Adjuvant Ketamine Offers No Net Benefit for Refractory Cancer Pain

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(ChemotherapyAdvisor) – Results of a randomized phase 3 clinical trial have failed to support “the current widespread practice of using subcutaneous ketamine as an adjuvant to opioids in the management of refractory pain in patients with advanced cancer,” investigators reported in the Journal of Clinical Oncology online September 10.

The study also found that ketamine, which is used off-label at subanesthetic doses based on anecdotal data from other settings, almost doubled incidence of adverse events, according to Prof. Janet Hardy, of Mater Adult Hospital, South Brisbane, Queensland, Australia, and colleagues. The double-blind, dose-escalation trial randomly assigned patients to either ketamine or placebo delivered subcutaneously over 3 to 5 days. “Ketamine would be considered of net benefit if it provided clinically relevant improvement in pain with limited breakthrough analgesia and acceptable toxicity,” they stated.

Among the 185 participants included in the primary analysis, no significant difference was observed between the proportion of positive outcomes (0.04; 95% CI,-0.10 to 0.18; P=0.55) in the placebo and ketamine arms.

“Although there was a greater improvement per day in the ketamine group in worst and average pain scores, this never reached a level that would be considered clinically relevant,” Prof. Hardy noted. Type of pain (ie, nociceptive vs neuropathic) did not predict response, which was 27% in the placebo arm (25 of 92 patients) and 31% in the ketamine arm (29 of 93).

After day 1, almost twice the incidence of adverse events (AEs) worse than baseline was reported in the ketamine group and throughout the study; these included site irritation, nausea, dizziness, constipation, and cognitive disturbance. The incidence rate ratio was 1.95 (95% CI, 1.46–2.61; P<0.001). Per day, those in the ketamine arm were more likely to experience a more severe grade of AE (OR 1.09; 95% CI, 1.00–1.18; P=0.039).

“Importantly, for each person observed to achieve a benefit in pain control from ketamine, four people suffered enough from toxicity to cause them to withdraw,” they wrote.

For one additional patient to have a positive outcome from ketamine, 25 patients needed to be treated, whereas the number needed to harm was six, due to toxicity-related withdrawal.


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