RESUMO
BACKGROUND: Fatigue is common among glioma patients undergoing radiotherapy (RT) and impacts quality of life (QOL). We evaluated whether armodafinil, a wakefulness-promoting medication, improves fatigue in glioma patients undergoing RT. METHODS: Eligibility criteria included age ≥18 years, Karnofsky performance status ≥60, and grade 2-4 glioma undergoing RT to a total dose of 50-60 Gy. Patients were randomized 1:1 to armodafinil or placebo for 8 weeks beginning within 10 days of starting RT. Fatigue and QOL were assessed at baseline, day 22, day 43, and day 56 with the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F), the Functional Assessment of Cancer Therapy - General (FACT-G), the Brief Fatigue Inventory (BFI), and the Cancer Fatigue Scale (CFS). The primary aim was to detect a difference in the 42-day change in FACIT-F fatigue subscale between the 2 groups using a 2-sample Wilcoxon statistic. RESULTS: We enrolled 81 patients total (42 armodafinil and 39 placebo). Armodafinil did not significantly improve fatigue or QOL based on the 42-day change in FACIT-F fatigue subscale, FACT-G, CFS, or BFI. Further analysis suggests no difference between the arms even after accounting for the potential bias of missing data. Treatment was well tolerated with few grade 3 or 4 toxicities. CONCLUSIONS: While treatment was well-tolerated, an 8-week course of armodafinil did not improve fatigue or QOL in glioma patients undergoing RT in this pilot study. Further studies are needed to determine whether pharmacologic treatment improves fatigue in glioma patients undergoing RT.
Assuntos
Compostos Benzidrílicos/uso terapêutico , Fadiga/tratamento farmacológico , Glioma/radioterapia , Promotores da Vigília/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Método Duplo-Cego , Fadiga/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modafinila , Projetos Piloto , Radioterapia/efeitos adversos , Resultado do TratamentoRESUMO
Temozolomide is an alkylating agent used in the treatment of gliomas and, more recently, aggressive pituitary adenomas and carcinomas. Temozolomide methylates DNA and, thereby, has antitumor effects. O6-methylguanine-DNA methyltransferase, a DNA repair enzyme, removes the alkylating adducts that are induced by temozolomide, thereby counteracting its effects. A Medline search for all of the available publications regarding the use of temozolomide for the treatment of pituitary tumors was performed. To date, 46 cases of adenohypophysial tumors that were treated with temozolomide, including 30 adenomas and 16 carcinomas, have been reported. Eighteen of the 30 (60%) adenomas and 11 of the 16 (69%) carcinomas responded favorably to treatment. One patient with multiple endocrine neoplasia type 1 and an aggressive prolactin-producing adenoma was also treated and demonstrated a good response. No significant complications have been attributed to temozolomide therapy. Thus, temozolomide is an effective treatment for the majority of aggressive adenomas and carcinomas. Evidence indicates that there is an inverse correlation between levels of O6-methylguanine-DNA methyltransferase immunoexpression and therapeutic response. Alternatively, high-level O6-methylguanine-DNA methyltransferase immunoexpression correlates with an unfavorable response. Here, we review the use of temozolomide for treating pituitary neoplasms.
Assuntos
Adenoma/tratamento farmacológico , Antineoplásicos Alquilantes/uso terapêutico , Carcinoma/tratamento farmacológico , Dacarbazina/análogos & derivados , Neoplasias Hipofisárias/tratamento farmacológico , Dacarbazina/uso terapêutico , Humanos , TemozolomidaRESUMO
We report the case of a 44-year-old male patient with an aggressive silent corticotroph cell pituitary adenoma, subtype 2. In that it progressed to carcinoma despite temozolomide administration, anti-VEGF therapy was begun. MRI, PET scan and pathologic analysis were undertaken. After 10 months of anti-VEGF (bevacizumab) treatment no progression of the lesion was noted. The tumor was biopsied and morphological analysis showed severe cell injury, vascular abnormalities and fibrosis. Bevacizumab treatment has continued for additional 16 months to present with stabilization of disease as documented on serial MRI and PET scans. This is the first case of a bevacizumab-treated pituitary carcinoma with long-term, now 26 months, control of disease. The present findings are promising in that anti-angiogenic therapy appears to represent a new option in the treatment of aggressive pituitary tumors.
Assuntos
Adenoma Hipofisário Secretor de ACT/tratamento farmacológico , Adenoma/tratamento farmacológico , Inibidores da Angiogênese/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Neoplasias Hipofisárias/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Adulto , Bevacizumab , Dacarbazina/análogos & derivados , Dacarbazina/uso terapêutico , Humanos , Imageamento por Ressonância Magnética , Masculino , Neoplasias Hipofisárias/patologia , Tomografia por Emissão de Pósitrons , TemozolomidaRESUMO
Temozolomide is an alkylating agent used in the treatment of gliomas and, more recently, aggressive pituitary adenomas and carcinomas. Temozolomide methylates DNA and, thereby, has antitumor effects. O6-methylguanine-DNA methyltransferase, a DNA repair enzyme, removes the alkylating adducts that are induced by temozolomide, thereby counteracting its effects. A Medline search for all of the available publications regarding the use of temozolomide for the treatment of pituitary tumors was performed. To date, 46 cases of adenohypophysial tumors that were treated with temozolomide, including 30 adenomas and 16 carcinomas, have been reported. Eighteen of the 30 (60%) adenomas and 11 of the 16 (69%) carcinomas responded favorably to treatment. One patient with multiple endocrine neoplasia type 1 and an aggressive prolactin-producing adenoma was also treated and demonstrated a good response. No significant complications have been attributed to temozolomide therapy. Thus, temozolomide is an effective treatment for the majority of aggressive adenomas and carcinomas. Evidence indicates that there is an inverse correlation between levels of O6-methylguanine-DNA methyltransferase immunoexpression and therapeutic response. Alternatively, high-level O6-methylguanine-DNA methyltransferase immunoexpression correlates with an unfavorable response. Here, we review the use of temozolomide for treating pituitary neoplasms.
Assuntos
Humanos , Adenoma/tratamento farmacológico , Antineoplásicos Alquilantes/uso terapêutico , Carcinoma/tratamento farmacológico , Dacarbazina/análogos & derivados , Neoplasias Hipofisárias/tratamento farmacológico , Dacarbazina/uso terapêuticoRESUMO
The concept that the genesis of new cells in the adult mammalian brain is negligible has long influenced our perception and understanding of the origin and development of central nervous system (CNS) tumors. The discovery that neurons and glia are produced throughout life from neural stem cells provides new possibilities for candidate precursor cells of CNS neoplasms. The emerging hypothesis is that alterations in the cellular and genetic mechanisms that control adult neurogenesis might contribute to brain tumorigenesis. As such, opportunities become available to identify new therapeutic strategies.
Assuntos
Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/terapia , Transformação Celular Neoplásica/patologia , Glioma/patologia , Meduloblastoma/patologia , Antígeno AC133 , Animais , Antígenos CD/metabolismo , Neoplasias Encefálicas/metabolismo , Diferenciação Celular , Transformação Celular Neoplásica/metabolismo , Progressão da Doença , Glioma/metabolismo , Glioma/terapia , Glicoproteínas/metabolismo , Humanos , Mamíferos , Meduloblastoma/metabolismo , Meduloblastoma/terapia , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Células-Tronco Neurais/metabolismo , Células-Tronco Neurais/patologia , Neurogênese , Neurônios/metabolismo , Neurônios/patologia , Peptídeos/metabolismo , Transdução de Sinais , Nicho de Células-TroncoRESUMO
The patient was a 70-year-old man with a recurrent pituitary tumor. Three surgeries were performed but the tumor recurred. Based on histologic, immunohistochemical and ultrastructural studies, the diagnosis of oncocytic gonadotrophic pituitary adenoma was made. The tumor was a macroadenoma partly immunopositive for LH. Immunohistochemistry for O6 Methylguanine-DNA Methyl-Transferase (MGMT) showed an admixture of immunopositive and immunonegative cells. After recurrence following operations, the patient was treated with Temozolomide, an imidazotetrazine derivative, DNA-alkylating drug. Following Temozolomide administration the MRI demonstrated significant tumor necrosis. A few months later, the patient died of massive pulmonary embolism. No autopsy was performed. The present case indicates that benign, typically slow-growing pituitary adenomas of oncocytic gonadotrophic type may respond to Temozolomide even when the tumor consists of an admixture of MGMT immunopositive and immunonegative cells.