Comprehensive Assessment of the Effectiveness of the Use of Alpha-lipoic Acid and Ipidacrine Hydrochloride for the Prevention of Paclitaxel-indused Peripheral Neuropathy in Breast Cancer Patients
Abstract
Abstract. Almost 97% of women undergoing chemotherapy with paclitaxel for breast cancer suffer from symptoms of peripheral neuropathy, the severity of which directly depends on the single, cumulative dose and duration of infusion of the agent. Neurological manifestations of paclitaxel-induced peripheral neuropathy, such as bilateral numbness, neuropathic pain and paresthesias in the distal parts of the limbs, often lead to the need to reduce doses, up to the refusal of taxanes, which negatively affects the immediate and long-term results of treatment. Despite numerous scientific studies, there are no known means for prevention of chemotherapy-induced peripheral neuropathy. Of the more than 20 drugs studied so far for the prevention of chemotherapy-induced peripheral neuropathy, none has shown sustained and systemic clinically significant results.
The aim of the study: to assess the effectiveness of the combination of alpha-lipoic acid and acetylcholinesterase inhibitor ipidacrine hydrochloride for the prevention of paclitaxel-induced peripheral neuropathy in breast cancer patients.
Materials and methods of the study: a comprehensive assessment of clinical (survey regarding subjective symptoms and quality of life, neurological examination), neurophysiological (electroneuromyography) and morphological indices of paclitaxel-induced peripheral neuropathy in breast cancer patients who received polychemotherapy in neoadjuvant, adjuvant or palliative settings carried out according to the schemes of AT (paclitaxel, doxorubicin) or ET (paclitaxel, epirubicin) regimens with or without preventive treatment of neuropathy, has been performed.
Results of the study. The use of the studied scheme for the prevention of paclitaxel-induced peripheral neuropathy led to a significant improvement in neurological manifestations, neurophysiological and morphometric parameters of peripheral nerves, as well as quality of life and the severity of subjective symptoms and their impact on daily life activities in comparison with patients who received chemotherapy without treatment for the prevention of neuropathy.
Conclusions. The combination of alpha-lipoic acid and the acetylcholinesterase inhibitor - ipidacrine hydrochloride, could be recommended for prophylaxis of paclitaxel-induced peripheral neuropathy.
Key words: breast cancer, chemotherapy, polyneuropathy, prevention, questionnaires, electroneuromyography, morphometric analysis.
References
Škubník J, Pavlíčková V, Ruml T, Rimpelová S. Current Perspectives on Taxanes: Focus on Their Bioactivity, Delivery and Combination Therapy. Plants (Basel). 2021; 10(3):569. Available at: https://doi.org/10.3390/plants10030569
Cardoso F, Senkus E, Costa A, et al. 4th ESO-ESMO International Consensus Guidelines for Advanced Breast Cancer (ABC 4). Ann Oncol. 2018; 29(8):1634-1657. Available at: https://doi.org/10.1093/annonc/mdy192
Cortazar P, Zhang L, Untch M, et al. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis [published correction appears in Lancet. 2019 Mar 9;393(10175):986]. Lancet. 2014; 384(9938):164-172. Available at: https://doi.org/10.1016/S0140-6736(13)62422-8
Mackey JR, Martin M, Pienkowski T, et al. Adjuvant docetaxel, doxorubicin, and cyclophosphamide in node-positive breast cancer: 10-year follow-up of the phase 3 randomised BCIRG 001 trial. Lancet Oncol. 2013; 14(1):72-80. Available at: https://doi.org/10.1016/S1470-2045(12)70525-9
Nitz U, Gluz O, Huober J, et al. Final analysis of the prospective WSG-AGO EC-Doc versus FEC phase III trial in intermediate-risk (pN1) early breast cancer: efficacy and predictive value of Ki67 expression [published correction appears in Ann Oncol. 2017 Nov 1;28(11):2899]. Ann Oncol. 2014; 25(8):1551-1557. Available at: https://doi.org/10.1093/annonc/mdu186
Hershman DL, Unger JM, Crew KD, et al. Two-year trends of taxane-induced neuropathy inwomen enrolled in a randomized trial of acetyl-L-carnitine (SWOG S0715). J Natl Cancer Inst. 2018; 110 (6):669-76. Available at: https://doi.org/10.1093/jnci/djx259
Tanabe Y, Hashimoto K, Shimizu C, et al. Paclitaxel-induced peripheral neuropathy in patients receiving adjuvant chemotherapy for breast cancer. Int J Clin Oncol. 2013; 18(1):132-138. Available at: https://doi.org/10.1007/s10147-011-0352-x
Winters-Stone KM, Horak F, Jacobs PG, et al. Falls, Functioning, and Disability Among Women With Persistent Symptoms of Chemotherapy-Induced Peripheral Neuropathy. J Clin Oncol 2017; 35:2604-2612. Available at: https://doi.org/10.1200/JCO.2016.71.3552
Salgado TM, Quinn CS, Krumbach EK, et al. Reporting of paclitaxel-induced peripheral neuropathy symptoms to clinicians among women with breast cancer: a qualitative study. Support Care Cancer. 2020; 28(9):4163-4172. Available at: https://doi.org/10.1007/s00520-019-05254-6
Klein I, Lehmann HC. Pathomechanisms of Paclitaxel-Induced Peripheral Neuropathy. Toxics. 2021; 9(10):229. Available at: https://doi.org/10.3390/toxics9100229
Velasco-González R, Coffeen U. Neurophysiopathological Aspects of Paclitaxel-induced Peripheral Neuropathy. Neurotox Res. 2022; 40(6):1673-1689. Available at: https://doi.org/10.1007/s12640-022-00582-8
Velasco R, Bruna J. Taxane-Induced Peripheral Neurotoxicity. Toxics. 2015; 3(2):152-169. Available at: https://doi.org/10.3390/toxics3020152
Loprinzi CL, Lacchetti C, Bleeker J, et al. Prevention and Management of Chemotherapy-Induced Peripheral Neuropathy in Survivors of Adult Cancers: ASCO Guideline Update. J Clin Oncol. 2020; 38(28):3325-3348. Available at: https://doi.org/10.1200/JCO.20.01399
Bonetti M, Lauritano D, Ottaviani GM, et al. Oxygen-Ozone Therapy Associated with Alpha Lipoic Acid Plus Palmitoylethanolamide and Myrrh versus Ozone Therapy in the Combined Treatment of Sciatic Pain Due to Herniated Discs: Observational Study on 318 Patients. Int J Environ Res Public Health. 2022; 19(9):5716. Available at: https://doi.org/10.3390/ijerph19095716
Capece U, Moffa S, Improta I, et al. Alpha-Lipoic Acid and Glucose Metabolism: A Comprehensive Update on Biochemical and Therapeutic Features. Nutrients. 2022; 15(1):18. Available at: https://doi.org/10.3390/nu15010018
Agathos E, Tentolouris A, Eleftheriadou I, et al. Effect of α-lipoic acid on symptoms and quality of life in patients with painful diabetic neuropathy. J Int Med Res. 2018; 46(5):1779-1790. Available at: https://doi.org/10.1177/0300060518756540
Schloss J, Colosimo M, Vitetta L. New Insights into Potential Prevention and Management Options for Chemotherapy-Induced Peripheral Neuropathy. Asia Pac J Oncol Nurs. 2016; 3(1):73-85. Available at: https://doi.org/10.4103/2347-5625.170977
Kyte SL, Toma W, Bagdas D, et al. Nicotine Prevents and Reverses Paclitaxel-Induced Mechanical Allodynia in a Mouse Model of CIPN. J Pharmacol Exp Ther. 2018; 364(1):110-119. Available at: https://doi.org/10.1124/jpet.117.243972
Toma W, Kyte SL, Bagdas D, et al. The α7 nicotinic receptor silent agonist R-47 prevents and reverses paclitaxel-induced peripheral neuropathy in mice without tolerance or altering nicotine reward and withdrawal. Exp Neurol. 2019; 320:113010. Available at: https://doi.org/10.1016/j.expneurol.2019.113010
Ishii N, Tsubouchi H, Miura A, et al. Ghrelin alleviates paclitaxel-induced peripheral neuropathy by reducing oxidative stress and enhancing mitochondrial anti-oxidant functions in mice. Eur J Pharmacol. 2018; 819:35-42. Available at: https://doi.org/10.1016/j.ejphar.2017.11.024
Gornstein EL, Schwarz TL. Neurotoxic mechanisms of paclitaxel are local to the distal axon and independent of transport defects. Exp Neurol. 2017; 288:153-166. Available at: https://doi.org/10.1016/j.expneurol.2016.11.015
Da Costa R, Passos GF, Quintão NLM, et al. Taxane-induced neurotoxicity: Pathophysiology and therapeutic perspectives. Br J Pharmacol. 2020; 177(14):3127-3146. Available at: https://doi.org/10.1111/bph.15086
Duggett NA, Griffiths LA, McKenna OE, et al. Oxidative stress in the development, maintenance and resolution of paclitaxel-induced painful neuropathy. Neuroscience. 2016; 333:13-26. Available at: https://doi.org/10.1016/j.neuroscience.2016.06.050
Sisignano M, Baron R, Scholich K, Geisslinger G. Mechanism-based treatment for chemotherapy-induced peripheral neuropathic pain. Nat Rev Neurol. 2014; 10(12):694-707. Available at: https://doi.org/10.1038/nrneurol.2014.211
Hosseini A, Abdollahi M. Diabetic neuropathy and oxidative stress: therapeutic perspectives. Oxid Med Cell Longev. 2013; 2013:168039. Available at: https://doi.org/10.1155/2013/168039
Di Cesare Mannelli L, Zanardelli M, Ghelardini C. Nicotine is a pain reliever in trauma- and chemotherapy-induced neuropathy models. Eur J Pharmacol. 2013; 711(1-3):87-94.
Available at: https://doi.org/10.1016/j.ejphar.2013.04.022
Di Cesare Mannelli L, Pacini A, Matera C, et al. Involvement of α7 nAChR subtype in rat oxaliplatin-induced neuropathy: effects of selective activation. Neuropharmacology. 2014; 79:37-48. Available at: https://doi.org/10.1016/j.neuropharm.2013.10.034
Ferrier J, Bayet-Robert M, Dalmann R, et al. Cholinergic Neurotransmission in the Posterior Insular Cortex Is Altered in Preclinical Models of Neuropathic Pain: Key Role of Muscarinic M2 Receptors in Donepezil-Induced Antinociception. J Neurosci. 2015; 35(50):16418-16430. Available at: https://doi.org/10.1523/JNEUROSCI.1537-15.2015
Romero HK, Christensen SB, Di Cesare Mannelli L, et al. Inhibition of α9α10 nicotinic acetylcholine receptors prevents chemotherapy-induced neuropathic pain. Proc Natl Acad Sci U S A. 2017; 114(10):E1825-E1832. https://doi.org/10.1073/pnas.1621433114
Yamamoto S, Egashira N. Drug Repositioning for the Prevention and Treatment of Chemotherapy-Induced Peripheral Neuropathy: A Mechanism- and Screening-Based Strategy. Front Pharmacol. 2021; 11:607780. Available at: https://doi.org/10.3389/fphar.2020.607780
Kerckhove N, Tougeron D, Lepage C, et al. Efficacy of donepezil for the treatment of oxaliplatin-induced peripheral neuropathy: DONEPEZOX, a protocol of a proof of concept, randomised, triple-blinded and multicentre trial. BMC Cancer. 2022; 22(1):742. Available at: https://doi.org/10.1186/s12885-022-09806-8
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