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: Steven D Passik, Rudolph M Navari, Sin-Ho Jung, Cindy Nagy, Jake Vinson, Kenneth L Kirsh, Patrick Loehrer
• Journal: Cancer investigation (Cancer Invest) Vol. 22 Issue 3 Pg. 383-8 ( 2004) ISSN: 0735-7907 [Print] England
• PMID: 15493359 (Publication Type: Clinical Trial, Clinical Trial, Phase I, Journal Article, Multicenter Study)

Chemical References

• Antiemetics
• Antineoplastic Agents
• Organoplatinum Compounds
• Benzodiazepines
• Irinotecan
• Doxorubicin
• Cyclophosphamide
• Olanzapine
• Camptothecin

Topics

• Adult
• Aged
• Anorexia (chemically induced)
• Antiemetics (adverse effects, therapeutic use)
• Antineoplastic Agents (adverse effects)
• Benzodiazepines (adverse effects, therapeutic use)
• Camptothecin (administration & dosage, adverse effects, analogs & derivatives)
• Cohort Studies
• Cyclophosphamide (administration & dosage, adverse effects)
• Dose-Response Relationship, Drug
• Doxorubicin (administration & dosage, adverse effects)
• Female
• Humans
• Irinotecan
• Male
• Maximum Tolerated Dose
• Middle Aged
• Mood Disorders (chemically induced)
• Nausea (chemically induced, prevention & control)
• Neoplasms (complications, drug therapy)
• Olanzapine
• Organoplatinum Compounds (administration & dosage, adverse effects)
• Time Factors
• Treatment Outcome
• Vomiting (chemically induced, prevention & control)