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
9 resultados
Resultados de Busca
Agora exibindo 1 - 9 de 9
conferenceObject Ramucirumab (RAM) as a second-line treatment in patients with advanced hepatocellular carcinoma (HCC) following first-line therapy with sorafenib in the randomized phase III REACH study: Analysis of alpha-fetoprotein (AFP) kinetics during treatment(2015) CHAU, I.; PARK, J. O.; RYOO, B. Y.; YEN, C. J.; POON, R.; PASTORELLI, D.; BLANC, J. F.; KUDO, M.; PFIFFER, T. F.; HATANO, E.; CHUNG, H. C.; KUBACKOVA, K.; PHELIP, J. M.; BRANDI, G.; OHKAWA, S.; LI, C. P.; OKUSAKA, T.; YANG, L.; ABADA, P.; ZHU, A.- Phase II trial of metformin and paclitaxel for patients with gemcitabine-refractory advanced adenocarcinoma of the pancreas(2015) BRAGHIROLI, Maria Ignez; FERRARI, Anezka C. R. de Celis; PFIFFER, Tulio Eduardo; ALEX, Alexandra Kichfy; NEBULONI, Daniela; CARNEIRO, Allyne S.; CAPARELLI, Fernanda; SENNA, Luiz; LOBO, Juliana; HOFF, Paulo Marcelo; RIECHELMANN, Rachel P.Background: In patients with adenocarcinoma of the pancreas, there are no standard second-line regimens. Many pre-clinical studies have shown that metformin alone or when combined with paclitaxel has antitumour effects on this tumour. We have tested here the combination of paclitaxel and metformin for patients with gemcitabine-refractory pancreatic cancer. Methods: An uncontrolled phase II trial was carried out based on a two-stage Simon's design, with metformin and paclitaxel for patients with locally advanced or metastatic pancreatic cancer whose disease had progressed during first line treatment with a gemcitabine-based regimen. The primary endpoint was the disease control rate at eight weeks as per response evaluation criteria in solid tumours (RECIST) 1.1. Patients received paclitaxel 80 mg/m(2) weekly for three weeks every 28 days and metformin 850 mg p.o. t.i.d. continuously until progression or intolerance state was reached. Results: Twenty patients were enrolled from July 2011 to January 2014: N = 6 (31.6%) achieved the primary endpoint, with all presenting stable disease. Median overall survival (OS) was 128 days (range 17-697) and the median progression free survival (PFS) was 44 days (range 14-210). Eight patients (40%) presented treatment-related G3-4 toxicities with the most common one being diarrhoea. Conclusions: Despite the encouraging pre-clinical evidence of the antitumour activity of metformin in adenocarcinoma of the pancreas, the primary endpoint of the disease control rate was not met. Besides, the treatment combination was poorly tolerated and could not be studied further. This study highlights the importance of performing clinical trials to reassure preclinical or observational data.
- 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.
- Safety and efficacy of sorafenib in patients with Child-Pugh B advanced hepatocellular carcinoma(2015) FONSECA, Leonardo Gomes Da; BARROSO-SOUSA, Romualdo; BENTO, Afonso Da Silva Alves; BLANCO, Bruna Paccola; VALENTE, Gabriel Luis; PFIFFER, Tulio Eduardo Flesch; HOFF, Paulo Marcelo; SABBAGA, JorgeSorafenib demonstrated a survival benefit in the treatment of advanced hepatocellular carcinoma (HCC) in phase III trials. However, almost all the patients included in those trials exhibited well-preserved liver function (Child-Pugh A). The aim of this study was to describe our experience with sorafenib in Child-Pugh B HCC patients. A database of patients with advanced HCC treated with sorafenib was retrospectively evaluated. The median overall survival of Child-Pugh B patients (n=20) was 2.53 months [95% confidence interval (CI): 0.33-5.92 months] and of Child-Pugh A patients (n=100) 9.71 months (95% CI: 6.22-13.04). Child-Pugh B patients had a significantly poorer survival compared to Child-Pugh A patients (P=0.002). The toxicities were similar between the two groups. Metastasis, vascular invasion and alpha-fetoprotein level >1,030 ng/ml were not associated with survival among Child-Pugh B patients (P=0.281, 0.189 and 0.996, respectively). Although the survival outcomes were worse in Child-Pugh B patients treated with sorafenib, the toxicity profile was manageable. Therefore, there remains the question of whether to treat this subgroup of patients and more data are required to define the role of sorafenib in the context of liver dysfunction.
conferenceObject VAGINAL MORCELLATION INSIDE PROTECTIVE POUCH AND UTERINE EXTRATION IN CASES OF BULKY ENDOMETRIAL CANCERS: REPORT OF 30 CASES(2015) FAVERO, G.; MIGLINO, G.; KOEHLER, C.; PFIFFER, T.; SILVA, A.; RIBEIRO, A.; DOGAN, N. U.; ANTON, C.; BARACAT, E.; CARVALHO, J.conferenceObject High-grade extrapulmonary neuroendocrine carcinomas and small cell lung cancer: Different entities, same treatment.(2015) REGO, Juliana Florinda De Mendonga; MEDEIROS, Raphael Salles S.; BRAGHIROLI, Maria Ignez Freitas Melro; GALVAO, Breno; BEZERRA NETO, Joao Evangelista; MUNHOZ, Rodrigo Ramella; GUERRA, Juliana Mariotti; KIMURA, Lidia; NONOGAKI, Suely; PFIFFER, Tulio Eduardo Flesch; CASTRO, Gilberto; HOFF, Paulo Marcelo; ROCHA FILHO, Duilio; COSTA, Frederico; RIECHELMANN, Rachel Pimenta- Hepatocellular Carcinoma Related to Schistosoma mansoni Infection: Case Series and Literature Review(2015) TODA, Karla Sawada; KIKUCHI, Luciana; CHAGAS, Aline Lopes; TANIGAWA, Ryan Yukimatsu; PARANAGUA-VEZOZZO, Denise Cerqueira; PFIFFER, Tulio; ROCHA, Manoel de Souza; ALVES, Venancio Avancini Ferreira; CARRILHO, Flair JoseBackground and Aims: Schistosomiasis is a major chronic disease of humans in endemic regions, and infected individuals may develop a spectrumof pathology, including hepatic fibrosis, hepatosplenomegaly, and portal hypertension. Hepatocellular carcinoma (HCC) is considered the fifth most common cancer in the world, and there is limited and controversial evidence suggesting that Schistosoma mansoni infection may be a possible risk factor for HCC. The aim of this study was to report a case series of patients with HCC and S. mansoni infection and to conduct a literature review on the topic. Methods: From January 2002 to January 2015, an institutional database was screened retrospectively to identify patients with HCC and S. mansoni infection at a single center in the Department of Gastroenterology of University of Sao Paulo School of Medicine and Hospital das Clinicas, Brazil. Results: Seven cases were included. The mean age of patients was 62.1 +/- 10.3 years; six (85.7%) were male and one (14.3%) was female. All cases had positive epidemiology, coming from endemic areas of S. mansoni infection in Brazil, and four (57.1%) had previous complications (upper gastrointestinal bleeding) related toportal hypertension or surgery intervention (splenectomy) performed more than 10 years before the HCC diagnosis. Nontumoral portal vein thrombosis was identified in five (71.4%) patients. All patients had negative serology for HCV, and four (57.1%) had positivity of HBVcore antibodies without evidence of viral replication. According to BCLC staging, one (14.3%) patient was BCLC A and received TACE instead of RFA because HCC size was >30 mm; three (42.8%) BCLC B patients received sorafenib instead of local regional treatment due to the presence of nontumoral TPV. During follow-up, all patients developed tumoral progression and died. Conclusions: It remains unclear if S. mansoni infection alone has carcinogenic potential. The available literature indicates that S. Mansoni, in the presence of HBV and HCV infections, likely acts as a cofactor for the hepatic lesion and potentiates injury.
conferenceObject Evaluation of predictive biomarkers of response and prognosis in patients with high-grade extrapulmonary neuroendocrine carcinomas treated with platin-based chemotherapy.(2015) REGO, Juliana Florinda De Mendonga; MEDEIROS, Raphael Salles S.; BRAGHIROLI, Maria Ignez Freitas Melro; BEZERRA NETO, Joao Evangelista; MUNHOZ, Rodrigo Ramella; GUERRA, Juliana Mariotti; KIMURA, Lidia; NONOGAKI, Suely; PFIFFER, Tulio Eduardo Flesch; GALVAO, Breno; HOFF, Paulo Marcelo; ROCHA FILHO, Duilio; COSTA, Frederico; RIECHELMANN, Rachel PimentaconferenceObject Ramucirumab (RAM) as second-line treatment in patients (pts) with advanced hepatocellular carcinoma (HCC): Analysis of patients with elevated alpha-fetoprotein (AFP) from the randomized phase III REACH study(2015) ZHU, Andrew X.; RYOO, Baek-Yeol; YEN, Chia-Jui; KUDO, Masatoshi; POON, Ronnie Tung-Ping; PASTORELLI, Davide; BLANC, Jean-Frederic; CHUNG, Hyun Cheol; BARON, Ari David; PFIFFER, Tulio Eduardo Flesch; OKUSAKA, Takuji; KUBACKOVA, Katerina; TROJAN, Jorg; SASTRE, Javier; CHAU, Ian; CHANG, Shao-Chun; ABADA, Paolo; YANG, Ling; HSU, Yanzhi; PARK, Joon Oh