Treatment of pituitary neoplasms with temozolomide

Abstract

Temozolomide, an orally administered alkylating agent, is used to treat malignant gliomas. Recent reports also have documented its efficacy in the treatment of pituitary adenomas and carcinomas. Temozolomide methylates DNA and thereby exhibits an antitumor effect. O 6 -methylguanine-DNA methyltransferase (MGMT), a DNA repair enzyme, removes alkylating adducts induced by temozolomide, counteracting its effects. The authors of this review conducted a Medline database search regarding temozolomide in the treatment of pituitary tumors. Demographic characteristics, tumor types, and therapeutic responses were noted in all patients. Data regarding MGMT immunoexpression, which was documented in some studies, were correlated with information regarding clinical and radiologic responses. To date, there have been 19 reported cases of adenohypophyseal tumors treated with temozolomide, including 13 adenomas and 6 carcinomas. Ten of those 13 adenomas responded favorably, and 2 nonresponsive tumors had highlevel MGMT immunoexpression. All 6 carcinomas responded to therapy, but data regarding MGMT expression were available for only 3 patients, and each had low MGMT expression. In 2 adenomas, morphologic studies were performed both before and after the patients received temozolomide. The responsive tumor had necrosis, hemorrhage, fibrosis, and neuronal differentiation. The nonresponsive tumor had no changes. There have been no reported complications attributable to temozolomide. The current results indicated that temozolomide is efficacious in the treatment of aggressive pituitary adenomas and pituitary carcinomas. Evidence indicated that low-level MGMT immunoexpression is correlated with a favorable response. A significant proportion of pituitary adenomas and carcinomas had low MGMT immunoexpression. Cancer 2011;117:454-62.

Prolactinomas resistant to standard doses of cabergoline: a multicenter study of 92 patients

“…An appropriate use of extra-pituitary magnetic resonance imaging (MRI) and/or nuclear imaging (39,40) may lead to an earlier recognition of PRL-secreting carcinomas and increase their clinical relevance. Various chemotherapy regimens have been proposed (39), but TMZ is becoming a mainstream choice (33,41). In our series, TMZ was successfully used in two carcinomas and a highly aggressive prolactinoma.…”

“…In our series, TMZ was successfully used in two carcinomas and a highly aggressive prolactinoma. Tumors showing reduced methylguanine-DNA methyltransferase expression may be more sensitive to TMZ (41), but this finding is debatable and a 3-month trial is generally able to identify TMZ responders (42). Observational data on early chemotherapy associated with longlasting responses in pituitary carcinomas (39) support the need for an early recognition of their metastatic potential.…”

Treatment of Cushing's disease: a mechanistic update

“…MGMT reverses alkylation, and it has been initially suggested that low MGMT expression could predict a better response to temozolomide. After treatment with temozolomide, tumors become soft and friable, and display better differentiation, less mitoses, and a lower Ki-67 index, indicative of surgical benefits as well as a reduction in cell proliferation (Syro et al 2011). Temozolomide could be an efficacious drug in cases of aggressive CD, but the predictive role of MGMT expression remains to be determined (Syro et al 2011, Dillard et al 2011.…”

Emerging drugs for Cushing’s disease

“…In addition, a potential concern for the long-term use of rosiglitazone in CD is its pro-osteoporotic effects, already observed in diabetic patients [50]. Temozolomide, an orally administrated second-generation alkylating chemotherapeutic agent, could be an efficient drug in cases of aggressive CD [51]. Temozolomide has shown promise as monotherapy [52], and in combination with pasireotide [53], as a treatment for aggressive pituitary adenomas and carcinomas, and may represent another viable treatment option targeting aggressive corticotroph adenomas refractory to surgery, RT, or other medical treatments.…”