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1.
J Gastrointest Surg ; 24(1): 19-27, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31745892

RESUMO

BACKGROUND: Postoperative chemotherapy (CMT) or chemoradiotherapy (CRT) is commonly recommended for gastric cancer (GC) patients in order to improve survival. However, some factors that prevent patients from return to intended oncologic treatment (RIOT) may increase the risk of recurrence and decrease the survival benefits achieved with curative resection. The aim of this study was to determine the frequency and factors associated with inability to RIOT and their impact on survival. METHODS: This retrospective study included stage II/III GC patients treated with potentially curative gastrectomy. Patients who could return to intended oncologic treatment (RIOT group) and those who could not (inability to RIOT group) were analyzed. RESULTS: Of the 313 eligible GC patients, 89 (28.4%) and 85 (27.2%) patients receive CRT and CMT, respectively, representing a RIOT rate of 55.6%. The main reason was attributed to general poor performance status (30.2%), followed by surgical postoperative complications (POC) (20.1%). Older age, higher ASA, D1 lymphadenectomy, and major POC were related to inability to RIOT. Older age, neutrophil-lymphocyte ratio (NLR), and major POC were independent risk factors for inability to RIOT. Five-year DFS and OS were worse for the inability to RIOT group than for the RIOT group (p = 0.008 and p = 0.004, respectively). In multivariate analyses, absence of neoadjuvant therapy, total gastrectomy, pT3/T4, pN+, and inability to RIOT were associated with worse DFS. Type of gastrectomy, lymphadenectomy, pN status, Rx resection, and RIOT group were associated with OS. CONCLUSION: Older age, high NLR, and major POC were risk factors for inability to RIOT. RIOT was an independent predictor of survival.

2.
J Glob Oncol ; 5: 1-10, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31365299

RESUMO

PURPOSE: Despite epidemiologic and molecular differences between esophageal and stomach cancers, most published studies have included patients with either disease in a metastatic scenario. We evaluated the safety and effectiveness of chemotherapy in patients with metastatic esophageal cancer in the community setting. PATIENTS AND METHODS: We performed a retrospective cohort study of patients with synchronous metastatic esophageal cancer treated at a public hospital between 2008 and 2016. Patients were grouped according to a prescribed chemotherapy protocol: platinum and taxane (group A); platinum and irinotecan (group B); platinum and fluoropyrimidine (group C); and without platinum (group D). RESULTS: Of the 1,789 patients with esophageal cancer treated, we included 397 with metastatic disease at presentation. Squamous cell carcinoma was the most frequent histology (78.8%). Median overall survival (OS) was 7 months (95% CI, 6.15 to 7.85 months). Chemotherapy was administered to 285 patients, who reached a median OS of 9.0 months (95% CI, 8.0 to 9.9 months); for 112 patients who did not receive treatment, median OS was 3 months (95% CI, 2.3 to 3.7 months; P < .001). The most used combination was platinum plus irinotecan (A; 55.5%). Disease control with in groups A, B, C, and D was 39.2%, 30.1%, 53% and 14.3%, respectively. Patients in group C reached a median OS of 17 months (95% CI, 13.1 to 20.8 months; P = .034). No differences were observed in median OS obtained with other protocols (9 months). The toxicity profile was different according to chemotherapy, with more severe events (hematologic, diarrhea, and number of days hospitalized) occurring in group B. CONCLUSION: Platinum plus paclitaxel or platinum plus irinotecan provided similar OS in community patients, although patients receiving irinotecan experienced more severe events. In the adenocarcinoma population, a fluoropyrimidine plus platinum-based regimen, although less frequently used, had a more favorable toxicity profile, with superior median OS and disease control.

3.
Am J Physiol Heart Circ Physiol ; 317(7): H1-H12, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31002284

RESUMO

The purpose of the present study was to test the hypothesis that doxorubicin (DX) and cyclophosphamide (CY) adjuvant chemotherapy (CHT) acutely impairs neurovascular and hemodynamic responses in women with breast cancer. Sixteen women (age: 47.0 ± 2.0 yr; body mass index: 24.2 ± 1.5 kg/m) with stage II-III breast cancer and indication for adjuvant CHT underwent two experimental sessions, saline (SL) and CHT. In the CHT session, DX (60 mg/m2) and CY (600 mg/m2) were administered over 45 min. In the SL session, a matching SL volume was infused in 45 min. Muscle sympathetic nerve activity (MSNA) from peroneal nerve (microneurography), calf blood flow (CBF; plethysmography) and calf vascular conductance (CVC), heart rate (HR; electrocardiography), and beat-to-beat blood pressure (BP; finger plethysmography) were measured at rest before, during, and after each session. Venous blood samples (5 ml) were collected before and after both sessions for assessment of circulating endothelial microparticles (EMPs; flow cytometry), a surrogate marker for endothelial damage. MSNA and BP responses were increased (P < 0.001), whereas CBF and CVC responses were decreased (P < 0.001), during and after CHT session when compared with SL session. Interestingly, the vascular alterations were also observed at the molecular level through an increased EMP response to CHT (P = 0.03, CHT vs. SL session). No difference in HR response was observed (P > 0.05). Adjuvant CHT with DX and CY in patients treated for breast cancer increases sympathetic nerve activity and circulating EMP levels and, in addition, reduces muscle vascular conductance and elevates systemic BP. These responses may be early signs of CHT-induced cardiovascular alterations and may represent potential targets for preventive interventions. NEW & NOTEWORTHY It is known that chemotherapy regimens increase the risk of cardiovascular events in patients treated for cancer. Here, we identified that a single cycle of adjuvant chemotherapy with doxorubicin and cyclophosphamide in women treated for breast cancer dramatically increases sympathetic nerve activity and circulating endothelial microparticle levels, reduces the muscle vascular conductance, and elevates systemic blood pressure.

5.
J Gastrointest Cancer ; 50(4): 860-866, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30175393

RESUMO

PURPOSE: Advanced pancreatic adenocarcinoma (PA) is an aggressive disease that has poor prognosis and frequently interferes with patient's quality of life. There has been progress in first-line regimens; however, there is no standard second-line regimen. The aim of this study is to analyze second-line gemcitabine after first-line fluorouracil (FU) + leucovorin (LV) + irinotecan + oxaliplatin (FOLFIRINOX) regimen. METHODS: This study included consecutive patients with advanced PA treated at Hospital Sirio-Libanês from 2011 to 2016. The patients received FOLFIRINOX as first-line treatment and upon progression, received gemcitabine alone. Survival analysis was performed using the Kaplan-Meier method. RESULTS: A total of 54 patients were evaluated. Most patients were male (61.1%) and most had an ECOG performance status of 0 or 1 prior to the beginning of second-line treatment (66.6%). The mean number of gemcitabine cycles was 3.4. Most patients had disease progression as the best response to treatment (75.9%), 11.1% had stable disease, and 9.3% experienced a partial response. The median progression-free survival was 1.7 months, and the median overall survival was 6.8 months. CONCLUSIONS: Gemcitabine alone did not show meaningful clinical benefit as second-line treatment after FOLFIRINOX.

7.
BMC Cancer ; 18(1): 1250, 2018 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-30545331

RESUMO

BACKGROUND: Before 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. METHODS: A 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. RESULTS: Forty-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. CONCLUSION: In 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.


Assuntos
Antineoplásicos/administração & dosagem , Carcinoma Hepatocelular/tratamento farmacológico , Citotoxinas/administração & dosagem , Neoplasias Hepáticas/tratamento farmacológico , Sorafenibe/administração & dosagem , Adolescente , Adulto , Idoso , Antineoplásicos/efeitos adversos , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/mortalidade , Citotoxinas/efeitos adversos , Bases de Dados Factuais/tendências , Feminino , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Sorafenibe/efeitos adversos , Taxa de Sobrevida/tendências , Resultado do Tratamento , Adulto Jovem
8.
BMC Cancer ; 18(1): 378, 2018 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-29614980

RESUMO

BACKGROUND: Treatment of localized gastric cancer (LGC) consists of surgical resection followed by adjuvant treatment. Both chemoradiation (CRT) and chemotherapy (CT) regimens have shown benefit in survival outcomes versus observation. However, there are few data comparing these approaches. METHODS: This study included consecutive patients with LGC treated at Instituto do Cancer do Estado de Sao Paulo (ICESP) from 2012 to 2015. CRT was based on the INT-0116 regimen and CT consisted of a platinum and fluoropyrimidine doublet. Treatment choice was based on physician preference. Toxicity was evaluated for every cycle. Overall survival (OS) analysis was performed by Kaplan-Meier. A propensity score-matched analysis was performed to minimize selection bias. RESULTS: A total of 309 patients were evaluated, 227 in CRT group and 82 in CT group. The most prevalent grade 3/4 toxicities in CRT and CT groups were: nausea/vomiting (9.25 vs 4.9%), fatigue (9.3% vs 2.4%), mucositis (4.4% vs 1.2%), neutropenia (37.8% vs 20.9%), febrile neutropenia (3.9% vs 0%), anemia (4.3% vs 6.1%), thrombocytopenia (2.6% vs 4.9%), neuropathy (0 vs 2.4%) and hand-foot syndrome (0.4% vs 2.4%). Two grade 5 toxicities (febrile neutropenia and anemia) occurred in CRT group. There was no difference in the pattern of recurrence. After a median follow-up of 23.5 months (CRT) and 20.6 months (CT), there was no difference in OS between groups. CONCLUSIONS: CT and CRT present similar efficacy and tolerability as adjuvant treatment for LGC.


Assuntos
Quimiorradioterapia Adjuvante , Quimioterapia Adjuvante , Neoplasias Gástricas/patologia , Neoplasias Gástricas/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimiorradioterapia Adjuvante/efeitos adversos , Quimiorradioterapia Adjuvante/métodos , Quimioterapia Adjuvante/efeitos adversos , Quimioterapia Adjuvante/métodos , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Pontuação de Propensão , Modelos de Riscos Proporcionais , Recidiva , Estudos Retrospectivos , Neoplasias Gástricas/mortalidade , Resultado do Tratamento
9.
J Am Coll Cardiol ; 71(20): 2281-2290, 2018 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-29540327

RESUMO

BACKGROUND: Anthracycline (ANT) chemotherapy is associated with cardiotoxicity. Prevention with ß-blockers remains controversial. OBJECTIVES: This prospective, randomized, double-blind, placebo-controlled study sought to evaluate the role of carvedilol in preventing ANT cardiotoxicity. METHODS: The authors randomized 200 patients with HER2-negative breast cancer tumor status and normal left ventricular ejection fraction (LVEF) referred for ANT (240 mg/m2) to receive carvedilol or placebo until chemotherapy completion. The primary endpoint was prevention of a ≥10% reduction in LVEF at 6 months. Secondary outcomes were effects of carvedilol on troponin I, B-type natriuretic peptide, and diastolic dysfunction. RESULTS: Primary endpoint occurred in 14 patients (14.5%) in the carvedilol group and 13 patients (13.5%) in the placebo group (p = 1.0). No differences in changes of LVEF or B-type natriuretic peptide were noted between groups. A significant difference existed between groups in troponin I levels over time, with lower levels in the carvedilol group (p = 0.003). Additionally, a lower incidence of diastolic dysfunction was noted in the carvedilol group (p = 0.039). A nonsignificant trend toward a less-pronounced increase in LV end-diastolic diameter during the follow-up was noted in the carvedilol group (44.1 ± 3.64 mm to 45.2 ± 3.2 mm vs. 44.9 ± 3.6 mm to 46.4 ± 4.0 mm; p = 0.057). CONCLUSIONS: In this largest clinical trial of ß-blockers for prevention of cardiotoxicity under contemporary ANT dosage, the authors noted a 13.5% to 14.5% incidence of cardiotoxicity. In this scenario, carvedilol had no impact on the incidence of early onset of LVEF reduction. However, the use of carvedilol resulted in a significant reduction in troponin levels and diastolic dysfunction. (Carvedilol Effect in Preventing Chemotherapy-Induced Cardiotoxicity [CECCY]; NCT01724450).


Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Antineoplásicos/efeitos adversos , Cardiotoxicidade/diagnóstico por imagem , Cardiotoxicidade/prevenção & controle , Carvedilol/uso terapêutico , Adulto , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/epidemiologia , Cardiotoxicidade/epidemiologia , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos
12.
J Glob Oncol ; 3(6): 728-733, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29244985

RESUMO

Purpose 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 body mass index < 18 kg/m2 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.


Assuntos
Hipercalcemia/etiologia , Neoplasias/complicações , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/mortalidade , Prognóstico , Análise de Sobrevida , Adulto Jovem
13.
Ecancermedicalscience ; 11: 767, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28955403

RESUMO

BACKGROUND: Small cell lung cancer (SCLC) and high-grade extrapulmonary neuroendocrine carcinomas (EPNEC) share similar histopathological features and treatment, but outcomes may differ. We evaluated in our study the expression of biomarkers associated with response rate (RR) to chemotherapy and overall survival (OS) for these entities. MATERIALS AND METHODS: This is a multicentre retrospective analysis of advanced EPNEC and SCLC patients treated with platinum-based chemotherapy. Paraffin-embedded tumour samples were reviewed by a single pathologist and tested for immunohistochemistry (IHC) expression of Ki-67, ERCC1, Bcl-2, and Lin28a. All images were evaluated by the same radiologist and RR was determined by RECIST 1.1. RESULTS: From July, 2006 to July, 2014, 142 patients were identified, being 82 (57.7%) SCLC and 60 (42.3%) EPNEC. Clinical characteristics and median Ki-67 (SCLC: 60%; EPNEC: 50%; p = 0.86) were similar between the groups. RR was higher for SCLC patients (86.8% versus 44.6%; p<0.001), but median OS was similar (10.3 months in SCLC and 11.1 months in EPNEC; HR 0.69, p = 0.07). Bcl-2 expression was higher in SCLC patients (46.3% versus 28.3%, p = 0.03) and was associated with worse prognosis in EPNEC (median OS 8.0 months versus 14.7 months; HR 0.47, p = 0.02). CONCLUSION: EPNEC patients presented inferior RR to platinum-based chemotherapy than SCLC but tended to live longer. Neither ERCC1, Lin28, or Ki-67 were prognostic or predictive for RR in EPNEC or SCLC. High Bcl-2 expression was associated with poor prognosis in EPNEC patients.

14.
J Glob Oncol ; 3(1): 15-22, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28717737

RESUMO

BACKGROUND: Venous thromboembolic events (VTEs) are common and potentially fatal complications in cancer patients, and they are responsible for the second most common cause of death. Low molecular weight heparin (LMWH) is the gold-standard treatment, but the costs involved limit its use, especially in developing countries. Recently, the oral anticoagulant rivaroxaban, which directly inhibits factor Xa, was approved for VTE treatment. METHODS: We conducted a retrospective analysis from January 2009 to February 2014 with patients who had cancer and VTE who were receiving rivaroxaban. We compared the efficacy, safety, and cost of rivaroxaban and low molecular weight heparin (LMWH) alone or followed by vitamin K antagonists. RESULTS: Forty-one patients were identified, with a median age of 62.5 years. The most frequent tumor histology was adenocarcinoma (78%), which was most often found in the colon (26.8%). Most participants had advanced disease and an implanted central venous catheter. Patients' VTE risk-assessment scores were low (12.5%), intermediate (50%), and high (35.5%). Pulmonary thromboembolism was reported in 41.4% of patients, but inferior limb thrombosis was reported only in 14.6%; 43.9% of patients received enoxaparin before starting rivaroxaban. Rivaroxaban was used for a median time of 5.5 months. Nonmajor bleeding was reported in 12.2% of patients, and rethrombosis was reported in 12.2%. In our study, rivaroxaban was as safe and effective as enoxaparin/vitamin K antagonists (P = .54 and P = .25, respectively) or LMWH (P = .46 and P = .29, respectively). CONCLUSION: Although our study was a retrospective analysis, our results suggest that in this cohort of oncologic patients, rivaroxaban was safe and effective. Its oral route and lower cost make it an attractive alternative to LMWH, improving management of patients with cancer in low-income countries. Additional studies are necessary to confirm our data.

15.
J Gastrointest Cancer ; 47(1): 75-81, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26691173

RESUMO

UNLABELLED: This was a phase II study of capecitabine in substitution of 5-fluorouracil (5-FU) in the chemoradiotherapy regimen for patients with localized squamous cell carcinoma of the anal canal. BACKGROUND: Combined chemoradiation with infusional 5-FU and mitomycin is the standard treatment for localized squamous cell carcinoma (SCC) of the anal canal. Capecitabine is an oral fluoropirimidine that has been shown to be equally effective to 5-FU in many solid tumors. However, the efficacy of the substitution of 5-FU for capecitabine in anal SCC needs confirmation. METHODS: Patients with SCC of anal cancer T2-4N0M0 or T (any) N1-3M0, with good performance status and normal blood and renal function, were treated with capecitabine 825 mg/m(2) bid during radiotherapy associated with a single dose of mitomycin 15 mg/m(2) on day 1. The primary objective was local control rate at 6 months determined by clinical examination and radiological assessment. Sample size was calculated using the Fleming single-stage design. RESULTS: From November 2010 to February 2014, N = 51 patients were initially included; however, 43 patients were assessed. Seventeen patients (39.5%) were stage II, 11 patients (25.6%) stage IIIA, and 15 patients (34.9%) stage IIIB. Four patients (9.3%) were HIV positive. With a median follow-up of 23.1 months (range 4 to 44.4 months), 3 patients (7%) presented partial response, 37 (86%) had complete response, and 3 patients developed progression of the disease (7%) at 6 months. The colostomy rate was 18.6%. It was observed a locoregional control of 86% in 6 months (CI 95% 0.72-0.94). The main grade 3-4 toxicities were grade 3 radiodermitis in 10 patients (23.2%), grade 3 lymphopenia in 5 patients (11.6%), and grade 3 neutropenia in 2 patients (6.9%). One HIV-positive patient had septic shock, pneumonia, herpetic encephalitis, atrial fibrillation, and macrophage activation syndrome. CONCLUSIONS: Capecitabine can safely substitute infusional 5-FU in the standard chemoradiation regimen for SCC of the anal cancer, with a locoregional control of 86% in 6 months (CI 95% 0.72-0.94).


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Ânus/terapia , Carcinoma de Células Escamosas/terapia , Quimiorradioterapia , Recidiva Local de Neoplasia/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Ânus/patologia , Capecitabina/administração & dosagem , Carcinoma de Células Escamosas/patologia , Cisplatino/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Mitomicina/administração & dosagem , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Prognóstico , Indução de Remissão , Taxa de Sobrevida
16.
Thyroid ; 26(3): 414-9, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26701095

RESUMO

BACKGROUND: Treatment of advanced medullary thyroid carcinoma (MTC) was recently improved with the approval of vandetanib and cabozantinib. However, there is still a need to explore sequential therapy with more than one tyrosine kinase inhibitor (TKI) and to explore alternative therapies when vandetanib and cabozantinib are not available. This study reports the authors' experience with sorafenib as a treatment for advanced MTC. METHODS: This is a retrospective longitudinal study of 13 patients with progressive metastatic MTC treated with sorafenib 400 mg twice daily between December 2011 and January 2015. The primary endpoints were to evaluate response and progression-free survival (PFS) in patients treated with sorafenib outside a clinical trial. The secondary endpoint was an assessment of the toxicity profile. One patient was excluded because of a serious allergic skin rash one week after starting sorafenib. RESULTS: The analysis included 12 patients with metastatic MTC (median age 48 years), 10 with sporadic and 2 with hereditary disease. The median duration of treatment was 11 months, and the median follow-up was 15.5 months. At data cutoff, 2/12 (16%) patients were still on treatment for 16 and 34 months. According to Response Evaluation Criteria in Solid Tumors analysis, 10 (83.3%) patients showed stable disease, and two (16.6%) had progression of disease; no partial response was observed. The median PFS was nine months. However, three patients with extensive and rapidly progressive disease died within three months of sorafenib treatment. The median PFS excluding these three patients was 12 months. Adverse events (AE) occurred in nine (75%) patients. The main AEs were skin toxicity, weight loss, and fatigue. Five (41.6%) patients needed dose reduction, and one patient discontinued treatment because of toxicity. CONCLUSIONS: Treatment with sorafenib in progressive metastatic MTC is well tolerated and resulted in disease control and durable clinical benefit in 75% of patients. Sorafenib treatment could be considered when vandetanib and cabozantinib are not available or after failing these drugs.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Neuroendócrino/tratamento farmacológico , Niacinamida/análogos & derivados , Compostos de Fenilureia/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Neoplasias da Glândula Tireoide/tratamento farmacológico , Adulto , Idoso , Antineoplásicos/efeitos adversos , Carcinoma Neuroendócrino/enzimologia , Carcinoma Neuroendócrino/mortalidade , Carcinoma Neuroendócrino/secundário , Progressão da Doença , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Niacinamida/efeitos adversos , Niacinamida/uso terapêutico , Compostos de Fenilureia/efeitos adversos , Inibidores de Proteínas Quinases/efeitos adversos , Estudos Retrospectivos , Sorafenibe , Neoplasias da Glândula Tireoide/enzimologia , Neoplasias da Glândula Tireoide/mortalidade , Neoplasias da Glândula Tireoide/patologia , Fatores de Tempo , Resultado do Tratamento
17.
Autops Case Rep ; 5(2): 55-9, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26484336

RESUMO

Acquired hemophilia A (AHA) is a rare disorder that results from the presence of autoantibodies against the clotting factor VIII (FVIII) causing hemorrhagic disorders. This entity is mostly associated with autoimmune diseases, pregnancy, the postpartum period, drugs and malignancy. Among the solid cancers, prostate neoplasm is the most common cause of AHA. The management of AHA involves the control of active bleeding and the use of specific therapies to eliminate the inhibitor. The authors describe the case of an 87-year-old man with prostate cancer who developed a bleeding disorder 5 years after the cancer diagnosis. Treatment with prednisone did not reach a satisfactory clinical response, which was only achieved with the association of azathioprine. The patient became asymptomatic with no further bleeding episodes, but developed a fatal sepsis after 3 months of treatment with these immunosuppressive agents.

18.
Ecancermedicalscience ; 9: 563, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26316884

RESUMO

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.

19.
Mol Clin Oncol ; 3(4): 793-796, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26171182

RESUMO

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 α-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.

20.
Eur J Obstet Gynecol Reprod Biol ; 192: 86-9, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26182837

RESUMO

BACKGROUND: Cervical cancer (CC) is the second most common cancer in Brazilian women, and approximately 10% of cases occur in elderly patients (pts). In this age group, disease is usually diagnosed in more advanced stages and oncological therapies are usually less intensive, due to comorbidities and impaired performance status. METHODS: Retrospective analysis of pts ≥65 years old with CC admitted at a Brazilian University Cancer Center from August 2008 to February 2012. We performed a descriptive analysis of baseline performance status (PS), disease stage (FIGO), histology, body mass index (BMI), treatment received and overall survival, using the Kaplan-Meier method. RESULTS: 900 medical records were analyzed and 75 pts (8%) fulfilled the inclusion criteria. Median age was 73.4 years old (±5.5 years). Squamous cell carcinoma (SCC) was the most common histology (71 pts, 94.7%). 67 (89.3%) had PS 0 or 1 and 52 pts (69.3%) were eutrophic (BMI 18.5-25 kg/m(2)). At presentation, disease staging consisted of 18 pts (24%) stage I, 35 pts (46.7%) stage II, 8 pts (10.7%) stage III, 12 pts (16%) stage IVa and 2 pts (2.7%) stage IVb. 24 pts (32%) underwent surgery (hysterectomy, adnexectomy, pelvic and paraaortic lymphadenectomy). Adjuvant treatment with radiotherapy (RT) was performed in 13 pts (total dose of external RT in pelvis ranged from 39.6 to 45 Gy, parametrial boost ranged from 14 to 20 Gy and 4 inserts from 7 to 7.5 Gy of brachytherapy); 8 of them received concomitant platinum-based chemotherapy (CT). 30 pts underwent definitive CRT, 17 definitive RT, 1 palliative CT and 3 best supportive care. In the CRT group, 18 pts received cisplatin (CDDP 40 mg/m(2)/w/6w) and 12 carboplatin (AUC 2/w/6w). During definitive CRT, treatment was discontinued in 39% of pts who received CDDP and 25% of pts who received carboplatin, all due to treatment toxicities. CDDP was associated with more nefrotoxicity (5 pts, 28%) than carboplatin (1 pt, 8.3%). The CDDP group also presented more radiodermatitis and stroke. However, myelosuppression and diarrhea were similar in both groups. After a 26.1-month follow-up, median OS was not reached. CONCLUSIONS: Despite advanced age, more than 60% of pts underwent complete CRT treatment. Thus, age should not be the only factor to guide therapeutic decisions in CC. Carboplatin was better tolerated than CDDP in CRT group, but prospective trials are necessary to evaluate the best treatment option in this population.


Assuntos
Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Quimiorradioterapia , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/terapia , Lesão Renal Aguda/induzido quimicamente , Fatores Etários , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Quimiorradioterapia/efeitos adversos , Quimiorradioterapia/métodos , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Feminino , Nível de Saúde , Humanos , Histerectomia , Estadiamento de Neoplasias , Ovariectomia , Radiodermatite/etiologia , Dosagem Radioterapêutica , Radioterapia Adjuvante , Estudos Retrospectivos , Salpingectomia , Acidente Vascular Cerebral/etiologia , Taxa de Sobrevida
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