title: Anticonvulsant usage is associated with an increased risk of procarbazine hypersensitivity reactions in patients with brain tumors.
abstract: BACKGROUND
  Procarbazine usage in brain tumors has a high incidence of hypersensitivity reactions compared with its use in other malignancies. Procarbazine oxidation to a reactive intermediate is enhanced by phenobarbital. Patients with primary brain tumors would have a preferential exposure to anticonvulsants compared to patients with other malignancies.
  
  
  OBJECTIVE
  To determine whether anticonvulsant exposure is associated with procarbazine hypersensitivity reactions in patients with primary brain tumors.
  
  
  METHODS
  This retrospective cohort study included 83 patients with primary brain tumors who were treated with procarbazine between 1981 and 1996 at a university hospital-based regional oncology center. Data were extracted by chart review. The data collected included age, sex, race, tumor type, smoking, alcohol usage, and all concomitant medications, as well as creatinine, aspartate aminotransferase, total bilirubin, and anticonvulsant serum levels. Anticonvulsant exposure was determined by the presence of detectable serum levels. Cases of procarbazine hypersensitivity reactions were identified through a review of progress notes.
  
  
  RESULTS
  There were 20 patients with procarbazine hypersensitivity reactions. A significant association between the exposure to anticonvulsants and the development of procarbazine hypersensitivity reactions was found (p = 0.05). In addition, there was a significant dose-response association between the development of procarbazine hypersensitivity and the presence of therapeutic anticonvulsant serum levels (p = 0.03).
  
  
  CONCLUSIONS
  Concomitant exposure to anticonvulsants is associated with procarbazine hypersensitivity reactions, possibly though a reactive intermediate generated by CYP3A isoform induction. All patients in this cohort received enzyme-inducing anticonvulsants. New anticonvulsants devoid of this property are available. These data support trials that use these newer agents for the prophylaxis of seizures in patients with brain tumors who are to receive procarbazine.
authors.affiliation: Department of Medicine, School of Medicine, State University of New York Health Science Center at Syracuse 13210, USA.
authors.forename: D F
authors.initials: DF
authors.lastname: Lehmann
authors.forename: T E
authors.initials: TE
authors.lastname: Hurteau
authors.forename: N
authors.initials: N
authors.lastname: Newman
authors.forename: T E
authors.initials: TE
authors.lastname: Coyle
mesh_terms: D000328:Adult; D000927:Anticonvulsants / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols; D001932:Brain Neoplasms / Q000188:drug therapy*; D002220:Carbamazepine / Q000627:therapeutic use; D015331:Cohort Studies; D004342:Drug Hypersensitivity / Q000175:diagnosis / Q000209:etiology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010634:Phenobarbital / Q000627:therapeutic use; D010672:Phenytoin / Q000627:therapeutic use; D011344:Procarbazine / Q000009:adverse effects* / Q000627:therapeutic use; D012189:Retrospective Studies; D014635:Valproic Acid / Q000627:therapeutic use
chemical_list: D000927:Anticonvulsants; D000970:Antineoplastic Agents; D002220:Carbamazepine; D011344:Procarbazine; D014635:Valproic Acid; D010672:Phenytoin; D010634:Phenobarbital