Subscribe to our Newsletter and get informed about new publication regulary and special discounts for subscribers!

IJPPE > IJPPE Volume 6 > Pharmacological Approaches and Natural Products...
< Back to Volume

Pharmacological Approaches and Natural Products for Prevention of Chemotherapy-Induced Peripheral Neuropathy - A Review

Full Text PDF


Chemotherapy-induced peripheral neuropathy (CIPN) is a one of the most common and severe cancer treatment-related adverse effect. It can often cause the stop of the treatment and affects the long-term quality of life of cancer survivors, too. Unfortunately, there are no effective agent or protocol to prevent with strong evidence of effectiveness this toxicity prevention of CIPN. Thus, CIPN prevention mainly consists of cumulative dose-reduction or lower dose-intensities, especially in higher risk patients. After a brief description of pathophysiology and features of CIPN, the purpose of this study is to analyse the role of standard pharmacological approaches and natural products for prevention of this serious side effect.


International Journal of Pharmacology, Phytochemistry and Ethnomedicine (Volume 6)
M. Cascella and M. R. Muzio, "Pharmacological Approaches and Natural Products for Prevention of Chemotherapy-Induced Peripheral Neuropathy - A Review", International Journal of Pharmacology, Phytochemistry and Ethnomedicine, Vol. 6, pp. 47-53, 2017
Online since:
January 2017

[1] C. Parnell, P. J Woll, Principles of cancer treatment by chemotherapy, Surgery (Oxford). 21 (2003) 272-276.

[2] J. Hildebrand, Neurological Adverse Reactions to Anticancer Drugs, Springer, Verlag, (1990).

[3] S. Park et al., Chemotherapy-induced peripheral neurotoxicity: a critical analysis, CA Cancer J. Clin. 63 (2013) 419-437.

[4] E. M. Smith et al., The reliability and validity of a modified total neuropathy score-reduced and neuropathic pain severity items when used to measure chemotherapy-induced peripheral neuropathy in patients receiving taxanes and platinums, Cancer Nurs. 33 (2010).


[5] M. A Tanay, J. Armes, E. Ream, The experience of chemotherapy-induced peripheral neuropathy in adult cancer patients: a qualitative thematic synthesis, Eur. J. Cancer Care. (2016).

[6] K. Brzeziński, Chemotherapy-induced polyneuropathy. Part I. Pathophysiology, Contemp. Oncol. 16 (2012) 72-78.

[7] E.S. McDonald et al., Cisplatin preferentially binds to DNA in dorsal root ganglion neurons in vitro and in vivo: a potential mechanism for neurotoxicity, Neurobiol. Dis. 18 (2005) 305–313.

[8] L. E Ta et al., Neurotoxicity of oxaliplatin and cisplatin for dorsal root ganglion neurons correlates with platinum-DNA binding, Neurotoxicology. 27 (2006) 992–1002.

[9] S.M. Swain, J.C. Arezzo, Neuropathy associated with microtubule inhibitors: diagnosis, incidence, and management, Adv. Hematol. Oncol. 6 (2008) 455–467.

[10] G. Cavaletti et al., Bortezomib-induced peripheral neurotoxicity: a neurophysiological and pathological study in the rat, Experimental Neurology. 204 (2007) 317–325.

[11] J.P. Cata et al., Quantitative sensory findings in patients with bortezomib-induced pain, Journal of Pain 8 (2007) 296–306.

[12] A.A. Argyriou, G. Iconomou, H.P. Kalofonos, Bortezomib-induced peripheral neuropathy in multiple myeloma: a comprehensive review of the literature, Blood. 112 (2008) 1593–1599.

[13] A. A Argyriou et al., Chemotherapy-induced peripheral neurotoxicity (CIPN): an update, Crit. Rev. Oncol. Hematol. 82 (2012) 51-77.

[14] M. Cascella, A. Cuomo, D. Viscardi, Pain syndromes associated with cancer therapy, in: M. Cascella, A. Cuomo, D. Viscardi (Eds), Features and Management of the Pelvic Cancer Pain, Springer, Verlag, 2016, pp.25-62.


[15] G. Franconi et al., A systematic review of experimental and clinical acupuncture in chemotherapy-induced peripheral neuropathy, Evid. Based Complement. Alternat. Med. 2013 (2013).

[16] D. L Hershman 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. 32 (2014) 1941-(1967).

[17] R. Fernandes et al., Treatment of taxane acute pain syndrome (TAPS) in cancer patients receiving taxane-based chemotherapy-a systematic review, Supportive Care in Cancer. 24(4) (2016) 1583-1594.

[18] F. Hilpert et al., Neuroprotection with amifostine in the first-line treatment of advanced ovarian cancer with carboplatin/paclitaxelbased chemotherapy–a double-blind, placebocontrolled, randomized phase II study from the Arbeitsgemeinschaft Gynakologische Onkologoie (AGO) Ovarian Cancer Study Group, Supportive Care in Cancer. 13(10) (2005).

[19] O. Kanat et al., Protective effect of amifostine against toxicity of paclitaxel and carboplatin in non-small cell lung cancer: A single center randomized study, Med. Oncol. 20 (2003) 237-245.

[20] P.C. Lin et al., N-acetylcysteine has neuroprotective effects against oxaliplatin-based adjuvant chemotherapy in colon cancer patients: Preliminary data, Supportive Care in Cancer. 14(5) (2006) 484-487.


[21] M. Schmidinger et al., Glutathione in the prevention of cisplatin induced toxicities. A prospectively randomized pilot trial in patients with head and neck cancer and non small cell lung cancer, Wiener Klinische Wochenschrift. 112 (2000) 617-623.

[22] S. Cascinu et al., Neuroprotective effect of reduced glutathione on oxaliplatin-based chemotherapy in advanced colorectal cancer: A randomized, double-blind, placebo controlled trial, J. Clin. Oncol. 20 (2002) 3478-3483.

[23] A. Leal et al., The use of glutathione for prevention of paclitaxel/carboplatin induced peripheral neuropathy: A phase III randomized, double-blind placebo-controlled study, Cancer. 120 (2014) 1890-7.

[24] J. Cassidy et al., Clinical trials of nimodipine as a potential neuroprotector in ovarian cancer patients treated with cisplatin, Cancer Chem. Pharmacol. 41 (1998) 161-166.

[25] L. Gamelin et al., 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. 10 (2004).


[26] C.L. Loprinzi et al., Phase III randomized, placebo-controlled, double-blind study of intravenous calcium and magnesium to prevent oxaliplatin-induced sensory neurotoxicity (N08CB/Alliance), J. Clin. Oncol. 32 (2014) 997-1005.

[27] J. P. Durand 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. 23 (2012) 200-205.

[28] A. Pace et al., Vitamin E neuroprotection for cisplatin neuropathy: A randomized, placebo-controlled trial, Neurology. 74(9) (2010) 762-766.

[29] P.H. Wiernik et al., Hexamethylmelamine and low or moderate dose cisplatin with or without pyridoxine for treatment of advanced ovarian carcinoma: A study of the Eastern Cooperative Oncology Group, Cancer Invest. 10 (1992) 1-9.

[30] Z. Ghoreishi et al., Omega-3 fatty acids are protective against paclitaxel-induced peripheral neuropathy: A randomized double-blind placebo controlled trial, BMC Cancer. 12 (2012) 355.


[31] L. Bove et al., A pilot study on the relation between cisplatin neuropathy and vitamin E, J. Exp. Clin. Cancer Res. 20 (2001) 277-280.

[32] L.A. Kottschade et al., The use of vitamin E for the prevention of chemotherapy-induced peripheral neuropathy: results of a randomized phase III clinical trial, Supportive Care in Cancer. 19(11) (2011) 1769-1777.


[33] Ó. Arrieta et al., Retinoic acid reduces chemotherapy-induced neuropathy in an animal model and patients with lung cancer, Neurology. 77 (2011) 987–995.

[34] D.L. Hershman et al., Randomized double-blind placebo-controlled trial of acetyl-L-carnitine for the prevention of taxane-induced neuropathy in women undergoing adjuvant breast cancer therapy, J. Clin. Oncol. 31 (2013) 2627–2633.


[35] M.S. Al Moundhri et al., The effect of curcumin on oxaliplatin and cisplatin neurotoxicity in rats, J. Med. Toxicol. 9 (2013) 25–33.

[36] A.N.A. Abad et al., Effect of matricaria chamomilla hydroalcoholic extract on cisplatin-induced neuropathy in mice, Chin. J. Nat. Med. 9 (2011) 126–131.

[37] H.J. Park et al., Ginkgo biloba extract attenuates hyperalgesia in a rat model of vincristine-induced peripheral neuropathy, Anesth. Analg. 115 (2012) 1228–1233.

[38] J.S. Lee et al., Effect of green tea extracts on oxaliplatin-induced peripheral neuropathy in rats, BMC Complement, Altern. Med. 12(1) (2012) 124.

[39] G.M. Cole, B. Teter, S.A. Frautschy, Neuroprotective effects of curcumin, Adv. Exp. Med. Biol. 595 (2007) 197-212.

[40] J. Epstein, I.R. Sanderson, T.T. Macdonald, Curcumin as a therapeutic agent: the evidence from in vitro, animal and human studies, Br. J. Nutr. 103 (2010) 1545–1557.

[41] S. Agthong, A. Kaewsema, T. Charoensub, Curcumin Ameliorates Functional and Structural Abnormalities in Cisplatin-induced Neuropathy, Exp. Neurobiol. 24 (2015) 139-145.


[42] P. Anand et al., Bioavailability of curcumin: problems and promises, Mol. Pharm. 4 (2007) 807–818.

[43] T Kono et al., Goshajinkigan oxaliplatin neurotoxicity evaluation (GONE): a phase 2, multicenter, randomized, double‑blind, placebo‑controlled trial of goshajinkigan to prevent oxaliplatin‑induced neuropathy, Cancer Chemother. Pharmacol. 72 (2013).

[44] T. Uno et al., Effects of Goshajinkigan on insulin resistance in patients with type 2 diabetes, Diabetes Res. Clin. Pract. 69 (2005) 129-135.

[45] W. Watanabe et al., Long-term effects of goshajinkigan in prevention of diabetic complications: a randomized open-labeled clinical trial, Evidence-based Complementary and Alternative Medicine. 2014 (2014).

[46] M. Nishioka et al., The Kampo medicine, goshajinkigan, prevents neuropathy in patients treated by FOLFOX regimen, Int. J. Clin. Oncol. 16 (2011) 322–327.

[47] Y. Matsumura et al., The prophylactic effects of a traditional Japanese medicine, goshajinkigan, on paclitaxel-induced peripheral neuropathy and its mechanism of action, Molecular Pain. 10 (2014) 61.

[48] T. Kono et al., Goshajinkigan oxaliplatin neurotoxicity evaluation (GONE): a phase 2, multicenter, randomized, double‑blind, placebo‑controlled trial of goshajinkigan to prevent oxaliplatin‑induced neuropathy, Cancer. Chemother. Pharmacol. 72 (2013).


[49] M. A Bahar et al, Herbal Medicine Goshajinkigan Prevents Paclitaxel-Induced Mechanical Allodynia without Impairing Antitumor Activity of Paclitaxel. Evidence-based Complementary and Alternative Medicine. 2013 (2013).


[50] Y. Omiya et al., Analgesia-producing mechanism of processed Aconiti tuber: role of dynorphin, an endogenous kappa-opioid ligand, in the rodent spinal cord, The Japanese Journal of Pharmacology. 79(3) (1999) 295–301.

[51] A. Gotoh et al., Inhibition mechanism of Gosha-jinki-gan on the micturition reflex in rats, J. Pharm. Sci. 96 (2004) 115–123.

[52] T. Imamura et al., Gosha-jinki-gan reduces transmitter proteins and sensory receptors associated with C fiber activation induced by acetic acid in rat urinary bladder, Neurourol. Urodyn. 27 (2008) 832–837.


[53] E.K. Joseph et al., Oxaliplatin acts on IB4-positive nociceptors to induce an oxidative stress-dependent acute painful peripheral neuropathy, J. Pain. 9 (2008) 463–472.

[54] M. Nakanishi et al., Go-sha-jinki-Gan (GJG) ameliorates allodynia in chronic constriction injury-model mice via suppression of TNF-α expression in the spinal cord, Mol. Pain. 12 (2016).

[55] T. Tai et al., Anti-emetic principles of Poria cocos, Planta Med. 61 (1995) 527-530.

[56] S. Ushio et al., Goshajinkigan reduces oxaliplatin-induced peripheral neuropathy without affecting anti-tumour efficacy in rodents, Eur. J. Cancer. 48 (2012) 1407–1413.

[57] J. Schloss, M. Colosimo, L. Vitetta, Herbal medicines and chemotherapy induced peripheral neuropathy (CIPN): a critical literature review, Crit. Rev. Food. Sci. Nutr. (2015).

[58] E. Oki et al., Preventive effect of Goshajinkigan on peripheral neurotoxicity of FOLFOX therapy (GENIUS trial): a placebo-controlled, double-blind, randomized phase III study, Int. J. Clin. Oncol. 20 (2015) 767-775.

[59] C. Brami, T. Bao, G. Deng, Natural products and complementary therapies for chemotherapy-induced peripheral neuropathy: A systematic review, Crit. Rev. Oncol. Hematol. 98 (2016) 325-334.

Show More Hide
Cited By:
This article has no citations.