Effectiveness and Safety of Antiemetic Aprepitant in Japanese Patients Receiving High-Dose Chemotherapy Prior to Autologous Hematopoietic Stem Cell Transplantation

Abstract

For patients receiving high-dose chemotherapy, a 5-hydroxytryptamine 3 receptor antagonist combined with dexamethasone is a standard antiemetic therapy. Despite this prophylactic anti-emetic treatment, many patients still suffer from uncontrollable emesis. In this study, we retrospectively evaluated the antiemetic effectiveness and safety of aprepitant (a neurokinin-1 receptor antagonist) in addition to 5-HT 3 antagonist in Japanese patients with hematologic malignancy receiving high-dose chemotherapy prior to autologous peripheral blood stem cell transplantation (auto-PBSCT). Twenty-six patients received aprepitant and granisetron (the aprepitant group), whereas, 22 patients received granisetron alone (the control group). All patients received 3 mg of granisetron intravenously 30 min before chemotherapy administration. Patients in the aprepitant group additionally received 125 mg of aprepitant 60-90 min before administration of the first moderately to highly emetogenic chemotherapy. On the next day or thereafter, 80 mg of aprepitant was administered in the morning until the last administration of moderately to highly emetogenic anticancer drugs. The percentage of patients who achieved complete response (CR), defined as no emesis with only grade 1-2 nausea, in the aprepitant group was significantly higher than that in the control group (42% vs. 5%, p=0.003). Logistic regression analysis showed that non-prophylactic use of aprepitant was significantly associated with non-CR. The frequencies of adverse drug events (ADEs) were not significantly different between two groups. In conclusion, the results of this study suggest that the addition of aprepitant to granisetron can improve the antiemetic effect without increasing ADEs in patients receiving high-dose chemotherapy prior to auto-PBSCT.

Prevention of chemotherapy-induced nausea and vomiting after high-dose melphalan and stem cell transplantation: review of the evidence and suggestions

“…Eleven papers, reporting results of clinical trials, that explored the effectiveness of a certain prophylaxis for CINV in patients undergoing HDMel conditioning for autologous SCT are included (Table 1). Of these 11 studies, 2 are randomized, comparative, and prospective [7,18], 6 are single-arm prospective [7,12,15,16,18,20], 2 are comparative and retrospective [10,19], and 1 is single-arm retrospective [13] ( Table 1). From these experiments, only aprepitant, fosaprepitant, and olanzapine were compared to standard therapy in the setting of HDMel.…”

“…The retrospective comparative study by Uchida M. et al [19] was small, n of 48 with only 15 patients treated with HDMel conditioning, and compared a two-drug aprepitant + granisetron against granisetron alone. It is important to note that both regimens were steroid-free.…”

“…5HT3RA 5HT3RAs are recommended by guidelines for CINV prophylaxis in autologous SCT, as well as for highly emetogenic drugs as part of a three-drug combination (aprepitant + 5HT3RA + dexamethasone) [4,8,9]. In the setting of HDMel, palonosetron was investigated in five trials [7,11,13,15,20], granisetron in three trials [12,17,19], and ondansetron in three trials [14,16,18]. The efficacy of different 5HT3RA drugs was not evaluated in the setting of HDMel; therefore, they should perhaps be considered equivalent in terms of efficacy for CINV prevention.…”

“…Aprepitant and Fosaprepitant As for 5HT3RA, NK1RAs are recommended for CINV prophylaxis in autologous SCT and highly emetogenic chemotherapy in combination with 5HT3RA and dexamethasone. In the setting of HDMel, aprepitant or fosaprepitant were investigated in eight different trials [12,[14][15][16][17][18][19][20]. Two trials compared a three-drug regimen (aprepitant or fosaprepitant +5HT3 + dexamethasone) with a two-drug regimen (5HT3RA + dexamethasone), concluding that the three-drug regimen was more effective [16,17].…”

Clinical Impact of Aprepitant in Patients Receiving High-Dose Chemotherapy prior to Autologous Peripheral Blood Stem Cell Transplantation: A Cost-Effectiveness Analysis

“…It can be combined with dexamethasone and a 5-HT3 receptor antagonist [10][11][12] . Recently, several studies have reported that aprepitant exhibited antiemetic effects during treatment involving HDCT prior to APBSCT [13][14][15][16][17][18] . These results indicated that aprepitant should be considered for CINV prophylaxis, although there is limited evidence supporting its use in this context [8,9] .…”