RESUMO
INTRODUCTION: This literature review and exploratory network meta-analysis (NMA) aimed to compare the clinical effectiveness and tolerability of selective internal radiation therapy (SIRT) using yttrium-90 (Y-90) resin microspheres, regorafenib (REG), trifluridine-tipiracil (TFD/TPI), and best supportive care (BSC) in adult patients with chemotherapy-refractory or chemotherapy-intolerant metastatic colorectal cancer (mCRC). METHODS: In light of recently published data, the literature was searched to complement and update a review published in 2018. Studies up to December 2022 comparing two or more of the treatments and reporting overall survival (OS), progression-free survival (PFS), or incidence of adverse events (AE) were included. The NMA compared hazard ratios (HRs) for OS and PFS using Markov chain Monte Carlo techniques. RESULTS: Fifteen studies were included, with eight studies added (none addressing SIRT). All active treatments improved OS in relation to BSC. SIRT had the longest OS among all treatments, although without statistically significant differences (HR [95% credible interval] for SIRT, 0.48 [0.27, 0.87]; TFD/TPI, 0.62 [0.46, 0.83]; REG, 0.78 [0.57, 1.05]) in a fixed effects model. Information regarding SIRT was insufficient for PFS analysis, and TFD/TPI was the best intervention (HR 2.26 [1.6, 3.18]). One SIRT study reported radioembolization-induced liver disease in > 10% of the sample; this was symptomatically managed. Non-haematological AEs (hand-foot skin reaction, fatigue, diarrhoea, hypertension, rash or desquamation) were more common with REG, while haematological events (neutropoenia, leukopenia, and anaemia) were more common with TFD/TPI. CONCLUSION: Current evidence supports SIRT treatment in patients with chemotherapy-refractory or chemotherapy-intolerant mCRC compared to newer oral agents, with comparable OS and low incidence of AEs.
Assuntos
Neoplasias Colorretais , Microesferas , Metanálise em Rede , Radioisótopos de Ítrio , Humanos , Neoplasias Colorretais/radioterapia , Neoplasias Colorretais/tratamento farmacológico , Radioisótopos de Ítrio/uso terapêutico , Trifluridina/uso terapêutico , Combinação de Medicamentos , Compostos de Fenilureia/uso terapêutico , Compostos de Fenilureia/efeitos adversos , Braquiterapia/métodos , Braquiterapia/efeitos adversos , Pirrolidinas/uso terapêutico , Piridinas/uso terapêutico , TiminaRESUMO
INTRODUCTION: The gold-standard treatment for autoimmune hepatitis (AIH) is a prednisone/azathioprine combination. However, subgroups of patients may be unresponsive to this treatment. The aim of this study is to evaluate the efficacy of second-line immunosuppressive therapies for AIH through a systematic review and meta-analysis in adult patients. PATIENTS AND METHODS: The systematic review was registered at the PROSPERO platform under number 42015019831. Databases MEDLINE (PubMed), Lilacs, Cochrane, and Scielo were searched. The keywords used were 'Hepatitis, Autoimmune' and descriptors terms (MeSH and DeCS). These terms were linked with each immunosuppressant of interest. RESULTS: A total of 1532 studies were identified. Of these, 1492 were excluded on the basis of title and abstract reading. Among the 40 studies retrieved for detailed full-text analysis, a total of 15 fulfilled the inclusion criteria for the analysis. The most studied second-line immunosuppressive was mycophenolate mofetil (MM). The mean reduction of aminotransferases was observed in 94.3% with tacrolimus/prednisone, 91.3% for cyclosporine/prednisone, 85.5% for budesonide, and 78.7% MM/prednisone. For MM/prednisone, the mean rate of histological remission was 88.6%, liver transplantation was indicated in 11.4%, and the mortality rate was 7.2%. Limitations were also present, such as the lack of randomized-controlled trials and prospective studies, the small number of patients, and the heterogeneity between remission criteria. CONCLUSION: This is the first systematic review and meta-analysis to compare the second-line imunossupressant therapy for AIH. The most studied second-line immunosuppressive is the MM, with a reasonable histological remission. The use of combined tacrolimus/prednisone was the most effective for the normalization of aminotransferases.