Randomized, placebo‐controlled, pilot study evaluating aprepitant single dose plus palonosetron and dexamethasone for the prevention of acute and delayed chemotherapy‐induced nausea and vomiting

Abstract

BACKGROUND. The combination of palonosetron and aprepitant is safe and effective in the prevention of chemotherapy‐induced emesis (CIE). The purpose of this pilot study was to ascertain the effectiveness of 1‐day versus 3‐day aprepitant in the prevention of acute and delayed nausea and vomiting in patients who were receiving highly emetogenic chemotherapy. METHODS. This study was institutional review board‐approved and informed consent was obtained before this study was begun. This was a pilot, single‐institution, randomized, double‐blind, placebo‐controlled trial that evaluated 3 different treatment arms. All groups received palonosetron 0.25 mg intravenously on Day 1 and dexamethasone on Days 1–4. Arm A received aprepitant 125 mg orally on Day 1 followed by 80 mg on Days 2–3. Arm B received aprepitant 125 mg orally on Day 1 and placebo on Days 2–3. Arm C received placebos on Days 1–3. The primary endpoint was to evaluate the proportion of patients with acute and delayed emesis within each group. RESULTS. Seventy‐five patients were included in the analysis. The study commenced with 3 groups; however, an interim analysis displayed unacceptable emesis events in Arm C, and this group was terminated. There were no significant differences between Arms A and B for emesis, nausea, or the use of breakthrough antiemetics. In Arms A and B, 93% of patients were emesis‐free from Days 1–5 compared with only 50% in Arm C. CONCLUSIONS. From this pilot study of patients who were receiving palonosetron, aprepitant, and dexamethasone for highly emetogenic chemotherapy, a single dose of aprepitant displayed similar effectiveness compared with 3‐day aprepitant. Cancer 2008. © 2008 American Cancer Society.

Antiemetics: American Society of Clinical Oncology Clinical Practice Guideline Update

“…Such regimens should be used with initial chemotherapy, rather than assessing the patient's emetic response with less effective treatment. The pilot study by Herrington et al 4 compared two dosing schedules of aprepitant (1 day v 3 days). No differences in rates of complete response and emetic episodes for the overall study period were reported.…”

Aprepitant plus granisetron and dexamethasone for prevention of chemotherapy-induced nausea and vomiting in patients with gastric cancer treated with S-1 plus cisplatin

“…Thus, the question that whether palonosetron should be the preferred 5-HT 3 RA when aprepitant is used should be addressed. To date, limited information is available about the combination of palonosetron and aprepitant [30][31][32]. The newest combination antiemetic therapy with palonosetron and aprepitant plus corticosteroid may lead to further improvement in the control of CINV.…”

Antiemetic research: future directions

“…This paradox will need further study in the setting of single day antiemetic regimens, which are highly effective in emesis control, but also seem to lose on control of nausea over several days [16].…”