Tchekmedyian N S, Tait N, Abrams J, Aisner J
University of Maryland Cancer Center, Baltimore.
Semin Oncol. 1988 Apr;15(2 Suppl 1):44-9.
A dose-response relationship has long been suspected for progestin compounds in the treatment of breast cancer, but only recently have trials been implemented to investigate this issue. In 1985, we began a phase I-II study of high-dose megestrol acetate in dosages of 480 mg/d to 1,600 mg/d in heavily pretreated postmenopausal patients with advanced breast cancer. After establishing the safety of this therapy, we expanded our trial, which now includes 47 patients, 34 of whom have measurable disease. Of these 34 patients, 30 had disease progression on prior hormonal therapy and 29 had progression on chemotherapy. Six of the 34 patients had complete response and six had partial response for a median time on study of 10 months (range, 8 to 30 months). Ten patients had stabilization and 12 had progression. Thirteen patients had evaluable but nonmeasurable disease, and of these, ten had improvement or stabilization for a median period of 6 months (range, 2 to 18 months) and three had progression. Of 17 patients who had experienced disease progression while receiving standard-dose megestrol acetate, 13 (76%) achieved objective remissions or stabilization with high-dose therapy. The main side effects were weight gain and appetite enhancement, which were beneficial in 13 underweight patients. These data indicate that high-dose megestrol acetate is well tolerated and effective in patients with advanced breast cancer refractory to multiple previous therapies. While optimal dose levels for clinical use remain to be established by ongoing studies, our data suggest that doses higher than the standard dose may be more effective.
长期以来，人们一直怀疑孕激素类化合物在治疗乳腺癌方面存在剂量反应关系，但直到最近才开展试验来研究这个问题。1985年，我们开始了一项I-II期研究，对绝经后晚期乳腺癌的重度预处理患者使用剂量为480毫克/天至1600毫克/天的大剂量醋酸甲地孕酮。在确定了这种疗法的安全性后，我们扩大了试验，目前该试验包括47名患者，其中34名患者有可测量的疾病。在这34名患者中，30名在先前的激素治疗中病情进展，29名在化疗中病情进展。34名患者中有6名完全缓解，6名部分缓解，研究的中位时间为10个月（范围为8至30个月）。10名患者病情稳定，12名患者病情进展。13名患者有可评估但不可测量的疾病，其中10名患者病情改善或稳定，中位时间为6个月（范围为2至18个月），3名患者病情进展。在17名接受标准剂量醋酸甲地孕酮治疗期间病情进展的患者中，13名（76%）通过大剂量治疗实现了客观缓解或病情稳定。主要副作用是体重增加和食欲增强，这对13名体重过轻的患者有益。这些数据表明，大剂量醋酸甲地孕酮在先前接受过多种治疗的晚期乳腺癌患者中耐受性良好且有效。虽然临床使用的最佳剂量水平仍有待正在进行的研究确定，但我们的数据表明，高于标准剂量的剂量可能更有效。
