title: Randomized, double-blind, phase III trial of palonosetron versus granisetron in the triplet regimen for preventing chemotherapy-induced nausea and vomiting after highly emetogenic chemotherapy: TRIPLE study.
abstract: There has been no phase III study of comparing the efficacy of first- and second-generation 5-HT3 receptor antagonists in the triplet regimen with dexamethasone and aprepitant for preventing chemotherapy-induced nausea and vomiting after highly emetogenic chemotherapy (HEC).
  
  
  
  Patients with a malignant solid tumor who would receive HEC containing 50 mg/m(2) or more cisplatin were randomly assigned to either palonosetron (0.75 mg) arm (Arm P) or granisetron (1 mg) arm (Arm G), on day 1, both arms with dexamethasone (12 mg on day 1 and 8 mg on days 2-4) and aprepitant (125 mg on day 1 and 80 mg on days 2-3). The primary end point was complete response (CR; no vomiting/retching and no rescue medication) at the 0-120 h period and secondary end points included complete control (CC; no vomiting/retching, no rescue medication, and no more than mild nausea) and total control (TC; no vomiting/retching, no rescue medication, and no nausea).
  
  
  
  Between July 2011 and June 2012, 842 patients were enrolled. Of 827 evaluable, 272 of 414 patients (65.7%) in Arm P had a CR at the 0-120 h period when compared with 244 of 413 (59.1%) in Arm G (P = 0.0539). Both arms had the same CR rate of 91.8% at the acute (0-24 h) period, while at the delayed (24-120 h) period, Arm P had a significantly higher CR rate than Arm G (67.2% versus 59.1%; P = 0.0142). In secondary end points, Arm P had significantly higher rates than Arm G at the 0-120 h period (CC rate: 63.8% versus 55.9%, P = 0.0234; TC rate: 47.6% versus 40.7%, P = 0.0369) and delayed periods (CC rate: 65.2% versus 55.9%, P = 0.0053; TC rate: 48.6% versus 41.4%, P = 0.0369).
  
  
  
  The present study did not show the superiority of palonosetron when compared with granisetron in the triplet regimen regarding the primary end point.
  
  
  
  UMIN000004863.
authors.affiliation: Department of Pharmacy, Shizuoka Cancer Center, Shizuoka Department of Pharmacy, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo.
authors.forename: K
authors.initials: K
authors.lastname: Suzuki
authors.affiliation: Department of Biostatistics, Yokohama City University School of Medicine, Yokohama.
authors.forename: T
authors.initials: T
authors.lastname: Yamanaka
authors.affiliation: Division of Pharmacy.
authors.forename: H
authors.initials: H
authors.lastname: Hashimoto
authors.affiliation: Division of Gastrointestinal Oncology, National Cancer Center Hospital, Tokyo.
authors.forename: Y
authors.initials: Y
authors.lastname: Shimada
authors.affiliation: Department of Pharmacy, Shizuoka Cancer Center, Shizuoka.
authors.forename: K
authors.initials: K
authors.lastname: Arata
authors.affiliation: Department of Pharmacy.
authors.forename: R
authors.initials: R
authors.lastname: Matsui
authors.affiliation: Department of Thoracic Oncology, National Cancer Center Hospital East, Chiba.
authors.forename: K
authors.initials: K
authors.lastname: Goto
authors.affiliation: Department of Pharmacy, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo.
authors.forename: T
authors.initials: T
authors.lastname: Takiguchi
authors.affiliation: Department of Thoracic Medical Oncology, Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo.
authors.forename: F
authors.initials: F
authors.lastname: Ohyanagi
authors.affiliation: Department of Pharmacy.
authors.forename: Y
authors.initials: Y
authors.lastname: Kogure
authors.affiliation: Department of Thoracic Oncology, NHO Shikoku Cancer Center, Ehime.
authors.forename: N
authors.initials: N
authors.lastname: Nogami
authors.affiliation: Department of Pharmacy.
authors.forename: M
authors.initials: M
authors.lastname: Nakao
authors.affiliation: Department of Clinical Oncology, Osaka City General Hospital, Osaka.
authors.forename: K
authors.initials: K
authors.lastname: Takeda
authors.affiliation: Department of Pharmacy.
authors.forename: K
authors.initials: K
authors.lastname: Azuma
authors.affiliation: Department of Thoracic Surgery, Tokyo Medical University Hospital, Tokyo.
authors.forename: S
authors.initials: S
authors.lastname: Nagase
authors.affiliation: Department of Pharmacy, NHO Kyushu Cancer Center, Fukuoka.
authors.forename: T
authors.initials: T
authors.lastname: Hayashi
authors.affiliation: Department of Pharmacy, Kindai University Hospital, Osaka.
authors.forename: K
authors.initials: K
authors.lastname: Fujiwara
authors.affiliation: Department of Pharmacy.
authors.forename: T
authors.initials: T
authors.lastname: Shimada
authors.affiliation: Division of Medical Oncology, Teikyo University Hospital, Tokyo.
authors.forename: N
authors.initials: N
authors.lastname: Seki
authors.affiliation: Department of Thoracic Oncology, Shizuoka Cancer Center, Shizuoka Third Department of Internal Medicine, Wakayama Medical University, Wakayama, Japan nbyamamo@wakayama-med.ac.jp.
authors.forename: N
authors.initials: N
authors.lastname: Yamamoto
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects; D002945:Cisplatin / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D064420:Drug-Related Side Effects and Adverse Reactions / Q000473:pathology; D005260:Female; D017829:Granisetron / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007546:Isoquinolines / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced / Q000473:pathology; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000077924:Palonosetron; D011812:Quinuclidines / Q000008:administration & dosage* / Q000009:adverse effects; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000009:adverse effects; D014839:Vomiting / Q000139:chemically induced / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D002945:Cisplatin; D017829:Granisetron; D007546:Isoquinolines; D000077924:Palonosetron; D011812:Quinuclidines; D012702:Serotonin Antagonists
keywords: 5-HT3 receptor antagonist; NK-1 receptor antagonist; antiemetic therapy; aprepitant; chemotherapy-induced nausea and vomiting (CINV); palonosetron