LEONARDO GOMES DA FONSECA
Projetos de Pesquisa
Unidades Organizacionais
Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/07 - Laboratório de Gastroenterologia Clínica e Experimental, Hospital das Clínicas, Faculdade de Medicina
LIM/07 - Laboratório de Gastroenterologia Clínica e Experimental, Hospital das Clínicas, Faculdade de Medicina
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- Young-age onset colorectal cancer in Brazil: Analysis of incidence, clinical features, and outcomes in a tertiary cancer center(2019) SILVA, Andrea C. B.; VICENTINI, Maria Fernanda B.; MENDOZA, Elizabeth Z.; FUJIKI, Fernanda K.; FONSECA, Leonardo G. da; BRAGHIROLI, Maria Ignez F. M.; HOFF, Paulo M.Background: Recent studies report increasing incidence of colorectal cancer (CRC) in the young-age population, but data concerning clinical behavior, pathologic findings, and prognosis are controversial for this group. Early recognition of CRC in young patients is a challenge and diagnosis at advanced stage is clearly associated with worse outcomes. Materials and methods: We retrospectively reviewed medical records of 5806 patients diagnosed with CRC between January/2011 and November/2016 and identified 781 patients aged less than 50-years-old. Results: We found an absolute increasing in the incidence of CRC in patients <50 years old of 1.88%-2.23% annually, with a relative increasing of 35.3% between 2011 and 2016. Median age was 42 years, 57.4% were female and 20.9% reported family history of CRC. Left-sided tumors were more frequent and the majority of patients were symptomatic. The most common stages at diagnosis were III (34.1%) and IV (37.3%). The median overall survival (OS) for stage IV was 25 months (95% Cl 20.7-29.3) and was not reached for Stages I-III (P < 0.001). Family history of CRC was independently associated with better OS in stage IV(P= 0.02). For stages I-III, wild-type KRAS, family history of CRC, and absence of angiolymphatic invasion were associated with better OS (P.0.02, P=0.01 and P < 0.001, respectively). Conclusions: In our cohort, the incidence of early-onset CRC is increasing over the past years. Young patients were more likely to be diagnosed with metastatic disease, left-sided and/or rectum site and symptoms at presentation. These findings highlight the emerging importance of young-age onset CRC and the need to discuss strategies to early diagnosis.
- Regorafenib in Patients with Antiangiogenic-Naive and Chemotherapy-Refractory Advanced Colorectal Cancer: Results from a Phase IIb Trial(2019) RIECHELMANN, Rachel P.; LEITE, Luiz S.; BARIANI, Giovanni M.; GLASBERG, Joao; RIVELLI, Thomas G.; FONSECA, Leonardo Gomes da; NEBULONI, Daniela R.; I, Maria Braghiroli; QUEIROZ, Marcelo A.; ISEJIMA, Alice M.; KAPPELER, Christian; KIKUCHI, Luciana; HOFF, Paulo M.Background Regorafenib is a multikinase inhibitor with antiangiogenic effects that improves overall survival (OS) in metastatic colorectal cancer (mCRC) after failure of standard therapies. We investigated the efficacy and safety of regorafenib in antiangiogenic therapy-naive chemotherapy-refractory advanced colorectal cancer. Patients and Methods This single-center, single-arm, phase IIb study (NCT02465502) enrolled adults with mCRC whose disease had progressed on, or who were intolerant to, standard therapy, but who were antiangiogenic therapy-naive. Patients received regorafenib 160 mg once daily for 3 weeks per 4-week cycle. The primary endpoint was progression-free survival (PFS) rate at week 8. Results Of 59 treated patients, almost half had received at least four prior lines of therapy. Patients received a median of 86% of the planned dose. The week 8 PFS rate was 53% (95% confidence interval [CI], 39.1-64.3); median PFS was 3.5 months (95% CI, 1.8-3.6). Median OS was 7.4 months (95% CI, 5.3-8.9). Tumor response (RECIST version 1.1) was 2%, and metabolic response rate (criteria from the European Organisation for Research and Treatment of Cancer) was 41%. The most frequently reported regorafenib-related grade >= 3 adverse events were hypertension (36%), hand-foot skin reaction (HFSR, 25%), and hypophosphatemia (24%). There were no regorafenib-related deaths. An exploratory analysis showed that patients with grade >= 2 HFSR had longer OS (10.2 months) with regorafenib treatment versus those with grades 0-1 (5.4 months). Conclusion These findings support the antitumor activity of regorafenib in antiangiogenic-naive patients with chemotherapy-refractory mCRC. Implications for Practice The multikinase inhibitor regorafenib improved overall survival in the phase III CORRECT and CONCUR trials in heavily pretreated patients with treatment-refractory metastatic colorectal cancer (mCRC). Exploratory subgroup analysis from CONCUR suggested that regorafenib treatment prior to targeted therapy (including bevacizumab) may improve outcomes. In this single-center, single-arm phase IIb study, regorafenib demonstrated antitumor activity in 59 antiangiogenic-naive patients with chemotherapy-refractory mCRC. Further studies should assess the efficacy of regorafenib in this patient population, as well as explore the reasons behind improved outcomes among patients who had a metabolic response and those who developed hand-foot skin reaction.
conferenceObject Does cytotoxic chemotherapy (CT) have a role in palliative treatment of hepatocellular carcinoma (HCC)?(2018) MARTA, Guilherme Nader; FONSECA, Leonardo Gomes da; BRAGHIROLI, Maria Ignez Freitas Melro; HOFF, Paulo Marcelo; SABBAGA, JorgeconferenceObject Young-age onset colorectal cancer: Analysis of incidence, clinical features and outcomes(2017) FUJIKI, F. K.; VICENTINI, M. F. B.; SILVA, A. C. B.; ZAMBRANO, E. M.; FONSECA, L. G.; BRAGHIROLI, M. I.; SABBAGA, J.; HOFF, P. M.conferenceObject Irinotecan combined with Panitumumab or cetuximab as third-line treatment for metastatic colorectal cancer.(2022) BRAGHIROLI, Maria Ignez; VICENTINI, Maria Fernanda Batistuzzo; FONSECA, Leonardo Gomes da; SOUZA, Karla Teixeira; BONADIO, Renata Colombo; BRAGHIROLI, Oddone Freitas Melro; MATHIAS, Maria Cecilia Machado; TALANS, Aley; MENDOZA, Maria Elizabeth Zambrano; MARTINS, Juliana Goes; SABAGGA, Jorge; MONIZ, Camila Venchiarutti Motta Venchiarutti; HOFF, Paulo MarceloconferenceObject 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 Marcelo- Review on TAS-102 development and its use for metastatic colorectal cancer(2016) MOTA, Jose Mauricio; FONSECA, Leonardo G.; BRAGHIROLI, Maria Ignez; HOFF, Paulo M.TAS-102 is the combination of trifluridine (TFT) with tipiracil (TPI) in a 1:0.5 molar ratio. TFT is a fluoropyrimidine that retains cytotoxic activity in 5-fluorouracil resistant cell lines. Due to TFT short half-life, early clinical development was discouraging. Thereafter, TFT was shown to be promptly degraded by thymidine phosphorylase, also known as platelet-derived endothelial cell growth factor, a pro-angiogenic protein and a poor prognosis marker in colorectal cancer. TPI is a specific antagonist of thymidine phosphorylase and led to an increase in TFT serum levels when both agents are combined. Moreover, TPI is a potential anti-angiogenic molecule and could exert antitumor actions per se. TAS-102 was tested in several Phase I studies published in the early 21st century. The best regimen was settled as 70 mg/m(2)/day, q12 h, orally given at days 1-5 and days 8-13, each 28 days. Recently, the first Phase III trial evaluating TAS-102 in refractory colorectal cancer patients was published. The RECOURSE trial demonstrated a survival advantage of the agent over supportive care, and definitely established TAS-102 as a novel strategy in the current armamentarium against colorectal cancer. Here we review the preclinical data regarding TFT and TPI that led to the development of TAS-102, and the set of clinical data that ultimately proved that TAS-102 improved outcomes in colorectal cancer patients.
- Safety and efficacy of cytotoxic chemotherapy in hepatocellular carcinoma after first-line treatment with sorafenib(2018) FONSECA, Leonardo Gomes da; MARTA, Guilherme Nader; BRAGHIROLI, Maria Ignez Freitas Melro; CHAGAS, Aline Lopes; CARRILHO, Flair Jose; HOFF, Paulo Marcelo; SABBAGA, JorgeBackgroundBefore the targeted therapies era, cytotoxic chemotherapy (CCT) was an option for advanced hepatocellular carcinoma (HCC), even with the lack of supporting evidence. Since the last decade, sorafenib has been established as the first-line therapy. Although new agents are being incorporated, CCT is still considered in regions where new drugs are not available or for patients who progressed through the approved therapies and remain in good clinical condition. We aimed to describe our experience regarding the use of CCT as second-line treatment after sorafenib.MethodsA database of 273 patients was evaluated. Patients that received CCT after sorafenib progression were selected for the analysis. Descriptive statistics was used for categorical and continue variables. Median survival was estimated with Kaplan-Meier curves. Variables were found to be significant if the two-sided p value was 0.05 on multivariate testing using the Cox regression model.ResultsForty-five patients received CCT; 33 (73.3%) had Child-Pugh classification A, and 34 (75.6%) had stage C according to the Barcelona Clinic Liver Cancer (BCLC) staging system. The most used regimen was doxorubicin in 25 patients (55.6%). Median overall survival (OS) was 8.05 months (95% confidence interval [CI] 2.73 - 9.88 months). The 6-month and 1-year survival probability was 52.4% and 27.36%, respectively. Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1 and disease control with sorafenib was independently associated with better OS in patients treated with CCT. Any-grade toxicities were observed in 82.2% and grade 3-4 in 44.4% of the patients.ConclusionIn accordance with previous studies, CCT had a notable rate of adverse events. The poor prognosis of this cohort suggests that CCT may not alter the natural history of HCC after sorafenib progression.
conferenceObject Efficacy and safety of sorafenib (SFN) in elderly patients with hepatocellular carcinoma (HCC)(2018) FONSECA, L. Gomes Da; MARTA, G. Nader; BRAGHIROLI, M. I.; HOFF, P. M.; SABBAGA, J.- Efficacy and safety of sorafenib in elderly patients with advanced hepatocellular carcinoma(2021) MARTA, Guilherme Nader; FONSECA, Leonardo G. da; BRAGHIROLI, Maria Ignez; MOURA, Fernando; HOFF, Paulo M.; SABBAGA, JorgeOBJECTIVES: To evaluate the efficacy and safety of sorafenib in elderly patients with advanced hepatocellular carcinoma (HCC). METHODS: We analyzed data from a cohort of patients with advanced HCC treated using systemic treatment according to the local institutional protocol. Patients were divided into two groups, Group A, individuals <70 years of age, and Group B, individuals 70 years of age or older at the time of treatment initiation. Efficacy, measured based on overall survival (OS) and time to treatment failure (TTF), and toxicity were compared between groups. RESULTS: A total of 238 patients with advanced HCC who received sorafenib between 2007 and 2018 were evaluated. The median age for Group A was 59.1 years and that for Group B 73.6 years. The major prognostic characteristics were balanced between the groups. There were no significant differences in OS between Group A (8.0 months, 95%Cl 6.34-9.3) and Group B (9.0 months, 95%CI 5.38-12.62), p=0.433, or in TTF between Group A (3.0 months, 95%CI 2.39-3.60) and Group B (3.0 months, 95%CI 1.68-4.32), p=0.936. There were no significant differences between Groups A and B with respect to the incidence of adverse events or treatment discontinuation because of toxicity. CONCLUSION: Efficacy and safety of sorafenib did not differ significantly between younger and older patients with HCC. Our data suggest that age alone should not restrict clinical decision-making for patients with advanced HCC.