Korones David N, Smith Amy, Foreman Nicholas, Bouffet Eric
University of Rochester Medical Center, Rochester, New York 14642, USA.
Pediatr Blood Cancer. 2006 Jul;47(1):37-41. doi: 10.1002/pbc.20510.
Children and young adults with recurrent or treatment-induced malignant gliomas have limited responses to temozolomide or oral VP-16 when either is administered as a single agent. We postulated that a combination of these two drugs for patients with recurrent or treatment-induced malignant gliomas might result in better and more prolonged responses. A retrospective analysis was performed on patients treated with the combination of temozolomide and VP-16.
Eleven patients with recurrent or treatment-induced malignant gliomas were treated with varying combinations of temozolomide (150-210 mg/m2/d for 5 days) and oral VP-16 (50 mg/m2/d for 4-12 days). Responses were assessed by MRI scan, and data on clinical course and toxicity were retrospectively obtained from the medical record.
The median age of the 11 patients was 17 years (range 5-23 years). Diagnoses included recurrent brain stem glioma (2), recurrent anaplastic astrocytoma (2), and glioblastoma (7) (3 treatment-induced, 2 malignant transformations of lower grade tumors, 1 recurrence, and 1 second tumor arising 10 months after diagnosis of medulloblastoma). All 11 patients had received radiotherapy (including 4 who received craniospinal radiation), and 7 had prior chemotherapy. Nine patients were treated at first recurrence, two at second recurrence. One patient had a complete response (CR), six had partial responses (PR), and four had progressive disease (PD). The median progression-free survival for the seven responding patients was 6 months (range 4-15+ months). There was one grade 4 neutropenia, but no other grade 3 or 4 toxicities.
These data suggest there is activity of temozolomide in combination with oral VP-16 for children and young adults with recurrent malignant gliomas.
复发性或治疗诱导性恶性胶质瘤的儿童和年轻成人，当单独使用替莫唑胺或口服依托泊苷时，对其反应有限。我们推测，这两种药物联合用于复发性或治疗诱导性恶性胶质瘤患者可能会产生更好、更持久的反应。对接受替莫唑胺和依托泊苷联合治疗的患者进行了回顾性分析。
11例复发性或治疗诱导性恶性胶质瘤患者接受了替莫唑胺（150 - 210 mg/m²/天，共5天）和口服依托泊苷（50 mg/m²/天，共4 - 12天）的不同联合治疗。通过MRI扫描评估反应，并从病历中回顾性获取临床病程和毒性数据。
11例患者的中位年龄为17岁（范围5 - 23岁）。诊断包括复发性脑干胶质瘤（2例）、复发性间变性星形细胞瘤（2例）和胶质母细胞瘤（7例）（3例为治疗诱导性，2例为低级别肿瘤的恶性转化，1例为复发，1例为髓母细胞瘤诊断后10个月出现的第二肿瘤）。所有11例患者均接受过放疗（包括4例接受全脑全脊髓放疗），7例曾接受过化疗。9例患者在首次复发时接受治疗，2例在第二次复发时接受治疗。1例患者完全缓解（CR），6例部分缓解（PR），4例疾病进展（PD）。7例有反应患者的中位无进展生存期为6个月（范围4 - 15 +个月）。有1例4级中性粒细胞减少，但无其他3级或4级毒性反应。
这些数据表明，替莫唑胺与口服依托泊苷联合应用于复发性恶性胶质瘤的儿童和年轻成人具有活性。
