Adjunctive Ketamine Does Not Relieve Cancer Pain

Janet Hardy, MD

Subcutaneous ketamine administered in conjunction with opioids and conventional adjuvant therapy does not lessen chronic uncontrolled cancer pain, according to the results of a phase III study. The regimen also produces a significant spike in toxicity.

Janet Hardy, MD, professor of Palliative Care at Mater Adult Hospital in South Brisbane, Australia, and colleagues elsewhere randomized patients to ketamine or placebo delivered subcutaneously over 3 to 5 days.

All patients had refractory chronic pain due to cancer or its treatment, with a Brief Pain Inventory average pain score ≥3 in spite of ongoing treatment with opioids and analgesics at prespecified dose levels.

Pain management remains a significant problem in cancer care even when patients have ready access to a variety of opioids and adjuvant therapies, the researchers pointed out. While the dissociative agent ketamine is frequently used off-label with opioids for the management of pain secondary to cancer or its treatment, data on the use of ketamine for chronic cancer pain have been extrapolated largely from case series and uncontrolled studies in noncancer settings.

The primary outcome measure in the present study was a positive response, defined as a clinically relevant improvement in pain at the end of the 5-day study period.

Overall, 25 of 92 (27%) patients who r eceived a placebo had a r esponse versus 29 of 93 (31%) patients who r eceived the intervention, with no difference (P = .55) between the percentage of positive outcomes in each group (0.04; 95% CI, -0.10-0.18).

Pain type (nociceptive versus neuropathic) was not a statistically significant predictor of response.

The investigators also found nearly twice the incidence of adverse events determined to be worse than at baseline in the ketamine arm than the placebo arm at the end of day 1 (incidence rate ratio, 1.95; 95% CI, 1.46-2.61; P <.001) and throughout the study.

Ketamine-treated patients were also more likely to experience a more severe grade of adverse event per day (odds ratio, 1.09; 95% CI, 1.00-1.18; P = .039).

Significantly more ketamine-treated patients dropped out of the study because of toxicity.

Hardy et al said that they are confident that type II error did not contribute to the findings given “the consistency of the results across secondary outcomes and the fact that the study was adequately powered to detect our prespecified differences in responses.”

They also noted that while it may be tempting to consider the heterogeneous study sample as a possible limitation, the patient population is representative of those patients commonly referred to a palliative care service and who are given ketamine for pain.

J Clin Oncol

Hardy J, Quinn S, Fazekas B, et al. Randomized, double-blind, placebo-controlled study to assess the efficacy and toxicity of subcutaneous ketamine in the management of cancer pain. . 2012;30(29):3611-3617.