A review of traditional Korean medical treatment for cancer-related cognitive impairment

Article information

J Korean Med. 2016;37(3):74-86
Publication date (electronic) : 2016 September 30
doi : https://doi.org/10.13048/jkm.16036
Clinical Research Division, Korea Institute of Oriental Medicine
Correspondence to: 김주희 (Joo-Hee Kim), 대전시 유성구 유성대로 1672 한국한의학연구원 임상연구부, Tel: +82-42-223-4052, Fax: +82-42-223-2955, E-mail: jhkim714@kiom.re.kr
Received 2016 August 22; Revised 2016 September 19; Accepted 2016 September 29.

Abstract

Objectives

This article aims to review clinical studies related to traditional Korean medicine (TKM) for cancer-related cognitive impairment (CRCI) up to date.

Methods

EMBASE, Pubmed and eight Korean databases were searched for clinical studies about TKM for CRCI up to July 2016. We selected articles about subjects with cancer, using TKM interventions including acupuncture, moxibustion or herbal medicine, containing assessment about cognitive function.

Results

Two randomized controlled trials (RCTs) and one randomized controlled feasibility study were included. Selected studies were containing assessments about cognitive function but not as primary outcomes. The three studies included one acupuncture study and two herbal-medicine studies. Only one herbal-medicine study showed improvement in cognitive function.

Conclusions

Few clinical studies mainly focusing CRCI treated with TKM have been performed and have shown contradictory results until now. Future studies should be performed considering findings from pre-clinical and clinical studies altogether, and they should be controlled to minimize risk of bias thorough out overall courses of designing, conducting and reporting them.

Fig. 1

Study flow diagram about traditional Korean medicine for cancer-related cognitive impairment

KM, Korean medicine; EA, electroacupuncture; CRCI, cancer-related cognitive impairment; RCT, randomized controlled trial

Fig. 2

Risk of bias graph about traditional Korean medicine for cancer-related cognitive impairment

Fig. 3

Risk of bias summary about traditional Korean medicine for cancer-related cognitive impairment

Characteristics of Included Studies (n=3)

References

1. Denlinger CS, Ligibel JA, Are M, Baker KS, Demark-Wahnefried W, Friedman DL, et al. Survivorship: cognitive function, version 1.2014. Journal of the National Comprehensive Cancer Network : JNCCN 2014;12(7):976–86.
2. Cheung YT, Chui WK, Chan A. Neurocognitive impairment in breast cancer patients: pharmacological considerations. Critical reviews in oncology/hematology 2012;83(1):99–111.
3. Park JH, Bae SH, Jung YS, Jung YM. Prevalence and Characteristics of Chemotherapy-related Cognitive Impairment in Patients with Breast Cancer. J Korean Acad Nurs 2015;45(1):118–28.
4. Runowicz CD, Leach CR, Henry NL, Henry KS, Mackey HT, Cowens-Alvarado RL, et al. American Cancer Society/American Society of Clinical Oncology Breast Cancer Survivorship Care Guideline. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2016;34(6):611–35.
5. Wefel JS, Vardy J, Ahles T, Schagen SB. International Cognition and Cancer Task Force recommendations to harmonise studies of cognitive function in patients with cancer. The Lancet Oncology 2011;12(7):703–8.
6. Kohli S, Griggs JJ, Roscoe JA, Jean-Pierre P, Bole C, Mustian KM, et al. Self-reported cognitive impairment in patients with cancer. Journal of oncology practice/American Society of Clinical Oncology 2007;3(2):54–9.
7. Ahles TA, Correa DD. Neuropsychological impact of cancer and cancer treatments. Psycho-oncology 2010;:251–7.
8. Palmer JL, Trotter T, Joy AA, Carlson LE. Cognitive effects of Tamoxifen in pre-menopausal women with breast cancer compared to healthy controls. Journal of cancer survivorship : research and practice 2008;2(4):275–82.
9. Schilder CM, Seynaeve C, Beex LV, Boogerd W, Linn SC, Gundy CM, et al. Effects of tamoxifen and exemestane on cognitive functioning of postmenopausal patients with breast cancer: results from the neuropsychological side study of the tamoxifen and exemestane adjuvant multinational trial. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2010;28(8):1294–300.
10. Ahles TA, Saykin AJ, McDonald BC, Furstenberg CT, Cole BF, Hanscom BS, et al. Cognitive function in breast cancer patients prior to adjuvant treatment. Breast cancer research and treatment 2008;110(1):143–52.
11. Jansen CE, Cooper BA, Dodd MJ, Miaskowski CA. A prospective longitudinal study of chemotherapy-induced cognitive changes in breast cancer patients. Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer 2011;19(10):1647–56.
12. Janelsins MC, Kesler SR, Ahles TA, Morrow GR. Prevalence, mechanisms, and management of cancer-related cognitive impairment. International review of psychiatry (Abingdon, England) 2014;26(1):102–13.
13. Wefel JS, Schagen SB. Chemotherapy-related cognitive dysfunction. Current neurology and neuroscience reports 2012;12(3):267–75.
14. Vardy J, Rourke S, Tannock IF. Evaluation of cognitive function associated with chemotherapy: a review of published studies and recommendations for future research. Journal of Clinical Oncology 2007;25(17):2455–63.
15. Correa DD, Ahles TA. Neurocognitive changes in cancer survivors. Cancer journal (Sudbury, Mass) 2008;14(6):396–400.
16. Koppelmans V, Breteler MM, Boogerd W, Seynaeve C, Gundy C, Schagen SB. Neuropsychological performance in survivors of breast cancer more than 20 years after adjuvant chemotherapy. Journal of Clinical Oncology 2012;30(10):1080–6.
17. de Ruiter MB, Reneman L, Boogerd W, Veltman DJ, Caan M, Douaud G, et al. Late effects of high-dose adjuvant chemotherapy on white and gray matter in breast cancer survivors: converging results from multimodal magnetic resonance imaging. Human brain mapping 2012;33(12):2971–83.
18. Deprez S, Amant F, Yigit R, Porke K, Verhoeven J, Van den Stock J, et al. Chemotherapy-induced structural changes in cerebral white matter and its correlation with impaired cognitive functioning in breast cancer patients. Human brain mapping 2011;32(3):480–93.
19. Kesler SR, Watson C, Koovakkattu D, Lee C, O’Hara R, Mahaffey ML, et al. Elevated prefrontal myo-inositol and choline following breast cancer chemotherapy. Brain imaging and behavior 2013;7(4):501–10.
20. Janelsins MC, Mustian KM, Palesh OG, Mohile SG, Peppone LJ, Sprod LK, et al. Differential expression of cytokines in breast cancer patients receiving different chemotherapies: implications for cognitive impairment research. Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer 2012;20(4):831–9.
21. Ahles TA, Saykin AJ. Candidate mechanisms for chemotherapy-induced cognitive changes. Nature reviews. Cancer 2007;7(3):192–201.
22. Raffa RB. A proposed mechanism for chemotherapy-related cognitive impairment (‘chemo-fog’). Journal of clinical pharmacy and therapeutics 2011;36(3):257–9.
23. Wefel JS, Kesler SR, Noll KR, Schagen SB. Clinical characteristics, pathophysiology, and management of noncentral nervous system cancer-related cognitive impairment in adults. CA: a cancer journal for clinicians 2015;65(2):123–38.
24. Ju C. Hwang Jae Nae Kyeong Yeongchu Cheonghong; 2007.
25. Committee for the textbook of Traditional Korean neuropsychiatry. Traditonal Korean medical Neuropsychiatry 1Jipmoon; 2007.
26. Committee for the textbook of the acupuncture and moxibustion. Amnesia and Dementia. The acupuncture and moxibustion 3 2Jipmoon; 2008.
27. Lee BH, Kim HY, Park JH, Yang TY, Jang EY, Jeon HS, et al. Effect of acupuncture on the short term memory. The journal of East-West medicine 2015;40(3):13–23.
28. Yun J, Kim Y, Lee C. A prison without bars: defect-punctured cancer-survivors management. Segye newspaper 2016. Available at: URL: http://www.segye.com/content/html/2016/07/06/20160706003541.html. Accessed July 6, 2016.
29. Boykoff N, Moieni M, Subramanian SK. Confronting chemobrain: an in-depth look at survivors’ reports of impact on work, social networks, and health care response. Journal of cancer survivorship : research and practice 2009;3(4):223–32.
30. Towler P, Molassiotis A, Brearley S. What is the evidence for the use of acupuncture as an intervention for symptom management in cancer supportive and palliative care: an integrative overview of reviews. Supportive Care in Cancer 2013;21(10):2913–23.
31. Liu F, Li ZM, Jiang YJ, Chen LD. A meta-analysis of acupuncture use in the treatment of cognitive impairment after stroke. Journal of alternative and complementary medicine (New York, NY) 2014;20(7):535–44.
32. Cao H, Wang Y, Chang D, Zhou L, Liu J. Acupuncture for vascular mild cognitive impairment: a systematic review of randomised controlled trials. Acupuncture in medicine : journal of the British Medical Acupuncture Society 2013;31(4):368–74.
33. Sun DZJ, Zhang JP, Xu X, Ye JY, Xiu M, Zhao LJ, et al. Therapeutic effect of Jinlongshe Granule () on quality of life of stage IV gastric cancer patients using EORTC QLQ-C30: A double-blind placebo-controlled clinical trial. Chinese journal of integrative medicine 2015;21(8):579–86.
34. Chan KKY, Jones TJ, Zhao B, Ma JF, Leung FK, Lau CY, et al. The use of Chinese herbal medicine to improve quality of life in women undergoing chemotherapy for ovarian cancer: a double-blind placebo-controlled randomized trial with immunological monitoring. Annals of oncology : official journal of the European Society for Medical Oncology / ESMO 2011;22(10):2241–9.
35. Johnston MFH, Subramanian RD, Elashoff SK, Axe RM, Li EK, Kim JJ, et al. Patient education integrated with acupuncture for relief of cancer-related fatigue randomized controlled feasibility study. BMC complementary and alternative medicine 2011;11:49.
36. Yun YH, Park YS, Lee ES, Bang SM, Heo D, Park S, et al. Validation of the Korean version of the EORTC QLQ-C30. Quality of Life Research 2004;13(4):863–8.
37. Deng M, Wang XF. Acupuncture for amnestic mild cognitive impairment: a meta-analysis of randomised controlled trials. Acupuncture in Medicine 2016;acupmed-2015-010989.
38. Hwang D. Bang-Yak-Hap-Pyun(方藥合編). Younglim 2010;
39. LI Cj, WEI Pk, YU Bl. Study on the mechanism of Xiaotan Sanjie Recipe for inhibiting proliferation of gastric cancer cells. Journal of Traditional Chinese Medicine 2010;30(4):249–53.
40. Joo SK, Kim GW, Goo BS, Kim CH. Effects of Arisaematics rhizoma on Ischemic Damage and Cytotoxicity in Brain. Journal of Korean Medicine 2001;2(1)
41. Won HY, Choi CW, Kim KS, Kim KO, Lee DW, Kim SY. The effects of Banhabaekchulchunma-Tang (BCT) on Dementia induced by focal brain ischemic injury in rats. Journal of Oriental Neuropsychiatry 2006;17(2):61–73.
42. Kim S, Ryu B, Ryu K, Park D. Study of (386) 대한한의학회지 제 37 권 제 3 호 (2016 년 9 월) anti-cancer effects of Cremastrae Appendiculatae Tuber on stomach cancer cells. J Korean Oriental Med 2001;22(2):75–83.
43. Seo B, Lee E. A Philological Study on poisoning of Pseudobulbus Cremastrae Appendiculatae. Journal of applied oriental medicine 2003;3(1):73–82.
44. Kim H, Hong S. The anti-inflammatory effects of Huang-Lyun (Coptidis Rhizoma, CR) on injured tissue after burn elicitation. J Korean Oriental Med 2011;32(2):1–13.
45. Jeong MY, Kim YH, Lee NK, Lee JY, Herr Y, Lee JH, et al. Antimicrobial effect on the periodontal pathogens and anti-inflammatory effect of Eriobotryae Folium. J Korean Orient Med 2008;29:182–92.
46. Avisar AR, Schiff Y, Bar-Sela E, Steiner G, Ben-Arye M. Chemotherapy-related cognitive impairment: does integrating complementary medicine have something to add? Review of the literature. Breast cancer research and treatment 2012;136(1):1–7.
47. Johnston MFY, Hui C, Xiao KK, Li B, Rusiewicz X. Acupuncture for chemotherapy -associated cognitive dysfunction: a hypothesis -generating literature review to inform clinical advice. Integrative cancer therapies 2007;6(1):36–41.
48. Yu SJ, Tseng J, Fu Ling. a Chinese herbal drug, modulates cytokine secretion by human peripheral blood monocytes. International journal of immunopharmacology 1996;18(1):37–44.
49. Sparkman NL, Buchanan JB, Heyen JR, Chen J, Beverly JL, Johnson RW. Interleukin-6 facilitates lipopolysaccharide-induced disruption in working memory and expression of other proinflammatory cytokines in hippocampal neuronal cell layers. The Journal of neuroscience 2006;26(42):10709–16.
50. O’Sullivan E, Higginson I. Clinical effectiveness and safety of acupuncture in the treatment of irradiation-induced xerostomia in patients with head and neck cancer: a systematic review. Acupuncture in Medicine 2010;28(4):191–9.
51. Sun X, Zhang X, Nian JY, Guo J, Yin Y, Zhang GL, et al. Chinese Herbal Medicine as Adjunctive Therapy to Chemotherapy for Breast Cancer: A Systematic Review and Meta -Analysis. Evidence-based complementary and alternative medicine : eCAM 2016;2016:3281968.

Article information Continued

Fig. 1

Study flow diagram about traditional Korean medicine for cancer-related cognitive impairment

KM, Korean medicine; EA, electroacupuncture; CRCI, cancer-related cognitive impairment; RCT, randomized controlled trial

Fig. 2

Risk of bias graph about traditional Korean medicine for cancer-related cognitive impairment

Fig. 3

Risk of bias summary about traditional Korean medicine for cancer-related cognitive impairment

Table 1

Characteristics of Included Studies (n=3)

Study ID Subjects; N (TG: CG); mean age (TG:CG); Intervention (sessions, duration) Assessment for cognitive function (time point) Result
ATX
Johnston 201135) Breast cancer survivors, Female, 18–65yrs old, BFI ≥4, Finished primary cancer therapy; N= 5:7; Mean age= 55.0:53.0yrs old; TG: usual care + Education with ATX
(50 min*8 sessions ATX; 50 min *4 sessions education; for 8 wks)
CG: usual care only (8 wks)
FACT-COGv2
(Prior to beginning of Tx and after Tx ends. Up to an average of 44 wks)
  1. BFI: NS but clinically meaningful with ES 1.85

  2. FACT-COGv2: NS

HM
Chan 201134) Ovarian cancer, Female, ≥18yrs old, who need chemotherapy; N= 31:28; Mean age=52.9:51.5 yrs old; TG: standard CT + TCM herb powder CG: standard CT + placebo
(b.i.d., for 1st – 6th cycles of CT)
EORTC-cognition
(3rd cycle of CT and 4 wks after the 6th cycle)
  1. EORTC-QLQ-C30: NS between groups, both improved

  2. EORTC-cognition:

    • After 3 cycles: Worse in TG (−9.14±5.12) than CG (7.1±4.81). The change was significantly different*

    • After 6 cycles: NS in either group

  3. Immune function: total lymphocyte count maintained in TG only

Sun 201533) Stage IV Gastric cancer, Either sex, 18–90yrs old, KPS>30, expected survival >3mos; N=19:20; Mean age=NR; TG: CHD + Jinlongshe Granule
CG: CHD + placebo
(t.i.d., for ≥ 3 mos)
EORTC-cognition
(3, 6, 9, 12 and 15 mos after Tx)
  1. EORTC-QLQ-C30: generally improved in TG** except dyspnea, diarrhea

  2. EORTC-cognition: improved in TG with F=7.103 (p=0.001)**

BFI, brief fatigue inventory; ATX, acupuncture; TG, treatment group; CG, control group; FACT-COGv2, functional assessment of cancer treatment cognitive scale V2; NS, not significant; ES, effect size; HM, herbal medicine; TCM, traditional Chinese medicine; CT, chemotherapy; b.i.d., twice a day; CHD, Chinese herbal decoctions; t.i.d., three-times a day; KPS, Karnofsky performance score; NR, not reported; Tx, treatment; EORTC-cognition, EORTC-QLQ-C30 cognitive function subscale;

*

, statistically significant (p<0.05);

**

, statistically significant (p<0.01);

CT, 3 weekly;