A randomized, double-blind, placebo-controlled study to assess the efficacy and toxicity of subcutaneous ketamine in the management of cancer pain.
2604 Background: The dissociative anaesthetic ketamine is widely used for cancer related pain. A Cochrane review concluded that insufficient evidence was available to support its use in this setting. Methods: This phase III, multisite, double-blind, dose escalation, placebo, randomised controlled study aimed to determine whether ketamine, delivered subcutaneously over three to five days is more effective than placebo, when used in conjunction with adjuvant therapy in the management of chronic uncontrolled cancer pain. Ketamine would be considered to be of net benefit if it provided a reduction in average pain scores by ≥2/10 points from baseline, with limited breakthrough analgesia and acceptable toxicity. Results: For the 185 participants, there was no significant difference between the proportion of positive outcomes (0.04 (-0.10, 0.18) p=0.55) in the placebo and intervention arms (response rates 27% (25/92) and 31% (29/93)). Pain type (nociceptive versus neuropathic) was not a predictor of response. There was almost twice the incidence of adverse events worse than baseline in the ketamine group after day 1 (IRR = 1.95 (1.46, 2.61), p<0.001) and throughout the study. Those receiving ketamine were more likely to experience a more severe grade of adverse event/day (OR=1.09 (1.00, 1.18), p=0.039). The number needed to treat for one additional patient to get a positive outcome from ketamine was 25 (6, ∞). The number needed to harm, because of toxicity-related withdrawal was 6 (4, 13). Conclusions: Ketamine does not have net clinical benefit when used as an adjunct to opioids and standard co-analgesics in cancer pain.