Placebo-controlled trial of safety and efficacy of intraoperative controlled delivery by biodegradable polymers of chemotherapy for recurrent gliomas. The Polymer-brain Tumor Treatment Group.
Placebo-controlled trial of safety and efficacy of intraoperative controlled delivery by biodegradable polymers of chemotherapy for recurrent gliomas. The Polymer-brain Tumor Treatment Group.
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发表时间：
1995
期刊：
影响因子：
168.9
通讯作者：
H. Brem;S. Piantadosi;P. Burger;M. Walker;R. Selker;N. Vick;K. Black;M. Sisti;S. Brem;G. Mohr
中科院分区：
文献类型：
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作者：
H. Brem;S. Piantadosi;P. Burger;M. Walker;R. Selker;N. Vick;K. Black;M. Sisti;S. Brem;G. Mohr
脑肿瘤的化疗一直受到限制，因为很难在没有全身毒性的情况下充分暴露于肿瘤。我们开发了一种通过将化疗药物掺入可生物降解聚合物中来实现局部缓释的方法。在肿瘤部位植入药物浸渍聚合物可以在最小的全身暴露的情况下延长局部暴露时间。我们进行了一项随机的、安慰剂对照的前瞻性研究，以评估生物可降解聚合物浸渍卡莫司汀治疗复发恶性胶质瘤的有效性。在27个医疗中心，222名需要再次手术的复发恶性脑肿瘤患者被随机分配接受手术植入的可生物降解聚合物圆盘，其中包括3.85%卡莫司汀或不含3.85%卡莫司汀。随机化平衡了治疗组中所有被检查的预后因素。接受卡莫司汀聚合物治疗的患者的中位生存期为31周，而只接受安慰剂聚合物治疗的患者的中位生存期为23周(考虑了预后因素的影响后，风险比=0.67，p=0.006)。在胶质母细胞瘤患者中，接受卡莫司汀聚合物盘治疗的患者的6个月存活率比接受安慰剂治疗的患者高50%(死亡率=32/72[44%]vs 47/73[%]，p=0.02)。无论是在大脑还是在全身，都没有与卡莫司汀聚合物相关的临床上重要的不良反应。对于复发的恶性胶质瘤，手术时直接用聚合物进行间质化疗似乎是一种安全有效的治疗方法。
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.