Levin V A, Prados M D, Yung W K, Gleason M J, Ictech S, Malec M
Department of Neuro-oncology, University of Texas M. D. Anderson Cancer Center, Houston 77030.
J Natl Cancer Inst. 1992 Sep 16;84(18):1432-7. doi: 10.1093/jnci/84.18.1432.
Oral eflornithine in combination with intravenous mitoguazone (methylbisguanylhydrazone) has shown activity against recurrent anaplastic gliomas. Eflornithine alone, however, has not been evaluated against recurrent gliomas.
This study compared the antitumor activity of oral eflornithine with that of oral eflornithine combined with intravenous mitoguazone in the treatment of patients with recurrent or progressive glioblastoma multiforme as well as nonglioblastoma anaplastic gliomas.
During the 1st year of therapy with eflornithine alone, the drug was given at a dose of 3.6 g/m2 on days 1-14, 22-35, and 43-56 every 8 hours; cycles were repeated every 63 days until progression. For the 2nd year, the drug was given on days 1-14, 29-42, and 57-70, with 84 days between cycles. For the 1st and 2nd years of eflornithine-mitoguazone therapy, eflornithine was given at 1.8 g/m2 on the same schedule. Mitoguazone was given intravenously at 200 mg/m2 on the final day of each 2-week sequence of eflornithine therapy. Response was determined by evaluating changes in the size of contrast-enhanced neuroimages.
Because of two cases of lethal hepatic necrosis, the initial random allocation of patients to the eflornithine-mitoguazone arm was stopped after 23 patients had been accrued. Ninety-eight patients were entered in the eflornithine arm; 80 patients (36 glioblastoma multiforme patients and 44 anaplastic glioma patients) were assessable for response. Antitumor activity (partial response, minor response, and stable disease) was seen in 45% of the patients with anaplastic gliomas, for a median of 49 weeks, but in only 17% of patients with glioblastoma multiforme (median not attained). Twenty-one (20%) of the patients with anaplastic glioma and 33% of the patients with glioblastoma multiforme were removed from the study before completing the first 8-week course of therapy because of neurological deterioration and tumor progression by the 5th week of treatment.
This study suggests that eflornithine alone is an effective palliative therapy for recurrent anaplastic gliomas. Additional studies are needed to confirm our finding.
口服依氟鸟氨酸联合静脉注射丙脒腙已显示出对复发性间变性胶质瘤有活性。然而，单独使用依氟鸟氨酸尚未针对复发性胶质瘤进行评估。
本研究比较了口服依氟鸟氨酸与口服依氟鸟氨酸联合静脉注射丙脒腙在治疗复发性或进展性多形性胶质母细胞瘤以及非胶质母细胞瘤性间变性胶质瘤患者中的抗肿瘤活性。
在单独使用依氟鸟氨酸治疗的第1年，该药物在第1 - 14天、22 - 35天和43 - 56天，每8小时给药一次，剂量为3.6 g/m²；每63天重复一个周期，直至疾病进展。在第2年，药物在第1 - 14天、29 - 42天和57 - 70天给药，周期之间间隔84天。在依氟鸟氨酸 - 丙脒腙治疗的第1年和第2年，依氟鸟氨酸按相同方案以1.8 g/m²给药。在依氟鸟氨酸治疗的每2周疗程的最后一天，静脉注射丙脒腙，剂量为200 mg/m²。通过评估增强神经影像的大小变化来确定疗效。
由于两例致命性肝坏死病例，在纳入23例患者后，停止了将患者最初随机分配至依氟鸟氨酸 - 丙脒腙组。98例患者进入依氟鸟氨酸组；80例患者（36例多形性胶质母细胞瘤患者和44例间变性胶质瘤患者）可评估疗效。间变性胶质瘤患者中有45%出现抗肿瘤活性（部分缓解、轻微缓解和病情稳定），中位持续时间为49周，但多形性胶质母细胞瘤患者中只有17%出现抗肿瘤活性（未达到中位持续时间）。在间变性胶质瘤患者中，有21例（20%）以及多形性胶质母细胞瘤患者中有33%在完成第一个8周疗程治疗前因神经功能恶化和在治疗第5周时肿瘤进展而退出研究。
本研究表明，单独使用依氟鸟氨酸是复发性间变性胶质瘤的一种有效的姑息治疗方法。需要进一步的研究来证实我们的发现。
