Adrenal Bez Tümörlerinde Medikal Tedavi
Özet
Adrenal bez tümörleri, adrenal korteks veya medulladan köken alan nadir hastalık grupları olup, lokal ileri veya metastatik evrelerde primer olarak medikal tedavilerle yönetilir. Adrenokortikal karsinom (AKK) tedavisinde güncel standart başlangıç yaklaşımı, adrenolitik bir ilaç olan mitotanın monoterapi veya sisplatin-etoposid-doksorubisin (EDP) kemoterapisi ile kombinasyonudur. Klinik çalışmalar, EDP-mitotan kombinasyonunun sağkalım sürelerini ve tümör yanıt oranlarını anlamlı ölçüde artırdığını ortaya koymuştur. Mitotan kullanımı, steroid yapımını bozması nedeniyle adrenal yetmezlik, halsizlik ve gastrointestinal bozukluklar gibi ciddi yan etkilere yol açabilmektedir. Son yıllarda yapılan faz 2 çalışmalar, özellikle daha önce tedavi almış AKK hastalarında immün kontrol noktası inhibitörü pembrolizumabın tolere edilebilir bir yan etki profiliyle sınırda etkinlik gösterdiğini kanıtlamıştır. Diğer taraftan, malign feokromasitoma ve paraganglioma olgularında katekolamin salınımına bağlı semptomların kontrolü kritik öneme sahiptir. Bu tümörlerde, MIBG tutulumu gösteren metastatik vakalarda radyonüklit bir tedavi olan Iobenguane I-131 veya somatostatin reseptör ekspresyonu varlığında peptit reseptör radyoligand tedavileri (PRRT) öncelikli seçeneklerdir. Sistemik CVD (siklofosfomid, vinkristin, dakarbazin) kemoterapisi, tirozit kinaz inhibitörü sunitinib ve pembrolizumab ise progresyon gösteren veya semptomatik feokromasitoma olgularında klinik başarı sağlayan diğer önemli medikal alternatiflerdir.
Adrenal gland tumors are a rare group of diseases originating from the adrenal cortex or medulla, primarily managed with medical therapies in locally advanced or metastatic stages. In the treatment of adrenocortical carcinoma (ACC), the current standard initial approach is the adrenolytic drug mitotane, used either as monotherapy or in combination with cisplatin-etoposide-doxorubicin (EDP) chemotherapy. Clinical studies have demonstrated that the EDP-mitotane combination significantly improves survival times and tumor response rates. However, mitotane use can cause serious adverse effects, including adrenal insufficiency, fatigue, and gastrointestinal disturbances due to its disruption of steroid synthesis. In recent years, phase 2 trials have shown that the immune checkpoint inhibitor pembrolizumab offers marginal efficacy with a tolerable side effect profile, particularly in previously treated ACC patients. On the other hand, controlling symptoms related to catecholamine release is critical in cases of malignant pheochromocytoma and paraganglioma. For these tumors, radionuclide therapy with Iobenguane I-131 in metastatic cases with positive MIBG uptake, or peptide receptor radioligand therapies (PRRT) in the presence of somatostatin receptor expression, represent the primary therapeutic options. Furthermore, systemic CVD (cyclophosphamide, vincristine, dacarbazine) chemotherapy, the tyrosine kinase inhibitor sunitinib, and pembrolizumab serve as other vital medical alternatives that provide clinical benefit in progressive or symptomatic pheochromocytoma cases.
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