Alternative medicine for cancer pain reviewed in Journal of Clinical Oncology

Following from my previous post about the JCO paper on the medical ethics of managing pediatric cancer cases where parents refuse standard-of-care therapies, I wanted to discuss an accompanying review on complementary and alternative therapies for cancer-related pain. Unlike the previous article, this one is subscription-only but I’ll provide the highlights.
Cancer-related pain is serious business and is experienced by 75% of cancer patients. Opiates remain the most effective drugs for severe cancer pain, but they are underprescribed due to the convergence of regulatory and liability issues compounded by adverse reactions and complexities of individualized, escalated dosing as patients inevitably become tolerant to these pain medications. (More than you ever wanted to know about treating cancer pain can be found in this CA article (PDF) by Dr Nathan Cherny).
Clearly, any alternative to drug therapy that can relieve cancer pain would be welcomed by health care providers and patients alike. In my humble opinion, this is one area where some alternative medical modalities might have the potential to have great benefit and become validated and incorporated into standard medical practice.
Recognizing both the problems of pain medication and the promise alternative therapies may seem to hold, medical oncologists and library science specialists at the Mayo Clinic College of Medicine conducted an exhaustive review of the quality and outcome of randomized, controlled clinical trials across the spectrum of what the NCCAM arm of NIH considers to be complementary and alternative medicine. Their conclusion?

“There is paucity of multi-institutional RCTs evaluating CAM interventions for cancer pain with adequate power, duration, and sham control. Hypnosis, imagery, support groups, acupuncture, and healing touch seem promising, particularly in the short term, but none can be recommended because of a paucity of rigorous trials. Future research should focus on methodologically strong RCTs to determine potential efficacy of these CAM interventions.”

Yes, their bottom line is that the poor methodological design and rigor of published studies compromise the promise of even some modalities that may seem to be useful, especially in the short-term.
To give you some idea of the challenge faced by the authors, their search of numerous databases revealed a total of 101 articles, with only 16 that met their criteria of randomized controlled trials for cancer pain (two additional studies were identified from reference lists therein, bringing the grand total of studies to 18). So, despite the perception that alternative therapies are being tested in critical clinical situations, not even two dozen decent studies could be identified.
Using the Jadad scoring system for study quality, eight were deemed poor, three intermediate, and seven were of high quality. Although a total of 1,499 patients were enrolled across the 18 trials, a meta-analysis was not possible due to the diversity of modalities used in each study, from music therapy and hypnosis, to herbal therapy or acupuncture. Further complicating the issue was that two trials listed more than one modality in a single treatment arm.
Interestingly, the highest quality trial was that of Alimi et al., 2003, also published in JCO, that employed auricular acupuncture, including a sham acupuncture group (i.e., individuals who had needles placed at sites not associated with traditional Chinese spots for pain relief). Despite the fact that acupuncture subscribes to theories that rarely have counterparts in Western medicine, the treatment group experienced a 36% in pain at 2 months as opposed to 2% for acupuncture at placebo points and a 1% increase in pain in the non-acunpuncture placebo group. I will leave for another day a discussion of the merits and shortcomings of this study but it is, indeed, provocative.
What was most disappointing to me was the fact that studies involving massage and music therapy were dismal failures, due predominantly to poor methodological rigor (small sample sizes and relatively short durations of intervention).
I’ll close with one crucial paragraph from the Discussion:

Future RCTs assessing efficacy of CAM therapies for cancer pain should be well designed with adequate sample size, have sufficient duration, have good sham controls groups, involve multiple institutions, and adequately monitor and report adverse effects. Research should be standardized with clear definitions of procedures, area of intervention on body (if any), duration of intervention, standardized instrument for pain assessment, and a standard outcome. Such well-designed trials are particularly needed for CAM therapies that seem promising such as acupuncture, hypnosis, imagery, support groups, and healing touch. Larger well-designed studies of adequate duration assessing the effect of massage and music on cancer pain might also be fruitful. Other untested CAM therapies, such as yoga, tai chi, or qi gong, could be explored as pilot trials, if supported by anecdotal experience. Finally, there is also a need to understand the scientific mechanism by which these therapies are beneficial. This would optimize the likelihood of success. [emphasis mine]

This final point of the authors echoes a long-held view of mine that, unlike most medical research, expensive clinical trials in CAM often precede basic science investigations of the mechanisms by which the modalities are thought to work. Some of these therapies have already been debunked while others have mechanistic plausibility.
But if these modalities are going to have a chance to help cancer patients, they must be tested properly.
(The complete abstract is below for your convenience:)

Journal of Clinical Oncology
, Vol 24, No 34 (December 1), 2006: pp. 5457-5464
Efficacy of Complementary and Alternative Medicine Therapies in Relieving Cancer Pain: A Systematic Review
Aditya Bardia, Debra L. Barton, Larry J. Prokop, Brent A. Bauer, Timothy J. Moynihan
From the Departments of Internal Medicine, Medical Oncology, and Medical Library, Mayo Clinic College of Medicine, Rochester, MN
PURPOSE: Despite widespread popular use of complementary and alternative medicine (CAM) therapies, a rigorous evidence base about their efficacy for cancer-related pain is lacking. This is a systematic review of randomized controlled trials (RCTs) evaluating CAM therapies for cancer-related pain.
METHODS: RCTs using CAM interventions for cancer-related pain were abstracted using Medline, EMBASE, CINAHL, AMED, and Cochrane database.
RESULTS: Eighteen trials were identified (eight poor, three intermediate, and seven high quality based on Jadad score), with a total of 1,499 patients. Median sample size was 53 patients, and median intervention duration was 45 days. All studies were from single institutions, four had sample size justification, and none reported any adverse effects. Seven trials reported significant benefit for the following CAM therapies: acupuncture (n = 1), support groups (n = 2), hypnosis (n = 1), relaxation/imagery (n = 2), and herbal supplement/HESA-A (n = 1, but study was of low quality without control data). Seven studies reported immediate postintervention or short-term benefit of the following CAM interventions: acupuncture (n = 2), music (n = 1), herbal supplement/Ai-Tong-Ping (n = 1), massage (n = 1), and healing touch (n = 2). Four studies reported no benefit of CAM interventions (music, n = 2; massage, n = 2) in reducing cancer pain compared with a control arm.
CONCLUSION: There is paucity of multi-institutional RCTs evaluating CAM interventions for cancer pain with adequate power, duration, and sham control. Hypnosis, imagery, support groups, acupuncture, and healing touch seem promising, particularly in the short term, but none can be recommended because of a paucity of rigorous trials. Future research should focus on methodologically strong RCTs to determine potential efficacy of these CAM interventions.


4 thoughts on “Alternative medicine for cancer pain reviewed in Journal of Clinical Oncology

  1. I think there is some resistance in the CAM world to designing experiments that would “really” put claims about therapeutic efficacy to the test. For example, I’ve suggested to a number of healing touch practitioners that they conduct a “head to head” comparison of healing touch and visualization of same. The prospect of being shown to be redundant didn’t appeal to any of the practitioners in question. So much for patient empowerment…

  2. Clearly, you don’t want to spend the money it takes to do a really good clinical trial, unless there is both a pressing clinical need, and a good reason to think it might be worthwhile. For an intervention that lacks a theoretical mechanism of action, it is hard to satisfy the second criterion.
    The other thing is that it takes time to do the studies well, and if people are in great pain, you’ve got to wonder if it is ethical to withhold a treatment that you know is likely to work, to try one that might not.

  3. A couple of points here:
    * the risks of giving someone yoga, t’ai chi, visualization, or music therapy are not as serious as the risks as giving someone a pharmacological solution to the pain except in extreme or easily identifiable cases (I wouldn’t want to tell someone with terrible balance to do t’ai chi). With the other alternative therapies (acupuncture), the main risk is the expense of having a trained professional do the work.
    * while I do agree that there is a need to understand the scientific mechanism of these other modalities, and that a better understanding will assist in planning better, more explanatory studies, I don’t think they are necessary in planning some studies, and given the potential benefit of having non-drug therapies for cancer pain, it seems to me that in particular cases clinical trials (esp. pilot studies, not the huge confirmatory trials that NCCAM likes to run) can proceed in parallel to basic research.
    * I’m not getting why some of these alternative therapies “cannot be recommended.” What, exactly, is the problem with saying that anecdotal evidence and preliminary studies suggest benefit for some people, why not spend $15 and check it out? If it works, great, if not, we can try something else or go for the opiates. I mean, in a pharmacological mindset such a suggestion is very risky because the safety profile of an experimental therapy is not very well known, but for most of these therapies the safety profile is a lot better and the risk of drug interactions with chemotherapy a lot smaller (I recognize there is still a little risk) simply because we’re not putting a substance in the body.
    Maybe I’m reading too much into the recommendations from the conclusions of the article, where it seems to me that the authors want to first understand the scientific mechanism, then plan clinical trials, then, if they are successful, they can be used in patients. Perhaps the authors would agree with me that these can be used now, with the caveats above emphasized, along with basic and clinical research in parallel.

  4. Bob, indeed, I’ve seen some lack of enthusiasm for studies by CAM practitioners because pts are already willing to pay for such therapies regardless of clinical/statistical efficacy. In fact, the Reiki trial reviewed therein had to be terminated because too few pts wanted to stay in the placebo group.
    Joseph, you raise two really good points about the rationale for and ethics of such trials. I think it would be very difficult to justify any of these modalities as stand-alone approaches anyway; using them as adjuncts to pharmacotherapy could have great benefit but might further complicate interpretations of studies.
    John, the authors speak in the paper in greater detail about specific approaches (i.e., relaxation) – the abstract is constrained by the requirement to make some blanket statement about a very diverse spectrum of approaches.

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