Advertisement

Oxaliplatin-Induced Neuropathy: A Long-Term Clinical and Neurophysiologic Follow-Up Study

Published:February 25, 2016DOI:https://doi.org/10.1016/j.clcc.2016.02.009

      Abstract

      Background

      Oxaliplatin is an effective drug used mainly for advanced colorectal cancer. Neurotoxicity is the major side effect of oxaliplatin. The present clinical and neurophysiologic study was conducted to evaluate patients receiving oxaliplatin therapy.

      Patients and Methods

      Thirty-one consecutive patients with colorectal cancer who received oxaliplatin therapy were followed up for more than 3 years. The patients underwent clinical and neurophysiologic tests for large and small fiber function at every visit.

      Results

      Most of the patients received oxaliplatin-based chemotherapy at the initial dose of 130 mg/m2 for 6 to 8 cycles, normally every 3 weeks. Acute neurotoxicity with cold and mechanical hyperalgesia was reported by the vast majority of patients after each cycle of therapy and was confirmed by the quantitative sensory, filament, and axon reflex test. Chronic sensory cumulative neuropathy developed in most of the patients after the middle of therapy with numbness and was assessed using clinical scales, nerve conduction studies, and the vibration threshold. Our results support the persistence of the sensory nerve deficits for years after cessation of oxaliplatin therapy.

      Conclusion

      Our study has confirmed the results of a few previous long-term studies concerning the persistence of chronic large sensory fiber neuropathy and the influence of the cumulative dose of oxaliplatin on the development and severity of the chronic neuropathy. Our findings have improved the knowledge about the acute oxaliplatin-induced neurotoxicity using the C-fiber axon reflex response.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Clinical Colorectal Cancer
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • André T.
        • Boni C.
        • Navarro M.
        • et al.
        Improved overall survival with oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment in stage II or III colon cancer in the MOSAIC trial.
        J Clin Oncol. 2009; 27: 3109-3116
        • Haller D.G.
        • Tabernero J.
        • Maroun J.
        • et al.
        Capecitabine plus oxaliplatin compared with fluorouracil and folinic acid as adjuvant therapy for stage III colon cancer.
        J Clin Oncol. 2011; 29: 1465-1471
        • Ducreux M.
        • Bennouna J.
        • Hebbar M.
        • et al.
        Capecitabine plus oxaliplatin (XELOX) versus 5-fluorouracil/leucovorin plus oxaliplatin (FOLFOX-6) as first-line treatment for metastatic colorectal cancer.
        Int J Cancer. 2011; 128: 682-690
        • Krishnan A.V.
        • Goldstein D.
        • Friedlander M.
        • Kiernan M.C.
        Oxaliplatin-induced neurotoxicity and the development of neuropathy.
        Muscle Nerve. 2005; 32: 51-60
        • Park S.B.
        • Goldstein D.
        • Lin C.S.Y.
        • et al.
        Acute abnormalities of sensory nerve function associated with oxaliplatin-induced neurotoxicity.
        J Clin Oncol. 2009; 27: 1243-1249
        • Grothey A.
        Oxaliplatin-safety profile: neurotoxicity.
        Semin Oncol. 2003; 30: 5-13
        • Pietrangeli A.
        • Leandri M.
        • Terzoli E.
        • Jandolo B.
        • Garufi C.
        Persistence of high-dose oxaliplatin-induced neuropathy at long-term follow-up.
        Eur Neurol. 2006; 56: 13-16
        • Park S.B.
        • Lin C.S.
        • Krishnan A.V.
        • Goldstein D.
        • Friedlander M.L.
        • Kiernan M.C.
        Long-term neuropathy after oxaliplatin treatment: challenging the dictum of reversibility.
        Oncologist. 2011; 16: 708-716
        • Beijers A.J.M.
        • Mols F.
        • Vreugdenhil G.
        A systematic review on chronic oxaliplatin-induced peripheral neuropathy and the relation with oxaliplatin administration.
        Support Care Cancer. 2014; 22: 1999-2007
        • Labianca R.
        • Nordlinger B.
        • Beretta G.D.
        • et al.
        Early colon cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up.
        Ann Oncol. 2013; 24: 64-72
      1. Available at: ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm.

      2. Available at: https://cancerstaging.org/references-tools/quickreferences/pages/default.aspx.

        • Burakgazi A.Z.
        • Messermith W.
        • Vaidya D.
        • Hauer P.
        • Hoke A.
        • Polydefkis M.
        Longitudinal assessment of oxaliplatin-induced neuropathy.
        Neurology. 2011; 77: 980-986
        • Binder A.
        • Stengel M.
        • Maag R.
        • et al.
        Pain in oxaliplatin-induced neuropathy—sensitisation in the peripheral and central nociceptive system.
        Eur J Cancer. 2007; 43: 2658-2663
        • Baron R.
        Mechanisms of disease: neuropathic pain—a clinical perspective.
        Nat Clin Pract Neurol. 2006; 2: 95-106
        • Kokotis P.
        • Schmelz M.
        • Papagianni A.E.
        • Zambelis T.
        • Karandreas N.
        Objective assessment of C-fiber function by electrically induced axon reflex flare in patients with axonal and demyelinating polyneuropathy.
        J Clin Neurophysiol. 2013; 30: 422-427
        • de Gramont A.
        • Figer A.
        • Seymour M.
        • et al.
        Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer.
        J Clin Oncol. 2000; 18: 2938-2947
        • Raymond E.
        • Faivre S.
        • Woynarowski J.M.
        • et al.
        Oxaliplatin: mechanism of action and antineoplastic activity.
        Semin Oncol. 1998; 25: 4-12
        • André T.
        • Boni C.
        • Mounedji-Boudiaf L.
        • et al.
        Oxaliplatin, 5-fluorouracil, leucovorin as adjuvant treatment for colon cancer.
        N Engl J Med. 2004; 350: 2343-2351
        • Grothey A.
        • Goldberg R.M.
        A review of oxaliplatin and its clinical use in colorectal cancer.
        Expert Opin Pharmacother. 2004; 5: 2159-2170
        • Cavaletti G.
        • Tredici G.
        • Petruccioli M.G.
        • et al.
        Effects of different schedules of oxaliplatin treatment on the peripheral nervous system of the rat.
        Eur J Cancer. 2001; 37: 2457-2463
        • Screnci D.
        • McKeage M.J.
        • Galettis P.
        • Hambley T.W.
        • Palmer B.D.
        • Baguley B.C.
        Relationships between hydrophobicity, reactivity, accumulation and peripheral nerve toxicity of a series of platinum drugs.
        Br J Cancer. 2000; 82: 966-972
        • Pasetto L.M.
        • D'Andrea M.R.
        • Rossi E.
        • Monfardini S.
        Oxaliplatin-related neurotoxicity: how and why?.
        Crit Rev Oncol Hematol. 2006; 59: 159-168