Use of aminoglutethimide as second-line endocrine therapy in metastatic breast cancer

Sixty-five patients with advanced breast cancer, progressive despite prior endocrine therapy in all cases and prior chemotherapy in most cases, were treated with aminoglutethimide, 250 mg four times a day. At present, 52 are evaluable for response assessment, and of these 10 (19%) showed an overall objective response, major sites of response being soft tissue and lung. A further 12 patients (23%) had stable disease during aminoglutethimide therapy, while a total of 9 patients with bone metastases reported marked relief of pain without objective evidence of response. Forty-nine patients had received prior treatment with tamoxifen, and of the 10 tamoxifen responders 4 (40%) responded to subsequent aminoglutethimide, while of the 20 tamoxifen failures only 2 (10%) responded to subsequent aminoglutethimide. Aminoglutethimide was reasonably well tolerated, although 6 patients (0%) discontinued treatment because of intolerable side effects. Six of the 10 responding patients have subsequently relapsed, with a mean duration of response of 17 weeks, but 4 continued to respond at 24, 32, 55, and 111 weeks, respectively. The median survival from the start of aminoglutethimide therapy is in excess of 41 weeks for responders and 11 weeks for nonresponders, while the median survival from first relapse is 48 months for aminoglutethimide responders and 28 months for aminoglutethimide nonresponders. These results confirm that aminoglutethimide can offer a useful alternative form of endocrine therapy for advanced breast cancer, but the response rates obtained in heavily pretreated patients are inferior to those obtained when aminoglutethimide is used earlier in sequential treatment. For optimal results, particularly in terms of quality of life, aminoglutethimide should generally be used prior to chemotherapy.