title: The use of olanzapine versus metoclopramide for the treatment of breakthrough chemotherapy-induced nausea and vomiting in patients receiving highly emetogenic chemotherapy.
abstract: OBJECTIVE
  Olanzapine has been shown to be a safe and effective agent for the prevention of chemotherapy-induced nausea and vomiting (CINV). Olanzapine may also be an effective rescue medication for patients who develop breakthrough CINV despite having received guideline-directed CINV prophylaxis.
  
  
  METHODS
  A double-blind, randomized phase III trial was performed for the treatment of breakthrough CINV in chemotherapy-naive patients receiving highly emetogenic chemotherapy (cisplatin, ≥ 70 mg/m2 or doxorubicin, ≥ 50 mg/m2 and cyclophosphamide, ≥ 600 mg/m2), comparing olanzapine to metoclopramide. Patients who developed breakthrough emesis or nausea despite prophylactic dexamethasone (12 mg IV), palonosetron (0.25 mg IV), and fosaprepitant (150 mg IV) pre-chemotherapy and dexamethasone (8 mg p.o. daily, days 2-4) post-chemotherapy were randomized to receive olanzapine, 10 mg orally daily for 3 days or metoclopramide, 10 mg orally TID for 3 days. Patients were monitored for emesis and nausea for 72 h after taking olanzapine or metoclopramide. Two hundred seventy-six patients (median age 62 years, range 38-79; 43% women; Eastern Cooperative Oncology Group (ECOG) PS 0,1) consented to the protocol. One hundred twelve patients developed breakthrough CINV and 108 were evaluable.
  
  
  RESULTS
  During the 72-h observation period, 39 out of 56 (70%) patients receiving olanzapine had no emesis compared to 16 out of 52 (31%) patients with no emesis for patients receiving metoclopramide (p < 0.01). Patients without nausea (0, scale 0-10, M.D. Anderson Symptom Inventory) during the 72-h observation period were those who took olanzapine, 68% (38 of 56), and metoclopramide, 23% (12 of 52) (p < 0.01). There were no grade 3 or 4 toxicities.
  
  
  CONCLUSIONS
  Olanzapine was significantly better than metoclopramide in the control of breakthrough emesis and nausea in patients receiving highly emetogenic chemotherapy.
authors: Indiana University School of Medicine South Bend, 1234 Notre Dame Avenue, South Bend, IN 46617, USA. navari.1@nd.edu
authors: Rudolph M
authors: RM
authors: Navari
authors: Cindy K
authors: CK
authors: Nagy
authors: Sarah E
authors: SE
authors: Gray
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000932:Antiemetics / Q000008:administration & dosage / Q000009:adverse effects; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D000077608:Aprepitant; D001569:Benzodiazepines / Q000008:administration & dosage* / Q000009:adverse effects; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects; D004311:Double-Blind Method; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D007546:Isoquinolines / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008787:Metoclopramide / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D009025:Morpholines / Q000008:administration & dosage; D009325:Nausea / Q000139:chemically induced / Q000188:drug therapy / Q000517:prevention & control*; D009369:Neoplasms / Q000188:drug therapy*; D000077152:Olanzapine; D000077924:Palonosetron; D011812:Quinuclidines / Q000008:administration & dosage / Q000009:adverse effects; D014839:Vomiting / Q000139:chemically induced / Q000188:drug therapy / Q000517:prevention & control*
chemical_list: D000932:Antiemetics; D000970:Antineoplastic Agents; D007546:Isoquinolines; D009025:Morpholines; D011812:Quinuclidines; D001569:Benzodiazepines; D000077608:Aprepitant; D000077924:Palonosetron; D003907:Dexamethasone; D004317:Doxorubicin; D003520:Cyclophosphamide; D008787:Metoclopramide; D000077152:Olanzapine; D002945:Cisplatin