To establish the role of ketamine in hospitalized terminally ill cancer patients with refractory cancer pain, using continuous intravenous infusion of ketamine

• There are approximately 20 percent patients of refractory cancer pain, which is troubled with uncontrolled pain though treatment including opioids.
• Ketamine has been showed the performance of Ketamine, N-methyl-D-aspartate (NMDA) receptor blocker, in refractory cancer pain based on prior studies.
• We cannot yet confirm the role of Ketamine comparing the benefit and risk due to incompatible results of prior studies. Additionally, most of prior studies were studied in heterogenous groups, which are from beginning of palliative chemotherapy to terminal status, so role of ketamine was not assessed in homogeneous terminally ill cancer patients. And they has used mostly 'bolus intravenous infusion' or 'continuous subcutaneous infusion (CSCI)', relatively rare in continuous intravenous infusion (CIVI).
• The bolus intravenous method is convenient but is concerned with leading to relatively severe adverse events due to poor general condition of terminally ill cancer patients, the CSCI method is not recommended because of adverse events (AEs) such as skin irritation. On the contrary, the CIVI method using gradual increasing ketamine minimizes AEs and is free of skin irritation. Most of hospitalized terminally ill cancer patients has proper IV access using intravascular devices (chemoport or PICC). So, CIVI method is suitable to hospitalized terminally ill cancer patients.
• This study assess the efficacy and safety of 5-days CIVI gradual dose titration of Ketamine in terminally ill cancer patients with refractory cancer pain.

Inclusion Criteria:

1. Among patients with histologically or cytologically confirmed malignancy, patients with expected survival time of several months or less due to a progressive disease without additional anticancer treatment.
2. Patients with refractory cancer pain, which cases of requesting 4 or more breakthrough analgesics or increase of baseline analgesics (average pain score ≥ 4 or Personalized pain goal) in spite of 120 mg/day or more of intravenous Morphine Equivalent Daily Dose
3. Hospitalized patients with intravascular access during at least 5 days
4. Age 18 or older
5. Signed and dated informed consent of document indicating that the patient (or legally acceptable representative) has been informed about all pertinent aspects of the trial prior to enrollment

Exclusion Criteria:

1. Patients who were treated with ketamine for pain control within 6 months

2. Patients who have been treated with radiotherapy within 4 weeks or plan to intervention for pain control during study period

3. Cancer pain cannot be excluded the Opioid induced hyperalgesia

4. Concomitant severe medical, surgical, or disease or problems which were contraindicated to application of Ketamine or have possibilities of unexpected medical problems caused be the Ketamine

   • confirmed or assumed central nervous system lesion which lead to increased intracranial pressure
   • Arrhythmia (supra-ventricular tachycardia, ventricular arrhythmia (frequent premature ventricular contraction, bigeminy, Ventricular tachycardia)
   • history of hemorrhagic stroke or seizure within 3 months