Receptor Antagonists; Vomiting

We retrospectively examined the results of antiemetic therapy with granisetron and dexamethasone; with granisetron, dexamethasone and aprepitant; and with palonosetron, dexamethasone and aprepitant, in patients who received chemotherapy with cisplatin at 50 mg/m2 or more for the first time. Vomiting was dramatically reduced by the concomitant administration of aprepitant. There was no difference in this effect when palonosetron was used instead of granisetron as a serotonin receptor antagonist. There was also no significant difference in the percentage of patients without nausea among the 3 groups. The results of this study indicate that vomiting in patients receiving chemotherapy can be controlled using aprepitant in combination with two other drugs.

Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Cisplatin; Female; Humans; Male; Middle Aged; Morpholines; Nausea; Retrospective Studies; Vomiting

We retrospectively analyzed the efficacy and safety of aprepitant in breast cancer patients who were treated with FEC(5- fluorouracil, epirubicin, cyclophosphamide)or EC(epirubicin, cyclophosphamide). We divided patients into two groups according to the aprepitant approval period. The rate of severe nausea(@Grade 2)was significantly less in patients with aprepitant(acute 10. 0%, delayed 15. 0%)than those without aprepitant(acute 29. 1%, delayed 30. 9%). Complete response( no vomiting and no use of rescue therapy)in the acute phase was significantly higher in the aprepitant pretreated group than in the no aprepitant group(82. 5% vs 61. 8%, respectively). Moreover, complete response in the delayed phase was also higher in the aprepitant group than in the no aprepitant group(82. 5%vs 58. 2%, respectively). Pre-treatment with aprepitant did not increase adverse events including constipation and elevation of alanine transaminase. The aprepitant was effective in terms of prevention of chemotherapy-induced nausea and vomiting in patients treated with an anthracycline- based regimen.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Breast Neoplasms; Cyclophosphamide; Epirubicin; Female; Fluorouracil; Humans; Middle Aged; Morpholines; Nausea; Retrospective Studies

Topics: Animals; Antiemetics; Antineoplastic Agents; Aprepitant; Clinical Trials as Topic; Colloids; Disease Models, Animal; Drug Carriers; Gold; Humans; Melanoma, Experimental; Morpholines; Nanoparticles; Nanotechnology; Nausea; Neoplasms; Polyethylene Glycols; Silicon Dioxide

Nausea and vomiting are major adverse reactions in cancer chemotherapy, and affect quality of life (QOL). We performed a retrospective study that examined the efficacy of aprepitant and palonosetron for chemotherapy-induced nausea and vomiting (CINV) on patients taking cisplatin doublets for lung cancer. The study subjects were 73 patients. A 5-HT(3) group received old-generation 5-HT(3) receptor antagonists and dexamethasone for preventive treatment (32 patients). An A group received old-generation 5-HT(3) receptor antagonists, aprepitant and dexamethasone (22 patients). An A+P group received palonosetron, aprepitant and dexamethasone (19 patients). On acute emesis (occurring within 24 hours after chemotherapy), there was no significant difference in the complete suppression rate of nausea and vomiting among the three groups. However, on delayed onset emesis (occurring between 24 to 120 hours), the complete suppression rate of nausea was significantly higher in the A+P group (57. 9%) than in the 5- HT(3) group (16. 7%) and A group (23. 8%). Significantly better efficacy was seen in the 5-HT(3) group and A group in the complete suppression rate of vomiting, and in the need of rescue medication rates on delayed-onset emesis. The cost of antiemesis was 19, 735 yen for the 5-HT(3) group, 32, 252 yen for the A group and 15, 557 yen for the A+P group. In conclusion, it was suggested that concurrent administration of palonosetron, aprepitant and dexamethasone for CINV on cisplatin doublet in lung cancer is a clinically useful treatment that might reduce the economic burden on patients.

Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Cisplatin; Female; Humans; Isoquinolines; Lung Neoplasms; Male; Middle Aged; Morpholines; Nausea; Palonosetron; Quinuclidines; Retrospective Studies; Serotonin Antagonists; Vomiting

One of the most common and distressing side effects for cancer patients is chemotherapy-induced nausea and vomiting (CINV). New antiemetics, such as the NK-1 receptor inhibitor aprepitant, have been reported to improve control of this side effect in adults. However, little is known about its effect in the pediatric oncology population, with only a few reported cases in the literature.. This was a retrospective chart review on the use of aprepitant in the pediatric oncology population in our institution.. Thirty-two charts and a total of 146 cycles of chemotherapy were reviewed. Mean age was 10 years. Highly emetogenic chemotherapy was used in 23/32 patients and moderately emetogenic chemotherapy in 9/32. Antiemetic regimens consisted of aprepitant+5-HT3 RA+dexamethasone (Regimen 1, 20/32 patients) or aprepitant +5-HT3 RA (Regimen 2, in 12/32). Eight out of thirty-two patients were chemotherapy-naïve and received aprepitant on their first cycle. In 24/32 patients, aprepitant was added later in their treatment, with 12/24 reporting resolution of CINV after its addition.. Aprepitant when combined with standard antiemetics, was well tolerated in the pediatric oncology population studied. However, there is still a need to conduct prospective studies to determine the optimal efficacy of aprepitant in the pediatric oncology population.

Topics: Adolescent; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Child; Child, Preschool; Dexamethasone; Drug Therapy, Combination; Female; Glucocorticoids; Humans; Male; Morpholines; Nausea; Neoplasms; Retrospective Studies; Serotonin 5-HT3 Receptor Antagonists; Treatment Outcome; Vomiting

A 50-year-old-woman underwent high anterior resection for sigmoid colon adenocarcinoma. Modified oxaliplatin/l / -LV/ 5-FU(mFOLFOX6)was started as adjuvant treatment due to final-stage III b. Granisetron 3 mg and dexamethasone 8 mg for prophylaxis chemotherapy-induced nausea and vomiting (CINV) were administered intravenously 30 min before oxaliplatin administration. Grade 3 delayed CINV was observed at course 4. CINV could not be controlled by any rescue medications. We adopted a neurokinin-1 receptor antagonist (aprepitant) that alleviated the emetic effects of substance P. The oral aprepitant dose was 125 mg on day 1 and 80 mg on days 2 and 3. Afterward, delayed vomiting was completely controlled and chemotherapy could be continued to course 12. Aprepitant is a very active antiemetic drug for the prevention of delayed nausea and vomiting induced by mFOLFOX6 regimen.

Topics: Adenocarcinoma; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Female; Fluorouracil; Humans; Leucovorin; Middle Aged; Morpholines; Nausea; Organoplatinum Compounds; Sigmoid Neoplasms; Vomiting

Aprepitant is actually recommended in the prevention of nausea and vomiting induced by high emetic risk chemotherapy using cisplatin. We performed an observational prospective study on 101 patients evaluating the efficacy of aprepitant in the clinical conditions of use of cisplatin, out of context of clinical trial. We did not perform any intervention on the choice of anti-emetic treatment by the clinicians. Data on anti-emetic treatments were collected from prescriptions by a pharmacist after prior consultation with a medical doctor. Inclusions were closed when we lay 50 patients who received aprepitant associated to standard anti-emetic treatment (ondansetron and prednisolone) and 51 patients who received standard anti-emetic treatment. We observed a significant positive effect of aprepitant in the prevention of acute (84 vs 74.4 %, P = 0.24) and delayed vomiting (84 vs 60.8%, P = 0.009). But there was not a significant difference between the two groups regarding the prevention of nausea and the rate of complete response (absence of nausea and vomiting during five days).

Topics: Adult; Aged; Aged, 80 and over; Antiemetics; Antineoplastic Agents; Aprepitant; Cisplatin; Female; Humans; Male; Middle Aged; Morpholines; Nausea; Ondansetron; Prednisolone; Prospective Studies; Vomiting

Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Humans; Hungary; Insurance, Health, Reimbursement; Medical Oncology; Morpholines; Nausea; Selective Serotonin Reuptake Inhibitors; Societies, Medical; Vomiting

Topics: Adolescent; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Carboplatin; Cisplatin; Cyclophosphamide; Double-Blind Method; Drug Interactions; Etoposide; Fever; Humans; Ifosfamide; Incidence; Morpholines; Nausea; Neutropenia; Randomized Controlled Trials as Topic; Sample Size; Vomiting

Approximately one half of cancer patients experience nausea or vomiting during chemotherapy containing high-dose cisplatin, despite the use of a corticosteroid and 5-hydroxytryptamine(3) (5-HT(3)) receptor antagonists. The addition of aprepitant, a neurokinin 1 receptor antagonist, improves control of emesis by a further 15-20%, and improves late phase symptoms (>24 h after chemotherapy). The cornerstone of standard first line lung cancer chemotherapy is high-dose cisplatin. Our experience with aprepitant in the chemotherapy of 10 lung cancer patients is described, who reported more than one episode of vomiting caused by chemotherapy despite the use of ondansetron previously. Aprepitant prevented acute and late phase oncoming vomiting in all 10 patients and acute and late phase nausea in 9 of the 10 patients. According to our experience on a limited number of patients, aprepitant may be of clinical benefit in the supportive treatment of lung cancer, in achieving better quality of life during chemotherapeutic cycles in these patients.

Topics: Adult; Aged; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Cisplatin; Female; Humans; Lung Neoplasms; Male; Middle Aged; Morpholines; Nausea; Quality of Life; Treatment Outcome; Vomiting

A case of ifosfamide-induced neurotoxicity after the addition of aprepitant to an antiemetic regimen is reported.. A 24-year-old white man diagnosed with a malignant peripheral nerve sheath tumor initially in the late 1990s was admitted to the hospital for treatment of a recurrence of the tumor in the supra-clavicular region. In the previous five cycles of ifosfamide, carboplatin, and etoposide, the patient had no problems with the neurotoxic adverse effects associated with ifosfamide use. With the fifth cycle of therapy, the patient suffered severe nausea and vomiting that required his readmission to the hospital. With the initiation of the sixth cycle of chemotherapy, aprepitant was added to the existing antiemetic regimen of ondansetron and dexamethasone. During the sixth cycle, approximately six hours after the infusion of ifosfamide on day 3, the patient exhibited the classic symptoms of ifosfamide-induced neurotoxicity, including visual and auditory hallucinations, obvious sleepiness, confusion, and delirium. Since his symptoms resolved by morning, it was determined that the patient did not require treatment with methylene blue. With the initiation of the seventh cycle of chemotherapy, aprepitant was again added to the standard antiemetic regimen of a corticosteroid and serotonin receptor antagonist. During this hospitalization, around-the-clock methylene blue was added to prevent neurotoxicity. The patient tolerated chemotherapy well without any signs or symptoms of neurotoxicity and was discharged four days later.. A 24-year-old patient treated with ifosfamide, carboplatin, and etoposide for a malignant peripheral nerve sheath tumor developed ifosfamide-induced neurotoxicity after the addition of aprepitant to a standard antiemetic regimen consisting of ondansetron and dexamethasone.

Topics: Adult; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Carboplatin; Dexamethasone; Drug Therapy, Combination; Etoposide; Humans; Ifosfamide; Male; Morpholines; Nausea; Nerve Sheath Neoplasms; Neurotoxicity Syndromes

Chemotherapy-induced nausea and vomiting (CINV) remains a major adverse effect of cancer chemotherapy which may increase morbidity, reduce quality of life and threaten the success of cancer therapy. Aprepitant is effective in preventing CINV, achieving higher complete response (no emesis and no rescue therapy) compared to standard prevention, in patients receiving either highly (HEC) or moderately emetogenic chemotherapy (MEC; absolute reduction = 11 and 13%, respectively). We assessed the cost effectiveness of aprepitant-based vs standard prevention in these indications in Belgium.. A decision analytical model was developed in MS Excel (Fig. 1). To estimate resource use, two approaches were used. The first is based on the preventive regimens applied in randomized controlled trials comparing aprepitant-based CINV prevention (for HEC: aprepitant days 1-3, ondansetron 32 mg i.v. day 1, oral placebo twice daily days 2-4, oral dexamethasone days 1-4; for MEC: aprepitant days 1-3, ondansetron 16 mg p.o. day 1, placebo on days 2-3, oral dexamethasone day 1), vs a standard regimen (for HEC: oral placebo days 1-3, ondansetron 32 mg i.v. day 1 and 16 mg p.o. days 2-4, oral dexamethasone days 1-4; for MEC: oral placebo, ondansetron 16 mg p.o. days 1-3, dexamethasone day 1) The second analysis is based on current real-world resource use in the Belgian setting in the prevention of CINV using a longitudinal Hospital Database. CINV-specific utility values were used to calculate quality-adjusted life years (QALYs). Drug costs were obtained from official reimbursement listings. Treatment costs for CINV were obtained from a German study and adapted to Belgium.. The aprepitant-based regimen is associated with 0.003 and 0.014 more QALYs in HEC and MEC, respectively and with per patient savings of 66.84 (trial based) and 74.62 (real-life based) for HEC and 17.95 (trial based) and 21.70 (real-life based) for MEC. Hence, aprepitant is both more effective and less expensive (=dominant). One-way sensitivity analyses were performed on treatment cost of emesis, the clinical benefit of aprepitant and the cost of ondansetron and showed that the results were robust on the first two parameters but sensitive on the decrease in cost of ondansetron for the moderately emetogenic chemotherapy regimens.. In both approaches, the aprepitant-based strategy is more effective and less expensive compared to standard care.

Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Belgium; Cisplatin; Cost-Benefit Analysis; Decision Support Techniques; Decision Trees; Drug Costs; Humans; Morpholines; Nausea; Vomiting

Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Area Under Curve; Clinical Protocols; Drug Interactions; Humans; Medical Oncology; Morpholines; Nausea; Neoplasms; Neurokinin-1 Receptor Antagonists; Radiotherapy; Serotonin 5-HT3 Receptor Antagonists; Vomiting

Chemotherapy-induced nausea and vomiting (CINV) is an important cause of distress for cancer patients. We have evaluated the effectiveness and safety of a new antiemetic aprepitant in improving management of CINV refractory to standard antiemetic therapy in the general oncology setting.. Retrospective chart review of all patients who received aprepitant from 1 January 2004 to 31 May 2005.. Twenty-six patients received oral aprepitant in addition to 5-hydroxytryptamine blocker and corticosteroid. Eighty-five per cent of the patients were women. Median age was 49 years. More than half patients had early-stage cancers. Majority received anthracycline-based chemotherapy for breast cancer. Fourteen (54%) patients received aprepitant during cycle 2, seven patients (27%) started aprepitant during cycle 4 and one (4%) during cycle 5. Side-effects observed included constipation (27%), fatigue (27%) and diarrhoea (8%). Six (23%) patients did not complete chemotherapy. Two of these had persistent nausea and vomiting, and four experienced diarrhoea, febrile neutropenia and other chemotherapy-related events. Three patients (12%) were hospitalized prior to starting aprepitant because of CINV, and one patient was hospitalized because of CINV while receiving aprepitant. Only six (23%) patients would have been eligible for aprepitant under the reimbursement scheme available at the time.. The addition of aprepitant was associated with improved control of nausea and vomiting and reduction in hospitalization in patients receiving chemotherapy.

Topics: Adult; Aged; Antiemetics; Antineoplastic Agents; Aprepitant; Female; Humans; Male; Middle Aged; Morpholines; Nausea; Neoplasms; Vomiting

Topics: Administration, Oral; Anorexia; Antiemetics; Antineoplastic Agents; Aprepitant; Asthenia; Constipation; Diarrhea; Drug Interactions; Dyspepsia; Fatigue; Fever; Granisetron; Headache; Hiccup; Humans; Indoles; Injections, Intravenous; Isoquinolines; Morpholines; Nausea; Neoplasms; Ondansetron; Palonosetron; Quinolizines; Quinuclidines; Vomiting

The aim of this study was to assess the effectiveness of aetiology-based guidelines for the management of nausea and vomiting (N&V) in patients with advanced cancer.. This was a prospective study of 121 patients admitted to a hospice. Patients with N&V underwent assessments at presentation, 48 h and 1 week, to determine the aetiology of N&V and the response to treatment. Antiemetics were prescribed according to aetiology-based guidelines.. Sixty-one patients (50%) had N&V during their admission: 21 (17%) had isolated nausea, 2 (2%) had isolated vomiting and 38 (31%) had combined N&V. During the assessment period, physicians altered their opinion about the primary cause of N&V in 26% of cases and finally expressed confidence about the aetiology in 75% of patients. The most common cause of N&V was impaired gastric emptying (contributing in 44% of patients), followed by chemical causes (33%) and bowel obstruction (19%). At 1 week, nausea was controlled in 56% of patients, and vomiting in 89% of patients, and residual symptoms were generally mild.. An approach using aetiology-based guidelines in the management of N&V is moderately effective, although there are some patients with N&V refractory to standard antiemetic regimens.

Topics: Adult; Aged; Aged, 80 and over; Antiemetics; Aprepitant; Female; Guidelines as Topic; Humans; Male; Middle Aged; Morpholines; Nausea; Neoplasms; Palliative Care; Prospective Studies; United Kingdom; Vomiting

Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Comprehensive Health Care; Evidence-Based Medicine; Humans; Isoquinolines; Models, Organizational; Morpholines; Nausea; Neoplasms; Nurse's Role; Oncology Nursing; Palonosetron; Patient Care Team; Practice Guidelines as Topic; Quinuclidines; Total Quality Management; Vomiting

Nausea and vomiting are common side effects of chemotherapy in adult and pediatric patients. Even with standard antiemetic therapy, a significant number of patients continue to experience acute and delayed symptoms. When used in combination with standard antiemetic therapy, a new class of antiemetics, the neurokinin-1 (NK-1) receptor antagonists, have been shown to improve both acute and delayed nausea and vomiting in adults. In this report, we describe the NK-1 receptor antagonist aprepitant in two adolescent patients receiving highly emetogenic chemotherapy who had experienced refractory nausea and vomiting with previous chemotherapy courses. The addition of aprepitant to the antiemetic regimen in the patients resulted in significant subjective improvement in nausea and vomiting as well as quality of life. These results in our adolescent patients are promising, but there is a need for well-designed studies to determine the efficacy, dosing, and safety of aprepitant in children of all ages.

Topics: Adolescent; Antiemetics; Antineoplastic Agents; Aprepitant; Drug Therapy, Combination; Female; Humans; Male; Morpholines; Nausea; Neurokinin-1 Receptor Antagonists; Treatment Outcome

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

MK-0869 (aprepitant), a potent substance P antagonist, is the active ingredient of EMEND which has recently been approved by the FDA for the prevention of chemotherapy-induced nausea and vomiting. Early clinical tablet formulations of MK-0869 showed significant food effects on absorption, suggesting that formulation could have a significant role in improving bioavailability. A Beagle dog model was developed in an effort to guide novel formulation development. Using the suspension of the micronized bulk drug used for the tablet formulations, the food effect on absorption was confirmed in the dog at a similar magnitude to that observed in humans. Further dog studies demonstrated a clear correlation between particle size and in vivo exposures, with the nanoparticle (NanoCrystal) colloidal dispersion formulation providing the highest exposure, suggesting dissolution-limited absorption. The NanoCrystal dispersion also eliminated the food effect on oral absorption in the dog at a dose of 2mg/kg. Regional absorption studies using triport dogs indicated that the absorption of MK-0869 was limited to the upper gastrointestinal tract. These results provided strong evidence that the large increase in surface areas of the drug nanoparticles could overcome the narrow absorption window and lead to rapid in vivo dissolution, fast absorption, and increased bioavailability. In addition, the dog model was used for optimizing formulation processes in which the nanoparticles were incorporated into solid dosage forms, and for selecting excipients to effectively re-disperse the nanoparticles from the dosage units. The human pharmacokinetic data using the nanoparticle formulation showed excellent correlations with those generated in the dog.

Topics: Absorption; Administration, Oral; Animals; Antineoplastic Agents; Aprepitant; Area Under Curve; Biological Availability; Capsules; Chemistry, Pharmaceutical; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Dogs; Drug Administration Schedule; Drug Evaluation, Preclinical; Fasting; Food-Drug Interactions; Humans; Male; Models, Animal; Morpholines; Nanostructures; Nausea; Substance P; Tablets; Technology, Pharmaceutical; Upper Gastrointestinal Tract; Vomiting

Topics: Antineoplastic Agents; Aprepitant; Drug Interactions; Morpholines; Nausea; Neoplasms; Vomiting

Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Cisplatin; Clinical Trials as Topic; Drug Therapy, Combination; Humans; Morpholines; Nausea; Neoplasms; Neurokinin-1 Receptor Antagonists; Vomiting

Topics: Acetals; Antiemetics; Antineoplastic Agents; Aprepitant; Cisplatin; Dexamethasone; Female; Granisetron; Humans; Male; Morpholines; Multicenter Studies as Topic; Nausea; Neurokinin-1 Receptor Antagonists; Randomized Controlled Trials as Topic; Substance P; Vomiting