Fabian Carol J, Kimler Bruce F, Brady Deborah A, Mayo Matthew S, Chang C H Joseph, Ferraro John A, Zalles Carola M, Stanton Annette L, Masood Shahla, Grizzle William E, Boyd Norman F, Arneson Dora W, Johnson Karen A
University of Kansas Medical Center, Kansas City, Kansas 66160, USA.
Clin Cancer Res. 2002 Oct;8(10):3105-17.
A double-blind randomized Phase II chemoprevention trial of alpha-difluoromethylornithine (DFMO) was conducted in a group of women at high risk for development of breast cancer. DFMO is an irreversible inhibitor of ornithine decarboxylase, the limiting enzyme of polyamine synthesis that is often up-regulated in breast cancer.
Study entrants were required to have random periareolar fine-needle aspiration cytology prior to entry that exhibited hyperplasia or hyperplasia with atypia, as well as a mammogram and clinical breast exam judged as not suspicious for breast cancer and no clinical hearing loss. Subjects were randomized to 6 months of oral DFMO (0.5 g/m(2)/day) or placebo, followed by repeat fine-needle aspiration and biomarker assessment. The main study end point was an improvement in cytologic pattern.
Of 119 subjects entered, 96% completed the study and were evaluable for the main study end point. A modest reduction (28%) in average total urine polyamines was obtained in the DFMO group, but there was no reduction in the spermidine:spermine ratio. There was no difference in cytologic improvement between DFMO and placebo. Likewise, there was no difference between DFMO and placebo for the secondary end points of breast molecular marker changes (immunocytochemical expression of proliferating cell nuclear antigen, p53, and epidermal growth factor receptor), mammographic breast density, serum insulin-like growth factor I: insulin-like growth factor binding protein 3 ratio, adverse events, quality of life indices, or subsequent cancer development.
DFMO at a dose level of 0.5 g/m(2)/day administered for 6 months does not modulate breast risk biomarkers tested in this study.
在一组乳腺癌发病高危女性中开展了一项α-二氟甲基鸟氨酸（DFMO）的双盲随机II期化学预防试验。DFMO是鸟氨酸脱羧酶的不可逆抑制剂，鸟氨酸脱羧酶是多胺合成的限速酶，在乳腺癌中常上调。
研究参与者在入组前需进行随机乳晕周围细针穿刺细胞学检查，结果显示为增生或非典型增生，同时乳房X线摄影和临床乳腺检查判定为无乳腺癌可疑迹象且无临床听力损失。受试者被随机分为两组，一组口服DFMO（0.5 g/m²/天）6个月，另一组口服安慰剂，之后重复进行细针穿刺和生物标志物评估。主要研究终点是细胞学模式的改善。
119名入组受试者中，96%完成了研究并可用于主要研究终点评估。DFMO组平均总尿多胺适度降低（28%），但亚精胺：精胺比值未降低。DFMO组和安慰剂组在细胞学改善方面无差异。同样，在乳房分子标志物变化（增殖细胞核抗原、p53和表皮生长因子受体的免疫细胞化学表达）、乳房X线摄影乳房密度、血清胰岛素样生长因子I：胰岛素样生长因子结合蛋白3比值、不良事件、生活质量指标或后续癌症发生等次要终点方面，DFMO组和安慰剂组也无差异。
每天0.5 g/m²剂量的DFMO服用6个月，并未调节本研究中检测的乳腺癌风险生物标志物。
