干扰素-β与替莫唑胺联合治疗对替莫唑胺难治性复发性间变性星形细胞瘤的疗效
Effectiveness of interferon-beta and temozolomide combination therapy against temozolomide-refractory recurrent anaplastic astrocytoma.
作者信息
Fujimaki Takamitsu, Ishii Hisato, Matsuno Akira, Arai Hajime, Nakagomi Tadayoshi
机构信息
Department of Neurosurgery, Teikyo University School of Medicine, Tokyo, Japan.
出版信息
World J Surg Oncol. 2007 Aug 4;5:89. doi: 10.1186/1477-7819-5-89.
BACKGROUND
Malignant gliomas recur even after extensive surgery and chemo-radiotherapy. Although a relatively novel chemotherapeutic agent, temozolomide (TMZ), has demonstrated promising activity against recurrent glioma, the effects last only a few months and drug resistance develops thereafter in most cases. Induction of O6-methylguanine-DNA methyltransferase (MGMT) in tumors is considered to be responsible for resistance to TMZ. Interferon-beta has been reported to suppress MGMT in an experimental glioma model. Here we report a patient with TMZ-refractory anaplastic astrocytoma (AA) who was treated successfully with a combination of interferon-beta and TMZ.
CASE PRESENTATION
A patient with recurrent AA after radiation-chemotherapy and stereotactic radiotherapy was treated with TMZ. After 6 cycles, the tumor became refractory to TMZ, and the patient was treated with interferon-beta at 3 x 106 international units/body, followed by 5 consecutive days of 200 mg/m2 TMZ in cycles of 28 days. After the second cycle the tumor decreased in size by 50% (PR). The tumor showed further shrinkage after 8 months and the patient's KPS improved from 70% to 100%. The immunohistochemical study of the initial tumor specimen confirmed positive MGMT protein expression.
CONCLUSION
It is considered that interferon-beta pre-administration increased the TMZ sensitivity of the glioma, which had been refractory to TMZ monotherapy.
背景
恶性胶质瘤即使在广泛手术及放化疗后仍会复发。尽管替莫唑胺（TMZ）作为一种相对新型的化疗药物，已显示出对复发性胶质瘤有良好疗效，但效果仅持续数月，大多数情况下随后会产生耐药性。肿瘤中O6 - 甲基鸟嘌呤 - DNA甲基转移酶（MGMT）的诱导被认为是对TMZ耐药的原因。在实验性胶质瘤模型中，据报道β - 干扰素可抑制MGMT。在此，我们报告一例TMZ难治性间变性星形细胞瘤（AA）患者，其通过β - 干扰素与TMZ联合治疗获得成功。
病例介绍
一名接受过放化疗及立体定向放疗后复发AA的患者接受TMZ治疗。6个周期后，肿瘤对TMZ产生耐药，该患者接受3×10⁶国际单位/体的β - 干扰素治疗，随后每28天为一个周期，连续5天给予200mg/m² TMZ。第二个周期后肿瘤体积缩小50%（部分缓解）。8个月后肿瘤进一步缩小，患者的KPS评分从70%提高到100%。对初始肿瘤标本的免疫组化研究证实MGMT蛋白表达呈阳性。
结论
认为预先给予β - 干扰素增加了对TMZ单药治疗耐药的胶质瘤对TMZ的敏感性。
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