Acupuncture (PDQ®)–Health Professional Version
Human/Clinical Studies
Effect of Acupuncture on Immune Function
There has been limited research, mostly performed in China, evaluating the effect of acupuncture on immune system function in cancer patients, suggesting that acupuncture improves immune function.[1-7]
Effect of Acupuncture on Cancer Pain
Clinical studies and reviews of acupuncture as a treatment for cancer-related pain have been reported in the English language (refer to Table 1).[8-15] Two studies were randomized controlled trials (RCTs), with one study conducted in China and one in France.[9,13] Four studies were case series, with one each from England, France, Hong Kong, and the United States.[8,10-12]
One randomized trial compared classical Chinese acupuncture, acupuncture point injectionwith freeze-dried human transfer factor, and conventional analgesic treatment in patients with gastric cancer pain.[9] The investigators reported an equivalent analgesic effect among the three groups observed after 2 months of treatment; however, the conventionally treated group experienced significantly superior analgesia compared with both acupuncture treatment groups during the first 10 days of treatment. The researchers reported that the patients in both acupuncture treatment groups also experienced improved quality of life (QOL) and a decrease in the side effects of chemotherapy, in addition to analgesia.
Also, a nonrandomized, single-arm, observational clinical study evaluated the effect of auricular acupuncture in 20 cancer patients who were still experiencing pain after treatment with analgesics.[10] While patients continued their analgesic medication, auricular acupuncture needles were embedded in ear acupuncture points, chosen according to clinical symptoms and electrodermal response, and were left in place until they fell out. In some cases, the needles remained in place for 35 days, while in others they fell out after 5 days. Pain intensity was measured by a nurse on the visual analog scale(VAS) on day 0 and day 60, and the data were analyzed using a t test. The results showed that pain intensity decreased or remained stable after auricular acupuncture in all patients, with a significant average pain intensity decrease of 33 mm (P < .001). The same investigators later reported a larger (N = 90) randomized, blinded, controlled trial in which cancer pain intensity was significantly decreased (by 36%) in an auricular acupuncture treatment group, in comparison with control groups (by 2%, acupuncture at placebo points or auricular seeds placed at placebo points) after 2 months of treatment (P < .001).[13]
Although most of these studies were positive and demonstrated the effectiveness of acupuncture in cancer pain control, the findings have limited significance because of methodologic weaknesses such as small sample sizes, an absence of patient blinding to treatment in most cases, varying acupuncture treatment regimens, a lack of standard outcome measurements, and an absence of adequate randomization. A 2015 Cochrane systematic review of five RCTs reported benefits of acupuncture in reducing pancreatic cancer pain, pain from late-stage cancer, and chronic cancer-related neuropathic pain; the study found no difference between real and sham electroacupuncture (EA) for ovarian cancer pain.[16] However, because of small sample sizes and a high risk of bias, the authors concluded, “there is insufficient evidence to judge whether acupuncture is effective in treating cancer pain in adults.”[16] In addition, a 2016 systematic review and meta-analysis of 1,639 participants with cancer-related pain in 20 RCTs with a high risk of bias showed that acupuncture alone was not superior to conventional drug therapy, although acupuncture plus drug therapy appeared to be superior to drug therapy alone.[17] However, this study was limited by the poor quality of combination therapy trials. Further investigations into the effects of acupuncture on cancer pain using rigorous scientific methodology are warranted.
Effect of Acupuncture on Cancer Treatment–Related Side Effects
Pain
Acupuncture for postsurgical pain
Five RCTs published in English have addressed the use of acupuncture for pain related to cancer treatment, mostly postsurgical pain (refer to Table 2). One RCT of 106 cancer patients who experienced postthoracotomy pain showed no statistical difference in the real acupuncture (RA) group compared with the sham acupuncture (SA) group in patients' pain scores measured by the Brief Pain Inventory at the 30-, 60-, and 90-day follow-up.[18] The efficacy of the unique intradermal needles used in this study was questionable.
Another smaller RCT (N = 27) showed a trend of lower VAS pain scores in patients who received EA when compared with patients who received SA on postoperative days 2 and 6; and a statistically significant lower cumulative dose of patient controlled analgesia on postoperative day 2 (P < .05).[19] However, this study was limited by its small sample size.
One RCT (N = 93) compared acupuncture with massage therapy and usual care in controlling postoperative pain, nausea, vomiting, and depressive moods.[20] This study showed that postoperative acupuncture and massage in addition to usual care significantly improved pain control when compared with usual care alone.
Another study showed that in cancer patients with chronic pain or dysfunction as a result of neck dissection, four weekly acupuncture treatments significantly reduced pain and improved function compared with standard care alone.[21] Additionally, a study of 80 patients with breast cancer showed that when compared with usual care alone, acupuncture significantly improved postoperative pain and range of movement.[22] However, with no sham therapy group in these two studies, it is difficult to determine how much of the improvement is because of the placebo effect, and whether RA needles and professionally trained acupuncturists and massage therapists are required in the intervention.
Acupressure has been shown to be efficacious in reducing procedural pain. Two RCTs showed that acupressure at LI4 and HT7 significantly reduced patients’ pain and anxiety.[23,24]
Acupuncture for aromatase inhibitor-associated musculoskeletal symptoms
A 2012 meta-analysis of 29 trials with 17,922 patients found that RA is more beneficial than both SA and no acupuncture in the treatment of chronic pain, with a modest effect size of 0.23 (95% confidence interval [CI], 0.13–0.33).[25] However, none of the patients in these trials had pain due to cancer or cancer therapies. Recently published meta-analyses have examined outcomes from RCTs evaluating the effects of acupuncture on aromatase inhibitor -associated musculoskeletal symptoms (AIMSS) in breast cancer survivors with a history of stage I, II, or III nonmetastatic hormone receptor–positive breast cancer currently taking an aromatase inhibitor.
Three meta-analyses [26-28] identified five studies [29-33] that randomly assigned participants to receive SA or RA. Four of the studies were conducted in the United States and one was conducted in Australia. Two studies used EA [31,32] and three studies used manual acupuncture (MA).[29,30,33] Three of these studies were sham-controlled; one randomly assigned patients to receive either acupuncture followed by observation or vice versa, and one was a three-arm study where participants were randomly assigned to SA, EA, or wait-list control (WLC). All studies had relatively small sample sizes ranging from 19 to 67.
All studies included in the meta-analyses [26-28] classified changes in measures of jointpain and stiffness as primary outcomes. Participant symptom improvement was assessed by using self-reported measures for pain, and pain interference and stiffness at baselineand at specified intervals during and after the intervention. Results from these meta-analyses were not definitive and suggested further research needs to be conducted in this area.
Further extending the literature supporting the efficacy of acupuncture in treating AIMSS, an RCT was conducted using 226 participants (SWOG-S1200 [NCT01535066]) randomly assigned to three groups (MA, SA, and WLC) and found improvements in joint pain after treatment when compared with SA and WLC.[33] These findings are of uncertain clinical significance because the magnitude of difference in the primary outcome measure between groups (MA vs. SA) was less than the amount that was predetermined as being clinically meaningful by the researchers. However, these findings are consistent with results from existing observational studies showing the safety and feasibility of acupuncture in treating pain.
Nausea and vomiting
Chemotherapy-induced nausea and vomiting
Of all the investigated effects of acupuncture on cancer-related or chemotherapy-related symptoms and disorders, the positive effect of acupuncture on chemotherapy-induced nausea and vomiting (N/V) is the most convincing, as demonstrated by the consistency of the results of a variety of clinical study types, including RCTs, nonrandomized trials, prospective consecutive case series, and retrospective studies (refer to Table 4). Consistent with the findings from clinical studies of acupuncture on N/V due to other causes (i.e., postoperative N/V and morning sickness), these studies showed acupuncture to be effective in the treatment of chemotherapy-induced N/V (CINV).
A 2013 systematic review of literature on acupuncture in cancer care screened 2,151 publications and identified 41 RCTs studying the effect of using acupuncture to treat eight cancer treatment–related symptoms (pain, nausea, hot flashes, fatigue, radiation-induced xerostomia, prolonged postoperative ileus, anxiety/mood disorders, and sleep disturbance). The review concluded that acupuncture is an appropriate adjunctive treatment for CINV, but additional studies are needed because most RCTs had unclear bias or a high risk of bias.[34]
In 2005, a comprehensive meta-analysis of 11 RCTs (N = 1,247) evaluating the effect of acupuncture-point stimulation in controlling CINV showed that acupuncture-point stimulation significantly reduced the proportion of acute vomiting (relative risk, 0.82; 95% CI, 0.69–0.99, P = .04),[35] although the meta-analysis did not show that acupuncture reduced the mean number of acute emetic episodes or acute or delayed nausea severity compared with control.
The trials in the meta-analysis were published between 1987 and 2003, and the sample sizes ranged from ten patients in the smallest trial [36] to 747 patients in the largest trial.[37] Among the ten trials that reported a chemotherapy regimen, all patients received moderate to high emetogenic chemotherapy. Eight of the trials used ondansetron, a 5-HT3-receptor antagonist, as the antiemetic regimen. The other three trials used methotrexate alone, methotrexate with prednisone, or methotrexate with dopaminergic antagonists as the antiemetic regimen.[35] None of the antiemetic regimens contained aprepitant because the trials all predated this drug.
A meta-analysis of acupuncture in N/V is the most comprehensive summary of clinical research on the role of acupuncture-point stimulation in controlling CINV. It found that acupuncture-point stimulation decreases the proportion of patients who experience acute chemotherapy-induced vomiting and concurred with the previous systemic review and meta-analysis.[38,39] It suggested that acupressure may relieve chemotherapy-induced nausea, even though the studies were limited by lack of an effective control arm to rule out the placebo effect. It also suggested differences among acupuncture-point stimulation modalities, with invasive-point stimulation to be more effective than noninvasive -point stimulation in reducing acute CINV.[35] It has since been cited multiple times by review articles and oncology practice guidelines.[40-42]
The National Institutes of Health Consensus Development Conference held in 1997 reviewed studies that evaluated the safety and efficacy of acupuncture in treating postoperative- and chemotherapy-related N/V.[43] Studies discussed at the conference reported significantly less N/V compared with the control group.[36,44-47] The panel stated that “there is clear evidence that needle acupuncture treatment is effective for postoperative and chemotherapy N/V.”[43]
The acupuncture point specificity is worth mentioning because most of the earlier acupuncture CINV trials used the PC6 acupuncture point and showed positive results. A well-designed, randomized, placebo-controlled trial published in 2014 showed that K1 acupoint acustimulation combined with antiemetics did not prevent cisplatin -induced or oxaliplatin -induced nausea in 103 liver cancer patients who underwent a transarterial chemoembolization (TACE) procedure.[48] A single-blind, randomized, controlled trial in 2017 showed that transcutaneous electrical stimulation at P6, LI4, and ST36 acupoints did not significantly alleviate CINV associated with TACE, when compared with placebo in patients with liver cancer.[49] EA at P6, LI4, and ST36 points did, however, reduce anorexiascores more than SA.
A 2016 RCT showed that among 48 breast cancer patients receiving chemotherapy, patients randomly assigned to the auricular acupressure group (ear seed placed on point zero, stomach, brainstem, shenmen, and cardia) had significantly less intense and less frequent N/V in acute and delayed phases compared with the control group that had no auricular acupressure.[50] This study is limited by its small sample size and lack of placebo control. However, it describes an additional noninvasive method to control CINV that may deserve further investigation.
Radiation-induced nausea and vomiting
Vasomotor symptoms
Some studies have reported that acupuncture may be effective in reducing vasomotorsymptoms among postmenopausal women with breast cancer and prostate cancerpatients receiving androgen-deprivation therapy.[59-65]
Six RCTs have studied the role of acupuncture in reducing hot flashes in breast cancer survivors.
In 2007, one study reported results from a randomized, sham-controlled trial on the effect of acupuncture in treating breast cancer survivors who experienced three or more hot flashes per day.[59] The investigators reported that the mean number of hot flashes per day at week 6 changed from 8.7 to 6.2 in the RA arm, and from 10.0 to 7.6 in the SA arm. However, the difference between the RA group and the SA group was not statistically significant (P = .3). When patients in the SA group crossed over to receive RA, their hot flash frequency further reduced from 7.6 to 5.8. The reduction in hot flashes in all patients persisted during the 6 months of follow-up (RA arm, 6.1 per day; SA arm, 6.8 per day). On the basis of fewer hot flashes in both groups, the authors concluded that acupuncture reduced hot-flash frequency, although the difference between the RA and SA groups was not statistically significant.[59]
In 2009, one study reported another randomized SA-controlled trial on the effect of acupuncture in treating women with breast cancer who suffered from hot flashes after receiving tamoxifen for at least 3 months.[66] Fifty-nine women were randomly assigned to either 15 sessions (5 weeks biweekly followed by 5 weeks weekly) of RA or SA. The authors reported that at the end of the treatment period, the mean number of daytime hot flashes was reduced significantly from 9.5 to 4.7 (P = .001) in the RA group and from 12.3 to 11.7 (P= .382) in the SA group. At 12 weeks follow-up, further reduction was observed in the RA group (from 4.7 to 3.2) but not in the SA group (from 11.7 to 12.1). The difference between the RA group and SA group was statistically significant (P < .001). The authors concluded that acupuncture provided effective relief from hot flashes in women with breast cancer who suffered from hot flashes while taking tamoxifen.[66] The evidence generated from these two trials suggests that acupuncture effectively decreases hot-flash frequency, although it is not clear whether it is superior to SA.
Another clinical trial compared the effects of EA with hormonal therapy in breast cancer survivors with vasomotor symptoms; in 19 of 27 women who completed 12 weeks of EA treatment, the number of hot flashes was significantly reduced from 9.6 per day to 4.3 per day. The improvement persisted at the 12-month follow up.[67] In the hormonal treatment group, the median number of hot flashes dropped from 6.6 at baseline to 0 at week 12. Although hot flashes decreased less in the EA group than in the hormonal treatment group, health-related QOL improved at least to the same extent. It suggests that EA could be further evaluated as treatment for women with breast cancer and climacteric complaints, particularly since hormonal treatment is no longer recommended for breast cancer survivors.[67]
In 2010, another RCT compared the effect of acupuncture with venlafaxine in treating vasomotor symptoms in breast cancer patients suffering from more than 13 hot flashes per week.[61] Changes in hot flash frequency from baseline and at 3-, 6-, 9- and 12-month follow-up were used as the primary outcome. Fifty patients were randomly assigned to 12 weeks (biweekly for 4 weeks, followed by weekly for 8 weeks) of acupuncture versus daily venlafaxine (37.5 mg for 1 week, then 75 mg for 11 weeks). The investigators observed a significant reduction in hot flash frequency and severity in both groups. In addition, 2 weeks after treatments were stopped, patients randomly assigned to venlafaxine reported increased hot-flash frequency, whereas the acupuncture group remained at a low level of hot flashes. There was no significant difference between the acupuncture arm and the venlafaxine arm. There were 18 reported adverse events (i.e., nausea, dizziness, headache) in the venlafaxine arm and none in the acupuncture arm. The authors concluded that acupuncture appears to be as effective as venlafaxine and is a safe and durable treatment option for breast cancer patients experiencing vasomotor symptoms.[61]
In 2013, a study reported the results of a three-arm RCT (N = 94) comparing RA (N = 31) with SA (N = 29) and usual care alone (N = 34) in reducing hot flashes in breast cancer survivors. In the acupuncture group, 16 (52%) patients experienced a significant reduction in hot flashes compared with 7 (24%) in the SA group (P < .05). There was also a statistically positive effect on sleep when RA was compared with SA. Importantly, the researchers measured the plasma estradiol level and determined that there was not a correlation between symptoms improvement and an increase in estradiol level.[68]
In 2014, a study reported the results of a two-arm RCT (N = 47) on the effect of acupuncture in reducing AIMSS and hot flashes as one of the secondary end points. When compared with baseline, acupuncture significantly improved hot-flash severity, frequency, and function. SA significantly improved the Hot Flash Related Daily Interference Scale only. However, there was no significant difference between the two groups.[69]
These trials once again confirmed that acupuncture is safe. They showed that acupuncture reduced hot flashes significantly when compared with baseline, although the benefit of RA versus SA was not clear.
A 2015 systematic review of acupuncture to control hot flashes in cancer patients showed that in all eight studies included in the review, acupuncture resulted in significant improvement from the baseline, and three studies showed RA was significantly better than SA in different aspects of hot flashes. However, none of the studies were rated with a low risk of bias.[70] A 2016 meta-analysis of 12 RCTs published before April 2015 on the efficacy of acupuncture or EA on breast cancer survivors suffering from hot flashes failed to show a favorable effect of acupuncture on reducing the frequency of hot flashes when compared with control groups such as SA, hormone therapy, antidepressants, or relaxation intervention.[71] The authors explained that this finding may be due to heterogeneity of the studies, small sample size of the studies, and the underlying methodological issues with some studies. Another 2016 systematic review of 12 RCTs (including eight in the aforementioned meta-analysis) found that all RCTs showed the effect of acupuncture when compared with no acupuncture. However, only two of the six RCTs comparing RA with SA showed significant benefit of acupuncture over placebo. The other studies showed that acupuncture was no better than hormone therapy, venlafaxine, or relaxation controls.[72] Consequently, there is insufficient evidence supporting or refuting using acupuncture to treat hot flashes. Further studies are needed.
A study published in 2015 that used EA in the treatment of hot flashes randomly assigned 120 breast cancer survivors who were suffering from hot flashes at least twice daily to one of four of the following arms: EA, SA, gabapentin (GP), and placebo pills (PP) for 8 weeks.[73] Unlike other acupuncture efficacy trials, however, the primary end point was the change in hot flash composite scores (HFCS) between SA and PP at week 8, with secondary end points including posttreatment comparisons of all groups at different time points and examination of treatment durability at week 24. It showed that SA produced significantly greater reductions in HFCS than did PP by week 8, indicating a greater placebo effect with SA. Although all arms experienced HFCS reductions, SA produced significantly better results than did both GP and PP interventions (EA, −7.4; SA, −5.9; GP, −5.2; and PP, −3.4), compared with baseline scores. In addition, SA had a smaller nocebo effect than PP, as evidenced by the significantly higher percentage of reported adverse events for PP (20.0%) compared with SA (3.1%). Another intriguing finding is the more-durable effect in HFCS reductions produced at week 24 (16 weeks posttreatment) with both EA and SA treatments (EA, −8.5; SA, −6.1) than with GP (GP, −2.8), suggesting that both types of acupuncture may elicit underlying physiologic changes not induced by pharmacologic intervention. On the other hand, the effect size of EA compared with SA was small at week 8 (Cohen’s d, 0.21) but got bigger at week 24 (Cohen’s d, 0.31), suggesting EA may produce additional or longer-lasting physiological effects than would SA.[73]
A 2016 pragmatic RCT (N = 190) that compared individualized acupuncture plus enhanced self-care (as described in an information booklet provided to all patients) with enhanced self-care alone showed that the combination therapy is superior to self-care alone in reducing hot flash scores at the end of treatment, at the 3-month follow-up visit, and at the 6-month follow-up visit.[74][Level of evidence: 1iiC] In addition, this highly impactful study also showed that acupuncture significantly improved patients’ QOL without any serious adverse effects.[74] It used the standard traditional Chinese medicine acupuncture approach, which first identified menopausal syndromes according to Maciocia’s recommendations and consequently chose individualized acupoints in addition to three common acupoints: SP6, LI11, and CV4.[74] This study provides solid evidence to support the use of acupuncture to reduce hot flashes and improve breast cancer survivors’ QOL. However, further research is needed to understand the mechanisms of how acupuncture may have reduced hot flashes.
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