Paclitaxel-Eluting Polymer Film Reduces Locoregional Recurrence and Improves Survival in a Recurrent Sarcoma Model: A Novel Investigational Therapy
Paclitaxel-Eluting Polymer Film Reduces Locoregional Recurrence and Improves Survival in a Recurrent Sarcoma Model: A Novel Investigational Therapy
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DOI：
10.1245/s10434-011-1871-4
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发表时间：
2012-01-01
影响因子：
3.7
通讯作者：
Raut, Chandrajit P.
中科院分区：
文献类型：
--
作者：
Liu, Rong;Wolinsky, Jesse B.;Raut, Chandrajit P.
腹腔、盆腔和腹膜后肉瘤肉眼完全切除（R 0/R1）后，高达50%的患者发生局部复发。在小鼠复发性肉瘤模型中评价药物洗脱聚合物膜在降低局部复发率方面的功效。合成了含有和不含有300 μ g紫杉醇的聚（单硬脂酸甘油酯-共-己内酯）聚合物膜（Pax膜和未负载膜）。在体外和裸鼠体内评估了对CS-1（人软骨肉瘤）细胞的细胞毒性。在R 0/R1切除原发性皮下肿瘤后，将小鼠盲法随机分为：（1）Pax膜植入，（2）未负载的膜植入，（3）紫杉醇300 μ g IV（Pax IV），或（4）无其他治疗（“未治疗”）。评价局部复发、总生存期（OS）和肿瘤有丝分裂指数，Pax片，而非未载片，在体外降低CS-1存活率> 50天（P < 0.001）。在体内，局部复发率分别为17%（2/12）、69%（9/13）、89%（89）和88%（7/8）（P < 0.01）。中位OS分别为81、64、48和56天。与Pax IV小鼠相比，Pax膜小鼠局部组织中的紫杉醇水平高50至300倍。肿瘤有丝分裂指数附近的Pax-电影显着低于相邻的卸载film.Tumor床植入的Pax-电影后，R 0/R1切除术是优于Pax IV的上级，证明了减少局部复发和改善OS在小鼠复发性肉瘤模型。通过聚合物膜持续局部药物暴露代表了治疗局部侵袭性肉瘤的潜在新方法。
Locoregional recurrences occur in up to 50% of patients after macroscopically complete (R0/R1) resections of abdominal, pelvic, and retroperitoneal sarcomas. Efficacy of a drug-eluting polymer film in reducing locoregional recurrence rates was assessed in a murine recurrent sarcoma model.Poly(glycerol monostearate-co-caprolactone) polymer films were synthesized with and without 300 mu g paclitaxel (Pax-film and unloaded film). Cytotoxicity was assessed against CS-1 (human chondrosarcoma) cells in vitro and in vivo in nude mice. Following R0/R1 resection of primary subcutaneous tumors, mice were blindly randomized to: (1) Pax-film implant, (2) unloaded film implant, (3) paclitaxel 300 mu g IV (Pax IV), or (4) no other therapy ("untreated"). Locoregional recurrence, overall survival (OS), and tumor mitotic index were evaluated.Pax-films, but not unloaded films, reduced CS-1 viability in vitro for > 50 days (P < 0.001). In vivo, locoregional recurrence was observed in 2 of 12 Pax-film mice (17%), 9 of 13 unloaded film mice (69%), 8 of 9 Pax IV mice (89%), and 7 of 8 untreated mice (88%) (P < 0.01). Median OS was 81, 64, 48, and 56 days, respectively. Paclitaxel levels in local tissues were 50- to 300-fold greater in Pax-film mice compared with Pax IV mice. Tumor mitotic index adjacent to Pax-films was significantly lower than adjacent to unloaded films.Tumor bed implantation of Pax-films after R0/R1 resection is superior to Pax IV as evidenced by reduced locoregional recurrence and improved OS in a murine recurrent sarcoma model. Continuous local drug exposure via polymer films represents a potentially novel approach for treatment of locally aggressive sarcomas.