aprepitant and Neoplasms

Although chemotherapy is predominantly used for cancer treatment, it can be ineffective and can induce serious side effects and lead to chemoresistance. It is essential to discover novel drugs that can enhance the antitumor activity and at the same time, counteract the severe side effects, of chemotherapy. The substance P (SP)/neurokinin-1 receptor (NK-1R) interaction system is known to play a key role in the pathogenesis of cancer. Studies with NK-1R antagonists (such as aprepitant) denote that the NK-1R is a potential target for the treatment of cancer. Aprepitant combined with major chemotherapeutic drugs has shown the potential to increase antitumor activity and decrease side effects.. Since malignant tumor cancer cells overexpress the NK-1R, this combination therapy is a promising approach for the treatment of all kinds of cancer. Since aprepitant shows potential of being a broad-antitumor drug, the repurposing of this NK-1R antagonist as an antitumor agent is warranted. Studies pertaining to combination therapy of aprepitant/radiotherapy will also be outlined in this review. The aim of this review is to provide an update on combinational studies pertaining to chemotherapy/radiotherapy and NK-1R antagonist in cancer.. This combination strategy once confirmed, might open the door to a new era in chemotherapy and radiotherapy with greater antitumor activity and fewer side effects. This treatment strategy could possibly translate into higher cure rates, better quality of life and fewer sequelae in cancer patients.

Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Chemoradiotherapy; Drug Repositioning; Humans; Neoplasms; Neurokinin-1 Receptor Antagonists; Substance P

The substance P (SP)/neurokinin-1 receptor (NK-1R) system is involved in cancer progression. NK-1R, activated by SP, promotes tumor cell proliferation and migration, angiogenesis, the Warburg effect, and the prevention of apoptosis. Tumor cells overexpress NK-1R, which influences their viability. A typical specific anticancer strategy using NK-1R antagonists, irrespective of the tumor type, is possible because these antagonists block all the effects mentioned above mediated by SP on cancer cells. This review will update the information regarding using NK-1R antagonists, particularly Aprepitant, as an anticancer drug. Aprepitant shows a broad-spectrum anticancer effect against many tumor types. Aprepitant alone or in combination therapy with radiotherapy or chemotherapy could reduce the sequelae and increase the cure rate and quality of life of patients with cancer. Current data open the door to new cancer research aimed at antitumor therapeutic strategies using Aprepitant. To achieve this goal, reprofiling the antiemetic Aprepitant as an anticancer drug is urgently needed.

Topics: Antineoplastic Agents; Aprepitant; Drug Repositioning; Humans; Neoplasms; Neurokinin-1 Receptor Antagonists; Quality of Life; Receptors, Neurokinin-1; Substance P

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

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

In the current guidelines to prevent hemotherapyinduced nausea and vomiting, multiple antiemetic drugs are administered simultaneously. In patients who receive highly emetogenic chemotherapy, aprepitant, an NK1-receptor antagonist, is combined with ondansetron and dexamethasone. Aprepitant can influence the pharmacokinetics of other drugs, as it is an inhibitor and inducer of CYP3A4. Some anticancer drugs and other co-medication frequently used in cancer patients are CYP3A4 or CYP29C substrates. We give an overview of the metabolism and current data on clinically relevant drug-drug interactions with aprepitant during chemotherapy. Physicians should be aware of the potential risk of drug-drug interactions with aprepitant, especially in regimens with curative intent. More research should be performed on drug-drug interactions with aprepitant and their clinical consequences to make evidence-based recommendations.

Topics: Analgesics; Anticoagulants; Antiemetics; Antineoplastic Agents; Aprepitant; Chemoprevention; Dexamethasone; Drug Interactions; Glucocorticoids; Humans; Neoplasms; Neurokinin-1 Receptor Antagonists; Psychotropic Drugs; 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

Paraneoplastic itch occurs as the result of a systemic reaction to an underlying malignancy. Paraneoplastic itch is most commonly associated with lymphoproliferative malignancies and solid tumors that result in cholestasis. Paraneoplastic itch may occur in the absence of a primary rash or in association with dermatologic conditions such as erythroderma, acanthosis nigricans, dermatomyositis, Grover's disease, and eruptive seborrheic keratosis. Treatment of paraneoplastic itch is centered on targeting the underlying malignancy responsible for the systemic reaction. In cases of malignancy that are refractive to treatment, other therapies have been found to be effective for paraneoplastic itch, including selective serotonin reuptake inhibitors, mirtazapine, gabapentin, thalidomide, opioids, aprepitant, and histone deacetylase inhibitors.

Topics: Acantholysis; Acanthosis Nigricans; Analgesics, Opioid; Anticonvulsants; Antidepressive Agents; Aprepitant; Dermatitis, Exfoliative; Dermatomyositis; Histone Deacetylase Inhibitors; Humans; Ichthyosis; Immunosuppressive Agents; Keratosis, Seborrheic; Mianserin; Mirtazapine; Morpholines; Neoplasms; Neurokinin-1 Receptor Antagonists; Paraneoplastic Syndromes; Pruritus; Selective Serotonin Reuptake Inhibitors; Thalidomide

The substance P (SP)/neurokinin (NK)-1 receptor system plays an important role in cancer. SP promotes the proliferation of tumour cells, angiogenesis and the migration of tumour cells. We review the involvement of SP, the NK-1 receptor and NK-1 receptor antagonists in cancer. Tumour cells overexpress NK-1 receptors, which are involved in their viability. This overexpression suggests the possibility of specific treatment against tumour cells using NK-1 receptor antagonists, thus promoting a considerable decrease in the side effects of the treatment. This strategy opens up new approaches for cancer treatment, since these antagonists, after binding to their molecular target, induce the death of tumour cells by apoptosis, exert an antiangiogenic action and inhibit the migration of tumour cells. The use of NK-1 receptor antagonists such as aprepitant (used in clinical practice) as antitumour agents could be a promising innovation. The value of aprepitant as an antitumour agent could be determined faster than for less wellknown compounds because many studies addressing its safety and characterization have already been completed. The NK-1 receptor may be a promising target in the treatment of cancer; NK-1 receptor antagonists could act as specific drugs against tumour cells; and these antagonists could be new candidate anti-cancer drugs.

Topics: Angiogenesis Inhibitors; Antineoplastic Agents; Apoptosis; Aprepitant; Cell Movement; Cell Proliferation; Emotions; Humans; Inflammation; Morpholines; Neoplasms; Neovascularization, Pathologic; Neurokinin-1 Receptor Antagonists; Receptors, Neurokinin-1; Substance P

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

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

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

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

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

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

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

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

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

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

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

Advances in antiemetic therapy for chemotherapy-induced emesis have resulted in improved protection against symptoms occurring within 24 h of chemotherapy. However, the vomiting which tends to occur beyond 24 h after chemotherapy (delayed-phase vomiting) is still relatively poorly controlled by the currently available drugs, suggesting that more than one mechanism may mediate these symptoms. The standard antiemetic regimen currently recommended for prevention of chemotherapy-induced emesis includes a serotonin (5-HT(3)) antagonist and a corticosteroid. The neurokinin-1 (NK(1)) antagonist aprepitant represents a new class of antiemetic currently in clinical development. Using data obtained in 2 Phase II clinical trials of aprepitant in patients receiving chemotherapy based on the highly emetogenic chemotherapeutic agent cisplatin, we compared the time course of antiemetic effect of aprepitant, a 5-HT(3) antagonist, or a combination of both. Over the entire observation period (up to 7 days post-cisplatin), patients who received the NK(1) antagonist had a superior prevention of emesis. However, in the first 24 h after cisplatin, emesis occurred in fewer patients who received the 5-HT(3) antagonist than in patients who did not receive this class of drug. Furthermore, the majority of treatment failures in patients who received the NK(1) antagonist occurred within the first 8-12 h of chemotherapy, whereas the treatment failures in patients who received a 5-HT(3) antagonist were more evenly distributed over time. Patients who received both drugs had superior control of symptoms compared with patients who received one or the other. The difference in the time course of emesis blockade observed with two different classes of receptor antagonists provides substantial evidence for involvement of separate pathophysiological mechanisms in chemotherapy-induced vomiting. Serotonin mediates the early vomiting process that occurs within 8-12 h following cisplatin-based chemotherapy, after which time substance P acting at NK(1) receptors becomes the dominant mediator of vomiting

Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Cisplatin; Clinical Trials, Phase II as Topic; Drug Therapy, Combination; Granisetron; Humans; Morpholines; Neoplasms; Neurokinin-1 Receptor Antagonists; Neurotransmitter Agents; Ondansetron; Prodrugs; Serotonin; Serotonin Antagonists; Substance P; 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

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

Aquagenic pruritus (AP), an intense sensation of scratching induced after water contact, is the most troublesome aspect of BCR-ABL1-negative myeloproliferative neoplasms (MPNs). Mostly described in polycythemia vera (PV, ~ 40%), it is also present in essential thrombocythemia (ET) and primary myelofibrosis (PMF) (10%). Even if this symptom can decrease or disappear under cytoreductive treatments, 30% of treated MPN patients still persist with a real impact on the quality of life (QoL). Because its pathophysiology is poorly understood, efficient symptomatic treatments of AP are missing. The neuropeptide substance P (SP) plays a crucial role in the induction of pruritus. Several studies showed the efficacy of aprepitant, an antagonist of SP receptor (NK-1R), in the treatment of chronic pruritus but never evaluated in AP. The objectives of APHYPAP are twofold: a clinical aim with the evaluation of the efficacy of two drugs in the treatment of a persistent AP for MPN patients and a biological aim to find clues to elucidate AP pathophysiology.. A multicentric, double-blind, double-placebo, randomized study will include 80 patients with MPN (PV or ET or PMF) treated since at least 6 months for their hemopathy but suffering from a persistent AP (VAS intensity ≥6/10). Patients will be randomized between aprepitant (80 mg daily) + placebo to match to hydroxyzine OR hydroxyzine (25 mg daily) + placebo to match to aprepitant for 14 days. At D0, baseline information will be collected and drugs dispense. Outcome measures will be assessed at D15, D30, D45, and D60. The primary study endpoint will be the reduction of pruritus intensity below (or equal) at 3/10 on VAS at D15. Secondary outcome measures will include the number of patients with a reduction or cessation of AP at D15 or D60; evaluation of QoL and AP characteristics at D0, D15, D30, D45, and D60 with MPN-SAF and AP questionnaires, respectively; modification of plasmatic concentrations of cytokines and neuropeptides at D0, D15, D30, and D60; and modification of epidermal innervation density and pruriceptor expression at D0 and D15.. The APHYPAP trial will examine the efficacy of aprepitant vs hydroxyzine (reference treatment for AP) to treat persistent AP in MPN patients. The primary objective is to demonstrate the superiority of aprepitant vs hydroxyzine to treat persistent AP of MPN patients. The treatment received will be considered efficient if the AP intensity will be reduced at 3/10 or below on VAS after 14 days of treatment. The results of this study may provide a new treatment option for this troublesome symptom and also give us more insights in the pathophysiology understanding of AP.. APHYPAP. NCT03808805 , first posted: January 18, 2019; last update posted: June 10, 2021. EudraCT 2018-090426-66.

Topics: Aprepitant; Cytoreduction Surgical Procedures; Humans; Hydroxyzine; Neoplasms; Pruritus; Quality of Life

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 aim of this phase II study was to evaluate the efficacy and safety of two doses (10 and 5 mg) of olanzapine in combination with standard antiemetic treatment (aprepitant, palonosetron, and dexamethasone) for patients receiving highly emetogenic chemotherapy (HEC).. A multi-institutional, double-blind, randomized phase II, dose-finding study of olanzapine was performed in patients with a malignant solid tumor who were receiving HEC with cisplatin (≥ 50 mg/m. 153 patients were randomized to the 10 mg group (n = 76) or the 5 mg group (n = 77). The CR rate in the delayed phase was 77.6% (80% CI: 70.3-83.8, P = 0.01) in the 10 mg group and 85.7% (80% CI: 79.2-90.7, P < 0.001) in the 5 mg group (P value for H. Both doses of 10 and 5 mg olanzapine provided a significant improvement in delayed emesis. A dose of 5 mg olanzapine was determined as the recommended dose for a further phase III study based on higher CR and lower somnolence rates.. UMIN000014214.

Topics: Adult; Aged; Antiemetics; Antineoplastic Agents; Aprepitant; Benzodiazepines; Cisplatin; Dexamethasone; Double-Blind Method; Female; Humans; Isoquinolines; Male; Middle Aged; Morpholines; Neoplasms; Olanzapine; Palonosetron; Quinuclidines; Treatment Outcome; 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

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

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

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

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

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

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

Oxycodone is a µ-opioid receptor agonist widely used in the treatment of cancer pain. The predominant metabolic pathway of oxycodone is CYP3A4-mediated N-demethylation to noroxycodone, while a minor proportion undergoes 3-O-demethylation to oxymorphone by CYP2D6. The aim of this study was to investigate the effects of the mild CYP3A4 inhibitor aprepitant on the pharmacokinetics of orally administered controlled-release (CR) oxycodone.. This study design was an open-label, single-sequence with two phases in cancer patients with pain who continued to be administered orally with multiple doses of CR oxycodone every 8 or 12 hours. Plasma concentration of oxycodone and its metabolites were measured up to 8 hours after administration as follows: on day 1, CR oxycodone was administered alone; on day 2, CR oxycodone was administered with aprepitant (125 mg, at the same time of oxycodone dosing in the morning). The steady-state trough concentrations (Css) were measured from day 1 to day 3.. Aprepitant increased the area under the plasma concentration-time curve (AUC0-8) of oxycodone by 25% (p<0.001) and of oxymorphone by 34% (p<0.001), as well as decreased the AUC0-8 of noroxycodone by 14% (p<0.001). Moreover, aprepitant increased Css of oxycodone by 57% (p = 0.001) and of oxymorphone by 36% (p<0.001) and decreased Css of noroxycodone by 24% (p = 0.02) at day 3 compared to day 1.. The clinical use of aprepitant in patients receiving multiple doses of CR oxycodone for cancer pain significantly altered plasma concentration levels, but would not appear to need modification of the CR oxycodone dose.. UMIN.ac.jp UMIN000003580.

Topics: Adult; Aged; Analgesics, Opioid; Aprepitant; Area Under Curve; Delayed-Action Preparations; Female; Humans; Male; Middle Aged; Morphinans; Morpholines; Neoplasms; Oxycodone; Oxymorphone; Pain

Cabazitaxel is primarily metabolized by CYP3A. This study evaluated the impact of moderate/strong CYP3A inhibitors [aprepitant (Study Part 2); ketoconazole (Study Part 3)] or strong CYP3A inducers [rifampin (Study Part 4)] on the pharmacokinetics of cabazitaxel.. Adult patients received IV cabazitaxel/cisplatin 15/75 mg/m(2) on Day 1 of 3-week cycles (5/75 mg/m(2) in Cycles 1 and 2 of Part 3 to allow a safety margin to the cabazitaxel MTD). Patients received repeated oral doses of aprepitant, ketoconazole or rifampin before/during Cycle 2. Cabazitaxel clearance was the primary endpoint; clearance and area under the plasma concentration-time curve (AUC) were normalized to body surface area and dose, respectively.. The PK population included 13 (Part 2), 23 (Part 3) and 21 patients (Part 4). Repeated aprepitant administration did not affect cabazitaxel clearance [geometric mean ratio (GMR) 0.98; 90 % confidence interval (CI) 0.80-1.19]. Repeated ketoconazole administration resulted in 20 % decrease in cabazitaxel clearance (GMR 0.80; 90 % CI 0.55-1.15), associated with 25 % increase in AUC (GMR 1.25; 90 % CI 0.86-1.81). Repeated rifampin administration resulted in 21 % increase in cabazitaxel clearance (GMR 1.21; 90 % CI 0.95-1.53), associated with 17 % decrease in AUC (GMR 0.83; 90 % CI 0.65-1.05). The GMR of AUC0-24 with rifampin administration was 1.09 (90 % CI 0.9-1.33), suggesting that rifampin had a low impact during the initial phases of cabazitaxel elimination. Safety findings were consistent with previous results.. Cabazitaxel pharmacokinetics are modified by drugs strongly affecting CYP3A. Co-administration of cabazitaxel with strong CYP3A inhibitors or inducers should be avoided.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Area Under Curve; Cisplatin; Cytochrome P-450 CYP3A; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inducers; Drug Interactions; Female; Humans; Ketoconazole; Male; Middle Aged; Morpholines; Neoplasms; Rifampin; Taxoids

We evaluated the efficacy of aprepitant plus granisetron and an increased dose of dexamethasone in selected patients undergoing moderately emetogenic chemotherapy (MEC).. Nondrinking women <70 years undergoing MEC were randomly assigned to aprepitant (day 1, 125 mg; days 2 and 3, 80 mg) or placebo. Dexamethasone on days 1-3 was 12, 4, and 4 mg with aprepitant and 20, 8, and 8 mg with placebo. The primary end point was complete response (CR; no emesis or rescue therapy) during 120 h of the first cycle. Logistic regression analysis was performed to identify predictors of overall CR.. Of the 94 patients enrolled, 91 were assessable. Most received carboplatin-based chemotherapy. In the aprepitant (n=45) and placebo (n=46) groups, the overall, acute (day 1), and delayed (days 2-5) CR rates were 62% and 52%, 98% and 96%, and 62% and 52%, respectively. Although not statistically significant, the overall CR rate was 10% higher in the aprepitant group. Both regimens were well tolerated. On multivariate analysis, advanced ovarian cancer (OR, 0.26 (0.10-0.72)) was independently associated with a lower CR.. Even with an increased dose of dexamethasone, aprepitant seemed more effective than placebo in these selected patients undergoing MEC; however, delayed phase management remains a significant problem.

Topics: Adult; Aged; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Camptothecin; Carboplatin; Dexamethasone; Double-Blind Method; Drug Therapy, Combination; Endometrial Neoplasms; Female; Granisetron; Humans; Irinotecan; Logistic Models; Middle Aged; Morpholines; Neoplasms; Ovarian Neoplasms; Temperance; Treatment Outcome; 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

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

The pharmacokinetics of aprepitant, a neurokinin-1 receptor antagonist, have not been fully evaluated in clinical settings. The aim of this study was to characterize the plasma pharmacokinetics of aprepitant and reveal their influence of laboratory tests and cytochrome P450 (CYP) 3A5 gene polymorphisms in cancer patients. Forty-four 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 patients did not have gastrointestinal disease and the clinical laboratory values were within their normal reference levels. The plasma concentrations of aprepitant 24 (day 2 predose), 72, and 120 h after the first aprepitant administration were determined using LC-MS/MS. The relationships between plasma exposure to aprepitant and body weight, clinical laboratory values, age, gender, or CYP3A5*3 were investigated. The median and interquartile ranges of the 120-h area under the plasma concentration time curve (AUC)(0-120) of aprepitant were 73215 and 55518-91121 ng h/mL. The coefficient of variation value for aprepitant AUC(0-120) was 53%. The AUC(0-120) of aprepitant was correlated with the levels of total bilirubin and serum albumin, respectively (r=0.454, p<0.01 and r=0.287, p=0.06), but not with other non-genetic factors and CYP3A5 genetic variants in a univariate analysis. The AUC(0-120) of aprepitant was significantly correlated with the level of total bilirubin (adjusted R(2)=0.187, p<0.01) in a multivariate analysis. In conclusion, the plasma pharmacokinetics of aprepitant varied markedly in cancer patients receiving cisplatin-based chemotherapy for the first time and were correlated with the level of total bilirubin.

Topics: Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Area Under Curve; Cisplatin; Cytochrome P-450 CYP3A; Female; Humans; Male; Middle Aged; Morpholines; Neoplasms; Polymorphism, Genetic

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

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

Itch is a common side-effect of treatment with anti-EGFR antibodies and tyrosine-kinase inhibitors. We designed a pilot single-centre study to assess the effects of aprepitant-a neurokinin receptor inhibitor-for management of severe pruritus induced by biological drugs.. In this single-group, prospective study, we consecutively enrolled 45 outpatients with metastatic solid tumours treated with biological drugs at the Campus Bio-Medico Hospital of Rome, Rome, Italy, between September, 2010, and November, 2011. We classified patients into two groups: a refactory group, for patients with pruritis refractory to standard treatment, or a naive group, for patients who had not been previously treated for pruritis. Aprepitant (125 mg on day 1; 80 mg on day 3; 80 mg on day 5) was given to patients in the refractory group after at least 1 week of standard systemic treatment. In the naive group, aprepitant was given in the same schedule as the refractory group, after first onset of severe pruritus. Intensity of itch was evaluated by Visual Analogue Scale (VAS) score. The primary endpoint was change in median VAS score. This trial is registered with ClinicalTrials.gov, number NCT01683552.. Median VAS in the refractory group was 8·00 (95% CI 7·93-8·57) at baseline and 1·00 (0·00-2·00) after 1 week of treatment with aprepitant (p<0·0001). In the naive group, VAS score was 8·00 (7·43-8·37) at baseline and 0·00 (0·06-1·08) after 1 week of treatment (p<0·0001). 41 (91%) patients responded to aprepitant (ie, had a >50% reduction in intensity of pruritis) and pruritus recurred in only six (13%) patients. No adverse events related to aprepitant occurred.. Aprepitant decreases severe pruritus induced by biological treatments; it is an old drug, widely available, and therefore easy to add to the armamentarium of supportive treatment. Although to our knowledge no other studies of the anti-itch activity of aprepitant are planned, the results of our trial warrant confirmation in phase 2 and 3 trials.. None.

Topics: Adult; Aged; Antineoplastic Agents; Aprepitant; ErbB Receptors; Female; Humans; Male; Middle Aged; Morpholines; Neoplasms; Neurokinin-1 Receptor Antagonists; Pain Measurement; Pilot Projects; Prospective Studies; Pruritus

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

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

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

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

We compared an aprepitant regimen with a control regimen of ondansetron + dexamethasone given for 4 days.. Patients scheduled to receive cisplatin > or =70 mg/m(2) were randomized to either the aprepitant regimen (aprepitant, ondansetron and dexamethasone on day 1; aprepitant and dexamethasone on days 2-3; dexamethasone on day 4) or control regimen (ondansetron + dexamethasone on days 1-4). Patients recorded vomiting, nausea and rescue therapy use. The primary end point was complete response (no vomiting and no use of rescue therapy) in the overall phase (days 1-5 post-cisplatin).. Complete response rates were higher in the aprepitant than control group in the overall (72% versus 61%; P = 0.003), acute (day 1; 88% versus 79%; P = 0.005) and delayed phases (days 2-5; 74% versus 63%; P = 0.004), as were rates of no vomiting (overall 77% versus 62%, P < or = 0.001; acute 89% versus 81%, P = 0.004; delayed 79% versus 64%, P < or = 0.001). Rates of no rescue therapy were similar between groups.. Compared with an antiemetic regimen in which ondansetron + dexamethasone were given for 4 days, the aprepitant regimen was superior in the acute, delayed and overall phases of chemotherapy-induced nausea and vomiting. The aprepitant regimen should be considered a new standard of antiemetic therapy for cisplatin-treated patients. www.ClinicalTrials.gov Identifier: NTC00090207.

Topics: Adult; Aged; Aged, 80 and over; Antiemetics; Antineoplastic Agents; Aprepitant; Cisplatin; Dexamethasone; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Morpholines; Neoplasms; Ondansetron; Patient Selection

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

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

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

Recent studies have suggested that antiemetic therapy with a triple combination of the neurokinin-1 receptor antagonist MK-869, a serotonin (5-HT(3)) antagonist, and dexamethasone provides enhanced control of cisplatin-induced emesis compared with standard therapy regimens. The authors compared the antiemetic activity of a dual combination of MK-869 and dexamethasone with that of a standard dual combination of ondansetron and dexamethasone to characterize further the efficacy and tolerability profile of MK-869.. This was a multicenter, double-blind, randomized, active agent-controlled study of 177 cisplatin-naïve patients with malignant disease. On Day 1, MK-869 was given intravenously as its water-soluble prodrug, L-758,298. Patients were randomized to one of three groups as follows. Group I received L-758,298 100 mg intravenously (i.v.), then dexamethasone 20 mg i.v., and cisplatin >or= 70 mg/m(2) on Day 1 followed by 300 mg MK-869 (tablet) orally on Days 2-5; Group II received L-758,298 100 mg i.v., then dexamethasone 20 mg i.v., and cisplatin >or= 70 mg/m(2) on Day 1 followed by placebo on Days 2-5; and Group III received ondansetron 32 mg i.v., then dexamethasone 20 mg i.v., and cisplatin >or= 70 mg/m(2) on Day 1 followed by placebo on Days 2-5. Emesis was recorded over Days 1-5 in a diary. Nausea was assessed every 24 hours by visual analog scale. Additional medication was available for emesis or nausea at any time. The primary efficacy parameters of interest were the proportion of patients without emesis and the proportion without emesis or rescue therapy on Day 1 (acute phase) and on Days 2-5 (delayed phase).. No serious adverse events were attributed to L-758,298 or MK-869. On Day 1, the proportions of patients with no emesis and no use of rescue medication were 44% of patients in Group I, 36% of patients in Group II, 40% of patients in Groups I and II combined, and 83% of patients in Group III (P < 0.001 for Group III vs. the combined Groups I and II). The proportions of patients with no emesis and no use of rescue medication on Days 2-5 were 59% of patients in Group I, 46% of patients in Group II, and 38% of patients in Group III (P < 0.05 for Group I vs. Group III). The proportions of patients who were without emesis on Day 1 were 49% of patients in Group I, 47% of patients in Group II, and 84% of patients in Group III (P < 0.01 for Group I or II vs. Group III). On Days 2-5, however, the proportions of patients who were without emesis on Days 2-5 were 65% of patients in Group I, 61% of patients in Group II, and 41% of patients in Group III (P < 0.05 for Group I or II vs. Group III). Nausea scores in the acute phase were lower for Group III than for Group I, Group II, or Groups I and II combined (P < 0.05), although there was no significant difference among groups either for the delayed phase or overall for Days 1-5.. Although the L-758,298 and dexamethasone combination reduced acute (Day 1) emesis compared with historic rates, dual therapy with ondansetron and dexamethasone was superior in controlling acute emesis. Continued dosing with MK-869 may enhance control of other measures of delayed emesis, such as the use of rescue medication, although confirmation is required before a definitive conclusion may be drawn. MK-869 given as dual therapy with dexamethasone was superior to ondansetron with dexamethasone for the control of delayed emesis (Days 2-5) and control of the need for rescue medication on Days 2-5.

Topics: Adolescent; Adult; Aged; Antiemetics; Antineoplastic Agents; Aprepitant; Cisplatin; Dexamethasone; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Morpholines; Neoplasms; Neurokinin-1 Receptor Antagonists; Ondansetron; Vomiting

The NK1-receptor antagonist MK-869 (L-754,030) has demonstrated antiemetic activity in humans receiving chemotherapy. Objectives of the present trial included the first assessment of oral MK-869 plus dexamethasone compared with a 5HT(3) antagonist plus dexamethasone for prevention of acute and delayed emesis after high-dose cisplatin. Furthermore, the study sought to confirm that addition of MK-869 to a 5HT(3) antagonist plus dexamethasone was more effective than just the 5HT(3) antagonist plus dexamethasone for prevention of acute and delayed emesis.. This multicenter, double-blind, parallel-group trial in 351 cisplatin-naïve patients evaluated prevention of acute (0 to 24 hours) and delayed emesis (primary efficacy parameter; days 2 to 5) after cisplatin (> or =70 mg/m(2)). Patients were randomized to four groups (I to IV) (n = number randomized; number evaluable): granisetron (10 microg/kg intravenously) pre-cisplatin followed by placebo on days 2 to 5 (group I) (n = 90; 90); granisetron and MK-869 (400 mg PO [by mouth]) pre-cisplatin, followed by MK-869 (300 mg PO) on days 2 to 5 (group II) (n = 86; 84); MK-869 (400 mg PO) the evening before and pre-cisplatin, followed by MK-869 (300 mg PO) on days 2 to 5 (group III) (n = 89; 88); or MK-869 (400 mg PO) pre-cisplatin, followed by MK-869 (300 mg PO) on days 2 to 5 (group IV) (n = 86; 84). All patients also received dexamethasone (20 mg PO) before cisplatin. Additional medication was available to treat emesis or nausea at any time.. In the acute period, 57%, 80%, 46%, and 43% of patients were without emesis in groups I, II, III, and IV, respectively (P <.01 for group II v group I). In the delayed period, the proportion of patients without emesis in groups I, II, III, and IV was 29%, 63%, 51%, and 57%, respectively (P <.01 for groups II, III, and IV v group I). The distribution of nausea scores in the delayed period was lower when comparing group II with group I (P <.05 for days 1 to 5 and days 2 to 5). One serious adverse event (dizziness) was rated as possibly related to MK-869.. Once daily oral administration of MK-869 was effective in reducing delayed emesis and nausea after high-dose cisplatin. However, the combination of the 5HT3 antagonist plus dexamethasone was numerically superior to MK-869 plus dexamethasone in reducing acute emesis. Confirming and extending previous findings, the triple combination of a 5HT(3) antagonist, MK-869, and dexamethasone provided the best control of acute emesis.

Topics: Adult; Aged; Antidepressive Agents, Second-Generation; Antiemetics; Aprepitant; Cisplatin; Dexamethasone; Double-Blind Method; Drug Therapy, Combination; Female; Granisetron; Humans; Male; Middle Aged; Morpholines; Neoplasms; Vomiting

Chemotherapy-induced hiccups are understudied but can cause sleep deprivation, fatigue, pain in the chest and abdomen, poor oral intake, aspiration, and even death. As a critical next step toward investigating better palliative methods, this study reported patient-reported incidence of hiccups after oxaliplatin- or cisplatin-based chemotherapy.. The current study relied on 2 previous studies that sought to acquire consecutive direct patient report of hiccups among patients who had recently received chemotherapy with cisplatin or oxaliplatin. These patient-reported data in conjunction with information from the medical record are the focus of this report.. Of 541 patients, 337 were successful contacted by phone; and 95 (28%; 95% CI: 23%, 33%) of these contacted patients reported hiccups. In univariable analyses, male gender (odds ratio (OR): 2.17 (95% confidence ratio (95% CI): 1.30, 3.62); p = 0.002), increased height (OR: 1.03 (95% CI: 1.00, 1.06); p = 0.02), and concomitant aprepitant/fosaprepitant (OR: 2.23 (95% CI: 1.31, 3.78); p = 0.002) were associated with hiccups. In multivariable analyses, these statistically significant associations persisted except for height.. These patient-reported data demonstrate that oxaliplatin- or cisplatin-induced hiccups occur in a notable proportion of patients with cancer. Male gender and concomitant aprepitant/fosaprepitant appear to increase risk.

Topics: Antiemetics; Aprepitant; Cisplatin; Hiccup; Humans; Male; Neoplasms; Oxaliplatin; Patient Reported Outcome Measures

Exosomes are membrane-derived nano-vesicles upregulated in pathological conditions like cancer. Therefore, inhibiting their release is a potential strategy for the development of more efficient combination therapies. Neutral sphingomyelinase 2 (nSMase2) is a key component in exosome release; however, a clinically safe yet efficient nSMase2 inhibitor remains to be used discovered. Accordingly, we made an effort to identify potential nSMase2 inhibitor(s) among the approved drugs.. Virtual screening was performed and aprepitant was selected for further investigation. To evaluate the reliability of the complex, molecular dynamics were performed. Finally, using the CCK-8 assay in HCT116 cells, the highest non-toxic concentrations of aprepitant were identified and the nSMase2 activity assay was performed to measure the inhibitory activity of aprepitant, in vitro.. To validate the screening results, molecular docking was performed, and the retrieved scores were in line with the screening results. The root-mean-square deviation (RMSD) plot of aprepitant-nSMase2 showed proper convergence. Following treatment with different concentrations of aprepitant in both cell-free and cell-dependent assays, nSMase2 activity was remarkably decreased.. Aprepitant, at a concentration as low as 15 µM, was able to inhibit nSmase2 activity in HCT116 cells without any significant effects on their viability. Aprepitant is therefore suggested to be a potentially safe exosome release inhibitor.

Topics: Aprepitant; Early Detection of Cancer; Exosomes; Humans; Molecular Docking Simulation; Neoplasms; Reproducibility of Results; Sphingomyelin Phosphodiesterase

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

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

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

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

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, a lipophilic and small molecular representative of neurokinin 1 receptor antagonists, is known for its anti-proliferative activity on numerous cancer cell lines that are sensitive to Substance P mitogen action. In the presented research, we developed two novel structural modifications of aprepitant to create aprepitant conjugates with different radionuclide chelators. All of them were radiolabeled with

Topics: Animals; Aprepitant; Brain; Neoplasms; Neurokinin-1 Receptor Antagonists; Radiochemistry; Radiopharmaceuticals; Rats; Receptors, Neurokinin-1

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

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

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

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

Antiemetic triplet therapy including dexamethasone (DEX) is widely used for patients receiving highly emetogenic chemotherapy (HEC). In Japan, the appropriate dose of DEX has not been established for this combination.. To assess the efficacy and safety of increased-dose DEX, we retrospectively examined patients receiving HEC with antiemetic triplet therapy.. Twenty-four patients (fosaprepitant group) were given an increased-dose of DEX (average total dose: 45.8mg), fosaprepitant, and 5-HT3 antagonist. A lower-dose of DEX (33.6mg), oral aprepitant, and 5-HT3 antagonist were administered to the other 48 patients (aprepitant group). The vomiting control rates in the fosaprepitant and aprepitant groups were 100% and 85.4% in the acute phase, and were 75.0% and 64.6% in the delayed phase. The incidences of toxicity were similar comparing the two groups.. Triplet therapy using an increased-dose of DEX is suggested to be safe and effective for patients receiving HEC.

Topics: Adult; Aged; Antiemetics; Antineoplastic Agents; Aprepitant; Benzimidazoles; Dexamethasone; Drug Therapy, Combination; Female; Granisetron; Humans; Isoquinolines; Japan; Male; Middle Aged; Morpholines; Neoplasms; Palonosetron; Quinuclidines; Retrospective Studies; Serotonin Antagonists; 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

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

Chemotherapy-induced emesis remains a problem despite prophylaxis with 5-hydroxytryptamine (5-HT3) antagonists and dexamethasone. The purpose of the current study was to evaluate the efficacy of adding aprepitant, a neurokinin-1(NK-1) receptor antagonist, as a secondary antiemetic prophylaxis in cases failing to achieve full protection against emesis during the first cycle of a cisplatin-based regimen.. Patients receiving chemotherapy with a dose of at least 50 mg/m(2) of cisplatin-based regimens were eligible. If patients failed to achieve complete protection against vomiting when antiemetics (5-HT3 antagonists and dexamethasone) were given in cycle 1, aprepitant was added in subsequent cycles. The primary endpoint was complete response (no emetic episodes and no rescue antiemetics) during days 1-6.. We analyzed 257 patients consecutively. Forty-nine patients (19%) had acute and/or delayed emesis during the first cycle of chemotherapy. Forty of 49 patients received aprepitant for secondary prophylaxis of emesis in the second cycle. Complete protection from vomiting and nausea was achieved in 63% and 55% of patients, respectively. Thirty-five patients received aprepitant for the third cycle. Complete protection from vomiting and nausea was achieved in 77% and 71% of patients, respectively.. Primary antiemetic prophylaxis with 5-HT3 antagonists plus dexamethasone provided more than 80% complete protection against cisplatin-induced emesis. Addition of aprepitant as secondary antiemetic prophylaxis in subsequent cycles provided adequate emesis protection in patients who failed primary prophylaxis. Using aprepitant as secondary antiemetic prophylaxis for cancer patients with cisplatin-induced emesis is feasible and cost-effective.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antiemetics; Antineoplastic Agents; Aprepitant; Cisplatin; Female; Humans; Male; Middle Aged; Morpholines; Neoplasms; 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

Topics: Antineoplastic Agents; Aprepitant; ErbB Receptors; Female; Humans; Male; Morpholines; Neoplasms; Neurokinin-1 Receptor Antagonists; Pruritus

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

Topics: Antiemetics; Aprepitant; Female; Humans; Male; Morpholines; Neoplasms; Pruritus; Receptors, Neurokinin-1

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

In multiple-day chemotherapy (MDC), the combination of a 5-HT(3)-antagonist plus dexamethasone is still a standard of care. The role of a NK-1-antagonist remains to be defined.. Seventy eight cancer patients undergoing multiple-day chemotherapy of high (HEC) or moderate (MEC) emetic risk received granisetron, dexamethasone plus aprepitant during chemotherapy. After the end of chemotherapy, aprepitant plus dexamethasone was given for another 2 days. Primary end-point was complete response (CR) in the overall phase (day 1 until 5 days after the end of chemotherapy).. Thirty eight patients underwent HEC and 40 patients underwent MEC for a median of 3.5 days. CR was seen in 57.9% and 72.5% of patients receiving HEC and MEC, respectively. The tolerability of the aprepitant regimen over 5-7 days was comparable with a 3-day aprepitant regimen.. This is the first report in MDC with a NK-1-antagonist containing antiemetic regimen showing a favourable safety profile with good antiemetic efficacy.

Topics: Adult; Aged; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Dexamethasone; Drug Administration Schedule; Female; Granisetron; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Morpholines; Neoplasms; Neurokinin-1 Receptor Antagonists; Safety; Treatment Outcome

Aprepitant, a selective neurokinin-1 (NK-1) receptor antagonist approved for the treatment and prevention of emesis caused by moderately and highly emetogenic chemotherapy, is an inhibitor, inducer, and substrate of the cytochrome P450 3194 pathway. The CYP3A4 pathway is the major pathway of the metabolism of vinorelbine, a vinca alkaloid frequently used in combination with cisplatin. Therefore, we studied the potential interaction of the aprepitant 3-day antiemetic regimen on the pharmacokinetics of vinorelbine.. Fourteen patients with metastatic solid tumors were included in this open-label, balanced, 2-period crossover study. In treatment arm A, vinorelbine (25 mg/m2 weekly) was administered alone, while in treatment arm B the same dose of vinorelbine was administered following the administration of the aprepitant antiemetic regimen on day 1 and alone on day 8. The antiemetic regimen of aprepitant was comprised of the following; on day 1: 125 mg aprepitant, 12 mg dexamethasone, and 32 mg ondansetron; on days 2 and 3: 80 mg aprepitant and 8 mg dexamethasone and on day 4: 8 mg dexamethasone. Blood samples for vinorelbine pharmacokinetic analysis were collected over 96 h.. Two patients discontinued the study due to adverse events that were judged not to be drug-related. Complete pharmacokinetic data of vinorelbine administered alone and with the aprepitant antiemetic regimen were obtained in 12 patients. The mean plasma concentration profile of vinorelbine administered with aprepitant was identical to that following vinorelbine administered alone, with geometric mean vinorelbine plasma AUC ratios of treatment B day 1/treatment A day 1 and of treatment B day 8/treatment A day of 1.01 (0.93, 1.10) and 1.00 (0.92, 1.08), respectively.. As the aprepitant antiemetic regimen has no detectable inhibitory or inductive effect on the pharmacokinetics of vinorelbine, aprepitant when added to a standard antiemetic regimen consisting of ondansetron and dexamethasone can be safely combined with vinorelbine at clinically recommended doses.

Topics: Antiemetics; Antineoplastic Agents, Phytogenic; Aprepitant; Area Under Curve; Cross-Over Studies; Dexamethasone; Drug Therapy, Combination; Female; Half-Life; Humans; Infusions, Intravenous; Male; Middle Aged; Morpholines; Neoplasms; Ondansetron; Vinblastine; Vinorelbine

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

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