Skip to main content
SpringerLink
Log in

Prevention of Chemotherapy-Induced Peripheral Neuropathy (CIPN): Current Clinical Data and Future Directions

  • Chapter
  • First Online:
Diagnosis, Management and Emerging Strategies for Chemotherapy-Induced Neuropathy

  • 661 Accesses

Abstract

Chemotherapy-induced peripheral neurotoxicity (CIPN) is a treatment related toxicity that burdens the quality of life of cancer survivors. Unfortunately, no efficacious treatment (symptomatic or preventive) is available for this condition for many reasons. First, a still incomplete pathogenetic knowledge hampers the recognition of a strong biological rationale for clinical trials. Second, there are some methodological issues in clinical trial design that still need to be addressed. In this chapter we will present an overview of strategies that were undertaken in the past and some that are now undergoing clinical investigation for prevention of CIPN. This is a complex challenge that will require multidisciplinary collaborative research between basic scientists, health care professionals, and patient representatives.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 199.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Cavaletti G, Alberti P, Argyriou AA, Lustberg M, Staff NP, Tamburin S, Toxic Neuropathy Consortium of the Peripheral Nerve Society (2019) Chemotherapy-induced peripheral neurotoxicity: A multifaceted, still unsolved issue. J Peripher Nerv Syst 24(Suppl 2):S6–S12

    PubMed  Google Scholar 

  2. Pike CT, Birnbaum HG, Muehlenbein CE, Pohl GM, Natale RB (2012) Healthcare costs and workloss burden of patients with chemotherapy-associated peripheral neuropathy in breast, ovarian, head and neck, and nonsmall cell lung cancer. Chemother Res Pract 2012:913848

    PubMed  PubMed Central  Google Scholar 

  3. Song X, Wilson KL, Kagan J, Panjabi S (2019) Cost of peripheral neuropathy in patients receiving treatment for multiple myeloma: a US administrative claims analysis. Ther Adv Hematol 10:2040620719839025

    Article  PubMed  PubMed Central  Google Scholar 

  4. Cavaletti G, Cornblath DR, ISJ M, Postma TJ, Rossi E, Alberti P, Bruna J, Argyriou AA, Briani C, Velasco R, Kalofonos HP, Psimaras D, Ricard D, Pace A, Faber CG, Lalisang RI, Brandsma D, Koeppen S, Kerrigan S, Schenone A, Grisold W, Mazzeo A, Padua L, Dorsey SG, Penas-Prado M, Valsecchi MG, CI-PeriNomS Group (2019) Patients’ and physicians’ interpretation of chemotherapy-induced peripheral neurotoxicity. J Peripher Nerv Syst. 24(1):111–119

    Article  CAS  PubMed  Google Scholar 

  5. Argyriou AA, Bruna J, Genazzani AA, Cavaletti G (2017) Chemotherapy-induced peripheral neurotoxicity: management informed by pharmacogenetics. Nat Rev Neurol 13:492–504

    Article  PubMed  Google Scholar 

  6. Seretny M, Currie GL, Sena ES, Ramnarine S, Grant R, MacLeod MR, Colvin LA, Fallon M (2014) Incidence, prevalence, and predictors of chemotherapy-induced peripheral neuropathy: A systematic review and meta-analysis. Pain 155:2461–2470

    Article  PubMed  Google Scholar 

  7. Argyriou AA, Park SB, Islam B, Tamburin S, Velasco R, Alberti P, Bruna J, Psimaras D, Cavaletti G, Cornblath DR, TNC (2019) Neurophysiological, nerve imaging and other techniques to assess chemotherapy-induced peripheral neurotoxicity in the clinical and research settings. J Neurol Neurosurg Psychiatry 90(12):1361–1369

    Google Scholar 

  8. Dorsey SG, Kleckner IR, Barton D, Mustian K, O’Mara A, St Germain D, Cavaletti G, Danhauer SC, Hershman D, Hohmann AG, Hoke A, Hopkins JO, Kelly KP, Loprinzi CL, McLeod HL, Mohile S, Paice J, Rowland JH, Salvemini D, Segal RA, Lavoie Smith E, McCaskill Stevens W, Janelsins MC (2019) NCI Clinical Trials Planning Meeting for prevention and treatment of chemotherapy-induced peripheral neuropathy. J Natl Cancer Inst 111(6):531–537

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. Gewandter JS, Brell J, Cavaletti G, Dougherty PM, Evans S, Howie L, McDermott MP, O’Mara A, Smith AG, Dastros-Pitei D, Gauthier LR, Haroutounian S, Jarpe M, Katz NP, Loprinzi C, Richardson P, Lavoie-Smith EM, Wen PY, Turk DC, Dworkin RH, Freeman R (2018) Trial designs for chemotherapy-induced peripheral neuropathy prevention: ACTTION recommendations. Neurology 91:403–413

    Article  PubMed  PubMed Central  Google Scholar 

  10. Fuglsang-Frederiksen A, Pugdahl K (2011) Current status on electrodiagnostic standards and guidelines in neuromuscular disorders. Clin Neurophysiol 122:440–455

    Article  PubMed  Google Scholar 

  11. Mileshkin L, Stark R, Day B, Seymour JF, Zeldis JB, Prince HM (2006) Development of neuropathy in patients with myeloma treated with thalidomide: patterns of occurrence and the role of electrophysiologic monitoring. J Clin Oncol 24:4507–4514

    Article  CAS  PubMed  Google Scholar 

  12. Frigeni B, Cacciavillani M, Ermani M, Briani C, Alberti P, Ferrarese C, Cavaletti G (2012) Neurophysiological examination of dorsal sural nerve. Muscle Nerve 46:895–898

    Article  PubMed  Google Scholar 

  13. Alberti P, Rossi E, Argyriou AA, Kalofonos HP, Briani C, Cacciavillani M, Campagnolo M, Bruna J, Velasco R, Cazzaniga ME, Cortinovis D, Valsecchi MG, Cavaletti G (2018) Risk stratification of oxaliplatin induced peripheral neurotoxicity applying electrophysiological testing of dorsal sural nerve. Support Care Cancer 26:3143–3151

    Article  PubMed  Google Scholar 

  14. Dalla Torre C, Zambello R, Cacciavillani M, Campagnolo M, Berno T, Salvalaggio A, De March E, Barilà G, Lico A, Lucchetta M, Ermani M, Briani C (2016) Lenalidomide long-term neurotoxicity: Clinical and neurophysiologic prospective study. Neurology 87:1161–1166

    Article  CAS  PubMed  Google Scholar 

  15. Koçer A, Domaç FM, Boylu E, Us O, Tanridağ T (2007) A comparison of sural nerve conduction studies in patients with impaired oral glucose tolerance test. Acta Neurol Scand 116:399–405

    Article  PubMed  Google Scholar 

  16. Turgut B, Turgut N, Akpinar S, Balci K, Pamuk GE, Tekgündüz E, Demir M (2006) Dorsal sural nerve conduction study in vitamin B(12) deficiency with megaloblastic anemia. J Peripher Nerv Syst 11:247–252

    Article  PubMed  Google Scholar 

  17. Uluc K, Isak B, Borucu D, Temucin CM, Cetinkaya Y, Koytak PK, Tanridag T, Us O (2008) Medial plantar and dorsal sural nerve conduction studies increase the sensitivity in the detection of neuropathy in diabetic patients. Clin Neurophysiol 119:880–885

    Article  PubMed  Google Scholar 

  18. Hershman DL, Lacchetti C, Dworkin RH, Lavoie Smith EM, Bleeker J, Cavaletti G, Chauhan C, Gavin P, Lavino A, Lustberg MB, Paice J, Schneider B, Smith ML, Smith T, Terstriep S, Wagner-Johnston N, Bak K, Loprinzi CL, American Society of Clinical Oncology (2014) Prevention and management of chemotherapy-induced peripheral neuropathy in survivors of adult cancers: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol 32:1941–1967

    Article  CAS  PubMed  Google Scholar 

  19. Loprinzi CL, Lacchetti C, Bleeker J, Cavaletti G, Chauhan C, Hertz DL, Kelley MR, Lavino A, Lustberg MB, Paice JA, Schneider BP, Lavoie Smith EM, Smith ML, Smith TJ, Wagner-Johnston N, Hershman DL (2020) Prevention and management of chemotherapy-induced peripheral neuropathy in survivors of adult cancers: ASCO guideline update. J Clin Oncol 38(28):3325–3348

    Google Scholar 

  20. Calls A, Carozzi V, Navarro X, Monza L, Bruna J (2020) Pathogenesis of platinum-induced peripheral neurotoxicity: Insights from preclinical studies. Exp Neurol 325:113141

    Article  CAS  PubMed  Google Scholar 

  21. Geisler S (2021) Vincristine- and bortezomib-induced neuropathies—from bedside to bench and back. Exp Neurol 336:113519

    Article  CAS  PubMed  Google Scholar 

  22. Staff NP, Fehrenbacher JC, Caillaud M, Damaj MI, Segal RA, Rieger S (2020) Pathogenesis of paclitaxel-induced peripheral neuropathy: A current review of in vitro and in vivo findings using rodent and human model systems. Exp Neurol 324:113121

    Article  CAS  PubMed  Google Scholar 

  23. Aureli M, Mauri L, Ciampa MG, Prinetti A, Toffano G, Secchieri C, Sonnino S (2016) GM1 ganglioside: past studies and future potential. Mol Neurobiol 53:1824–1842

    Article  CAS  PubMed  Google Scholar 

  24. Su Y, Huang J, Wang S, Unger JM, Arias-Fuenzalida J, Shi Y, Li J, Gao Y, Shi W, Wang X, Peng R, Xu F, An X, Xue C, Xia W, Hong R, Zhong Y, Lin Y, Huang H, Zhang A, Zhang L, Cai L, Zhang J, Yuan Z (2020) The effects of ganglioside-monosialic acid in taxane-induced peripheral neurotoxicity in patients with breast cancer: a randomized trial. J Natl Cancer Inst 112:55–62

    PubMed  Google Scholar 

  25. Wang DS, Wang ZQ, Chen G, Peng JW, Wang W, Deng YH, Wang FH, Zhang JW, Liang HL, Feng F, Xie CB, Ren C, Jin Y, Shi SM, Fan WH, Lu ZH, Ding PR, Wang F, Xu RH, Li YH (2020) Phase III randomized, placebo-controlled, double-blind study of monosialotetrahexosylganglioside for the prevention of oxaliplatin-induced peripheral neurotoxicity in stage II/III colorectal cancer. Cancer Med 9:151–159

    Article  CAS  PubMed  Google Scholar 

  26. Carozzi VA, Canta A, Chiorazzi A (2015) Chemotherapy-induced peripheral neuropathy: What do we know about mechanisms? Neurosci Lett 596:90–107

    Article  CAS  PubMed  Google Scholar 

  27. Glimelius B, Manojlovic N, Pfeiffer P, Mosidze B, Kurteva G, Karlberg M, Mahalingam D, Buhl Jensen P, Kowalski J, Bengtson M, Nittve M, Näsström J (2018) Persistent prevention of oxaliplatin-induced peripheral neuropathy using calmangafodipir (PledOx). Acta Oncol 57:393–402

    Article  CAS  PubMed  Google Scholar 

  28. Karlsson JOG, Jynge P (2018) Is it possible to draw firm conclusions from the PLIANT trial? Acta Oncol 57:862–864

    Article  PubMed  Google Scholar 

  29. Bouchenaki H, Danigo A, Sturtz F, Hajj R, Magy L, Demiot C (2020) An overview of ongoing clinical trials assessing pharmacological therapeutic strategies to manage chemotherapy-induced peripheral neuropathy, based on preclinical studies in rodent models. Fundam Clin Pharmacol. https://doi.org/10.1111/fcp.12617

  30. Vela JM, Merlos M, Almansa C (2015) Investigational sigma-1 receptor antagonists for the treatment of pain. Expert Opin Investig Drugs 24:883–896

    Article  CAS  PubMed  Google Scholar 

  31. Bruna J, Videla S, Argyriou AA, Velasco R, Villoria J, Santos C, Nadal C, Cavaletti G, Alberti P, Briani C, Kalofonos HP, Cortinovis D, Sust M, Vaqué A, Klein T, Plata-Salamán C (2018) Efficacy of a novel sigma-1 receptor antagonist for oxaliplatin-induced neuropathy: a randomized, double-blind, placebo-controlled phase IIa clinical trial. Neurotherapeutics 15(1):178–189

    Article  CAS  PubMed  Google Scholar 

  32. Fujita S, Hirota T, Sakiyama R, Baba M, Ieiri I (2019) Identification of drug transporters contributing to oxaliplatin-induced peripheral neuropathy. J Neurochem 148:373–385

    Article  CAS  PubMed  Google Scholar 

  33. Liu JJ, Kim Y, Yan F, Ding Q, Ip V, Jong NN, Mercer JF, McKeage MJ (2013) Contributions of rat Ctr1 to the uptake and toxicity of copper and platinum anticancer drugs in dorsal root ganglion neurons. Biochem Pharmacol 85:207–215

    Article  CAS  PubMed  Google Scholar 

  34. Sprowl JA, Ong SS, Gibson AA, Hu S, Du G, Lin W, Li L, Bharill S, Ness RA, Stecula A, Offer SM, Diasio RB, Nies AT, Schwab M, Cavaletti G, Schlatter E, Ciarimboli G, Schellens JHM, Isacoff EY, Sali A, Chen T, Baker SD, Sparreboom A, Pabla N (2016) A phosphotyrosine switch regulates organic cation transporters. Nat Commun 7:10880

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Roth M, Obaidat A, Hagenbuch B (2012) OATPs, OATs and OCTs: the organic anion and cation transporters of the SLCO and SLC22A gene superfamilies. Br J Pharmacol 165:1260–1287

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Sprowl JA, Ciarimboli G, Lancaster CS, Giovinazzo H, Gibson AA, Du G, Janke LJ, Cavaletti G, Shields AF, Sparreboom A (2013) Oxaliplatin-induced neurotoxicity is dependent on the organic cation transporter OCT2. Proc Natl Acad Sci U S A 110:11199–11204

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Hu S, Mathijssen RH, de Bruijn P, Baker SD, Sparreboom A (2014) Inhibition of OATP1B1 by tyrosine kinase inhibitors: in vitro-in vivo correlations. Br J Cancer 110:894–898

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Leblanc AF, Sprowl JA, Alberti P, Chiorazzi A, Arnold WD, Gibson AA, Hong KW, Pioso MS, Chen M, Huang KM, Chodisetty V, Costa O, Florea T, de Bruijn P, Mathijssen RH, Reinbolt RE, Lustberg MB, Sucheston-Campbell LE, Cavaletti G, Sparreboom A, Hu S (2018) OATP1B2 deficiency protects against paclitaxel-induced neurotoxicity. J Clin Invest 128:816–825

    Article  PubMed  PubMed Central  Google Scholar 

  39. Beretta S, Begni B, Ferrarese C (2003) Pharmacological manipulation of glutamate transport. Drug News Perspect 16:435–445

    Article  CAS  PubMed  Google Scholar 

  40. Ferrier J, Bayet-Robert M, Pereira B, Daulhac L, Eschalier A, Pezet D, Moulinoux JP, Balayssac D (2013) A polyamine-deficient diet prevents oxaliplatin-induced acute cold and mechanical hypersensitivity in rats. PLoS One 8:e77828

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Miller RG, Mitchell JD, Moore DH (2012). Riluzole for amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND). Cochrane Database Syst Rev (2):CD001447.

    Google Scholar 

  42. Kretschmer BD, Kratzer U, Schmidt WJ (1998) Riluzole, a glutamate release inhibitor, and motor behavior. Naunyn Schmiedebergs Arch Pharmacol 358:181–190

    Article  CAS  PubMed  Google Scholar 

  43. Nakae A, Nakai K, Tanaka T, Hosokawa K, Mashimo T (2013) Serotonin 2C receptor alternative splicing in a spinal cord injury model. Neurosci Lett 532:49–54

    Article  CAS  PubMed  Google Scholar 

  44. Baptista-de-Souza D, Di Cesare ML, Zanardelli M, Micheli L, Nunes-de-Souza RL, Canto-de-Souza A, Ghelardini C (2014) Serotonergic modulation in neuropathy induced by oxaliplatin: effect on the 5HT2C receptor. Eur J Pharmacol 735:141–149

    Article  CAS  PubMed  Google Scholar 

  45. Sharretts J, Galescu O, Gomatam S, Andraca-Carrera E, Hampp C, Yanoff L (2020) Cancer risk associated with lorcaserin—the FDA’s review of the CAMELLIA-TIMI 61 trial. N Engl J Med 383:1000–1002

    Article  CAS  PubMed  Google Scholar 

  46. Pralhada Rao R, Vaidyanathan N, Rengasamy M, Mammen Oommen A, Somaiya N, Jagannath MR (2013) Sphingolipid metabolic pathway: an overview of major roles played in human diseases. J Lipids 2013:178910

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  47. Patti GJ, Yanes O, Shriver LP, Courade JP, Tautenhahn R, Manchester M, Siuzdak G (2012) Metabolomics implicates altered sphingolipids in chronic pain of neuropathic origin. Nat Chem Biol 8:232–234

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Alroughani R, Inshasi J, Al-Asmi A, Alkhabouri J, Alsaadi T, Alsalti A, Boshra A, Canibano B, Ahmed SF, Shatila A (2020) Disease-modifying drugs and family planning in people with multiple sclerosis: a consensus narrative review from the Gulf region. Neurol Ther 9:265–280

    Article  PubMed  PubMed Central  Google Scholar 

  49. Heinen A, Beyer F, Tzekova N, Hartung HP, Küry P (2015) Fingolimod induces the transition to a nerve regeneration promoting Schwann cell phenotype. Exp Neurol 271:25–35

    Article  CAS  PubMed  Google Scholar 

  50. Szepanowski F, Derksen A, Steiner I, Meyer Zu Hörste G, Daldrup T, Hartung HP, Kieseier BC (2016) Fingolimod promotes peripheral nerve regeneration via modulation of lysophospholipid signaling. J Neuroinflammation 13:143

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  51. Alberti P (2019) Platinum-drugs induced peripheral neurotoxicity: clinical course and preclinical evidence. Expert Opin Drug Metab Toxicol 15:487–497

    Article  CAS  PubMed  Google Scholar 

  52. Windebank AJ, Grisold W (2008) Chemotherapy-induced neuropathy. J Peripher Nerv Syst 13:27–46

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Experimental Neurology Unit, School of Medicine and Surgery, University of Milano-Bicocca, Monza (MB), Italy

    Paola Alberti

  2. NeuroMI (Milan Center for Neuroscience), Milan, Italy

    Paola Alberti

  3. Border Medical Oncology, Albury Wodonga Regional Cancer Centre, Albury, NSW, Australia

    Christopher B. Steer

  4. UNSW Rural Clinical School, Albury Campus, Albury, NSW, Australia

    Christopher B. Steer

Authors
  1. Paola Alberti
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Christopher B. Steer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Paola Alberti .

Editor information

Editors and Affiliations

  1. Yale University School of Medicine, New Haven, CT, USA

    Maryam Lustberg

  2. Mayo Clinic, Rochester, MN, USA

    Charles Loprinzi

Rights and permissions

Reprints and permissions

Copyright information

© 2021 The Author(s), under exclusive license to Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Alberti, P., Steer, C.B. (2021). Prevention of Chemotherapy-Induced Peripheral Neuropathy (CIPN): Current Clinical Data and Future Directions. In: Lustberg, M., Loprinzi, C. (eds) Diagnosis, Management and Emerging Strategies for Chemotherapy-Induced Neuropathy. Springer, Cham. https://doi.org/10.1007/978-3-030-78663-2_5

Download citation

Publish with us

Policies and ethics

Search

Navigation