局部他莫昔芬治疗对导管原位癌有效

《临床癌症研究》（Clinical Cancer Research）7月15日在线发表的一项小型研究显示，与口服他莫昔芬相比，局部使用4-羟基他莫昔芬（4-OHT，他莫昔芬的抗雌激素代谢产物）凝胶制剂也可有效治疗导管原位癌（DCIS），支持对这一局部经皮治疗进行进一步研究（Clin. Cancer Res. 2014;20:3672-82）。

这项随机、双盲、II期研究由芝加哥西北大学Robert H. Lurie癌症中心的Oukseub Lee医生及其同事进行，入选26例绝经前和绝经后雌激素受体阳性DCIS女性患者，14例接受口服他莫昔芬治疗（20 mg/d），12例接受局部4-OHT凝胶制剂治疗（4 mg/d）。这些女性在诊断性核芯针活检后至手术切除前接受为期6周（中位数）治疗。

结果显示，研究者对核芯针活检和手术切除的组织进行比较发现，两组患者乳腺组织中的癌细胞生长标志物（Ki-67）的降幅相似。两组患者乳腺中的4-OHT平均浓度也相似，但口服他莫昔芬组的平均血浆4-OHT浓度约为局部治疗组的5倍（1.1 ng/mL vs. 0.2 ng/mL）。在口服他莫昔芬组患者中检测到凝血相关蛋白增加，但在局部治疗组未观察到这一现象。两组的潮热发生率无差异。

另一名研究者——Lurie癌症中心乳腺癌项目联合主任Seema Khan医生表示，如果4-OHT凝胶制剂在样本量更大的研究中被证明有效，则可能代替口服他莫昔芬用于乳腺癌预防和DCIS，并促使更多的女性使用该凝胶制剂。该凝胶制剂可最大程度上减少身体其他地方暴露于药物，使药物集中于所需治疗的乳房上，这应可避免潜在血凝块的产生和子宫癌风险增加。

该研究获美国国立卫生研究院和BHR Pharma公司资助。研究者声明无经济利益冲突。

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By: ELIZABETH MECHCATE, Oncology Practice Digital Network

The encouraging results of a small study of women with ductal carcinoma in situ comparing oral tamoxifen to a gel formulation of a tamoxifen metabolite support further testing of local transdermal therapy, investigators report.

The data "support the notion that local transdermal drug delivery to the breast will achieve sufficient drug concentrations to be effective, with low systemic exposure," wrote the authors, led by Dr. Oukseub Lee of the Robert H. Lurie Cancer Center of Northwestern University, Chicago. The study was published on July 15 in Clinical Cancer Research (Clin. Cancer Res. 2014;20:3672-82).

The randomized, double-blind, phase II study compared transdermal application of a gel containing 4-hydroxytamoxifen (4-OHT), an antiestrogenic metabolite of tamoxifen (4 mg/day), to oral tamoxifen (20 mg/day) in pre- and postmenopausal women with estrogen receptor–positive ductal carcinoma in situ (DCIS). Women were treated for a median of 6 weeks, between the time of the diagnostic core needle biopsy and surgical excision.

Among the 26 women who completed the study (14 on oral treatment and 12 on topical treatment), the drop in a marker for cancer cell growth (Ki-67) in the breast tissue was similar in both groups – based on comparisons of tissue from the core biopsy and the surgical excision. The mean concentration of 4-OHT in the breasts was also similar in the two groups, but mean plasma 4-OHT levels were about fivefold higher among those on oral tamoxifen (1.1 ng/mL vs. 0.2 ng/mL). Increases in coagulation-related proteins were detected among those on oral tamoxifen, but not in the women on topical treatment. The rate of hot flashes was not different in the two groups.

"Delivering the drug through a gel, if proven effective in larger trials, could potentially replace oral tamoxifen for breast cancer prevention and DCIS and encourage many more women to take it," another author, surgical oncologist Dr. Seema Khan, said in a press release on the results issued by Northwestern on July 15. "The gel minimized exposure to the rest of the body and concentrated the drug in the breast where it is needed, ... which should avoid potential blood clots as well as an elevated risk for uterine cancer," added Dr. Khan, professor of surgery and coleader of the breast cancer program at the Lurie cancer center.

The authors, which included others from Northwestern University; Washington University, St. Louis; and the National Cancer Institute, Bethesda, Md.; had no disclosures. The study was funded by the National Institutes of Health and BHR Pharma.