Moxibustion for cancer care: a systematic review and meta-analysis

Most cancer patients experience multiple symptoms related to either the cancer itself or late treatment effects [1]. The frequently experienced and severe adverse events associated with such treatments lead patients to seek supportive complementary and alternative medicine (CAM) [2]. Most patients use CAM as an adjunct to conventional treatments [3‐5]. Acupuncture type interventions are one of the most popular forms of CAM [6]. It is now a widely accepted intervention for the treatment of a variety of conditions [7]. Several reviews claim that acupuncture offers therapeutic benefits for cancer patients [8‐10]. Moxibustion is a traditional Chinese method that uses the heat generated by burning herbal preparations containing Artemisia vulgaris to stimulate acupuncture points [11]. There are two types of moxibustion. Direct moxibustion is applied directly to the skin surface at the acupuncture point [11]. In indirect moxibustion some insulating materials (ginger, salts and etc) were placed between the moxa cone and the skin [11]. Considering moxibustion is closely related to acupuncture, it seems pertinent to evaluate the effectiveness of moxibustion as a treatment of symptoms of cancer. Several reviews of moxibustion for cancer care are currently available [12‐16]. However, most of these review failed to employ systematic and transparent methods and are open to bias [12, 14‐16]. Furthermore, they did not focus on moxbustion and do not provide specific evidence for moxibustion during cancer care. One overview [13], was not also comprehensive and open to selection bias. Currently, no systematic review of this subject is available. The aim of this systematic review was to critically evaluate all of currently available randomised clinical trials regarding the effectiveness of any type of moxibustion as adjunct therapy during cancer care.

This systematic review identified only very few RCTs for moxibustion. Their results fail to provide convincing evidence for the effectiveness of moxibustion. However, two RCTs demonstrate that moxibution as an adjunctive therapy is more effective for reduction of side effects (from chemotherapy) than chemotherapy alone [19, 20], specifically for nausea and vomiting. In the present set of studies, an absence of adequate statistical analysis of the variability of therapeutic protocols and poor quality of reporting are frequent methodological problems. Collectively, the current evidence from RCTs of moxibustion as supportive cancer care is not convincing. However, the number of trials and the total sample size and their methodological quality are too low to draw firm conclusions.

The risk of bias in the studies was assessed based on the descriptions of sequence generation, blinding, incomplete outcome data, and allocation concealment. All of the studies were burdened with a high risk of bias. One RCT [19] employed allocation concealment and none of the RCTs made an attempt to blind assessors. One RCT [19] reported details of drop-outs and withdrawals, while the others didn't describe that may have led to exclusion or attrition biases. Thus the reliability of the evidence presented is clearly limited.

All of included trials compared indirect moxibustion with chemotherapy or morphine. The fact that there is no good trial evidence in support of moxibustion is in line with several different interpretations. Moxibustion may be ineffective, the studies may have been incorrectly designed or the treatment may not have been administered optimally in the existing studies. In the absence of a sufficient number of RCTs, other types of evidence might be helpful. Two controlled trials reported positive effects of moxibustion compared with chemotherapy, drug or no treatment in cancer patients [23, 24]. Uncontrolled trials also imply that moxibustion is beneficial for symptom management of various cancers [25‐29]. Unfortunately, such data are highly susceptible to bias and hence, they provide little useful information on the specific effects of moxibustion as it relates to supportive cancer care.

One argument for using moxubustion for the supportive care for cancer might be that it is safer than drug treatment. None of included trials assessed adverse events. Currently 3 studies evaluated the adverse events or possible risks of moxibution [30‐32]. Mild or no adverse effects of were noted in previous reports [30, 32], while one study [31] concerned possible hazardous in health by smoke from mouldering moxibustion. Relative to those of other conventional treatments, these are mild, infrequent and perhaps even negligible. Further study is needed to clarify this.

Assuming that moxibustuon is beneficial for cancer patients, possible mechanisms of action are of interest. Moxibustion may exert not only absorption of extract from moxa on acupuncture points but also direct effects due to acupuncture point stimulation from heat. Some aspect of mechanism may be similar that of acupuncture. One of them is that moxibustion may influence the multiple cortical, subcortical/limbic, and brainstem areas [33‐37]. Involving these modulation therapeutic effects of moxibustion may mediate partially through opioidergic and/or monoaminergic neurotransmission [35, 38]. Acupuncture often evokes complex somatosensory sensations and may modulate the cognitive/affective perception of pain, suggesting that many effects are supported by the brain and extending central nervous system networks [36, 39, 40]. Another possible mechanism includes an influence on the heat shock proteins and the function of immune cells. It has been shown that moxibustion up-regulated heat shock protein 70 and decreased the gastric injury and apoptosis of gastric mucosal cells [41]. The third hypothesis is that the moxibustion improves the function of immune cells. Moxibustion induced higher cellular immune function and increased the content of β-endorphin in the lymphocyte of the spleen in HAC cancer mice [42]. Moxibustion may modulate immunity through neurohormonal regulatory mechanism. Moxibustion also inhibited the growth of tumor and enhanced cellular immune functions via cytokine production (IL-2 or IL-12) [43] and increase of natural killer cell activity in tumor-bearing mice [44]. None of these theories are, however, currently fully established.

One could also argue about the value of conducting systematic reviews or meta-analyses of a limited number of included studies. They can increase power, improve precision, answer questions not asked by individual studies, settle controversies arising from conflicting results, improve the quality of future primary studies, and generate new hypotheses [45‐47]. Systematic review can also avoid biases and make results and conclusions as objective as possible [46]. Even systematic reviews that find no primary studies to include can be valuable in that they may point towards important gaps in our knowledge. However, systematic reviews are retrospective and strongly depend on the quality of the primary studies [46]. They may also lead to contradictory overall conclusions [46]. The use of statistics does not guarantee that the results are valid. In our case, as the conclusions from the meta-analyses are from only 4 RCTs, the conclusions must remain tentative.

Limitations of our systematic review pertain to the potential incompleteness of the evidence reviewed. We aimed to identify all studies on the topic. The distorting effects of publication bias and location bias on systematic reviews are well documented [48‐50]. In the present review there were no restrictions on the review publication language, and a large number of different databases were searched. We are therefore confident that our search strategy located all relevant data on the subject. Most of the included RCTs that reported positive results come from China, a country which has been shown to produce no negative results [51]. Further limitations include the paucity and the often suboptimal quality of the primary data.

The evidence is limited to suggest moxibustion is an effective supportive cancer care in nausea and vomiting. However, all studies have a high risk of bias so effectively there is not enough evidence to draw any conclusion. Further research is required to investigate whether there are specific benefits of moxibustion for supportive cancer care.