title: Effect of azole antifungal therapy on vincristine toxicity in childhood acute lymphoblastic leukaemia.
abstract: BACKGROUND
  Vincristine is one of the cornerstones of the treatment of children with acute lymphoblastic leukaemia (ALL). Constipation, and peripheral and central neurotoxicities are the most common side effects. A comparative study exploring vincristine toxicity in individual patients receiving vincristine with and without azoles, however, is lacking.
  
  
  METHODS
  In total, 20 paediatric patients with de novo ALL were included. In each patient, vincristine toxicity in the period with and without azole co-medication was retrospectively graded according to the US National Cancer Institute toxicity scale. Statistical analysis was performed using the Wilcoxon signed rank test and McNemar's test.
  
  
  RESULTS
  Patients receiving vincristine in combination with azole treatment experienced significantly more constipation and peripheral neurotoxicity (P = 0.001 and P < 0.001, respectively). Vincristine-induced CNS toxicity was only seen in patients (30%) receiving vincristine in combination with azole treatment.
  
  
  CONCLUSIONS
  Vincristine toxicity is significantly enhanced when combined with azole treatment and can even be life threatening. Therefore, we advise avoidance of the combination of azole and vincristine treatments in patients with ALL.
authors.affiliation: Department of Pediatric Oncology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: Rosalin M
authors.initials: RM
authors.lastname: van Schie
authors.forename: Roger J M
authors.initials: RJ
authors.lastname: Brüggemann
authors.forename: Peter M
authors.initials: PM
authors.lastname: Hoogerbrugge
authors.forename: D M W M
authors.initials: DM
authors.lastname: te Loo
mesh_terms: D000935:Antifungal Agents / Q000008:administration & dosage*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001393:Azoles / Q000008:administration & dosage*; D002648:Child; D002675:Child, Preschool; D003248:Constipation / Q000139:chemically induced; D004347:Drug Interactions; D006801:Humans; D009181:Mycoses / Q000517:prevention & control*; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000150:complications / Q000188:drug therapy*; D012189:Retrospective Studies; D012720:Severity of Illness Index; D014481:United States; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D000935:Antifungal Agents; D000970:Antineoplastic Agents; D001393:Azoles; D014750:Vincristine