fosaprepitant and Esophageal-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

Fosaprepitant, an NK1 receptor antagonist, inhibits and induces cytochrome P450 3A4 (CYP3A4) as its substrate. Contrarily dexamethasone is metabolized by CYP3A4. Therefore, in combination therapy wherein both agents interact with each other, it is recommended that the dexamethasone dose be reduced in the first two days. Thus far, there are only a few studies on the optimum dose of dexamethasone after day 3. Thus, we aimed to determine the pharmacokinetics of dexamethasone on day3 when administered together with fosaprepitant and investigate the dose-dependent differences in its antiemetic effect in patients with cancer.. Twelve patients with esophageal, stomach, or lung cancer received primary highly emetogenic chemotherapy (HEC). We intravenously administered 9.9 mg and 6.6 mg of dexamethasone on days 1 and 2, respectively, and 6.6 mg or 13.2 mg on day 3 together with the administration of 150 mg fosaprepitant and 0.75 mg palonosetron. We assessed the pharmacokinetics of dexamethasone on day 3 by dose and examined the dose-dependent antiemetic effect.. No differences were observed in the time-to-maximum concentration and blood half-life of dexamethasone between patient groups that received dexamethasone at doses of 6.6 mg and 13.2 mg. In contrast, the area under the blood concentration-time curve and the maximum concentration of dexamethasone correlated with its dose. Moreover, the blood dexamethasone concentration on day 3 increased by twofold after the administration of a higher dose than after a lower dose. The severity of nausea in the delayed phase significantly decreased in a dose-dependent manner.. Administration of a higher dexamethasone dose on day 3 improved the antiemetic effect of the combined regimen in patients with cancer who underwent HEC.
.

Topics: Aged; Antiemetics; Antineoplastic Agents; Cytochrome P-450 CYP3A; Cytochrome P-450 CYP3A Inducers; Cytochrome P-450 CYP3A Inhibitors; Dexamethasone; Dose-Response Relationship, Drug; Drug Interactions; Esophageal Neoplasms; Female; Humans; Lung Neoplasms; Male; Middle Aged; Morpholines; Nausea; Stomach Neoplasms; Vomiting

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

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