GILBERTO DE CASTRO JUNIOR

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Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/24 - Laboratório de Oncologia Experimental, Hospital das Clínicas, Faculdade de Medicina - Líder

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  • conferenceObject
    PROs With Ceritinib Versus Chemotherapy in Patients With Previously Untreated ALK-rearranged Nonsquamous NSCLC (ASCEND-4)
    (2017) TAN, Daniel Shao-Weng; SORIA, Jean-Charles; CASTRO JR., Gilberto De; WU, Yi Long; PAZ-ARES, Luis; WOLF, Juergen; GEATER, Sarayut; ORLOV, Sergey; CORTINOVIS, Diego; YU, Chong-Jen; HOCHMAIR, Maximilian; CORTOT, Alexis; TSAI, Chun-Ming; MORO-SIBILOT, Denis; CAMPELO, Rosario Garcia; BRANLE, Fabrice; SEN, Paramita; STRUEBBE, Gero; MCCULLOCH, Tracey; CRINO, Lucio
  • article 57 Citação(ões) na Scopus
    Responses to Crizotinib Can Occur in High-Level MET-Amplified Non-Small Cell Lung Cancer Independent of MET Exon 14 Alterations
    (2017) CAPARICA, Rafael; YEN, Cheng Tzu; COUDRY, Renata; IGNATIUS, Sai-Hong; VARELLA-GARCIA, Marileila; CAMIDGE, D. Ross; CASTRO JR., Gilberto de
    Activation of the MET proto-oncogene (MET) highly sensitive to MET inhibition has recently been described in NSCLC through two mechanisms: high-level amplification of the MNNG HOS Transforming gene (MET) (usually expressed relative to the chromosome 7 centromere [CEP7] when using fluorescence in situ hybridization) and exon 14 alterations. As partial overlap of these biomarkers occurs, whether one is purely a surrogate for the other or both can represent true oncogenic driver states continues to be explored. Cases of MET inhibitor-sensitive NSCLC harboring exon 14 alterations without coincident amplification have already been described. Here we report two cases of MET inhibitor-sensitive NSCLC harboring high-level MET amplification (MET/CEP7 ratio >= 5) without coincident exon 14 alterations, suggesting that these two methods of MET activation can produce independent MET-addicted states in NSCLC. Molecular profiling designed to capture all cases of potentially MET-addicted NSCLC should address both activation mechanisms.
  • article 946 Citação(ões) na Scopus
    First-line ceritinib versus platinum-based chemotherapy in advanced ALK-rearranged non-small-cell lung cancer (ASCEND-4): a randomised, open-label, phase 3 study
    (2017) SORIA, Jean-Charles; TAN, Daniel S. W.; CHIARI, Rita; WU, Yi-Long; PAZ-ARES, Luis; WOLF, Juergen; GEATER, Sarayut L.; ORLOV, Sergey; CORTINOVIS, Diego; YU, Chong-Jen; HOCHMAIR, Maximillian; CORTOT, Alexis B.; TSAI, Chun-Ming; MORO-SIBILOT, Denis; CAMPELO, Rosario G.; MCCULLOCH, Tracey; SEN, Paramita; DUGAN, Margaret; PANTANO, Serafino; BRANLE, Fabrice; MASSACESI, Cristian; CASTRO JR., Gilberto de
    Background The efficacy of ceritinib in patients with untreated anaplastic lymphoma kinase (ALK)-rearranged non-small-cell lung cancer (NSCLC) is not known. We assessed the efficacy and safety of ceritinib versus platinum-based chemotherapy in these patients. Methods This randomised, open-label, phase 3 study in untreated patients with stage IIIB/IV ALK-rearranged non-squamous NSCLC was done in 134 centres across 28 countries. Eligible patients were assigned via interactive response technology to oral ceritinib 750 mg/day or platinum-based chemotherapy ([cisplatin 75 mg/m(2) or carboplatin AUC 5-6 plus pemetrexed 500 mg/m(2)] every 3 weeks for four cycles followed by maintenance pemetrexed); randomisation was stratified by World Health Organization performance status (0 vs 1-2), previous neoadjuvant or adjuvant chemotherapy, and presence of brain metastases as per investigator's assessment at screening. Investigators and patients were not masked to treatment assignment. The primary endpoint was blinded independent review committee assessed progression-free survival, based on all randomly assigned patients (the full analysis set). Efficacy analyses were done based on the full analysis set. All safety analyses were done based on the safety set, which included all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, number NCT01828099. Findings Between Aug 19, 2013, and May 11, 2015, 376 patients were randomly assigned to ceritinib (n=189) or chemotherapy (n=187). Median progression-free survival (as assessed by blinded independent review committee) was 16.6 months (95% CI 12.6-27.2) in the ceritinib group and 8.1 months (5.8-11.1) in the chemotherapy group (hazard ratio 0.55 [95% CI 0.42-0.73]; p<0.00001). The most common adverse events were diarrhoea (in 160 [85%] of 189 patients), nausea (130 [69%]), vomiting (125 [66%]), and an increase in alanine aminotransferase (114 [60%]) in the ceritinib group and nausea (in 97 [55%] of 175 patients), vomiting (63 [36%]), and anaemia (62 [35%]) in the chemotherapy group. Interpretation First-line ceritinib showed a statistically significant and clinically meaningful improvement in progression-free survival versus chemotherapy in patients with advanced ALK-rearranged NSCLC.
  • bookPart
    Câncer de cabeça e pescoço
    (2017) LIMA, Rafael Caires Alvino de; MAK, Milena Perez; CASTRO JUNIOR, Gilberto de
  • bookPart
    Câncer de tireoide
    (2017) FONSECA, Leonardo Gomes da; HOFF, Ana Amélia O.; CASTRO JUNIOR, Gilberto de
  • conferenceObject
    Survival predictors in patients with head and neck cancer treated with surgical resection
    (2017) FRANCO, R. C. D. O.; MATOS, L. L. De; CASTRO JUNIOR, G. De; KULCSAR, M. A. V.; MARTA, G. N.
  • article 17 Citação(ões) na Scopus
    An Open-Label, Multicenter, Randomized, Phase II Study of Cisplatin and Pemetrexed With or Without Cixutumumab (IMC-A12) as a First -Line Therapy in Patients With Advanced Nonsquamous Non-Small Cell Lung Cancer
    (2017) NOVELL, Silvia; SCAGLIOTTI, Giorgio; CASTRO JR., Gilberto de; KIYIK, Murat; KOWALYSZYN, Ruben; DEPPERMANN, Karl-Matthias; ARRIOLA, Edurne; BOSQUEE, Lionel; NOVOSIADLY, Ruslan D.; NGUYEN, Tuan S.; FOREST, Amelie; TANG, Shande; KAMBHAMPATI, Siva Rama Prasad; COSAERT, Jan; RECK, Martin
    Introduction: Type 1 insulin-like growth factor receptor is deregulated in solid tumors. Cixutumumab, a monoclonal antibody that inhibits the activity of type 1 insulin-like growth factor receptor, was investigated in combination with pemetrexed/cisplatin in the frontline setting. Methods: In this open-label, phase II study, patients with stage IV nonsquamous NSCLC and a performance status of 0 to 1 were randomized (1:1) to receive 20 mg/kg cixutumumab, 500 mg/m(2) pemetrexed, and 75 mg/m(2) cisplatin (cixutumumab [n = 87]) or pemetrexed and cisplatin (control [n = 85]). Eligible patients received pemetrexed-based maintenance therapy with cixutumumab (cixutumumab arm) or without it (control arm). The primary end point was progression-free survival. Secondary end points assessed overall survival, objective response rate, and safety. Survival was analyzed by the Kaplan-Meier method and Cox proportional hazard model. Exploratory correlative analyses were also performed. Results: The mean age of the intent-to-treat population (n = 172) was 59 years (range 32-83). Median progression free survival was 5.45 months with cixutumumab versus 5.22 months in the control (hazard ratio = 1.15, 95% confidence interval: 0.81-1.61; p = 0.44). Median overall survival was 11.33 months with cixutumumab versus 10.38 months in the control (hazard ratio = 0.93, 95% confidence interval: 0.64-1.36). Objective response rate did not differ between treatments (p = 0.338). Grade 3 or 4 hyperglycemia occurred at a higher rate with cixutumumab than in the control (9.4% versus 1.2%). One death possibly related to cixutumumab occurred. Conclusions: Efficacy was not improved in patients with nonsquamous NSCLC when cixutumumab was added to pemetrexed/cisplatin. Combination therapy was well tolerated and no new safety concerns were reported. (C) 2016 International Association for the Study of Lung Cancer.
  • bookPart
    Câncer de pulmão
    (2017) FêDE, Angelo Bezerra de Souza; TAKAHASHI, Tiago Kenji; MAK, Milena Perez; CASTRO JUNIOR, Gilberto de
  • conferenceObject
    Consolidation Chemotherapy Following Concurrent Chemoradiation for Stage III Non-Small Cell Lung Cancer: A Brazilian Multicentric Cohort
    (2017) LIMA, Vladmir Cordeiro De; BALDOTTO, Clarissa; BARRIOS, Carlos; SOBRINHO, Eldsamira; ZUKIN, Mauro; MATHIAS, Clarissa; ZAFFARONI, Facundo; NERY, Rodrigo; MADEIRA, Gabriel; AMADIO, Alex; GEIB, Guilherme; COELHO, Juliano; SIMOES, Maria Fernanda; CASTRO JR., Gilberto De
  • article 5 Citação(ões) na Scopus
    Prophylactic Cranial Irradiation for Extensive-Stage Small-Cell Lung Cancer: A Retrospective Analysis
    (2017) MATUTINO, Adriana; MAK, Milena P.; TAKAHASHI, Tiago K.; BITTON, Rafael C.; NAKAZATO, Denyei; FRAILE, Natalia M. P.; GUIMARAES, Roger G. R.; GABRIELLI, Flavia C. G.; VASCONCELOS, Karina G. M. C.; CARVALHO, Heloisa de A.; CASTRO JR., Gilberto de
    Purpose Extensive-stage small-cell lung cancer (esSCLC) is an incurable disease and represents a therapeutic challenge because of its poor prognosis. Studies in prophylactic cranial irradiation (PCI) in esSCLC have shown a decreased incidence of symptomatic brain metastases in patients who respond to systemic chemotherapy. However, its effect on overall survival is debatable. We evaluated the benefit of PCI in patients with esSCLC in terms of overall survival, progression-free survival, incidence of brain metastases, recurrence rate, and exposure to postrecurrence therapies. Materials and Methods We retrospectively reviewed electronic charts from patients diagnosed with esSCLC from 2008 to 2014 at our institution. All patients had negative baseline brain imaging before chemotherapy and PCI and received at least 4 cycles of platinum-based chemotherapy in the first-line setting without progressive disease on follow-up. PCI was performed at the discretion of the treating physician. Analyses were based on descriptive statistics. Survival curves were calculated by Kaplan-Meier method. Results Among 46 eligible patients, 16 (35%) received PCI and 30 (65%) did not. Compared with no PCI, PCI led to improved progression-free survival (median, 10.32 v 7.66 months; hazard ratio, 0.4521; 95% CI, 0.2481 to 0.8237; P < .001) and overall survival (median, 20.94 v 11.05 months; hazard ratio, 0.2655; 95% CI, 0.1420 to 0.4964; P < .001) as well as lower incidence of brain metastases (19% v 53%; P = .0273) and higher exposure to second-line chemotherapy (87% v 57%; P = .0479). Conclusion Careful patient selection for PCI can improve not only brain metastases control and higher second-line chemotherapy exposure but also patient survival. (c) 2017 by American Society of Clinical Oncology