{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T20:41:06Z","timestamp":1767991266171,"version":"3.49.0"},"reference-count":21,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2014,12,24]],"date-time":"2014-12-24T00:00:00Z","timestamp":1419379200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2015,6]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Vincristine causes known side effects of peripheral sensory, motor, autonomic and cranial neuropathies. No preventive interventions are known.<\/jats:p><\/jats:sec><jats:sec><jats:title>Procedure<\/jats:title><jats:p>We performed a randomized, placebo\u2010controlled, double\u2010blind trial of oral glutamic acid as a preventive agent in pediatric patients with cancer who would be receiving vincristine therapy for at least 9 consecutive weeks (Stratum 1\u2009=\u2009Wilms tumor and rhabdomyosarcoma) or 4 consecutive weeks in conjunction with steroids (Stratum 2\u2009=\u2009Acute lymphoblastic leukemia and non\u2010Hodgkin lymphoma). At designated time points, a scored neurologic exam using the Modified Balis Pediatric Scale of Peripheral Neuropathies was performed to document neurologic toxicity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Between 2007 and 2012, 250 patients were enrolled (Stratum 1\u2009=\u200950, Stratum 2\u2009=\u2009200). The glutamic acid treated group did not have a significantly lower percentage of neurotoxicity compared to placebo treated group either overall or within stratum or age subgroups. The only subgroup which was suggestive of treatment effect was for age. Patients 13 years or older showed a larger benefit in favor of glutamic acid (<jats:italic>P<\/jats:italic>\u2009=\u20090.055) compared to patients less than 13 years (<jats:italic>P<\/jats:italic>\u2009=\u20091.00). Constipation was the most frequently reported (14%) Grade II or higher neurotoxicity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Vincristine\u2010associated neurotoxicity in pediatric oncology remains a frequent complication of chemotherapy for multiple diagnoses with an approximate 30% of patients affected. Glutamic acid is not effective for prevention in pre\u2010adolescents. There is a suggestion of benefit in patients 13 years or older, but the study was not designed to provide adequate power to test the treatment effect within this age group alone. Pediatr Blood Cancer 2015;62:1004\u20131010. \u00a9 2014 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pbc.25384","type":"journal-article","created":{"date-parts":[[2014,12,24]],"date-time":"2014-12-24T20:27:37Z","timestamp":1419452857000},"page":"1004-1010","source":"Crossref","is-referenced-by-count":32,"title":["Glutamic acid not beneficial for the prevention of vincristine neurotoxicity in children with cancer"],"prefix":"10.1002","volume":"62","author":[{"given":"Scott M.","family":"Bradfield","sequence":"first","affiliation":[{"name":"Division of Hematology\u2010Oncology Department of Pediatrics Nemours Children's Clinic Jacksonville Florida"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric","family":"Sandler","sequence":"additional","affiliation":[{"name":"Division of Hematology\u2010Oncology Department of Pediatrics Nemours Children's Clinic Jacksonville Florida"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Geller","sequence":"additional","affiliation":[{"name":"Division of Child Neurology Department of Neurology and Psychiatry Saint Louis University School of Medicine St. Louis Missouri"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roy N.","family":"Tamura","sequence":"additional","affiliation":[{"name":"Pediatric Epidemiology Center University of South Florida College of Medicine Tampa Florida"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey P.","family":"Krischer","sequence":"additional","affiliation":[{"name":"Pediatric Epidemiology Center University of South Florida College of Medicine Tampa Florida"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,12,24]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.2174\/1568011023354452"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0163-7258(91)90086-2"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.19.4.367"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-80-6-733"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005072-197107000-00012"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9861(19980615)395:4<481::AID-CNE5>3.0.CO;2-Y"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/1096-9861(20000904)424:4<563::AID-CNE1>3.0.CO;2-U"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(75)90185-9"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.11.4685"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/0167-4838(92)90044-E"},{"key":"e_1_2_6_12_1","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1242\/jcs.107.4.869","article-title":"Sense and antisense transfection analysis of tau function: tau influences net microtubule assembly, neurite outgrowth and neuritic stability","volume":"107","author":"Esmaeli\u2010Azad B","year":"1994","journal-title":"J Cell Sci"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(88)90306-3"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM197407112910205"},{"key":"e_1_2_6_15_1","first-page":"323","article-title":"Clinical and electrophysiological studies in vincristine induced neuropathy","volume":"39","author":"Pal PK","year":"1999","journal-title":"Electromyogr Clin Neurophysiol"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00253273"},{"key":"e_1_2_6_17_1","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1016\/S0022-3565(25)20981-8","article-title":"Glutamate ameliorates experimental vincristine neuropathy","volume":"279","author":"Boyle FM","year":"1996","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPH.0b013e3181e9038d"},{"key":"e_1_2_6_19_1","first-page":"245","article-title":"Glutamic acid modification of vincristine toxicity","volume":"7","author":"Jackson DV","year":"1984","journal-title":"Cancer Biochem Biophys"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1097\/NCC.0b013e318299ad23"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.22845"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1097\/00043426-200304000-00010"}],"container-title":["Pediatric Blood &amp; 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