Uchida, M., Ikesue, H., Miyamoto, T., Kato, K., Suetsugu, K., Ichinose, K., ... Oishi, R. (2013). Effectiveness and safety of antiemetic aprepitant in Japanese patients receiving high-dose chemotherapy prior to autologous hematopoietic stem cell transplantation. Biological & Pharmaceutical Bulletin, 36(5), 819–824. 

To evaluate the antiemetic effect and safety of aprepitant in combination with 5-HT3 receptor antagonist in patients undergoing autologous peripheral blood stem cell transplantation (auto-PBSCT)

This was a retrospective evaluation of patients who received conditioning high-dose chemotherapies prior to auto-PBSCT for hematologic malignancies comparing 26 consecutive patients who received antiemetic therapy that included both aprepitant and granisetron (the aprepitant group) between April 1, 2010, and January 31, 2010, and 22 patients who received granisetron alone (control group) between January 1, 2008, and March 31, 2010, before the introduction of aprepitant. In both groups, IV granisetron 3 mg was started 30 minutes prechemotherapy on day 1 and then repeated every 12 hours while receiving chemotherapy. In the aprepitant group, 125 mg of aprepitant was administered orally 60–90 minutes preadministration of the first moderately to highly emetogenic anticancer drug on day 1 and aprepitant 80 mg PO was given the following two days. Rescue medication including metoclopramide or hydroxyzine was used for breakthrough nausea or vomiting. A corticosteroid was not administered in either group for emetic control.

• N = 48              
• MEDIAN AGE = 52 years (range = 20–66 years)
• MALES:  58%, FEMALES:  42%
• KEY DISEASE CHARACTERISTICS: Patients with non-hodgkin lymphoma, multiple myeloma, hodgkin lymphoma, and leukemia. Conditioning regimens: MCEC (ranimustine 200 mg/m², carboplatin 300 mg/m², etoposide 500 mg/m², cyclophosphamide 50 mg/m²) or melphalan (100 mg/m²) +/– bortezomibor; LEED (etoposide 500 mg/m², cyclophosphamide 60 mg/m², melphalan 130 mg/m²). 
• OTHER KEY SAMPLE CHARACTERISTICS: Japanese descent

• SITE: Single-site  
• SETTING TYPE: Not specified  
• LOCATION: Japan

• PHASE OF CARE: Active antitumor treatment

Retrospective study design with a historical control.

Nausea, vomiting, and other adverse events (ADEs) were monitored twice daily (morning and evening), mainly by nurses, and recorded into EMRs. Primary endpoint was achievement of complete response (CR, defined as no emesis with only grades 1–2 nausea using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0) during and until five days after the last chemotherapy dose was administered. Secondary endpoints included percent of patients without vomiting, percent without severe nausea, and the frequency of other ADEs. Severity of ADEs was classified by CTCAE version 4.0.

The percentage of patients who achieved CR in the aprepitant group was significantly higher than in the control group (42% versus 4.5%, p = 0.003). The percentage of patients without vomiting was higher in the aprepitant group (57%) versus the control group (4.5%; p < 0.001), and the percentage of patients without severe nausea was higher in the aprepitant group (58% versus 23%, p = 0.02) in the control group. There was no significant increase in ADEs when adding aprepitant to the antiemetic regimen.

The prophylactic administration of aprepitant significantly enhanced the effectiveness of antiemetic therapy without increasing the frequency and severity of ADEs in Japanese patients receiving high-dose chemotherapy prior to auto-PBSCT for hematologic malignancies.

• Small sample (< 100)
• Risk of bias (sample characteristics)
• Unintended interventions or applicable interventions that would influence results are not described.
• Measurement/methods not well described
• Other limitations/explanation: The study design is limited in that it is a purely retrospective comparison of a very small group. There is limited of description of data collection. There was no report on the use of rescue medication in any of the analyses.

This study suggests that the addition of aprepitant to a 5-HT3 as prophylaxis for CINV in HEC regimens results in significant improvement in the control of CINV. This comparison of treatment regimens before and after the availability of aprepitant validates the added benefit of including a neurokinin 1 receptor antagonist to 5-HT3 in HEC regimens for improved CINV prophylaxis. Also, this antiemetic regimen did not incorporate the use of steroids, demonstrating a good level of efficacy with a 5-HT3 in addition to neurokinin 1 receptor antagonist.