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Goshajinkigan for prevention of chemotherapy-induced peripheral neuropathy: a systematic review and meta-analysis

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Abstract

Purpose

Chemotherapy-induced peripheral neuropathy (CIPN) limits the dose of chemotherapy and reduces patients’ quality of life. Goshajinkigan is a Japanese herbal medicine used to alleviate neuropathy and general pain. A clinical guideline for prevention and management of CIPN stated that the prophylactic efficacy of goshajinkigan against CIPN was inconclusive. We conducted a systematic review to examine whether goshajinkigan prevents CIPN in patients receiving neurotoxic chemotherapy.

Methods

We searched PubMed, EMBASE, Ichushi, and the Cochrane Central Register of Controlled Trials for eligible trials. Randomized controlled trials that examined the efficacy and safety of goshajinkigan for prevention of CIPN were included. Our primary outcomes were incidence of CIPN, response to chemotherapy, and adverse effects. We pooled data using a random effects model.

Results

We analyzed five trials involving a total of 397 patients. When evaluated with Neurotoxicity Criteria of Debiopharm, goshajinkigan was associated with reduced incidence of CIPN of grade ≥ 1 (risk ratio [RR] 0.43; 95% CI, 0.27 to 0.66) and grade 3 (RR 0.42; 95% CI, 0.25 to 0.71), but this beneficial association was not found for grade ≥ 2 of CIPN. Goshajinkigan was not associated with reduced incidence of CIPN when assessed with the National Cancer Institute Common Terminology Criteria for Adverse Events, or improved response to chemotherapy. Goshajinkigan was well tolerated based on one trial.

Conclusions

Goshajinkigan is unlikely to prevent CIPN in patients undergoing neurotoxic chemotherapy. Given the low quality and insufficient amount of the evidence, use of goshajinkigan as standard of care is not currently recommended.

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References

  1. Abe H, Kawai Y, Mori T, Tomida K, Kubota Y, Umeda T, Tani T (2013) The Kampo medicine Goshajinkigan prevents neuropathy in breast cancer patients treated with docetaxel. Asian Pac J Cancer Prev 14(11):6351–6356. https://doi.org/10.7314/APJCP.2013.14.11.6351

    Article  PubMed  Google Scholar 

  2. Andoh T, Kitamura R, Fushimi H, Komatsu K, Shibahara N, Kuraishi Y (2014) Effects of goshajinkigan, hachimijiogan, and rokumigan on mechanical allodynia induced by paclitaxel in mice. J Tradit Complement Med 4(4):293–297. https://doi.org/10.4103/2225-4110.128906

    Article  PubMed  PubMed Central  Google Scholar 

  3. Andoh T, Kato M, Kitamura R, Mizoguchi S, Uta D, Toume K, Komatsu K, Kuraishi Y (2016) Prophylactic administration of an extract from Plantaginis Semen and its major component aucubin inhibits mechanical allodynia caused by paclitaxel in mice. J Tradit Complement Med 6(3):305–308. https://doi.org/10.1016/j.jtcme.2015.12.001

    Article  PubMed  PubMed Central  Google Scholar 

  4. Bahar MA, Andoh T, Ogura K, Hayakawa Y, Saiki I, Kuraishi Y (2013) Herbal medicine goshajinkigan prevents paclitaxel-induced mechanical allodynia without impairing antitumor activity of paclitaxel. Evid Based Complement Alternat Med 2013:849754

    Article  PubMed  PubMed Central  Google Scholar 

  5. Cascella M, Muzio MR (2017) Potential application of the Kampo medicine goshajinkigan for prevention of chemotherapy-induced peripheral neuropathy. J Integr Med 15(2):77–87. https://doi.org/10.1016/S2095-4964(17)60313-3

    Article  PubMed  Google Scholar 

  6. DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7(3):177–188. https://doi.org/10.1016/0197-2456(86)90046-2

    Article  CAS  PubMed  Google Scholar 

  7. Gagnier JJ, DeMelo J, Boon H, Rochon P, Bombardier C (2006) Quality of reporting of randomized controlled trials of herbal medicine interventions. Am J Med 119:800 e801–800 e811

    Article  Google Scholar 

  8. Galbraith RF (1988) A note on graphical presentation of estimated odds ratios from several clinical trials. Stat Med 7:889–894

    Article  CAS  PubMed  Google Scholar 

  9. Hershman DL, Lacchetti C, Dworkin RH, Lavoie Smith EM, Bleeker J, Cavaletti G, Chauhan C, Gavin P, Lavino A, Lustberg MB, Paice J, Schneider B, Smith ML, Smith T, Terstriep S, Wagner-Johnston N, Bak K, Loprinzi CL, American Society of Clinical O (2014) 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

    Article  CAS  PubMed  Google Scholar 

  10. Higgins J, Green S (2008) Cochrane handbook for systematic reviews of interventions. John Wiley & Sons, Ltd, Chichester. https://doi.org/10.1002/9780470712184

    Book  Google Scholar 

  11. Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ (Clin Res ed) 327(7414):557–560. https://doi.org/10.1136/bmj.327.7414.557

    Article  Google Scholar 

  12. Hirayama Y, Sasaki J, Dosaka-Akita H, Ishitani K (2016) Survey of the management of chemotherapy-induced peripheral neuropathy in Japan: Japanese Society of Medical Oncology. ESMO open 1:e000053

    Article  PubMed  PubMed Central  Google Scholar 

  13. Hosokawa A, Ogawa K, Ando T, Suzuki N, Ueda A, Kajiura S, Kobayashi Y, Tsukioka Y, Horikawa N, Yabushita K, Fukuoka J, Sugiyama T (2012) Preventive effect of traditional Japanese medicine on neurotoxicity of FOLFOX for metastatic colorectal cancer: a multicenter retrospective study. Anticancer Res 32(7):2545–2550

    CAS  PubMed  Google Scholar 

  14. Inoue N, Ishida H, Sano M, Kishino T, Okada N, Kumamoto K, Ishibashi K (2012) Discrepancy between the NCI-CTCAE and DEB-NTC scales in the evaluation of oxaliplatin-related neurotoxicity in patients with metastatic colorectal cancer. Int J Clin Oncol 17(4):341–347. https://doi.org/10.1007/s10147-011-0298-z

    Article  CAS  PubMed  Google Scholar 

  15. Kajiwara M, Mutaguchi K (2008) Clinical efficacy and tolerability of gosha-jinki-gan, Japanese traditional herbal medicine, in females with overactive bladder. Hinyokika kiyo Acta urologica Japonica 54:95–99

    PubMed  Google Scholar 

  16. Kaku H, Kumagai S, Onoue H, Takada A, Shoji T, Miura F, Yoshizaki A, Sato S, Kigawa J, Arai T, Tsunoda S, Tominaga E, Aoki D, Sugiyama T (2012) Objective evaluation of the alleviating effects of Goshajinkigan on peripheral neuropathy induced by paclitaxel/carboplatin therapy: a multicenter collaborative study. Exp Ther Med 3(1):60–65. https://doi.org/10.3892/etm.2011.375

    Article  CAS  PubMed  Google Scholar 

  17. Kamei J, Hayashi S-S, Miyata S (2008) Effect of Gosha-jinki-gan on vincristine-induced painful neuropathy in mice. Jpn J Pharm Palliat Care Sci 1:19–24

    Google Scholar 

  18. Kawabata K, Kawajiri H, Takashima T, Nakano T, Mitukawa Y, Kawakami N (2013) P2-043 * reduction of paclitaxel-related peripheral sensory neuropathy by Gosha-jinki-gan or carbon dioxide feet and hand bathing. Ann Oncol 24:ix80

    Article  Google Scholar 

  19. Kono T, Mamiya N, Chisato N, Ebisawa Y, Yamazaki H, Watari J, Yamamoto Y, Suzuki S, Asama T, Kamiya K (2011) Efficacy of goshajinkigan for peripheral neurotoxicity of oxaliplatin in patients with advanced or recurrent colorectal cancer. Evid Based Compl Alternat Med 2011:418481

    Google Scholar 

  20. Kono T, Hata T, Morita S, Munemoto Y, Matsui T, Kojima H, Takemoto H, Fukunaga M, Nagata N, Shimada M, Sakamoto J, Mishima H (2013) Goshajinkigan oxaliplatin neurotoxicity evaluation (GONE): a phase 2, multicenter, randomized, double-blind, placebo-controlled trial of goshajinkigan to prevent oxaliplatin-induced neuropathy. Cancer Chemother Pharmacol 72(6):1283–1290. https://doi.org/10.1007/s00280-013-2306-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Kono T, Suzuki Y, Mizuno K, Miyagi C, Omiya Y, Sekine H, Mizuhara Y, Miyano K, Kase Y, Uezono Y (2015) Preventive effect of oral goshajinkigan on chronic oxaliplatin-induced hypoesthesia in rats. Sci Rep 5(1):16078. https://doi.org/10.1038/srep16078

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gotzsche PC, Ioannidis JP, Clarke M, Devereaux PJ, Kleijnen J, Moher D (2009) The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration. Ann Intern Med 151(4):W65–W94

    Article  PubMed  Google Scholar 

  23. Matsumura Y, Yokoyama Y, Hirakawa H, Shigeto T, Futagami M, Mizunuma H (2014) The prophylactic effects of a traditional Japanese medicine, goshajinkigan, on paclitaxel-induced peripheral neuropathy and its mechanism of action. Mol Pain 10:61

    Article  PubMed  PubMed Central  Google Scholar 

  24. Mizuno K, Kono T, Suzuki Y, Miyagi C, Omiya Y, Miyano K, Kase Y, Uezono Y (2014) Goshajinkigan, a traditional Japanese medicine, prevents oxaliplatin-induced acute peripheral neuropathy by suppressing functional alteration of TRP channels in rat. J Pharmacol Sci 125(1):91–98. https://doi.org/10.1254/jphs.13244FP

    Article  CAS  PubMed  Google Scholar 

  25. Mols F, Beijers T, Vreugdenhil G, van de Poll-Franse L (2014) Chemotherapy-induced peripheral neuropathy and its association with quality of life: a systematic review. Support Care Cancer 22(8):2261–2269. https://doi.org/10.1007/s00520-014-2255-7

    Article  PubMed  Google Scholar 

  26. Nishioka M, Shimada M, Kurita N, Iwata T, Morimoto S, Yoshikawa K, Higashijima J, Miyatani T, Kono T (2011) The Kampo medicine, Goshajinkigan, prevents neuropathy in patients treated by FOLFOX regimen. Int J Clin Oncol 16(4):322–327. https://doi.org/10.1007/s10147-010-0183-1

    Article  PubMed  Google Scholar 

  27. Oki E, Emi Y, Kojima H, Higashijima J, Kato T, Miyake Y, Kon M, Ogata Y, Takahashi K, Ishida H, Saeki H, Sakaguchi Y, Yamanaka T, Kono T, Tomita N, Baba H, Shirabe K, Kakeji Y, Maehara Y (2015) Preventive effect of Goshajinkigan on peripheral neurotoxicity of FOLFOX therapy (GENIUS trial): a placebo-controlled, double-blind, randomized phase III study. Int J Clin Oncol 20(4):767–775. https://doi.org/10.1007/s10147-015-0784-9

    Article  CAS  PubMed  Google Scholar 

  28. Pan X, Lopez-Olivo MA, Song J, Pratt G, Suarez-Almazor ME (2017) Systematic review of the methodological quality of controlled trials evaluating Chinese herbal medicine in patients with rheumatoid arthritis. BMJ Open 7(3):e013242. https://doi.org/10.1136/bmjopen-2016-013242

    Article  PubMed  PubMed Central  Google Scholar 

  29. Pereira TV, Horwitz RI, Ioannidis JP (2012) Empirical evaluation of very large treatment effects of medical interventions. JAMA 308(16):1676–1684. https://doi.org/10.1001/jama.2012.13444

    Article  CAS  PubMed  Google Scholar 

  30. Pike CT, Birnbaum HG, Muehlenbein CE, Pohl GM, Natale RB (2012) Healthcare costs and workloss burden of patients with chemotherapy-associated peripheral neuropathy in breast, ovarian, head and neck, and nonsmall cell lung cancer. Chemother Res Pract 2012:913848

    PubMed  PubMed Central  Google Scholar 

  31. Seretny M, Currie GL, Sena ES, Ramnarine S, Grant R, MacLeod MR, Colvin LA, Fallon M (2014) Incidence, prevalence, and predictors of chemotherapy-induced peripheral neuropathy: a systematic review and meta-analysis. Pain 155(12):2461–2470. https://doi.org/10.1016/j.pain.2014.09.020

    Article  PubMed  Google Scholar 

  32. Sweeting MJ, Sutton AJ, Lambert PC (2004) What to add to nothing? Use and avoidance of continuity corrections in meta-analysis of sparse data. Stat Med 23(9):1351–1375. https://doi.org/10.1002/sim.1761

    Article  PubMed  Google Scholar 

  33. Tawata M, Kurihara A, Nitta K, Iwase E, Gan N, Onaya T (1994) The effects of goshajinkigan, a herbal medicine, on subjective symptoms and vibratory threshold in patients with diabetic neuropathy. Diabetes Res Clin Pract 26(2):121–128. https://doi.org/10.1016/0168-8227(94)90149-X

    Article  CAS  PubMed  Google Scholar 

  34. UMIN000021361. Comparing investigation of the curative effect by Goshajinkigan and Pregabalin for -Induced Peripheral Neuropathy. (Accessed as of May 5, 2017). In: Editor (ed)^(eds) Book Comparing investigation of the curative effect by Goshajinkigan and Pregabalin for -Induced Peripheral Neuropathy. (Accessed as of May 5, 2017), City

  35. Ushio S, Egashira N, Sada H, Kawashiri T, Shirahama M, Masuguchi K, Oishi R (2012) Goshajinkigan reduces oxaliplatin-induced peripheral neuropathy without affecting anti-tumour efficacy in rodents. Eur J Cancer (Oxford, England: 1990) 48(9):1407–1413. https://doi.org/10.1016/j.ejca.2011.08.009

    Article  CAS  Google Scholar 

  36. Watanabe K, Shimada A, Miyaki K, Hirakata A, Matsuoka K, Omae K, Takei I (2014) Long-term effects of goshajinkigan in prevention of diabetic complications: a randomized open-labeled clinical trial. Evid Based Complement Alternat Med 2014:128726

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Yoshida N, Hosokawa T, Ishikawa T, Yagi N, Kokura S, Naito Y, Nakanishi M, Kokuba Y, Otsuji E, Kuroboshi H, Taniwaki M, Taguchi T, Hosoi H, Nakamura T, Miki T (2013) Efficacy of goshajinkigan for oxaliplatin-induced peripheral neuropathy in colorectal cancer patients. J Oncol 2013:139740

    Article  PubMed  PubMed Central  Google Scholar 

  38. Yoshimura K, Shimizu Y, Masui K, Okuno H, Ueda T, Soda T, Ogawa O (2012) Furosemide versus gosha-jinki-gan, a blended herbal medicine, for nocturnal polyuria: a randomized crossover trial. Lower Urinary Tract Symptoms 4(2):77–81. https://doi.org/10.1111/j.1757-5672.2011.00132.x

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of General Medicine, Emergency and Critical Care Center, Kurashiki Central Hospital, 1-1-1 Miwa Kurashiki, Okayama, 710-8602, Japan

    Akira Kuriyama

  2. Department of General Internal Medicine, Tottori Prefectural Central Hospital, 730 Ezu Tottori, Tottori, 680-0901, Japan

    Koji Endo

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  1. Akira Kuriyama
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Correspondence to Akira Kuriyama.

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The authors declare that they have no conflicts of interest.

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Kuriyama, A., Endo, K. Goshajinkigan for prevention of chemotherapy-induced peripheral neuropathy: a systematic review and meta-analysis. Support Care Cancer 26, 1051–1059 (2018). https://doi.org/10.1007/s00520-017-4028-6

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