Nicholson H Stacy, Kretschmar Cynthia S, Krailo Mark, Bernstein Mark, Kadota Richard, Fort Daniel, Friedman Henry, Harris Michael B, Tedeschi-Blok Nicole, Mazewski Claire, Sato Judith, Reaman Gregory H
Department of Pediatrics, Oregon Health Science & University, Portland, Oregon, USA.
Cancer. 2007 Oct 1;110(7):1542-50. doi: 10.1002/cncr.22961.
Effective chemotherapy is lacking for most types of central nervous system (CNS) tumors in children. Temozolomide, an agent with activity against adult brain tumors, was investigated in children and adolescents with recurrent CNS tumors.
Temozolomide was administered orally as monthly 5-day courses at doses of 200 mg/m(2)/d (patients with no prior craniospinal irradiation [CSI]) or 180 mg/m(2)/d (prior CSI). Patients with a complete (CR) or partial (PR) response or stable disease (SD) could continue temozolomide for up to 12 cycles.
The cohort comprised 122 patients, including 113 with CNS tumors. Median age was 11 years (range, 1-23 years). Among 104 evaluable patients with CNS tumors, 5 PRs and 1 CR were observed. PRs occurred in 1 of 23 evaluable patients with high-grade astrocytoma, 1 of 21 with low-grade astrocytoma, and 3 of 25 with medulloblastoma/primitive neuroectodermal tumor (PNET). The CR occurred in an additional patient with medulloblastoma/PNET. No responses were observed in patients with ependymoma, brain-stem glioma, or other CNS tumors. Notably, 41% of patients with low-grade astrocytoma had SD through 12 courses. The most frequent toxicities were grade 3 or 4 neutropenia (19%) and thrombocytopenia (25%); nonhematologic toxicity was infrequent.
Although overall objective responses were limited, further exploration of temozolomide may be warranted in children with medulloblastoma and other PNETs, or in patients with low-grade astrocytoma, perhaps in a setting of less pretreatment than the patients in the current study, or in the context of multiagent therapy.
大多数类型的儿童中枢神经系统（CNS）肿瘤缺乏有效的化疗方法。替莫唑胺是一种对成人大脑肿瘤有活性的药物，本研究对患有复发性CNS肿瘤的儿童和青少年进行了调查。
替莫唑胺口服给药，每月进行5天疗程，剂量为200mg/m²/d（未接受过颅脑脊髓放疗[CSI]的患者）或180mg/m²/d（接受过CSI的患者）。完全缓解（CR）或部分缓解（PR）或疾病稳定（SD）的患者可继续使用替莫唑胺长达12个周期。
该队列包括122例患者，其中113例患有CNS肿瘤。中位年龄为11岁（范围1 - 23岁）。在104例可评估的CNS肿瘤患者中，观察到5例PR和1例CR。PR发生在23例可评估的高级别星形细胞瘤患者中的1例、21例低级别星形细胞瘤患者中的1例以及25例髓母细胞瘤/原始神经外胚层肿瘤（PNET）患者中的3例。CR发生在另1例髓母细胞瘤/PNET患者中。室管膜瘤、脑干胶质瘤或其他CNS肿瘤患者未观察到缓解。值得注意的是，41%的低级别星形细胞瘤患者在12个疗程中病情稳定。最常见的毒性反应是3级或4级中性粒细胞减少（19%）和血小板减少（25%）；非血液学毒性反应不常见。
尽管总体客观缓解有限，但对于患有髓母细胞瘤和其他PNETs的儿童，或低级别星形细胞瘤患者，可能有必要进一步探索替莫唑胺，或许在预处理比本研究中的患者少的情况下，或在多药联合治疗的背景下。
