Endocrine Abstracts

Dopamine agonists (DA), mainly cabergoline, are nowadays recommended as the treatment of choice for patients with prolactinomas of any size to lower PRL levels, decrease tumour size, and restore gonadal function. However, some patients do not adequately respond to DA, and resistance to DA may occur in 20-30% of patients treated with bromocriptine and nearly 10-20% of those receiving cabergoline. In these patients, multimodal therapy, including surgery and/or radiotherapy, may be required. Recent evidence also supports the use of surgery as first-line therapy for patients with enclosed and not invasive prolactinomas. Aggressive and malignant prolactinomas refractory to all treatment strategies may benefit from the administration of the oral alkylating chemotherapeutic agent temozolomide, whose efficacy in terms of tumour growth control accounts for up to 50% of patients with prolactinomas. Temozolomide is nowadays recommended as first-line chemotherapy for aggressive pituitary tumours and pituitary carcinomas, following documented tumour growth. Responsiveness to temozolomide may be predicted by the evaluation of O(6)-methylguanine methyl transferase (MGMT) status by immunohistochemistry, as high MGMT expression is generally suggestive of a lack of response. The effectiveness of temozolomide has been shown to increase when combined with radiotherapy given its radio-sensitizing properties, thus offering a further therapeutic option for those individuals with aggressive or malignant prolactinomas. Aside from surgery, radiotherapy, and chemotherapy with temozolomide, alternative treatment schedules have been investigated or are nowadays tested in clinical and preclinical models, but the experience is still too scant to draw definitive conclusions. Among them, alternative hormonal treatments, cytotoxic drugs, peptide receptor radionuclide therapy, mTOR/Akt inhibitors, anti-VEGF bevacizumab, tyrosine kinase inhibitors and immunotherapy with immune checkpoint inhibitors, appeared to offer promising results. Future research will clarify the potential applications of such treatments, driving endocrinologists in the choice of the best-tailored therapy for patients with aggressive and malignant prolactinomas.