title: Aprepitant, granisetron, 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.
abstract: OBJECTIVE
  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.
  
  
  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/m(2) 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).
  
  
  CONCLUSIONS
  The addition of aprepitant resulted in significantly less CINV and had a positive effect on quality of life.
authors.affiliation: 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. thomas.schmitt@med.uni-heidelberg.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Schmitt
authors.affiliation: 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.
authors.forename: Hartmut
authors.initials: H
authors.lastname: Goldschmidt
authors.affiliation: 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.
authors.forename: Kai
authors.initials: K
authors.lastname: Neben
authors.affiliation: 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.
authors.forename: Anja
authors.initials: A
authors.lastname: Freiberger
authors.affiliation: 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.
authors.forename: Johannes
authors.initials: J
authors.lastname: Hüsing
authors.affiliation: 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.
authors.forename: Martina
authors.initials: M
authors.lastname: Gronkowski
authors.affiliation: 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.
authors.forename: Markus
authors.initials: M
authors.lastname: Thalheimer
authors.affiliation: 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.
authors.forename: Le Hang
authors.initials: le H
authors.lastname: Pelzl
authors.affiliation: 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.
authors.forename: Gerd
authors.initials: G
authors.lastname: Mikus
authors.affiliation: 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.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Burhenne
authors.affiliation: 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.
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Ho
authors.affiliation: 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.
authors.forename: Gerlinde
authors.initials: G
authors.lastname: Egerer
mesh_terms: D000077608:Aprepitant; D003907:Dexamethasone / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D017829:Granisetron / Q000008:administration & dosage* / Q000009:adverse effects; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008558:Melphalan / Q000009:adverse effects*; D009025:Morpholines / Q000008:administration & dosage* / Q000009:adverse effects; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000523:psychology; D009325:Nausea / Q000517:prevention & control*; D011446:Prospective Studies; D011788:Quality of Life; D014182:Transplantation, Autologous; D014839:Vomiting / Q000517:prevention & control*
chemical_list: D000077608:Aprepitant; D003907:Dexamethasone; D017829:Granisetron; D008558:Melphalan; D009025:Morpholines