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少突胶质细胞瘤分子特征及治疗的最新进展

Recent developments in the molecular characterization and treatment of oligodendroglial tumors.

作者信息

van den Bent Martin, Chinot Olivier-Louis, Cairncross J Gregory

机构信息

Department of Neuro-Oncology, Dr. Daniel den Hoed Cancer Center, 3008 AE Rotterdam, The Netherlands.

出版信息

Neuro Oncol. 2003 Apr;5(2):128-38. doi: 10.1215/s1522-8517-02-00028-5.

Abstract

Although many patients with oligodendrogliomas (ODs) and oligoastrocytomas (OAs) benefit from a combination of surgery and adjuvant radiotherapy, most patients eventually experience recurrence of their disease. Recent evidence has shown that ODs are more chemosensitive than other gliomas, including astrocytomas or glioblastoma multiforme. These initial findings have prompted further study of chemotherapy in treating ODs and mixed OAs. Advances in molecular genetic analysis have led to improvements in predicting response to chemotherapy and prognosis for ODs, OAs, and astrocytomas. Pure ODs are more chemosensitive than mixed ODs. This difference is related to different proportions of 1p/19q loss of heterozygosity in these neoplasms. Therefore, genetic analysis is likely to be key in determining appropriate treatment. The most common first-line chemotherapy for patients with OD is a procarbazine, lomustine, and vincristine (PCV) combination regimen. However, this regimen is associated with cumulative myelosuppression, nausea, vomiting, and weight loss. Therefore, other chemotherapy agents and regimens have been investigated. Perhaps the most promising is temozolomide, a novel alkylating agent that freely crosses the blood-brain barrier. Temozolomide is approved in the United States for the treatment of recurrent anaplastic astrocytomas and in Europe for any recurrent high-grade gliomas. Initial reports suggest that temozolomide is effective in treating ODs as first- and second-line chemotherapy. Unlike the PCV regimen, temozolomide is not associated with cumulative myelosuppression and is usually well tolerated. Further studies are needed to confirm the efficacy and safety profile of temozolomide and to determine the optimal dose and schedule for treating ODs.

摘要

尽管许多少突胶质细胞瘤(ODs)和少突星形细胞瘤(OAs)患者受益于手术和辅助放疗的联合治疗,但大多数患者最终疾病仍会复发。最近的证据表明,ODs比其他胶质瘤,包括星形细胞瘤或多形性胶质母细胞瘤,对化疗更敏感。这些初步发现促使人们进一步研究化疗在治疗ODs和混合性OAs中的作用。分子遗传学分析的进展已使在预测ODs、OAs和星形细胞瘤对化疗的反应及预后方面取得了进步。纯ODs比混合性ODs对化疗更敏感。这种差异与这些肿瘤中1p/19q杂合性缺失的不同比例有关。因此,基因分析可能是确定合适治疗方法的关键。OD患者最常见的一线化疗方案是丙卡巴肼、洛莫司汀和长春新碱(PCV)联合方案。然而,该方案会导致累积性骨髓抑制、恶心、呕吐和体重减轻。因此,人们对其他化疗药物和方案进行了研究。也许最有前景的是替莫唑胺,一种新型烷化剂,可自由通过血脑屏障。替莫唑胺在美国被批准用于治疗复发性间变性星形细胞瘤,在欧洲被批准用于治疗任何复发性高级别胶质瘤。初步报告表明,替莫唑胺作为一线和二线化疗药物治疗ODs有效。与PCV方案不同,替莫唑胺不会导致累积性骨髓抑制,且通常耐受性良好。需要进一步研究以确认替莫唑胺的疗效和安全性,并确定治疗ODs的最佳剂量和疗程。

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