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

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Agora exibindo 1 - 10 de 17
  • 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.
  • article 37 Citação(ões) na Scopus
    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.
  • article 668 Citação(ões) na Scopus
    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, Masatoshi
    Background 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.
  • article
    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, Jorge
    Sorafenib 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.
  • article 25 Citação(ões) na Scopus
    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 Pimenta
  • article 10 Citação(ões) na Scopus
    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.
  • 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