aprepitant and Head-and-Neck-Neoplasms

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

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

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

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

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

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

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

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

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

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