Abstract
Dear Editor:
In the December 2011 issue of this journal, Professor Hardy 1 and colleagues highlighted some of the shortcomings of case reports as evidence in support of ketamine in the management of cancer-related pain, especially in comparison with controlled trials. Here we briefly report our experience with ketamine in the management of cancer-related pain over a 6-year period.
Between January 2005 and August 2011, 30 patients in our service were considered for a therapeutic trial of ketamine in the management of difficult-to-control cancer-related pain; of these, 24 went on to a trial of ketamine. All of the patients were on high-dose opioids and a variety of co-analgesics. Interventional techniques were either not available or not appropriate; radiotherapy was used when indicated. Charts were reviewed retrospectively and an assessment made as to whether or not treatment with ketamine had improved pain control, as judged by evidence of either a sustained improvement in analgesia, or a reduction in the doses of other pharmacological therapy.
Patients were treated for between 1 and 516 days (median 35 days), with doses ranging from 75 to 500 mg of ketamine a day (median 275 mg/day). Of the 24 patients treated, 8 were judged to have shown a clear therapeutic response, 8 showed an equivocal response, and 8 showed no benefit. Of the 8 responders, one patient with two sites of pain showed a clear differential response with improvement in interscapular pain, but not deep pelvic pain; when treatment was suspended due to adverse effects the interscapular pain returned, but it resolved again when treatment with ketamine was re-introduced. This series shows an apparent response rate of 1:3.
Indications for the use of ketamine in cancer pain remain unclear, a situation mirrored in noncancer-related pain management. 2 While Hardy rightly calls for more clinical trials, the call by Jackson and associates not to “throw out the baby with the bathwater” by insisting on only level I or II evidence should also be heeded. 3
In 2003 Bell and colleagues concluded that “The available evidence is not sufficient to conclude that ketamine improves the effectiveness of opioid treatment in cancer pain.” 4 In reply to Jackson, however, Bell subsequently argued that “lack of evidence is different from evidence for lack of effect,” meaning more clinical trials are needed. 5 As clinicians, what are we to believe?
While our experience with ketamine is not consistent with other more favorable reported series, it does demonstrate some apparent therapeutic success, albeit in an unpredictable manner. We are, however, reluctant to believe that our variable experience is unique. There is a strong, possibly overwhelming, tendency to report only our successes, lest reporting our failures bring professional criticism. When clinical trials are difficult to recruit into and complete, and if only positive case reports are published, clinicians need to be encouraged and supported in reporting complete series, including their therapeutic disappointments, in a non-judgemental environment in an attempt to resolve some of the difficulties encountered in patient selection.