Department of Endocrinology, King's College Hospital, London, SE5 9RS, UK.
Clin Endocrinol (Oxf). 2012 Jun;76(6):877-86. doi: 10.1111/j.1365-2265.2012.04373.x.
The majority of prolactinomas respond to dopamine agonist therapy, but a proportion are resistant, requiring other treatments including surgery and/or radiotherapy. Temozolomide is an oral chemotherapy agent, which has been used as a salvage therapy to treat aggressive pituitary adenomas and carcinomas, including prolactinomas, unresponsive to all conventional treatment.
We report three patients where temozolomide was used in the treatment of refractory prolactinomas. Case 1 describes a patient with a highly invasive prolactinoma, resistant to all conventional therapy, which responded dramatically to temozolomide used as a salvage treatment. In case 2, temozolomide was used after incomplete surgical resection to relieve chiasmal compression and avoid chiasm exposure to radiotherapy. In case 3, temozolomide enabled radiotherapy to be deferred in a 16-year old with a resistant prolactinoma. In all three cases, the tumours were negative by immunostaining for methylguanine methyltransferase (MGMT).
A review of the published literature reveals 51 reported cases of temozolomide treatment for pituitary tumours, including 20 prolactinomas. Fifteen of the 20 prolactinomas showed a good response to temozolomide. Our analysis demonstrates a strong association between MGMT-negative staining and a good response to temozolomide (OR 9.35, P = 0.0030). Current clinical practice is to use temozolomide as a salvage therapy after all conventional modalities of treatment have failed. We suggest that, in selected cases, consideration should be given to using temozolomide earlier in the treatment algorithm.
大多数泌乳素瘤对多巴胺激动剂治疗有反应,但也有一部分是耐药的,需要其他治疗方法,包括手术和/或放疗。替莫唑胺是一种口服化疗药物,已被用作挽救治疗,用于治疗包括泌乳素瘤在内的侵袭性垂体腺瘤和癌,这些肿瘤对所有常规治疗均无反应。
我们报告了三例使用替莫唑胺治疗难治性泌乳素瘤的患者。病例 1 描述了一位患有高度侵袭性泌乳素瘤的患者,对所有常规治疗均耐药,用替莫唑胺进行挽救治疗后反应显著。在病例 2 中,替莫唑胺在不完全手术切除后使用,以缓解视交叉受压并避免视交叉暴露于放疗。在病例 3 中,替莫唑胺使一位耐药性泌乳素瘤的 16 岁患者能够推迟放疗。在所有三种情况下,肿瘤的免疫染色均为甲基鸟嘌呤甲基转移酶(MGMT)阴性。
对已发表文献的回顾显示,有 51 例使用替莫唑胺治疗垂体肿瘤的病例报告,其中包括 20 例泌乳素瘤。20 例泌乳素瘤中有 15 例对替莫唑胺有良好的反应。我们的分析表明,MGMT 阴性染色与替莫唑胺良好反应之间存在很强的相关性(OR 9.35,P = 0.0030)。目前的临床实践是在所有常规治疗方法均失败后,将替莫唑胺用作挽救治疗。我们建议,在某些情况下,应考虑在治疗算法中更早地使用替莫唑胺。