Addition of Aprepitant (Emend®) to Standard Antiemetic Regimen Continued for 7 Days after Chemotherapy for Stem Cell Transplantation Provides Significant Reduction of Vomiting

Abstract

Chemotherapy-induced nausea/vomiting (CINV) is a major problem for patients treated with high-dose chemotherapy (HDCT) conditioning before stem cell transplantation (SCT), both during chemotherapy and afterwards (delayed nausea/vomiting). The standard of care (5-HT₃ antagonist and dexamethasone) appears to be ineffective against delayed nausea and vomiting. The objective of this study was to compare standard antiemetic treatment with standard treatment plus prolonged treatment with aprepitant (Emend®) until 7 days after the end of chemotherapy in patients treated with HDCT before autologous SCT. Ninety-six patients were randomized to the experiment (EXP) group receiving Emend in addition to standard antiemetics or to the control (CTR) group receiving placebo. Emend or placebo treatment started 1 h before the first HDCT dose for SCT and ended 7 days after HDCT. Thirty-eight patients in the EXP group experienced complete response (no vomiting) compared to 16 patients in the CTR group. There was a significant difference between the EXP (0.63 ± 2.71) and the CTR (3.72 ± 4.91) group during 10 days after the end of HDCT (p = 0.001) with regard to the number of vomiting episodes. No difference with regard to days of nausea or in the use of antiemetic rescue was noted between the groups. We conclude that standard antiemetic treatment can be improved by addition of aprepitant continued for 7 days after the end of chemotherapy.

Efficacy and safety of multiple doses of NEPA without dexamethasone in preventing nausea and vomiting induced by multiple-day and high-dose chemotherapy in patients with non-Hodgkin’s lymphoma undergoing autologous hematopoietic stem cell transplantation: a phase IIa, multicenter study

“…Indeed, studies have evaluated that CINV prophylaxis based on palonosetron and dexamethasone, either in single or multiple dose, do not provide an extensive control of nausea and vomiting in patients undergoing MD-CT and MD-HD-CT [27,28]. Similar rates were found in trials that evaluated the efficacy of the triple combination 5HT 3 -RA/NK 1 -RA/ dexamethasone using ondansetron or tropisetron and aprepitant in patients treated for several days with ablative preparative regimens [18,20,21]. However, proper comparisons are hampered by the lack of comparable endpoints and discrepancies in schedules, including inconsistent length of acute/delayed phases, different drug administrations, and distinct usage of corticosteroids.…”

“…Although the international guidelines recommend the three-drug combination 5HT 3 -RA/NK 1 -RA/dexamethasone for patients treated with HD-CT and stem cell or bone marrow transplantation, CINV management remains a significant problem in this setting of patients [5,6]. Some studies have been conducted with different 5HT 3 -RAs in combination with aprepitant (NK 1 -RA) and dexamethasone using different schedules [18][19][20][21]. However, trials investigating the efficacy and the safety of NEPA in hematological settings are not yet available.…”

Antiemetic prophylaxis in patients undergoing hematopoietic stem cell transplantation: a multicenter survey of the Gruppo Italiano Trapianto Midollo Osseo (GITMO) transplant programs

“…The CR rate was 82% with the aprepitant arm versus 66%, however, there was no effect in the overall visual analog scale (VAS). The efficacy of aprepitant in patients with multiple myeloma undergoing high-dose chemotherapy with autologous SCT was investigated in phase II [17] and phase III clinical studies [18]. In the phase III study, patients with multiple myeloma were randomized to receive either aprepitant administered at a dose of 125 mg orally on day 1 and 80 mg orally on days 2 to 4, granisetron and dexamethasone or matching placebo, granisetron and dexamethasone.…”

“…The CR rate was significantly higher in the aprepitant arm compared to the control group (58 vs 41%); absence of major nausea ( 94 vs 88%) and vomiting (78 vs 65%) within 120 hours was significantly improved by aprepitant. Svanberg et al [17] randomized 96 patients to the 5-HT3 receptor antagonist and dexamethasone with or without aprepitant for 7 days following HDCT and autologous SCT. Thirty-eight patients in the triple therapy regimen had no vomiting compared to 16 patients in the control group, and this difference was statistically significant.…”

Efficacy and safety of netupitant/palonosetron combination (NEPA) in preventing nausea and vomiting in non-Hodgkin’s lymphoma patients undergoing to chemomobilization before autologous stem cell transplantation

“…Evidence-based antiemetic guidelines now recommend co-administration of a combination regimen consisting of a neurokinin-1 (NK 1 ) receptor antagonist (RA), 5-hydroxytryptamine-3 (5-HT 3 ) RA, and dexamethasone (DEX) to prevent CINV in patients who are undergoing conditioning regimens for SCT [4,5]. However, the guidelines are remiss in providing specific recommendations on the schedule of these agents in this setting beyond citing aprepitant studies where aprepitant was administered daily during and after the preparatory regimen [6][7][8]. In addition, the guidelines are focused on the conditioning phase prior to ASCT and do not provide any guidance for antiemetic regimens to be used during chemotherapy for mobilization of hematopoietic stem cells.…”