Supportive Care in Cancer

, Volume 21, Issue 5, pp 1313–1319 | Cite as

Identification of clinical predictive factors of oxaliplatin-induced chronic peripheral neuropathy in colorectal cancer patients treated with adjuvant Folfox IV

  • Bruno Vincenzi
  • Anna Maria Frezza
  • Gaia Schiavon
  • Chiara SpotoEmail author
  • Raffaele Addeo
  • Vincenzo Catalano
  • Francesco Graziano
  • Daniele Santini
  • Giuseppe Tonini
Original Article



Oxaliplatin-induced neuropathy is a dose-related side effect which occurs in almost 40 % of patients treated with oxaliplatin. Aim of the present study was to identify reliable clinical factors predicting its development and duration.


One hundred sixty-nine completely resected colorectal cancer patients treated with adjuvant Folfox IV regimen were retrospectively included. The following pre-treatment clinical parameters were collected: hypocalcaemia, hypomagnesaemia, hypoalbuminaemia, anaemia, diabetes, chronic renal failure (CRF), folate deficiency, vitamin B12 deficiency, number of cycles received and habit to alcohol consumption. Incidence, grade (NCI-CTCAE v.3) and duration of neuropathy were recorded.


Incidence of neuropathy was found to be higher in patients with pre-treatment anaemia (p = 0.001), hypoalbuminaemia (p = 0.01) and hypomagnesaemia (p = 0.001) as well in those with habit to alcohol consumption (p = 0.003). Neuropathy durations were conversely associated with age, being longer in younger patients (p = 0.03), and again with hypoalbuminaemia (p = 0.04) and hypomagnesaemia (p = 0.002). No correlation was found with gender, hypocalcaemia, diabetes and CRF. The correlation between vitamin B12 and folate levels and the development of neurotoxicity were not analysed because of the high number of missing data in the population.


Age, anaemia, hypoalbuminaemia, hypomagnesaemia and alcohol consumption are reliable and easily assessable clinical factors predicting incidence and length of oxaliplatin-induced neuropathy.


Oxaliplatin-induced neuropathy Colorectal cancer Neurotoxicity Clinical predictive factors 


Conflict of interest

Authors have not any conflict of interest to declare.


  1. 1.
    André T, Boni C, Mounedji-Boudiaf L et al (2004) Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. Multicenter International Study of Oxaliplatin/5-Fluorouracil/Leucovorin in the Adjuvant Treatment of Colon Cancer (MOSAIC) Investigators. N Engl J Med 350:2343–2351PubMedCrossRefGoogle Scholar
  2. 2.
    Haller DG, Tabernero J, Maroun J et al (2011) Capecitabine plus oxaliplatin compared with fluorouracil and folinic acid as adjuvant therapy for stage III colon cancer. J Clin Oncol 29:1465–1471PubMedCrossRefGoogle Scholar
  3. 3.
    Attal N, Bouhassira D, Gautron M et al (2009) Thermal hyperalgesia as a marker of oxaliplatin neurotoxicity: a prospective quantified sensory assessment study. Pain 144:245–252PubMedCrossRefGoogle Scholar
  4. 4.
    Won HH, Lee J, Park JO et al (2012) Polymorphic markers associated with severe oxaliplatin-induced, chronic peripheral neuropathy in colon cancer patients. Cancer 118(11):2828–2836PubMedCrossRefGoogle Scholar
  5. 5.
    Cancer Therapy Evaluation Program, Common terminology criteria for adverse events, version 3.0, DCTD, NCI, NIH, DHHS March 31, 2003 (, Publish Date: August 9, 2006
  6. 6.
    Engelen W, Bouten A, De Leeuw I, De Block C (2000) Are low magnesium levels in type 1 diabetes associated with electromyographical signs of polyneuropathy? Magnes Res 13:197–203PubMedGoogle Scholar
  7. 7.
    De Leeuw I, Engelen W, De Block C, Van Gaal L (2004) Long-term magnesium supplementation influences favourably the natural evolution of neuropathy in Mg-depleted type 1 diabetic patients (T1dm). Magnes Res 17:109–114PubMedGoogle Scholar
  8. 8.
    Grothey A, Nikcevich DA, Sloan JA et al (2011) Intravenous calcium and magnesium for oxaliplatin-induced sensory neurotoxicity in adjuvant colon cancer: NCCTG N04C7. J Clin Oncol 29:421–427PubMedCrossRefGoogle Scholar
  9. 9.
    Gamelin L, Boisdron-Celle M, Delva R et al (2004) Prevention of oxaliplatin-related neurotoxicity by calcium and magnesium infusion: 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
  10. 10.
    Grothey A, Hart LL, Rowland KM et al (2008) Intermittent oxaliplatin administration and time-to-treatment-failure (TTF) in metastatic colorectal cancer (mCRC): final results of the phase III CONcePT trial. J Clin Oncol 26:2008Google Scholar
  11. 11.
    Ferrari LF, Levine JD (2010) Alcohol consumption enhances antiretroviral painful peripheral neuropathy by mitochondrial mechanisms. Eur J Neurosci 32:811–818PubMedCrossRefGoogle Scholar
  12. 12.
    Ramanathan RK, Rothenberg ML, de Gramont A (2010) Incidence and evolution of oxaliplatin-induced peripheral sensory neuropathy in diabetic patients with colorectal cancer: a pooled analysis of three phase III studies. Ann Oncol 21:754–758PubMedCrossRefGoogle Scholar
  13. 13.
    Goldberg RM, Tabah-Fisch I, Bleiberg H et al (2006) Pooled analysis of safety and efficacy of oxaliplatin plus fluorouracil/leucovorin administered bimonthly in elderly patients with colorectal cancer. J Clin Oncol 24:4085–4091PubMedCrossRefGoogle Scholar
  14. 14.
    Yang YH, Lin JK, Chen WS et al (2012) Duloxetine improves oxaliplatin-induced neuropathy in patients with colorectal cancer: an open-label pilot study. Support Care Cancer 20(7):1491–1497PubMedCrossRefGoogle Scholar
  15. 15.
    Durand JP, Deplanque G, Montheil V et al (2012) Efficacy of venlafaxine for the prevention and relief of oxaliplatin-induced acute neurotoxicity: results of EFFOX, a randomized, double-blind, placebo-controlled phase III trial. Ann Oncol 23:200–205PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Bruno Vincenzi
    • 1
  • Anna Maria Frezza
    • 1
  • Gaia Schiavon
    • 2
  • Chiara Spoto
    • 1
    Email author
  • Raffaele Addeo
    • 3
  • Vincenzo Catalano
    • 4
  • Francesco Graziano
    • 5
  • Daniele Santini
    • 1
  • Giuseppe Tonini
    • 1
  1. 1.Medical OncologyUniversità Campus Bio-MedicoRomeItaly
  2. 2.Department of Medical OncologyErasmus University Medical Center–Daniel den Hoed Cancer CenterRotterdamNetherlands
  3. 3.Ospedale San Giovanni Di DioFrattaminoreItaly
  4. 4.UOC OncologiaA.O. “Ospedali Riuniti Marche Nord”PesaroItaly
  5. 5.Dipartimento di Medicina OncologicaOspedale di UrbinoUrbinoItaly

Personalised recommendations