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Prevention and treatment of chemotherapy-induced peripheral neuropathy

Charles L Loprinzi, MD
Section Editors
Reed E Drews, MD
Richard M Goldberg, MD
Deputy Editor
Diane MF Savarese, MD


Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse effect of cancer therapy that can have a profound impact on quality of life and survivorship [1]. Long-term neurotoxicity is an important issue for the growing number of cancer survivors, with the highest number of affected patients having been treated for breast and/or colon cancer. CIPN may also adversely affect oncologic outcomes by forcing dose modifications and/or premature treatment discontinuation. (See "Patterns of relapse and long-term complications of therapy in breast cancer survivors", section on 'Neurologic' and "Approach to the long-term survivor of colorectal cancer", section on 'Oxaliplatin-induced peripheral neuropathy'.)

The incidence of CIPN varies according to the chemotherapeutic agent, dose, duration of exposure, and method of assessment. The agents with the highest incidence are the platinum drugs, especially cisplatin and oxaliplatin, taxanes, vinca alkaloids, and bortezomib. The incidence, risk factors, pathogenetic mechanisms, and clinical characteristics of CIPN from these classes of agents as well as other chemotherapeutic drugs are discussed in detail elsewhere. (See "Overview of neurologic complications of platinum-based chemotherapy" and "Overview of neurologic complications of non-platinum cancer chemotherapy".)

This topic review will cover approaches to prevention and treatment of CIPN focusing mainly on platinum drugs, taxanes, vinca alkaloids, and bortezomib. An overview of neurologic complications with platinum and non-platinum chemotherapy drugs, and recommendations for dose modification for platinum and non-platinum chemotherapeutic drugs when neuropathy develops during therapy are provided elsewhere. (See "Overview of neurologic complications of platinum-based chemotherapy" and "Overview of neurologic complications of non-platinum cancer chemotherapy".)


Chronic neurotoxicity — Regardless of the specific drug, chronic chemotherapy-induced peripheral neuropathy (CIPN) has similar distinguishing clinical features that help to differentiate it from other neuropathies (table 1) (see "Overview of neurologic complications of non-platinum cancer chemotherapy" and "Overview of neurologic complications of platinum-based chemotherapy"):

CIPN is typically dose-dependent and cumulative.

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Literature review current through: Oct 2017. | This topic last updated: Oct 13, 2017.
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  1. Mols F, Beijers T, Vreugdenhil G, van de Poll-Franse L. Chemotherapy-induced peripheral neuropathy and its association with quality of life: a systematic review. Support Care Cancer 2014; 22:2261.
  2. Bennett BK, Park SB, Lin CS, et al. Impact of oxaliplatin-induced neuropathy: a patient perspective. Support Care Cancer 2012; 20:2959.
  3. Hershman DL, Weimer LH, Wang A, et al. Association between patient reported outcomes and quantitative sensory tests for measuring long-term neurotoxicity in breast cancer survivors treated with adjuvant paclitaxel chemotherapy. Breast Cancer Res Treat 2011; 125:767.
  4. 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; 18:132.
  5. Richardson PG, Sonneveld P, Schuster MW, et al. Reversibility of symptomatic peripheral neuropathy with bortezomib in the phase III APEX trial in relapsed multiple myeloma: impact of a dose-modification guideline. Br J Haematol 2009; 144:895.
  6. 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.
  7. Miaskowski C, Mastick J, Paul SM, et al. Chemotherapy-Induced Neuropathy in Cancer Survivors. J Pain Symptom Manage 2017; 54:204.
  8. Loprinzi CL, Maddocks-Christianson K, Wolf SL, et al. The Paclitaxel acute pain syndrome: sensitization of nociceptors as the putative mechanism. Cancer J 2007; 13:399.
  9. Loprinzi CL, Reeves BN, Dakhil SR, et al. Natural history of paclitaxel-associated acute pain syndrome: prospective cohort study NCCTG N08C1. J Clin Oncol 2011; 29:1472.
  10. Reeves BN, Dakhil SR, Sloan JA, et al. Further data supporting that paclitaxel-associated acute pain syndrome is associated with development of peripheral neuropathy: North Central Cancer Treatment Group trial N08C1. Cancer 2012; 118:5171.
  11. von Delius S, Eckel F, Wagenpfeil S, et al. Carbamazepine for prevention of oxaliplatin-related neurotoxicity in patients with advanced colorectal cancer: final results of a randomised, controlled, multicenter phase II study. Invest New Drugs 2007; 25:173.
  12. Lévi F, Misset JL, Brienza S, et al. A chronopharmacologic phase II clinical trial with 5-fluorouracil, folinic acid, and oxaliplatin using an ambulatory multichannel programmable pump. High antitumor effectiveness against metastatic colorectal cancer. Cancer 1992; 69:893.
  13. Argyriou AA, Chroni E, Polychronopoulos P, et al. Efficacy of oxcarbazepine for prophylaxis against cumulative oxaliplatin-induced neuropathy. Neurology 2006; 67:2253.
  14. Albers JW, Chaudhry V, Cavaletti G, Donehower RC. Interventions for preventing neuropathy caused by cisplatin and related compounds. Cochrane Database Syst Rev 2014; :CD005228.
  15. Hershman DL, Lacchetti C, Dworkin RH, 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; 32:1941.
  16. Shinde SS, Seisler D, Soori G, et al. Can pregabalin prevent paclitaxel-associated neuropathy?--An ACCRU pilot trial. Support Care Cancer 2016; 24:547.
  17. de Andrade DC, Jacobsen Teixeira M, Galhardoni R, et al. Pregabalin for the Prevention of Oxaliplatin-Induced Painful Neuropathy: A Randomized, Double-Blind Trial. Oncologist 2017; 22:1154.
  18. Kautio AL, Haanpää M, Leminen A, et al. Amitriptyline in the prevention of chemotherapy-induced neuropathic symptoms. Anticancer Res 2009; 29:2601.
  19. Durand JP, Deplanque G, Montheil V, 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; 23:200.
  20. Zimmerman C, Atherton PJ, Pachman D, et al. MC11C4: a pilot randomized, placebo-controlled, double-blind study of venlafaxine to prevent oxaliplatin-induced neuropathy. Support Care Cancer 2016; 24:1071.
  21. Kautio AL, Haanpää M, Kautiainen H, et al. Oxaliplatin scale and National Cancer Institute-Common Toxicity Criteria in the assessment of chemotherapy-induced peripheral neuropathy. Anticancer Res 2011; 31:3493.
  22. Castiglione F, Dalla Mola A, Porcile G. Protection of normal tissues from radiation and cytotoxic therapy: the development of amifostine. Tumori 1999; 85:85.
  23. Kemp G, Rose P, Lurain J, et al. Amifostine pretreatment for protection against cyclophosphamide-induced and cisplatin-induced toxicities: results of a randomized control trial in patients with advanced ovarian cancer. J Clin Oncol 1996; 14:2101.
  24. Planting AS, Catimel G, de Mulder PH, et al. Randomized study of a short course of weekly cisplatin with or without amifostine in advanced head and neck cancer. EORTC Head and Neck Cooperative Group. Ann Oncol 1999; 10:693.
  25. Glover D, Ibrahim J, Kirkwood J, et al. Phase II randomized trial of cisplatin and WR-2721 versus cisplatin alone for metastatic melanoma: an Eastern Cooperative Oncology Group Study (E1686). Melanoma Res 2003; 13:619.
  26. Leong SS, Tan EH, Fong KW, et al. Randomized double-blind trial of combined modality treatment with or without amifostine in unresectable stage III non-small-cell lung cancer. J Clin Oncol 2003; 21:1767.
  27. De Vos FY, Bos AM, Schaapveld M, et al. A randomized phase II study of paclitaxel with carboplatin +/- amifostine as first line treatment in advanced ovarian carcinoma. Gynecol Oncol 2005; 97:60.
  28. Kanat O, Evrensel T, Baran I, 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 2003; 20:237.
  29. Hilpert F, Stähle A, Tomé O, et al. Neuroprotection with amifostine in the first-line treatment of advanced ovarian cancer with carboplatin/paclitaxel-based chemotherapy--a double-blind, placebo-controlled, randomized phase II study from the Arbeitsgemeinschaft Gynäkologische Onkologoie (AGO) Ovarian Cancer Study Group. Support Care Cancer 2005; 13:797.
  30. Moore DH, Donnelly J, McGuire WP, et al. Limited access trial using amifostine for protection against cisplatin- and three-hour paclitaxel-induced neurotoxicity: a phase II study of the Gynecologic Oncology Group. J Clin Oncol 2003; 21:4207.
  31. Gelmon K, Eisenhauer E, Bryce C, et al. Randomized phase II study of high-dose paclitaxel with or without amifostine in patients with metastatic breast cancer. J Clin Oncol 1999; 17:3038.
  32. Lorusso D, Ferrandina G, Greggi S, et al. Phase III multicenter randomized trial of amifostine as cytoprotectant in first-line chemotherapy in ovarian cancer patients. Ann Oncol 2003; 14:1086.
  33. Gallardo D, Mohar A, Calderillo G, et al. Cisplatin, radiation, and amifostine in carcinoma of the uterine cervix. Int J Gynecol Cancer 1999; 9:225.
  34. Cassidy J, Paul J, Soukop M, et al. Clinical trials of nimodipine as a potential neuroprotector in ovarian cancer patients treated with cisplatin. Cancer Chemother Pharmacol 1998; 41:161.
  35. Davis ID, Kiers L, MacGregor L, et al. A randomized, double-blinded, placebo-controlled phase II trial of recombinant human leukemia inhibitory factor (rhuLIF, emfilermin, AM424) to prevent chemotherapy-induced peripheral neuropathy. Clin Cancer Res 2005; 11:1890.
  36. Zhang RX, Lu ZH, Wan DS, et al. Neuroprotective effect of neurotropin on chronic oxaliplatin-induced neurotoxicity in stage II and stage III colorectal cancer patients: results from a prospective, randomised, single-centre, pilot clinical trial. Int J Colorectal Dis 2012; 27:1645.
  37. Gandara DR, Nahhas WA, Adelson MD, et al. Randomized placebo-controlled multicenter evaluation of diethyldithiocarbamate for chemoprotection against cisplatin-induced toxicities. J Clin Oncol 1995; 13:490.
  38. Roberts JA, Jenison EL, Kim K, et al. A randomized, multicenter, double-blind, placebo-controlled, dose-finding study of ORG 2766 in the prevention or delay of cisplatin-induced neuropathies in women with ovarian cancer. Gynecol Oncol 1997; 67:172.
  39. van Kooten B, van Diemen HA, Groenhout KM, et al. A pilot study on the influence of a corticotropin (4-9) analogue on Vinca alkaloid-induced neuropathy. Arch Neurol 1992; 49:1027.
  40. Koeppen S, Verstappen CC, Körte R, et al. Lack of neuroprotection by an ACTH (4-9) analogue. A randomized trial in patients treated with vincristine for Hodgkin's or non-Hodgkin's lymphoma. J Cancer Res Clin Oncol 2004; 130:153.
  41. van der Hoop RG, Vecht CJ, van der Burg ME, et al. Prevention of cisplatin neurotoxicity with an ACTH(4-9) analogue in patients with ovarian cancer. N Engl J Med 1990; 322:89.
  42. Hovestadt A, van der Burg ME, Verbiest HB, et al. The course of neuropathy after cessation of cisplatin treatment, combined with Org 2766 or placebo. J Neurol 1992; 239:143.
  43. van Gerven JM, Hovestadt A, Moll JW, et al. The effects of an ACTH (4-9) analogue on development of cisplatin neuropathy in testicular cancer: a randomized trial. J Neurol 1994; 241:432.
  44. Pisano C, Pratesi G, Laccabue D, et al. Paclitaxel and Cisplatin-induced neurotoxicity: a protective role of acetyl-L-carnitine. Clin Cancer Res 2003; 9:5756.
  45. Bianchi G, Vitali G, Caraceni A, et al. Symptomatic and neurophysiological responses of paclitaxel- or cisplatin-induced neuropathy to oral acetyl-L-carnitine. Eur J Cancer 2005; 41:1746.
  46. Maestri A, De Pasquale Ceratti A, Cundari S, et al. A pilot study on the effect of acetyl-L-carnitine in paclitaxel- and cisplatin-induced peripheral neuropathy. Tumori 2005; 91:135.
  47. Hershman DL, Unger JM, Crew KD, 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 2013; 31:2627.
  48. Gamelin L, Boisdron-Celle M, Delva R, 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 2004; 10:4055.
  49. Grothey A, Hart LL, Rowland KM, et al. Intermittent oxaliplatin administration and time to treatment failure in metastatic colorectal cancer: Final results of the phase III CONcePT trial (abstract). J Clin Oncol 2008; 26s:abstr 4010. http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst_detail_view&confID=55&abstractID=34113 (Accessed on July 26, 2012).
  50. Grothey A, Nikcevich DA, Sloan JA, et al. Intravenous calcium and magnesium for oxaliplatin-induced sensory neurotoxicity in adjuvant colon cancer: NCCTG N04C7. J Clin Oncol 2011; 29:421.
  51. Chay WY, Tan SH, Lo YL, et al. Use of calcium and magnesium infusions in prevention of oxaliplatin induced sensory neuropathy. Asia Pac J Clin Oncol 2010; 6:270.
  52. Ishibashi K, Okada N, Miyazaki T, et al. Effect of calcium and magnesium on neurotoxicity and blood platinum concentrations in patients receiving mFOLFOX6 therapy: a prospective randomized study. Int J Clin Oncol 2010; 15:82.
  53. Hochster HS, Grothey A, Shpilsky A, Childs BH. Effect of intravenous (IV) calcium and magnesium vs placebo on response to FOLFOX + bevacizumab in the CONcePT trial. Presented at the 2008 Gastrointestinal Cancers Symposium, Orlando, FL, January 20, 2008.
  54. Gamelin L, Boisdron-Celle M, Morel A, et al. Oxaliplatin-related neurotoxicity: interest of calcium-magnesium infusion and no impact on its efficacy. J Clin Oncol 2008; 26:1188.
  55. Loprinzi CL, Qin R, Dakhil SR, 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 2014; 32:997.
  56. Postma TJ, Aaronson NK, Heimans JJ, et al. The development of an EORTC quality of life questionnaire to assess chemotherapy-induced peripheral neuropathy: the QLQ-CIPN20. Eur J Cancer 2005; 41:1135.
  57. Wang WS, Lin JK, Lin TC, et al. Oral glutamine is effective for preventing oxaliplatin-induced neuropathy in colorectal cancer patients. Oncologist 2007; 12:312.
  58. Loven D, Levavi H, Sabach G, et al. Long-term glutamate supplementation failed to protect against peripheral neurotoxicity of paclitaxel. Eur J Cancer Care (Engl) 2009; 18:78.
  59. Mokhtar GM, Shaaban SY, Elbarbary NS, Fayed WA. A trial to assess the efficacy of glutamic acid in prevention of vincristine-induced neurotoxicity in pediatric malignancies: a pilot study. J Pediatr Hematol Oncol 2010; 32:594.
  60. Jackson DV, Wells HB, Atkins JN, et al. Amelioration of vincristine neurotoxicity by glutamic acid. Am J Med 1988; 84:1016.
  61. Cascinu S, Catalano V, Cordella L, 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 2002; 20:3478.
  62. Smyth JF, Bowman A, Perren T, et al. Glutathione reduces the toxicity and improves quality of life of women diagnosed with ovarian cancer treated with cisplatin: results of a double-blind, randomised trial. Ann Oncol 1997; 8:569.
  63. Colombo N, Bini S, Miceli D, et al. Weekly cisplatin +/- glutathione in relapsed ovarian carcinoma. Int J Gynecol Cancer 1995; 5:81.
  64. Cascinu S, Cordella L, Del Ferro E, et al. Neuroprotective effect of reduced glutathione on cisplatin-based chemotherapy in advanced gastric cancer: a randomized double-blind placebo-controlled trial. J Clin Oncol 1995; 13:26.
  65. Milla P, Airoldi M, Weber G, et al. Administration of reduced glutathione in FOLFOX4 adjuvant treatment for colorectal cancer: effect on oxaliplatin pharmacokinetics, Pt-DNA adduct formation, and neurotoxicity. Anticancer Drugs 2009; 20:396.
  66. Schmidinger M, Budinsky AC, Wenzel C, 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. Wien Klin Wochenschr 2000; 112:617.
  67. Bogliun G, Marzorati L, MArzola M, et al. Neurotoxicity of cisplatin +/- reduced glutathione in the first-line treatment of advanced ovarian cancer. Int J Gynecol Cancer 1996; 6:415.
  68. Leal AD, Qin R, Atherton PJ, et al. North Central Cancer Treatment Group/Alliance trial N08CA-the use of glutathione for prevention of paclitaxel/carboplatin-induced peripheral neuropathy: a phase 3 randomized, double-blind, placebo-controlled study. Cancer 2014; 120:1890.
  69. Lin PC, Lee MY, Wang WS, et al. N-acetylcysteine has neuroprotective effects against oxaliplatin-based adjuvant chemotherapy in colon cancer patients: preliminary data. Support Care Cancer 2006; 14:484.
  70. Nishioka M, Shimada M, Kurita N, et al. The Kampo medicine, Goshajinkigan, prevents neuropathy in patients treated by FOLFOX regimen. Int J Clin Oncol 2011; 16:322.
  71. Shirao K, Matsumura Y, Yamada Y, et al. Phase I study of single-dose oxaliplatin in Japanese patients with malignant tumors. Jpn J Clin Oncol 2006; 36:295.
  72. Kono T, Hata T, Morita S, 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 2013; 72:1283.
  73. Oki E, Emi Y, Kojima H, 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 2015; 20:767.
  74. Zirpoli GR, McCann SE, Sucheston-Campbell LE, et al. Supplement Use and Chemotherapy-Induced Peripheral Neuropathy in a Cooperative Group Trial (S0221): The DELCaP Study. J Natl Cancer Inst 2017; 109.
  75. Ghoreishi Z, Esfahani A, Djazayeri A, et al. Omega-3 fatty acids are protective against paclitaxel-induced peripheral neuropathy: a randomized double-blind placebo controlled trial. BMC Cancer 2012; 12:355.
  76. Guo Y, Jones D, Palmer JL, et al. Oral alpha-lipoic acid to prevent chemotherapy-induced peripheral neuropathy: a randomized, double-blind, placebo-controlled trial. Support Care Cancer 2014; 22:1223.
  77. Pace A, Savarese A, Picardo M, et al. Neuroprotective effect of vitamin E supplementation in patients treated with cisplatin chemotherapy. J Clin Oncol 2003; 21:927.
  78. Argyriou AA, Chroni E, Koutras A, et al. Vitamin E for prophylaxis against chemotherapy-induced neuropathy: a randomized controlled trial. Neurology 2005; 64:26.
  79. Pace A, Giannarelli D, Galiè E, et al. Vitamin E neuroprotection for cisplatin neuropathy: a randomized, placebo-controlled trial. Neurology 2010; 74:762.
  80. Argyriou AA, Chroni E, Koutras A, et al. Preventing paclitaxel-induced peripheral neuropathy: a phase II trial of vitamin E supplementation. J Pain Symptom Manage 2006; 32:237.
  81. Kottschade LA, Sloan JA, Mazurczak MA, et al. The use of vitamin E for the prevention of chemotherapy-induced peripheral neuropathy: results of a randomized phase III clinical trial. Support Care Cancer 2011; 19:1769.
  82. Arrieta Ó, Hernández-Pedro N, Fernández-González-Aragón MC, et al. Retinoic acid reduces chemotherapy-induced neuropathy in an animal model and patients with lung cancer. Neurology 2011; 77:987.
  83. Petrioli R, Pascucci A, Francini E, et al. Neurotoxicity of FOLFOX-4 as adjuvant treatment for patients with colon and gastric cancer: a randomized study of two different schedules of oxaliplatin. Cancer Chemother Pharmacol 2008; 61:105.
  84. Bringhen S, Larocca A, Rossi D, et al. Efficacy and safety of once-weekly bortezomib in multiple myeloma patients. Blood 2010; 116:4745.
  85. Arnulf B, Pylypenko H, Grosicki S, et al. Updated survival analysis of a randomized phase III study of subcutaneous versus intravenous bortezomib in patients with relapsed multiple myeloma. Haematologica 2012; 97:1925.
  86. Moreau P, Pylypenko H, Grosicki S, et al. Subcutaneous versus intravenous administration of bortezomib in patients with relapsed multiple myeloma: a randomised, phase 3, non-inferiority study. Lancet Oncol 2011; 12:431.
  87. Streckmann F, Kneis S, Leifert JA, et al. Exercise program improves therapy-related side-effects and quality of life in lymphoma patients undergoing therapy. Ann Oncol 2014; 25:493.
  88. Kleckner I, Kamen CS, Peppone LJ, et al. A URCC NCORP nationwide randomized controlled trial investigating the effect of exercise on chemotherapy-induced peripheral neuropathy in 314 cancer patients (abstract). J Clin Oncol 34, 2016 (suppl; abstr 10000). Abstract available online at http://meetinglibrary.asco.org/content/170470-176 (Accessed on June 29, 2016).
  89. Courneya KS, McKenzie DC, Mackey JR, et al. Subgroup effects in a randomised trial of different types and doses of exercise during breast cancer chemotherapy. Br J Cancer 2014; 111:1718.
  90. Greenlee H, et al. Body mass index, lifestyle factors, and taxane-induced neuropathy in women with brewast cancer: the PAthways study (abstract). J Clin Oncol 34, 2016 (suppl; abstr 10002). Abstract available at http://meetinglibrary.asco.org/content/171378-176 (Accessed on July 05, 2016).
  91. Mols F, Beijers AJ, Vreugdenhil G, et al. Chemotherapy-induced peripheral neuropathy, physical activity and health-related quality of life among colorectal cancer survivors from the PROFILES registry. J Cancer Surviv 2015; 9:512.
  92. Stevinson C, Steed H, Faught W, et al. Physical activity in ovarian cancer survivors: associations with fatigue, sleep, and psychosocial functioning. Int J Gynecol Cancer 2009; 19:73.
  93. Hanai A, Ishiguro H, Sozu T, et al. The effects of frozen gloves and socks on paclitaxel-induced peripheral neuropathy among patients with breast cancer: A self-controlled clinical trial (abstract). J Clin oncol 34, 2016 (suppl; abstr 10022). Abstract available online at http://meetinglibrary.asco.org/content/166655-176 (Accessed on June 30, 2016).
  94. Hsu HY, Shieh SJ, Kuan TS, et al. Manual Tactile Test Predicts Sensorimotor Control Capability of Hands for Patients With Peripheral Nerve Injury. Arch Phys Med Rehabil 2016; 97:983.
  95. Sundar R, Bandla A, Tan S, et al. The role of limb hypothermia in preventing paclitaxel-induced peripheral neuropathy (abstraact). J Clin Oncol 34, 2016 (suppl; abstr e21696). Abstract available online at http://meetinglibrary.asco.org/content/167023-176 (Accessed on July 05, 2016).
  96. Gewandter JS, Mohile SG, Heckler CE, et al. A phase III randomized, placebo-controlled study of topical amitriptyline and ketamine for chemotherapy-induced peripheral neuropathy (CIPN): a University of Rochester CCOP study of 462 cancer survivors. Support Care Cancer 2014; 22:1807.
  97. Smith EM, Pang H, Cirrincione C, 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; 309:1359.
  98. Calhoun EA, Welshman EE, Chang CH, et al. Psychometric evaluation of the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (Fact/GOG-Ntx) questionnaire for patients receiving systemic chemotherapy. Int J Gynecol Cancer 2003; 13:741.
  99. Aaronson NK, Ahmedzai S, Bergman B, et al. The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst 1993; 85:365.
  100. Hirayama Y, Ishitani K, Sato Y, et al. Effect of duloxetine in Japanese patients with chemotherapy-induced peripheral neuropathy: a pilot randomized trial. Int J Clin Oncol 2015; 20:866.
  101. Hammack JE, Michalak JC, Loprinzi CL, et al. Phase III evaluation of nortriptyline for alleviation of symptoms of cis-platinum-induced peripheral neuropathy. Pain 2002; 98:195.
  102. Kautio AL, Haanpää M, Saarto T, Kalso E. Amitriptyline in the treatment of chemotherapy-induced neuropathic symptoms. J Pain Symptom Manage 2008; 35:31.
  103. Rao RD, Michalak JC, Sloan JA, et al. Efficacy of gabapentin in the management of chemotherapy-induced peripheral neuropathy: a phase 3 randomized, double-blind, placebo-controlled, crossover trial (N00C3). Cancer 2007; 110:2110.
  104. Rao RD, Flynn PJ, Sloan JA, et al. Efficacy of lamotrigine in the management of chemotherapy-induced peripheral neuropathy: a phase 3 randomized, double-blind, placebo-controlled trial, N01C3. Cancer 2008; 112:2802.
  105. Nihei S, Sato J, Kashiwaba M, et al. [Efficacy and safety of pregabalin for oxaliplatin- and paclitaxel-induced peripheral neuropathy]. Gan To Kagaku Ryoho 2013; 40:1189.
  106. Nagahara H, Noda E, Maeda K, et al. [Promising effects of pregabalin in the treatment of oxaliplatin-induced sensory neuropathy in patients with colorectal carcinoma]. Gan To Kagaku Ryoho 2013; 40:1181.
  107. Saif MW, Syrigos K, Kaley K, Isufi I. Role of pregabalin in treatment of oxaliplatin-induced sensory neuropathy. Anticancer Res 2010; 30:2927.
  108. ClinicalTrials.gov. Prevention and treatment of chemotherapy-induced peripheral neuropathy in subjects with advanced colorectal cancer. http://clinicaltrials.gov/ct2/show/NCT00380874 (Accessed on May 02, 2014).
  109. Sands S, Ladas EJ, Kelly KM, et al. Glutamine for the treatment of vincristine-induced neuropathy in children and adolescents with cancer. Support Care Cancer 2017; 25:701.
  110. Barton DL, Wos EJ, Qin R, et al. A double-blind, placebo-controlled trial of a topical treatment for chemotherapy-induced peripheral neuropathy: NCCTG trial N06CA. Support Care Cancer 2011; 19:833.
  111. Colvin LA, Johnson PR, Mitchell R, et al. From bench to bedside: a case of rapid reversal of bortezomib-induced neuropathic pain by the TRPM8 activator, menthol. J Clin Oncol 2008; 26:4519.
  112. Storey DJ, Colvin LA, Mackean MJ, et al. Reversal of dose-limiting carboplatin-induced peripheral neuropathy with TRPM8 activator, menthol, enables further effective chemotherapy delivery. J Pain Symptom Manage 2010; 39:e2.
  113. Davies SJ, Harding LM, Baranowski AP. A novel treatment of postherpetic neuralgia using peppermint oil. Clin J Pain 2002; 18:200.
  114. Fallon MT, Storey DJ, Krishan A, et al. Cancer treatment-related neuropathic pain: proof of concept study with menthol--a TRPM8 agonist. Support Care Cancer 2015; 23:2769.
  115. Ravaglia S, Corso A, Piccolo G, et al. Immune-mediated neuropathies in myeloma patients treated with bortezomib. Clin Neurophysiol 2008; 119:2507.
  116. Smith TJ, Coyne PJ, Parker GL, et al. Pilot trial of a patient-specific cutaneous electrostimulation device (MC5-A Calmare®) for chemotherapy-induced peripheral neuropathy. J Pain Symptom Manage 2010; 40:883.
  117. Coyne PJ, Wan W, Dodson P, et al. A trial of Scrambler therapy in the treatment of cancer pain syndromes and chronic chemotherapy-induced peripheral neuropathy. J Pain Palliat Care Pharmacother 2013; 27:359.
  118. Pachman DR, Weisbrod BL, Seisler DK, et al. Pilot evaluation of Scrambler therapy for the treatment of chemotherapy-induced peripheral neuropathy. Support Care Cancer 2015; 23:943.
  119. Prinsloo S, Novy D, Driver L, et al. Randomized controlled trial of neurofeedback on chemotherapy-induced peripheral neuropathy: A pilot study. Cancer 2017; 123:1989.
  120. Hainsworth JD, Urba WJ, Hon JK, et al. One-hour paclitaxel plus carboplatin in the treatment of advanced non-small cell lung cancer: results of a multicentre, phase II trial. Eur J Cancer 1998; 34:654.
  121. Smith RE, Brown AM, Mamounas EP, et al. Randomized trial of 3-hour versus 24-hour infusion of high-dose paclitaxel in patients with metastatic or locally advanced breast cancer: National Surgical Adjuvant Breast and Bowel Project Protocol B-26. J Clin Oncol 1999; 17:3403.
  122. Nabholtz JM, Gelmon K, Bontenbal M, et al. Multicenter, randomized comparative study of two doses of paclitaxel in patients with metastatic breast cancer. J Clin Oncol 1996; 14:1858.
  123. Gordon AN, Stringer CA, Matthews CM, et al. Phase I dose escalation of paclitaxel in patients with advanced ovarian cancer receiving cisplatin: rapid development of neurotoxicity is dose-limiting. J Clin Oncol 1997; 15:1965.
  124. Choy H, Akerley W, Safran H, et al. Phase I trial of outpatient weekly paclitaxel and concurrent radiation therapy for advanced non-small-cell lung cancer. J Clin Oncol 1994; 12:2682.
  125. Johnson DH, Paul DM, Hande KR, et al. Paclitaxel plus carboplatin in advanced non-small-cell lung cancer: a phase II trial. J Clin Oncol 1996; 14:2054.
  126. Markman M, Kennedy A, Webster K, et al. Use of low-dose oral prednisone to prevent paclitaxel-induced arthralgias and myalgias. Gynecol Oncol 1999; 72:100.
  127. Thomas P, Castelnau O, Paillotin D, et al. Phase II trial of paclitaxel and carboplatin in metastatic small-cell lung cancer: a Groupe Français de Pneumo-Cancérologie study. J Clin Oncol 2001; 19:1320.
  128. Jacobson SD, Loprinzi CL, Sloan JA, et al. Glutamine does not prevent paclitaxel-associated myalgias and arthralgias. J Support Oncol 2003; 1:274.
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