Treatment of Nelson's syndrome with temozolomide

Moyes, Veronica; Alusi, Ghassan; Sabin, HI; Evanson, Jane; Berney, Daniel M.; Kovács, Kálmán; Monson, John P.; Plowman, P. N.; Drake, WM

doi:10.1530/eje-08-0557

Cited by 75 publications

(61 citation statements)

References 23 publications

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“…These included tumor necrosis and hemorrhage, 15,23 tumor degenerative and cystic changes, 22 and tumor shrinkage. 2,10,11,14,[19][20][21]24 These changes could be observed as early as 2 months after the onset of temozolomide treatment.…”

Section: Morphologic Changesmentioning

confidence: 99%

“…Fully 10 more patients with pituitary adenomas have received treatment with temozolomide 2,10,11,14,19,20,22 (unpublished results), bringing the current total to 13 patients, including 9 men and 4 women ages 20 to 61 years (mean, 47.9 years) ( Table 2). Aside from 1 incidentally discovered tumor in a patient with concomitant glioblastoma multiforme, all tumors have been studied morphologically.…”

Section: Pituitary Adenomasmentioning

confidence: 99%

“…Two additional case reports of invasive, ACTH-producing adenomas with low-level MGMT expression also demonstrated the corresponding efficacy of temozolomide therapy. 2,20 Thus, determining the level of MGMT immunostaining appears to be useful for predicting the response of aggressive pituitary adenomas and carcinomas to temozolomide. 2 The reports of Kovacs et al 16 and McCormack et al 19 underscored the inverse relation between MGMT immunoexpression and the efficacy of temozolomide therapy, a relation that also has been noted in high-grade gliomas.…”

Section: Mgmt Immunoexpressionmentioning

confidence: 99%

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Treatment of pituitary neoplasms with temozolomide

Syro

Ortíz

Scheithauer

et al. 2010

Cancer

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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.

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Section: Morphologic Changesmentioning

confidence: 99%

Section: Pituitary Adenomasmentioning

confidence: 99%

Section: Mgmt Immunoexpressionmentioning

confidence: 99%

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Treatment of pituitary neoplasms with temozolomide

Syro

Ortíz

Scheithauer

et al. 2010

Cancer

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“…In patients with re-growth of non-functioning pituitary adenomas, low MGMT expression was shown to correlate with tumour responsiveness to temozolomide (100). A recent case report of an aggressive Nelson's tumour, which failed to respond to both surgical and radiotherapy (including gamma knife treatment), revealed an excellent response to temozolomide with a significant reduction in plasma ACTH and regression of the underlying tumour after just four cycles of treatment (101). There is clearly a need for larger studies on the use of temozolomide in patients with Nelson's syndrome, although we believe that it represents a promising treatment for this condition.…”

Section: Temozolomidementioning

confidence: 99%

Nelson's syndrome

Barber

Adams²,

Ansorge³

et al. 2010

European Journal of Endocrinology

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Nelson's syndrome is a potentially life-threatening condition that does not infrequently develop following total bilateral adrenalectomy (TBA) for the treatment of Cushing's disease. In this review article, we discuss some controversial aspects of Nelson's syndrome including diagnosis, predictive factors, aetiology, pathology and management based on data from the existing literature and the experience of our own tertiary centre. Definitive diagnostic criteria for Nelson's syndrome are lacking. We argue in favour of a new set of criteria. We propose that Nelson's syndrome should be diagnosed in any patient with prior TBA for the treatment of Cushing's disease and with at least one of the following criteria: i) an expanding pituitary mass lesion compared with pre-TBA images; ii) an elevated 0800 h plasma level of ACTH (O500 ng/l) in addition to progressive elevations of ACTH (a rise of O30%) on at least three consecutive occasions. Regarding predictive factors for the development of Nelson's syndrome post TBA, current evidence favours the presence of residual pituitary tumour on magnetic resonance imaging (MRI) post transsphenoidal surgery (TSS); an aggressive subtype of corticotrophinoma (based on MRI growth rapidity and histology of TSS samples); lack of prophylactic neoadjuvant pituitary radiotherapy at the time of TBA and a rapid rise of ACTH levels in year 1 post TBA. Finally, more studies are needed to assess the efficacy of therapeutic strategies in Nelson's syndrome, including the alkylating agent, temozolomide, which holds promise as a novel and effective therapeutic agent in the treatment of associated aggressive corticotroph tumours. It is timely to review these controversies and to suggest guidelines for future audit.

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“…More studies of temozolomide in NS treatment involving larger populations is needed. [18][19][20][21] …”

Section: Discussionmentioning

confidence: 99%