Prevalence of Oxaliplatin-induced Chronic Neuropathy and Influencing Factors in Patients with Colorectal Cancer in Iran

  • Shahriari-Ahmadi, Ali (Rasoul-e-Akram Hospital, Hematology and Medical Oncology Ward, Iran University of Medical Sciences) ;
  • Fahimi, Ali (Rasoul-e-Akram Hospital, Hematology and Medical Oncology Ward, Iran University of Medical Sciences) ;
  • Payandeh, Mehrdad (Department of Hematology and Medical Oncology, Kermanshah University of Medical Sciences) ;
  • Sadeghi, Masoud (Medical Biology Research Center, Kermanshah University of Medical Sciences)
  • Published : 2015.12.03


Background: The chemotherapeutic agent oxaliplatin can cause acute and chronic forms of peripheral neuropathy. The aim of this study was to evaluate the incidence of chronic neuropathy and its risk factors in colorectal cancer (CRC) patients treated with FOLFOX or XELOX regimens in the Oncology Ward of Hazrate-Rasoul Hospital in Tehran. Materials and Methods: A total of 130 patients with CRC were entered into our study, aged over 18 years, without history of receiving other neurotoxic agents or other predisposing factors such as diabetes or neurologic diseases and kidney and liver dysfunction. For the FOLFOX regimen, patients received oxaliplatin, 85mg/m2, every 2 weeks for 12 courses and with the XELOX regimen, oxaliplatin was $130mg/m^2$, every 3 weeks for 8 courses. Based on Common Toxicity Criteria (CTC or NCI-CTC v.3), the patients were divided into 5 groups (grades) based on the severity of their symptoms. Results: Fifty-seven patients (43.8%) were male and 73(56.2%) female. Some 19 patients (14.7%) had BMI<20, 97(74.6%) were between 20-25 and 14 (10.8%) ${\geq}25$. In 105 patients (80.7%) neuropathy was found. There was significant correlation between BMI, hypomagnesaemia and especially, severity of anemia in patients with neuropathy compared to those without. Conclusions: Oxaliplatin regimens can induce chronic neuropathy in CRC patients, with anemia, high BMI and hypomagnesaemia as risk factors that can predispose to this kind of neurotoxicity.


  1. Alejandro LM, Behrendt CE, Chen K, Openshaw H, Shibata S (2013). Predicting acute and persistent neuropathy associated with oxaliplatin. Am J Clin Oncol, 36, 331-7.
  2. Andre T, Boni C, Mounedji-Boudiaf L, et al (2004). Multicenter International Study of Oxaliplatin/5-Fluorouracil/Leucovorin in the Adjuvant Treatment of Colon Cancer (MOSAIC) Investigators. Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med, 350, 2343-51.
  3. Argyriou AA, Bruna J, Marmiroli P, Cavaletti G(2012). Chemotherapy-induced peripheral neurotoxicity (CIPN): an update. Crit Rev Oncol Hematol, 82, 51-77.
  4. Argyriou AA, Polychronopoulos P, Iconomou G, et al (2007). Incidence and characteristics of peripheral neuropathy during oxaliplatin-based chemotherapy for metastatic colon cancer. Acta Oncol, 46, 1131-7.
  5. Argyriou AA, Zolota V, Kyriakopoulou O, Kalofonos HP(2010). Toxic peripheral neuropathy associated with commonly used chemotherapeutic agents. J BUON, 15, 435-46.
  6. Azadeh S, Moghimi-Dehkordi B, Fatem SR, et al (2008). Colorectal cancer in Iran: an epidemiological study. Asian Pac J Cancer Prev, 9, 123-6.
  7. Baek KK, Lee J, Park SH, et al (2010). Oxaliplatin-induced chronic peripheral neurotoxicity: a prospective analysis in patients with colorectal cancer. Cancer Res Treat, 42, 185-90.
  8. Cassidy J, Clarke S, Diaz-Rubio E, et al (2011). XELOX vs FOLFOX-4 as first-line therapy for metastatic colorectal cancer: NO16966 updated results. Br J Cance, 105, 58-64.
  9. Cassidy J, Tabernero J, Twelves C, et al (2004). XELOX (capecitabine plus oxaliplatin): active first-line therapy for patients with metastatic colorectal cancer. J Clin Oncol, 22, 2084-91.
  10. Cersosimo RJ(2005). Oxaliplatin-associated neuropathy: a review. The Annals of Pharmacology, 39, 128-35.
  11. Chau I, Cunningham D(2006). Adjuvant therapy in colon cancer- -what, when and how? Ann Oncol, 17, 1347-59.
  12. 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, 2938-47.
  13. 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, 4055-61.
  14. Gamelin E, Gamelin L, Bossi L, Quasthoff S(2002). Clinical aspects and molecular basis of oxaliplatin neurotoxicity: current management and development of preventive measures. Semin Oncol, 29, 21-33.
  15. Kalofonos HP, Aravantinos G, Kosmidis P, et al (2005). Irinotecan or oxaliplatin combined with leucovorin and 5-fluorouracil as first-line treatment in advanced colorectal cancer: a multicenter, randomized, phase II study. Ann Oncol, 16, 869-77.
  16. Kono T, Satomi M, Asama T, et al (2010). Cetuximabinduced hypomagnesaemia aggravates peripheral sensory neurotoxicity caused by oxaliplatin. J Gastrointest Oncol, 1, 97-101.
  17. Meyerhardt JA, Tepper JE, Niedzwiecki D, et al (2004). Impact of body mass index on outcomes and treatment-related toxicity in patients with stage II and III rectal cancer: findings from Intergroup Trial 0114. J Clin Oncol, 22, 648-57.
  18. Park SB, Goldstein D, Lin CS, et al(2009). Acute abnormalities of sensory nerve function associated with oxaliplatininduced neurotoxicity. J Clin Oncol, 27, 1243-9.
  19. Payandeh M, Sadeghi M, Sadeghi E, Gholami F (2015). Analysis of KRAS, BRAF and NRAS in Patients with Colorectal Cancer: the First Report of Western Iran. Am J Cancer Prev, 3, 19-22.
  20. Rothenberg ML, Cox JV, Butts C, et al (2008). Capecitabine plus oxaliplatin (XELOX) versus 5-fluorouracil/folinic acid plus oxaliplatin (FOLFOX-4) as second-line therapy in metastatic colorectal cancer: a randomized phase III noninferiority study. Ann Oncol, 19, 1720-6.
  21. Saif MW, Wilson RH, Harold N, et al (2001). Peripheral neuropathy associated with weekly oral 5-fluorouracil, leucovorin and eniluracil. Anticancer Drugs, 12, 525-31.
  22. Sittl R, Lampert A, Huth T, et al (2012). Anticancer drug oxaliplatin induces acute cooling-aggravated neuropathy via sodium channel subtype Na(V)1.6-resurgent and persistent current. Proc Natl Acad Sci U S A, 109, 6704-9.
  23. Stone WL, Krishnan K, Campbell SE, et al (2004). Tocopherols and the treatment of colon cancer. Ann NY Acad Sci, 1031, 223-33.
  24. Storey DJ, Sakala M, McLean CM, et al (2010). Capecitabine combined with oxaliplatin (CapOx) in clinical practice: how significant is peripheral neuropathy? Ann Oncol, 21, 1657-61.
  25. Vincenzi B, Frezza AM, Schiavon G, et al (2013). Identification of clinical predictive factors of oxaliplatin-induced chronic peripheral neuropathy in colorectal cancer patients treated with adjuvant Folfox IV. Support Care Cancer, 21, 1313-9.

Cited by

  1. Long-term chemotherapy-induced peripheral neuropathy among breast cancer survivors: prevalence, risk factors, and fall risk vol.159, pp.2, 2016,
  2. Fit for Chemo: Nerves May Thank You vol.109, pp.2, 2017,
  3. Chemotherapy-induced peripheral neuropathy: A current review vol.81, pp.6, 2017,
  4. Risk factors for paclitaxel-induced peripheral neuropathy in patients with breast cancer vol.18, pp.1, 2018,
  5. Chemotherapy-induced peripheral neuropathy in breast cancer patients treated with eribulin: interim data from a post-marketing observational study pp.1880-4233, 2018,
  6. Incidence and disease burden of chemotherapy-induced peripheral neuropathy in a population-based cohort vol.89, pp.6, 2018,