Temozolomide: a novel treatment for pituitary carcinoma

Lim, Stephen; Shahinian, Hrayr K.; Maya, Menahem M.; Yong, William H.; Heaney, Anthony P.

doi:10.1016/s1470-2045(06)70728-8

Cited by 165 publications

(142 citation statements)

References 10 publications

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“…Consequently, the agent is ideal for the treatment of relatively slow-growing pituitary tumors. 17 Temozolomide is accepted as an essential component of adjuvant therapy in the treatment of glioblastoma multiforme and other tumors of the central nervous system. [30][31][32] Recent reports indicate its efficacy in advancedstage, malignant neuroendocrine neoplasia 33,34 and in melanoma.…”

Section: Temozolomidementioning

confidence: 99%

“…Their 2 patients, 1 patient who had systemic metastases of a luteinizing hormone (LH)-producing (gonadotropic) pituitary carcinoma and 1 patient who had a prolactin (PRL)-producing (lactotrophic) carcinoma with spinal dissemination, were treated, and both achieved a sustained response. Thereafter, Zhu et al 25 and Lim et al 17 administered temozolomide to a patient who had a PRL-producing pituitary carcinoma. In these first 3 patients, persistent, significant clinical and biochemical improvement as well as substantial radiographic tumor shrinkage were noted.…”

Section: Pituitary Carcinomasmentioning

confidence: 99%

“…To date, 6 patients with pituitary carcinomas have received treatment with temozolomide 10,[12][13][14]17,19,[23][24][25] (Table 1). These included 4 men and 2 women ages 26 to 77 years (mean, 49.8 years).…”

Section: Pituitary Carcinomasmentioning

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: Temozolomidementioning

confidence: 99%

Section: Pituitary Carcinomasmentioning

confidence: 99%

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Treatment of pituitary neoplasms with temozolomide

Syro

Ortíz

Scheithauer

et al. 2010

Cancer

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“…We have shown recently that even higher than licensed doses of rosiglitazone (12 mg/day) are not effective in reducing plasma ACTH levels, and by inference tumour growth (45) (figure 1). The orally active alkylating agent temozolomide has been shown to be highly effective in a few aggressive pituitary tumours and in lowering prolactin and controlling tumour growth in highly aggressive prolactinomas (46)(47)(48). Although there are no reports of its use in Nelson's syndrome, temozolomide could be considered in patients with Nelson's syndrome not responding to other modalities of therapy.…”

Section: Medicalmentioning

confidence: 99%

Nelson's Syndrome

Munir

Newell‐Price

2007

Arq Bras Endocrinol Metab

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Nelson's syndrome is a potentially severe complication of bilateral adrenalectomy performed in the treatment of Cushing's disease, and its management remains difficult. Of all of the features of Nelson's syndrome, the one that causes most concern is the development of a locally aggressive pituitary tumour, which, unusually for pituitary disease, may occasionally cause death from the tumour itself. This feature is especially pertinent given the increasing use in Cushing's disease of laparoscopic bilateral adrenal surgery as a highly effective treatment modality to control cortisol-excess. Despite numerous studies and reports, there is no formal consensus of what defines Nelson's syndrome. Thus, some will define Nelson's syndrome according to the classical description with an evolving pituitary mass after bilateral adrenalectomy, whereas others will rely on increasing plasma ACTH levels, even in the absence of a clear pituitary mass lesion on MRI. These factors need to be borne in mind when considering the reports of Nelson's syndrome, as there is great heterogeneity, and it is likely that overall the modern 'Nelson's syndrome' represents a different disease entity from that of the last century. In the present paper, clinical and epidemiological features of Nelson's syndrome, as well as its treatment modalities, are reviewed.

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“…In addition, TMZ clinical trials have been performed to test its activity against brain metastatic solid tumors, leukemia (8), pancreatic neuro endocrine tumors (9) and refractory pituitary adenomas (10)(11)(12)(13)(14). Two case studies related to gonadotroph adenoma patients report that their lesions decreased after TMZ therapy (15,16), and studies of TMZ on MMQ, GH3, and AtT20 cell lines suggested that this drug may have efficacy in pituitary adenoma cells (17 to attain biochemical control in a severe case of acromegaly (18).…”

Section: Introductionmentioning

confidence: 99%

Effect of temozolomide on cell viability in gonadotroph adenoma cell lines

Liu²,

Yao³

et al. 2011

Oncol Rep

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Abstract. Invasive pituitary adenomas are usually refractory to routine neurosurgery, radiosurgery or medications, and alternative therapies are needed. The effects of temozolomide (TMZ) on the inhibition of gonadotroph adenoma cell viability and hormone secretion were evaluated. Cell viability and IC 50 values were evaluated after αT3-1 cells were treated with TMZ (31.25-1000 µM) or vehicle for 0-72 h. Cell cycle changes and the extent of apoptosis were detected using flow cytometry, TUNEL and TEM. The molecular mechanism of TMZ action was investigated by the Caspase-Glo ® assay and immunoblotting. Gonadotropin secretion was assessed using an immunoassay system. TMZ dose-and time-dependently suppressed cell proliferation (P<0.01 vs. control, 250 µM, 24 h) and induced S-phase accumulation and G2/M-phase arrest (P<0.05 vs. control, 250 µM, 24 h). Early apoptotic cells increased following a 24-h TMZ incubation (P<0.001 vs. control, 250 µM), consistent with TEM and TUNEL detection that exhibited morphological features of apoptosis. TMZ (250 µM) increased the level of caspase-3/7 by 6-fold, caspase-9 by 7-fold and caspase-8 by 3-fold after a 24-h incubation, while it attenuated Bcl-2 expression (P<0.001 vs.control) and raised the proteolysis of PARP. Both FSH and LH levels were significantly decreased by TMZ (P<0.01 vs. control, 250 µM, 24 h). TMZ inhibited cell proliferation and hormone secretion, and induced cell cycle arrest and apoptotic cell death in gonadotroph adenoma cells via both death receptor and mitochondrial pathways, suggesting that it may represent a useful medical management strategy of invasive gonadotroph adenomas.

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Temozolomide: a novel treatment for pituitary carcinoma

Cited by 165 publications

References 10 publications

Treatment of pituitary neoplasms with temozolomide

Treatment of pituitary neoplasms with temozolomide

Nelson's Syndrome

Effect of temozolomide on cell viability in gonadotroph adenoma cell lines

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