Chemotherapy-induced peripheral neuropathy is a debilitating and enduring adverse effect of many antineoplastic agents, which negatively impacts the quality of life of patients with cancer and survivors. Current pharmacotherapy has limited efficacy and causes undesirable effects. In this installment of The ASCO Post’s Integrative Oncology series, Ting Bao, MD, DABMA, MS, summarizes the findings of her group’s recent randomized trial investigating the effects of acupuncture on chemotherapy-induced peripheral neuropathy.

Overview

Many cancer survivors live with chronic toxicities from their cancer treatments, which can be debilitating and cause functional impairment.¹ The most common of these toxicities is chemotherapy-induced peripheral neuropathy,² which can manifest as paresthesia, hyperalgesia, and allodynia, and can significantly worsen patients’ quality of life.^3-8

Currently, symptoms of chemotherapy-induced peripheral neuropathy are managed with narcotics, antidepressants, anticonvulsants, and dietary supplements.⁹ Of note, duloxetine is the only drug supported by a large (n = 231) randomized trial, which reported moderate efficacy against chemotherapy-induced peripheral neuropathy.¹⁰ However, similar to other pharmacologic agents, duloxetine is limited by significant side effects such as nausea, headache, and fatigue. Therefore, well-tolerated, evidence-based interventions are needed to address chemotherapy-induced peripheral neuropathy.

“Acupuncture has been shown to be safe and possibly effective in treating persistent symptoms of chemotherapy-induced peripheral neuropathy, especially pain, in our study.”

— Ting Bao, MD, DABMA, MS

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Acupuncture is a widely used and safe nonpharmacologic traditional Chinese medicine technique that involves inserting fine, sterile needles in specific body points to achieve therapeutic effect. Over the past 40 years, multiple in vivo studies have demonstrated the neuroprotective effects of acupuncture exerted via brain-derived neurotrophic factor¹¹; and its analgesic effects through neurotransmitters such as enkephalins, beta-endorphins, and dynorphins.¹² Its effectiveness against chronic musculoskeletal pain is also well established.¹³ However, the role of acupuncture in controlling neuropathic pain remains unclear. Several studies have evaluated its potential for managing symptoms of chemotherapy-induced peripheral neuropathy ,^14-23 but findings are inconclusive due to small sample sizes as well as the lack of a placebo arm.

Acupuncture Trial

Our group recently completed a pilot, three-arm, phase IIb trial involving cancer (solid tumors) survivors with persistent moderate-to-severe chemotherapy-induced peripheral neuropathy to assess the role of acupuncture in reducing the severity of symptoms. Findings from this study will inform the design of a larger, definitive trial.²⁴

We enrolled 75 patients with chemotherapy-induced peripheral neuropathy to compare the effects of 8 weeks of real acupuncture (n = 27) with sham acupuncture (n = 24) and usual care (n = 24). Data showed that real acupuncture affected statistically significant improvements in pain compared with usual care. The absolute mean reduction in chemotherapy-induced peripheral neuropathy pain at week 8 was greatest for real acupuncture (−1.75 [95% confidence interval (CI) = −2.69 to −0.81]); moderate with sham acupuncture (−0.91 [95% CI = −2.0 to 0.18]); and least with usual care (−0.19 [95% CI = −1.13 to 0.75]). At the 12-week follow-up, we also observed that real acupuncture had a mean absolute reduction in numeric rating scale–measured pain of −1.74 (95% CI = −2.6 to −0.83) from baseline, whereas sham treatment had a reduction of −0.34 (95% CI = −1.3 to 0.61).

The magnitude of pain reduction observed in our real acupuncture group was noticeably significant as well when compared with duloxetine, currently the most supported treatment for chemotherapy-induced peripheral neuropathy. Duloxetine demonstrated a 1.06-point reduction in pain on the same 10-point pain scale,¹⁰ whereas real acupuncture produced a greater 1.75-point reduction in pain upon treatment completion. Furthermore, the improvement was maintained at the 12-week follow-up, highlighting the sustainable nature of acupuncture as a treatment for chemotherapy-induced peripheral neuropathy.

Acupuncture is also safer compared to duloxetine, which is associated with intolerable adverse effects such as fatigue and nausea. In fact, these adverse events with duloxetine resulted in a high dropout rate (12%) in the Alliance trial.¹⁰

Distinctively, our study is the first to incorporate a sham and nontreatment control to evaluate the efficacy of acupuncture in treating chemotherapy-induced peripheral neuropathy. The addition of a sham control has been considered difficult due to the challenge of incorporating a truly inert placebo. A meta-analysis found that many effective controls used in acupuncture trials were not truly inert.²⁵ In addition, a sham control limits the ability of a small effect size to elucidate a true difference between real and sham acupuncture. Not only did our study demonstrate the feasibility of conducting a sham-controlled acupuncture trial, it generated sufficient data to inform a definitive sham-controlled efficacy study.

Limitations of this trial are small sample size that hinders our ability to determine any specific difference in effects between real and sham acupuncture and short-term follow-up.

Recommendations

Acupuncture has been shown to be safe and possibly effective in treating persistent symptoms of chemotherapy-induced peripheral neuropathy, especially pain, in our study. A larger randomized controlled trial is being planned. Cancer survivors suffering from persistent moderate-to-severe pain from chemotherapy-induced peripheral neuropathy should be encouraged to participate in this upcoming trial to determine the definitive role of acupuncture in its treatment. 

DISCLOSURE: Dr. Bao has served as a consultant or advisor to Eisai.

GUEST EDITOR

Integrative Oncology is guest edited by Jun J. Mao, MD, MSCE, Laurance S. Rockefeller Chair in Integrative Medicine and Chief of Integrative Medicine Service at Memorial Sloan Kettering Cancer Center, New York.

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Dr. Bao is Director of Integrative Breast Oncology, Integrative Medicine Service at Memorial Sloan Kettering Cancer Center, New York.