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An Overview of Chemotherapy-Induced Peripheral Neuropathy Resulting from Regimens Used in Gynecologic Malignancies

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Indian Journal of Gynecologic Oncology Aims and scope Submit manuscript

Abstract

Purpose

Chemotherapy-induced peripheral neuropathy poses a significant impact on patients’ quality of life and often results in chemotherapy dose reductions or discontinuation. Multiple treatment modalities have been investigated, with few that have shown measurable clinical improvement. This paper is a review of the pathophysiology of chemotherapy-induced peripheral neuropathy and the utility of the available prevention and treatment modalities. We narrowed the focus of the review to only include chemotherapy regimens used in gynecologic oncology.

Methods

Over 50 articles were reviewed across various search engines using keywords such as “chemotherapy-induced neuropathy” with specific agents including taxanes, platinum-based therapies, vincristine, and bortezomib individually researched to provide a comprehensive review of their mechanisms of action and etiologies of neuropathy. Gynecologic and non-gynecologic literature was reviewed with keywords “chemotherapy-induced neuropathy treatment” or “prevention.” A total of 43 references were included.

Results

A comprehensive review of the etiology, pathophysiology, clinical patterns, diagnosis, prognosis, and management of chemotherapy-induced peripheral neuropathy as result of regimens used in gynecologic malignancies was summarized in this paper. The therapies identified to have significance for treatment were duloxetine, photobiomodulation, and possibly capsaicin patches.

Conclusion

Chemotherapy-induced peripheral neuropathy can greatly impact a large portion of the gynecologic oncology population. It is important for the clinician to have a fundamental understanding of clinical manifestations and treatment modalities available. Continued dedicated research in both prevention and treatment is needed to improve the care of our patients, especially given the paucity of research specific to the gynecologic oncology population.

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References

  1. Grisold W, Cavaletti G, Windebank AJ. Peripheral neuropathies from chemotherapeutics and targeted agents: diagnosis, treatment, and prevention. Neuro Oncol. 2012;14(Suppl 4):iv45–54.

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Staff NP, Grisold A, Grisold W, Windebank AJ. Chemotherapy-induced peripheral neuropathy: a current review. Ann Neurol. 2017;81(6):772–81.

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Han Y, Smith MT. Pathobiology of cancer chemotherapy-induced peripheral neuropathy (CIPN). Front Pharmacol. 2013;4:156.

    PubMed  PubMed Central  Google Scholar 

  4. Kerckhove N, Collin A, Condé S, Chaleteix C, Pezet D, Balayssac D. Long-term effects, pathophysiological mechanisms, and risk factors of chemotherapy-induced peripheral neuropathies: a comprehensive literature review. Front Pharmacol. 2017;8:86.

    PubMed  PubMed Central  Google Scholar 

  5. Gutierrez-Gutierrez G, Sereno M, Miralles A, Casado-Saenz E, Gutierrez-Rivas E. Chemotherapy-induced peripheral neuropathy: clinical features, diagnosis, prevention and treatment strategies. Clin Transl Oncol. 2010;12(2):81–91.

    PubMed  Google Scholar 

  6. Doyle T, Chen Z, Muscoli C, Bryant L, Esposito E, Cuzzocrea S, et al. Targeting the overproduction of peroxynitrite for the prevention and reversal of paclitaxel-induced neuropathic pain. J Neurosci. 2012;32(18):6149–60.

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Siau C, Xiao W, Bennett GJ. Paclitaxel- and vincristine-evoked painful peripheral neuropathies: loss of epidermal innervation and activation of Langerhans cells. Exp Neurol. 2006;201(2):507–14.

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Ta LE, Bieber AJ, Carlton SM, Loprinzi CL, Low PA, Windebank AJ. Transient receptor potential vanilloid 1 is essential for cisplatin-induced heat hyperalgesia in mice. Mol Pain. 2010;6:15.

    PubMed  PubMed Central  Google Scholar 

  9. Waseem M, Kaushik P, Tabassum H, Parvez S. Role of mitochondrial mechanism in chemotherapy-induced peripheral neuropathy. Curr Drug Metab. 2018;19(1):47–54.

    CAS  PubMed  Google Scholar 

  10. Barajon I, Bersani M, Quartu M, Del Fiacco M, Cavaletti G, Holst JJ, et al. Neuropeptides and morphological changes in cisplatin-induced dorsal root ganglion neuronopathy. Exp Neurol. 1996;138(1):93–104.

    CAS  PubMed  Google Scholar 

  11. Tatsushima Y, Egashira N, Kawashiri T, Mihara Y, Yano T, Mishima K, et al. Involvement of substance P in peripheral neuropathy induced by paclitaxel but not oxaliplatin. J Pharmacol Exp Ther. 2011;337(1):226–35.

    CAS  PubMed  Google Scholar 

  12. Zhang H, Li Y, de Carvalho-Barbosa M, Kavelaars A, Heijnen CJ, Albrecht PJ, et al. Dorsal root ganglion infiltration by macrophages contributes to paclitaxel chemotherapy-induced peripheral neuropathy. J Pain. 2016;17(7):775–86.

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Xiao WH, Bennett GJ. Effects of mitochondrial poisons on the neuropathic pain produced by the chemotherapeutic agents, paclitaxel and oxaliplatin. Pain. 2012;153(3):704–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Zheng FY, Xiao WH, Bennett GJ. The response of spinal microglia to chemotherapy-evoked painful peripheral neuropathies is distinct from that evoked by traumatic nerve injuries. Neuroscience. 2011;176:447–54.

    CAS  PubMed  Google Scholar 

  15. Amptoulach S, Tsavaris N. Neurotoxicity caused by the treatment with platinum analogues. Chemother Res Pract. 2011;2011:843019.

    PubMed  PubMed Central  Google Scholar 

  16. Florea AM, Busselberg D. Cisplatin as an anti-tumor drug: cellular mechanisms of activity, drug resistance and induced side effects. Cancers. 2011;3(1):1351–71.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Podratz JL, Knight AM, Ta LE, Staff NP, Gass JM, Genelin K, et al. Cisplatin induced mitochondrial DNA damage in dorsal root ganglion neurons. Neurobiol Dis. 2011;41(3):661–8.

    CAS  PubMed  Google Scholar 

  18. Di Cesare ML, Zanardelli M, Failli P, Ghelardini C. Oxaliplatin-induced neuropathy: oxidative stress as pathological mechanism. Protective effect of silibinin J Pain. 2012;13(3):276–84.

    Google Scholar 

  19. Krishnan AV, Goldstein D, Friedlander M, Kiernan MC. Oxaliplatin-induced neurotoxicity and the development of neuropathy. Muscle Nerve. 2005;32(1):51–60.

    CAS  PubMed  Google Scholar 

  20. Jaggi AS, Singh N. Mechanisms in cancer-chemotherapeutic drugs-induced peripheral neuropathy. Toxicology. 2012;291(1–3):1–9.

    CAS  PubMed  Google Scholar 

  21. Kamei J, Tamura N, Saitoh A. Possible involvement of the spinal nitric oxide/cGMP pathway in vincristine-induced painful neuropathy in mice. Pain. 2005;117(1–2):112–20.

    CAS  PubMed  Google Scholar 

  22. Grolleau F, Gamelin L, Boisdron-Celle M, Lapied B, Pelhate M, Gamelin E. A possible explanation for a neurotoxic effect of the anticancer agent oxaliplatin on neuronal voltage-gated sodium channels. J Neurophysiol. 2001;85(5):2293–7.

    CAS  PubMed  Google Scholar 

  23. Kagiava A, Tsingotjidou A, Emmanouilides C, Theophilidis G. The effects of oxaliplatin, an anticancer drug, on potassium channels of the peripheral myelinated nerve fibres of the adult rat. Neurotoxicology. 2008;29(6):1100–6.

    CAS  PubMed  Google Scholar 

  24. Mihara Y, Egashira N, Sada H, Kawashiri T, Ushio S, Yano T, et al. Involvement of spinal NR2B-containing NMDA receptors in oxaliplatin-induced mechanical allodynia in rats. Mol Pain. 2011;7:8.

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Geisler S, Doan RA, Cheng GC, Cetinkaya-Fisgin A, Huang SX, Hoke A, et al. Vincristine and bortezomib use distinct upstream mechanisms to activate a common SARM1-dependent axon degeneration program. JCI Insight. 2019. https://doi.org/10.1172/jci.insight.129920.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Sahenk Z, Brady ST, Mendell JR. Studies on the pathogenesis of vincristine-induced neuropathy. Muscle Nerve. 1987;10(1):80–4.

    CAS  PubMed  Google Scholar 

  27. Legha SS. Vincristine neurotoxicity. Pathophysiol Manag Med Toxicol. 1986;1(6):421–7.

    CAS  Google Scholar 

  28. Thibault K, Van Steenwinckel J, Brisorgueil MJ, Fischer J, Hamon M, Calvino B, et al. Serotonin 5-HT2A receptor involvement and Fos expression at the spinal level in vincristine-induced neuropathy in the rat. Pain. 2008;140(2):305–22.

    CAS  PubMed  Google Scholar 

  29. Geisler SDR, Strickland A, Huang X, Milbrandt J, DiAntonio A. Prevention of vincristine-induced peripheral neuropathy by genetic deletion of SARM1 in mice. Brain. 2016;139:3092–108.

    PubMed  PubMed Central  Google Scholar 

  30. Wang M. Comparative mechanisms of action of proteasome inhibitors. Oncology. 2011;25(Suppl 2):19–24.

    CAS  PubMed  Google Scholar 

  31. Molassiotis A, Cheng HL, Leung KT, Li YC, Wong KH, Au JSK, et al. Risk factors for chemotherapy-induced peripheral neuropathy in patients receiving taxane- and platinum-based chemotherapy. Brain Behav. 2019;9(6):e01312.

    PubMed  PubMed Central  Google Scholar 

  32. Schneider B, Li L, Miller K, Flockhart D, Radovich M, Hancock B, et al. Genetic associations with taxane-induced neuropathy by a genome-wide association study (GWAS) in E5103. J Clin Oncol. 2011;29(15s_uppl):1000.

    Google Scholar 

  33. Argyriou AA, Cavaletti G, Bruna J, Kyritsis AP, Kalofonos HP. Bortezomib-induced peripheral neurotoxicity: an update. Arch Toxicol. 2014;88(9):1669–79.

    PubMed  Google Scholar 

  34. Cavaletti G, Cornblath D, Merkies I, Postma T, Rossi E, Frigeni B, et al. The chemotherapy-induced peripheral neuropathy outcome measures standardization study: from consensus to the first validity and reliability findings. Ann Oncol. 2013;24(2):454–62.

    CAS  PubMed  Google Scholar 

  35. Hershman DL, Lacchetti C, Dworkin RH, Lavoie Smith EM, Bleeker J, Cavaletti G, et al. Prevention and management of chemotherapy-induced peripheral neuropathy in survivors of adult cancers: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol. 2014;32(18):1941–67.

    CAS  PubMed  Google Scholar 

  36. Jordan B, Margulies A, Cardoso F, Cavaletti G, Haugnes HS, Jahn P, et al. Systemic anticancer therapy-induced peripheral and central neurotoxicity: ESMO-EONS-EANO clinical practice guidelines for diagnosis, prevention, treatment and follow-up. Ann Oncol. 2020;31(10):1306–19.

    CAS  PubMed  Google Scholar 

  37. Loprinzi CL, Lacchetti C, Bleeker J, Cavaletti G, Chauhan C, Hertz DL, et al. Prevention and management of chemotherapy-induced peripheral neuropathy in survivors of adult cancers: ASCO guideline update. J Clin Oncol. 2020;38(28):3325–48.

    PubMed  Google Scholar 

  38. Durand JP, Deplanque G, Montheil V, Gornet JM, Scotte F, Mir O, et al. 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. 2012;23(1):200–5.

    CAS  PubMed  Google Scholar 

  39. Pachman DRDT, Zekan PJ, et al. A pilot study of minocycline for the prevention of paclitaxel-associated neuropathy: ACCRU study RU221408I. Support Care Cancer. 2017;25(11):3407–16.

    PubMed  Google Scholar 

  40. Smith EM, Pang H, Cirrincione C, Fleishman S, Paskett ED, Ahles T, et al. Effect of duloxetine on pain, function, and quality of life among patients with chemotherapy-induced painful peripheral neuropathy: a randomized clinical trial. JAMA. 2013;309(13):1359–67.

    PubMed  PubMed Central  Google Scholar 

  41. Argenta PABK, Geller MA, et al. The effect of photobiomodulation on chemotherapy-induced peripheral neuropathy: a randomized, sham-controlled clinical trial. Gynecol Oncol. 2017;144(1):159–66.

    PubMed  Google Scholar 

  42. Anand P, Elsafa E, Privitera R, Naidoo K, Yiangou Y, Donatien P, et al. Rational treatment of chemotherapy-induced peripheral neuropathy with capsaicin 8% patch: from pain relief towards disease modification. J Pain Res. 2019;12:2039–52.

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Duregon F, Vendramin B, Bullo V, Gobbo S, Cugusi L, Di Blasio A, et al. Effects of exercise on cancer patients suffering chemotherapy-induced peripheral neuropathy undergoing treatment: a systematic review. Crit Rev Oncol Hematol. 2018;121:90–100.

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Gynecologic Oncology, University of Colorado, 12631 East 17th Ave., AO Room 4403, B198-4, Aurora, CO, 80045, USA

    Breana L. Hill & Jill Alldredge

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  1. Breana L. Hill
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BH contributed to the development, data collection, and editing of this manuscript. JA contributed to the original idea, data collection, and manuscript editing.

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Correspondence to Breana L. Hill.

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Hill, B.L., Alldredge, J. An Overview of Chemotherapy-Induced Peripheral Neuropathy Resulting from Regimens Used in Gynecologic Malignancies. Indian J Gynecol Oncolog 19, 62 (2021). https://doi.org/10.1007/s40944-021-00564-2

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