文献标题：Temozolomide treatment in aggressive pituitary tumors and pituitary carcinomas: a French multicenter experience.
文献出处：J Clin Endocrinol Metab. 2010,95(10):4592-9.
期刊影响因子：6.202
文献类型：Evaluation Studies, Multicenter Study

   本文介绍了替莫唑胺治疗侵袭性垂体瘤/癌患者的抗肿瘤疗效和毒性。这是迄今为止有关该课题中已发表的最大的一项。

   垂体瘤约占所有颅内肿瘤的15％，35-40％的病例与局部侵润有关。垂体癌是一种罕见的疾病（约0.2％的垂体瘤）以出现脑脊髓和/或全身转移存灶来确诊。替莫唑胺是一种口服的二代DNA烷化剂，在中枢神经系统有着优良生物利用度。替莫唑胺用来治疗神经内分泌肿瘤和胶质母细胞瘤。

   8例患者包括5例垂体癌（催乳素[PRL]型3例和促肾上腺皮质激素[ACTH] 型2例），3例侵袭性垂体瘤（催乳素[PRL]型1例和促肾上腺皮质激素[ACTH] 型2例）。由于在这个多中心研究中存在转移灶或常规治疗（药物治疗，手术[每例患者都有1-4次重复手术]或放射治疗[1-3分次立体定向放射治疗]）、放疗后肿瘤控制不良，因此给予替莫唑胺治疗。对 MGMT表达和MGMT启动子甲基化进行评估。

   1例催乳素型癌和2例促肾上腺皮质激素型瘤显示激素样和肿瘤样治疗反应但未证实与MGMT表达或MGMT启动子甲基化有关。1例患者因粒细胞缺乏症，2例因血小板减少而中止治疗，需要减小剂量。由于延迟肿瘤反应在患者中出现的可能性不大， 3个疗程的替莫唑胺治疗足以确定治疗反应。

   这项研究证实，替莫唑胺治疗有益于常规治疗没有反应的侵袭性垂体瘤或癌。 MGMT状态不能很好预测疗效。有必要进行更大型的前瞻性研究以确定替莫唑胺反应预测因素。

医脉通推荐英文摘要
J Clin Endocrinol Metab. 2010 Oct;95(10):4592-9.

Temozolomide treatment in aggressive pituitary tumors and pituitary carcinomas: a French multicenter experience.
Raverot G, Sturm N, de Fraipont F, Muller M, Salenave S, Caron P, Chabre O, Chanson P,et al.

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.

文献来源
Raverot G, et al.Temozolomide treatment in aggressive pituitary tumors and pituitary carcinomas: a French multicenter experience.J Clin Endocrinol Metab. 2010 Oct;95(10):4592-9. [PubMed链接|期刊链接]
更多阅读
Pituitary Tumors - MedlinePlus Health Information