A phase I trial of olanzapine (Zyprexa) for the prevention of delayed emesis in cancer patients: a Hoosier Oncology Group study.

Journal Article (Clinical Trial;Journal Article;Multicenter Study)

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.

Full Text

Duke Authors

Cited Authors

  • Passik, SD; Navari, RM; Jung, S-H; Nagy, C; Vinson, J; Kirsh, KL; Loehrer, P

Published Date

  • 2004

Published In

Volume / Issue

  • 22 / 3

Start / End Page

  • 383 - 388

PubMed ID

  • 15493359

International Standard Serial Number (ISSN)

  • 0735-7907

Digital Object Identifier (DOI)

  • 10.1081/cnv-200029066


  • eng

Conference Location

  • England