Randomized, double-blind placebo-controlled study to assess the efficacy and toxicity of subcutaneous ketamine in the management of cancer pain

Purpose The anesthetic ketamine is widely used for pain related to cancer, but the

evidence to support its use in this setting is weak. This study aimed to determine

whether ketamine is more effective than placebo when used in conjunction with opioids

and standard adjuvant therapy in the management of chronic uncontrolled cancer pain.

Ketamine would be considered of net benefit if it provided clinically relevant

improvement in pain with limited breakthrough analgesia and acceptable toxicity.

Patients and Methods In this multisite, dose-escalation, double-blind, randomized,

placebo-controlled phase III trial, ketamine or placebo was delivered subcutaneously

over 3 to 5 days.

Results In all, 185 participants were included in the primary analysis. There was no

significant difference between the proportion of positive outcomes (0.04; 95% CI,

−0.10 to 0.18; P = .55) in the placebo and intervention arms (response rates, 27% [25

of 92] and 31% [29 of 93]). Pain type (nociceptive v 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 (incidence rate ratio, 1.95; 95% CI, 1.46 to 2.61; P <

.001) and throughout the study. Those receiving ketamine were more likely to

experience a more severe grade of adverse event per day (odds ratio, 1.09; 95% CI,

1.00 to 1.18; P = .039). The number of patients needed to treat for one additional

patient to have a positive outcome from ketamine was 25 (95% CI, six to ∞). The

number needed to harm, because of toxicity-related withdrawal, was six (95% CI, four

to 13).

Conclusion Ketamine does not have net clinical benefit when used as an adjunct to

opioids and standard coanalgesics in cancer pain.