GILBERTO DE CASTRO JUNIOR
Projetos de Pesquisa
Unidades Organizacionais
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
LIM/24 - Laboratório de Oncologia Experimental, Hospital das Clínicas, Faculdade de Medicina - Líder
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conferenceObject Characterization of EGFR Activating Mutations in Brazilian Patients with Pulmonary Adenocarcinoma(2015) YEN, Cheng T.; BITTON, Rafael C.; LIMA, Luiz G. C. A. De; AMADIO, Alex V.; TAKAHASHI, Tiago K.; MARINI, Andrea M.; TAKAGAKI, Tereza Y.; TERRA, Ricardo M.; MELLO, Evandro S.; CASTRO JR., Gilberto DeconferenceObject Long term toxicities after cisplatin-based concurrent chemoradiation in head & neck squamous cell carcinoma (HNSCC) disease-free patients: A cross-sectional study(2015) RIVELLI, T. G.; SIMAO, E. F.; MAK, M. P.; MARTINS, R. Eiras; TAKAHASHI, T. K.; MARINI, A. M.; ROITBERG, F. S. R.; MESQUITA, C.; KULCSAR, M. A. V.; CASTRO JR., G.conferenceObject KEYNOTE-010: Phase 2/3 study of pembrolizumab (MK-3475) vs docetaxel for PD-L1-positive NSCLC after platinum-based therapy(2015) HERBST, R. S.; KIM, D-W.; FELIP, E.; PEREZ-GRACIA, J. L.; GARON, E. B.; HAN, J-Y.; MOLINA, J.; KIM, J-H.; GERVAIS, R.; AHN, M-J.; MAJEM, M.; FIDLER, M. J.; CASTRO JR., G. De; GARRIDO, M.; LUBINIECKI, G. M.; SHENTU, Y.; IM, E.; BAAS, P.- MicroRNA expression in saliva in locally advanced oral and oropharyngeal squamous cell carcinoma(2015) GARCIA, Fabyane Oliveira Teixeira; CONSTANTINO, Vivian Marinelli; MAK, Milena Perez; CASTRO- JR., Gilberto de; PASINI, Fatima S.
- Metronomic oral cyclophosphamide plus prednisone in docetaxel-pretreated patients with metastatic castration-resistant prostate cancer(2015) BARROSO-SOUSA, Romualdo; FONSECA, Leonardo Gomes da; SOUZA, Karla Teixeira; CHAVES, Ana Carolina Ribeiro; KANN, Ariel Galapo; CASTRO JR., Gilberto de; DZIK, CarlosWe evaluated the efficacy and safety of metronomic oral cyclophosphamide (CTX) and prednisone in metastatic castration-resistant prostate cancer (mCRPC) patients. We analyzed retrospectively patients with mCRPC previously treated with docetaxel, and who received metronomic CTX (from 50 mg PO daily to 150 mg PO, 14 days/7 days off) and prednisone 10 mg PO daily between September 2009 and April 2014 were analyzed. The primary endpoint was prostate-specific antigen (PSA) decrease >= 50 %. Secondary analysis included PSA decrease >= 30 %, time-to-treatment failure (TTF) and toxicity. Demographics and baseline characteristics were summarized using descriptive statistics. PSA response and adverse events were reported as relative rates. Kaplan-Meier estimates were calculated and plotted for time-to-event endpoints. Forty patients were evaluated. The median age was 69 years old (52-86), 12 (30.0 %) patients presented a Karnofsky performance status (KPS) of <80 %, and 34 (85 %) presented with bone with or without nodal metastases. Median pretreatment PSA was 192 ng/dL (7-2696 ng/dL). All patients were previously exposed to docetaxel, including 33 (82.5 %) with docetaxel-refractory disease. PSA response rate was achieved in eight (20.0 %) out of 40 patients. Additionally, PSA declines of >= 30 % occurred in 14 (35.0 %) patients. The median TTF was 3 months (95 % confidence interval 2.5-3.5). The treatment was well tolerated. Grade 3/4 lymphopenia was reported in 11 (27.5 %) patients and was the only grade 3-4 toxicity reported. Metronomic oral CTX showed activity and safety in docetaxel-pretreated mCRPC patients. This regimen deserves further investigation in this setting.
article 30 Citação(ões) na Scopus Cisplatin Based Chemoradiation Late Toxicities in Head and Neck Squamous Cell Carcinoma Patients(2015) RIVELLI, Thomas Giollo; MAK, Milena Perez; MARTINS, Renata Eiras; SILVA, Veronica Torres da Costa e; CASTRO JR., Gilberto deBackground: Cisplatin-based chemoradiation (CRT) offers head and neck squamous cell carcinoma (HNSCC) patients better overall survival when compared to radiation alone. However, it also increases acute and late toxicity (LT). Here we aimed to review the main aspects of diagnosis and treatment of long-term toxicities in HNSCC patients after CRT. Methods: We crossed-searched PubMed MeshTerms: Survivors, Deglutition Disorders, Xerostomia, Hypothyroidism, Cisplatin, Kidney, Hearing, and Osteoradionecrosis, with keywords: ""Head and Neck Neoplasms"" and ""Chemoradiotherapy."" A total of 5,541 publications were retrieved and 48 were selected for this systematic review. Results: Dysphagia (25%), xerostomia (40-80%, depending on the technique used), hypothyroidism (42%), ototoxicity (27%), and osteoradionecrosis (4%) were the most commonly reported LT and were related to compromised quality of life aspects in HNSCC patients. Concurrent cisplatin and higher radiation doses, especially to normal tissue, increased the rates of LT. Conclusions: Late CRT toxicities were reported mostly in retrospective studies. Addressing these adverse effects as endpoints in future clinical trials is necessary to provide tools to prevent and treat them adequately, allowing better quality of life and survival results.bookPart Evolução do tratamento do câncer(2015) MORAIS, Mauro C. Cafundó de; JúNIOR, Gilberto de Castro- Induction chemotherapy prior to surgery with or without postoperative radiotherapy for oral cavity cancer patients: Systematic review and meta-analysis(2015) MARTA, Gustavo N.; RIERA, Rachel; BOSSI, Paolo; ZHONG, Lai-ping; LICITRA, Lisa; MACEDO, Cristiane R.; CASTRO JUNIOR, Gilberto de; CARVALHO, Andre L.; WILLIAM JR., William N.; KOWALSKI, Luis PauloBackground: Locoregionally advanced oral cavity cancers are aggressive tumours with high risk of relapse after definitive treatment. This study was performed to assess the effectiveness and safety of induction chemotherapy prior to surgery for untreated oral cavity cancer patients. Material and methods: Only prospective phase III randomised studies comparing induction chemotherapy followed by surgery with or without postoperative radiotherapy (Chemo Group) compared with surgery with or without postoperative radiotherapy (Control Group) were eligible. Two of the authors independently selected and assessed the studies regarding eligibility criteria and risk of bias. Results: Two studies were selected. A total of 451 patients were randomly assigned to Chemo Group (n = 226) versus Control Group (n = 225). Most patients had tumours at clinical stages III/IV (89.1%). Both trials were classified as having low risk of bias. No significant overall benefit in favour of induction chemotherapy was found regarding loco-regional recurrence, disease-free survival and overall survival. A subgroup analysis of individual data from cN2 patients showed statistically significant overall survival benefit in favour of induction chemotherapy. The included studies did not directly compare toxicity between the groups and no statistical analysis was performed regarding safety outcomes. Conclusions: Based on the available studies, induction chemotherapy when administered before surgery with curative intent did not improve clinical outcomes in locoregionally advanced oral cavity cancer patients. Clinically assessed N2 patients might benefit from induction chemotherapy.
bookPart Câncer de cabeça e pescoço(2015) LIMA, Rafael Caires Alvino de; MAK, Milena Perez; CASTRO JUNIOR, Gilberto de- Afatinib versus methotrexate as second-line treatment in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck progressing on or after platinum-based therapy (LUX-Head & Neck 1): an open-label, randomised phase 3 trial(2015) MACHIELS, Jean-Pascal H.; HADDAD, Robert I.; FAYETTE, Jerome; LICITRA, Lisa F.; TAHARA, Makoto; VERMORKEN, Jan B.; CLEMENT, Paul M.; GAULER, Thomas; CUPISSOL, Didier; GRAU, Juan Jose; GUIGAY, Joel; CAPONIGRO, Francesco; CASTRO JR., Gilberto de; VIANA, Luciano de Souza; KEILHOLZ, Ulrich; CAMPO, Joseph M. del; CONG, Xiuyu Julie; EHRNROOTH, Eva; COHEN, Ezra E. W.Background Patients with recurrent or metastatic squamous-cell carcinoma of the head and neck (HNSCC) progressing after first-line platinum regimens have a poor prognosis and few treatment options. Afatinib, an irreversible ERBB family blocker, has shown efficacy in a phase 2 study in this setting. We aimed to assess the efficacy and safety of afatinib compared with methotrexate as second-line treatment in patients with recurrent or metastatic HNSCC progressing on or after platinum-based therapy. Methods In this open-label, phase 3, randomised controlled trial conducted in 101 centres in 19 countries, we enrolled patients aged 18 years or older with histologically or cytologically confirmed HNSCC that was recurrent, metastatic, or both who had progressed on or after first-line platinum-based therapy, were not amenable for salvage surgery or radiotherapy, and who had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Previous treatment with more than one systemic regimen in this setting was not allowed; previous treatment with EGFR-targeted antibody therapy (but not EGFR-targeted tyrosine-kinase inhibitors) was allowed. We randomly assigned eligible patients in a 2: 1 ratio to receive oral afatinib (40 mg/day) or intravenous methotrexate (40 mg/m(2) per week), stratified by ECOG performance status and previous EGFR-targeted antibody therapy for recurrent or metastatic disease. Randomisation was done centrally with an interactive voice or web-based response system. Clinicians and patients were not masked to treatment allocation; independent review of tumour response was done in a blinded manner. The primary endpoint was progression-free survival as assessed by an independent, central imaging review committee. Efficacy analyses were done in the intention-to-treat population and safety analyses were done in patients who received at least one dose of study drug. This ongoing study is registered with ClinicalTrials.gov, number NCT01345682. Findings Between Jan 10, 2012, and Dec 12, 2013, we enrolled 483 patients and randomly assigned 322 to afatinib and 161 to methotrexate. After a median follow-up of 6.7 months (IQR 3.1-9.0), progression-free survival was longer in the afatinib group than in the methotrexate group (median 2.6 months [95% CI 2.0-2.7] for the afatinib group vs 1.7 months [1.5-2.4] for the methotrexate group; hazard ratio [HR] 0.80 [95% CI 0.65-0.98], p=0.030). The most frequent grade 3 or 4 drug-related adverse events were rash or acne (31 [10%] of 320 patients in the afatinib group vs none of 160 patients in the methotrexate group), diarrhoea (30 [9%] vs three [2%]), stomatitis (20 [6%] vs 13 [8%]), fatigue (18 [6%] vs five [3%]), and neutropenia (1 [<1%] vs 11 [7%]); serious adverse events occurred in 44 (14%) of afatinib-treated patients and 18 (11%) of methotrexate-treated patients. Interpretation Afatinib was associated with significant improvements in progression-free survival and had a manageable safety profile. These findings provide important new insights into the treatment of this patient population and support further investigations with irreversible ERBB family blockers in HNSCC.