Skip to main content

Advertisement

SpringerLink
Log in

A descriptive study of persistent oxaliplatin-induced peripheral neuropathy in patients with colorectal cancer

  • Original Article
  • Published:
Supportive Care in Cancer Aims and scope Submit manuscript

Abstract

Background

Prolonged neurotoxicity after systemic chemotherapy has the potential to impact on quality of life. We explored the frequency of persistent peripheral neuropathy in patients who received oxaliplatin for colorectal cancer at two local centres.

Patients and methods

Questionnaires were sent to patients who completed treatment with oxaliplatin for colorectal cancer at least 20 months prior to entering the study. Neuropathy questions were adapted from the FACT/GOG-Ntx (V.4) questionnaire.

Results

Of the 56 eligible patients, 27 returned the questionnaire. Twenty-five patients (93 %) experienced neuropathic symptoms during their treatment; 11 had grade-2, and two had grade-3 symptoms. At the time of completing the questionnaire, 17 patients (63.0 %; 95%CI 43.9–79.4 %) were still symptomatic with 12 patients (44.4 %; 95%CI 26.8–63.3) having grade-2 or grade-3 symptoms and three patients (11.1 %; 95%CI 2.9–27.3) having grade-3 neuropathic symptoms. Participants who received more than 900 mg/m2 oxaliplatin had a significantly higher risk of persistent grade-2 or grade-3 neuropathy (p = 0.031, RR = 8.3 95%CI = 1.2–57.4). There was a trend toward increased risk of persistent neuropathy of any grade among participants with a history of regular alcohol use (p = 0.051; RR = 1.7 95%CI 1.0–2.8).

Conclusion

Persistent oxaliplatin-induced neuropathy is not as uncommon as previously suggested, and the rate of grade-2 and grade-3 symptoms could be considerably higher than previous reports.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011) Global cancer statistics. CA Cancer J Clin 61(2):69–90

    Article  PubMed  Google Scholar 

  2. Center MM, Jemal A, Smith RA, Ward E (2009) Worldwide variations in colorectal cancer. CA Cancer J Clin 59(6):366–378

    Article  PubMed  Google Scholar 

  3. Edwards BK, Ward E, Kohler BA et al (2010) Annual report to the nation on the status of cancer, 1975–2006, featuring colorectal cancer trends and impact of interventions (risk factors, screening, and treatment) to reduce future rates. Cancer 116(3):544–573

    Article  PubMed Central  PubMed  Google Scholar 

  4. Jemal A, Center MM, Desantis C, Ward EM (2010) Global patterns of cancer incidence and mortality rates and trends. Cancer Epidemiol Biomark Prev Publ Am Assoc Cancer Res cosponsored by the Am Soc Prev Oncol 19(8):1893–1907

    Google Scholar 

  5. Andre T, Boni C, Mounedji-Boudiaf L et al (2004) Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Eng J Med 350(23):2343–2351

    Article  CAS  Google Scholar 

  6. 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 Off J Am Soc Clin Oncol 18(16):2938–2947

    Google Scholar 

  7. Grothey A, Sargent D, Goldberg RM, Schmoll HJ (2004) Survival of patients with advanced colorectal cancer improves with the availability of fluorouracil-leucovorin, irinotecan, and oxaliplatin in the course of treatment. J Clin Oncol Off J Am Soc Clin Oncol 22(7):1209–1214

    Article  CAS  Google Scholar 

  8. Kuebler JP, Wieand HS, O'connell MJ et al (2007) Oxaliplatin combined with weekly bolus fluorouracil and leucovorin as surgical adjuvant chemotherapy for stage II and III colon cancer: results from NSABP C-07. J Clin Oncol Off J Am Soc Clin Oncol 25(16):2198–2204

    Article  CAS  Google Scholar 

  9. Cunningham D, Starling N, Rao S et al (2008) Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Eng J Med 358(1):36–46

    Article  CAS  Google Scholar 

  10. Conroy T, Desseigne F, Ychou M et al (2011) FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Eng J Med 364(19):1817–1825

    Article  CAS  Google Scholar 

  11. Grothey A (2003) Oxaliplatin-safety profile: neurotoxicity. Semin Oncol 30(4 Suppl 15):5–13

    Article  CAS  PubMed  Google Scholar 

  12. Argyriou AA, Polychronopoulos P, Iconomou G, Chroni E, Kalofonos HP (2008) A review on oxaliplatin-induced peripheral nerve damage. Cancer Treat Rev 34(4):368–377

    Article  CAS  PubMed  Google Scholar 

  13. Saif MW, Reardon J (2005) Management of oxaliplatin-induced peripheral neuropathy. Ther Clin Risk Manag 1(4):249–258

    CAS  PubMed Central  PubMed  Google Scholar 

  14. Jamieson SM, Liu J, Connor B, Mckeage MJ (2005) Oxaliplatin causes selective atrophy of a subpopulation of dorsal root ganglion neurons without inducing cell loss. Cancer Chemother Pharmacol 56(4):391–399

    Article  CAS  PubMed  Google Scholar 

  15. Scuteri A, Galimberti A, Ravasi M et al (2010) NGF protects dorsal root ganglion neurons from oxaliplatin by modulating JNK/Sapk and ERK1/2. Neurosci Lett 486(3):141–145

    Article  CAS  PubMed  Google Scholar 

  16. Ta LE, Espeset L, Podratz J, Windebank AJ (2006) Neurotoxicity of oxaliplatin and cisplatin for dorsal root ganglion neurons correlates with platinum-DNA binding. Neurotoxicology 27(6):992–1002

    Article  CAS  PubMed  Google Scholar 

  17. Grothey A (2005) Clinical management of oxaliplatin-associated neurotoxicity. Clin Color Cancer 5(Suppl 1):S38–S46

    CAS  Google Scholar 

  18. Andre T, Boni C, Navarro M et al (2009) 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 Off J Am Soc Clin Oncol 27(19):3109–3116

    Article  CAS  Google Scholar 

  19. Park SB, Lin CS, Krishnan AV, Goldstein D, Friedlander ML, Kiernan MC (2011) Long-term neuropathy after oxaliplatin treatment: challenging the dictum of reversibility. Oncologist 16(5):708–716

    Article  CAS  PubMed  Google Scholar 

  20. Denlinger CS, Barsevick AM (2009) The challenges of colorectal cancer survivorship. J Nat Compr Cancer Netw JNCCN 7(8):883–893, quiz 894

    Google Scholar 

  21. Calhoun EA, Welshman EE, Chang CH et al (2003) Psychometric evaluation of the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (Fact/GOG-Ntx) questionnaire for patients receiving systemic chemotherapy. Int J Gynecol Cancer Off J Int Gynecol Cancer Soc 13(6):741–748

    Article  CAS  Google Scholar 

  22. Huang HQ, Brady MF, Cella D, Fleming G (2007) Validation and reduction of FACT/GOG-Ntx subscale for platinum/paclitaxel-induced neurologic symptoms: a gynecologic oncology group study. Int J Gynecol Cancer Off J Int Gynecol Cancer Soc 17(2):387–393

    Article  CAS  Google Scholar 

  23. 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 Off J Am Soc Clin Oncol 25(16):2205–2211

    Article  CAS  Google Scholar 

  24. Cassidy J, Misset JL (2002) Oxaliplatin-related side effects: characteristics and management. Semin Oncol 29(5 Suppl 15):11–20

    Article  CAS  PubMed  Google Scholar 

  25. Combination chemotherapy after surgery in treating patients with high-risk stage II or stage III colorectal cancer: clinicaltrials.gov Identifier: NCT00749450. http://clinicaltrials.gov/ct2/show/NCT00749450. Accessed 25 August 2013

  26. Koike H, Iijima M, Sugiura M et al (2003) Alcoholic neuropathy is clinicopathologically distinct from thiamine-deficiency neuropathy. Ann Neurol 54(1):19–29

    Article  PubMed  Google Scholar 

  27. D'amour ML, Bruneau J, Butterworth RF (1991) Abnormalities of peripheral nerve conduction in relation to thiamine status in alcoholic patients. Can J Neurol Sci Le journal canadien des sciences neurologiques 18(2):126–128

    Google Scholar 

  28. Chopra K, Tiwari V (2012) Alcoholic neuropathy: possible mechanisms and future treatment possibilities. Br J Clin Pharmacol 73(3):348–362

    Article  CAS  PubMed  Google Scholar 

  29. Uwah AN, Ackler J, Leighton JC Jr, Pomerantz S, Tester W (2012) The effect of diabetes on oxaliplatin-induced peripheral neuropathy. Clin Color Cancer 11(4):275–279

    Article  CAS  Google Scholar 

  30. 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 Off J Multinatl Assoc Support Care Cancer 21(5):1313–1319

    Google Scholar 

  31. Oguri T, Mitsuma A, Inada-Inoue M et al (2013) Genetic polymorphisms associated with oxaliplatin-induced peripheral neurotoxicity in Japanese patients with colorectal cancer. Int J Clin Pharmacol Ther 51(6):475–481

    Article  CAS  PubMed  Google Scholar 

  32. 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 Off J Am Assoc Cancer Res 10(12 Pt 1):4055–4061

    Article  CAS  Google Scholar 

  33. Wen F, Zhou Y, Wang W et al (2013) Ca/Mg infusions for the prevention of oxaliplatin-related neurotoxicity in patients with colorectal cancer: a meta-analysis. Annal Oncol Off J Eur Soc Med Oncol / ESMO 24(1):171–178

    Article  CAS  Google Scholar 

  34. 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 Off J Am Soc Clin Oncol 29(4):421–427

    Article  CAS  Google Scholar 

  35. Khattak MA (2011) Calcium and magnesium prophylaxis for oxaliplatin-related neurotoxicity: is it a trade-off between drug efficacy and toxicity? Oncologist 16(12):1780–1783

    Article  CAS  PubMed  Google Scholar 

  36. Charles L. Loprinzi RQ, Shaker R. Dakhil, Louis Fehrenbacher, Philip J. Stella, Pamela J. Atherton, Drew K. Seisler, Rubina Qamar, Grant Carlton Lewis, Axel Grothey: Phase III randomized, placebo (PL)-controlled, double-blind study of intravenous calcium/magnesium (CaMg) to prevent oxaliplatin-induced sensory neurotoxicity (sNT), N08CB: an alliance for clinical trials in oncology study. http://meetinglibrary.asco.org/content/113106-132. Accessed 25 August 2013

  37. Bennett BK, Park SB, Lin CS, Friedlander ML, Kiernan MC, Goldstein D (2012) Impact of oxaliplatin-induced neuropathy: a patient perspective. Support Care Cancer Off J Multinatl Assoc Support Care Cancer 20(11):2959–2967

    Google Scholar 

  38. Sheikh K, Mattingly S (1981) Investigating non-response bias in mail surveys. J Epidemiol Community Health 35(4):293–296

    Article  CAS  PubMed  Google Scholar 

Download references

Sources of support/financial disclosure

This study did not have any financial support.

Conflicts of interest

None exist.

Author information

Author notes

  1. Sina Vatandoust

    Present address: Department of Medical Oncology, Flinders Centre for Innovation in Cancer, Adelaide, Australia

Authors and Affiliations

  1. Department of Medical Oncology, LyellMcEwin Hospital, Adelaide, Australia

    Sina Vatandoust, Rohit Joshi, Jacqueline Adams & Nimit Singhal

  2. Department of Medical Oncology, The Queen Elizabeth Hospital, Adelaide, Woodville, SA, 5011, Australia

    Kenneth B. Pittman, Vy Broadbridge & Susan Yeend

  3. Sansom Institute of Health Service Research and School of Nursing and Midwifery, The University of South Australia, Adelaide, Australia

    Adrian Esterman

  4. The Queen Elizabeth Hospital and University of Adelaide, Adelaide, Woodville, SA, 5011, Australia

    Timothy Jay Price

Authors
  1. Sina Vatandoust
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rohit Joshi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kenneth B. Pittman
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Adrian Esterman
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Vy Broadbridge
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jacqueline Adams
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Nimit Singhal
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Susan Yeend
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Timothy Jay Price
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Timothy Jay Price.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Vatandoust, S., Joshi, R., Pittman, K.B. et al. A descriptive study of persistent oxaliplatin-induced peripheral neuropathy in patients with colorectal cancer. Support Care Cancer 22, 513–518 (2014). https://doi.org/10.1007/s00520-013-2004-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00520-013-2004-3

Keywords

Search

Navigation