title: Preliminary study on pharmacokinetics of dacarbazine and fotemustine in glioblastoma multiforme patients does not indicate gender-specific differences.
abstract: Twelve patients (six female and six male) with histologically proven glioblastoma multiforme were investigated during the administration of the first cycle of dacarbazine (D; 200 mg/m) and fotemustine (F; 100 mg/m). In total, 18 blood samples were collected for pharmacokinetic analysis (maximum plasma concentration, area under the concentration-time curve and total clearance) of D and F at 14 time points during therapy. D, its metabolite 5-aminoimidazole-4-carboxamide and F were evaluated by reversed-phase HPLC. For statistical calculations, groups were compared by the non-parametric Wilcoxon test. p<0.05 was considered statistically significant. No significant gender-dependent differences were observed in the pharmacokinetics of D and F. An additional response re-evaluation of 100 patients (50 female and 50 male) with glioblastoma multiforme, treated at our institution with D and F, gave no hint of any gender-dependent different response rates. We conclude that there is no evidence, neither from pharmacokinetic nor from our clinical data, to consider different dosages of D and F in female and male patients with glioblastoma multiforme.
authors.affiliation: Department of Medicine I, Clinical Division of Oncology and Ludwig Boltzmann Institute for Clinical Experimental Oncology, University of Vienna, Vienna, Austria. barbara.doerner@chello.at
authors.forename: Barbara
authors.initials: B
authors.lastname: Fazeny-Dörner
authors.forename: Robert M
authors.initials: RM
authors.lastname: Mader
authors.forename: Maria
authors.initials: M
authors.lastname: Piribauer
authors.forename: Blanka
authors.initials: B
authors.lastname: Rizovski
authors.forename: Barbara
authors.initials: B
authors.lastname: Stögermaier
authors.forename: Christine
authors.initials: C
authors.lastname: Marosi
mesh_terms: D000328:Adult; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D016543:Central Nervous System Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D003606:Dacarbazine / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009607:Nitrosourea Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D009943:Organophosphorus Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D012737:Sex Factors
chemical_list: D018906:Antineoplastic Agents, Alkylating; D009607:Nitrosourea Compounds; D009943:Organophosphorus Compounds; D003606:Dacarbazine; C054368:fotemustine