Aprepitant (EMEND), Granisetron (

KYTRIL) , and Dexamethasone for Prevention of Chemotherapy-Induced Nausea and Vomiting After High-Dose Melphalan in Autologous Transplantation for Multiple Myeloma: Results of a Randomized, Placebo-Controlled Phase III Trial

1. Thomas Schmitt⇑,
2. Hartmut Goldschmidt,
3. Kai Neben,
4. Anja Freiberger,
5. Johannes Hüsing,
6. Martina Gronkowski,
7. Markus Thalheimer,
8. Le Hang Pelzl,
9. Gerd Mikus,
10. Jürgen Burhenne,
11. Anthony D. Ho and
12. Gerlinde Egerer

+ Author Affiliations

1. Thomas Schmitt, Hartmut Goldschmidt, Anja Freiberger, Johannes Hüsing, Martina Gronkowski, Markus Thalheimer, Le Hang Pelzl, Gerd Mikus, Jürgen Burhenne, Anthony D. Ho, and Gerlinde Egerer, Heidelberg University Hospital, Heidelberg; and Kai Neben, Klinikum Mittelbaden, Baden-Baden, Germany.

1. Corresponding author: Thomas Schmitt, MD, Department of Hematology, Oncology, and Rheumatology, Heidelberg University Hospital, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany; e-mail: thomas.schmitt@med.uni-heidelberg.de.

1. Presented at the 49th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, May 31-June 4, 2013.

Abstract

Purpose The optimal regimen to prevent chemotherapy-induced nausea and vomiting (CINV) for patients undergoing high-dose chemotherapy and autologous stem-cell transplantation (ASCT) is unclear. To evaluate the effect of aprepitant in addition to a standard regimen, we conducted this randomized, placebo-controlled phase III trial. 

Patients and Methods Patients with multiple myeloma were randomly assigned at a one-to-one ratio to receive either aprepitant (125 mg orally on day 1 and 80 mg orally on days 2 to 4), granisetron (2 mg orally on days 1 to 4), and dexamethasone (4 mg orally on day 1 and 2 mg orally on days 2 to 3) or matching placebo, granisetron (2 mg orally on days 1 to 4), and dexamethasone (8 mg orally on day 1 and 4 mg orally on days 2 to 3). Melphalan 100 mg/m² was administered intravenously on days 1 to 2. ASCT was performed on day 4. The primary end point (complete response) was defined as no emesis and no rescue therapy within 120 hours of melphalan administration. Quality of life was assessed by modified Functional Living Index–Emesis (FLIE) questionnaire on days −1 and 6. 

Results Overall, 362 patients were available for the efficacy analysis (181 in each treatment arm). Significantly more patients receiving aprepitant reached the primary end point (58% v 41%; odds ratio [OR], 1.92; 95% CI, 1.23 to 3.00; P = .0042). Absence of major nausea (94% v 88%; OR, 2.37; 95% CI, 1.09 to 5.15; P = .026) and emesis (78% v 65%; OR, 1.99; 95% CI, 1.25 to 3.18; P = .0036) within 120 hours was increased by aprepitant. Mean total FLIE score (± standard deviation) was 114 ± 18 for aprepitant and 106 ± 26 for placebo (P < .001). 

Conclusion The addition of aprepitant resulted in significantly less CINV and had a positive effect on quality of life.