A Feasibility Study of the Intraductal Administration of Chemotherapy
A Feasibility Study of the Intraductal Administration of Chemotherapy
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DOI：
10.1158/1940-6207.capr-12-0228
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发表时间：
2013-01-01
影响因子：
3.3
通讯作者：
Zhang, Baoning
中科院分区：
文献类型：
--
作者：
Love, Susan M.;Zhang, Wei;Zhang, Baoning
临床前数据显示了导管内化疗预防乳腺癌的潜力。由于啮齿动物（每个乳头有一个导管）和女性（每个乳房有5-9个导管系统）之间的解剖学差异，这项工作的直接翻译受到阻碍。本I期研究的目的是证明在等待乳房切除术治疗浸润性癌症的女性中，将化疗药物导管内给药至一个乳房内的多个导管的安全性和可行性。在中国北京的一家单中心进行的这项剂量递增研究入组了30例受试者。在局部麻醉下，两种化疗药物之一，卡铂或聚乙二醇脂质体多柔比星（PLD），以三种剂量水平注入五至八个导管。药代动力学分析表明，卡铂被迅速吸收到血液中，而PLD，虽然更不稳定，吸收后延迟。病理学分析显示，与未处理的导管相比，用任一药物处理的导管对乳腺导管上皮有显著影响。除了一例中央癌累及乳晕下外，研究者在识别或插管导管方面没有困难。本研究显示了乳腺癌预防的安全性和可行性的化疗导管内管理到多个管道的目的。这是实施该策略的重要一步，作为“化学乳房切除术”，其中在导管上皮中致癌的可能性被局部消除，而不需要手术。Cancer Prev Res; 6（1）; 51-58. (C)2012年AACR。
Preclinical data have shown the potential of the intraductal administration of chemotherapy for breast cancer prevention. Direct translation of this work has been stymied by the anatomical differences between rodents (one duct per teat) and women (5-9 ductal systems per breast). The objective of this phase I study was to show the safety and feasibility of intraductal administration of chemotherapy drugs into multiple ducts within one breast in women awaiting mastectomy for treatment of invasive cancer. Thirty subjects were enrolled in this dose escalation study conducted at a single center in Beijing, China. Under local anesthetic, one of two chemotherapy drugs, carboplatin or pegylated liposomal doxorubicin (PLD), was administered into five to eight ducts at three dose levels. Pharmacokinetic analysis has shown that carboplatin was rapidly absorbed into the bloodstream, whereas PLD, though more erratic, was absorbed after a delay. Pathologic analysis showed marked effects on breast duct epithelium in ducts treated with either drug compared with untreated ducts. The study investigators had no difficulty in identifying or cannulating ducts except in one case with a central cancer with subareolar involvement. This study shows the safety and feasibility of intraductal administration of chemotherapy into multiple ducts for the purpose of breast cancer prevention. This is an important step toward implementation of this strategy as a "chemical mastectomy", where the potential for carcinogenesis in the ductal epithelium is eliminated pharmacologically, locally, and without the need for surgery. Cancer Prev Res; 6(1); 51-58. (C) 2012 AACR.