Temozolomide Treatment in Aggressive Pituitary Tumors and Pituitary Carcinomas: A French Multicenter Experience

Raverot, Gérald; Stürm, Nathalie; Fraipont, Florence de; Müller, Marie; Salenave, Sylvie; Caron, Philippe; Chabre, Olivier; Chanson, Philippe; Cortet‐Rudelli, Christine; Assaker, R.; Dufour, Henry; Gaillard, Stéphan; François, P.; Jouanneau, Emmanuel; Passagia, J.-G.; Bernier, Michèle; Cornelius, Aurélie; Figarella‐Branger, Dominique; Trouillas, Jacqueline; Borson‐Chazot, Françoise; Brue, Thierry

doi:10.1210/jc.2010-0644

Cited by 203 publications

(162 citation statements)

References 24 publications

Supporting

Mentioning

145

Contrasting

Unclassified

Order By: Relevance

“…The alkylating compound, temozolomide, recently demonstrated a significant response against aggressive pituitary adenomas and carcinomas (19,37,38). A recent relatively large cohort study (nZ24) (19) demonstrated that immunohistochemically low MGMT expression predicts a better response to temozolomide.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

The USP8 mutational status may predict drug susceptibility in corticotroph adenomas of Cushing's disease

Hayashi

Inoshita

Kawaguchi

et al. 2016

European Journal of Endocrinology

136

156

View full text Add to dashboard Cite

Context: Somatic mutations in the ubiquitin-specific peptidase USP8 gene were recently detected in one-to two-third(s) of corticotroph adenomas of Cushing's disease (CD). These mutations may lead to the deubiquitination of EGFR, thereby increasing EGFR signaling, which has been implicated in ACTH hypersecretion. Objective: Our objective was to determine the impact of USP8 mutations on the clinicopathological features of CD. Subjects and methods: USP8 mutations as well as clinicopathological characteristics were examined in 60 corticotroph adenomas including 15 Crooke's cell adenomas (CCAs), a rare histological variant presenting with generally aggressive behavior, using qRT-PCR and/or immunohistochemistry. Results: USP8 mutations were exclusively detected in women, except for one case, with a prevalence of 42.2% in non-CCA and 13.3% in CCA (overall 35%). Clinically well-behaved presentations including microadenoma and curative resection were more common in mutated cases. The expression of EGFR was not associated with the mutation status. In contrast, mutated tumors expressed significantly higher levels of POMC, SSTR5, and MGMT. Conclusions: Microadenomas that strongly express POMC were common among mutated tumors, which may lead to the mechanisms by which very small adenomas secrete excess ACTH to present overt CD. While USP8 mutations were less likely to enhance tumorous ACTH hypersecretion via EGFR-mediated activation, the presence of USP8 mutations may predict favorable responses to the somatostatin analog pasireotide, which exhibits high affinity for SSTR5. In contrast, non-mutated aggressive tumors such as CCA may respond better to the alkylating agent temozolomide because of their significantly weak expression of MGMT.

show abstract

Section: Discussionmentioning

confidence: 99%

“…Several studies have argued that an immunohistochemical MGMT expression analysis is not clinically useful in predicting tumor responses to temozolomide therapy (20,37,38). One possible explanation of the controversy is the acquisition of temozolomide resistance due to the loss of MSH6 expression during temozolomide treatments (19,20,39).…”

Section: Discussionmentioning

confidence: 99%

The USP8 mutational status may predict drug susceptibility in corticotroph adenomas of Cushing's disease

Hayashi

Inoshita

Kawaguchi

et al. 2016

European Journal of Endocrinology

136

156

View full text Add to dashboard Cite

show abstract

“…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.…”

Section: Discussionmentioning

confidence: 99%

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

Vroonen

Jaffrain-Rea

Pétrossians

et al. 2012

European Journal of Endocrinology

Self Cite

178

113

View full text Add to dashboard Cite

Background: Dopamine agonist resistance in prolactinoma is an infrequent phenomenon. Doses of cabergoline (CAB) of up to 2.0 mg/week are usually effective in controlling prolactin (PRL) secretion and reducing tumor size in prolactinomas. The clinical presentation, management, and outcome of patients that are not well controlled by such commonly used doses of CAB-resistant patients are poorly understood. Design and methods: A multicenter retrospective study was designed to collect a large series of resistant prolactinoma patients, defined by uncontrolled hyperprolactinemia on CAB R2.0 mg weekly.

show abstract

“…1%) are rare entities of pituitary tumours (Saeger et al 2007). Medical treatment regimens with dopamine agonists and somatostatin analogues are established for prolactinomas and somatotropinomas respectively (Colao & Savastano 2011, Giustina et al 2011, and promising treatment results with temozolomide have been reported in a few cases of pituitary carcinoma (Raverot et al 2010). The other pituitary adenoma types as well as drug-resistant prolactinomas and somatotropinomas have to be removed by transsphenoidal or transcranial surgery.…”

Section: Introductionmentioning

confidence: 99%

Curcumin suppresses HIF1A synthesis and VEGFA release in pituitary adenomas

Shan

Schaaf

Schmidt³

et al. 2012

Journal of Endocrinology

View full text Add to dashboard Cite

Curcumin (diferuloylmethane), a polyphenolic compound derived from the spice plantCurcuma longa, displays multiple actions on solid tumours including anti-angiogenic effects. Here we have studied in rodent and human pituitary tumour cells the influence of curcumin on the production of hypoxia inducible factor 1α (HIF1A) and vascular endothelial growth factor A (VEGFA), two key components involved in tumour neovascularisation through angiogenesis. Curcumin dose-dependently inhibited basal VEGFA secretion in corticotroph AtT20 mouse and lactosomatotroph GH3 rat pituitary tumour cells as well as in all human pituitary adenoma cell cultures (n=32) studied. Under hypoxia-mimicking conditions (CoCl2treatment) in AtT20 and GH3 cells as well as in all human pituitary adenoma cell cultures (n=8) studied, curcumin strongly suppressed the induction of mRNA synthesis and protein production of HIF1A, the regulated subunit of the hypoxia-induced transcription factor HIF1. Curcumin also blocked hypoxia-induced mRNA synthesis and secretion of VEGFA in GH3 cells and in all human pituitary adenoma cell cultures investigated (n=18). Thus, curcumin may inhibit pituitary adenoma progression not only through previously demonstrated anti-proliferative and pro-apoptotic actions but also by its suppressive effects on pituitary tumour neovascularisation.

show abstract

Temozolomide Treatment in Aggressive Pituitary Tumors and Pituitary Carcinomas: A French Multicenter Experience

Abstract: 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.

Cited by 203 publications

References 24 publications

The USP8 mutational status may predict drug susceptibility in corticotroph adenomas of Cushing's disease

The USP8 mutational status may predict drug susceptibility in corticotroph adenomas of Cushing's disease

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

Curcumin suppresses HIF1A synthesis and VEGFA release in pituitary adenomas

Contact Info

Product

Resources

About