RESUMO
INTRODUCTION: Innovation through the repurposing of generic drugs encloses several advantages when compared with the process of developing new drugs from scratch. Metformin is an established and inexpensive antidiabetic drug for which anticancer properties have been hypothesised. A systematic review of observational studies found promising results for metformin related to breast cancer in women with diabetes. Although the number of randomised clinical trials of metformin for the treatment of breast cancer increased over the last decades, the overall landscape of those studies in this heterogeneous field remains unclear. Hence, we designed the present scoping review protocol to map the literature on randomised clinical trials of metformin in the treatment of breast cancer to determine the value and scope of future systematic reviews on this subject and identify research gaps. METHODS: We will search MEDLINE (via PubMed), EMBASE, CENTRAL, LILACS, Web of Science and sources of grey literature. We will include any randomised clinical trial of metformin for the treatment of breast cancer in adult women, and will not impose restrictions regarding context, language or publication date. Two independent reviewers will screen and select studies, and chart the data. We will structure the presentation of our results based on the molecular types of breast cancer, their stages and treatment modalities. ETHICS AND DISSEMINATION: As a literature review, this study is exempt from ethics approval. Findings will be disseminated through presentations in conferences and a peer-reviewed publication. OPEN SCIENCE FRAMEWORK REGISTRATION: osf.io/yquba.
Assuntos
Neoplasias da Mama , Metformina , Neoplasias da Mama/tratamento farmacológico , Atenção à Saúde , Feminino , Humanos , Metformina/uso terapêutico , Revisão por Pares , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Revisões Sistemáticas como AssuntoRESUMO
Diabetes mellitus type 2 and cancer share many risk factors. The pleiotropic insulin-dependent and insulin-independent effects of metformin might inhibit pathways that are frequently amplified in neoplastic tissue. Particularly, modulation of inflammation, metabolism, and cell cycle arrest are potential therapeutic cancer targets utilized by metformin to boost the anti-cancer effects of chemotherapy. Studies in vitro and in vivo models have demonstrated the potential of metformin as a chemo- and radiosensitizer, besides its chemopreventive and direct therapeutic activity in digestive system (DS) tumors. Hence, these aspects have been considered in many cancer clinical trials. Case-control and cohort studies and associated meta-analyses have evaluated DS cancer risk and metformin usage, especially in colorectal cancer, pancreatic cancer, and hepatocellular carcinoma. Most clinical studies have demonstrated the protective role of metformin in the risk for DS cancers and survival rates. On the other hand, the ability of metformin to enhance the actions of chemotherapy for gastric and biliary cancers is yet to be investigated. This article reviews the current findings on the anti-cancer mechanisms of metformin and its apparatus from pre-clinical and ongoing studies in DS malignancies.
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Neoplasias Colorretais , Diabetes Mellitus Tipo 2 , Metformina , Humanos , Hipoglicemiantes/uso terapêutico , Insulina , Metformina/uso terapêuticoRESUMO
BACKGROUND: Patients with refractory colorectal (CRC) cancer have few treatment options. This trial tests the combination of metformin and irinotecan in this setting. METHODS: A phase 2 single-arm trial was conducted, patients received metformin 2500 mg orally a day plus irinotecan 125 mg/m2 intravenously weekly D1 and D8 every 21 days. The primary endpoint was the disease control rate according to the Response Evaluation Criteria in Solid Tumors version 1.1 at 12 weeks. RESULTS: Between December 2015 and January 2018, 41 patients were enrolled. Seventeen patients (41%) met the primary endpoint of disease control in 12 weeks; hence, the study was deemed positive. The median progression-free survival was 3.3 months (CI 95%, 2.0-4.5 months), and the median overall survival was 8.4 months (CI 95%, 5.9-10.8 months). Both mutation RAS status and disease control at 12 weeks impacted overall survival in the multivariate model (HR 2.28, CI 95%, 1.12-4.7, p = 0.02; and HR 0.21, CI 95%, 0.08-0.5, p = 0.001, respectively). The most common adverse event was diarrhoea (29.2% grade 3). CONCLUSIONS: In this trial, metformin plus irinotecan demonstrated disease control in patients with refractory CRC. Further trials with optimised diarrhoea control are needed to confirm these results.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Adulto , Idoso , Neoplasias Colorretais/patologia , Feminino , Seguimentos , Humanos , Irinotecano/administração & dosagem , Masculino , Metformina/administração & dosagem , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Prognóstico , Taxa de Sobrevida , Adulto JovemRESUMO
Imatinib mesylate represents a revolution in the management of patients with metastatic gastrointestinal stromal tumors (GISTs). More recently, postoperative imatinib has been shown to improve both disease-free and overall survivals in patients with a high risk of recurrence. This article presents a well-documented case of a patient with painful and reversible bone edema related to imatinib.
Assuntos
Antineoplásicos/efeitos adversos , Benzamidas/efeitos adversos , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/patologia , Edema/induzido quimicamente , Piperazinas/efeitos adversos , Inibidores de Proteínas Quinases/efeitos adversos , Pirimidinas/efeitos adversos , Antineoplásicos/uso terapêutico , Benzamidas/uso terapêutico , Edema/diagnóstico , Tumores do Estroma Gastrointestinal/complicações , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Humanos , Mesilato de Imatinib , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Piperazinas/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas/uso terapêutico , Tomografia Computadorizada por Raios XRESUMO
Introdução: O sarcoma de Ewing representa 10% dos tumores ósseos, com predomínio no sexo masculino. A maior incidência é dos 5 aos 14 anos. Acomete mais as extremidades e em 25% dos casos há metástases ao diagnóstico. O acometimento do sistema nervoso central ocorre em 3% dos pacientes. A infiltração das leptomeninges é rara e ocorre predominantemente por contiguidade de uma lesão óssea subjacente. Relato do caso: Mulher de 27 anos com lesão em tíbia direita de 17 cm. A biópsia diagnosticou sarcoma de Ewing. Estadiamento sistêmico foi negativo e planejada quimioterapia neoadjuvante com esquema VAC-IE para preservação do membro. Após o primeiro ciclo de VAC teve neutropenia precoce, infecção de sítio tumoral, sepse e síndrome compartimental do membro. Submetida a amputação suprapatelar. Após 30 dias apresentou paralisia do VII, VI e III pares cranianos à esquerda e VII e III à direita, tomografia computadorizada do crânio foi normal e o líquor confirmou infiltração meníngea. A paciente evoluiu a óbito três dias após o diagnóstico de metástase meníngea. Discussão: A literatura é escassa em informações sobre a frequência do envolvimento meníngeo no sarcoma de Ewing. A forma peculiar do acometimento neste caso, sem metástase óssea que invadisse o sistema nervoso por contiguidade, faz-nos concluir que tal disseminação ocorreu pela via hematogênica. A paciente apresentava fatores de mau prognóstico (tumor > 100ml, idade > 26 anos, intervalo diagnóstico-metástases < 2 anos). O acometimento meníngeo contribuiu para o desfecho desfavorável, pois é um local de difícil controle da doença, considerado um santuário.