Tamoxifen versus aminoglutethimide versus combined tamoxifen and aminoglutethimide in the treatment of advanced breast carcinoma.

In a control randomized cross-over trial, 117 patients with advanced breast cancer were treated initially either with tamoxifen (10 mg p.o. twice daily) or aminoglutethimide (250 mg p.o. 4 times daily) with hydrocortisone (20 mg twice daily). Patients failing to respond or relapsing were switched to the alternative treatment. Eighteen (30%) of the 60 patients initially treated with tamoxifen achieved an objective response, and 11 (18%) achieved stable disease. Seventeen (30%) of the 57 patients treated initially with aminoglutethimide achieved an objective response, and 13 (23%) achieved stable disease. Aminoglutethimide achieved a 35% objective response and a further 26% subjective bone pain relief in patients with bone metastases (overall, 61%) compared with a 17% objective response and a further 17% objective bone pain relief with tamoxifen (total, 34%). None of six premenopausal patients responded to aminoglutethimide compared with two of four responding to tamoxifen. The median response duration to aminoglutethimide was 16 months compared with 20 months for tamoxifen. Side effects for aminoglutethimide (including lethargy, rash, and depression) were more common than for tamoxifen, and 7% of aminoglutethimide-treated patients had to discontinue treatment because of these compared with 0% on tamoxifen. In cross-over studies, 6 of 12 tamoxifen responders who relapsed achieved a second response to aminoglutethimide (50%), as did 6 of 29 patients who initially failed to respond to tamoxifen (21%). In contrast, none of 11 patients relapsing after response to aminoglutethimide achieved a second response to tamoxifen; only 1 of 18 nonresponders to aminoglutethimide subsequently responded to tamoxifen (6%). In a subsequent study in which 62 patients were treated with combined tamoxifen and aminoglutethimide, the overall response rate of 37% was not significantly better than that for either agent used alone.

RCT Entities:   Population Interventions Outcomes