Opioids With or Without Olanzapine in Treating Patients With Moderate to Severe Cancer Pain

RATIONALE: Opioids lessen pain caused by cancer. It is not yet known whether opioids are more effective when given together with or without olanzapine in treating cancer pain.

PURPOSE: This randomized clinical trial is studying opioids to see how well they work when given together with or without olanzapine in treating patients with moderate to severe cancer pain.

OBJECTIVES:

* To assess the analgesic effect of olanzapine when administered in combination with opioids in patients with cancer pain.
* To assess the opiod-sparing effect of olanzapine vs placebo.
* To assess the effect of olanzapine on opioid adverse effects.

OUTLINE: Patients undergo opioid titration with a step 3 opioid to maintain a less than 4/10 level of pain (on a 0-10 numeric pain rating scale) to establish a opioid starting dose. When the pain rating increases, patients are randomized to 1 of 3 treatment arms.

* Arm I: Patients receive oral opioid and oral placebo once daily for 4 weeks.
* Arm II: Patients receive oral opioid and 2.5 mg oral olanzapine once daily for 4 weeks.
* Arm III: Patients receive oral opioid and 5 mg oral olanzapine once daily for 4 weeks.

Patients undergo quality of life assessments at baseline and three times weekly by questionnaires using a scale from 0-3 and pain assessments periodically by Brief Pain Inventory, Edmonton Symptom Assessment Scale, Linear Analogue Scale Assessments, and Mini-Mental State Examination.

Eligibility Criteria:
DISEASE CHARACTERISTICS:

* Moderate to severe cancer pain

  * Pain score ≥ 7/10 (0-10 numeric pain rating scale)
  * Requires strong opioids (step 3) for pain control or are already on stable doses of step 3 opioids
* Opioid induced cognitive dysfunction or cognitive impairment, defined as cognitive disorder not otherwise specified according to Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) allowed
* No nonmalignant pain

  * If patient has both malignant and nonmalignant pain, eligibility will be determined by the predominant site of pain

PATIENT CHARACTERISTICS:

* Life expectancy ≥ 3 months
* Normal renal function
* Not pregnant or nursing
* Negative pregnancy test
* Must have a telephone
* Able to complete patient questionnaires alone or with assistance
* No delirium
* No hepatic dysfunction
* No nursing home patients
* No intractable nausea or vomiting
* No true allergy or intolerance to opioids
* No gastrointestinal pathology that influences absorption of opioids
* No drug seeking behavior or recent substance abuse history
* No major depression
* No respiratory compromise
* No evidence of severe or uncontrolled systemic disease (e.g., unstable or uncompensated respiratory, cardiac, hepatic, or renal disease)
* No evidence of any other significant clinical disorder or laboratory finding that makes it undesirable for the patient to participate in the study

PRIOR CONCURRENT THERAPY:

* More than 1 month since prior radiotherapy, chemotherapy, or radionuclides
* More than 1 month since prior bisphosphonates
* No prior surgery that influences absorption of opioids
* No concurrent therapeutic procedures or treatments that influence pain
* No concurrent active radiation or antineoplastic therapies
* No concurrent retroviral therapies
* No concurrent drugs that interfere with CYP34A, CYP1A2, or CYP2D6
* No concurrent drugs that interfere with morphine metabolism
* No concurrent medications that will influence the disposition of morphine or methadone
* No other concurrent antiemetics, antianxiety, or neuroleptic agents