Temozolomide Treatment in Aggressive Pituitary Tumors and Pituitary Carcinomas: A French Multicenter Experience
Temozolomide Treatment in Aggressive Pituitary Tumors and Pituitary Carcinomas: A French Multicenter Experience
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DOI：
10.1210/jc.2010-0644
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发表时间：
2010-10-01
影响因子：
5.8
通讯作者：
Brue, Thierry
中科院分区：
文献类型：
--
作者：
Raverot, Gerald;Sturm, Nathalie;Brue, Thierry
背景：迄今为止，只有18例侵袭性垂体瘤或癌患者接受替莫唑胺治疗的报道。O 6-甲基鸟嘌呤-DNA-甲基转移酶（MGMT）的表达增加被认为是预测替莫唑胺耐药的指标。目的：本研究的目的是描述替莫唑胺在侵袭性垂体瘤或癌患者中的抗肿瘤疗效和毒性，并评估MGMT启动子甲基化和蛋白表达的可能预后价值。患者：我们的法国多中心研究纳入了8例患者，5例垂体癌（3例催乳素（PRL）和2例ACTH）和3例侵袭性垂体瘤（1例PRL和2例ACTH），均接受替莫唑胺口服治疗4至24个周期。设计：通过免疫组织化学和焦磷酸测序法评估MGMT表达和MGMT启动子甲基化。结果如下：8例患者中有3例（2例ACTH腺瘤和1例PRL癌）对替莫唑胺有反应，表现为显著的肿瘤缩小和激素分泌减少。三个周期的替莫唑胺足以识别治疗反应的患者。额外的周期并没有改善那些没有反应的治疗效果，即使与卡铂和vepeside联合使用。MGMT表达不能预测肿瘤对替莫唑胺的反应，因为它在一个反应者中为阳性，在两个无反应者中为阴性。同样，MGMT启动子甲基化（7个肿瘤中的3个）也不能预测临床反应。所有患者的毒性均为轻度。结论：替莫唑胺治疗某些侵袭性垂体瘤或癌可能是一种有效的选择。对三个治疗周期的试验的响应似乎足以识别响应者，并且比患者MGMT状态更可靠。（临床内分泌代谢杂志95：4592-4599，2010）
Context: To date only 18 patients with aggressive pituitary tumors or carcinomas treated with temozolomide have been reported. Increased expression of O6-methylguanine-DNA-methyltranferase (MGMT) has been suggested to predict resistance to temozolomide. Objectives: The objective of the study was to describe the antitumoral efficacy and toxicity of temozolomide in patients with aggressive pituitary tumors or carcinomas and evaluate the possible prognostic value of MGMT promoter methylation and protein expression. Patients: Eight patients, five with pituitary carcinomas (three prolactin (PRL) and two ACTH) and three with aggressive pituitary tumors (one PRL and two ACTH), all treated with temozolomide administered orally for four to 24 cycles, were included in our French multicenter study. Design: MGMT expression was assessed by immunohistochemistry and MGMT promoter methylation by pyrosequencing. Results: Three of the eight patients (two ACTH adenomas and one PRL carcinoma) responded to temozolomide as demonstrated by significant tumor shrinkage and reduced hormone secretion. Three cycles of temozolomide were sufficient to identify treatment-responsive patients. Additional cycles did not improve treatment efficacy in those not responding, even when associated with carboplatin and vepeside. MGMT expression did not predict tumoral response to temozolomide because it was positive in one responder and negative in two nonresponders. Similarly, MGMT promoter methylation (three of seven tumors) did not predict clinical response. Toxicity remained mild in all patients. Conclusion: Temozolomide treatment may be an effective option for some aggressive pituitary tumors or carcinomas. Response to a trial of three cycles of treatment seems sufficient to identify responders and more reliable than patient MGMT status. (J Clin Endocrinol Metab 95: 4592-4599, 2010)