Vaage J, Donovan D, Loftus T, Abra R, Working P, Huang A
Department of Molecular Immunology, Roswell Park Cancer Institute, Buffalo, New York 14263.
Cancer. 1994 May 1;73(9):2366-71. doi: 10.1002/1097-0142(19940501)73:9<2366::aid-cncr2820730920>3.0.co;2-6.
The objective of this study was to determine the ability of doxorubicin, encapsulated in sterically stabilized liposomes (Doxil [Liposome Technology, Inc., Menlo Park, CA]), to inhibit the spontaneous development of mammary carcinomas in mice.
Monthly prophylactic intravenous injections of 6 mg/kg doses of Doxil were started when retired breeding C3H/He mice were 26 weeks old. Mice that developed a mammary carcinoma were then given weekly intravenous injections of 6 mg/kg doses to determine whether the tumors were susceptible or resistant to Doxil therapy.
The monthly injections reduced the incidence of first mammary carcinomas in up to 88-week-old retired breeding C3H/He mice from 65 of 66 (98%) in untreated mice to 22 of 47 (47%) in treated mice. The first 15 mice that developed a mammary tumor while on the prophylactic protocol were then placed on a weekly therapeutic protocol. The therapeutic use of Doxil cured 3 of 15 mice and inhibited the growth of 12 tumors. Drug resistance as a result of treatments was not observed. The mean survival of tumor-bearing mice was extended from 24 days in untreated mice to 87 days in treated mice. Toxic side effects were limited to transient weight loss during the weekly Doxil treatments and to epidermal necrosis and dermal fibrosis due to drug extravasation at the sites of intravenous injections.
The authors concluded that doxorubicin in sterically stabilized liposomes deserves to be explored further in comparative studies with free doxorubicin for the prophylaxis and therapy of mammary cancer.
本研究的目的是确定包裹于空间稳定脂质体中的阿霉素（多柔比星，商品名多美素[脂质体技术公司，加利福尼亚州门洛帕克]）抑制小鼠乳腺癌自发发展的能力。
当处于繁殖后期的C3H/He小鼠26周龄时，开始每月静脉注射6mg/kg剂量的多美素进行预防性治疗。对发生乳腺癌的小鼠，随后每周静脉注射6mg/kg剂量，以确定肿瘤对多美素治疗是敏感还是耐药。
每月注射将88周龄以下处于繁殖后期的C3H/He小鼠首次发生乳腺癌的发生率，从未经治疗小鼠的66只中的65只（98%）降至经治疗小鼠的47只中的22只（47%）。在预防性治疗方案期间首次发生乳腺肿瘤的前15只小鼠随后进入每周治疗方案。多美素的治疗使15只小鼠中的3只治愈，并抑制了12个肿瘤的生长。未观察到因治疗导致的耐药性。荷瘤小鼠的平均生存期从未经治疗小鼠的24天延长至经治疗小鼠的87天。毒性副作用仅限于每周多美素治疗期间的短暂体重减轻，以及静脉注射部位因药物外渗导致的表皮坏死和皮肤纤维化。
作者得出结论，空间稳定脂质体包裹的阿霉素在与游离阿霉素对比研究中，值得进一步探索其在乳腺癌预防和治疗中的应用。
