Topical medicinesin chemotherapy-induced peripheral neuropathy

Karolina Pawelec; Sabina Jóźwiak; Karolina Iwanicka; Ewelina Wesołek-Bielaska; Katarzyna Szklener; Slawomir Mandziuk

doi:10.12923/

Authors

Karolina Pawelec Student Academic Group, Department of Clinical Oncology and Chemotherapy, Medical University of Lublin, Poland Author https://orcid.org/0009-0000-0543-9395
Sabina Jóźwiak Student Academic Group, Department of Clinical Oncology and Chemotherapy, Medical University of Lublin, Poland Author https://orcid.org/0009-0004-5262-9967
Karolina Iwanicka Student Academic Group, Department of Clinical Oncology and Chemotherapy, Medical University of Lublin, Poland Translator https://orcid.org/0000-0002-8803-332X
Ewelina Wesołek-Bielaska Department of Clinical Oncology and Chemotherapy, Medical University of Lublin, Poland Author https://orcid.org/0000-0001-7819-2661
Katarzyna Szklener Department of Clinical Oncology and Chemotherapy, Medical University of Lublin, Poland Author https://orcid.org/0000-0001-8033-3574
Slawomir Mandziuk Department of Clinical Oncology and Chemotherapy, Medical University of Lublin, Poland Author https://orcid.org/0000-0002-9812-0777

DOI:

https://doi.org/10.12923/

Keywords:

chemotherapy-induced peripheral neuropathy, topical medications, pain management

Abstract

Oncology patients face numerous challenges resulting both from their underlying disease and from the adverse effects of anticancer treatment. Chemotherapy-induced peripheral neuropathy (CIPN) is among the most serious complications associated with chemotherapy. The sensory and motor disturbances observed in the course of CIPN are often progressive and may be irreversible, while severe and chronic pain leads to a substantial reduction in patients’ quality of life (QoL).
This narrative review summarizes currently available topical treatment options for CIPN, focusing on substances that have shown potential clinical benefit. The pathogenesis of CIPN remains incompletely understood, and existing treatment strategies are frequently insufficient or associated with significant adverse effects. Consequently, both the prevention and management of CIPN remain important challenges in contemporary medicine.
Recently, increasing attention has been directed toward topically administered agents, including formulations based on phenytoin, lidocaine, amitriptyline, capsaicin, cannabinoids, duloxetine, ketamine, and baclofen. These therapies may alleviate neuropathic symptoms and improve QoL without the systemic complications commonly associated with oral or intravenous pharmacotherapy. The use of topical medications may also allow for a reduction in systemic analgesic doses and is often favored due to their more favorable safety profile. Therefore, topical agents should be considered promising therapeutic options aimed at minimizing systemic side effects and optimizing the current pharmacological management of patients with CIPN.

References

1. Scholz J, Finnerup NB, Attal N, Aziz Q, Baron R, Bennett MI, et al. The IASP classification of chronic pain for ICD-11: chronic neuropathic pain. Pain. 2019;160(1):53–59. doi:10.1097/j.pain.0000000000001365.

2. Edwards HL, Mulvey MR, Bennett MI. Cancer-related neuropathic pain. Cancers (Basel). 2019;11(3):373. doi:10.3390/cancers11030373.

3. Park HJ. Chemotherapy-induced peripheral neuropathic pain. Korean J Anesthesiol. 2014;67(1):4–7. doi:10.4097/kjae.2014.67.1.4.

4. Zhang S. Chemotherapy-induced peripheral neuropathy and rehabilitation: a review. Semin Oncol. 2021;48(3):193–207. doi:10.1053/j.seminoncol.2021.09.004.

5. Avallone A, Bimonte S, Cardone C, Cascella M, Cuomo A. Pathophysiology and therapeutic perspectives for chemotherapy-induced peripheral neuropathy. Anticancer Res. 2022;42(10):4667–4678. doi:10.21873/anticanres.15971.

6. Zajączkowska R, Kocot-Kępska M, Leppert W, Wrzosek A, Mika J, Wordliczek J. Mechanisms of chemotherapy-induced peripheral neuropathy. Int J Mol Sci. 2019;20(6):1451. doi:10.3390/ijms20061451.

7. Maihöfner C, Diel I, Tesch H, Quandel T, Baron R. Chemotherapy-induced peripheral neuropathy (CIPN): current therapies and topical treatment option with high-concentration capsaicin. Support Care Cancer. 2021;29(8):4223–4238. doi:10.1007/s00520-021-06042-x.

8. Brown TJ, Sedhom R, Gupta A. Chemotherapy-induced peripheral neuropathy. JAMA Oncol. 2019;5(5):750. doi:10.1001/jamaoncol.2018.6771.

9. 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):1306–1319. doi:10.1016/j.annonc.2020.07.003.

10. Kanzawa-Lee GA, Knoerl R, Donohoe C, Bridges CM, Smith EML. Mechanisms, predictors, and challenges in assessing and managing painful chemotherapy-induced peripheral neuropathy. Semin Oncol Nurs. 2019;35(3):253–260. doi:10.1016/j.soncn.2019.04.006.

11. DiAntonio A. Axon degeneration: mechanistic insights lead to therapeutic opportunities for the prevention and treatment of peripheral neuropathy. Pain. 2019;160(Suppl 1):S17–S22. doi:10.1097/j.pain.0000000000001528.

12. Malacrida A, Meregalli C, Rodriguez-Menendez V, Nicolini G. Chemotherapy-induced peripheral neuropathy and changes in cytoskeleton. Int J Mol Sci. 2019;20(9):2287. doi:10.3390/ijms20092287.

13. Sałat K. Chemotherapy-induced peripheral neuropathy: part 1—current state of knowledge and perspectives for pharmacotherapy. Pharmacol Rep. 2020;72(3):486–507. doi:10.1007/s43440-020-00109-y.

14. Carozzi VA, Canta A, Chiorazzi A. Chemotherapy-induced peripheral neuropathy: what do we know about mechanisms? Neurosci Lett. 2015;596:90–107. doi:10.1016/j.neulet.2014.10.014.

15. Bae EH, Greenwald MK, Schwartz AG. Chemotherapy-induced peripheral neuropathy: mechanisms and therapeutic avenues. Neurotherapeutics. 2021;18(4):2384–2396. doi:10.1007/s13311-021-01142-2.

16. Prager K, Passig K, Micke O, Zomorodbakhsch B, Keinki C, Hübner J. Chemotherapy-induced polyneuropathy in cancer care—the patient perspective. Support Care Cancer. 2023;31(4):235. doi:10.1007/s00520-023-07688-5.

17. Kocot-Kępska M, Zajączkowska R, Mika J, Kopsky DJ, Wordliczek J, Dobrogowski J, et al. Topical treatments and their molecular/cellular mechanisms in patients with peripheral neuropathic pain: narrative review. Pharmaceutics. 2021;13(4):450. doi:10.3390/pharmaceutics13040450.

18. Pedowitz EJ, Abrams RMC, Simpson DM. Management of neuropathic pain in the geriatric population. Clin Geriatr Med. 2021;37(2):361–376. doi:10.1016/j.cger.2021.01.008.

19. Keppel Hesselink JM, Kopsky DJ. Phenytoin: 80 years young, from epilepsy to breast cancer, a remarkable molecule with multiple modes of action. J Neurol. 2017;264(8):1617–1621. doi:10.1007/s00415-017-8391-5.

20. Kopsky DJ, Keppel Hesselink JM. Topical phenytoin for the treatment of neuropathic pain. J Pain Res. 2017;10:469–473. doi:10.2147/JPR.S129749.

21. Kopsky DJ, Vrancken AFJE, Keppel Hesselink JM, van Eijk RPA, Notermans NC. Usefulness of a double-blind placebo-controlled response test to demonstrate rapid onset analgesia with phenytoin 10% cream in polyneuropathy. J Pain Res. 2020;13:877–882. doi:10.2147/JPR.S243434.

22. Keppel Hesselink JM, Kopsky DJ. Fast onset of relief after topical phenytoin in neuropathic pain after chemotherapy. [conference paper / report]. 2018.

23. Kopsky DJ, Keppel Hesselink JM. Phenytoin cream for the treatment of neuropathic pain: case series. Pharmaceuticals (Basel). 2018;11(2):53. doi:10.3390/ph11020053.

24. Hermanns H, Hollmann MW, Stevens MF, Lirk P, Brandenburger T, Piegeler T, et al. Molecular mechanisms of action of systemic lidocaine in acute and chronic pain: a narrative review. Br J Anaesth. 2019;123(3):335–349. doi:10.1016/j.bja.2019.06.014.

25. de León-Casasola OA, Mayoral V. The topical 5% lidocaine medicated plaster in localized neuropathic pain: a reappraisal of the clinical evidence. J Pain Res. 2016;9:67–79. doi:10.2147/JPR.S99231.

26. Voute M, Morel V, Pickering G. Topical lidocaine for chronic pain treatment. Drug Des Devel Ther. 2021;15:4091–4103. doi:10.2147/DDDT.S328228.

27. Wordliczek J, Zajączkowska R, Leppert W. Farmakoterapia bólu neuropatycznego. Med Paliat Prakt. 2017;11(2):61–73.

28. Baron R, Allegri M, Correa-Illanes G, et al. The 5% lidocaine-medicated plaster: its inclusion in international treatment guidelines for treating localized neuropathic pain, and clinical evidence supporting its use. Pain Ther. 2016;5(2):149–169. doi:10.1007/s40122-016-0060-3.

29. Attal N, Bouhassira D. Pharmacotherapy of neuropathic pain: which drugs, which treatment algorithms? Pain. 2015;156(Suppl 1):S104–S114. doi:10.1097/01.j.pain.0000460358.01998.15.

30. Shkodra M, Caraceni A. Treatment of neuropathic pain directly due to cancer: an update. Cancers (Basel). 2022;14(8):1992. doi:10.3390/cancers14081992.

31. Colloca L, Ludman T, Bouhassira D, Baron R, Dickenson AH, Yarnitsky D, et al. Neuropathic pain. Nat Rev Dis Primers. 2017;3:17002. doi:10.1038/nrdp.2017.2.

32. Genevois AL, Ruel J, Penalba V, Hatton S, Petitfils C, Ducrocq M, et al. Analgesic effects of topical amitriptyline in patients with chemotherapy-induced peripheral neuropathy. J Pain. 2021;22(4):440–453. doi:10.1016/j.jpain.2020.11.002.

33. Obata H. Analgesic mechanisms of antidepressants for neuropathic pain. Int J Mol Sci. 2017;18(11):2483. doi:10.3390/ijms18112483.

34. Shakshuki A, Yeung P, Agu RU. Compounded topical amitriptyline for neuropathic pain: in vitro release from compounding bases and potential correlation with clinical efficacy. Can J Hosp Pharm. 2020;73(2):133–140.

35. Basith S, Cui M, Hong S, Choi S. Harnessing the therapeutic potential of capsaicin and its analogues in pain and other diseases. Molecules. 2016;21(8):966. doi:10.3390/molecules21080966.

36. Sultana A, Singla RK, He X, Sun Y, Alam MS, Shen B. Topical capsaicin for the treatment of neuropathic pain. Curr Drug Metab. 2021;22(3):198–207. doi:10.2174/1389200221999201116143701.

37. Frias B, Merighi A. Capsaicin, nociception and pain. Molecules. 2016;21(6):797. doi:10.3390/molecules21060797.

38. Privitera R, Anand P. Capsaicin 8% patch (Qutenza) and other current treatments for neuropathic pain in chemotherapy-induced peripheral neuropathy. Curr Opin Support Palliat Care. 2021;15(2):125–131. doi:10.1097/SPC.0000000000000545.

39. VanDolah HJ, Bauer BA, Mauck KF. Clinicians’ guide to cannabidiol and hemp oils. Mayo Clin Proc. 2019;94(9):1840–1851. doi:10.1016/j.mayocp.2019.01.003.

40. D’Andre S, McAllister S, Nagi J, Giridhar KV, Ruiz-Macias E, Loprinzi C. Topical cannabinoids for treating chemotherapy-induced neuropathy: a case series. Integr Cancer Ther. 2021;20:15347354211061739. doi:10.1177/15347354211061739.

41. Blanton HL, Brelsfoard J, DeTurk N, Pruitt K, Narasimhan M, Morgan DJ, et al. Cannabinoids: current and future options to treat chronic and chemotherapy-induced neuropathic pain. Drugs. 2019;79(9):969–995. doi:10.1007/s40265-019-01132-x.

42. Chou R, Ahmed AY, Morasco BJ, Bougatsos C, Dana T, Fu R, et al. Living systematic review on cannabis and other plant-based treatments for chronic pain: 2023 update. Rockville (MD): Agency for Healthcare Research and Quality; 2023.

43. Silva NR, Gomes FIF, Lopes AHP, Cortez IL, Dos Santos JC, Silva CEA, et al. The cannabidiol analog PECS-101 prevents chemotherapy-induced neuropathic pain via PPARγ receptors. Neurotherapeutics. 2022;19(1):434–449. doi:10.1007/s13311-021-01164-w.

44. D’Souza RS, Alvarez GAM, Dombovy-Johnson M, Eller J, Abd-Elsayed A. Evidence-based treatment of pain in chemotherapy-induced peripheral neuropathy. Curr Pain Headache Rep. 2023;27(5):99–116. doi:10.1007/s11916-023-01107-4.

45. Xu DH, Cullen BD, Tang M, Fang Y. The effectiveness of topical cannabidiol oil in symptomatic relief of peripheral neuropathy of the lower extremities. Curr Pharm Biotechnol. 2020;21(5):390–402. doi:10.2174/1389201020666191202111534.

46. Waissengrin B, Mirelman D, Pelles S, Bukstein F, Blumenthal DT, Wolf I, et al. Effect of cannabis on oxaliplatin-induced peripheral neuropathy among oncology patients: a retrospective analysis. Ther Adv Med Oncol. 2021;13:1758835921990203. doi:10.1177/1758835921990203.

47. Chahal SK, Sodhi RK, Madan J. Duloxetine hydrochloride loaded film-forming dermal gel enriched with methylcobalamin and geranium oil attenuates paclitaxel-induced peripheral neuropathy in rats. IBRO Rep. 2020;9:85–95. doi:10.1016/j.ibror.2020.07.006.

Topical medicinesin chemotherapy-induced peripheral neuropathy

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