RESUMO
BACKGROUND: Neuroendocrine tumors are uncommon tumors that are histopathologically and biologically heterogeneous and include the multiple endocrine neoplasia (MEN) 1 and 2 syndromes. The morbidity of MEN-1 and MEN-2 is often due to the symptomatology of the endocrine hormones produced, and the mortality mainly occurs from hepatic dysfunction incurred by liver metastases. At present, there is essentially no effective cure once the tumor has metastasized to the liver. PATIENT: We present a patient with progressive, metastatic MEN-1 with the classic '3 P's' triad of neuroendocrine tumor of the pancreas, parathyroid adenoma and a pituitary adenoma. RESULTS: After progression on high-dose Sandostatin LAR (60 mg/month) and multiple surgeries, the patient had a partial response (40% decrease) to a novel regimen of capecitabine and temozolomide (CAPTEM) and progression-free survival of 18 months. He had minor grade 1 toxicities and no grade 2, 3 or 4 toxicities. DISCUSSION: The history and treatment options for MEN-1/2 cancers are reviewed, as well as the data behind our novel regimen, CAPTEM. CONCLUSION: The CAPTEM regimen is a tolerable, safe, easy to administer oral regimen with possible efficacy for MEN-1 tumors.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasia Endócrina Múltipla Tipo 1/tratamento farmacológico , Neoplasia Endócrina Múltipla Tipo 2a/tratamento farmacológico , Capecitabina , Dacarbazina/administração & dosagem , Dacarbazina/análogos & derivados , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Fluoruracila/administração & dosagem , Fluoruracila/análogos & derivados , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Literatura de Revisão como Assunto , Temozolomida , Tomografia Computadorizada por Raios XRESUMO
PURPOSE: We evaluated the efficacy and safety of capecitabine and temozolomide (CAPTEM) in patients with metastatic neuroendocrine tumors (NETs) to the liver. This regimen was based on our studies with carcinoid cell lines that showed synergistic cytotoxicity with sequence-specific dosing of 5-fluorouracil preceding temozolomide (TMZ). METHODS: A retrospective review was conducted of 18 patients with NETs metastatic to the liver who had failed 60 mg/month of Sandostatin LAR™ (100%), chemotherapy (61%), and hepatic chemoembolization (50%). Patients received capecitabine at 600 mg/m(2) orally twice daily on days 1-14 (maximum 1,000 mg orally twice daily) and TMZ 150-200 mg/m(2) divided into two doses daily on days 10-14 of a 28-day cycle. Imaging was performed every 2 cycles, and serum tumor markers were measured every cycle. RESULTS: Using RECIST parameters, 1 patient (5.5%) with midgut carcinoid achieved a surgically proven complete pathological response (CR), 10 patients (55.5%) achieved a partial response (PR), and 4 patients (22.2%) had stable disease (SD). Total response rate was 61%, and clinical benefit (responders and SD) was 83.2%. Of four carcinoid cases treated with CAPTEM, there was 1 CR, 1 PR, 1 SD, and 1 progressive disease. Median progression-free survival was 14.0 months (11.3-18.0 months). Median overall survival from diagnosis of liver metastases was 83 months (28-140 months). The only grade 3 toxicity was thrombocytopenia (11%). There were no grade 4 toxicities, hospitalizations, opportunistic infections, febrile neutropenias, or deaths. CONCLUSIONS: CAPTEM is highly active, well tolerated and may prolong survival in patients with well-differentiated, metastatic NET who have progressed on previous therapies.