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
15 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 15
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.- 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.
- The Impact of Early Dermatologic Events in the Survival of Patients with Hepatocellular Carcinoma Treated with Sorafenib(2017) BRANCO, Fernanda; ALENCAR, Regiane S. M.; VOLT, Fernanda; SARTORI, Giovana; DODE, Andressa; KIKUCHI, Luciana; TANI, Claudia M.; CHAGAS, Aline L.; PFIFFER, Tulio; HOFF, Paulo; CARRILHO, Flair J.; MATTOS, Angelo Alves deBackground and Aims. The presence of dermatologic reaction as an adverse event to sorafenib treatment in patients with unresectable hepatocellular carcinoma has been indicated as a prognostic factor for survival in a recent prospective analysis. To date, this is the only clinical predictor of treatment response , which can be eavaluated earlier in the treatment and, therefore, contribute to a better and more individualized patient management. Material and methods. This retrospective study included 127 patients treated with sorafenib under real-life practice conditions in two hepatology reference centers in Brazil, Demographic data, disease/medical history and time of sorafenib administration as well as adverse events related to the medication were recorded in a database Results. Cirrhosis was present in 94% of patients, 85.6% were child-pugh A, 80.3%BCLC-C,81% had vascular invasion and/or extrahepatic spread and 95% had a performance status 0 to 1. The median duration of treatment was 10.1 months (range: 0.1-47 months). The most common adverse event within the first 60 days of treatment were diarrhea (62.2%) and dermatological reaction (42%). The median overall survival for the cohort was 20 months, and it was higher for patients who developed dermatological reactions within the first 60 days compared to those who did not present this adverse event. Conclusion. This retrospective analysis showed the use of sorafenib in patients selected according to BCLC staging, and it is the first external validation of early dermatologic adverse events as a predictor of overall survival in patients with advanced hepatocellular carcinoma.
- 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.
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 LAPAROSCOPIC MODIFIED MCCALL CULDOPLASTY FOR THE CORRECTION OF UTEROVAGINAL PROLAPSE IN PATIENTS WITH CONCOMITANT GYNECOLOGIC TUMORS(2013) FAVERO, G.; HADDAD, J.; PFIFFER, T.; RIBEIRO, A.; ARAUJO, M. Pereira; MIGLINO, G.; MANCUSI, J.; BARACAT, E.; CARVALHO, J.conferenceObject Phase II trial of inetforrnin and paclitaxel for patients with gemcitabine-refractory advanced adenocarcinoma of the pancreas(2014) FERRARI, Anezlca Carvalho Rubin De Celia; PFIFFER, Tulio Eduardo Flesch; ALEX, Alexandra Khichfy; NEBULONL, Danielle R.; CARNELRO, Allyne Q.; CAPARELL, Fernanda Cunha; LEITE, Luiz Antonio Senna; BRAGHIROLI, Maria Ignez Freitas Meiro; LOBO, Juliana; HOFF, Paulo Marcelo; RIECHELMANN, Rachel PimentaconferenceObject 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 PimentaconferenceObject Pretreatment neutrophil to lymphocyte ratio and prognosis of patients with advanced hepatocelullar carcinoma treated with sorafenib.(2014) FONSECA, Leonardo Gomes; BARROSO-SOUSA, Romualdo; BLANCO, Bruna Paccola; VALENTE, Gabriel Luls; BRAGHLROLL, Maria Ignez Freltas Melro; PFIFFER, Tullo Eduardo Flesch; SABBAGA, Jorge; HOFF, Paulo MarceloconferenceObject Predictive Biomarkers of Response in Patients with Extrapulmonary Neuroendocrine Tumors (EPNET) Treated with Platin-Based Chemotherapy(2014) REGO, J. F.; MEDEIROS, R.; I, M. Braghiroli; BEZERRA NETO, J. E.; MUNHOZ, R.; PFIFFER, T.; GALVAO, B.; SIQUEIRA, S.; HOFF, P.; RIECHELMANN, R.