aprepitant and Lung-Neoplasms

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

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

Lung cancer is a bad prognostic illness with a limited survival and many side effects related to treatment used. Supportive care in cancer attends to enhance patient care among cancer and treatments suffering. Opioids are one of the most important treatments in the management of dyspnoea and pain. Every new drug in supportive care is tested to diminish side effects of treatment like erythropoietin against anemia or aprepitant against emesis. Many trials are developed to enhance this supportive care especially in lung cancer management.

Topics: Algorithms; Analgesics, Opioid; Angiogenesis Inhibitors; Antiemetics; Antineoplastic Agents; Aprepitant; Carcinoma, Bronchogenic; Dyspnea; Erythropoietin; Granulocyte Colony-Stimulating Factor; Humans; Lung Neoplasms; Morphine; Morpholines; Pain; Palliative Care; Prognosis; Recombinant Proteins

Pruritus is one of the most common and challenging side effects of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) and has impaired patients' quality of life and treatment compliance. Our study evaluated the efficacy and safety of aprepitant in managing EGFR-TKIs-related pruritus.. This randomized, double-blind, placebo-controlled study was conducted between December 2016 and August 2020 in China. Patients were eligible if they were 18 years or older and had histologically confirmed locally advanced or metastatic non-small cell lung cancer (NSCLC) with first onset of moderate to severe pruritus during EGFR-TKI treatment.. A total of 130 eligible patients were randomly assigned to aprepitant (n = 65) or desloratadine (n = 65) groups. The median (interquartile range [Q1, Q3]) age was 63 (54, 70) years, and 79 (60.8%) were women. Mean visual analog scale scores at baseline were 6.35 (95% confidence interval [CI], 5.89-6.82) in the aprepitant group and 5.94 (95% CI, 5.56-6.32) in the desloratadine group. After 1 week of treatment, 33 (53.2%) patients responded to aprepitant, which was significantly higher than that of 14 (23.7%) patients responded to desloratadine (p = .001). Moreover, patients in the aprepitant group had a significantly shorter response time than patients in the desloratadine group (mean [days], 13.39 [95% CI, 11.08-15.70] vs. 16.67 [95% CI, 14.19-19.13], p = .04). The most frequent drug-related adverse events in aprepitant group and desloratadine were constipation and dry mouth, and all adverse events were grade 1-2.. To the authors' knowledge, this is the first study to prospectively present that aprepitant elicited a better and faster response and mild toxicity for managing EGFR-TKI induced pruritus than desloratadine.. ClinicalTrials.gov Identifier: NCT02646020.

Topics: Aged; Aprepitant; Carcinoma, Non-Small-Cell Lung; ErbB Receptors; Female; Humans; Lung Neoplasms; Male; Middle Aged; Protein Kinase Inhibitors; Pruritus; Quality of Life

Topics: Aged; Antitussive Agents; Aprepitant; Cough; Double-Blind Method; Female; Humans; Lung Neoplasms; Male; Middle Aged; Vagus Nerve Stimulation

Although cough is a common and distressing symptom in patients with lung cancer, there is almost no evidence to guide treatment. Aprepitant, a centrally acting neurokinin-1 inhibitor, significantly decreased cough frequency in a pilot study.. Patients with advanced lung cancer and cough lasting over 2 weeks despite a cough suppressant were randomized 1:1 to aprepitant 125 mg orally on day 1 and then 80 mg orally on days 2 to 7 with physician's choice of antitussive; or to physician's choice of antitussive alone. Evaluation was at baseline and on days 3, 7, 9, and 12. The primary end point was subjective cough improvement on day 9, measured by the Visual Analog Scale and Manchester Cough in Lung Cancer Scale. Secondary end points included quality of life (QoL) as measured by the European Organization for Research and Treatment of Cancer (EORTC) Core Quality of Life Questionnaire and the EORTC Lung Cancer-Specific Quality of Life Questionnaire and toxicity.. Between 2017 and 2018, 128 patients were randomized. Median baseline cough duration was 90 days. Mean Visual Analog Scale scores (in mm) at baseline and day 9 were 68 and 39 in the aprepitant arm and 62 and 49 in the control arm, respectively (P < .001); mean Manchester Cough in Lung Cancer Scale scores at baseline and day 9 were 33 and 23 in the aprepitant arm and 30 and 25 in the control arm, respectively (P < .001). Overall QoL was not significantly different between the two arms; however, aprepitant led to a significant improvement in the cough-specific QoL domain (P = .017). Aprepitant did not increase severe adverse events.. Aprepitant led to a significant improvement in cough in advanced lung cancer, without increasing severe side effects.. Clinical Trials Registry-India; No.: CTRI/2017/05/008691; URL: http://ctri.nic.in.

Topics: Adult; Aged; Aprepitant; Carcinoma, Non-Small-Cell Lung; Cough; Female; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Staging; Neurokinin-1 Receptor Antagonists; Pilot Projects; Treatment Outcome; Young Adult

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

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

This study aimed to determine the efficacy and safety of aprepitant, palonosetron, and dexamethasone to prevent chemotherapy-induced nausea and vomiting in patients with locally advanced or metastatic lung cancer receiving full-dose single-day cisplatin-based combination chemotherapy.. Patients diagnosed with locally advanced or metastatic lung cancer who received full dose single-day cisplatin-based chemotherapy were randomized (1:1) to aprepitant plus palonosetron and dexamethasone, or placebo plus palonosetron and dexamethasone. The primary endpoint was complete response of nausea and vomiting in the first cycle. The secondary endpoints were the proportion of patients with nausea and vomiting who received rescue antiemetic medication, the response of cross-over patients, and safety.. A total of 244 patients were randomized. There was no difference between the 2 groups regarding personal characteristics. The administration of aprepitant significantly improved the complete response for vomiting in the overall period (92.6% vs. 79.93%; P < .01), but not a nausea-free response (75.4% vs. 71.3%; P > .05) in the first cycle. The percentage of patients who received rescue antiemetic medication was decreased for the aprepitant group (14.8% vs. 37.1%; P < .001). Patients who did not use aprepitant and suffered with nausea and vomiting in cycle 1 were crossed over to the aprepitant group (N = 32), and the rate of nausea and vomiting in cycle 2 was decreased to 37.5% (P < .05) and 25% (P < .05), respectively. There were no drug-related adverse effects.. Aprepitant plus palonosetron and dexamethasone proved to be effective and well-tolerated in preventing chemotherapy-induced nausea and vomiting after administration of full-dose single-day cisplatin-based combination chemotherapy.

Topics: Adult; Aged; Antiemetics; Antineoplastic Combined Chemotherapy Protocols; Aprepitant; Cisplatin; Dexamethasone; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Palonosetron; Vomiting

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Aprepitant is used with dexamethasone and 5-HT. Urinary 11β-hydroxytestosterone (11β-OHT)/testosterone concentration ratio and plasma 4β-hydroxycholesterol (4β-OHC) concentrations were measured before and after cisplatin treatment (days 1, 4, and 8). CYP3A5 was genotyped, and plasma aprepitant concentrations were measured on day 4 to examine its influence on CYP3A endogenous markers.. The urinary 11β-OHT/testosterone concentration ratio in the 35 patients included in this study increased by 2.65-fold and 1.21-fold on days 4 and 8 compared with day 1, respectively. Their plasma 4β-OHC concentration increased by 1.46-fold and 1.66-fold, respectively. The mean plasma aprepitant concentration on day 4 was 1,451 ng/mL, which is far lower than its inhibitory constant. The allele frequencies of CYP3A5*1 and CYP3A5*3 were 0.229 and 0.771, respectively. In patients with the CYP3A5*1 allele, the plasma 4β-OHC concentration was significantly lower at baseline but more potently increased with chemotherapy.. CYP3A activity was significantly induced from day 4 to day 8 in patients receiving cisplatin and three antiemetic drugs.

Topics: Antiemetics; Aprepitant; Carcinoma, Non-Small-Cell Lung; Cisplatin; Cytochrome P-450 CYP3A; Dexamethasone; Humans; Lung Neoplasms; Vomiting

Topics: Antitussive Agents; Aprepitant; Humans; Lung Neoplasms

Topics: Antitussive Agents; Aprepitant; Cough; Humans; Lung Neoplasms; Receptors, Neurokinin-1

To report a case of second-degree atrioventricular block associated with concomitant use of aprepitant and amlodipine.. A 73-year-old man with lung cancer was treated with aprepitant for prophylactic use for the prevention of nausea and vomiting, concomitantly with cisplatin, gemcitabine, and an investigational drug (anti-epidermal growth factor receptor monoclonal antibody). He was diagnosed with first-degree atrioventricular block and was taking amlodipine for hypertension. During the first cycle of chemotherapy, 5 days after the start of aprepitant, he experienced Wenckebach second-degree atrioventricular block (Mobitz type I), and amlodipine was discontinued. After day 6, the atrioventricular block was not shown. According to the Naranjo adverse drug reaction scale, a score of 7 was obtained (causality: probable). In addition, using the Drug Interaction Probability Scale, a score of 6 was obtained (causality: probable).. The drug-drug interaction between aprepitant and amlodipine was considered to have deteriorated his atrioventricular block, conceivably due to the inhibition of cytochrome P450 (CYP) 3A-mediated metabolism of amlodipine by aprepitant.

Topics: Aged; Amlodipine; Antiemetics; Aprepitant; Atrioventricular Block; Humans; Lung Neoplasms; Male; Morpholines; Vomiting

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

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

Lung adenocarcinoma is the most common pathologic pattern of lung cancer. During the past decades, a number of targeted agents have been explored to treat advanced lung adenocarcinoma. Recently, Crizotinib, the antagonist of anaplastic lymphoma kinase (ALK), has been widely used in ALK-rearranged lung cancer treatment. Crizotinib is generally well tolerated while its most frequent adverse events include visual disorders, gastrointestinal disturbances, cardiac and endocrine abnormalities. Rash caused by crizotinib is rarely seen, and there are few case reports of severe rash caused by crizotinib.. Here we report cases of an 81-year-old man and a 66-year-old woman with ALK-rearranged advanced lung adenocarcinoma. When patients came to our department, they both had crizotinib-induced severe rash.. Crizotinib was initiated as the 1st-line treatment without other therapies. We treated severe rash with traditional Chinese medicine (TCM) therapy called Zhiyang Pingfu liquid along with Western medicine. Zhiyang Pingfu liquid consists of Scutellaria baicalensis 20 g, Portulaca oleracea 30 g, Cortex Dictamni 30 g, Sophora flavescens 30 g, and other substances. Western medicine includes Minocycline hydrochloride tablets and Aprepitant capsules.. Both patients achieved a partial response when treated with crizotinib, and suffered from severe rash. With Zhiyang Pingfu liquid and Western medicine, their rash gradually disappeared with no sign of cancer progression. Also the male patient did not relieve after taking only antibiotics (standard therapy) and anti-allergic medicine.. Despite the dramatic benefit of crizotinib for patients with ALK rearrangement, crizotinib-induced severe rash needs to be dealt with caution. This is the 1st case in which TCM and Western medicine are used to successfully treat crizotinib-induced severe rash. The mechanism of crizotinib-induced rash deserves further attention in future research.

Topics: Adenocarcinoma of Lung; Aged; Aged, 80 and over; Anti-Bacterial Agents; Aprepitant; Crizotinib; Drug Therapy, Combination; Exanthema; Female; Humans; Lung Neoplasms; Male; Medicine, Chinese Traditional; Minocycline

Although substantial progress has been made in the treatment of non-small-cell lung cancer (NSCLC) patients with immune checkpoint inhibitors (ICIs), severe immune-related adverse events (irAEs) sometimes occur. Here, we report a case of severe refractory pruritus after Stevens-Johnson syndrome (SJS) in a patient with NSCLC treated with nivolumab. The patient was a 76-year-old Japanese woman with advanced NSCLC treated with nivolumab. After the second dose, she experienced severe rash with mucous involvement. We diagnosed SJS and started 50mg of oral prednisolone (1mg/kg). The rash completely resolved after prednisolone was started, but we could not manage the severe pruritus with emollients, antihistamines, and steroids. Finally, we administered aprepitant, an oral neurokinin-1 receptor antagonist, for her refractory pruritus. Her symptoms improved within 5days. Severe refractory pruritus can arise from ICIs, and aprepitant may be a useful treatment.

Topics: Aged; Antibodies, Monoclonal; Antineoplastic Agents; Aprepitant; Carcinoma, Non-Small-Cell Lung; Female; Humans; Immunotherapy; Japan; Lung Neoplasms; Morpholines; Neurokinin-1 Receptor Antagonists; Nivolumab; Programmed Cell Death 1 Receptor; Pruritus; Remission Induction; Stevens-Johnson Syndrome

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

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

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

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

The last decades have seen no significant progress in extending the survival of lung cancer patients and there is an urgent need to improve current therapies. The substance P (SP)/neurokinin-1 receptor (NK-1R) system plays an important role in the development of cancer: SP and NK-1R antagonists respectively induce cell proliferation and inhibition in human cancer cell lines. No study of the involvement of this system in non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) cells has been carried out in depth. Here, we demonstrate the involvement of the SP/NK-1R system in human H-69 (SCLC) and COR-L23 (NSCLC) cell lines: (1) they express isoforms of the NK-1R and mRNA for the NK-1R; (2) they overexpress the tachykinin 1 gene; (3) the NK-1R is involved in their viability; (4) SP induces their proliferation; (5) NK-1R antagonists (Aprepitant (Emend), L-733,060, L-732,138) inhibit the growth of both cell lines in a concentration-dependent manner; (6) the specific antitumor action of these antagonists against such cells occurs through the NK-1R; and (7) lung cancer cell death is due to apoptosis. We also demonstrate the presence of NK-1Rs and SP in all the human SCLC and NSCLC samples studied. Our findings indicate that the NK-1R may be a promising new target in the treatment of lung cancer and that NK-1R antagonists could be new candidate antitumor drugs in the treatment of SCLC and NSCLC.

Topics: Antineoplastic Agents; Apoptosis; Aprepitant; Cell Proliferation; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Humans; Lung Neoplasms; Morpholines; Neurokinin-1 Receptor Antagonists; Piperidines; Receptors, Neurokinin-1; Structure-Activity Relationship; Substance P; Tryptophan; Tumor Cells, Cultured

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

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

Topics: Adenocarcinoma; Aprepitant; Drug Interactions; Drug Therapy, Combination; Erlotinib Hydrochloride; Humans; Lung Neoplasms; Middle Aged; Morpholines; Neurokinin-1 Receptor Antagonists; Off-Label Use; Protein Kinase Inhibitors; Pruritus; Quinazolines

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

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

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

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