Brem H, Piantadosi S, Burger P C, Walker M, Selker R, Vick N A, Black K, Sisti M, Brem S, Mohr G
Department of Neurological Surgery, John Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Lancet. 1995 Apr 22;345(8956):1008-12. doi: 10.1016/s0140-6736(95)90755-6.
Chemotherapy for brain tumours has been limited because of difficulty in achieving adequate exposure to the tumour without systemic toxicity. We have developed a method for local sustained release of chemotherapeutic agents by their incorporation into biodegradable polymers. Implantation of the drug-impregnated polymer at the tumour site allows prolonged local exposure with minimal systemic exposure. We conducted a randomised, placebo-controlled, prospective study to evaluate the effectiveness of biodegradable polymers impregnated with carmustine to treat recurrent malignant gliomas. In 27 medical centres, 222 patients with recurrent malignant brain tumours requiring re-operation were randomly assigned to receive surgically implanted biodegradable polymer discs with or without 3.85% carmustine. Randomisation balanced the treatment groups for all of the prognostic factors examined. Median survival of the 110 patients who received carmustine polymers was 31 weeks compared with 23 weeks for the 112 patients who received only placebo polymers (hazard ratio = 0.67, p = 0.006, after accounting for the effects of prognostic factors). Among patients with glioblastoma, 6-month survival in those treated with carmustine-polymer discs was 50% greater than in those treated with placebo (mortality = 32 of 72 [44%] vs 47 of 73 [64%], p = 0.02). There were no clinically important adverse reactions related to the carmustine polymer, either in the brain or systemically. Interstitial chemotherapy delivered with polymers directly to brain tumours at the time of surgery seems to be a safe and effective treatment for recurrent malignant gliomas.
由于难以在不产生全身毒性的情况下使肿瘤充分接触化疗药物，脑肿瘤的化疗一直受到限制。我们开发了一种将化疗药物掺入可生物降解聚合物中实现局部持续释放的方法。将载药聚合物植入肿瘤部位可实现长时间的局部暴露，同时使全身暴露降至最低。我们进行了一项随机、安慰剂对照的前瞻性研究，以评估含卡莫司汀的可生物降解聚合物治疗复发性恶性胶质瘤的有效性。在27个医疗中心，222例需要再次手术的复发性恶性脑肿瘤患者被随机分配接受手术植入含或不含3.85%卡莫司汀的可生物降解聚合物圆盘。随机分组使各治疗组在所有检查的预后因素方面达到平衡。接受卡莫司汀聚合物治疗的110例患者的中位生存期为31周，而仅接受安慰剂聚合物治疗的112例患者为23周（风险比=0.67，在考虑预后因素的影响后，P=0.006）。在胶质母细胞瘤患者中，接受卡莫司汀聚合物圆盘治疗的患者6个月生存率比接受安慰剂治疗的患者高50%（死亡率分别为72例中的32例[44%]和73例中的47例[64%]，P=0.02）。无论是在脑部还是全身，均未出现与卡莫司汀聚合物相关的具有临床意义的不良反应。手术时通过聚合物将间质化疗直接递送至脑肿瘤似乎是一种治疗复发性恶性胶质瘤的安全有效的方法。
