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Overview of neurologic complications of non-platinum cancer chemotherapy

Eudocia Quant Lee, MD, MPH
Section Editors
Jay S Loeffler, MD
Patrick Y Wen, MD
Deputy Editor
Diane MF Savarese, MD


Neurologic complications of anticancer therapy may result from direct toxic effects on the nervous system or indirectly from drug-induced metabolic derangements, cerebrovascular disorders, or in the case of ipilimumab, autoimmune disorders. A wide range of neurologic complications is associated with antineoplastic drug treatment (table 1), the most common of which is chemotherapy-induced peripheral neuropathy (CIPN) (table 2) [1-4]. The site of peripheral nerve injury is variable (table 3).

Depending on its severity, CIPN can be dose-limiting and may also significantly diminish quality of life because it can persist and even intensify after the completion of chemotherapy.

Recognition of neurologic complication of anticancer therapy is important because of potential confusion with metastatic disease, paraneoplastic syndromes, or comorbid neurologic disorders that do not require dose reduction or discontinuation. (See "Overview of paraneoplastic syndromes of the nervous system".)

The neurotoxicity associated with a variety of conventional cytotoxic chemotherapy agents will be reviewed here. The neurologic complications of the platinum compounds (cisplatin, carboplatin, and oxaliplatin), biological response modifiers, and monoclonal antibodies are discussed elsewhere, as are strategies to prevent and manage chemotherapy-induced peripheral neuropathy. (See "Overview of neurologic complications of platinum-based chemotherapy" and "Neurologic complications of cancer treatment with biologic agents".)


Risk factors are best established for chemotherapy-induced peripheral neuropathy (CIPN), which include dose, dose intensity, length of treatment, concurrent administration of other neurotoxic agents (especially platinum derivatives), age, and in the case of bortezomib, route of administration. (See 'Bortezomib' below.)

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Literature review current through: Sep 2017. | This topic last updated: Oct 16, 2017.
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  1. DeAngelis LM, Posner JB. Side Effects of Chemotherapy. In: Neurologic Complications of Cancer, 2nd, Oxford University Press, New York 2009. p.447.
  2. Dietrich J, Wen PY. Neurologic complications of chemotherapy. In: Cancer Neurology in Clinical Practice, 2nd, Schiff D, Kesari S, Wen PY (Eds), Humana Press, Totowa, New Jersey 2008. p.287.
  3. Schiff D, Wen PY, van den Bent MJ. Neurological adverse effects caused by cytotoxic and targeted therapies. Nat Rev Clin Oncol 2009; 6:596.
  4. Sioka C, Kyritsis AP. Central and peripheral nervous system toxicity of common chemotherapeutic agents. Cancer Chemother Pharmacol 2009; 63:761.
  5. Chaudhry V, Chaudhry M, Crawford TO, et al. Toxic neuropathy in patients with pre-existing neuropathy. Neurology 2003; 60:337.
  6. Chauvenet AR, Shashi V, Selsky C, et al. Vincristine-induced neuropathy as the initial presentation of charcot-marie-tooth disease in acute lymphoblastic leukemia: a Pediatric Oncology Group study. J Pediatr Hematol Oncol 2003; 25:316.
  7. Trobaugh-Lotrario AD, Smith AA, Odom LF. Vincristine neurotoxicity in the presence of hereditary neuropathy. Med Pediatr Oncol 2003; 40:39.
  8. Kalfakis N, Panas M, Karadima G, et al. Hereditary neuropathy with liability to pressure palsies emerging during vincristine treatment. Neurology 2002; 59:1470.
  9. Miller BR. Neurotoxicity and vincristine. JAMA 1985; 253:2045.
  10. Windebank AJ, Grisold W. Chemotherapy-induced neuropathy. J Peripher Nerv Syst 2008; 13:27.
  11. Cavaletti G, Alberti P, Marmiroli P. Chemotherapy-induced peripheral neurotoxicity in the era of pharmacogenomics. Lancet Oncol 2011; 12:1151.
  12. Saif MW, Lee AM, Offer SM, et al. A DPYD variant (Y186C) specific to individuals of African descent in a patient with life-threatening 5-FU toxic effects: potential for an individualized medicine approach. Mayo Clin Proc 2014; 89:131.
  13. McWhinney-Glass S, Winham SJ, Hertz DL, et al. Cumulative genetic risk predicts platinum/taxane-induced neurotoxicity. Clin Cancer Res 2013; 19:5769.
  14. Beutler AS, Kulkarni AA, Kanwar R, et al. Sequencing of Charcot-Marie-Tooth disease genes in a toxic polyneuropathy. Ann Neurol 2014; 76:727.
  15. Diouf B, Crews KR, Lew G, et al. Association of an inherited genetic variant with vincristine-related peripheral neuropathy in children with acute lymphoblastic leukemia. JAMA 2015; 313:815.
  16. Schmiegelow K. Advances in individual prediction of methotrexate toxicity: a review. Br J Haematol 2009; 146:489.
  17. Phillips PC. Phillips, PC. In: Neurological Complications of Cancer Treatment, Rottenberg DA (Ed), Butterworth-Heinemann, Boston 1991. p.115.
  18. Geiser CF, Bishop Y, Jaffe N, et al. Adverse effects of intrathecal methotrexate in children with acute leukemia in remission. Blood 1975; 45:189.
  19. Dicuonzo F, Salvati A, Palma M, et al. Posterior reversible encephalopathy syndrome associated with methotrexate neurotoxicity: conventional magnetic resonance and diffusion-weighted imaging findings. J Child Neurol 2009; 24:1013.
  20. Winick NJ, Bowman WP, Kamen BA, et al. Unexpected acute neurologic toxicity in the treatment of children with acute lymphoblastic leukemia. J Natl Cancer Inst 1992; 84:252.
  21. Yim YS, Mahoney DH Jr, Oshman DG. Hemiparesis and ischemic changes of the white matter after intrathecal therapy for children with acute lymphocytic leukemia. Cancer 1991; 67:2058.
  22. Anderson SC, Baquis GD, Jackson A, et al. Ventral polyradiculopathy with pediatric acute lymphocytic leukemia. Muscle Nerve 2002; 25:106.
  23. Koh S, Nelson MD Jr, Kovanlikaya A, Chen LS. Anterior lumbosacral radiculopathy after intrathecal methotrexate treatment. Pediatr Neurol 1999; 21:576.
  24. Pascual AM, Coret F, Casanova B, Láinez MJ. Anterior lumbosacral polyradiculopathy after intrathecal administration of methotrexate. J Neurol Sci 2008; 267:158.
  25. Bernstein ML, Sobel DB, Wimmer RS. Noncardiogenic pulmonary edema following injection of methotrexate into the cerebrospinal fluid. Cancer 1982; 50:866.
  26. Gutin PH, Green MR, Bleyer WA, et al. Methotrexate pneumonitis induced by intrathecal methotrexate therapy: a case report with pharmacokinetic data. Cancer 1976; 38:1529.
  27. Boogerd W, vd Sande JJ, Moffie D. Acute fever and delayed leukoencephalopathy following low dose intraventricular methotrexate. J Neurol Neurosurg Psychiatry 1988; 51:1277.
  28. Teh HS, Fadilah SA, Leong CF. Transverse myelopathy following intrathecal administration of chemotherapy. Singapore Med J 2007; 48:e46.
  29. Cachia D, Kamiya-Matsuoka C, Pinnix CC, et al. Myelopathy following intrathecal chemotherapy in adults: a single institution experience. J Neurooncol 2015; 122:391.
  30. Gagliano RG, Costanzi JJ. Paraplegia following intrathecal methotrexate: report of a case and review of the literature. Cancer 1976; 37:1663.
  31. Rubnitz JE, Relling MV, Harrison PL, et al. Transient encephalopathy following high-dose methotrexate treatment in childhood acute lymphoblastic leukemia. Leukemia 1998; 12:1176.
  32. Walker RW, Allen JC, Rosen G, Caparros B. Transient cerebral dysfunction secondary to high-dose methotrexate. J Clin Oncol 1986; 4:1845.
  33. Inaba H, Khan RB, Laningham FH, et al. Clinical and radiological characteristics of methotrexate-induced acute encephalopathy in pediatric patients with cancer. Ann Oncol 2008; 19:178.
  34. Borgna-Pignatti C, Battisti L, Marradi P, et al. Transient neurologic disturbances in a child treated with moderate-dose methotrexate. Br J Haematol 1992; 81:448.
  35. Bhojwani D, Sabin ND, Pei D, et al. Methotrexate-induced neurotoxicity and leukoencephalopathy in childhood acute lymphoblastic leukemia. J Clin Oncol 2014; 32:949.
  36. Janeway KA, Grier HE. Sequelae of osteosarcoma medical therapy: a review of rare acute toxicities and late effects. Lancet Oncol 2010; 11:670.
  37. Vagace JM, Caceres-Marzal C, Jimenez M, et al. Methotrexate-induced subacute neurotoxicity in a child with acute lymphoblastic leukemia carrying genetic polymorphisms related to folate homeostasis. Am J Hematol 2011; 86:98.
  38. Cole PD, Beckwith KA, Vijayanathan V, et al. Folate homeostasis in cerebrospinal fluid during therapy for acute lymphoblastic leukemia. Pediatr Neurol 2009; 40:34.
  39. Vezmar S, Schüsseler P, Becker A, et al. Methotrexate-associated alterations of the folate and methyl-transfer pathway in the CSF of ALL patients with and without symptoms of neurotoxicity. Pediatr Blood Cancer 2009; 52:26.
  40. Kishi S, Griener J, Cheng C, et al. Homocysteine, pharmacogenetics, and neurotoxicity in children with leukemia. J Clin Oncol 2003; 21:3084.
  41. Reddick WE, Glass JO, Helton KJ, et al. Prevalence of leukoencephalopathy in children treated for acute lymphoblastic leukemia with high-dose methotrexate. AJNR Am J Neuroradiol 2005; 26:1263.
  42. Rubinstein LJ, Herman MM, Long TF, Wilbur JR. Disseminated necrotizing leukoencephalopathy: a complication of treated central nervous system leukemia and lymphoma. Cancer 1975; 35:291.
  43. Pizzo PA, Poplack DG, Bleyer WA. Neurotoxicities of current leukemia therapy. Am J Pediatr Hematol Oncol 1979; 1:127.
  44. Oka M, Terae S, Kobayashi R, et al. MRI in methotrexate-related leukoencephalopathy: Disseminated necrotising leukoencephalopathy in comparison with mild leukoencephalopathy. Neuroradiology 2003; 45:493.
  45. Robain O, Dulac O, Dommergues JP, et al. Necrotising leukoencephalopathy complicating treatment of childhood leukaemia. J Neurol Neurosurg Psychiatry 1984; 47:65.
  46. Bernini JC, Fort DW, Griener JC, et al. Aminophylline for methotrexate-induced neurotoxicity. Lancet 1995; 345:544.
  47. Afshar M, Birnbaum D, Golden C. Review of dextromethorphan administration in 18 patients with subacute methotrexate central nervous system toxicity. Pediatr Neurol 2014; 50:625.
  48. Posner J, Memorial Sloan-Kettering Cancer Center, 2015, personal communication.
  49. Ackermann R, Semmler A, Maurer GD, et al. Methotrexate-induced myelopathy responsive to substitution of multiple folate metabolites. J Neurooncol 2010; 97:425.
  50. Ettinger LJ. Pharmacokinetics and biochemical effects of a fatal intrathecal methotrexate overdose. Cancer 1982; 50:444.
  51. O'Marcaigh AS, Johnson CM, Smithson WA, et al. Successful treatment of intrathecal methotrexate overdose by using ventriculolumbar perfusion and intrathecal instillation of carboxypeptidase G2. Mayo Clin Proc 1996; 71:161.
  52. Widemann BC, Balis FM, Shalabi A, et al. Treatment of accidental intrathecal methotrexate overdose with intrathecal carboxypeptidase G2. J Natl Cancer Inst 2004; 96:1557.
  53. Spiegel RJ, Cooper PR, Blum RH, et al. Treatment of massive intrathecal methotrexate overdose by ventriculolumbar perfusion. N Engl J Med 1984; 311:386.
  54. Addiego JE Jr, Ridgway D, Bleyer WA. The acute management of intrathecal methotrexate overdose: pharmacologic rationale and guidelines. J Pediatr 1981; 98:825.
  55. www.btgplc.com/contact-us/contacts (Accessed on February 14, 2012).
  56. Freilich RJ, Balmaceda C, Seidman AD, et al. Motor neuropathy due to docetaxel and paclitaxel. Neurology 1996; 47:115.
  57. Lee JJ, Swain SM. Peripheral neuropathy induced by microtubule-stabilizing agents. J Clin Oncol 2006; 24:1633.
  58. Krzakowski M, Ramlau R, Jassem J, et al. Phase III trial comparing vinflunine with docetaxel in second-line advanced non-small-cell lung cancer previously treated with platinum-containing chemotherapy. J Clin Oncol 2010; 28:2167.
  59. Argyriou AA, Polychronopoulos P, Iconomou G, et al. Paclitaxel plus carboplatin-induced peripheral neuropathy. A prospective clinical and electrophysiological study in patients suffering from solid malignancies. J Neurol 2005; 252:1459.
  60. Grisold W, Cavaletti G, Windebank AJ. Peripheral neuropathies from chemotherapeutics and targeted agents: diagnosis, treatment, and prevention. Neuro Oncol 2012; 14 Suppl 4:iv45.
  61. Argyriou AA, Koltzenburg M, Polychronopoulos P, et al. Peripheral nerve damage associated with administration of taxanes in patients with cancer. Crit Rev Oncol Hematol 2008; 66:218.
  62. LaPointe NE, Morfini G, Brady ST, et al. Effects of eribulin, vincristine, paclitaxel and ixabepilone on fast axonal transport and kinesin-1 driven microtubule gliding: implications for chemotherapy-induced peripheral neuropathy. Neurotoxicology 2013; 37:231.
  63. Peters CM, Jimenez-Andrade JM, Jonas BM, et al. Intravenous paclitaxel administration in the rat induces a peripheral sensory neuropathy characterized by macrophage infiltration and injury to sensory neurons and their supporting cells. Exp Neurol 2007; 203:42.
  64. Hershman DL, Till C, Wright JD, et al. Comorbidities and Risk of Chemotherapy-Induced Peripheral Neuropathy Among Participants 65 Years or Older in Southwest Oncology Group Clinical Trials. J Clin Oncol 2016; 34:3014.
  65. Greenlee H, Hershman DL, Shi Z, et al. BMI, Lifestyle Factors and Taxane-Induced Neuropathy in Breast Cancer Patients: The Pathways Study. J Natl Cancer Inst 2017; 109.
  66. Rowinsky EK, Cazenave LA, Donehower RC. Taxol: a novel investigational antimicrotubule agent. J Natl Cancer Inst 1990; 82:1247.
  67. Fernandes R, Mazzarello S, Majeed H, et al. Treatment of taxane acute pain syndrome (TAPS) in cancer patients receiving taxane-based chemotherapy-a systematic review. Support Care Cancer 2016; 24:1583.
  68. 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.
  69. 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.
  70. 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.
  71. Fernandes R, Mazzarello S, Hutton B, et al. Taxane acute pain syndrome (TAPS) in patients receiving taxane-based chemotherapy for breast cancer-a systematic review. Support Care Cancer 2016; 24:3633.
  72. Perry JR, Warner E. Transient encephalopathy after paclitaxel (Taxol) infusion. Neurology 1996; 46:1596.
  73. Rook J, Rosser T, Fangusaro J, Finlay J. Acute transient encephalopathy following paclitaxel treatment in an adolescent with a recurrent suprasellar germinoma. Pediatr Blood Cancer 2008; 50:699.
  74. Khattab J, Terebelo HR, Dabas B. Phantom limb pain as a manifestation of paclitaxel neurotoxicity. Mayo Clin Proc 2000; 75:740.
  75. Openshaw H, Beamon K, Synold TW, et al. Neurophysiological study of peripheral neuropathy after high-dose Paclitaxel: lack of neuroprotective effect of amifostine. Clin Cancer Res 2004; 10:461.
  76. Pace A, Bove L, Aloe A, et al. Paclitaxel neurotoxicity: clinical and neurophysiological study of 23 patients. Ital J Neurol Sci 1997; 18:73.
  77. Muggia FM, Braly PS, Brady MF, et al. Phase III randomized study of cisplatin versus paclitaxel versus cisplatin and paclitaxel in patients with suboptimal stage III or IV ovarian cancer: a gynecologic oncology group study. J Clin Oncol 2000; 18:106.
  78. Piccart MJ. RESPONSE: re: randomized intergroup trial of cisplatin-paclitaxel versus cisplatin-cyclophosphamide in women with advanced epithelial ovarian cancer: three-year results. J Natl Cancer Inst 2000; 92:1446.
  79. Argyriou AA, Polychronopoulos P, Koutras A, et al. Is advanced age associated with increased incidence and severity of chemotherapy-induced peripheral neuropathy? Support Care Cancer 2006; 14:223.
  80. Baldwin RM, Owzar K, Zembutsu H, et al. A genome-wide association study identifies novel loci for paclitaxel-induced sensory peripheral neuropathy in CALGB 40101. Clin Cancer Res 2012; 18:5099.
  81. Hertz DL, Roy S, Motsinger-Reif AA, et al. CYP2C8*3 increases risk of neuropathy in breast cancer patients treated with paclitaxel. Ann Oncol 2013; 24:1472.
  82. de Graan AJ, Elens L, Sprowl JA, et al. CYP3A4*22 genotype and systemic exposure affect paclitaxel-induced neurotoxicity. Clin Cancer Res 2013; 19:3316.
  83. Leandro-García LJ, Leskelä S, Jara C, et al. Regulatory polymorphisms in β-tubulin IIa are associated with paclitaxel-induced peripheral neuropathy. Clin Cancer Res 2012; 18:4441.
  84. Abraham JE, Guo Q, Dorling L, et al. Replication of genetic polymorphisms reported to be associated with taxane-related sensory neuropathy in patients with early breast cancer treated with Paclitaxel. Clin Cancer Res 2014; 20:2466.
  85. Apellániz-Ruiz M, Lee MY, Sánchez-Barroso L, et al. Whole-exome sequencing reveals defective CYP3A4 variants predictive of paclitaxel dose-limiting neuropathy. Clin Cancer Res 2015; 21:322.
  86. Komatsu M, Wheeler HE, Chung S, et al. Pharmacoethnicity in Paclitaxel-Induced Sensory Peripheral Neuropathy. Clin Cancer Res 2015; 21:4337.
  87. Schneider BP, Li L, Radovich M, et al. Genome-Wide Association Studies for Taxane-Induced Peripheral Neuropathy in ECOG-5103 and ECOG-1199. Clin Cancer Res 2015; 21:5082.
  88. Eisenhauer EA, ten Bokkel Huinink WW, Swenerton KD, et al. European-Canadian randomized trial of paclitaxel in relapsed ovarian cancer: high-dose versus low-dose and long versus short infusion. J Clin Oncol 1994; 12:2654.
  89. Seidman AD, Berry D, Cirrincione C, et al. Randomized phase III trial of weekly compared with every-3-weeks paclitaxel for metastatic breast cancer, with trastuzumab for all HER-2 overexpressors and random assignment to trastuzumab or not in HER-2 nonoverexpressors: final results of Cancer and Leukemia Group B protocol 9840. J Clin Oncol 2008; 26:1642.
  90. Sparano JA, Wang M, Martino S, et al. Weekly paclitaxel in the adjuvant treatment of breast cancer. N Engl J Med 2008; 358:1663.
  91. Mauri D, Kamposioras K, Tsali L, et al. Overall survival benefit for weekly vs. three-weekly taxanes regimens in advanced breast cancer: A meta-analysis. Cancer Treat Rev 2010; 36:69.
  92. 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.
  93. Moulder SL, Holmes FA, Tolcher AW, et al. A randomized phase 2 trial comparing 3-hour versus 96-hour infusion schedules of paclitaxel for the treatment of metastatic breast cancer. Cancer 2010; 116:814.
  94. Gradishar WJ, Tjulandin S, Davidson N, et al. Phase III trial of nanoparticle albumin-bound paclitaxel compared with polyethylated castor oil-based paclitaxel in women with breast cancer. J Clin Oncol 2005; 23:7794.
  95. Goldstein D, Von Hoff DD, Moore M, et al. Development of peripheral neuropathy and its association with survival during treatment with nab-paclitaxel plus gemcitabine for patients with metastatic adenocarcinoma of the pancreas: A subset analysis from a randomised phase III trial (MPACT). Eur J Cancer 2016; 52:85.
  96. Gradishar WJ, Krasnojon D, Cheporov S, et al. Significantly longer progression-free survival with nab-paclitaxel compared with docetaxel as first-line therapy for metastatic breast cancer. J Clin Oncol 2009; 27:3611.
  97. Rivera E, Mejia JA, Arun BK, et al. Phase 3 study comparing the use of docetaxel on an every-3-week versus weekly schedule in the treatment of metastatic breast cancer. Cancer 2008; 112:1455.
  98. van den Bent MJ, Hilkens PH, Sillevis Smitt PA, et al. Lhermitte's sign following chemotherapy with docetaxel. Neurology 1998; 50:563.
  99. Jones SE, Erban J, Overmoyer B, et al. Randomized phase III study of docetaxel compared with paclitaxel in metastatic breast cancer. J Clin Oncol 2005; 23:5542.
  100. Di Maio M, Perrone F, Chiodini P, et al. Individual patient data meta-analysis of docetaxel administered once every 3 weeks compared with once every week second-line treatment of advanced non-small-cell lung cancer. J Clin Oncol 2007; 25:1377.
  101. Roché H, Fumoleau P, Spielmann M, et al. Sequential adjuvant epirubicin-based and docetaxel chemotherapy for node-positive breast cancer patients: the FNCLCC PACS 01 Trial. J Clin Oncol 2006; 24:5664.
  102. Jones SE, Savin MA, Holmes FA, et al. Phase III trial comparing doxorubicin plus cyclophosphamide with docetaxel plus cyclophosphamide as adjuvant therapy for operable breast cancer. J Clin Oncol 2006; 24:5381.
  103. Martin M, Pienkowski T, Mackey J, et al. Adjuvant docetaxel for node-positive breast cancer. N Engl J Med 2005; 352:2302.
  104. Horgan AM, Seruga B, Pond GR, et al. Tolerability and efficacy of docetaxel in older men with metastatic castrate-resistant prostate cancer (mCRPC) in the TAX 327 trial. J Geriatr Oncol 2014; 5:119.
  105. Shim BY, Kim CH, Song SH, et al. The safety and efficacy of second-line single docetaxel (75 mg/m²) therapy in advanced non-small cell lung cancer patients who were previously treated with platinum-based chemotherapy. Cancer Res Treat 2005; 37:339.
  106. Wang Y, Herrstedt J, Havsteen H, et al. A multicenter, non-randomized, phase II study of docetaxel and carboplatin administered every 3 weeks as second line chemotherapy in patients with first relapse of platinum sensitive epithelial ovarian, peritoneal or fallopian tube cancer. BMC Cancer 2014; 14:937.
  107. Pivot X, Koralewski P, Hidalgo JL, et al. A multicenter phase II study of XRP6258 administered as a 1-h i.v. infusion every 3 weeks in taxane-resistant metastatic breast cancer patients. Ann Oncol 2008; 19:1547.
  108. de Bono JS, Oudard S, Ozguroglu M, et al. Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial. Lancet 2010; 376:1147.
  109. Argyriou AA, Polychronopoulos P, Koutras A, et al. Clinical and electrophysiological features of peripheral neuropathy induced by administration of cisplatin plus paclitaxel-based chemotherapy. Eur J Cancer Care (Engl) 2007; 16:231.
  110. Postma TJ, Vermorken JB, Liefting AJ, et al. Paclitaxel-induced neuropathy. Ann Oncol 1995; 6:489.
  111. 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.
  112. 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.
  113. Eckhoff L, Knoop A, Jensen MB, Ewertz M. Persistence of docetaxel-induced neuropathy and impact on quality of life among breast cancer survivors. Eur J Cancer 2015; 51:292.
  114. Osmani K, Vignes S, Aissi M, et al. Taxane-induced peripheral neuropathy has good long-term prognosis: a 1- to 13-year evaluation. J Neurol 2012; 259:1936.
  115. Casey EB, Jellife AM, Le Quesne PM, Millett YL. Vincristine neuropathy. Clinical and electrophysiological observations. Brain 1973; 96:69.
  116. Legha SS. Vincristine neurotoxicity. Pathophysiology and management. Med Toxicol 1986; 1:421.
  117. Postma TJ, Benard BA, Huijgens PC, et al. Long-term effects of vincristine on the peripheral nervous system. J Neurooncol 1993; 15:23.
  118. Verstappen CC, Koeppen S, Heimans JJ, et al. Dose-related vincristine-induced peripheral neuropathy with unexpected off-therapy worsening. Neurology 2005; 64:1076.
  119. DeAngelis LM, Gnecco C, Taylor L, Warrell RP Jr. Evolution of neuropathy and myopathy during intensive vincristine/corticosteroid chemotherapy for non-Hodgkin's lymphoma. Cancer 1991; 67:2241.
  120. McLeod JG, Penny R. Vincristine neuropathy: an electrophysiological and histological study. J Neurol Neurosurg Psychiatry 1969; 32:297.
  121. Jain P, Gulati S, Seth R, et al. Vincristine-induced neuropathy in childhood ALL (acute lymphoblastic leukemia) survivors: prevalence and electrophysiological characteristics. J Child Neurol 2014; 29:932.
  122. Weintraub M, Adde MA, Venzon DJ, et al. Severe atypical neuropathy associated with administration of hematopoietic colony-stimulating factors and vincristine. J Clin Oncol 1996; 14:935.
  123. Teusink AC, Ragucci D, Shatat IF, Kalpatthi R. Potentiation of vincristine toxicity with concomitant fluconazole prophylaxis in children with acute lymphoblastic leukemia. Pediatr Hematol Oncol 2012; 29:62.
  124. Harnicar S, Adel N, Jurcic J. Modification of vincristine dosing during concomitant azole therapy in adult acute lymphoblastic leukemia patients. J Oncol Pharm Pract 2009; 15:175.
  125. Hogan-Dann CM, Fellmeth WG, McGuire SA, Kiley VA. Polyneuropathy following vincristine therapy in two patients with Charcot-Marie-Tooth syndrome. JAMA 1984; 252:2862.
  126. Naumann R, Mohm J, Reuner U, et al. Early recognition of hereditary motor and sensory neuropathy type 1 can avoid life-threatening vincristine neurotoxicity. Br J Haematol 2001; 115:323.
  127. O'Brien S, Schiller G, Lister J, et al. High-dose vincristine sulfate liposome injection for advanced, relapsed, and refractory adult Philadelphia chromosome-negative acute lymphoblastic leukemia. J Clin Oncol 2013; 31:676.
  128. Kornblith AB, Anderson J, Cella DF, et al. Comparison of psychosocial adaptation and sexual function of survivors of advanced Hodgkin disease treated by MOPP, ABVD, or MOPP alternating with ABVD. Cancer 1992; 70:2508.
  129. Pal PK. Clinical and electrophysiological studies in vincristine induced neuropathy. Electromyogr Clin Neurophysiol 1999; 39:323.
  130. Robertson GL, Bhoopalam N, Zelkowitz LJ. Vincristine neurotoxicity and abnormal secretion of antidiuretic hormone. Arch Intern Med 1973; 132:717.
  131. Forsyth P, Cascino T. Neurological complications of chemotherapy. In: Neurological Complications of Cancer, Wiley R (Ed), Marcel Dekker, Inc., New York 1995. p.241.
  132. http://www.clinicaltrials.gov/ct2/show/NCT00365768 (Accessed on April 15, 2011).
  133. 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.
  134. Paleologos N. Complications of chemotherapy. In: Iatrogenic Neurology, Biller J (Ed), Butterworth-Heinemann, Boston 1998. p.439.
  135. Fazeny B, Zifko U, Meryn S, et al. Vinorelbine-induced neurotoxicity in patients with advanced breast cancer pretreated with paclitaxel--a phase II study. Cancer Chemother Pharmacol 1996; 39:150.
  136. Norris B, Pritchard KI, James K, et al. Phase III comparative study of vinorelbine combined with doxorubicin versus doxorubicin alone in disseminated metastatic/recurrent breast cancer: National Cancer Institute of Canada Clinical Trials Group Study MA8. J Clin Oncol 2000; 18:2385.
  137. Park SB, Krishnan AV, Lin CS, et al. Mechanisms underlying chemotherapy-induced neurotoxicity and the potential for neuroprotective strategies. Curr Med Chem 2008; 15:3081.
  138. Argyriou AA, Marmiroli P, Cavaletti G, Kalofonos HP. Epothilone-induced peripheral neuropathy: a review of current knowledge. J Pain Symptom Manage 2011; 42:931.
  139. Argyriou AA, Bruna J, Marmiroli P, Cavaletti G. Chemotherapy-induced peripheral neurotoxicity (CIPN): an update. Crit Rev Oncol Hematol 2012; 82:51.
  140. Thomas ES, Gomez HL, Li RK, et al. Ixabepilone plus capecitabine for metastatic breast cancer progressing after anthracycline and taxane treatment. J Clin Oncol 2007; 25:5210.
  141. Federal Drug Administration. Highlights of prescribing information for ixabepilone http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/022065s002lbl.pdf (Accessed on April 15, 2011).
  142. Twelves, C, Loesch, D. Blum, JA, et al. A phase III study (EMBRACE) of eribulin mesylate versus treatment of physician's choice in patients with locally recurrent or metastatic breast cancer previously treated with an anthracycline and a taxane (abstract CRA 1004). J Clin Oncol 2010; 28:958s. Abstract available online at http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst_detail_view&confID=74&abstractID=50309 (Accessed on November 22, 2010).
  143. http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/201532lbl.pdf (Accessed on November 22, 2010).
  144. Glasmacher A, Hahn C, Hoffmann F, et al. A systematic review of phase-II trials of thalidomide monotherapy in patients with relapsed or refractory multiple myeloma. Br J Haematol 2006; 132:584.
  145. Kocer B, Sucak G, Kuruoglu R, et al. Clinical and electrophysiological evaluation of patients with thalidomide-induced neuropathy. Acta Neurol Belg 2009; 109:120.
  146. Mileshkin L, Stark R, Day B, et al. Development of neuropathy in patients with myeloma treated with thalidomide: patterns of occurrence and the role of electrophysiologic monitoring. J Clin Oncol 2006; 24:4507.
  147. Tosi P, Zamagni E, Cellini C, et al. Neurological toxicity of long-term (>1 yr) thalidomide therapy in patients with multiple myeloma. Eur J Haematol 2005; 74:212.
  148. Plasmati R, Pastorelli F, Cavo M, et al. Neuropathy in multiple myeloma treated with thalidomide: a prospective study. Neurology 2007; 69:573.
  149. Isoardo G, Bergui M, Durelli L, et al. Thalidomide neuropathy: clinical, electrophysiological and neuroradiological features. Acta Neurol Scand 2004; 109:188.
  150. Cavaletti G, Beronio A, Reni L, et al. Thalidomide sensory neurotoxicity: a clinical and neurophysiologic study. Neurology 2004; 62:2291.
  151. Rajkumar SV, Rosiñol L, Hussein M, et al. Multicenter, randomized, double-blind, placebo-controlled study of thalidomide plus dexamethasone compared with dexamethasone as initial therapy for newly diagnosed multiple myeloma. J Clin Oncol 2008; 26:2171.
  152. Facon T, Mary JY, Hulin C, et al. Melphalan and prednisone plus thalidomide versus melphalan and prednisone alone or reduced-intensity autologous stem cell transplantation in elderly patients with multiple myeloma (IFM 99-06): a randomised trial. Lancet 2007; 370:1209.
  153. Hulin C, Facon T, Rodon P, et al. Efficacy of melphalan and prednisone plus thalidomide in patients older than 75 years with newly diagnosed multiple myeloma: IFM 01/01 trial. J Clin Oncol 2009; 27:3664.
  154. Prince HM, Mileshkin L, Roberts A, et al. A multicenter phase II trial of thalidomide and celecoxib for patients with relapsed and refractory multiple myeloma. Clin Cancer Res 2005; 11:5504.
  155. Spencer A, Prince HM, Roberts AW, et al. Consolidation therapy with low-dose thalidomide and prednisolone prolongs the survival of multiple myeloma patients undergoing a single autologous stem-cell transplantation procedure. J Clin Oncol 2009; 27:1788.
  156. Cundari S, Cavaletti G. Thalidomide chemotherapy-induced peripheral neuropathy: actual status and new perspectives with thalidomide analogues derivatives. Mini Rev Med Chem 2009; 9:760.
  157. Mohty B, El-Cheikh J, Yakoub-Agha I, et al. Peripheral neuropathy and new treatments for multiple myeloma: background and practical recommendations. Haematologica 2010; 95:311.
  158. Waage A, Gimsing P, Fayers P, et al. Melphalan and prednisone plus thalidomide or placebo in elderly patients with multiple myeloma. Blood 2010; 116:1405.
  159. Murphy PT, O'Donnell JR. Thalidomide induced impotence in male hematology patients: a common but ignored complication? Haematologica 2007; 92:1440.
  160. Clark TE, Edom N, Larson J, Lindsey LJ. Thalomid (Thalidomide) capsules: a review of the first 18 months of spontaneous postmarketing adverse event surveillance, including off-label prescribing. Drug Saf 2001; 24:87.
  161. Hinterseer M, Becker A, Kääb S, et al. Thalidomide-induced symptomatic third-degree atrioventricular block. Clin Res Cardiol 2006; 95:474.
  162. Steurer M, Spizzo G, Mitterer M, Gastl G. Low-dose thalidomide for multiple myeloma: interim analysis of a compassionate use program. Onkologie 2004; 27:150.
  163. Delforge M, Bladé J, Dimopoulos MA, et al. Treatment-related peripheral neuropathy in multiple myeloma: the challenge continues. Lancet Oncol 2010; 11:1086.
  164. Briani C, Torre CD, Campagnolo M, et al. Lenalidomide in patients with chemotherapy-induced polyneuropathy and relapsed or refractory multiple myeloma: results from a single-centre prospective study. J Peripher Nerv Syst 2013; 18:19.
  165. Dimopoulos MA, Chen C, Spencer A, et al. Long-term follow-up on overall survival from the MM-009 and MM-010 phase III trials of lenalidomide plus dexamethasone in patients with relapsed or refractory multiple myeloma. Leukemia 2009; 23:2147.
  166. Richardson PG, Siegel DS, Vij R, et al. Pomalidomide alone or in combination with low-dose dexamethasone in relapsed and refractory multiple myeloma: a randomized phase 2 study. Blood 2014; 123:1826.
  167. San Miguel J, Weisel K, Moreau P, et al. Pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone alone for patients with relapsed and refractory multiple myeloma (MM-003): a randomised, open-label, phase 3 trial. Lancet Oncol 2013; 14:1055.
  168. Richardson PG, Briemberg H, Jagannath S, et al. Frequency, characteristics, and reversibility of peripheral neuropathy during treatment of advanced multiple myeloma with bortezomib. J Clin Oncol 2006; 24:3113.
  169. Badros A, Goloubeva O, Dalal JS, et al. Neurotoxicity of bortezomib therapy in multiple myeloma: a single-center experience and review of the literature. Cancer 2007; 110:1042.
  170. Argyriou AA, Iconomou G, Kalofonos HP. Bortezomib-induced peripheral neuropathy in multiple myeloma: a comprehensive review of the literature. Blood 2008; 112:1593.
  171. Richardson PG, Barlogie B, Berenson J, et al. A phase 2 study of bortezomib in relapsed, refractory myeloma. N Engl J Med 2003; 348:2609.
  172. Jagannath S, Durie BG, Wolf J, et al. Bortezomib therapy alone and in combination with dexamethasone for previously untreated symptomatic multiple myeloma. Br J Haematol 2005; 129:776.
  173. Caravita T, Petrucci MT, Spagnoli A, et al. Neuropathy in Multiple Myeloma Patients Treated with Bortezomib: A Multicenter Experience. ASH Annual Meeting Abstracts 2007; 110:4823.
  174. Richardson PG, Sonneveld P, Schuster MW, et al. Bortezomib or high-dose dexamethasone for relapsed multiple myeloma. N Engl J Med 2005; 352:2487.
  175. San Miguel JF, Schlag R, Khuageva NK, et al. Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma. N Engl J Med 2008; 359:906.
  176. Mateos MV, Oriol A, Martínez-López J, et al. Bortezomib, melphalan, and prednisone versus bortezomib, thalidomide, and prednisone as induction therapy followed by maintenance treatment with bortezomib and thalidomide versus bortezomib and prednisone in elderly patients with untreated multiple myeloma: a randomised trial. Lancet Oncol 2010; 11:934.
  177. Palumbo A, Bringhen S, Rossi D, et al. Bortezomib-melphalan-prednisone-thalidomide followed by maintenance with bortezomib-thalidomide compared with bortezomib-melphalan-prednisone for initial treatment of multiple myeloma: a randomized controlled trial. J Clin Oncol 2010; 28:5101.
  178. Rajkumar SV. Optimising bortezomib in newly diagnosed multiple myeloma. Lancet Oncol 2010; 11:909.
  179. Kumar SK, Laubach JP, Giove TJ, et al. Impact of concomitant dexamethasone dosing schedule on bortezomib-induced peripheral neuropathy in multiple myeloma. Br J Haematol 2017; 178:756.
  180. Lanzani F, Mattavelli L, Frigeni B, et al. Role of a pre-existing neuropathy on the course of bortezomib-induced peripheral neurotoxicity. J Peripher Nerv Syst 2008; 13:267.
  181. Broyl A, Corthals SL, Jongen JL, et al. Mechanisms of peripheral neuropathy associated with bortezomib and vincristine in patients with newly diagnosed multiple myeloma: a prospective analysis of data from the HOVON-65/GMMG-HD4 trial. Lancet Oncol 2010; 11:1057.
  182. Magrangeas F, Kuiper R, Avet-Loiseau H, et al. A Genome-Wide Association Study Identifies a Novel Locus for Bortezomib-Induced Peripheral Neuropathy in European Patients with Multiple Myeloma. Clin Cancer Res 2016; 22:4350.
  183. Cata JP, Weng HR, Burton AW, et al. Quantitative sensory findings in patients with bortezomib-induced pain. J Pain 2007; 8:296.
  184. 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.
  185. Argyriou AA, Kyritsis AP, Makatsoris T, Kalofonos HP. Chemotherapy-induced peripheral neuropathy in adults: a comprehensive update of the literature. Cancer Manag Res 2014; 6:135.
  186. Cavaletti G, Gilardini A, Canta A, et al. Bortezomib-induced peripheral neurotoxicity: a neurophysiological and pathological study in the rat. Exp Neurol 2007; 204:317.
  187. Ravaglia S, Corso A, Piccolo G, et al. Immune-mediated neuropathies in myeloma patients treated with bortezomib. Clin Neurophysiol 2008; 119:2507.
  188. Jagannath S, Barlogie B, Berenson J, et al. A phase 2 study of two doses of bortezomib in relapsed or refractory myeloma. Br J Haematol 2004; 127:165.
  189. Terwiel E, Hanrahan R, Lueck C, D'Rozario J. Reversible posterior encephalopathy syndrome associated with bortezomib. Intern Med J 2010; 40:69.
  190. Ho CH, Lo CP, Tu MC. Bortezomib-induced posterior reversible encephalopathy syndrome: clinical and imaging features. Intern Med 2014; 53:1853.
  191. Wick W, Hertenstein A, Platten M. Neurological sequelae of cancer immunotherapies and targeted therapies. Lancet Oncol 2016; 17:e529.
  192. Cavaletti G, Jakubowiak AJ. Peripheral neuropathy during bortezomib treatment of multiple myeloma: a review of recent studies. Leuk Lymphoma 2010; 51:1178.
  193. Treon SP, Hunter ZR, Matous J, et al. Multicenter clinical trial of bortezomib in relapsed/refractory Waldenstrom's macroglobulinemia: results of WMCTG Trial 03-248. Clin Cancer Res 2007; 13:3320.
  194. 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.
  195. Vij R, Wang M, Kaufman JL, et al. An open-label, single-arm, phase 2 (PX-171-004) study of single-agent carfilzomib in bortezomib-naive patients with relapsed and/or refractory multiple myeloma. Blood 2012; 119:5661.
  196. Jakubowiak AJ, Dytfeld D, Griffith KA, et al. A phase 1/2 study of carfilzomib in combination with lenalidomide and low-dose dexamethasone as a frontline treatment for multiple myeloma. Blood 2012; 120:1801.
  197. Singhal S, Siegel DS, Martin T, et al. Integrated safety from phase II studies of monotherapy carfilzomib inpatients with relapsed and refractory multiple myeloma: An updated analysis (abstract). Blood 2011; 118:abstr 1876). Abstract available online at http://abstracts.hematologylibrary.org/cgi/content/abstract/118/21/1876?maxtoshow=&hits=10&RESULTFORMAT=&fulltext=1876&searchid=1&FIRSTINDEX=0&sortspec=relevance&resourcetype=HWCIT (Accessed on July 23, 2012).
  198. Siegel DS, Martin T, Wang M, et al. A phase 2 study of single-agent carfilzomib (PX-171-003-A1) in patients with relapsed and refractory multiple myeloma. Blood 2012; 120:2817.
  199. Kumar SK, LaPlant B, Roy V, et al. Phase 2 trial of ixazomib in patients with relapsed multiple myeloma not refractory to bortezomib. Blood Cancer J 2015; 5:e338.
  200. Moreau P, Masszi T, Grzasko N, et al. Ixazomib, an investigational oral proteasome inhibitor (PI), in combination with lenalidomide and dexamethasone (IRd), significantly extends progression-free survival for patients with relapsed and/or refractory multiple myeloma: the phase 3 Tourmaline-MM1 study (NCT01564537) (abstract). Data presented at the 57th annual meeting of the American Society for Hematology, Orlando Fl, December 7, 2015. Abstract available online at https://ash.confex.com/ash/2015/webprogram/Paper79829.html (Accessed on December 04, 2015).
  201. Berg SL, Blaney SM, Devidas M, et al. Phase II study of nelarabine (compound 506U78) in children and young adults with refractory T-cell malignancies: a report from the Children's Oncology Group. J Clin Oncol 2005; 23:3376.
  202. DeAngelo DJ, Yu D, Johnson JL, et al. Nelarabine induces complete remissions in adults with relapsed or refractory T-lineage acute lymphoblastic leukemia or lymphoblastic lymphoma: Cancer and Leukemia Group B study 19801. Blood 2007; 109:5136.
  203. Cohen MH, Johnson JR, Massie T, et al. Approval summary: nelarabine for the treatment of T-cell lymphoblastic leukemia/lymphoma. Clin Cancer Res 2006; 12:5329.
  204. Herzig RH, Hines JD, Herzig GP, et al. Cerebellar toxicity with high-dose cytosine arabinoside. J Clin Oncol 1987; 5:927.
  205. Jolson HM, Bosco L, Bufton MG, et al. Clustering of adverse drug events: analysis of risk factors for cerebellar toxicity with high-dose cytarabine. J Natl Cancer Inst 1992; 84:500.
  206. Dunton SF, Nitschke R, Spruce WE, et al. Progressive ascending paralysis following administration of intrathecal and intravenous cytosine arabinoside. A Pediatric Oncology Group study. Cancer 1986; 57:1083.
  207. Smith GA, Damon LE, Rugo HS, et al. High-dose cytarabine dose modification reduces the incidence of neurotoxicity in patients with renal insufficiency. J Clin Oncol 1997; 15:833.
  208. Friedman JH, Shetty N. Permanent cerebellar toxicity of cytosine arabinoside (Ara C) in a young woman. Mov Disord 2001; 16:575.
  209. Openshaw H, Slatkin NE, Stein AS, et al. Acute polyneuropathy after high dose cytosine arabinoside in patients with leukemia. Cancer 1996; 78:1899.
  210. Nevill TJ, Benstead TJ, McCormick CW, Hayne OA. Horner's syndrome and demyelinating peripheral neuropathy caused by high-dose cytosine arabinoside. Am J Hematol 1989; 32:314.
  211. Saito T, Asai O, Dobashi N, et al. Peripheral neuropathy caused by high-dose cytosine arabinoside treatment in a patient with acute myeloid leukemia. J Infect Chemother 2006; 12:148.
  212. Hoffman DL, Howard JR Jr, Sarma R, Riggs JE. Encephalopathy, myelopathy, optic neuropathy, and anosmia associated with intravenous cytosine arabinoside. Clin Neuropharmacol 1993; 16:258.
  213. Hwang TL, Yung WK, Estey EH, Fields WS. Central nervous system toxicity with high-dose Ara-C. Neurology 1985; 35:1475.
  214. Luque FA, Selhorst JB, Petruska P. Parkinsonism induced by high-dose cytosine arabinoside. Mov Disord 1987; 2:219.
  215. Ventura GJ, Keating MJ, Castellanos AM, Glass JP. Reversible bilateral lateral rectus muscle palsy associated with high-dose cytosine arabinoside and mitoxantrone therapy. Cancer 1986; 58:1633.
  216. Glantz MJ, LaFollette S, Jaeckle KA, et al. Randomized trial of a slow-release versus a standard formulation of cytarabine for the intrathecal treatment of lymphomatous meningitis. J Clin Oncol 1999; 17:3110.
  217. Glantz MJ, Jaeckle KA, Chamberlain MC, et al. A randomized controlled trial comparing intrathecal sustained-release cytarabine (DepoCyt) to intrathecal methotrexate in patients with neoplastic meningitis from solid tumors. Clin Cancer Res 1999; 5:3394.
  218. Jabbour E, O'Brien S, Kantarjian H, et al. Neurologic complications associated with intrathecal liposomal cytarabine given prophylactically in combination with high-dose methotrexate and cytarabine to patients with acute lymphocytic leukemia. Blood 2007; 109:3214.
  219. Gállego Pérez-Larraya J, Palma JA, Carmona-Iragui M, et al. Neurologic complications of intrathecal liposomal cytarabine administered prophylactically to patients with non-Hodgkin lymphoma. J Neurooncol 2011; 103:603.
  221. Gottlieb JA, Luce JK. Cerebellar ataxia with weekly 5-fluorouracil administration. Lancet 1971; 1:138.
  222. Liaw CC, Liaw SJ, Wang CH, et al. Transient hyperammonemia related to chemotherapy with continuous infusion of high-dose 5-fluorouracil. Anticancer Drugs 1993; 4:311.
  223. Liaw CC, Wang HM, Wang CH, et al. Risk of transient hyperammonemic encephalopathy in cancer patients who received continuous infusion of 5-fluorouracil with the complication of dehydration and infection. Anticancer Drugs 1999; 10:275.
  224. Nott L, Price TJ, Pittman K, et al. Hyperammonemia encephalopathy: an important cause of neurological deterioration following chemotherapy. Leuk Lymphoma 2007; 48:1702.
  225. Kikuta S, Asakage T, Nakao K, et al. The aggravating factors of hyperammonemia related to 5-fluorouracil infusion--a report of two cases. Auris Nasus Larynx 2008; 35:295.
  226. Delval L, Klastersky J. Optic neuropathy in cancer patients. Report of a case possibly related to 5 fluorouracil toxicity and review of the literature. J Neurooncol 2002; 60:165.
  227. Bixenman WW, Nicholls JV, Warwick OH. Oculomotor disturbances associated with 5-fluorouracil chemotherapy. Am J Ophthalmol 1977; 83:789.
  228. Brashear A, Siemers E. Focal dystonia after chemotherapy: a case series. J Neurooncol 1997; 34:163.
  229. El Amrani M, Heinzlef O, Debroucker T, et al. Brain infarction following 5-fluorouracil and cisplatin therapy. Neurology 1998; 51:899.
  230. Bergevin PR, Patwardhan VC, Weissman J, Lee SM. Letter: Neurotoxicity of 5-fluorouracil. Lancet 1975; 1:410.
  231. Stein ME, Drumea K, Yarnitsky D, et al. A rare event of 5-fluorouracil-associated peripheral neuropathy: a report of two patients. Am J Clin Oncol 1998; 21:248.
  232. Pirzada NA, Ali II, Dafer RM. Fluorouracil-induced neurotoxicity. Ann Pharmacother 2000; 34:35.
  233. Takimoto CH, Lu ZH, Zhang R, et al. Severe neurotoxicity following 5-fluorouracil-based chemotherapy in a patient with dihydropyrimidine dehydrogenase deficiency. Clin Cancer Res 1996; 2:477.
  234. Heier MS, Fosså SD. Neurological manifestations in a phase 2 study of 13 patients treated with doxyfluridine. Acta Neurol Scand 1985; 72:171.
  235. Kuzuhara S, Ohkoshi N, Kanemaru K, et al. Subacute leucoencephalopathy induced by carmofur, a 5-fluorouracil derivative. J Neurol 1987; 234:365.
  236. Ohara S, Hayashi R, Hata S, et al. Leukoencephalopathy induced by chemotherapy with tegafur, a 5-fluorouracil derivative. Acta Neuropathol 1998; 96:527.
  237. Renouf D, Gill S. Capecitabine-induced cerebellar toxicity. Clin Colorectal Cancer 2006; 6:70.
  238. Formica V, Leary A, Cunningham D, Chua YJ. 5-Fluorouracil can cross brain-blood barrier and cause encephalopathy: should we expect the same from capecitabine? A case report on capecitabine-induced central neurotoxicity progressing to coma. Cancer Chemother Pharmacol 2006; 58:276.
  239. Videnovic A, Semenov I, Chua-Adajar R, et al. Capecitabine-induced multifocal leukoencephalopathy: a report of five cases. Neurology 2005; 65:1792.
  240. Meanwell CA, Blake AE, Kelly KA, et al. Prediction of ifosfamide/mesna associated encephalopathy. Eur J Cancer Clin Oncol 1986; 22:815.
  241. David KA, Picus J. Evaluating risk factors for the development of ifosfamide encephalopathy. Am J Clin Oncol 2005; 28:277.
  242. Rieger C, Fiegl M, Tischer J, et al. Incidence and severity of ifosfamide-induced encephalopathy. Anticancer Drugs 2004; 15:347.
  243. Lorigan P, Verweij J, Papai Z, et al. Phase III trial of two investigational schedules of ifosfamide compared with standard-dose doxorubicin in advanced or metastatic soft tissue sarcoma: a European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group Study. J Clin Oncol 2007; 25:3144.
  244. Pratt CB, Goren MP, Meyer WH, et al. Ifosfamide neurotoxicity is related to previous cisplatin treatment for pediatric solid tumors. J Clin Oncol 1990; 8:1399.
  245. Durand JP, Gourmel B, Mir O, Goldwasser F. Antiemetic neurokinin-1 antagonist aprepitant and ifosfamide-induced encephalopathy. Ann Oncol 2007; 18:808.
  246. Howell JE, Szabatura AH, Hatfield Seung A, Nesbit SA. Characterization of the occurrence of ifosfamide-induced neurotoxicity with concomitant aprepitant. J Oncol Pharm Pract 2008; 14:157.
  247. Hansen Ho, Yuen C. Aprepitant-associated ifosfamide neurotoxicity. J Oncol Pharm Pract 2010; 16:137.
  248. Jarkowski A 3rd. Possible contribution of aprepitant to ifosfamide-induced neurotoxicity. Am J Health Syst Pharm 2008; 65:2229.
  249. Küpfer A, Aeschlimann C, Wermuth B, Cerny T. Prophylaxis and reversal of ifosfamide encephalopathy with methylene-blue. Lancet 1994; 343:763.
  250. Pelgrims J, De Vos F, Van den Brande J, et al. Methylene blue in the treatment and prevention of ifosfamide-induced encephalopathy: report of 12 cases and a review of the literature. Br J Cancer 2000; 82:291.
  251. Buesa JM, García-Teijido P, Losa R, Fra J. Treatment of ifosfamide encephalopathy with intravenous thiamin. Clin Cancer Res 2003; 9:4636.
  252. Bernard PA, McCabe T, Bayliff S, Hayes D Jr. Successful treatment of ifosfamide neurotoxicity with dexmedetomidine. J Oncol Pharm Pract 2010; 16:262.
  253. Taupin D, Racela R, Friedman D. Ifosfamide chemotherapy and nonconvulsive status epilepticus: case report and review of the literature. Clin EEG Neurosci 2014; 45:222.
  254. Primavera A, Audenino D, Cocito L. Ifosfamide encephalopathy and nonconvulsive status epilepticus. Can J Neurol Sci 2002; 29:180.
  255. Patel SR, Forman AD, Benjamin RS. High-dose ifosfamide-induced exacerbation of peripheral neuropathy. J Natl Cancer Inst 1994; 86:305.
  256. Anderson NR, Tandon DS. Ifosfamide extrapyramidal neurotoxicity. Cancer 1991; 68:72.
  257. Ames B, Lewis LD, Chaffee S, et al. Ifosfamide-induced encephalopathy and movement disorder. Pediatr Blood Cancer 2010; 54:624.
  258. Savica R, Rabinstein AA, Josephs KA. Ifosfamide associated myoclonus-encephalopathy syndrome. J Neurol 2011; 258:1729.
  259. Burger PC, Kamenar E, Schold SC, et al. Encephalomyelopathy following high-dose BCNU therapy. Cancer 1980; 48:1318.
  260. Shapiro WR, Green SB, Burger PC, et al. A randomized comparison of intra-arterial versus intravenous BCNU, with or without intravenous 5-fluorouracil, for newly diagnosed patients with malignant glioma. J Neurosurg 1992; 76:772.
  261. Shapiro WR, Green SB. Reevaluating the efficacy of intra-arterial BCNU. J Neurosurg 1987; 66:313.
  262. Hiesiger EM, Green SB, Shapiro WR, et al. Results of a randomized trial comparing intra-arterial cisplatin and intravenous PCNU for the treatment of primary brain tumors in adults: Brain Tumor Cooperative Group trial 8420A. J Neurooncol 1995; 25:143.
  263. Rosenblum MK, Delattre JY, Walker RW, Shapiro WR. Fatal necrotizing encephalopathy complicating treatment of malignant gliomas with intra-arterial BCNU and irradiation: a pathological study. J Neurooncol 1989; 7:269.
  264. Subach BR, Witham TF, Kondziolka D, et al. Morbidity and survival after 1,3-bis(2-chloroethyl)-1-nitrosourea wafer implantation for recurrent glioblastoma: a retrospective case-matched cohort series. Neurosurgery 1999; 45:17.
  265. Weiss HD, Walker MD, Wiernik PH. Neurotoxicity of commonly used antineoplastic agents (second of two parts). N Engl J Med 1974; 291:127.
  266. Postma TJ, van Groeningen CJ, Witjes RJ, et al. Neurotoxicity of combination chemotherapy with procarbazine, CCNU and vincristine (PCV) for recurrent glioma. J Neurooncol 1998; 38:69.
  267. Feinberg WM, Swenson MR. Cerebrovascular complications of L-asparaginase therapy. Neurology 1988; 38:127.
  268. Barbui T, Rambaldi A, Parenzan L, et al. Neurological symptoms and coma associated with doxorubicin administration during chronic cyclosporin therapy. Lancet 1992; 339:1421.
  269. Schachter S, Freeman R. Transient ischemic attack and adriamycin cardiomyopathy. Neurology 1982; 32:1380.
  270. Marcus RE, Goldman JM. Convulsions due to high-dose busulphan. Lancet 1984; 2:1463.
  271. Wyllie AR, Bayliff CD, Kovacs MJ. Myoclonus due to chlorambucil in two adults with lymphoma. Ann Pharmacother 1997; 31:171.
  272. Salloum E, Khan KK, Cooper DL. Chlorambucil-induced seizures. Cancer 1997; 79:1009.
  273. Lubiniecki GM, Berlin JA, Weinstein RB, Vaughn DJ. Thromboembolic events with estramustine phosphate-based chemotherapy in patients with hormone-refractory prostate carcinoma: results of a meta-analysis. Cancer 2004; 101:2755.
  274. Dormann AJ, Grünewald T, Wigginghaus B, Huchzermeyer H. Gemcitabine-associated autonomic neuropathy. Lancet 1998; 351:644.
  275. Ardavanis AS, Ioannidis GN, Rigatos GA. Acute myopathy in a patient with lung adenocarcinoma treated with gemcitabine and docetaxel. Anticancer Res 2005; 25:523.
  276. Friedlander PA, Bansal R, Schwartz L, et al. Gemcitabine-related radiation recall preferentially involves internal tissue and organs. Cancer 2004; 100:1793.
  277. Larsen FO, Hansen SW. Severe neurotoxicity caused by gemcitabine treatment. Acta Oncol 2004; 43:590.
  278. Han CH, Findlay MP. Chemotherapy-induced reversible posterior leucoencephalopathy syndrome. Intern Med J 2010; 40:153.
  279. Cunningham D, Glimelius B. A phase III study of irinotecan (CPT-11) versus best supportive care in patients with metastatic colorectal cancer who have failed 5-fluorouracil therapy. V301 Study Group. Semin Oncol 1999; 26:6.
  280. Hamberg P, Donders RC, ten Bokkel Huinink D. Central nervous system toxicity induced by irinotecan. J Natl Cancer Inst 2006; 98:219.
  281. Doll DC, Yarbro JW. Vascular toxicity associated with antineoplastic agents. Semin Oncol 1992; 19:580.
  282. Cheson BD, Vena DA, Foss FM, Sorensen JM. Neurotoxicity of purine analogs: a review. J Clin Oncol 1994; 12:2216.
  283. Gonzalez H, Bolgert F, Camporo P, Leblond V. Progressive multifocal leukoencephalitis (PML) in three patients treated with standard-dose fludarabine (FAMP). Hematol Cell Ther 1999; 41:183.
  284. Warrell RP Jr, Berman E. Phase I and II study of fludarabine phosphate in leukemia: therapeutic efficacy with delayed central nervous system toxicity. J Clin Oncol 1986; 4:74.
  285. Selleri C, Pane F, Notaro R, et al. All-trans-retinoic acid (ATRA) responsive skin relapses of acute promyelocytic leukaemia followed by ATRA-induced pseudotumour cerebri. Br J Haematol 1996; 92:937.
  286. Yamaji S, Kanamori H, Mishima A, et al. All-trans retinoic acid-induced multiple mononeuropathies. Am J Hematol 1999; 60:311.
  287. Brandi G, de Rosa F, Calzà L, et al. Can the tyrosine kinase inhibitors trigger metabolic encephalopathy in cirrhotic patients? Liver Int 2013; 33:488.
  288. Marks AB, Gerard R, Fournier P, et al. Sorafenib-induced hepatic encephalopathy. Ann Pharmacother 2009; 43:2121.
  289. Arnaud L, Schartz NE, Bousquet G, et al. Transient sunitinib-induced coma in a patient with fibromyxoid sarcoma. J Clin Oncol 2008; 26:1569.
  290. Mannavola D, Coco P, Vannucchi G, et al. A novel tyrosine-kinase selective inhibitor, sunitinib, induces transient hypothyroidism by blocking iodine uptake. J Clin Endocrinol Metab 2007; 92:3531.
  291. Lele AV, Clutter S, Price E, De Ruyter ML. Severe hypothyroidism presenting as myxedema coma in the postoperative period in a patient taking sunitinib: case report and review of literature. J Clin Anesth 2013; 25:47.
  292. Martín G, Bellido L, Cruz JJ. Reversible posterior leukoencephalopathy syndrome induced by sunitinib. J Clin Oncol 2007; 25:3559.
  293. Chen A, Agarwal N. Reversible posterior leucoencephalopathy syndrome associated with sunitinib. Intern Med J 2009; 39:341.
  294. Padhy BM, Shanmugam SP, Gupta YK, Goyal A. Reversible posterior leucoencephalopathy syndrome in an elderly male on sunitinib therapy. Br J Clin Pharmacol 2011; 71:777.
  295. Palma JA, Gomez-Ibañez A, Martin B, et al. Nonconvulsive status epilepticus related to posterior reversible leukoencephalopathy syndrome induced by cetuximab. Neurologist 2011; 17:273.
  296. Khan KH, Fenton A, Murtagh E, et al. Reversible posterior leukoencephalopathy syndrome following sunitinib therapy: a case report and review of the literature. Tumori 2012; 98:139e.
  297. Cairncross G, Swinnen L, Bayer R, et al. Myeloablative chemotherapy for recurrent aggressive oligodendroglioma. Neuro Oncol 2000; 2:114.
  298. Gutin PH, Levi JA, Wiernik PH, Walker MD. Treatment of malignant meningeal disease with intrathecal thioTEPA: a phase II study. Cancer Treat Rep 1977; 61:885.
  299. Klein O, Ribas A, Chmielowski B, et al. Facial palsy as a side effect of vemurafenib treatment in patients with metastatic melanoma. J Clin Oncol 2013; 31:e215.