Couldwell W T, Hinton D R, Surnock A A, DeGiorgio C M, Weiner L P, Apuzzo M L, Masri L, Law R E, Weiss M H
Departments of Neurological Surgery, Division of Biometry, University of Southern California School of Medicine, Los Angeles, California 90033, USA.
Clin Cancer Res. 1996 Apr;2(4):619-22.
The present clinical trial was undertaken to assess the clinical safety and possible efficacy of administering tamoxifen to patients with recurrent malignant glial tumors at dosages calculated to achieve levels sufficient to inhibit protein kinase C within the tumor cells. Chronic p.o. tamoxifen was administered in very high dosages to 32 patients (20 males and 12 females; age range, 26-75 years; mean, 49 years) with histologically verified malignant glioma [anaplastic astrocytoma (12 patients) or glioblastoma multiforme (20 patients)] who had demonstrated clinical and radiographical progression or recurrence following external beam radiation therapy (and additional chemotherapy in 11; immunotherapy in 2). The dosage of tamoxifen administered was 200 mg/day to males and 160 mg/day to females given in a twice daily schedule. Clinical and radiographical (defined as a greater than 50% decrease in volume of the enhancing lesion volume on magnetic resonance imaging and a decrease in metabolic activity on serial positron emission tomographic scans) response was noted in 8 patients (25%; 4/12 with anaplastic astrocytoma and 4/20 glioblastoma multiforme), with an additional 6 patients (19%) exhibiting stabilization of disease with minimal side effects. Median survival from the time of diagnosis for the entire cohort was 24 months (104 weeks), for the anaplastic astrocytoma group 42.5 months (185 weeks), and for the glioblastoma group 17.4 months (75.5 weeks). From the initiation of tamoxifen, median survival for the entire cohort was 10.1 months (44 weeks), for the anaplastic astrocytoma group 16 months (69 weeks), and for the glioblastoma group 7.2 months (31 weeks). The mean length of follow-up of all patients after initiating tamoxifen was 16 months (69 weeks), while the mean length of follow-up of alive patients is 22.6 months (98 weeks) (range up to 51 months). These data suggest that a subgroup of patients with malignant gliomas respond or stabilize with chronic high-dose tamoxifen therapy. This therapy may represent an alternative or adjuvant to existing chemotherapies for these tumors; further clinical trials are warranted.
本临床试验旨在评估对复发性恶性胶质瘤患者给予他莫昔芬的临床安全性及可能的疗效，给药剂量经计算可在肿瘤细胞内达到足以抑制蛋白激酶C的水平。对32例患者（20例男性，12例女性；年龄范围26 - 75岁，平均49岁）长期口服非常高剂量的他莫昔芬，这些患者经组织学证实患有恶性胶质瘤[间变性星形细胞瘤（12例）或多形性胶质母细胞瘤（20例）]，在接受外照射放疗（11例还接受了额外化疗；2例接受了免疫治疗）后出现了临床和影像学进展或复发。给予男性患者的他莫昔芬剂量为200 mg/天，女性患者为160 mg/天，每日分两次给药。8例患者（25%；间变性星形细胞瘤患者中4/12，多形性胶质母细胞瘤患者中4/20）出现了临床和影像学反应（定义为磁共振成像上强化病灶体积减少超过50%，以及连续正电子发射断层扫描上代谢活性降低），另有6例患者（19%）病情稳定且副作用极小。整个队列从诊断时起的中位生存期为24个月（104周），间变性星形细胞瘤组为42.5个月（185周），多形性胶质母细胞瘤组为17.4个月（75.5周）。从开始使用他莫昔芬起，整个队列的中位生存期为10.1个月（44周），间变性星形细胞瘤组为16个月（69周），多形性胶质母细胞瘤组为7.2个月（31周）。所有患者开始使用他莫昔芬后的平均随访时间为16个月（69周），而存活患者的平均随访时间为22.6个月（98周）（范围长达51个月）。这些数据表明，一部分恶性胶质瘤患者对长期高剂量他莫昔芬治疗有反应或病情稳定。这种治疗可能是这些肿瘤现有化疗的替代或辅助治疗方法；有必要进行进一步的临床试验。
