Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

N-acetylcysteine has neuroprotective effects against oxaliplatin-based adjuvant chemotherapy in colon cancer patients: preliminary data


Although adding oxaliplatin to fluorouracil and leucovorin in adjuvant chemotherapy for colon cancer may improve disease-free survival, grade 3–4 sensory neuropathy also increases. To determine whether oral N-acetylcysteine is neuroprotective against oxaliplatin-induced neuropathy, we did a pilot study. Fourteen stage III colon cancer patients with 4 or more regional lymph nodes metastasis (N2 disease) receiving adjuvant biweekly oxaliplatin (85 mg/m2) plus weekly fluorouracil boluses and low-dose leucovorin were randomized to oral N-acetylcysteine (1,200 mg) (arm A) or placebo (arm B). Clinical neurological and electrophysiological evaluations were performed at baseline and after 4, 8, and 12 treatment cycles. Treatment-related toxicity was evaluated based on National Cancer Institute (NCI) Criteria. After four cycles of chemotherapy, seven of nine patients in arm B and two of five in arm A experienced grade 1 sensory neuropathy. After eight cycles, five experienced sensory neuropathy (grade 2–4 toxicity) in arm B; none in arm A (p<0.05). After 12 cycles, grade 2–4 sensory neuropathy was observed in eight patients in arm B, one in arm A (p<0.05). There were no significant electrophysiological changes in arm A after 4, 8, or 12 cycles of chemotherapy. We concluded that oral N-acetylcysteine reduces the incidence of oxaliplatin-induced neuropathy in colon cancer patients receiving oxaliplatin-based adjuvant chemotherapy.

This is a preview of subscription content, log in to check access.


  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 l8:2938–2947

  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 350:2343–2351

  3. 3.

    Raymond E, Chaney SG, Taamma A, Cvitkovic E (1998) Oxaliplatin: a review of preclinical and clinical studies. Ann Oncol 9:1053–1071

  4. 4.

    Grolleau F, Gamelin L, Boisdron-Celle M et al (2001) A possible explanation for a neurotoxic effect of the anticancer agent oxaliplatin on neuronal voltage-gated sodium channels. J Neurophysiol 85:2293–2297

  5. 5.

    Cavaletti G, Tredici G, Petruccioli MG et al (2001) Effects of different schedules of oxaliplatin treatment on the peripheral nervous system of the rat. Eur J Cancer 37:2457–2463

  6. 6.

    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 20:3478–3483

  7. 7.

    Albini A, D’Agostini F, Giunciuglio D et al (1995) Inhibition of invasion, gelatinase activity, tumor take and metastasis of malignant cells by N-acetylcysteine. Int J Cancer 61:121–129

  8. 8.

    Roes EM, Raijmakers MT, Peters WH, Steegers EA (2002) Effects of oral N-acetylcysteine on plasma homocysteine and whole blood glutathione levels in healthy, non-pregnant women. Clin Chem Lab Med 40:496–498

  9. 9.

    de Luis D, Fernandez N, Aller R (2004) Homocysteine in patients with diabetes mellitus. Med Clin (Barc) 22:27–32

  10. 10.

    Maler JM, Seifert W, Huther G et al (2003) Homocysteine induces cell death of rat astrocytes in vitro. Neurosci Lett 347:85–88

  11. 11.

    Borgstrom L, Kagedal B (1990) Dose dependent pharmacokinetics of N-acetylcysteine after oral dosing to man. Biopharm Drug Dispos 11:131–136

  12. 12.

    Pendyala L, Creaven PJ (1995) Pharmacokinetic and pharmacodynamic studies of N-acetylcysteine, a potential chemopreventive agent during a phase I trial. Cancer Epidemiol Biomarkers Prev 4:245–251

  13. 13.

    Park SA, Choi KS, Bang JH, Huh K, Kim SU (2000) Cisplatin-induced apoptotic cell death in mouse hybrid neurons is blocked by antioxidants through suppression of cisplatin-mediated accumulation of p53 but not of Fas/Fas ligand. J Neurochem 75:946–953

  14. 14.

    Krishnan AV, Goldstein D, Friedlander M, Kiernan MC (2005) Oxaliplatin-induced neurotoxicity and the development of neuropathy. Muscle Nerve 32:51–60

  15. 15.

    Lehky TJ, Leonard GD, Wilson RH, Grem JL, Floeter MK (2004) Oxaliplatin-induced neurotoxicity: acute hyperexcitability and chronic neuropathy. Muscle Nerve 29:387–392

Download references


The authors would like to thank the Taiwan Cancer Foundation and Taipei Veterans General Hospital for support.

Author information

Correspondence to Tzeon-Jye Chiou.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Lin, P., Lee, M., Wang, W. et al. N-acetylcysteine has neuroprotective effects against oxaliplatin-based adjuvant chemotherapy in colon cancer patients: preliminary data. Support Care Cancer 14, 484–487 (2006).

Download citation


  • N-Acetylcysteine
  • Oxaliplatin-based adjuvant chemotherapy
  • Colon cancer