title: Combined endocrine treatment of elderly postmenopausal patients with metastatic breast cancer. A randomized trial of tamoxifen vs. tamoxifen + aminoglutethimide and hydrocortisone and tamoxifen + fluoxymesterone in women above 65 years of age.
abstract: The efficacy of combined endocrine therapy with tamoxifen (TAM), aminoglutethimide (AG), and hydrocortisone (H) or tamoxifen and fluoxymesterone (FLU) was evaluated against treatment with tamoxifen alone in 311 patients above 65 years of age with a first recurrence of a metastatic breast cancer. A total of 279 patients were eligible. The response rates were assessed for 258 fully evaluable patients and were the following for the TAM (N = 94), the TAM+AG+H (N = 83), and the TAM+FLU (N = 81) groups, respectively, PR: 14, 18, and 21%, and CR: 20, 11, and 23%. The overall response rates are not statistically different (p = 0.30). The 95% CL of difference in response rates for TAM vs. TAM+AG+H are -9-19% and for TAM vs. TAM+FLU -4-25%. Time to treatment failure was comparable with median values of 9.2, 7.7, and 9.2 months in the TAM, TAM+AG+H, and TAM + FLU group, respectively (p = 0.17). The corresponding figures for survival are median times of 22.0, 24.1, and 21.1 months with a p-value of 0.62. Toxicity was more pronounced in both the combined treatment groups, and could in most instances be attributed to treatment with either AG+H or FLU. Currently, new specific aromatase inhibitors with lesser toxicity than AG are being evaluated in combination with TAM for treatment of primary and metastatic breast cancer. In conclusion, the simultaneous use of TAM and AG +H or FLU does not seem to improve the therapeutic efficacy in elderly postmenopausal patients with metastatic disease. So far, combined endocrine therapy in this group of patients should only be used in the context of clinical trials.
authors.affiliation: Department of Oncology, Odense University Hospital, Denmark. carsten.rose@ouh.dk
authors.forename: C
authors.initials: C
authors.lastname: Rose
authors.forename: C
authors.initials: C
authors.lastname: Kamby
authors.forename: H T
authors.initials: HT
authors.lastname: Mouridsen
authors.forename: M
authors.initials: M
authors.lastname: Andersson
authors.forename: L
authors.initials: L
authors.lastname: Bastholt
authors.forename: K A
authors.initials: KA
authors.lastname: Møller
authors.forename: J
authors.initials: J
authors.lastname: Andersen
authors.forename: P
authors.initials: P
authors.lastname: Munkholm
authors.forename: P
authors.initials: P
authors.lastname: Dombernowsky
authors.forename: I J
authors.initials: IJ
authors.lastname: Christensen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000616:Aminoglutethimide / Q000008:administration & dosage / Q000009:adverse effects; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D047072:Aromatase Inhibitors; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D018450:Disease Progression; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D005474:Fluoxymesterone / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage; D015993:Life Tables; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors; D016879:Salvage Therapy; D020845:Selective Estrogen Receptor Modulators / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016019:Survival Analysis; D013629:Tamoxifen / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D018931:Antineoplastic Agents, Hormonal; D047072:Aromatase Inhibitors; D004791:Enzyme Inhibitors; D009363:Neoplasm Proteins; D020845:Selective Estrogen Receptor Modulators; D013629:Tamoxifen; D000616:Aminoglutethimide; D005474:Fluoxymesterone; D006854:Hydrocortisone