JOAO GLASBERG
Projetos de Pesquisa
Unidades Organizacionais
14 resultados
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- EXPLORING THE ROLE OF METFORMIN IN ANTICANCER TREATMENTS: A SYSTEMATIC REVIEW(2014) MIRANDA, V. C.; BARROSO-SOUSA, R.; GLASBERG, J.; RIECHELMANN, R. P.Many clinical and preclinical studies suggest that metformin has antitumor activity. There are two main mechanisms that justify this effect: its ability to activate AMPK, preventing the gluconeogenesis in the liver and stimulating glucose uptake in muscle (insulin-independent), and its potential to negatively regulate mTOR activity (insulin-dependent). Thus, numerous studies have evaluated its role in cancer risk, prognosis and as an antitumor therapy in different malignancies. The following is a systematic review on the clinical evidence about the effects of metformin in cancer. Uncontrolled studies suggest that metformin is associated with reduced risk of different types of cancers among patients with hyperinsulinemia conditions, such as diabetes and obesity. However, among cancer patients, the literature is conflicting about the real impact of metformin on survival and outcomes of cancer treatments. The effects of metformin in nondiabetic patients remain unknown. Ongoing randomized trials are awaited to prove the true antineoplastic activity of metformin.
- Adjuvant chemotherapy in biliary tract cancer patients: A systematic review and meta-analysis of randomized controlled trials(2020) CAPARICA, Rafael; BRUZZONE, Marco; HACHEM, Georges El; CEPPI, Marcello; LAMBERTINI, Matteo; GLASBERG, Joao; AZAMBUJA, Evandro de; LAETHEM, Jean-Luc Van; HENDLISZ, AlainBackground: The role of adjuvant chemotherapy in biliary tract cancer is controversial. We performed a systematic review and meta-analysis to assess the effect of adjuvant chemotherapy in biliary tract cancer patients. Methods: A literature search was performed to identify randomized controlled trials (RCTs) comparing adjuvant chemotherapy versus observation, and a pooled analysis was conducted using the random-effect model. Results: Three RCTs (N = 866) were included. No difference was observed between chemotherapy and observation in terms of OS (HR 0.91; 95 %CI, 0.75-1.09; p = 0.295), whereas a significant improvement in RFS was shown (HR 0.83; 95 %CI, 0.69-0.99; p = 0.040). No subgroup that benefited most from adjuvant chemotherapy was identified, although a trend was observed in N+ patients (HR 0.83; 95 %CI, 0.65-1.08; p = 0.165). Discussion: Adjuvant chemotherapy yields a significant RFS benefit in biliary tract cancer patients and should be considered for those who are able to tolerate additional treatment after surgery.
- Regorafenib in Patients with Antiangiogenic-Naive and Chemotherapy-Refractory Advanced Colorectal Cancer: Results from a Phase IIb Trial(2019) RIECHELMANN, Rachel P.; LEITE, Luiz S.; BARIANI, Giovanni M.; GLASBERG, Joao; RIVELLI, Thomas G.; FONSECA, Leonardo Gomes da; NEBULONI, Daniela R.; I, Maria Braghiroli; QUEIROZ, Marcelo A.; ISEJIMA, Alice M.; KAPPELER, Christian; KIKUCHI, Luciana; HOFF, Paulo M.Background Regorafenib is a multikinase inhibitor with antiangiogenic effects that improves overall survival (OS) in metastatic colorectal cancer (mCRC) after failure of standard therapies. We investigated the efficacy and safety of regorafenib in antiangiogenic therapy-naive chemotherapy-refractory advanced colorectal cancer. Patients and Methods This single-center, single-arm, phase IIb study (NCT02465502) enrolled adults with mCRC whose disease had progressed on, or who were intolerant to, standard therapy, but who were antiangiogenic therapy-naive. Patients received regorafenib 160 mg once daily for 3 weeks per 4-week cycle. The primary endpoint was progression-free survival (PFS) rate at week 8. Results Of 59 treated patients, almost half had received at least four prior lines of therapy. Patients received a median of 86% of the planned dose. The week 8 PFS rate was 53% (95% confidence interval [CI], 39.1-64.3); median PFS was 3.5 months (95% CI, 1.8-3.6). Median OS was 7.4 months (95% CI, 5.3-8.9). Tumor response (RECIST version 1.1) was 2%, and metabolic response rate (criteria from the European Organisation for Research and Treatment of Cancer) was 41%. The most frequently reported regorafenib-related grade >= 3 adverse events were hypertension (36%), hand-foot skin reaction (HFSR, 25%), and hypophosphatemia (24%). There were no regorafenib-related deaths. An exploratory analysis showed that patients with grade >= 2 HFSR had longer OS (10.2 months) with regorafenib treatment versus those with grades 0-1 (5.4 months). Conclusion These findings support the antitumor activity of regorafenib in antiangiogenic-naive patients with chemotherapy-refractory mCRC. Implications for Practice The multikinase inhibitor regorafenib improved overall survival in the phase III CORRECT and CONCUR trials in heavily pretreated patients with treatment-refractory metastatic colorectal cancer (mCRC). Exploratory subgroup analysis from CONCUR suggested that regorafenib treatment prior to targeted therapy (including bevacizumab) may improve outcomes. In this single-center, single-arm phase IIb study, regorafenib demonstrated antitumor activity in 59 antiangiogenic-naive patients with chemotherapy-refractory mCRC. Further studies should assess the efficacy of regorafenib in this patient population, as well as explore the reasons behind improved outcomes among patients who had a metabolic response and those who developed hand-foot skin reaction.
- METNET: a phase II trial of metformin in patients with well-differentiated neuroendocrine tumours(2022) GLASBERG, Joao; TALANS, Aley; GIOLLO, Thomas Rivelli; RECCHIMUZZI, Debora Zachello; BEZERRA NETO, Joao Evangelista; LOPEZ, Rossana Veronica Mendonza; HOFF, Paulo Marcelo Gehm; RIECHELMANN, Rachel P.Background: Preclinical studies have suggested that metformin has anti-tumour effects, likely due to blockage of mammalian target of rapamycin pathway through adenosine monophosphate-activated protein kinase and decreased insulin levels. A retrospective study showed that metformin added to everolimus to treat type 2 diabetes mellitus offered longer progression-free survival (PFS) in patients with pancreatic neuroendocrine tumours (NET). Aim(s): To evaluate the efficacy and safety of metformin monotherapy in patients with advanced/metastatic well-differentiated NET (WD-NET) of gastroenteropancreatic (GEP) or pulmonary origin. Patients and methods: Single-arm phase II trial of metformin 850 mg PO twice daily until progression or intolerance for patients with progressive metastatic well-differentiated GEP or pulmonary NET. The primary endpoint was disease control rate (DCR) by RECIST 1.1 at 6 months. Secondary endpoints were response rate, PFS, toxicity and variations in glycaemic profiles (glycaemia, glycated haemoglobin and peptide C and insulin) at baseline, at 30 and 90 days. Results: From 2014 to 2019, 28 patients were enrolled: median age was 50 years; 84% had non-functional NET, 86% were of GEP origin and 62% had G2 NET. At the time of last follow-up, 26 patients had progression, with 13 (46%) presenting DCR at 6 months and a median PFS of 6.3 months (95% confidence interval: 3.2-9.3). There was no objective response, but one patient with refractory carcinoid syndrome had complete symptom relief, lasting for more than 5 years. Variations in glycaemic profiles were not associated with DCR at 6 months. Diarrhoea was the most common adverse event, being grade 3 or 4 in 10% of the cases. Conclusion: Metformin monotherapy offers modest anti-tumour activity in well-differentiated GEP or lung NET.
- Carbamazepine for prevention of chemotherapy-induced nausea and vomiting: a pilot study(2014) SANTANA, Thaiana Aragão; CRUZ, Felipe Melo; TRUFELLI, Damila Cristina; GLASBERG, João; DEL GIGLIO, AuroCONTEXT AND OBJECTIVE: Nausea and vomiting are major inconveniences for patients undergoing chemotherapy. Despite standard preventive treatment, chemotherapy-induced nausea and vomiting (CINV) still occurs in approximately 50% of these patients. In an attempt to optimize this treatment, we evaluated the possible effects of carbamazepine for prevention of CINV. DESIGN AND LOCATION: Prospective nonrandomized open-label phase II study carried out at a Brazilian public oncology service. METHODS: Patients allocated for their first cycle of highly emetogenic chemotherapy were continuously recruited. In addition to standard antiemetic protocol that was made available, they received carbamazepine orally, with staggered doses, from the third day before until the fifth day after chemotherapy. Considering the sparseness of evidence about the efficacy of anticonvulsants for CINV prevention, we used Simon's two-stage design, in which 43 patients should be included unless overall complete prevention was not achieved in 9 out of the first 15 entries. The Functional Living Index-Emesis questionnaire was used to measure the impact on quality of life. RESULTS: None of the ten patients (0%) presented overall complete prevention. In three cases, carbamazepine therapy was withdrawn because of somnolence and vomiting before chemotherapy. Seven were able to take the medication for the entire period and none were responsive, so the study was closed. There was no impact on the patients' quality of life. CONCLUSION: Carbamazepine was not effective for prevention of CINV and also had a deleterious side-effect profile in this population.
conferenceObject Germline mutations in Brazilian pancreatic carcinoma patients.(2020) RODRIGUES, Livia Munhoz; MAISTRO, Simone; KATAYAMA, Maria Lucia Hirata; LEITE, Luiz A. Senna; GLASBERG, Joao; RIBEIRO, Ulysses; GUINDALINI, Rodrigo Santa Cruz; FOLGUEIRA, Maria A. A. KoikeconferenceObject Quality Oncology Practice Initiative (QOPI): Preliminary results from a Brazilian academic public oncology service(2012) CUBERO, Daniel Iracema; CRUZ, Felipe Melo; MARTINS, Suelen Patricia dos Santos; GLASBERG, Joao; RIVELLI, Thomas Giollo; CAMPOS, Arinilda Silva; MATOS, Leandro Luongo; GIGLIO, Auro Del- Regorafenib in antiangiogenic-naive, chemotherapy-refractory advanced colorectal cancer: A phase IIb trial.(2018) RIECHELMANN, Rachel Pimenta; LEITE, Luiz Antonio Senna; GLASBERG, Joao; BARIANI, Giovanni Mendonca; RIVELLI, Thomas Giollo; NEBULONI, Daniela R.; PUTY, Fabiola; KAPPELER, Christian; PEREIRA, Kaline M. C.; QUEIROZ, Marcelo A.; HOFF, Paulo Marcelo
- Does chemotherapy work in reversal of malignant obstruction due to gastric cancer?(2017) SANTOS, Vanessa Montes; AZEVEDO, Renata Gondim Meira Velame; LOPEZ, Rossana Veronica Mendoza; HOFF, Paulo Marcelo; SABBAGA, Jorge; GLASBERG, Joao
- Guidelines for the management of neuroendocrine tumours by the Brazilian gastrointestinal tumour group(2017) RIECHELMANN, Rachel P.; WESCHENFELDER, Rui F.; COSTA, Frederico P.; ANDRADE, Aline Chaves; OSVALDT, Alessandro Bersch; QUIDUTE, Ana Rosa P.; SANTOS, Allan dos; HOFF, Ana Amelia O.; GUMZ, Brenda; BUCHPIGUEL, Carlos; PEREIRA, Bruno S. Vilhena; LOURENCO JUNIOR, Delmar Muniz; ROCHA FILHO, Duilio Reis da; FONSECA, Eduardo Antunes; MELLO, Eduardo Linhares Riello; MAKDISSI, Fabio Ferrari; WAECHTER, Fabio Luiz; CARNEVALE, Francisco Cesar; COURA-FILHO, George B.; PAULO, Gustavo Andrade de; GIROTTO, Gustavo Colagiovanni; BEZERRA NETO, Joao Evangelista; GLASBERG, Joao; CASALI-DA-ROCHA, Jose Claudio; REGO, Juliana Florinda M.; MEIRELLES, Luciana Rodrigues de; HAJJAR, Ludhmila; MENEZES, Marcos; BRONSTEIN, Marcello D.; SAPIENZA, Marcelo Tatit; FRAGOSO, Maria Candida Barisson Villares; PEREIRA, Maria Adelaide Albergaria; BARROS, Milton; FORONES, Nora Manoukian; AMARAL, Paulo Cezar Galvao do; MEDEIROS, Raphael Salles Scortegagna de; ARAUJO, Raphael L. C.; BEZERRA, Regis Otaviano Franca; PEIXOTO, Renata D'Alpino; AGUIAR JR., Samuel; RIBEIRO JR., Ulysses; PFIFFER, Tulio; HOFF, Paulo M.; COUTINHO, Anelisa K.Neuroendocrine tumours are a heterogeneous group of diseases with a significant variety of diagnostic tests and treatment modalities. Guidelines were developed by North American and European groups to recommend their best management. However, local particularities and relativisms found worldwide led us to create Brazilian guidelines. Our consensus considered the best feasible strategies in an environment involving more limited resources. We believe that our recommendations may be extended to other countries with similar economic standards.