Preliminary study on pharmacokinetics of dacarbazine and fotemustine in glioblastoma multiforme patients does not indicate gender-specific differences

Anticancer Drugs. 2004 Jun;15(5):495-8.

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.

Publication types

  • Clinical Trial
  • Comparative Study

MeSH terms

  • Adult
  • Antineoplastic Agents, Alkylating / administration & dosage
  • Antineoplastic Agents, Alkylating / adverse effects
  • Antineoplastic Agents, Alkylating / pharmacokinetics*
  • Central Nervous System Neoplasms / drug therapy*
  • Central Nervous System Neoplasms / metabolism
  • Dacarbazine / administration & dosage
  • Dacarbazine / adverse effects
  • Dacarbazine / pharmacokinetics*
  • Dose-Response Relationship, Drug
  • Female
  • Glioblastoma / drug therapy*
  • Glioblastoma / metabolism
  • Humans
  • Male
  • Middle Aged
  • Nitrosourea Compounds / administration & dosage
  • Nitrosourea Compounds / adverse effects
  • Nitrosourea Compounds / pharmacokinetics*
  • Organophosphorus Compounds / administration & dosage
  • Organophosphorus Compounds / adverse effects
  • Organophosphorus Compounds / pharmacokinetics*
  • Sex Factors

Substances

  • Antineoplastic Agents, Alkylating
  • Nitrosourea Compounds
  • Organophosphorus Compounds
  • Dacarbazine
  • fotemustine