Efficacy of temozolomide combined with capecitabine (CAPTEM) on refractory prolactinomas as assessed using an ex vivo 3D spheroid assay

Ishida, Atsushi; Shichi, Hiroki; Fukuoka, Hidenori; Inoshita, Naoko; Ogawa, Wataru; Yamada, Shozo

doi:10.1007/s11102-021-01192-x

Cited by 10 publications

(14 citation statements)

References 37 publications

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“…The effect of CAPTEM was assessed in an ex vivo culture from two patients with refractory prolactinomas. CAPTEM reduced prolactin levels moderately (9070→4046 ng/mL) in one patient and significantly (17,500→210 ng/mL) in another, while it suppressed the tumor growth in both cases 62 .…”

Section: Prolactinοmasmentioning

confidence: 81%

Recent advances in understanding and managing pituitary adenomas

Markou¹,

Lavrentaki²,

Ntali³

2023

Fac Rev

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Pituitary adenomas (PAs) are common intracranial tumors. Despite their benign nature, PAs may cause a significant burden of disease, leading to either hormonal disturbances or local compression. A subset of PAs presents an aggressive behavior that remains difficult to predict, and in rare cases they metastasize. Therefore, early diagnosis and treatment are important. Advances in molecular pathology have improved the understanding of their pathogenesis and offer opportunities to identify and target novel pathways. Improved imaging and functional molecular techniques precisely detect even very small tumors and guide targeted treatment. Transsphenoidal surgery is the first-line treatment for the majority of PAs, and advances in the field of endoscopic neurosurgery offer excellent outcomes. Dopamine agonists (DAs) are traditionally the first-line treatment for prolactinomas. For patients with acromegaly, first- and second-generation somatostatin analogues (SSAs) are applied when surgery is not successful or not indicated. For Cushing’s disease (CD), drugs targeting adrenal steroidogenesis, somatostatin receptors in the pituitary, and glucocorticoid receptors are used to treat hypercortisolism in patients with persistent or recurrent CD, for those who are not good surgical candidates, and as a bridge treatment for those who have undergone radiation treatment until cortisol levels are controlled. Temozolomide (TMZ) is the first-line chemotherapy for aggressive PAs, but new experimental therapies, like the anti-vascular endothelial growth factor (anti-VEGF) therapy, mechanistic target of rapamycin (mTOR) inhibitors, tyrosine kinase inhibitors, and cell cycle and checkpoint inhibitors, are now available. Radiotherapy is offered to patients with residual, recurrent, or progressive tumors. Modern techniques in radiotherapy planning and delivery are able to deliver high doses to the target tissue while sparing vital structures. As we familiarize ourselves with the biological behavior of PAs and our therapeutic armamentarium expands, the next goal is to tailor and personalize treatment to each individual patient so as to achieve the best outcome.

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Section: Prolactinοmasmentioning

confidence: 81%

Recent advances in understanding and managing pituitary adenomas

Markou¹,

Lavrentaki²,

Ntali³

2023

Fac Rev

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“…Some case reports have suggested that other medications might be useful in combination with TMZ. These include TMZ and capecitabine [66,67], bevacizumab, thalidomide, and BCNU. VEGF-targeted therapy (bevacizumab) has been tried as monotherapy and in combination with TMZ with some degree of success in a few patients [27,68].…”

Section: Alternative Treatments For Tmz-resistant Tumorsmentioning

confidence: 99%

Aggressive pituitary tumors (PitNETs)

Nishioka

2023

Endocr J

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The majority of anterior pituitary tumors behave benignly, that is, they grow slowly and do not metastasize, and were therefore called adenomas. However, they would frequently invade adjacent structures, leading to recurrence. One of the misleading assumptions in their previous classification was the simplistic distinction made between adenoma and carcinoma. In the upcoming WHO 2022 classification, a new terminology will be introduced: pituitary neuroendocrine tumor (PitNET) which is consistent with that used for other neuroendocrine neoplasms. In general, aggressive PitNETs are invasive and proliferative tumors with frequent recurrences, resistant to conventional treatments, and yet virtually without metastases. At present, no single morphological or histological marker has been shown as yet to reliably predict their aggressive behavior. In terms of treatment, temozolomide (TMZ) had been considered promising and the sole therapeutic option for aggressive and malignant PitNETs following failure of standard therapies. However, recent reports have disclosed that TMZ does not provide long-term control of many aggressive PitNETs. A further multidisciplinary approach is necessary for both reliable prediction and successful management of aggressive PitNETs.

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“…TMZ can control about 70% of prolactinomas cell proliferation, normalize PRL level, and have less adverse effect [4,21]. However, when high O6 methylguanine DNA methyltransferase (MGMT) is highly expressed in prolactinomas cells, patients are resistant to TMZ [7,22].…”

Section: Temozolomide (Tmz) As Medication Replacementmentioning

confidence: 99%

Medical Therapies in Prolactinomas Patients Resistant to Bromocriptine

Shen¹

2023

HSET

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Prolactinoma is the most common pituitary tumor. Bromocriptine(BRC) is a dopamine receptor agonist(DAs), which is one of the medical treatments for prolactinomas. However, about a quarter of patients are resistant to BRC. The aim of this article is to explore medical treatment for prolactinoma patients who are resistant to BRC, including increasing the dose of BRC and substituting drugs (cabagoline, temozolomide). Since prolactinomas is predominantly microadenoma, medical therapy based on DAs is the first-line treatment. Cabergoline (CAB), belong to DAs, is progressively substituted for BRC because of its excellent tolerability and better efficacy. In addition, small percentage of patients with prolactinomas are aggressive, this means that they are naturally resistant to DAs. High doses of CAB and standard doses of TMZ are treatments for aggressive prolactinoma, however, the use of high-dose CAB has been linked to an increased risk of cardiac valvopathy in patients with both Parkinson's disease and prolactinoma. Hence, TMZ, last conservative treatment, is recommended for this subset of patients.

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Efficacy of temozolomide combined with capecitabine (CAPTEM) on refractory prolactinomas as assessed using an ex vivo 3D spheroid assay

Cited by 10 publications

References 37 publications

Recent advances in understanding and managing pituitary adenomas

Recent advances in understanding and managing pituitary adenomas

Aggressive pituitary tumors (PitNETs)

Medical Therapies in Prolactinomas Patients Resistant to Bromocriptine

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