title: Glutamic acid not beneficial for the prevention of vincristine neurotoxicity in children with cancer.
abstract: BACKGROUND
  Vincristine causes known side effects of peripheral sensory, motor, autonomic and cranial neuropathies. No preventive interventions are known.
  
  
  METHODS
  We performed a randomized, placebo-controlled, double-blind 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 = Wilms tumor and rhabdomyosarcoma) or 4 consecutive weeks in conjunction with steroids (Stratum 2 = Acute lymphoblastic leukemia and non-Hodgkin lymphoma). At designated time points, a scored neurologic exam using the Modified Balis Pediatric Scale of Peripheral Neuropathies was performed to document neurologic toxicity.
  
  
  RESULTS
  Between 2007 and 2012, 250 patients were enrolled (Stratum 1 = 50, Stratum 2 = 200). 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 (P = 0.055) compared to patients less than 13 years (P = 1.00). Constipation was the most frequently reported (14%) Grade II or higher neurotoxicity.
  
  
  CONCLUSIONS
  Vincristine-associated 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-adolescents. 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.
authors.affiliation: Division of Hematology-Oncology, Department of Pediatrics, Nemours Children's Clinic, Jacksonville, Florida.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Bradfield
authors.forename: Eric
authors.initials: E
authors.lastname: Sandler
authors.forename: Thomas
authors.initials: T
authors.lastname: Geller
authors.forename: Roy N
authors.initials: RN
authors.lastname: Tamura
authors.forename: Jeffrey P
authors.initials: JP
authors.lastname: Krischer
mesh_terms: D000293:Adolescent; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D004311:Double-Blind Method; D005260:Female; D018698:Glutamic Acid / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D009369:Neoplasms / Q000188:drug therapy*; D020258:Neurotoxicity Syndromes / Q000517:prevention & control*; D014750:Vincristine / Q000009:adverse effects*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D018698:Glutamic Acid; D014750:Vincristine
keywords: chemotherapy neurotoxicities; lymphoblastic leukemia/neurology; pediatric oncology; quality of life; support care