title: Combined treatment with 4-hydroxyandrostenedione and aminoglutethimide: effects on aromatase inhibition and oestrogen suppression.
abstract: The effects of a combination of aminoglutethimide (AG) 1,000 mg daily and 4-hydroxy-androstenedione (4OHA) 500 mg i.m. weekly on peripheral aromatase activity as measured by in vivo radioisotopic tracer methodology and serum oestrogen suppression were investigated in ten post-menopausal women with advanced breast cancer. Patients were treated for a minimum of 4 weeks with 4OHA before addition of AG for a minimum of 6 weeks. Aromatase inhibition was found to be nearly identical in the two treatment situations (92.5 +/- 4.7% and 93.8 +/- 3.8% respectively). There was no further significant suppression of plasma oestradiol or plasma oestrone levels when AG was added to 4OHA treatment (mean decrease of 7.6 +/- 12.1% and 2.8 +/- 12.0% respectively). In contrast, adding AG caused a further suppression of plasma oestrone sulphate (Oe1S) compared with 4OHA monotherapy (mean suppression of 35.2 +/- 9.1%, P < 0.025). This effect on Oe1S may be due to an influence of AG on oestrogen metabolism.
authors.affiliation: Section of Medicine, Royal Marsden Hospital, Surrey, UK.
authors.forename: F A
authors.initials: FA
authors.lastname: MacNeill
authors.forename: S
authors.initials: S
authors.lastname: Jacobs
authors.forename: P E
authors.initials: PE
authors.lastname: Lønning
authors.forename: T J
authors.initials: TJ
authors.lastname: Powles
authors.forename: M
authors.initials: M
authors.lastname: Dowsett
mesh_terms: D000328:Adult; D000368:Aged; D000616:Aminoglutethimide / Q000008:administration & dosage / Q000627:therapeutic use*; D000735:Androstenedione / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D047072:Aromatase Inhibitors; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D002250:Carbon Radioisotopes; D004967:Estrogens / Q000097:blood*; D005260:Female; D006801:Humans; D008875:Middle Aged; D017698:Postmenopause; D011865:Radioisotope Dilution Technique
chemical_list: D000970:Antineoplastic Agents; D047072:Aromatase Inhibitors; D002250:Carbon Radioisotopes; D004967:Estrogens; D000616:Aminoglutethimide; D000735:Androstenedione; C014594:formestane