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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bookPart Câncer de tireoide(2017) FONSECA, Leonardo Gomes da; HOFF, Ana Amélia O.; CASTRO JUNIOR, Gilberto de- 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.
bookPart Câncer de tireoide(2015) FONSECA, Leonardo Gomes da; HOFF, Ana Amélia O.; CASTRO JUNIOR, Gilberto deconferenceObject Malignancy-related hypercalcemia in the bisphosphonate era(2013) ALVES, M. F. S.; MAK, M. P.; PIOTTO, G. H. M.; TAKAHASHI, T. K.; RAMOS, R. E. O.; FONSECA, L. G.; SILVINO, M.; MANO, M. S.; HOFF, P. M.; CASTRO JR., G.conferenceObject ORAL METRONOMIC CYCLOPHOSPHAMIDE IN PATIENTS WITH METASTATIC CASTRATION-RESISTANT PROSTATE CANCER STRATIFIED BY PRIOR DOCETAXEL THERAPY(2012) BARROSO-SOUSA, R.; CHAVES, A. C. R.; FONSECA, L. G.; CASTRO JR., G. De; DZIK, C.; HOFF, P. M.Background: Treatment options remain limited for patients (pts) with metastatic castration-resistant prostate cancer (mCRPC). Here we aimed to investigate the efficacy and safety of low-dose oral cyclophosphamide (CTX), an intermittent metronomic chemotherapy regimen, in pts with mCRPC, previously treated or not with docetaxel. Methods: All pts previously diagnosed with mCRPC and treated with CTX 100mg/ day (3 weeks on and 1 week off, every 28 days) plus prednisone 10mg/day between Oct/2006 and Feb/2012 at our institution were included in this retrospective analysis. The primary efficacy endpoint was prostate-specific antigen (PSA) decrease ≥ 50%. Secondary endpoints were PSA decrease ≥ 30% and toxicity. Kaplan-Meier estimates were calculated and plotted for time to treatment failure (TTF). Single and multivariate Cox proportional hazards modeling was used to estimate hazard ratios with 95% confidence intervals (95% CI). Results: 51 pts with mCRPC were identified, of which 30 (59%) had been already treated with docetaxel. The median age was 72 y.o. (56-86) and 27 pts (53%) were ECOG PS0-1 and 24 pts (47%) PS2-3. Five pts presented with visceral metastasis (10%) and median PSA 525 ng/dL (12-4099) before treatment. Median number of previous cytotoxic lines was 1 (0-2). After a median number of cycles CTX of 3, PSA decrease of ≥ 50% was achieved in 28.6% and 16.7% of docetaxel-naive and docetaxel-pretreated pts, respectively (p= 0.30). Besides, PSA declines of ≥ 30% occurred in 38.1% and 30.0% of docetaxel-naive and docetaxel-pretreated patients, respectively (p= 0.54). Overall, the median TTF was estimated to be 2.4 mo. (95% CI 1.87 – 3.73). Previously treatment with docetaxel was not statistically significant to TTF, and the median TTF was 2.1 mo. (95% CI 1.6 – 3.2) for docetaxel-pretreated and 3.4 mo. (95% CI 1.7 – 5.4) for docetaxel-naïve patients (HR 1.47; 95% CI 0.78 – 2.74; p = 0.22). In general, oral CTX was safe and well tolerated and the most commonly observed G3-4 AE was lymphopenia (29%). Conclusions: Oral metronomic CTX plus prednisone seems to be active and safe in mCRPC, even in pts previously treated with docetaxel. Its convenient oral administration, low cost, and acceptable toxicity profile may justify future investigations of this classic alkylating agent in mCRPC. Disclosure: All authors have declared no conflicts of interest.- Malignancy-Related Hypercalcemia in Advanced Solid Tumors: Survival Outcomes(2017) RAMOS, Ricardo Emanuel de Oliveira; MAK, Milena Perez; ALVES, Michel Fabiano Silva; PIOTTO, Gustavo Henrique Munhoz; TAKAHASHI, Tiago Kenji; FONSECA, Leonardo Gomes da; SILVINO, Marina Cavalcanti Maroja; HOFF, Paulo Marcelo; CASTRO JR., Gilberto dePurpose Malignancy-related hypercalcemia (MRH) is associated with a dismal prognosis. The widespread use of bisphosphonates (BPs), availability of more effective drugs in cancer treatment, and improvement in supportive care might have attenuated its impact. Patients and Methods To assess overall survival (OS) of patients with MRH in a contemporary setting, we conducted a retrospective analysis of 306 patients with solid cancer hospitalized for symptomatic hypercalcemia. A multivariable Cox proportional hazards regression model was performed to evaluate possible prognostic factors associated with MRH. Results All patients had serum ionized calcium > 5.5 mg/dL or total Ca > 10.5 mg/dL. Median age was 57 years, and the majority had squamous cell carcinoma (62%) and Eastern Cooperative Oncology Group performance status > 1 (96%). Head and neck was the most frequent primary site (28%). Forty-five percent had no previous chemotherapy (CT), and subsequent CT was administered to 32%. Eighty-three percent received BP with no survival gain. Median OS was 40 (95% CI, 33 to 47) days. Patients with a performance status > 2, altered mental status, C-reactive protein > 30 mg/L, albumin < 2.5 g/dL, or bodymass index < 18 kg/m(2) had significantly poorer survival in a univariable analysis, and longer OS was related to treatment-naive patients, subsequent CT, and breast primary site. In the multivariable analysis, subsequent CT led to a median OS improvement of 144 versus 25 days (hazard ratio, 0.24; 95% CI, 0.14 to 0.40; P <.001). Conclusion In a contemporary setting, MRH remains a marker of poor prognosis. Patients treated with CT had better survival, which suggests that appropriate treatment of selected patients might alter the course of this syndrome. (C) 2017 by American Society of Clinical Oncology Licensed under the Creative Commons Attribution 4.0 License