Medical Therapy of Aggressive Pituitary Tumors

Petersenn, Stephan

doi:10.1055/a-1331-6939

Cited by 6 publications

(5 citation statements)

References 49 publications

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“…Clinical practice guidelines for aggressive PitNETs recommend surgery and radiotherapy for most patients, along with standard medical treatment for functioning tumours, but they become less precise when it comes to propose subsequent treatments for tumours that progress afterwards, since scientific evidence is lacking ( 1 , 18 , 19 ). We found a great variability in the treatments our patients had received prior to TMZ.…”

Section: Discussionmentioning

confidence: 99%

“…Corticotroph tumours, both silent and functioning, represented the most frequent lineage among these aggressive PitNETs and pituitary carcinomas, followed by lactotroph tumours, both in our cohort and all the previous multicentric studies, but we found a lower percentage of carcinomas, only 14.3%, in comparison to previously reported percentages between 19 and 32%. Clinical practice guidelines for aggressive PitNETs recommend surgery and radiotherapy for most patients, along with standard medical treatment for functioning tumours, but they become less precise when it comes to propose subsequent treatments for tumours that progress afterwards, since scientific evidence is lacking (1,18,19). We found a great variability in the treatments our patients had received prior to TMZ.…”

Section: Functioning Tumours 10mentioning

confidence: 92%

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Efficacy and safety of temozolomide in the treatment of aggressive pituitary neuroendocrine tumours in Spain

Lamas,

Cámara,

Fajardo

et al. 2023

Front. Endocrinol.

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Current guidelines recommend temozolomide as the first-line chemotherapy for aggressive pituitary neuroendocrine tumours. However, no clinical trials have been conducted to date and clinical experience is quite limited. We retrospectively analyzed 28 patients (9 women and 19 men), aged 46.6 + 16.9, with aggressive pituitary tumours (4 pituitary carcinomas and 24 aggressive adenomas) treated with temozolomide in 10 Spanish pituitary reference centres. Four patients had Cushing’s disease, 9 prolactinomas and 15 clinically non-functioning pituitary tumours (seven silent corticotroph, three silent somatotroph, one silent lactotroph, one silent gondotroph and three null-cell tumours). Median size at diagnosis was 10.5 cm3 (IQR 4.7-22.5), with cavernous sinus invasion in 88% and no metastases. Pre-temozolomide treatment, these data were 5.2 cm3 (IQR 1.9-12.3), 89.3% and 14.3% (2 intracranial and 2 spinal metastases). All patients had undergone surgery (1-5 surgeries), 25 (89.3%) had received radiotherapy (7 of them reirradiated) and 13(46.4%) had received cabergoline. One patient interrupted temozolomide prematurely. The remaining 27 patients received a median of 13 cycles (range 3-66) of 5 days every 28 days, with a mean initial dose of 265 ± 73 mg when administered alone and of 133 ± 15 mg when co-administered with radiotherapy. Eight patients (29.6%) had a significant reduction (>30%) in tumour volume and 14 (51.9%) attained tumour stabilization. After a median follow-up of 29 months (IQR 10-55), 8 out of these 22 showed disease progression. A longer progression-free survival was found in the five patients who received concomitant radiotherapy. Seven patients (25%) died (all of them because of tumour progression or complications of treatments) at 77 months (IQR 42-136) after diagnosis and 29 months (IQR 16-55) after the first dose of temozolomide. Adverse effects occurred in 18 patients (14 mild and 4 moderate or severe). In conclusion, temozolomide is an effective medical treatment for aggressive pitNET and pituitary carcinomas but is sometimes followed by tumour progression. Co-administration with radiotherapy may increase progression-free survival.

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Section: Discussionmentioning

confidence: 99%

Section: Functioning Tumours 10mentioning

confidence: 92%

Efficacy and safety of temozolomide in the treatment of aggressive pituitary neuroendocrine tumours in Spain

Lamas,

Cámara,

Fajardo

et al. 2023

Front. Endocrinol.

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“…Tumor monitoring in rats was conducted using MRI at day 0 (pretreatment) and every 14 days post-treatment (days 14,28,42,56). MRI was performed on a 7T preclinical scanner (Bruker BioSpin MRI GmbH, Ettlingen, Germany) using previously published procedures suitable to visualize the rat pituitary tumors.…”

Section: Magnetic Resonance Imaging (Mri)mentioning

confidence: 99%

“…SSAs such as Octreotide ( Figure 1 A) and Lanreotide ( Figure 1 D), which bind to somatostatin receptor 2 (SSTR2), and to a lesser extent, to SSTR5 and SSTR3, are effective in the treatment of secreting pituitary adenomas [ 11 , 12 , 13 ], but are poorly efficacious in NFPAs [ 14 ]. Similarly, the panagonist Pasireotide ( Figure 1 B), which binds to SSTR1, 2, 3, 5, showed only modest efficacy in a recent phase II clinical trial (NCT01283542—Evaluate the Efficacy and Safety of Pasireotide LAR (Long Acting Release) on the Treatment of Patients With Clinically Nonfunctioning Pituitary Adenoma—Passion I), with only 16.7% of patients reaching a tumor size reduction of at least 20% [ 8 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

Identification of a Novel SSTR3 Full Agonist for the Treatment of Nonfunctioning Pituitary Adenomas

Modena

Moras

Sandrone

et al. 2023

Cancers

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Somatostatin receptor (SSTR) agonists have been extensively used for treating neuroendocrine tumors. Synthetic therapeutic agonists showing selectivity for SSTR2 (Octreotide) or for SSTR2 and SSTR5 (Pasireotide) have been approved for the treatment of patients with acromegaly and Cushing’s syndrome, as their pituitary tumors highly express SSTR2 or SSTR2/SSTR5, respectively. Nonfunctioning pituitary adenomas (NFPAs), which express high levels of SSTR3 and show only modest response to currently available SSTR agonists, are often invasive and cannot be completely resected, and therefore easily recur. The aim of the present study was the evaluation of ITF2984, a somatostatin analog and full SSTR3 agonist, as a new potential treatment for NFPAs. ITF2984 shows a 10-fold improved affinity for SSTR3 compared to Octreotide or Pasireotide. Molecular modeling and NMR studies indicated that the higher affinity for SSTR3 correlates with a higher stability of a distorted β-I turn in the cyclic peptide backbone. ITF2984 induces receptor internalization and phosphorylation, and triggers G-protein signaling at pharmacologically relevant concentrations. Furthermore, ITF2984 displays antitumor activity that is dependent on SSTR3 expression levels in the MENX (homozygous mutant) NFPA rat model, which closely recapitulates human disease. Therefore, ITF2984 may represent a novel therapeutic option for patients affected by NFPA.

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“…It starts with a review on the clinical implications of the new WHO classification of pituitary tumors [12], followed by manuscripts addressing the rhinological consequences of pituitary surgery [13] and the outcome of transsphenoidal surgery in prolactinomas [14], and a review article covering recent advances in craniopharyngioma [15]. An original study reports 3 cases of aggressive pituitary tumors treated by bevacizumab [16] and a more general review addresses medical options in these tumors [17]. Cushing's disease is covered by an original study reporting neuropsychologic changes in affected patients, and by reviews on mortality in Cushing's disease [18] and secondary treatment options if pituitary surgery failed [19].…”

Section: Which Topics Will You Find In This Special Issue?mentioning

confidence: 99%

Pituitary in the Spotlight

Reincke

Honegger

2021

Exp Clin Endocrinol Diabetes

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The German Society of Endocrinology (DGE) has a long-standing scientific and clinical focus on the pituitary. The pituitary working group ‘Arbeitsgemeinschaft Hypophyse’ is an interdisciplinary special interest group with a focus on advancing diagnosis and treatment of pituitary conditions. On the occasion of the English publication of the S2K clinical guideline Diagnosis and therapy of clinically hormonally inactive pituitary tumors, we present here a series of 12 articles from internationally renowned authors from inside and outside of Germany.

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Medical Therapy of Aggressive Pituitary Tumors

Cited by 6 publications

References 49 publications

Efficacy and safety of temozolomide in the treatment of aggressive pituitary neuroendocrine tumours in Spain

Efficacy and safety of temozolomide in the treatment of aggressive pituitary neuroendocrine tumours in Spain

Identification of a Novel SSTR3 Full Agonist for the Treatment of Nonfunctioning Pituitary Adenomas

Pituitary in the Spotlight

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