Evaluation of a neurokinin-1 antagonist in preventing multiple-day cisplatin-induced nausea and vomiting

Abstract

<jats:title>Abstract</jats:title><jats:sec id="j_med-2018-0005_s_006_w2aab3b8d450b1b7b1aab1c15b1Aa"><jats:title>Objective</jats:title><jats:p>To perform a prospective non-randomized comparison of the effectiveness and safety of combined neurokinin-1 antagonist aprepitant treatment with the standard multiple-day cisplatin regimen for the prevention of cisplatin-induced nausea and vomiting (CINV).</jats:p></jats:sec><jats:sec id="j_med-2018-0005_s_007_w2aab3b8d450b1b7b1aab1c15b2Aa"><jats:title>Methods</jats:title><jats:p>Patients being administered 3-day cisplatin-based chemotherapy (25 mg/m<jats:sup>2</jats:sup>/d) who had never received aprepitant were given either the standard regimen (tropisetron and dexamethasone) or the aprepitant regimen (aprepitant plus tropisetron and dexamethasone). The primary endpoint was the complete response (CR) in the overall phase (OP, 0–120 h) between the combined aprepitant triple regimen group and the standard group. Secondary endpoints were the CR in the acute phase (AP, 0–24 h) and delay phase (DP, 25–120 h) between the two groups. The first time of vomiting was also compared by Kaplan–Meier curves. The impact of CINV on the quality of life was assessed by the Functional Living Index-Emesis (FLIE). Aprepitant-related adverse effects (AEs) were also recorded.</jats:p></jats:sec><jats:sec id="j_med-2018-0005_s_008_w2aab3b8d450b1b7b1aab1c15b3Aa"><jats:title>Results</jats:title><jats:p>A CR was achieved by 80.0% in the aprepitant group compared with 56.0% in the standard group during the OP (P =0.018)as well as during the DP. However, during the AP, the aprepitant and standard therapy groups achieved identical CR rates (98.0%, P =1.000). A longer time to first emesis was documented for the aprepitant group than for the standard group. No effect of CINV on quality of life as assessed by FLIE was reported by 44.7% of aprepitant therapy patients and 24.0% of standard therapy patients (P=0.035). The main aprepitant-related AEs were fatigue and constipation, but there was no significant difference between groups.</jats:p></jats:sec><jats:sec id="j_med-2018-0005_s_009_w2aab3b8d450b1b7b1aab1c15b4Aa"><jats:title>Conclusion</jats:title><jats:p>Combined aprepitant therapy is recommended for the prevention of multiple-day CINV because of its improved CINV control rate and safety.</jats:p></jats:sec>

Olanzapine (5 mg) Plus Standard Triple Antiemetic Therapy for the Prevention of Multiple-Day Cisplatin Chemotherapy-Induced Nausea and Vomiting: A Prospective Randomized Controlled Study

“…The most common aprepitant-and olanzapine-related AEs included sedation, fatigue and constipation.The occurrences between two groups were identical and it were consistent with other studies examining aprepitant and olanzapine-related AEs [4,8,14] . In general, the tolerability in the study was safe, no grade 3 or 4 adverse events were observed in this study, and no patients discontinued the study because of undesired sedation.…”

“…Patients receiving multiple-day cisplatin chemotherapy are at risk of both acute and delayed nausea and vomiting for each day, as acute and delayed emesis may overlap after the initial day chemotherapy until the last day of chemotherapy [1,2] . Although the combination of aprepitant, 5-HT3 receptor antagonist(5-HT3RA) and dexamethasone(DXM) had showed higher complete response than the combination of 5-HT3RA plus dexamethasone in cisplatin multiple-day chemotherapy clinical studies, nausea remains a major problem for many patients [3,4,5] . The activity of olanzapine on multiple receptors, particularly the D2, 5-HT2c and 5-HT3 receptors, may be involved in nausea and vomiting.…”

Clinical Observation of Gene Polymorphism of Olanzapine or Aprepitant in Prevention of CINV

“…The previous study confirmed a higher CR rate with multi-day chemotherapy than with single-day chemotherapy. 16 Second, the vast majority of patients in the former study were young women, while the present study had more older and male patients, and being both young and female were high-risk factors for CINV, thus possibly leading to a higher CR rate. 17 In this study, the TP rate in both groups reached over 90% in the acute phase but was low in the delayed phase, indicating that prevention and treatment of CINV in the delayed phase might be more difficult and deserves clinical attention.…”

“…The previous study confirmed a higher CR rate with multi-day chemotherapy than with single-day chemotherapy. 16 Second, the vast majority of patients in the former study were young women, while the present study had more older and male patients, and being both young and female were high-risk factors for CINV, thus possibly leading to a higher CR rate. 17 …”

Pharmacokinetics of maropitant citrate after oral administration of multiple doses in adult horses

“…However, a study in mice showed that maropitant administration reduced intestinal motility and delayed intestinal transit time of labeled luminal contents (Mikawa et al, ). Similarly, humans using similar NK‐1 receptor antagonists have reported side effects of constipation in up to 16% of patients studied in one population (Jacob et al, ; Li et al, ). Peer‐reviewed data are unavailable describing intestinal motility disorders associated with maropitant in species other than mice, and further investigation is warranted prior to administering maropitant to horses at risk for gastrointestinal impaction.…”