INTERSTITIAL CHEMOTHERAPY WITH DRUG POLYMER IMPLANTS FOR THE TREATMENT OF RECURRENT GLIOMAS
INTERSTITIAL CHEMOTHERAPY WITH DRUG POLYMER IMPLANTS FOR THE TREATMENT OF RECURRENT GLIOMAS
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DOI：
10.3171/jns.1991.74.3.0441
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发表时间：
1991-03-01
影响因子：
4.1
通讯作者：
KENEALY, JN
中科院分区：
文献类型：
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作者：
BREM, H;MAHALEY, S;KENEALY, JN
恶性神经胶质瘤很难用化疗治疗。 最有效的药物BCNU（卡莫司汀）具有相当大的全身毒性和在血清中的短半衰期。 为了解决这些问题，已经开发了一种通过将化学治疗剂掺入生物可降解聚合物中来局部持续释放化学治疗剂的方法。 在肿瘤部位植入药物浸渍的聚合物允许延长局部暴露，全身暴露最小。 在这项I-II期研究中，21例复发性恶性胶质瘤患者接受了BCNU治疗，BCNU通过聚酸酐生物降解聚合物植入物释放。 在完成肿瘤减积后，术中将多达8个聚合物薄片放置在切除腔中。 聚合物释放治疗药物约3周。研究了三种增加浓度的BCNU;治疗在所有三个水平都耐受良好。 BCNU晶片治疗本身没有不良反应。 再次手术后的平均生存期，第一剂量组为65周，第二剂量组为64周，最高剂量组为32周。 再次手术后的平均生存时间为48周，初次手术后的平均生存时间为94周。 总体中位生存时间为植入后46周和初次手术后87周。 21例患者中有18例（86%）从初次诊断起存活超过1年，21例患者中有8例（38%）在颅内植入聚合物后存活超过1年。 频繁的血液学、血生化和尿分析检查未显示这种间质化疗有任何全身性影响。由于这种治疗耐受性良好且安全，因此已开始进行安慰剂对照临床试验。 该试验将测量第二次治疗剂量对复发性恶性胶质瘤患者生存率的影响。
Malignant gliomas have been difficult to treat with chemotherapy. The most effective agent, BCNU (carmustine), has considerable systemic toxicity and a short half-life in serum. To obviate these problems, a method has been developed for the local sustained release of chemotherapeutic agents by their incorporation into biodegradable polymers. Implantation of the drug-impregnated polymer at the tumor site allows prolonged local exposure with minimal systemic exposure. In this Phase I-II study, 21 patients with recurrent malignant glioma were treated with BCNU released interstitially by means of a polyanhydride biodegradable polymer implant. Up to eight polymer wafers were placed in the resection cavity intraoperatively, upon completion of tumor debulking. The polymer releases the therapeutic drug for approximately 3 weeks.Three increasing concentrations of BCNU were studied; the treatment was well tolerated at all three levels. There were no adverse reactions to the BCNU wafer treatment itself. The average survival period after reoperation was 65 weeks for the first dose group, 64 weeks for the second dose group, and 32 weeks for the highest dose group. The overall mean survival time was 48 weeks from reoperation and 94 weeks from the original operation. The overall median survival times were 46 weeks postimplant and 87 weeks from initial surgery. Eighteen (86%) of 21 patients lived more than 1 year from the time of their initial diagnosis and eight (38%) of 21 patients lived more than 1 year after intracranial implantation of the polymer. Frequent hematology, blood chemistry, and urinalysis tests did not reveal any systemic effect from this interstitial chemotherapy.Since the therapy is well tolerated and safe, a placebo-controlled clinical trial has been started. The trial will measure the effect of the second treatment dose on survival of patients with recurrent malignant glioma.