title: Efficacy of aprepitant for the prevention of chemotherapy-induced nausea and vomiting with a moderately emetogenic chemotherapy regimen: a multicenter, placebo-controlled, double-blind, randomized study in patients with gynecologic cancer receiving paclitaxel and carboplatin.
abstract: BACKGROUND
  Substance P contributes to the hypersensitivity reaction (HSR) to paclitaxel in a rat model. Aprepitant acts as an inhibitor of the binding of substance P to the neurokinin-1 receptor and, consequently, may reduce the frequency of paclitaxel-induced HSR. While aprepitant has a prophylactic effect against vomiting caused by high-dose cisplatin, the benefits of aprepitant have not been clearly demonstrated in patients receiving paclitaxel and carboplatin (TC) combination chemotherapy.
  
  
  METHODS
  We conducted a multicenter, placebo-controlled, double-blind, randomized study in Japanese patients with gynecologic cancer who received TC combination chemotherapy. Patients received aprepitant or placebo together with both a 5-HT3 receptor antagonist and dexamethasone prior to chemotherapy. The primary endpoint was the proportion of patients with HSR, and the secondary endpoints were the proportion of patients with "no vomiting", "no significant nausea", and complete response, respectively.
  
  
  RESULTS
  Of the 324 randomized patients, 297 (151 in the aprepitant group; 146 in the placebo group) were evaluated. The percentage of patients with HSR (9.2 vs. 7.5 %, respectively; P = 0.339) was not significantly different between the groups. The percentage of "no vomiting" patients (78.2 vs. 54.8 %; P < 0.0001), "no significant nausea" patients (85.4 vs. 74.7 %; P = 0.014), and patients showing complete response (61.6 vs. 47.3 %, P = 0.0073) was significantly higher in the aprepitant group than in the placebo group.
  
  
  CONCLUSIONS
  The administration of aprepitant did not have a prophylactic effect on the HSR but was effective in reducing nausea and vomiting in gynecologic cancer patients receiving TC combination chemotherapy.
authors.affiliation: Department of Obstetrics and Gynecology, Kyushu University Hospital, Fukuoka, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Yahata
authors.affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine, Kagoshima University Hospital, Kagoshima, Japan. hirokoba@m2.kufm.kagoshima-u.ac.jp.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kobayashi
authors.affiliation: Department of Obstetrics and Gynecology, Kyushu University Hospital, Fukuoka, Japan.
authors.forename: Kenzo
authors.initials: K
authors.lastname: Sonoda
authors.affiliation: Center of Clinical Research, National Kyushu Cancer Center, Fukuoka, Japan.
authors.forename: Mototsugu
authors.initials: M
authors.lastname: Shimokawa
authors.affiliation: Department of Obstetrics and Gynecology, Miyazaki Prefectural Hospital, Miyazaki, Japan.
authors.forename: Tatsuhiro
authors.initials: T
authors.lastname: Ohgami
authors.affiliation: Gynecology Service, National Kyushu Cancer Center, Fukuoka, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Saito
authors.affiliation: Department of Obstetrics and Gynecology, Kyushu Hospital, Kitakyushu, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Ogawa
authors.affiliation: Department of Obstetrics and Gynecology, Saiseikai Fukuoka Hospital, Fukuoka, Japan.
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Sakai
authors.affiliation: Department of Obstetrics and Gynecology, Kitakyushu Municipal Medical Center, Kitakyushu, Japan.
authors.forename: Akimasa
authors.initials: A
authors.lastname: Ichinoe
authors.affiliation: Department of Obstetrics and Gynecology, Hamanomachi Hospital, Fukuoka, Japan.
authors.forename: Yousuke
authors.initials: Y
authors.lastname: Ueoka
authors.affiliation: Department of Obstetrics and Gynecology, National Kyushu Medical Center, Fukuoka, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Hasuo
authors.affiliation: Department of Obstetrics and Gynecology, Fukuoka Red Cross Hospital, Fukuoka, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Nishida
authors.affiliation: Department of Pharmacy, Kyushu University Hospital, Fukuoka, Japan.
authors.forename: Satohiro
authors.initials: S
authors.lastname: Masuda
authors.affiliation: Department of Obstetrics and Gynecology, Kyushu University Hospital, Fukuoka, Japan.
authors.forename: Kiyoko
authors.initials: K
authors.lastname: Kato
mesh_terms: D000328:Adult; D000368:Aged; D000932:Antiemetics / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D000077608:Aprepitant; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D003907:Dexamethasone / Q000627:therapeutic use; D004311:Double-Blind Method; D004342:Drug Hypersensitivity / Q000209:etiology / Q000517:prevention & control*; D004359:Drug Therapy, Combination; D005260:Female; D005833:Genital Neoplasms, Female / Q000188:drug therapy*; D006801:Humans; D008875:Middle Aged; D009025:Morpholines / Q000627:therapeutic use*; D009325:Nausea / Q000139:chemically induced / Q000517:prevention & control*; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D012074:Remission Induction; D058831:Serotonin 5-HT3 Receptor Antagonists / Q000627:therapeutic use; D014839:Vomiting / Q000139:chemically induced / Q000517:prevention & control*; D055815:Young Adult
chemical_list: D000932:Antiemetics; D009025:Morpholines; D058831:Serotonin 5-HT3 Receptor Antagonists; D000077608:Aprepitant; D003907:Dexamethasone; D016190:Carboplatin; D017239:Paclitaxel
keywords: Aprepitant; CINV; Gynecologic cancer; Hypersensitivity reaction; MEC regimen