Wells S A, Santen R J, Lipton A, Haagensen D E, Ruby E J, Harvey H, Dilley W G
Ann Surg. 1978 May;187(5):475-84. doi: 10.1097/00000658-197805000-00004.
The use of adrenalectomy and hypophysectomy in the management of postmenopausal patients with metastatic breast carcinoma is reserved for highly selected patients. As an alternate approach, a pharmacologic method of inhibiting adrenal cortical secretion was developed which consisted of the daily administration of 1000 mg of aminoglutethimide to block steroidogensis and either dexamethasone (2.0-3.0 mg/day) or hydrocortisone (40-60 mg/day) as replacement glucocorticoid. This regimen markedly suppressed plasma levels of DHA-S, androstenedione, estrone, and estradiol, and urinary levels of aldosterone. Of 50 patients treated, 19 (38%) demonstrated either a complete (8/19) or a partial (11/19) objective disease remission which lasted for 18.05 +/- 3.1 months (mean +/- SEM). In 10 (20%) patients, there was stabilization of disease (7.8 +/- 1.2 months), accompanied by symptomatic relief of bone pain in six (12%). There was disease progression in 20 (40%) patients. The acute side effects of aminoglutethimide therapy were significant and consisted of transient lethargy (41.5%) and a cutaneous rash (35.8%). Chronic toxicity was negligible. The medical adrenalectomy regimen of aminoglutethimide plus glucocorticoid offers a suitable alternative to surgical adrenalectomy or hypophysectomy in the management of postmenopausal patients with metastatic breast carcinoma.
肾上腺切除术和垂体切除术用于治疗绝经后转移性乳腺癌患者时,仅适用于经过严格筛选的患者。作为一种替代方法,人们开发了一种抑制肾上腺皮质分泌的药理学方法,即每天服用1000毫克氨鲁米特以阻断类固醇生成,并使用地塞米松(2.0 - 3.0毫克/天)或氢化可的松(40 - 60毫克/天)作为糖皮质激素替代物。该方案显著抑制了血浆中硫酸脱氢表雄酮、雄烯二酮、雌酮和雌二醇的水平,以及尿中醛固酮的水平。在接受治疗的50例患者中,19例(38%)出现了完全缓解(8/19)或部分缓解(11/19),客观疾病缓解持续时间为18.05±3.1个月(平均值±标准误)。10例(20%)患者病情稳定(7.8±1.2个月),其中6例(12%)伴有骨痛症状缓解。20例(40%)患者病情进展。氨鲁米特治疗的急性副作用较为明显,包括短暂嗜睡(41.5%)和皮疹(35.8%)。慢性毒性可忽略不计。氨鲁米特加糖皮质激素的药物性肾上腺切除方案为绝经后转移性乳腺癌患者的治疗提供了一种合适的替代手术肾上腺切除术或垂体切除术的方法。