高剂量持续输注磷雌酚治疗激素抵抗型前列腺癌
High-dose continuous-infusion fosfestrol in hormone-resistant prostate cancer.
作者信息
Droz J P, Kattan J, Bonnay M, Chraibi Y, Bekradda M, Culine S
机构信息
Department of Medicine, Institut Gustave-Roussy, Villejuif, France.
出版信息
Cancer. 1993 Feb 1;71(3 Suppl):1123-30. doi: 10.1002/1097-0142(19930201)71:3+<1123::aid-cncr2820711434>3.0.co;2-t.
BACKGROUND
The initial treatment of advanced-stage prostate cancer is total androgen deprivation. Autonomous proliferation of primarily or secondarily hormonal unresponsive cells may explain the development of hormone-refractory status. The median survival of patients with hormone-resistant disease is short; there is no standard regimen of chemotherapy.
METHODS
Fosfestrol or diethylstilbestrol diphosphate and its metabolites have cytotoxic activity in hormone-refractory prostatic cell lines. Pharmacokinetic studies have shown that fosfestrol metabolites have a short half-life that supports the use of long-term infusion in the clinic.
RESULTS
A review of the literature shows that high-dose fosfestrol induces no objective response, a greater than 50% tumor marker decrease in 50% of patients, a subjective improvement in 75% of patients, and cardiovascular complications in 5% of patients. The median survival time of patients is 5 months after the onset of treatment.
CONCLUSIONS
An exact evaluation of the role of high-dose estrogens requires additional investigation.
背景
晚期前列腺癌的初始治疗是完全雄激素剥夺。原发性或继发性激素无反应性细胞的自主增殖可能解释激素难治状态的发展。激素抵抗性疾病患者的中位生存期较短；尚无标准化的化疗方案。
方法
磷雌酚或己烯雌酚二磷酸酯及其代谢产物在激素难治性前列腺癌细胞系中具有细胞毒性活性。药代动力学研究表明，磷雌酚代谢产物的半衰期较短，这支持在临床上采用长期输注的方式。
结果
文献综述显示，高剂量磷雌酚未诱导出客观反应，50%的患者肿瘤标志物下降超过50%，75%的患者有主观改善，5%的患者出现心血管并发症。患者开始治疗后的中位生存时间为5个月。
结论
需要进一步研究以准确评估高剂量雌激素的作用。
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