Background : Guidelines for cancer pain management include nonsteroidal antiinflammatory drugs with opioids administered in a time-contingent manner. This study was designed to evaluate the role of oral ketamine or transdermal nitroglycerin polymer, a nitric oxide donor, as coadjuvants to oral morphine II cancer pain therapy. Methods: After institutional approval and Informed patient consent were obtained, GO patients with cancer pain were randomized to one of four groups (n = 15) and studied prospectively to evaluate analgesia and anp adverse effects. A visual analog scale that consisted of a 10-cm line with 0 representing "no pain at all" and 10 representing -the worst possible pain" R ns introduced. All patients were regularly taking oral amitriptyline 50 mg at bedtime, The morphine regimen was adjusted individually to a maximal, oral dose of 80-30 mg/day to keep the visual analog scale score less than 4. when patients reported pain (visual analog scale of 4 or more), despite taking 80-90 mg oral morphine daily, the test drug was added as follows: the control group (CG) received an additional 20 mg oral morphine (10 mg at 12-h intervals); the nitroglycerin group (NG) received a 5-mg nitroglycerin patch daily; the ketamine group (KG) received 0.5 mg/kg oral ketamine at 12-h intervals; and the dlpyrone group (DG) received 500 mg oral dipyrone at 6-h intervals. Patients were free to manipulate their daily morphine consumption n hen the test drug was introduced to keep their visual analog scale score less than 4. Results: The groups were similar with respect to demographic data and visual analog scale pain scores before treatment. The visual analog scale scores after the test drug was introduced ct ere similar among the groups. The daily consumption of oral morphine was as follows: on dag 15: CG = DG = NG (P > 0.05, CG > KG (P = 0.036); on day 20: CG > NG = ICG (p < 0.02) CG > ICG, P < 0.005; CG > NG, P < 0.02), DG > ICG (P < 0.05); on day SO: CG = DG > KG = NG CP < 0.05, Patients in the CG and DG groups reported somnolence, but patients in the KG and KG groups did not. Conclusions: Low-dose ketamine and transdermal nitroglycerin were effective coadjuvant an:analgesics. In conjunction with their opioid tolerance-sparing function, joint delivery of ketamine or nitric oxide donors with opiates may he of significant benefit In cancer pain management.