Khan Raja B, Raizer Jeffrey J, Malkin Mark G, Bazylewicz Kimberley A, Abrey Lauren E
Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Neuro Oncol. 2002 Jan;4(1):39-43. doi: 10.1093/neuonc/4.1.39.
Temozolomide is an effective agent in the treatment of recurrent malignant gliomas. The standard dosage is 150-200 mg/m2 per day for 5 days in a 28-day cycle. A prior phase I study established a chronic daily temozolomide dose that significantly increased the total dose administered and suggested a superior response rate. In a prospective phase II trial, we treated 35 patients with recurrent malignant gliomas with temozolomide 75 mg/m2 per day for 42 consecutive days in a 70-day cycle. Median age was 55 years (range, 27-73 years) and median Karnofsky performance score was 70 (range, 60-90). Twenty-eight (79%) patients had glioblastoma multiforme, 3 (9%) anaplastic astrocytoma, 2 (6%) anaplastic oligodendroglioma, and 2 (6%) anaplastic oligoastrocytoma. All but one had prior radiotherapy, and 27 had prior chemotherapy. There were 2 partial (anaplastic astrocytoma) and 3 minor (glioblastoma multiforme) radiographic responses; 17 patients had progressive disease at the end of the first cycle. In 55 cycles of temozolomide, there were 8 episodes of asymptomatic drug-related grade 3 toxicity: 6 lymphopenia, 1 neutropenia, and 1 thrombocytopenia. Median progression-free survival and overall survival were 2.5 and 8.7 months (2.3 and 7.7 months in glioblastoma multiforme patients). At 6 months, progression-free survival and overall survival rates were 27% and 67% (19% and 60% in glioblastoma multiforme). Quality of life scores did not change significantly during treatment. We conclude that the extended low-dose schedule of temozolomide is well tolerated in heavily pre-treated patients; however, our results do not support an improved rate of response or survival.
替莫唑胺是治疗复发性恶性胶质瘤的一种有效药物。标准剂量为每天150 - 200mg/m²，持续5天，每28天为一个周期。先前的一项I期研究确定了替莫唑胺的慢性每日剂量，该剂量显著增加了给药的总剂量，并提示有更高的缓解率。在一项前瞻性II期试验中，我们对35例复发性恶性胶质瘤患者进行治疗，替莫唑胺剂量为每天75mg/m²，连续42天，每70天为一个周期。中位年龄为55岁（范围27 - 73岁），中位卡诺夫斯基功能状态评分是70分（范围60 - 90分）。28例（79%）患者为多形性胶质母细胞瘤，3例（9%）为间变性星形细胞瘤，2例（6%）为间变性少突胶质细胞瘤，2例（6%）为间变性少突星形细胞瘤。除1例患者外其余均接受过放疗，27例接受过化疗。有2例部分缓解（间变性星形细胞瘤）和3例轻微缓解（多形性胶质母细胞瘤）的影像学反应；17例患者在第一个周期结束时病情进展。在55个替莫唑胺治疗周期中，有8次无症状的3级药物相关毒性反应：6例淋巴细胞减少，1例中性粒细胞减少，1例血小板减少。中位无进展生存期和总生存期分别为2.5个月和8.7个月（多形性胶质母细胞瘤患者分别为2.3个月和7.7个月）。在6个月时，无进展生存率和总生存率分别为27%和67%（多形性胶质母细胞瘤患者分别为l9%和60%）。治疗期间生活质量评分无显著变化。我们得出结论，替莫唑胺延长低剂量方案在接受过大量预处理的患者中耐受性良好；然而，我们的结果并不支持缓解率或生存率的提高。
