TULIO EDUARDO FLESCH PFIFFER
Índice h a partir de 2011
9
Projetos de Pesquisa
Unidades Organizacionais
Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas, Faculdade de Medicina - Médico
5 resultados
Resultados de Busca
Agora exibindo 1 - 5 de 5
- Ramucirumab versus placebo as second-line treatment in patients with advanced hepatocellular carcinoma following first-line therapy with sorafenib (REACH): a randomised, double-blind, multicentre, phase 3 trial(2015) ZHU, Andrew X.; PARK, Joon Oh; RYOO, Baek-Yeol; YEN, Chia-Jui; POON, Ronnie; PASTORELLI, Davide; BLANC, Jean-Frederic; CHUNG, Hyun Cheol; BARON, Ari D.; PFIFFER, Tulio Eduardo Flesch; OKUSAKA, Takuji; KUBACKOVA, Katerina; TROJAN, Jorg; SASTRE, Javier; CHAU, Ian; CHANG, Shao-Chun; ABADA, Paolo B.; YANG, Ling; SCHWARTZ, Jonathan D.; KUDO, MasatoshiBackground VEGF and VEGF receptor-2-mediated angiogenesis contribute to hepatocellular carcinoma pathogenesis. Ramucirumab is a recombinant IgG1 monoclonal antibody and VEGF receptor-2 antagonist. We aimed to assess the safety and efficacy of ramucirumab in advanced hepatocellular carcinoma following first-line therapy with sorafenib. Methods In this randomised, placebo-controlled, double-blind, multicentre, phase 3 trial (REACH), patients were enrolled from 154 centres in 27 countries. Eligible patients were aged 18 years or older, had hepatocellular carcinoma with Barcelona Clinic Liver Cancer stage C disease or stage B disease that was refractory or not amenable to locoregional therapy, had Child-Pugh A liver disease, an Eastern Cooperative Oncology Group performance status of 0 or 1, had previously received sorafenib (stopped because of progression or intolerance), and had adequate haematological and biochemical parameters. Patients were randomly assigned (1:1) to receive intravenous ramucirumab (8 mg/kg) or placebo every 2 weeks, plus best supportive care, until disease progression, unacceptable toxicity, or death. Randomisation was stratified by geographic region and cause of liver disease with a stratified permuted block method. Patients, medical staff, investigators, and the funder were masked to treatment assignment. The primary endpoint was overall survival in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT01140347. Findings Between Nov 4, 2010, and April 18, 2013, 565 patients were enrolled, of whom 283 were assigned to ramucirumab and 282 were assigned to placebo. Median overall survival for the ramucirumab group was 9.2 months (95% CI 8.0-10.6) versus 7.6 months (6.0-9.3) for the placebo group (HR 0.87 [95% CI 0.72-1.05]; p=0.14). Grade 3 or greater adverse events occurring in 5% or more of patients in either treatment group were ascites (13 [5%] of 277 patients treated with ramucirumab vs 11 [4%] of 276 patients treated with placebo), hypertension (34 [12%] vs ten [4%]), asthenia (14 [5%] vs five [2%]), malignant neoplasm progression (18 [6%] vs 11 [4%]), increased aspartate aminotransferase concentration (15 [5%] vs 23 [8%]), thrombocytopenia (13 [5%] vs one [<1%]), hyperbilirubinaemia (three [1%] vs 13 [5%]), and increased blood bilirubin (five [2%] vs 14 [5%]). The most frequently reported (>= 1%) treatment-emergent serious adverse event of any grade or grade 3 or more was malignant neoplasm progression. Interpretation Second-line treatment with ramucirumab did not significantly improve survival over placebo in patients with advanced hepatocellular carcinoma. No new safety signals were noted in eligible patients and the safety profile is manageable.
- Alpha-fetoprotein kinetics in patients with hepatocellular carcinoma receiving ramucirumab or placebo: an analysis of the phase 3 REACH study(2018) CHAU, Ian; PARK, Joon Oh; RYOO, Baek-Yeol; YEN, Chia-Jui; POON, Ronnie; PASTORELLI, Davide; BLANC, Jean-Frederic; KUDO, Masatoshi; PFIFFER, Tulio; HATANO, Etsuro; CHUNG, Hyun Cheol; KOPECKOVA, Katerina; PHELIP, Jean-Marc; BRANDI, Giovanni; OHKAWA, Shinichi; LI, Chung-Pin; OKUSAKA, Takuji; HSU, Yanzhi; ABADA, Paolo B.; ZHU, Andrew X.BACKGROUND: Post-hoc analyses of AFP response and progression and their relationship with objective measures of response and survival were performed in patients from REACH. METHODS: Serum AFP was measured at baseline and every 3 cycles (2 weeks/cycle). Associations between AFP and radiographic progression and efficacy end points were analysed. RESULTS: Median percent AFP increase from baseline was smaller in the ramucirumab than in the placebo arm throughout treatment. Time to AFP progression (HR 0.621; P < 0.0001) and to radiographic progression (HR 0.613; P < 0.0001) favoured ramucirumab. Association between AFP and radiographic progression was shown at 6 (OR 6.44, 95% CI 4.03, 10.29; P < 0.0001) and 12 weeks (OR 2.28, 95% CI 1.47, 3.53; P = 0.0002). AFP response was higher with ramucirumab compared with placebo (P < 0.0001). More patients in the ramucirumab arm experienced tumour shrinkage and AFP response compared with placebo. Survival was longer in patients with AFP response (13.6 months) than in patients without (6.2 months), irrespective of treatment (HR 0.457, P < 0.0001). CONCLUSIONS: Treatment with ramucirumab prolonged time to AFP progression, slowed AFP increase and was more likely to induce AFP response. Similar benefits in radiographic progression and response correlated with AFP changes.
- Validation of questionnaire on the Spiritual Needs Assessment for Patients (SNAP) questionnaire in Brazilian Portuguese(2016) TOLOI, Diego de Araujo; UEMA, Deise; MATSUSHITA, Felipe; ANDRADE, Paulo Antonio da Silva; BRANCO, Tiago Pugliese; CHINO, Fabiana Tomie Becker de Carvalho; GUERRA, Raquel Bezerra; PFIFFER, Tulio Eduardo Flesch; CHIBA, Toshio; GUINDALINI, Rodrigo Santa Cruz; SULMASY, Daniel P.; RIECHELMANN, Rachel P.Objectives: Spirituality is related to the care and the quality of life of cancer patients. Thus, it is very important to assess their needs. The objective of this study was the translation and cultural adjustment of the Spiritual Needs Assessment for Patients ( SNAP) questionnaire to the Brazilian Portuguese language. Methodology: The translation and cultural adjustment of the SNAP questionnaire involved six stages: backtranslation, revision of backtranslation, translation to the original language and adjustments, pre-test on ten patients, and test and retest with 30 patients after three weeks. Adult patients, with a solid tumour and literate with a minimum of four years schooling were included. For analysis and consistency we used the calculation of the Cronbach alpha coefficient and the Pearson linear correlation. Results: The final questionnaire had some language and content adjustments compared to the original version in English. The correlation analysis of each item with the total score of the questionnaire showed coefficients above 0.99. The calculation of the Cronbach alpha coefficient was 0.9. The calculation of the Pearson linear correlation with the test and retest of the questionnaire was equal to 0.95. Conclusion: The SNAP questionnaire translated into Brazilian Portuguese is adequately reliable and consistent. This instrument allows adequate access to spiritual needs and can help patient care.
- 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.
- Pre-treatment neutrophil-to-lymphocyte ratio affects survival in patients with advanced hepatocellular carcinoma treated with sorafenib(2014) FONSECA, Leonardo Gomes da; BARROSO-SOUSA, Romulado; BENTO, Afonso da Silva Alves; BLANCO, Bruna Paccola; VALENTE, Gabriel Luis; PFIFFER, Tulio Eduardo Flesch; HOFF, Paulo Marcelo; SABBAGA, JorgeSorafenib is the first systemic therapy to demonstrate survival benefit in advanced hepatocellular carcinoma (HCC) in randomized controlled trials with rigorous patient selection. Neutrophil-to-lymphocyte ratio (NLR) has been shown to be associated with poor survival in various solid tumors. Our aim is to evaluate the prognostic role of NLR in HCC patients treated with sorafenib. A total of 105 advanced HCC patients treated with sorafenib were retrospectively reviewed, and relevant data from the clinical records were collected. Univariate and multivariate analysis were carried out to identify factors associated with survival. The median age of the cohort was 59.7 years, and 84.8 % were Child-Pugh class A, and 86.7 % had ECOG performance status 0 or 1. Median duration of sorafenib treatment was 100 days. Median overall survival (OS) of the entire cohort was 8.03 months. Median OSwas 5.23 months (95 % CI 2.96-7.50 months) and 10.05 months (95 % IC 2.52-18.47 months) for patients with NLR>3.5 and NLR <= 3.5, respectively (p = 0.002). Alpha-fetoprotein [1,030 ng/mL and serum albumin B3.8 g/dL were also associated with worse prognosis (p = 0.006 and p = 0.042, respectively). The subgroup of patients with high alpha-fetoprotein, low albumin and NLR>3.5 had median OS of 1.7 months, whereas the subgroup with none of these parameters had median OS of 16.5 months (p< 0.001). NLR affects survival in advanced HCC patients treated with sorafenib. Selecting HCC patients based on the laboratorial features may improve the therapeutic effectiveness of sorafenib.