title: Nitroso-urea-cisplatin-based chemotherapy associated with valproate: increase of haematologic toxicity.
abstract: BACKGROUND
  The incidence of haematologic toxicity of valproate (VPA) ranges from 1% to 32% and consists mainly of asymptomatic, dose-dependent thrombopenia. We describe a potentiation of haematologic side-effects of nitroso-urea (NU) when prescribed in association with VPA.
  
  
  METHODS
  We followed a cohort of 70 patients (58 men, 22 women, mean age: 56 years, range 20-75 years). Patients with high-grade gliomas were treated with up-front chemotherapy regimen consisting of fotemustine (d3: 100 mg/m2), cisplatin (d1-3: 33 mg/m2) and etoposide (d1-3: 75 mg/m2) followed by whole brain radiotherapy at progression. Sixty patients required anti-epileptic drugs (AED) for either a single, well-documented epileptic seizure, or immediatly initiated after neurosurgical procedures. AED included VPA (35 of 60), phenobarbital (PB) (17 of 60), carbamazepine (CBZ) (2 of 60) and phenytoin (PHT) (3 of 60). Two patients had both PB and CBZ and one PB and PHT.
  
  
  RESULTS
  Haematologic toxicity (grade 3-4 thrombopenia, neutropenia or both) was observed in 37 of 70 (52.85%) patients. Among them 24 (65%) had VPA. Group C were patients treated with fotemustine alone with or without VPA (23 patients).
  
  
  CONCLUSIONS
  When prescribed in association with a fotemustine-cisplatin regimen, VPA treatment results in a three-fold higher incidence of reversible thrombopenia, neutropenia or both. Haematologic side-effects decrease after AED modification during the continued chemotherapy. This adverse event should be managed with caution.
authors: Service de Neurologie, H pital Pasteur, Nice, France.
authors: V
authors: V
authors: Bourg
authors: C
authors: C
authors: Lebrun
authors: R M
authors: RM
authors: Chichmanian
authors: P
authors: P
authors: Thomas
authors: M
authors: M
authors: Frenay
mesh_terms: D000328:Adult; D000368:Aged; D000927:Anticonvulsants / Q000009:adverse effects* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000188:drug therapy; D002945:Cisplatin / Q000008:administration & dosage; D004347:Drug Interactions; D004827:Epilepsy / Q000188:drug therapy; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D005910:Glioma / Q000188:drug therapy; D006403:Hematologic Tests; D006801:Humans; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced*; D009607:Nitrosourea Compounds / Q000008:administration & dosage; D009943:Organophosphorus Compounds / Q000008:administration & dosage; D012189:Retrospective Studies; D013921:Thrombocytopenia / Q000139:chemically induced*; D014635:Valproic Acid / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D000927:Anticonvulsants; D009607:Nitrosourea Compounds; D009943:Organophosphorus Compounds; D014635:Valproic Acid; D005047:Etoposide; C054368:fotemustine; D002945:Cisplatin