Mayhew E, Cimino M, Klemperer J, Lazo R, Wiernikowski J, Arbuck S
Department of Experimental Pathology, Roswell Park Cancer Institute, Buffalo, New York.
Sel Cancer Ther. 1990 Winter;6(4):193-209. doi: 10.1089/sct.1990.6.193.
Intraperitoneal (i.p.) chemotherapy is being investigated as an adjunct to surgery to kill residual cancer cells, inhibit cancer cell seeding, local recurrence, and metastases for ovarian, gastric, and colon cancers. In this report, the therapeutic effects of Doxorubicin (Dox) and liposome-entrapped Dox (Dox-Lip) against i.p. mouse colon 26 (C26) tumor were compared. It was found that Dox-Lip was less toxic than Dox after i.p. administration in non-tumor bearing animals. I.P. Dox and Dox-Lip significantly inhibited the growth of C26 tumor when the treatment was initiated 1 day after tumor cell inoculation, but both administration forms were ineffective against well-established (8-day) tumors. Multiple dose schedules did not improve the therapeutic response. Dox-Lip was not therapeutically superior to Dox at equal doses or at approximately equi-toxic doses. In addition, the relative retention of Dox and Dox-Lip in the peritoneal cavity and their plasma pharmacokinetics were investigated. It was found that Dox levels in the peritoneal cavity were maintained for longer periods after i.p. Dox-Lip was administered. However, the results show that maintenance of elevated drug levels in the peritoneal cavity does not necessarily lead to increased therapeutic effects.
腹腔内（i.p.）化疗作为手术辅助手段，用于杀灭残余癌细胞、抑制癌细胞播散、局部复发及转移，目前正针对卵巢癌、胃癌和结肠癌展开研究。在本报告中，比较了阿霉素（Dox）和脂质体包裹的阿霉素（Dox-Lip）对腹腔内小鼠结肠26（C26）肿瘤的治疗效果。结果发现，在未荷瘤动物腹腔给药后，Dox-Lip的毒性低于Dox。当在肿瘤细胞接种后1天开始治疗时，腹腔注射Dox和Dox-Lip均能显著抑制C26肿瘤的生长，但两种给药形式对已形成（8天）的肿瘤均无效。多剂量方案并未改善治疗反应。在同等剂量或近似等毒性剂量下，Dox-Lip在治疗上并不优于Dox。此外，还研究了Dox和Dox-Lip在腹腔内的相对滞留情况及其血浆药代动力学。结果发现，腹腔注射Dox-Lip后，腹腔内Dox水平维持的时间更长。然而，结果表明，腹腔内维持较高的药物水平并不一定会导致治疗效果增强。
