Palonosetron in combination with 1-day versus 3-day dexamethasone for prevention of nausea and vomiting following moderately emetogenic chemotherapy: a randomized, multicenter, phase III trial

Abstract

PurposeA phase III trial assessed the efficacy of palonosetron plus dexamethasone given once in preventing acute and delayed chemotherapy-induced nausea and vomiting (CINV) following a broad range of moderately emetogenic chemotherapy (MEC) regimens.MethodsThis multicentre, randomized, open-label, non-inferiority trial evaluated two different treatment groups. One group received palonosetron (0.25 mg intravenously) and dexamethasone (8 mg intravenously) before chemotherapy, while the other was administered the same regimen on day 1 followed by dexamethasone 8 mg orally on days 2 and 3. The primary endpoint was complete response (CR; defined as no emetic episodes and no rescue medication) during the overall phase (days 1–5 after chemotherapy initiation). The non-inferiority margin was predefined as a 15% difference between groups in the primary endpoint.ResultsOf 332 chemotherapy-naïve patients included in the intention-to-treat analysis, 65.1% were female, and 35.2% received anthracycline plus cyclophosphamide (AC)-based regimens. Overall CR rates were 67.5% for those administered dexamethasone only on day 1 (n = 166), and 71.1% for those also administered dexamethasone on days 2 and 3 (n = 166; difference −3.6% (95% confidence interval, −13.5 to 6.3)). CR rates were not significantly different between groups during the acute (0–24 h post-chemotherapy; 88.6% versus 84.3%; P = 0.262) and delayed phases (days 2–5; 68.7% versus 77.7%; P = 0.116).ConclusionsPalonosetron plus single-dose dexamethasone administered before common MEC regimens provide protection against acute and delayed CINV which is non-inferior to that of palonosetron plus dexamethasone for 3 days. However, the major benefit of the single-day regimen occurs in patients receiving non-AC MEC regimens.

Antiemetic research: future directions

“…For these reasons, there is a particular interest in reducing their administration in certain clinical situations and/or in certain subsets of patients. Thus recently one double-blind study and one open-label study in patients receiving palonosetron plus dexamethasone on day 1 randomly assigned to receive either placebo or dexamethasone on days 2 and 3 have shown that there is an opportunity to reduce the total corticosteroid dose with no loss of efficacy in delayed MEC, although some patients experience an increase of nausea on some periods of observation [1,6].…”

Antiemetic therapy options for chemotherapy-induced nausea and vomiting in breast cancer patients

“…The result showed that singleday palonosetron and dexamethasone can offer similar extents of protection to CINV when compared to that of multiple-day dexamethasone administration. Although the exact type of chemotherapeutic regimen was not stated in the studied population in the report by Aapro et al, 24 another study 25 confirmed that this single-day regimen of intravenous palonosetron plus dexamethasone was effective in the subgroup of patients who received AC.…”

Efficacy of triple antiemetic therapy (palonosetron, dexamethasone, aprepitant) for chemotherapy-induced nausea and vomiting in patients receiving carboplatin-based, moderately emetogenic chemotherapy.

“…Results of antiemetic studies in patients treated with MEC are summarized in Table 3. Celio et al (2011) reported that the prevalence of a CR in the acute phase and delayed phase was 88.6 and 68.7%, respectively, in patients treated with palonosetron and dexamethasone as antiemetic treatment. Prevalence of a CR in other reports treated MEC not specified regimen tended to be equal or less than in that report.…”