title: Efficacy and safety of olanzapine combined with aprepitant, palonosetron, and dexamethasone for preventing nausea and vomiting induced by cisplatin-based chemotherapy in gynecological cancer: KCOG-G1301 phase II trial.
abstract: OBJECTIVE
  Olanzapine is effective in chemotherapy-induced nausea and vomiting (CINV). In patients receiving highly emetogenic chemotherapy (HEC), its efficacy was reported as rescue therapy for breakthrough emesis refractory to triplet therapy (palonosetron, aprepitant, and dexamethasone). However, its preventive effects with triplet therapy for CINV are unknown. This study aimed to investigate efficacy and safety of preventive use of olanzapine with triplet therapy for CINV of HEC.
  
  
  METHODS
  This study is a prospective multicenter study conducted by Kansai Clinical Oncology Group. Forty chemo-naïve gynecological cancer patients receiving HEC with cisplatin (≥50 mg/m(2)) were enrolled. Oral olanzapine (5 mg) was administered with triplet therapy a day prior to cisplatin administration and on days 1-5. The primary endpoint was complete response (no vomiting and no rescue) rate for the overall phase (0-120 h post-chemotherapy). Secondary endpoints were complete response rate for acute phase (0-24 h post-chemotherapy) and delayed phase (24-120 h post-chemotherapy) and complete control (no vomiting, no rescue, and no significant nausea) rate and total control (no vomiting, no rescue, and no nausea) rate for each phase. These endpoints were evaluated during the first cycle of chemotherapy.
  
  
  RESULTS
  Complete response rates for acute, delayed, and overall phases were 97.5, 95.0, and 92.5 %, respectively. Complete control rates were 92.5, 87.5, and 82.5 %, respectively. Total control rates were 87.5, 67.5, and 67.5 %, respectively. There were no grade 3 or 4 adverse events.
  
  
  CONCLUSIONS
  Preventive use of olanzapine combined with triplet therapy gives better results than those from previously reported studies of triplet therapy.
authors.affiliation: Department of Gynecology, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan. ma.abe@scchr.jp.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Abe
authors.affiliation: Department of Gynecology, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan.
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Hirashima
authors.affiliation: Department of Gynecology, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Kasamatsu
authors.affiliation: Department of Gynecology, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Kado
authors.affiliation: Department of Gynecology, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan.
authors.forename: Satomi
authors.initials: S
authors.lastname: Komeda
authors.affiliation: Department of Gynecology, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan.
authors.forename: Shiho
authors.initials: S
authors.lastname: Kuji
authors.affiliation: Department of Gynecology, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan.
authors.forename: Aki
authors.initials: A
authors.lastname: Tanaka
authors.affiliation: Department of Gynecology, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan.
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Takahashi
authors.affiliation: Department of Gynecology, Shizuoka Cancer Center, 1007 Shimonagakubo, Nagaizumi-cho, Sunto-gun, Shizuoka, 411-8777, Japan.
authors.forename: Munetaka
authors.initials: M
authors.lastname: Takekuma
authors.affiliation: Department of Obstetrics and Gynecology, Japanese Red Cross Shizuoka Hospital, 8-2 Outemachi, Aoi-Ward, Shizuoka City, Shizuoka, 420-0853, Japan.
authors.forename: Hanako
authors.initials: H
authors.lastname: Hihara
authors.affiliation: Department of Obstetrics and Gynecology, Japanese Red Cross Shizuoka Hospital, 8-2 Outemachi, Aoi-Ward, Shizuoka City, Shizuoka, 420-0853, Japan.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Ichikawa
authors.affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hasamamachi, Yufu City, Oita, 879-5593, Japan.
authors.forename: Yui
authors.initials: Y
authors.lastname: Itonaga
authors.affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hasamamachi, Yufu City, Oita, 879-5593, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Hirakawa
authors.affiliation: Department of Obstetrics and Gynecology, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hasamamachi, Yufu City, Oita, 879-5593, Japan.
authors.forename: Kaei
authors.initials: K
authors.lastname: Nasu
authors.affiliation: Department of Obstetrics and Gynecology, Kansai Rousai Hospital, 3-1-69 Inabaso, Amagasaki-City, Hyogo, 660-8511, Japan.
authors.forename: Kanoko
authors.initials: K
authors.lastname: Miyagi
authors.affiliation: Department of Obstetrics and Gynecology, Kansai Rousai Hospital, 3-1-69 Inabaso, Amagasaki-City, Hyogo, 660-8511, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Murakami
authors.affiliation: Department of Obstetrics and Gynecology, Kansai Rousai Hospital, 3-1-69 Inabaso, Amagasaki-City, Hyogo, 660-8511, Japan.
authors.forename: Kimihiko
authors.initials: K
authors.lastname: Ito
mesh_terms: D000328:Adult; D000368:Aged; D000932:Antiemetics / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D000077608:Aprepitant; D001569:Benzodiazepines / Q000008:administration & dosage; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003907:Dexamethasone / Q000008:administration & dosage; D005260:Female; D005833:Genital Neoplasms, Female / Q000188:drug therapy*; D006801:Humans; D007546:Isoquinolines / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009025:Morpholines / Q000008:administration & dosage; D009325:Nausea / Q000139:chemically induced / Q000188:drug therapy / Q000517:prevention & control*; D000077152:Olanzapine; D000077924:Palonosetron; D011446:Prospective Studies; D011812:Quinuclidines / Q000008:administration & dosage; D012702:Serotonin Antagonists / Q000008:administration & dosage*; D014839:Vomiting / Q000139:chemically induced / Q000188:drug therapy / Q000517:prevention & control*
chemical_list: D000932:Antiemetics; D007546:Isoquinolines; D009025:Morpholines; D011812:Quinuclidines; D012702:Serotonin Antagonists; D001569:Benzodiazepines; D000077608:Aprepitant; D000077924:Palonosetron; D003907:Dexamethasone; D000077152:Olanzapine; D002945:Cisplatin
keywords: Antiemetic therapy; Chemotherapy-induced nausea and vomiting; Cisplatin; Highly-emetogenic chemotherapy; Olanzapine