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Abstract
ABSTRACT
Background: Vincristine is a chemotherapeutic agent frequently used in the treatment of childhood cancer. Peripheral neuropathy is an important side effect of Vincristine. We assessed the incidence, severity and type of peripheral neuropathy in children on Vincristine using clinical parameters and nerve conduction studies.
Methods: Children with cancer treated with Vincristine were enrolled. Symptoms and signs of motor, sensory and autonomic peripheral neuropathy at baseline and at 3, 6 and 12 month follow up were documented. A modified total neuropathy score grading was undertaken. Nerve conduction studies (NCS) were undertaken and vitamin E levels measured at the time of these assessments.
Results: 28 patients were enrolled over 12 months. 93% had evidence of neuropathy clinically and/or electrophysiologically. Weakness, pain and constipation were the most common symptoms and the most common sign was loss of ankle reflexes. The peripheral neuropathy was mild in most cases. Plasma levels of vitamin E remained in the normal range, however they dropped significantly from the baseline value.
Conclusions: Peripheral neuropathy assessed clinically and electrophysiologically, occurs in the majority of children on Vincristine treatment. The neuropathy is sensory-motor and generally mild. There was a statistically significant drop in average vitamin E levels during treatment.
Keywords: Vincristine, peripheral neuropathy, vitamin E
Keywords
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Copyright (c) 2017 Lakshmi Nagarajan
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References
- REFERENCES
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- Hausheer FH, Schilsky RL, Bain S, et al. Diagnosis, management, and evaluation of chemotherapy-induced peripheral neuropathy. Seminars in oncology 2006:33(1):15-49.
- Cavaletti G, Marmiroli P. Chemotherapy-induced peripheral neurotoxicity. Expert opinion on drug safety 2004:3(6):535-546.
- Hilkens PH, ven den Bent MJ. Chemotherapy-induced peripheral neuropathy. Journal of the peripheral nervous system : JPNS 1997:2(4):350-361.
- Marrs J, Newton S. Updating your peripheral neuropathy "know-how". Clinical journal of oncology nursing 2003:7(3):299-303.
- Pachman DR, Barton DL, Watson JC, et al. Chemotherapy-induced peripheral neuropathy: prevention and treatment. Clinical pharmacology and therapeutics 2011:90(3):377-387.
- Lavoie Smith EM, Li L, Chiang C, et al. Patterns and severity of vincristine-induced
- peripheral neuropathy in children with acute lymphoblastic leukemia. Journal of the
- Peripheral Nervous System 2015 :20(1):37-46.
- Berg SL, Parsons DW. The pharmacogenomics of vincristine-induced neuropathy: on
- pins and needles. The Journal of the American Medical Association Oncology 2015
- :1(7):975-6.
- Beijers AJ, Jongen JL, Vreugdenhil G. Chemotherapy-induced neurotoxicity: the value of neuroprotective strategies. The Netherlands journal of medicine 2012:70(1):18-25.
- Park SB, Krishnan AV, Lin CS, et al. Mechanisms underlying chemotherapy-induced
- neurotoxicity and the potential for neuroprotective strategies. Current medicinal chemistry 2008:15(29):3081-3094.
- Carozzi VA, Canta A, Chiorazzi A. Chemotherapy-induced peripheral neuropathy:
- What do we know about mechanisms? Neuroscience Letters 2015 Jun 2; 596:90-107.
- Sisignano M , Baron R, Scholich K et al. Mechanism-based treatment for
- chemotherapy-induced peripheral neuropathic pain. Nature Reviews Neurology
- :10(12):694-707.
- 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(7):932-937.
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- Gilchrist L, Tanner L. Gait Patterns in Children With Cancer and Vincristine Neuropathy.
- Pediatric Physical Therapy. 2016: 28(1):16-22.
- Courtemanche H, Magot A, Ollivier Y et al. Vincristine-induced neuropathy: Atypical
- electrophysiological patterns in children. Muscle Nerve. 2015 :52(6):981-5.
- Muller DP, Goss-Sampson MA. Neurochemical, neurophysiological, and neuropathological studies in vitamin E deficiency. Critical reviews in neurobiology 1990:5(3):239-263.
- Zouari M, Feki M, Ben Hamida C, et al. Electrophysiology and nerve biopsy: comparative study in Friedreich's ataxia and Friedreich's ataxia phenotype with vitamin E deficiency. Neuromuscular disorders: NMD 1998:8(6):416-425.
- Kennedy DD, Tucker KL, Ladas ED, et al. Low antioxidant vitamin intakes are associated with increases in adverse effects of chemotherapy in children with acute lymphoblastic leukemia. The American journal of clinical nutrition 2004:79(6):1029-1036.
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- Bove L, Picardo M, Maresca V, et al. A pilot study on the relation between cisplatin neuropathy and vitamin E. Journal of experimental & clinical cancer research: CR 2001:20(2):277-280.
- Battisti V, Maders LD, Bagatini MD, et al. Measurement of oxidative stress and antioxidant status in acute lymphoblastic leukemia patients. Clinical biochemistry 2008:41(7-8):511-518.
- Dasgupta J, Sanyal U, Das S. Vitamin E--its status and role in leukemia and lymphoma. Neoplasma 1993: 40(4):235-240.
- Argyriou AA, Chroni E, Koutras A, et al. Vitamin E for prophylaxis against chemotherapy-induced neuropathy: a randomized controlled trial. Neurology 2005:64(1):26-31.
- Pace A, Savarese A, Picardo M, et al. Neuroprotective effect of vitamin E supplementation in patients treated with cisplatin chemotherapy. Journal of Clinical Oncology : official journal of the American Society of Clinical Oncology 2003:21(5):927-931.
- Pace A, Giannarelli D, Galie E, et al. Vitamin E neuroprotection for cisplatin neuropathy: a randomized, placebo-controlled trial. Neurology 2010:74(9):762-766.
- 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. Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer 2011:19(11):1769-1777.
- Al-Tonbary Y, Al-Haggar M, El-Ashry R, et al. Vitamin e and N-acetylcysteine as antioxidant adjuvant therapy in children with acute lymphoblastic leukemia. Advances in Hematology 2009:2009:689639.
- Leonetti C, Biroccio A, Gabellini C, et al. Alpha-tocopherol protects against cisplatin-induced toxicity without interfering with antitumor efficacy. International journal of cancer Journal international du cancer 2003:104(2):243-250.
- Davis EA, Jones TW, Walsh P, et al. The use of biothesiometry to detect neuropathy in children and adolescents with IDDM. Diabetes care 1997:20(9):1448-1453.
- Smith EM, Beck SL, Cohen J. The total neuropathy score: a tool for measuring chemotherapy-induced peripheral neuropathy. Oncology nursing forum 2008:35(1):96-102.
- Melvin JL, Schuchmann JA, Lanese RR. Diagnostic specificity of motor and sensory nerve conduction variables in the carpal tunnel syndrome. Archives of physical medicine and rehabilitation 1973:54(2):69-74.
- Jimenez J, Easton JK, Redford JB. Conduction studies of the anterior and posterior tibial nerves. Archives of physical medicine and rehabilitation 1970:51(3):164-169.
- Johnson EW, Kukla RD, Wongsam PE, et al. Sensory latencies to the ring finger: normal values and relation to carpal tunnel syndrome. Archives of physical medicine and rehabilitation 1981:62(5):206-208.
- Schuchmann JA. Sural nerve conduction: a standardized technique. Archives of physical medicine and rehabilitation 1977:58(4):166-168.
- Lavoie Smith EM, Cohen JA, Pett MA, et al. The validity of neuropathy and neuropathic pain measures in patients with cancer receiving taxanes and platinums. Oncology nursing forum 2011:38(2):133-142.
- Reinders-Messelink HA, Schoemaker MM, Snijders TA, et al. Analysis of handwriting of children during treatment for acute lymphoblastic leukemia. Medical and pediatric oncology 2001:37(4):393-399.
- Harila-Saari AH, Huuskonen UE, Tolonen U, et al. Motor nervous pathway function is impaired after treatment of childhood acute lymphoblastic leukemia: a study with motor evoked potentials. Medical and pediatric oncology 2001:36(3):345-351.
- Reinders-Messelink H, Schoemaker M, Snijders T, et al. Motor performance of children during treatment for acute lymphoblastic leukemia. Medical and pediatric oncology 1999:33(6):545-550.
- Ramchandren S, Leonard M, Mody RJ, et al. Peripheral neuropathy in survivors of childhood acute lymphoblastic leukemia. Journal of the peripheral nervous system : JPNS 2009:14(3):184-189.
- Gilchrist LS, Tanner L. The pediatric-modified total neuropathy score: a reliable and valid measure of chemotherapy-induced peripheral neuropathy in children with non-CNS cancers. Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer 2013:21(3):847-856.
- van den Berg MM, Benninga MA, Di Lorenzo C. Epidemiology of childhood constipation: a systematic review. The American journal of gastroenterology 2006:101(10):2401-2409.
References
REFERENCES
Armenian SH, Robison LL. Childhood cancer survivorship: an update on evolving paradigms for understanding pathogenesis and screening for therapy-related late effects. Current opinion in pediatrics. 2013:25(1):16-22.
Hausheer FH, Schilsky RL, Bain S, et al. Diagnosis, management, and evaluation of chemotherapy-induced peripheral neuropathy. Seminars in oncology 2006:33(1):15-49.
Cavaletti G, Marmiroli P. Chemotherapy-induced peripheral neurotoxicity. Expert opinion on drug safety 2004:3(6):535-546.
Hilkens PH, ven den Bent MJ. Chemotherapy-induced peripheral neuropathy. Journal of the peripheral nervous system : JPNS 1997:2(4):350-361.
Marrs J, Newton S. Updating your peripheral neuropathy "know-how". Clinical journal of oncology nursing 2003:7(3):299-303.
Pachman DR, Barton DL, Watson JC, et al. Chemotherapy-induced peripheral neuropathy: prevention and treatment. Clinical pharmacology and therapeutics 2011:90(3):377-387.
Lavoie Smith EM, Li L, Chiang C, et al. Patterns and severity of vincristine-induced
peripheral neuropathy in children with acute lymphoblastic leukemia. Journal of the
Peripheral Nervous System 2015 :20(1):37-46.
Berg SL, Parsons DW. The pharmacogenomics of vincristine-induced neuropathy: on
pins and needles. The Journal of the American Medical Association Oncology 2015
:1(7):975-6.
Beijers AJ, Jongen JL, Vreugdenhil G. Chemotherapy-induced neurotoxicity: the value of neuroprotective strategies. The Netherlands journal of medicine 2012:70(1):18-25.
Park SB, Krishnan AV, Lin CS, et al. Mechanisms underlying chemotherapy-induced
neurotoxicity and the potential for neuroprotective strategies. Current medicinal chemistry 2008:15(29):3081-3094.
Carozzi VA, Canta A, Chiorazzi A. Chemotherapy-induced peripheral neuropathy:
What do we know about mechanisms? Neuroscience Letters 2015 Jun 2; 596:90-107.
Sisignano M , Baron R, Scholich K et al. Mechanism-based treatment for
chemotherapy-induced peripheral neuropathic pain. Nature Reviews Neurology
:10(12):694-707.
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(7):932-937.
Lavoie Smith EM, Li L, Hutchinson RJ, et al. Measuring vincristine-induced peripheral neuropathy in children with acute lymphoblastic leukemia. Cancer nursing 2013:36(5):E49-60.
Gilchrist L, Tanner L. Gait Patterns in Children With Cancer and Vincristine Neuropathy.
Pediatric Physical Therapy. 2016: 28(1):16-22.
Courtemanche H, Magot A, Ollivier Y et al. Vincristine-induced neuropathy: Atypical
electrophysiological patterns in children. Muscle Nerve. 2015 :52(6):981-5.
Muller DP, Goss-Sampson MA. Neurochemical, neurophysiological, and neuropathological studies in vitamin E deficiency. Critical reviews in neurobiology 1990:5(3):239-263.
Zouari M, Feki M, Ben Hamida C, et al. Electrophysiology and nerve biopsy: comparative study in Friedreich's ataxia and Friedreich's ataxia phenotype with vitamin E deficiency. Neuromuscular disorders: NMD 1998:8(6):416-425.
Kennedy DD, Tucker KL, Ladas ED, et al. Low antioxidant vitamin intakes are associated with increases in adverse effects of chemotherapy in children with acute lymphoblastic leukemia. The American journal of clinical nutrition 2004:79(6):1029-1036.
Weijl NI, Hopman GD, Wipkink-Bakker A, et al. Cisplatin combination chemotherapy induces a fall in plasma antioxidants of cancer patients. Annals of oncology : official journal of the European Society for Medical Oncology / ESMO 1998:9(12):1331-1337.
Bove L, Picardo M, Maresca V, et al. A pilot study on the relation between cisplatin neuropathy and vitamin E. Journal of experimental & clinical cancer research: CR 2001:20(2):277-280.
Battisti V, Maders LD, Bagatini MD, et al. Measurement of oxidative stress and antioxidant status in acute lymphoblastic leukemia patients. Clinical biochemistry 2008:41(7-8):511-518.
Dasgupta J, Sanyal U, Das S. Vitamin E--its status and role in leukemia and lymphoma. Neoplasma 1993: 40(4):235-240.
Argyriou AA, Chroni E, Koutras A, et al. Vitamin E for prophylaxis against chemotherapy-induced neuropathy: a randomized controlled trial. Neurology 2005:64(1):26-31.
Pace A, Savarese A, Picardo M, et al. Neuroprotective effect of vitamin E supplementation in patients treated with cisplatin chemotherapy. Journal of Clinical Oncology : official journal of the American Society of Clinical Oncology 2003:21(5):927-931.
Pace A, Giannarelli D, Galie E, et al. Vitamin E neuroprotection for cisplatin neuropathy: a randomized, placebo-controlled trial. Neurology 2010:74(9):762-766.
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. Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer 2011:19(11):1769-1777.
Al-Tonbary Y, Al-Haggar M, El-Ashry R, et al. Vitamin e and N-acetylcysteine as antioxidant adjuvant therapy in children with acute lymphoblastic leukemia. Advances in Hematology 2009:2009:689639.
Leonetti C, Biroccio A, Gabellini C, et al. Alpha-tocopherol protects against cisplatin-induced toxicity without interfering with antitumor efficacy. International journal of cancer Journal international du cancer 2003:104(2):243-250.
Davis EA, Jones TW, Walsh P, et al. The use of biothesiometry to detect neuropathy in children and adolescents with IDDM. Diabetes care 1997:20(9):1448-1453.
Smith EM, Beck SL, Cohen J. The total neuropathy score: a tool for measuring chemotherapy-induced peripheral neuropathy. Oncology nursing forum 2008:35(1):96-102.
Melvin JL, Schuchmann JA, Lanese RR. Diagnostic specificity of motor and sensory nerve conduction variables in the carpal tunnel syndrome. Archives of physical medicine and rehabilitation 1973:54(2):69-74.
Jimenez J, Easton JK, Redford JB. Conduction studies of the anterior and posterior tibial nerves. Archives of physical medicine and rehabilitation 1970:51(3):164-169.
Johnson EW, Kukla RD, Wongsam PE, et al. Sensory latencies to the ring finger: normal values and relation to carpal tunnel syndrome. Archives of physical medicine and rehabilitation 1981:62(5):206-208.
Schuchmann JA. Sural nerve conduction: a standardized technique. Archives of physical medicine and rehabilitation 1977:58(4):166-168.
Lavoie Smith EM, Cohen JA, Pett MA, et al. The validity of neuropathy and neuropathic pain measures in patients with cancer receiving taxanes and platinums. Oncology nursing forum 2011:38(2):133-142.
Reinders-Messelink HA, Schoemaker MM, Snijders TA, et al. Analysis of handwriting of children during treatment for acute lymphoblastic leukemia. Medical and pediatric oncology 2001:37(4):393-399.
Harila-Saari AH, Huuskonen UE, Tolonen U, et al. Motor nervous pathway function is impaired after treatment of childhood acute lymphoblastic leukemia: a study with motor evoked potentials. Medical and pediatric oncology 2001:36(3):345-351.
Reinders-Messelink H, Schoemaker M, Snijders T, et al. Motor performance of children during treatment for acute lymphoblastic leukemia. Medical and pediatric oncology 1999:33(6):545-550.
Ramchandren S, Leonard M, Mody RJ, et al. Peripheral neuropathy in survivors of childhood acute lymphoblastic leukemia. Journal of the peripheral nervous system : JPNS 2009:14(3):184-189.
Gilchrist LS, Tanner L. The pediatric-modified total neuropathy score: a reliable and valid measure of chemotherapy-induced peripheral neuropathy in children with non-CNS cancers. Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer 2013:21(3):847-856.
van den Berg MM, Benninga MA, Di Lorenzo C. Epidemiology of childhood constipation: a systematic review. The American journal of gastroenterology 2006:101(10):2401-2409.