Kong Q, Kleinschmidt-Demasters B K, Lillehei K O
Department of Surgery, University of Colorado Health Sciences Center, Denver 80262, USA.
J Surg Oncol. 1997 Apr;64(4):268-73. doi: 10.1002/(sici)1096-9098(199704)64:4<268::aid-jso4>3.0.co;2-7.
Chemotherapy has added little to the overall survival of the patients with primary malignant brain tumors, primarily due to its difficulty penetrating the blood-brain barrier. Use of polymers, releasing high doses of chemotherapy locally over time, is a promising new treatment strategy. Three experiments were conducted to test the effect of cisplatin, released from biodegradable polymer, on rats with 1 week established brain tumor.
9L gliosarcoma cells and drug-free or cisplatin-loaded polymer were administered through a right frontal lobe cannula in male Fischer 344 rats. Tumor cells were infused on day 0 and polymer on day 7. Animals were monitored for 60 days.
In experiment one, 0.5 mg/m2 of cisplatin loaded in polymer resulted in a mean survival time (MST) of 51 +/- 14 days with 63% (10/16) rats surviving to day 60. MST for the control group was 24 +/- 4 days (p = 2.5 x 10(-9)). Evidence of clinical or histologic brain toxicity was minimal. In a second experiment, using drug-free polymer (n = 7), MST was 24 +/- 3 days. This was compared against an MST of 24 +/- 4 days in the tumor control group (n = 7) and 49 +/- 7 days in a cisplatin-polymer treated group (n = 6). In a third experiment, two doses of drug-free polymer and three doses of cisplatin-loaded polymer were tested in normal nontumor-bearing rats and found to be well tolerated.
Intralesional sustained release of cisplatin from biodegradable polymer is safe and effective for the treatment of brain 9L gliosarcoma in rats.
化疗对原发性恶性脑肿瘤患者的总生存期改善甚微，主要原因是其难以穿透血脑屏障。使用能随时间局部释放高剂量化疗药物的聚合物是一种很有前景的新治疗策略。我们进行了三项实验，以测试从可生物降解聚合物中释放的顺铂对已患脑肿瘤1周的大鼠的影响。
将9L胶质肉瘤细胞以及不含药物或载有顺铂的聚合物通过右额叶套管注入雄性Fischer 344大鼠体内。在第0天注入肿瘤细胞，第7天注入聚合物。对动物进行60天的监测。
在实验一中，聚合物中负载0.5mg/m²顺铂导致平均生存时间（MST）为51±14天，63%（10/16）的大鼠存活至第60天。对照组的MST为24±4天（p = 2.5×10⁻⁹）。临床或组织学脑毒性证据极少。在第二项实验中，使用不含药物的聚合物（n = 7），MST为24±3天。将其与肿瘤对照组（n = 7）的MST 24±4天以及顺铂 - 聚合物治疗组（n = 6）的MST 49±7天进行比较。在第三项实验中，对正常未患肿瘤的大鼠测试了两剂不含药物的聚合物和三剂载有顺铂的聚合物，发现耐受性良好。
可生物降解聚合物在瘤内持续释放顺铂对治疗大鼠脑9L胶质肉瘤是安全有效的。
