title: A phase I trial of olanzapine (Zyprexa) for the prevention of delayed emesis in cancer patients: a Hoosier Oncology Group study.
abstract: Chemotherapy-induced delayed emesis (DE) can affect up to 50% to 70% of patients receiving moderately and highly emetogenic chemotherapy, although rates are improving. DE most commonly occurs within the first 24 to 48 hours of chemotherapy administration and can persist for 2 to 5 days. Olanzapine, due to its activity at multiple dopaminergic, serotonergic, muscarinic, and histaminic receptor sites, has potential as antiemetic therapy. A phase I study was designed with olanzapine, using a four-cohort dose escalation of 3 to 6 patients per cohort, for the prevention of DE in cancer patients receiving their first cycle of chemotherapy consisting of cyclophosphamide, doxorubicin, platinum, and/or irinotecan. All patients received standard premedication. Olanzapine was administered on days -2 and -1 prior to chemotherapy and continued for 8 days (days 0-7). Episodes of vomiting as well as daily measurements of nausea, sedation, and toxicity were monitored at each dose level. Fifteen patients completed the protocol. No grade 4 toxicities were seen, and three patients experienced a dose-limiting toxicity (grade 3) of a depressed level of consciousness during the study. The maximum tolerated dose appeared to be 5 mg (for days -2 and -1) and 10 mg (for days 0-7). Four of six patients receiving highly emetogenic chemotherapy (cisplatin, > or = 70 mg/m2) and nine of nine patients receiving moderately emetogenic chemotherapy (doxorubicin, > or = 50 mg/m2) had complete control (no vomiting episodes) of DE. Therefore, olanzapine may be an effective agent for the prevention of chemotherapy-induced DE. A phase II trial is underway.
authors.affiliation: Hoosier Oncology Group, Walther Cancer Institute, Indianapolis, Indiana, USA. spassik@uky.edu
authors.forename: Steven D
authors.initials: SD
authors.lastname: Passik
authors.forename: Rudolph M
authors.initials: RM
authors.lastname: Navari
authors.forename: Sin-Ho
authors.initials: SH
authors.lastname: Jung
authors.forename: Cindy
authors.initials: C
authors.lastname: Nagy
authors.forename: Jake
authors.initials: J
authors.lastname: Vinson
authors.forename: Kenneth L
authors.initials: KL
authors.lastname: Kirsh
authors.forename: Patrick
authors.initials: P
authors.lastname: Loehrer
mesh_terms: D000328:Adult; D000368:Aged; D000855:Anorexia / Q000139:chemically induced; D000932:Antiemetics / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects; D001569:Benzodiazepines / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D015331:Cohort Studies; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D019964:Mood Disorders / Q000139:chemically induced; D009325:Nausea / Q000139:chemically induced / Q000517:prevention & control*; D009369:Neoplasms / Q000150:complications* / Q000188:drug therapy; D000077152:Olanzapine; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D013997:Time Factors; D016896:Treatment Outcome; D014839:Vomiting / Q000139:chemically induced / Q000517:prevention & control*
chemical_list: D000932:Antiemetics; D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D001569:Benzodiazepines; D000077146:Irinotecan; D004317:Doxorubicin; D003520:Cyclophosphamide; D000077152:Olanzapine; D002166:Camptothecin