Ingle J N, Krook J E, Schaid D J, Everson L K, Mailliard J A, Long H J, McCormack G W
Division of Medical Oncology, Mayo Clinic, Rochester, MN 55905.
Am J Clin Oncol. 1990 Apr;13(2):93-7. doi: 10.1097/00000421-199004000-00001.
Trilostane, which causes a perturbation of adrenal steroidogenesis, was studied in combination with hydrocortisone in 32 women with progressive metastatic breast cancer. Trilostane was administered orally at a dosage level of 240 mg four times daily after escalation over the first 10 days from 60 mg four times daily. Hydrocortisone was given orally at doses of 10 mg at 8 a.m. and 5 p.m. and 20 mg at bedtime. Patients must have been postmenopausal (81%) or previously castrated (19%), had a response to the hormonal treatment just prior to study (81%) or a positive estrogen receptor at time of entry on study (41%), and a measurable indicator lesion. The number of prior hormonal therapies was 1 in 19 patients (59%), 2 in 12 patients (38%), and 3 in 1 patient (3%), respectively. Twelve patients (38%) achieved an objective response, and a 95% confidence interval for this result is from 21 to 56%. The median time to disease progression was 140 days, median duration of response was 278 days, and median survival was 556 days. Common toxicities included lethargy, lightheadedness, diarrhea, and abdominal discomfort. Eleven patients required a dosage reduction, usually because of gastrointestinal side effects, and one additional patient had the trilostane discontinued because of leukopenia. We conclude that the combination of trilostane plus hydrocortisone appears to have definite antitumor activity in women with metastatic breast cancer who have characteristics favorable for response to hormonal therapy.
曲洛司坦可引起肾上腺类固醇生成紊乱，我们对32例进展期转移性乳腺癌女性患者进行了曲洛司坦与氢化可的松联合治疗的研究。曲洛司坦在前10天从每日4次、每次60mg逐步递增，之后以每日4次、每次240mg的剂量口服给药。氢化可的松于上午8点和下午5点各口服10mg，睡前口服20mg。患者必须为绝经后女性（81%）或既往已行去势手术者（19%），在研究前对激素治疗有反应（81%）或在进入研究时雌激素受体阳性（41%），且有可测量的指示性病灶。既往接受激素治疗的次数分别为：19例患者（59%）接受过1次，12例患者（38%）接受过2次，1例患者（3%）接受过3次。12例患者（38%）获得了客观缓解，该结果的95%置信区间为21%至56%。疾病进展的中位时间为140天，缓解的中位持续时间为278天，中位生存期为556天。常见的毒性反应包括嗜睡、头晕、腹泻和腹部不适。11例患者需要减量，通常是由于胃肠道副作用，另有1例患者因白细胞减少而停用曲洛司坦。我们得出结论，对于具有对激素治疗反应有利特征的转移性乳腺癌女性患者，曲洛司坦加氢化可的松联合治疗似乎具有明确的抗肿瘤活性。
