Olanzapine for the Treatment of Chronic Nausea and/or Vomiting in Advanced Cancer Patients

Patients with advanced cancer experience a variety of physical and psychosocial symptoms that
significantly affect the patients' quality of life. Chronic nausea is a particularly
distressing symptom present in >60% of patients with advanced cancer. A number of palliative
care studies have evaluated treatments of nausea with limited success. Olanzapine with its
unique formulation and decreased drug interactions compared to many other drugs appears to be
a reasonable candidate for further evaluation. Olanzapine has significant potential for use
in the prevention and treatment of nausea in a palliative care setting with a once-daily
dosing.

Inclusion Criteria:

- Be at least 18 years of age

- Have histologically or cytologically-confirmed malignant disease in an advanced
incurable stage

- Have not received chemotherapy or radiation for >14 days (advanced cancer patients
receiving hormonal therapy or targeted therapy that does not come with a
recommendation for prophylactic anti-emetic therapy are eligible)

- Have chronic nausea that has been present for at least one week (worst daily score >3,
0-10 visual analogue scale) or vomiting at least five times over past one week

- Have serum creatinine < 2.0 mg/dl and SGOT or SGPT < 3 times upper limits of normal
≤120 days prior to registration

- ANC >1500 mm3 <120 days prior to registration

- Women of childbearing potential must consent to use adequate contraception throughout
protocol therapy; females of childbearing potential must have a negative urine
pregnancy test <7 days prior to registration.

Exclusion Criteria:

- Not be receiving treatment with another antipsychotic agent such as risperidone,
quetiapine, clozapine, phenothiazine or butyrophenone for less than or equal to 30
days prior to registration or planned during protocol therapy (patients may have
received prochloperazine and other phenothiazines as prior anti-emetic therapy)

- Not have concurrent use of ethyol

- Not have severe cognitive compromise

- History of CNS disease (e.g. brain metastases, seizure disorder)

- Concurrent use of amifostine, concurrent abdominal radiotherapy; concurrent use of
quinolone antibiotic therapy

- Chronic alcoholism (as determined by the investigator)

- Known hypersensitivity to olanzapine

- Known cardiac arrhythmia, uncontrolled congestive heart failure or acute myocardial
infarction within the previous six months

- History of uncontrolled diabetes mellitus (stable insulin dose and/or stable oral
hypoglycemic agent permitted)

- Planned chemotherapy or radiation during the 7 days following study initiation.