Adding Aprepitant to Granisetron/Dexamethasone Reduces Chemotherapy-Induced Nausea and Vomiting After High-Dose Melphalan Conditioning in Myeloma
In a phase III trial reported in the Journal of Clinical Oncology, Schmitt et al found that adding aprepitant to granisetron and dexamethasone significantly reduced chemotherapy-induced nausea and vomiting in myeloma patients undergoing high-dose melphalan conditioning and autologous stem cell transplantation.
Study Details
In this double-blind, single-center trial, 362 myeloma patients from Heidelberg University Hospital were randomly assigned between July 2005 and January 2012 to receive aprepitant at 125 mg on day 1 and 80 mg on days 2 to 4, granisetron at 2 mg on days 1 to 4, and dexamethasone at 4 mg on day 1 and 2 mg on days 2 to 3 (n = 181) or matching placebo, granisetron at 2 mg on days 1 to 4, and dexamethasone at 8 mg on day 1 and 4 mg on days 2 to 3 (n = 181).
Aprepitant was given 60 minutes before and granisetron and dexamethasone 30 minutes before melphalan conditioning at 100 mg/m2 on days 1 to 2. Autologous stem cell transplantation was performed on day 4.
The primary endpoint, complete response, was defined as no emesis and no rescue therapy within 120 hours of melphalan administration. Quality of life was assessed by the modified Functional Living Index–Emesis (FLIE) questionnaire on days −1 and 6.
Response Improved With Aprepitant
Complete response was significantly more common in the aprepitant group (58% vs 41%, odds ratio [OR] = 1.92, P = .0042; 59% vs 39%, OR = 2.16, P = .003, on per-protocol analysis).
More aprepitant patients had absence of major nausea (94% vs 88%, OR = 2.37, P = .026) and emesis (78% vs 65%, OR = 1.99, P = .0036) within 120 hours after melphalan, and more aprepitant patients had no emesis or additional antiemetic treatment during the acute phase within 24 hours after melphalan (97% vs 90%, OR = 3.11, P = .022) and during the delayed phase (24–120 hours; 60% vs 46%, OR = 1.80, P = .011).
Quality of life measured by total FLIE score was significantly better in the aprepitant group (mean score, 114 vs 106; P < .001), and 74% vs 59% of patients had a FLIE score indicating no impact on daily life (P = .004).
The investigators concluded: “The addition of aprepitant resulted in significantly less [chemotherapy-induced nausea and vomiting] and had a positive effect on quality of life.”
Thomas Schmitt, MD, of Heidelberg University Hospital, is the corresponding author for the Journal of Clinical Oncology article.
The study was supported by Merck Sharp & Dohme. For full disclosures of the study authors, visit jco.ascopubs.org.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
