International Journal of Clinical Oncology

, Volume 16, Issue 4, pp 322–327 | Cite as

The Kampo medicine, Goshajinkigan, prevents neuropathy in patients treated by FOLFOX regimen

  • Masanori Nishioka
  • Mitsuo Shimada
  • Nobuhiro Kurita
  • Takashi Iwata
  • Shinya Morimoto
  • Kozo Yoshikawa
  • Jun Higashijima
  • Tomohiko Miyatani
  • Toru Kono
Original Article

Abstract

Background

Oxaliplatin is now considered a standard treatment for advanced or unresectable colorectal cancer, but its main dose-limiting toxicity is sensory neuropathy. The OPTIMOX (stop and go) approach offers a reasonable strategy, but the preventive agent is not established. It is reported that the Kampo medicine, Goshajinkigan (GJG), has recently been considered an effective agent for the neuropathy of taxanes and for vibration sensation in patients with diabetic neuropathy. The aim of this study was to clarify the efficacy of GJG for peripheral neuropathy associated with oxaliplatin therapy.

Patients and method

From 2007, 45 patients treated with modified FOLFOX6 for non-resectable or recurrent colorectal cancer participated in the study. Twenty-two patients (GJG group) received oral administration of 7.5 g/day of GJG every day during mFOLFOX6 therapy and 23 patients (control group) did not receive GJG. Neuropathy was evaluated during every course according to DEB-NTC (Neurotoxicity Criteria of Debiopharm).

Results

The median number of cycles per patient in the GJG group was 13 (range 4–32), and in the control group was 12 (range 4–28). The cumulative dose of oxaliplatin was 1105 mg/m2 (GJG group) and 1120 mg/m2 (control group). The incidence of grade 3 peripheral neuropathy in the GJG group was significantly lower than in the control group (p < 0.01, log-rank test). The incidence of grade 3 peripheral neuropathy after 10 courses was 0% in the GJG group and 12% in the control group, and after 20 courses was 33% in the GJG group and 75% in the control group. The percentage of grade 2 and 3 peripheral neuropathy in the GJG group was lower than that in the control group. There were no differences in adverse effects between the two groups except for peripheral neuropathy and influence on tumor response.

Conclusion

The Kampo medicine, Goshajinkigan, is useful in preventing neuropathy in non-resectable or recurrent colorectal cancer patients treated with a FOLFOX regimen.

Keywords

Neuropathy Kampo medicine Goshajinkigan Oxaliplatin Colorectal cancer 

References

  1. 1.
    de Gramont A, Figer A, Seymour M et al (2000) Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. J Clin Oncol 18:2938–2947PubMedGoogle Scholar
  2. 2.
    Andre′ T, Boni C, Mounedji-Boudiaf L et al (2004) Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med 350:2343–2351CrossRefGoogle Scholar
  3. 3.
    Cassidy J, Misset J-L (2002) Oxaliplatin-related side effects: characteristics and management. Semin Oncol 29:11–20PubMedCrossRefGoogle Scholar
  4. 4.
    Krishnan AV, Goldstein D, Friedlander M et al (2005) Oxaliplatin-induced neurotoxicity and the development of neuropathy. Muscle Nerve 32:51–60PubMedCrossRefGoogle Scholar
  5. 5.
    Land SR, Kopec JA, Cecchini RS et al (2007) Neurotoxicity from oxaliplatin combined with weekly bolus fluorouracil and leucovorin as surgical adjuvant chemotherapy for stage II and III colon cancer: NSABP C-07. J Clin Oncol 25:2205–2211PubMedCrossRefGoogle Scholar
  6. 6.
    Tournigand C, Cervantes A, Figer A et al (2006) OPTIMOX1: a randomized study of FOLFOX4 or FOLFOX7 with oxaliplatin in a stop-and-go fashion in advanced colorectal cancer: GERCOR study. J Clin Oncol 24:394–400PubMedCrossRefGoogle Scholar
  7. 7.
    Gamelin L, Boisdron-Celle M, Delva R et al (2004) Prevention of oxaliplatin-related neurotoxicity by calcium and magnesium infusions: a retrospective study of 161 patients receiving oxaliplatin combined with 5-fluorouracil and leucovorin for advanced colorectal cancer. Clin Cancer Res 10:4055–4061PubMedCrossRefGoogle Scholar
  8. 8.
    Gamelin E, Gamelin L, Bossi L et al (2002) Clinical aspects and molecular basis of oxaliplatin neurotoxicity: current management and development of preventive measures. Semin Oncol 29:21–33PubMedCrossRefGoogle Scholar
  9. 9.
    Cascinu S, Catalano V, Cordella L et al (2002) Neuroprotective effect of reduced glutathione on oxaliplatin-based chemotherapy in advanced colorectal cancer: a randomized, double-blind, placebo-controlled trial. J Clin Oncol 20:3478–3483PubMedCrossRefGoogle Scholar
  10. 10.
    Lin PC, Lee MY, Wang WS et al (2006) N-acetylcysteine has neuroprotective effects against oxaliplatin-based adjuvant chemotherapy in colon cancer patients: preliminary data. Support Care Cancer 14:484–487PubMedCrossRefGoogle Scholar
  11. 11.
    Susman E (2006) Xaliproden lessens oxaliplatin-mediated neuropathy. Lancet Oncol 7(4):288PubMedCrossRefGoogle Scholar
  12. 12.
    von Delius S, Eckel F, Wagenpfeil S et al (2007) Carbamazepine for prevention of oxaliplatinrelated neurotoxicity in patients with advanced colorectal cancer: final results of a randomised, controlled, multicenter phase II study. Invest New Drugs 25:173–180CrossRefGoogle Scholar
  13. 13.
    Wang WS, Lin JK, Lin TC et al (2007) Oral glutamine is effective for preventing oxaliplatin-induced neuropathy in colorectal cancer patients. Oncologist 12(3):312–319PubMedCrossRefGoogle Scholar
  14. 14.
    Nagaki Y, Hayasaka S, Hayasaka Y et al (2003) Effects of goshajinkigan on corneal sensitivity, superficial punctate keratopathy and tear secretion in patients with insulin-dependent diabetes mellitus. Am J Chin Med 31:103–109PubMedCrossRefGoogle Scholar
  15. 15.
    Yao X, Chen H, Emura S et al (2007) Effects of hPTH (1–34) and Gosha-jinki-gan on the trabecular bone microarchitecture in ovariectomized rat tibia. Okajimas Folia Anat Jpn 83:107–113PubMedCrossRefGoogle Scholar
  16. 16.
    Yamamoto T, Murai T, Ueda M et al (2009) Clinical features of paclitaxel-induced peripheral neuropathy and role of Gosya-jinki-gan. Gan To Kagaku Ryoho 36(1):89–92PubMedGoogle Scholar
  17. 17.
    Uno T, Ohsawa I, Tokudome M et al (2005) Effects of Goshajinkigan on insulin resistance in patients with type 2 diabetes. Diabetes Res Clin Pract 69:129–135PubMedCrossRefGoogle Scholar
  18. 18.
    Kono T, Mamiya N, Chisato N et al (2009) Efficacy of Goshajinkigan for peripheral neurotoxicity of oxaliplatin in patients with advanced or recurrent colorectal cancer. Evid Based Complement Alternat Med. 1. (eCAM. doi:10.1093/ecam/nep200)
  19. 19.
    Shirao K, Matsumura Y, Yamada Y et al (2006) Phase I study of single-dose oxaliplatin in Japanese patients with malignant tumors. Jpn J Clin Oncol 36:295–300PubMedCrossRefGoogle Scholar
  20. 20.
    Therasse P, Arbuck SG, Eisenhauer EA et al (2000) New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 92:205–216PubMedCrossRefGoogle Scholar
  21. 21.
    Ishibashi K, Okada N, Miyazaki T et al (2010) Effect of calcium and magnesium on neurotoxicity and blood platinum concentrations in patients receiving mFOLFOX6 therapy: a prospective randomized study. Int J Clin Oncol 15(1):82–87PubMedCrossRefGoogle Scholar
  22. 22.
    Gwag BJ, Sessler FM, Robine V et al (1997) Endogenous glutamate levels regulate nerve growth factor mRNA expression in the rat dentate gyrus. Mol Cells 7:425–430PubMedGoogle Scholar
  23. 23.
    Daikhin Y, Yudkoff M (2000) Compartmentation of brain glutamate metabolism in neurons and glia. J Nutr 130(4S Suppl):1026S–1031SGoogle Scholar
  24. 24.
    Meijer C, de Vries EG, Marmiroli P et al (1999) Cisplatin-induced DNA-platination in experimental dorsal root ganglia neuronopathy. Neurotoxicology 20:883–887PubMedGoogle Scholar
  25. 25.
    Kono T, Mishima H, Shimada M et al (2009) GONE Investigators. Preventive effect of goshajinkigan on peripheral neurotoxicity of FOLFOX therapy: a placebo-controlled double-blind randomized phase II study (the GONE Study). Jpn J Clin Oncol 39(12):847–849PubMedCrossRefGoogle Scholar
  26. 26.
    Hochster HS, Grothey A, Childs BH (2007) Use of calcium and magnesium salts to reduce oxaliplatin-related neurotoxicity. J Clin Oncol 25:4028–4029PubMedCrossRefGoogle Scholar
  27. 27.
    Yamada K, Suzuki E, Nakaki T et al (2005) Aconiti tuber increases plasma nitrite and nitrate levels in humans. J Ethnopharmacol 96:165–169PubMedCrossRefGoogle Scholar
  28. 28.
    Gotoh A, Goto K, Sengoku A et al (2004) Inhibition mechanism of Gosha-jinki-gan on the micturition reflex in rats. J Pharmacol Sci 96:115–123PubMedCrossRefGoogle Scholar
  29. 29.
    Hu X, Sato J, Oshida Y et al (2003) Effect of Gosha-jinki-gan (Chinese herbal medicine: Niu-Che-Sen-Qi-Wan) on insulin resistance in streptozotocin-induced diabetic rats. Diabetes Res Clin Pract 59:103–111PubMedCrossRefGoogle Scholar
  30. 30.
    Joseph EK, Chen X, Bogen O et al (2008) Oxaliplatin acts on IB4-positive nociceptors to induce an oxidative stress-dependent acute painful peripheral neuropathy. J Pain 9(5):463–472Google Scholar
  31. 31.
    Imamura T, Ishizuka O, Aizawa N et al (2008) Gosha-jinki-gan reduces transmitter proteins and sensory receptors associated with C fiber activation induced by acetic acid in rat urinary bladder. Neurourol Urodyn 27(8):832–837PubMedCrossRefGoogle Scholar

Copyright information

© Japan Society of Clinical Oncology 2011

Authors and Affiliations

  • Masanori Nishioka
    • 1
  • Mitsuo Shimada
    • 1
  • Nobuhiro Kurita
    • 1
  • Takashi Iwata
    • 1
  • Shinya Morimoto
    • 1
  • Kozo Yoshikawa
    • 1
  • Jun Higashijima
    • 1
  • Tomohiko Miyatani
    • 1
  • Toru Kono
    • 2
  1. 1.Department of Surgery, Institute of Health BiosciencesThe University of TokushimaTokushimaJapan
  2. 2.Department of Surgery, Division of Gastroenterologic and General SurgeryAsahikawa Medical CollegeAsahikawaJapan

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