title: Aminoglutethimide in advanced breast cancer: plasma levels and clinical results after low and high doses.
abstract: Drug plasma levels, metabolism data and clinical results were evaluated after the daily administration of either 500 or 1,000 mg aminoglutethimide (AG, Orimeten, Ciba-Geigy) plus hydrocortisone acetate (20 mg b. i. d.). A total of 34 patients with advanced breast cancer entered the study: 17 were given 1,000 mg/day and 17 received 500 mg/day for at least 3 months. A novel HPLC method was developed to determine the levels of AG and its known metabolites [N-acetyl-AG (NAG), formyl-AG, nitroglutethimide, hydroxy-AG] in the biological samples. AG plasma concentration was significantly higher during the 1,000-mg/day regimen. NAG was the only metabolite observed in plasma, always occurring at concentrations lower than those of the parent drug. The ratios between NAG and AG levels distinguish two statistically different groups of patients. Irrespective of the dose, a partial response was observed in 44% of the patients; no change in 32% of cases; and progressive disease had an incidence of 24%. The probability of response was not dependent on the drug AUC or on the NAG/AG ratio and did not significantly depend on previous hormone treatment. Neither the plasmatic level of the AG or metabolite concentrations nor the NAG/AG ratio seemed to affect the incidence of side effects.
authors.affiliation: Department of Organic Chemistry, University of Bologna, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Strocchi
authors.forename: C M
authors.initials: CM
authors.lastname: Camaggi
authors.forename: A
authors.initials: A
authors.lastname: Martoni
authors.forename: R
authors.initials: R
authors.lastname: Cellerino
authors.forename: S
authors.initials: S
authors.lastname: Miseria
authors.forename: P
authors.initials: P
authors.lastname: Malacarne
authors.forename: M
authors.initials: M
authors.lastname: Indelli
authors.forename: M
authors.initials: M
authors.lastname: Balli
authors.forename: G
authors.initials: G
authors.lastname: Bonciarelli
authors.forename: G
authors.initials: G
authors.lastname: Ambroso
mesh_terms: D000328:Adult; D000368:Aged; D000616:Aminoglutethimide / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000704:Analysis of Variance; D001682:Biological Availability; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D016000:Cluster Analysis; D016002:Discriminant Analysis; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D008875:Middle Aged; D012044:Regression Analysis; D012074:Remission Induction
chemical_list: D000616:Aminoglutethimide; C036163:N-acetylaminoglutethimide