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
Tweet this quote
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.
REFERENCES
1. Weaver KE, Forsythe LP, Reeve BB, et al: Mental and physical health-related quality of life among U.S. cancer survivors: Population estimates from the 2010 National Health Interview Survey. Cancer Epidemiol Biomarkers Prev 21:2108-2117, 2012.
2. Hershman DL, Lacchetti C, Dworkin RH, et al: Prevention and management of chemotherapy-induced peripheral neuropathy in survivors of adult cancers: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol 32:1941-1967, 2014.
3. Schneider BP, Hershman DL, Loprinzi C: Symptoms: Chemotherapy-induced peripheral neuropathy. Adv Exp Med Biol 862:77-87, 2015.
4. Ewertz M, Qvortrup C, Eckhoff L: Chemotherapy-induced peripheral neuropathy in patients treated with taxanes and platinum derivatives. Acta Oncol 54:587-591, 2015.
5. Seretny M, Currie GL, Sena ES, et al: Incidence, prevalence, and predictors of chemotherapy-induced peripheral neuropathy: A systematic review and meta-analysis. Pain 155:2461-2470, 2014.
6. Bao T, Basal C, Seluzicki C, et al: Long-term chemotherapy-induced peripheral neuropathy among breast cancer survivors: Prevalence, risk factors, and fall risk. Breast Cancer Res Treat 159:327-333, 2016.
7. Argyriou AA, Bruna J, Anastopoulou GG, et al: Assessing risk factors of falls in cancer patients with chemotherapy-induced peripheral neurotoxicity. Support Care Cancer 28:1991-1995, 2020.
8. Kolb NA, Smith AG, Singleton JR, et al: The association of chemotherapy-induced peripheral neuropathy symptoms and the risk of falling. JAMA Neurol 73:860-866, 2016.
9. Jensen MP, Friedman M, Bonzo D, et al: The validity of the neuropathic pain scale for assessing diabetic neuropathic pain in a clinical trial. Clin J Pain 22:97-103, 2006.
10. Smith EML, Pang H, Cirrincione C, et al: Effect of duloxetine on pain, function, and quality of life among patients with chemotherapy-induced painful peripheral neuropathy: A randomized clinical trial. JAMA 309:1359-1367, 2013.
11. Lin D, De La Pena I, Lin L, et al: The neuroprotective role of acupuncture and activation of the BDNF signaling pathway. Int J Mol Sci 15:3234-3252, 2014.
12. Zhao ZQ: Neural mechanism underlying acupuncture analgesia. Prog Neurobiol 85:355-375, 2008.
13. Vickers AJ, Vertosick EA, Lewith G, et al: Acupuncture for chronic pain: Update of an individual patient data meta-analysis. J Pain 19:455-474, 2018.
14. Bao T, Goloubeva O, Pelser C, et al: A pilot study of acupuncture in treating bortezomib-induced peripheral neuropathy in patients with multiple myeloma. Integr Cancer Ther 13:396-404, 2014.
15. Garcia MK, Cohen L, Guo Y, et al: Electroacupuncture for thalidomide/bortezomib-induced peripheral neuropathy in multiple myeloma: A feasibility study. J Hematol Oncol 7:41, 2014.
16. Alimi D, Rubino C, Pichard-Leandri E, et al: Analgesic effect of auricular acupuncture for cancer pain: A randomized, blinded, controlled trial. J Clin Oncol 21:4120-4126, 2003.
17. Schroeder S, Meyer-Hamme G, Epplee S: Acupuncture for chemotherapy-induced peripheral neuropathy: A pilot study using neurography. Acupunct Med 30:4-7, 2012.
18. Schröder S, Liepert J, Remppis A, et al: Acupuncture treatment improves nerve conduction in peripheral neuropathy. Eur J Neurol 14:276-281, 2007.
19. Wong R, Sagar S: Acupuncture treatment for chemotherapy-induced peripheral neuropathy: A case series. Acupunct Med 24:87-91, 2006.
20. Pan Y, Yang K, Wang Y, et al: Could yoga practice improve treatment-related side effects and quality of life for women with breast cancer? A systematic review and meta-analysis. Asia Pac J Clin Oncol 13:e79-e95, 2017.
21. Rostock M, Jaroslawski K, Guethlin C, et al: Chemotherapy-induced peripheral neuropathy in cancer patients: A four-arm randomized trial on the effectiveness of electroacupuncture. Evid Based Complement Alternat Med 2013:349653, 2013.
22. D’Alessandro EG, Nebuloni Nagy DR, de Brito CMM, et al: Acupuncture for chemotherapy-induced peripheral neuropathy: A randomised controlled pilot study. BMJ Support Palliat Care. June 29, 2019 (early release online).
23. Bao T, Seidman AD, Piulson L, et al: A phase IIA trial of acupuncture to reduce chemotherapy-induced peripheral neuropathy severity during neoadjuvant or adjuvant weekly paclitaxel chemotherapy in breast cancer patients. Eur J Cancer 101:12-19, 2018.
24. Bao T, Patil S, Chen C, et al: Effect of acupuncture vs sham procedure on chemotherapy-induced peripheral neuropathy symptoms: A randomized clinical trial. JAMA Netw Open 3:e200681, 2020.
25. Zhang CS, Tan HY, Zhang GS, et al: Placebo devices as effective control methods in acupuncture clinical trials: A systematic review. PLoS One 10:e0140825, 2015.
Dr. Bao is Director of Integrative Breast Oncology, Integrative Medicine Service at Memorial Sloan Kettering Cancer Center, New York.
