title: Effect of olanzapine for breast cancer patients resistant to triplet antiemetic therapy with nausea due to anthracycline-containing adjuvant chemotherapy.
abstract: OBJECTIVE
  Triplet antiemetic therapy with neurokinin 1 receptor blocker, 5-hydroxytryptamine receptor blocker and steroids is commonly used in patients who are highly emetic after chemotherapy. However, an alternative antiemetic therapy for patients who are resistant to triplet antiemetic therapy is not established. Olanzapine is recommended in the guidelines as an optional antiemetic drug. However, the effectiveness of adding olanzapine to triplet antiemetic therapy is unknown. In this study, the effectiveness and safety of adding olanzapine to triplet antiemetic therapy with aprepitant, palonosetron and dexamethasone as highly emetic anthracycline-containing adjuvant chemotherapy for primary breast cancer patients were prospectively investigated.
  
  
  METHODS
  Forty-five patients with breast cancer who experienced >Grade 1 nausea or any vomiting after the first cycle of chemotherapy using both epirubicin and cyclophosphamide were included. Low-dose olanzapine (2.5 mg/day) was administered orally from the first day of chemotherapy for 4 days, and the number of episodes of vomiting, scale of nausea, dietary intake and somnolence were compared with the symptoms after the first cycle.
  
  
  RESULTS
  As the primary endpoint, the nausea grade was significantly improved by adding olanzapine (P < 0.05). As the secondary endpoints, mean nausea scale (3.2→1.9, Day 1; 3→1.3-1, Days 2-6) and dietary intake (33.6→53.8%, Day 1; 42.0→60.7-78.1%, Days 2-6) were improved by adding olanzapine. Only four patients withdrew due to somnolence and/or dizziness.
  
  
  CONCLUSIONS
  This study demonstrated the effectiveness and tolerability of adding low-dose olanzapine for patients with insufficient nausea relief with triplet antiemetic therapy consisting of palonosetron, steroid and aprepitant.
authors.affiliation: Department of Pharmacy, Iwate Medical University Hospital, Morioka Department of Clinical Pharmaceutics, Faculty of Pharmaceutical Sciences, Iwate Medical University, Morioka.
authors.forename: Junya
authors.initials: J
authors.lastname: Sato
authors.affiliation: Department of Surgery, Faculty of Medicine, Iwate Medical University, Morioka, Japan mkashiwa@iwate-med.ac.jp.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kashiwaba
authors.affiliation: Department of Surgery, Faculty of Medicine, Iwate Medical University, Morioka, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Komatsu
authors.affiliation: Department of Surgery, Faculty of Medicine, Iwate Medical University, Morioka, Japan.
authors.forename: Kazushige
authors.initials: K
authors.lastname: Ishida
authors.affiliation: Department of Pharmacy, Iwate Medical University Hospital, Morioka.
authors.forename: Satoru
authors.initials: S
authors.lastname: Nihei
authors.affiliation: Department of Pharmacy, Iwate Medical University Hospital, Morioka Department of Clinical Pharmaceutics, Faculty of Pharmaceutical Sciences, Iwate Medical University, Morioka.
authors.forename: Kenzo
authors.initials: K
authors.lastname: Kudo
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000009:adverse effects / Q000627:therapeutic use*; D000932:Antiemetics / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D017024:Chemotherapy, Adjuvant; D019008:Drug Resistance, Neoplasm; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008875:Middle Aged; D009325:Nausea / Q000209:etiology; D000077152:Olanzapine; D012720:Severity of Illness Index; D014839:Vomiting / Q000209:etiology
chemical_list: D018943:Anthracyclines; D000932:Antiemetics; D000970:Antineoplastic Agents; D001569:Benzodiazepines; D000077152:Olanzapine
keywords: 5-HT3 blocker; NK1 receptor blocker; antiemetic effect; breast cancer; chemotherapy; olanzapine