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1.
Medicine (Baltimore) ; 99(5): e19077, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32000459

RESUMO

Retinal arterial macroaneurysms (RAMs) develop as outpouchings of the arterial wall that is weakened by arteriosclerosis. The traditional treatment of RAMs comprises observation, focal laser photocoagulation, or surgery. Recently, intravitreal injection of anti-vascular endothelial growth factor (VEGF) drugs has been announced as an effective therapy for fovea-threatening RAMs and quickly improve visual acuity and central retinal thickness (CRT).In the retrospective series, medical charts and ocular images of 24 patients diagnosed as having RAM between May 2011 and November 2018 in our facility were reviewed to delineate clinical manifestations and visual prognosis in RAM patients receiving different treatment modalities. Twenty-four patients (25 eyes; 11 men and 13 women) were enrolled, and one eye with comorbidity of branch retinal vein occlusion was excluded. The mean age of the patients was 69.00 ±â€Š13.45 years. Fourteen patients (58.33%) had a history of hypertension, and 17 patients (70.83%) were aged > 60 years. Furthermore, patients with fovea-threatening RAMs presented with either hypertension or were aged > 60 years.Eyes with fovea involvement (n = 18) were analyzed and separated into two groups according to their treatment modalities: those receiving anti-VEGF intravitreal injections (n = 13) and observation only (n = 5). The baseline visual acuity revealed no significant difference in the two groups. In patients receiving anti-VEGF intravitreal injections, a significantly better visual acuity was detected after anti-VEGF intravitreal injections than the baseline visual acuity (logMAR, 0.78 ±â€Š0.51 vs 1.52 ±â€Š0.48, P < .001), and CRT significantly improved (505.50 ±â€Š159.26 µm vs 243.60 ±â€Š60.17 µm, P = .001). Patients receiving anti-VEGF intravitreal injections also revealed better final visual acuity than those in the observation group (logMAR, 0.78 ±â€Š0.51 vs 1.34 ±â€Š0.48, P = .04).A systematic work-up for hypertension and arteriosclerotic disease could be considered the recommended procedure once RAM has been diagnosed. With better final visual acuity, significant visual improvements, and fast reduction of CRT observed in patients with fovea-threatening RAMs receiving anti-VEGF intravitreal injections, intravitreal anti-VEGF was considered an effective therapy for complicated RAM. During the follow-up period, the majority of RAM eyes had good maintenance of visual function even with foveal complications.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Bevacizumab/uso terapêutico , Tomada de Decisões , /tratamento farmacológico , Idoso , Feminino , Humanos , Injeções Intravítreas , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Acuidade Visual
2.
Int J Cancer ; 146(1): 223-235, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31444972

RESUMO

Angiogenesis is necessary for tumor growth and has been targeted in breast cancer; however, it is unclear which patients will respond and benefit from antiangiogenic therapy. We report noninvasive monitoring of patient response to neoadjuvant chemotherapy given alone or in combination with anti-vascular endothelial growth factor (bevacizumab) in a randomized clinical trial. At four time points during neoadjuvant chemotherapy ± bevacizumab of receptor tyrosine-protein kinase erbB-2-negative breast cancers, we measured metabolites and inflammation-related markers in patient's serum. We report significant changes in the levels of several molecules induced by bevacizumab, the most prominent being an increase in pentraxin 3 (PTX3) and von Willebrand factor (VWF). Serum levels of AXL, VWF and pulmonary and activation-regulated cytokine (PARC/CCL18) reflected response to chemotherapy alone or in combination with bevacizumab. We further analyzed serum cytokines in relation to tumor characteristics such as gene expression, tumor metabolites and tumor infiltrating leukocytes. We found that VWF and growth-differentiation factor 15 tumor mRNA levels correlated with their respective serum protein levels suggesting that these cytokines may be produced by tumors and outflow to the bloodstream while influencing the tumor microenvironment locally. Finally, we used binomial logistic regression which allowed to predict patient's response using only 10 noninvasive biomarkers. Our study highlights the potential of monitoring circulating levels of cytokines and metabolites during breast cancer therapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Quimioterapia Adjuvante , Mediadores da Inflamação/sangue , Bevacizumab/administração & dosagem , Biomarcadores/metabolismo , Neoplasias da Mama/sangue , Citocinas/sangue , Feminino , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante
3.
Medicine (Baltimore) ; 98(50): e18227, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31852082

RESUMO

OBJECTIVE: To identify the optimal treatment strategy after first-line induction chemotherapy for metastatic colorectal cancer (mCRC). METHODS: We conducted a meta-analysis of randomized controlled trials comparing bevacizumab-based maintenance therapy, observation, and continuous chemotherapy.We searched the PubMed, Embase, and Cochrane databases for relevant articles published through March 2018. All randomized phase-III trials evaluating bevacizumab-based maintenance treatment after bevacizumab-based induction treatment were eligible for inclusion. The primary and secondary endpoints were progression-free survival (PFS) and overall survival (OS), respectively. Hazard ratios (HRs) with 95% confidence intervals (CIs) or data for calculating HRs with 95% CIs were extracted. The RevMan v5.3 (Copenhagen, Denmark) software was used for data analysis. RESULTS: Nine trials (3121 patients) were included in this meta-analysis. Compared with observation alone, bevacizumab-based maintenance therapy significantly improved PFS (HR: 0.62, 95% CI: 0.47-0.82) and showed a trend toward prolonged OS (HR: 0.93, 95% CI: 0.83-1.05). The incidence of grade 3/4 toxicity, including hypertension and fatigue, was higher after maintenance therapy than after observation alone. PFS (HR: 0.91, 95% CI: 0.70-1.18) and OS (HR: 0.88, 95% CI: 0.74-1.04) did not differ between the maintenance treatment and continuous chemotherapy groups. Grade 3/4 toxicity, including diarrhea and sensory neuropathy, was less common after maintenance therapy than after continuous chemotherapy. CONCLUSION: Bevacizumab-based maintenance therapy significantly improved PFS, showed a trend toward prolonged OS, and reduced cumulative grade 3/4 toxicity relative to continuous chemotherapy with comparable efficacy. Although maintenance therapy was beneficial, the optimal strategy should be individualized.


Assuntos
Bevacizumab/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Quimioterapia de Manutenção/métodos , Antineoplásicos Imunológicos/uso terapêutico , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/secundário , Humanos , Metástase Neoplásica , Resultado do Tratamento
4.
Medicine (Baltimore) ; 98(51): e18333, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31860985

RESUMO

To determine characteristics of diabetic macular edema patients with serous retinal detachment (SRD).We classified naïve diabetic macular edema (DME) patients with or without SRD, and compared their baseline characteristics; intravitreal bevacizumab (IVB) responsiveness; aqueous concentrations of IL (interleukin)-1ß, -2, -8, -10, -17, placental growth factor (PlGF), and vascular endothelial growth factor (VEGF). In addition, factors associated with the existence of SRD were identified.Of the 64 DME patients, 14 had SRD. The average levels of aqueous VEGF and PlGF were significantly higher in the SRD group than in the control group (P = .022 and P = .041, respectively). The best-corrected visual acuity (BCVA) and central subfield thickness (CST) did not differ significantly between the 2 groups at baseline or after 3 consecutive monthly IVBs. In multivariate logistic regression analysis, the level of aqueous VEGF was the only factor associated with the existence of SRD (odds ratio: 1.03; P = .038).Rather than aqueous inflammatory cytokines, levels of aqueous VEGFs were associated with the occurrence of SRD in DME patients. In terms of prognosis, the existence of SRD was not related with BCVA or CST changes.


Assuntos
Humor Aquoso/metabolismo , Bevacizumab/uso terapêutico , Retinopatia Diabética/tratamento farmacológico , Edema Macular/tratamento farmacológico , Descolamento Retiniano/tratamento farmacológico , Inibidores da Angiogênese/uso terapêutico , Estudos de Casos e Controles , Retinopatia Diabética/metabolismo , Feminino , Humanos , Interleucina-1beta/metabolismo , Injeções Intravítreas , Edema Macular/metabolismo , Masculino , Pessoa de Meia-Idade , Fator de Crescimento Placentário/metabolismo , Prognóstico , Retina/patologia , Descolamento Retiniano/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Acuidade Visual/efeitos dos fármacos
5.
Buenos Aires; CONETEC; nov. 2019.
Não convencional em Espanhol | BRISA/RedTESA | ID: biblio-1025042

RESUMO

INTRODUCCIÓN: La degeneración macular asociada a la edad (DMAE) es una patología que afecta la mácula (zona central de la retina) y evoluciona frecuentemente a una disminución de la agudeza visual, constituyendo la principal causa de ceguera en mayores de 50 años en países desarrollados. Existen dos formas de presentación, la seca y la húmeda o exudativa, que representan el 90% y 10% de los casos respectivamente. La húmeda se caracteriza por la formación anormal de nuevos vasos coroideos (neovascularización), exudación y edema de la retina. Esta forma es la responsable del 90% de los casos de pérdida grave de la visión y se estima que el 70% de los ojos con signos de neovascularización evolucionarán a pérdida severa de la visión a los dos años del diagnóstico. Por lo cual es fundamental el inicio temprano del tratamiento y su mantenimiento adecuado para limitar la progresión de la pérdida de la agudeza visual. OBJETIVO: El objetivo del presente informe es evaluar la eficacia, seguridad, los costos asociados al uso de bevacizumab para degeneración macular húmeda asociada a la edad, en comparación con ranibizumab. DESCRIPCIÓN DE LA TECNOLOGÍA: Bevacizumab, un anticuerpo monoclonal IgG1 humanizado recombinante, se une al FCEV e inhibe su interacción con los receptores Flt1 y KDR en la superficie de las células endoteliales. En el proceso, previene la proliferación de células endoteliales y la formación de nuevos vasos sanguíneos. BÚSQUEDA BIBLIOGRÁFICA: Se realizó una búsqueda en las principales bases de datos bibliográficas: PubMed, CRD (del inglés Centre for Reviews and Dissemination- University of York), en Tripdatabase, en los sitios web de financiadores de salud y de sociedades científicas, así como en los buscadores genéricos de internet se buscó con el nombre de la tecnología y sus sinónimos y/o la patología. Se priorizó la inclusión de revisiones sistemáticas (RS), ensayos clínicos controlados aleatorizados (ECAs), evaluaciones de tecnologías sanitarias (ETS), evaluaciones económicas, guías de práctica clínica (GPC) y políticas de cobertura de diferentes sistemas de salud. RESULTADOS: Se incluyeron cuatro RS con metaanálisis, un metaanálisis de elaboración propia, cuatro GPC y cinco informes de ETS de bevacizumab para degeneración macular asociada a la edad. Todos los estudios incluidos fueron realizados con la administración de bevacizumab de marca comercial Avastin®. La evidencia hallada no mostró diferencias entre bevacizumab y ranibizumab en lo que respecta a la agudeza visual a uno y dos años de seguimiento. Asimismo, mostró que la mejoría en la calidad de vida y los eventos adversos serían similares entre estos tratamientos. En lo que se refiere específicamente a la endoftalmitis, la incidencia también resultó similar en ambos grupos. CONCLUSIONES: La evidencia disponible no mostró diferencias entre el bevacizumab y el ranibizumab en lo que se refiere a la eficacia y seguridad. No está demostrado que exista mayor riesgo de endoftalmitis asociado al uso de bevacizumab fraccionado. Este riesgo potencial de endoftalmitis puede ser mitigado con métodos de fraccionamiento adecuado. El tratamiento con bevacizumab es notablemente menos costoso que ranibizumab o aflibercept y recomendar su utilización redundará en un mayor acceso.


Assuntos
Humanos , Bevacizumab/uso terapêutico , Ranibizumab/uso terapêutico , Degeneração Macular/tratamento farmacológico , Avaliação da Tecnologia Biomédica , Análise Custo-Eficiência
6.
Zhonghua Yan Ke Za Zhi ; 55(10): 791-795, 2019 Oct 11.
Artigo em Chinês | MEDLINE | ID: mdl-31607068

RESUMO

Pathological myopia refers to high myopia with fundus pathological changes. Choroidal neovascularization is one of its serious complications, and also the main cause of visual loss. Currently, the first-line treatment is anti-VEGF treatment, with good efficacy, high safety, good prognosis, and other advantages of vision. Commonly used anti-VEGF drugs include bevacizumab, ranibizumab, aflibercept, and conbercept. The main treatment strategies include 1+pro re nata and 3+pro re nata, and the standard of REPAIR test is often used to evaluate the re-injection. This article reviews the advantages of anti-VEGF therapy, drug selection, treatment strategy, and re-injection criteria. (Chin J Ophthalmol, 2019, 55:791-795).


Assuntos
Inibidores da Angiogênese/uso terapêutico , Bevacizumab/uso terapêutico , Neovascularização de Coroide/tratamento farmacológico , Miopia Degenerativa/complicações , Ranibizumab/uso terapêutico , Inibidores da Angiogênese/administração & dosagem , Bevacizumab/administração & dosagem , Neovascularização de Coroide/etiologia , Humanos , Injeções Intravítreas , Ranibizumab/administração & dosagem , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular , Acuidade Visual
7.
Gan To Kagaku Ryoho ; 46(10): 1647-1649, 2019 Oct.
Artigo em Japonês | MEDLINE | ID: mdl-31631163

RESUMO

A 74-year-old man with recurrence of cecal cancer received systemic chemotherapy(CapeOX plus bevacizumab). After the administration of 9 courses, he reported sudden appearance of bloody bowel discharge. Endoscopic examination could not locate the bleeding point. A CT scan indicated that the small intestine was affected by the recurrence of cancer. Therefore, resection of the small intestine was performed after 6 weeks of drug withdrawal. Although direct closure with fascia incision was performed for the repair of wound dehiscence after surgery, re-dehiscence occurred because of paralytic ileus. Wound lavage and nutritional intervention were performed, followed by negative pressure wound therapy. Excellent wound healing was achieved by this therapeutic approach for 3 months.


Assuntos
Bevacizumab/uso terapêutico , Neoplasias do Ceco , Tratamento de Ferimentos com Pressão Negativa , Parede Abdominal , Idoso , Neoplasias do Ceco/tratamento farmacológico , Humanos , Masculino , Recidiva Local de Neoplasia , Deiscência da Ferida Operatória
8.
BMC Public Health ; 19(1): 1252, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31510981

RESUMO

BACKGROUND: Antiangiogenic therapy has proved to be an important therapeutic tool for many retinal vascular diseases; however, its availability is limited in developing countries. This study sought to describe the bevacizumab vial sharing process and to evaluate the impact of this repackaging system on the costs incurred in a Brazilian public hospital. METHOD: This retrospective study compared the number and costs of intravitreal antiangiogenic injections approved via court order in the first year of the study (2015) to the number and costs of the bevacizumab injections provided through the use of vial sharing in the second year of the study (2016). Vial sharing consists of the traditional process used to repackage bevacizumab; in this case, however, the drug samples used were the residual volume from the preparation of bevacizumab for oncology patients. The hospital adhered to the guidelines established by the Brazilian Health Surveillance Agency (ANVISA). RESULTS: In the first year of the study and using medication obtained through court orders, 550 intravitreal injections were performed in the ophthalmology ambulatory care center. Based on local pricing tables, the total cost of the medication was BRL$1,036,056.25 (USD$267,546.58), and the average cost of each application was BRL$1883.74 (USD$486.45). In the second year of the study, 1081 intravitreal applications were performed at the same hospital using doses obtained through bevacizumab vial sharing. The total cost was BRL$21,942.49 (USD$5663.30) and the per-unit cost was BRL$20.30, or USD$5.23 (a savings of 97.88%). CONCLUSION: This study found that bevacizumab vial sharing led to a significant reduction in public health care costs associated with antiangiogenic treatment and increased the availability of the drug to public health care patients. These results can be extrapolated to other types of drugs and health care systems.


Assuntos
Inibidores da Angiogênese/economia , Bevacizumab/economia , Custos de Medicamentos , Doenças Retinianas/tratamento farmacológico , Doenças Retinianas/economia , Idoso , Inibidores da Angiogênese/uso terapêutico , Bevacizumab/uso terapêutico , Brasil , Análise Custo-Benefício , Feminino , Custos de Cuidados de Saúde , Humanos , Injeções Intravítreas/economia , Pessoa de Meia-Idade , Estudos Retrospectivos
9.
Gynecol Oncol ; 155(2): 201-206, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31522837

RESUMO

OBJECTIVES: Patients with epithelial ovarian cancer (EOC) recurring between 6 and 12 months after primary platinum chemotherapy have worse prognosis than those recurring in >12 months. Artificially prolonging the platinum-free interval (PFI) with cytotoxic chemotherapy was tested in MITO-8 with poor outcomes. This study aimed to determine the impact of using non-platinum or targeted therapy in 2nd line treatment of EOC patients recurring 6-12 months after completion of primary platinum-based chemotherapy. METHODS: A multi-institutional retrospective review of 177 patients with recurrent EOC and PFI of 6-12 months following primary chemotherapy was performed comparing platinum versus non-platinum chemotherapy or targeted therapy for 2nd line treatment. PFI1 was defined as the date of last chemotherapy to date of recurrence. PFS2/3 were defined as start of 2nd or 3rd line chemotherapy to start of subsequent line. RESULTS: Of 177 patients, the majority of patients were Caucasian, had serous histology, and underwent primary cytoreductive surgery. Median PFI1 was 8.2 months (95% CI 8-9 months). Second line platinum was omitted in 28% of patients. Bevacizumab was used in 2nd line in 16% of patients; 19% received other targeted therapies. Median PFS2 for platinum chemotherapy was longer than non-platinum (7.1 vs 3 months, p = 0.0114). Median PFS2 was significantly longer for platinum vs. targeted therapy (7.1 vs. 3 months p = 0.0431). Median OS for platinum in 2nd line vs. no platinum was 43.6 vs. 37.6 months (p = 0.0174). CONCLUSIONS: Use of non-platinum chemotherapy and even targeted therapy to prolong PFI in patients with EOC recurring between 6 and 12 months leads to worse survival.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológico , Compostos de Platina/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Bevacizumab/uso terapêutico , Progressão da Doença , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Terapia de Alvo Molecular/métodos , Terapia de Alvo Molecular/mortalidade , Recidiva Local de Neoplasia/etiologia , Recidiva Local de Neoplasia/mortalidade , Neoplasias Ovarianas/mortalidade , Estudos Retrospectivos , Resultado do Tratamento
10.
BMC Ophthalmol ; 19(1): 200, 2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31519158

RESUMO

BACKGROUND: To compare the reoperation rate in patients with vitreous hemorrhage (VH) secondary to proliferative diabetic retinopathy (PDR) with or without preoperative intravitreal bevacizumab (IVB). METHODS: In this retrospective study, 280 patients (362 eyes) with diabetic VH were divided into a group that received preoperative IVB and a group that did not receive preoperative IVB. According to B-scan or color Doppler ultrasonography, the eyes were grouped as a VH group and a tractional retinal detachment (TRD) group. The reoperation rate, visual and anatomical outcomes of treatment were evaluated after 6 months. RESULTS: There were 17.4% of eyes in the VH group that did not receive preoperative IVB later required additional vitrectomy, while only 7.7% of the eyes in the VH group that received preoperative IVB required additional vitrectomy (P = 0.025). There were 45.5% of eyes in the TRD group that did not receive preoperative IVB had no reoperation, while only 21.4% of the eyes in the TRD group that received preoperative IVB had no reoperation (P = 0.004). The patients with one operation achieved better vision than those required reoperations in the VH group (P = 0.038) and TRD group (P = 0.019). CONCLUSIONS: Preoperative IVB significantly reduced the re-vitrectomy rate in patients with VH without TRD, but there was an increase in the reoperation rate in patients with VH combined with TRD.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Bevacizumab/uso terapêutico , Retinopatia Diabética/terapia , Vitrectomia , Hemorragia Vítrea/terapia , Idoso , Terapia Combinada , Retinopatia Diabética/tratamento farmacológico , Retinopatia Diabética/fisiopatologia , Retinopatia Diabética/cirurgia , Feminino , Humanos , Injeções Intravítreas , Masculino , Pessoa de Meia-Idade , Reoperação , Descolamento Retiniano/cirurgia , Estudos Retrospectivos , Ultrassonografia Doppler em Cores , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Acuidade Visual/fisiologia , Hemorragia Vítrea/tratamento farmacológico , Hemorragia Vítrea/fisiopatologia , Hemorragia Vítrea/cirurgia
11.
Ophthalmic Surg Lasers Imaging Retina ; 50(8): 510-513, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31415698

RESUMO

BACKGROUND AND OBJECTIVE: To describe a novel, simple technique for surgically draining a bullous serous pigment epithelial detachment (PED). PATIENTS AND METHODS: Pars plana vitrectomy was performed with confirmed elevation of the hyaloid face. Proportional diathermy allowed stepwise entry into the PED superotemporally through an initially small, needle-point focus while providing control of any potential bleeding. Thick fluid was aspirated with a soft-tipped cannula, fluid-air exchange was performed, and intravitreal bevacizumab was injected before removing the cannulas. RESULTS: The PED was successfully completely drained intraoperatively and remained flat at 1 week postoperatively. However, the draining site ultimately closed, and continued exudation from choroidal neovascularization led to recurrent PED and eventual nonhemorrhagic retinal pigment epithelial tear despite aggressive treatment with aflibercept and photodynamic therapy. The early visual acuity benefit may relate to resolution of hyperopic shift. CONCLUSION: Serous PED can be surgically reduced without hemorrhagic complications, but long-term success depends upon control of the underlying choroidal neovascularization. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:510-513.].


Assuntos
Descolamento Retiniano/cirurgia , Epitélio Pigmentado da Retina/cirurgia , Vitrectomia/métodos , Idoso , Inibidores da Angiogênese/uso terapêutico , Bevacizumab/uso terapêutico , Neovascularização de Coroide/etiologia , Feminino , Humanos , Fotoquimioterapia/métodos , Receptores de Fatores de Crescimento do Endotélio Vascular/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Descolamento Retiniano/tratamento farmacológico
12.
Tokai J Exp Clin Med ; 44(3): 40-44, 2019 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-31448394

RESUMO

Bevacizumab is an effective drug for recurrent/advanced cervical cancer. A 59-year-old patient diagnosed with FIGO stage I B2 squamous cell carcinoma of the cervix at our hospital was treated with concurrent chemoradiotherapy as initial treatment. The outcome was judged as close to CR. Local recurrence in the irradiation field and paraaortic lymph node metastasis were noted 2 months after completion of this treatment. Chemotherapy of bevacizumab combined with paclitaxel plus carboplatin (TC) was initiated for recurrent cervical cancer. At 17 days after the 4th cycle, abdominal pain suddenly developed, and a close examination detected free air on abdominal CT, based on which intestinal perforation was diagnosed. Laparoscopic surgery performed to investigate the intraabdominal cavity showed that the small intestine was perforated at 2 sites. These were treated with laparoscopy-assisted partial resection of the small intestine and functional end-to-end anastomosis. Drug therapy for the recurrent cervical cancer was considered, but the primary disease rapidly aggravated and the patient died of the primary disease 11 months after completion of the initial treatment.


Assuntos
Anastomose Cirúrgica/métodos , Anti-Inflamatórios não Esteroides/efeitos adversos , Bevacizumab/efeitos adversos , Carcinoma de Células Escamosas/terapia , Perfuração Intestinal/induzido quimicamente , Perfuração Intestinal/cirurgia , Intestino Delgado/cirurgia , Laparoscopia/métodos , Recidiva Local de Neoplasia/terapia , Neoplasias do Colo do Útero/terapia , Anti-Inflamatórios não Esteroides/administração & dosagem , Bevacizumab/uso terapêutico , Quimiorradioterapia , Evolução Fatal , Feminino , Humanos , Pessoa de Meia-Idade
13.
J Surg Oncol ; 120(4): 786-793, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31368160

RESUMO

BACKGROUND AND OBJECTIVES: The single-arm ROSiA study evaluated frontline bevacizumab for advanced ovarian cancer. We explored how discordant surgically and radiologically assessed postoperative residual disease affects outcomes. METHODS: After debulking surgery, 1021 patients received 4 to 8 cycles of carboplatin-paclitaxel plus bevacizumab until progression or up to 24 months. The primary endpoint was safety; progression-free survival (PFS) was a secondary endpoint. We performed post hoc exploratory PFS analyses in four subgroups: surgeon-reported no visible residuum (NVR) without target lesions; surgeon-reported NVR with target lesions; macroscopic (≤1 cm) residuum; and >1 cm residuum. RESULTS: Surgical and radiological assessments were concordant in 94% of patients; 61 patients (6%; 21% of those with surgeon-reported NVR) had NVR with target lesions. Median PFS was numerically longest in patients with concordant surgically/radiologically assessed NVR (35.5 months), intermediate for surgeon-reported NVR with target lesions (31.8 months), and shortest for visible residuum (27.9 and 20.2 months for visible residuum ≤1 and >1 cm, respectively). One-year and 2-year PFS rates showed the same pattern. CONCLUSIONS: These analyses suggest that prognosis is potentially worse in patients with radiologically detected target lesions despite surgeon-reported NVR compared with concordant NVR by both assessment methods. Postsurgical imaging may add valuable prognostic information.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/uso terapêutico , Neoplasia Residual/mortalidade , Neoplasias Ovarianas/mortalidade , Cirurgiões/estatística & dados numéricos , Tomografia Computadorizada por Raios X/métodos , Adenocarcinoma de Células Claras/diagnóstico por imagem , Adenocarcinoma de Células Claras/mortalidade , Adenocarcinoma de Células Claras/patologia , Antineoplásicos Imunológicos/uso terapêutico , Carcinossarcoma/diagnóstico por imagem , Carcinossarcoma/mortalidade , Carcinossarcoma/patologia , Feminino , Seguimentos , Humanos , Neoplasia Residual/diagnóstico por imagem , Neoplasia Residual/patologia , Neoplasias Ovarianas/diagnóstico por imagem , Neoplasias Ovarianas/patologia , Prognóstico , Taxa de Sobrevida
14.
Pediatrics ; 144(2)2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31337693

RESUMO

OBJECTIVE: Among extremely preterm infants, we evaluated whether bevacizumab therapy compared with surgery for retinopathy of prematurity (ROP) is associated with adverse outcomes in early childhood. METHODS: This study was a retrospective analysis of prospectively collected data on preterm (22-26 + 6/7 weeks' gestational age) infants admitted to the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network centers who received bevacizumab or surgery exclusively for ROP. The primary outcome was death or severe neurodevelopmental impairment (NDI) at 18 to 26 months' corrected age (Bayley Scales of Infant and Toddler Development, Third Edition cognitive or motor composite score <70, Gross Motor Functional Classification Scale level ≥2, bilateral blindness or hearing impairment). RESULTS: The cohort (N = 405; 214 [53%] boys; median [interquartile range] gestational age: 24.6 [23.9-25.3] weeks) included 181 (45%) infants who received bevacizumab and 224 (55%) who underwent ROP surgery. Infants treated with bevacizumab had a lower median (interquartile range) birth weight (640 [541-709] vs 660 [572.5-750] g; P = .02) and longer durations of conventional ventilation (35 [21-58] vs 33 [18-49] days; P = .04) and supplemental oxygen (112 [94-120] vs 105 [84.5-120] days; P = .01). Death or severe NDI (adjusted odds ratio [aOR] 1.42; 95% confidence interval [CI] 0.94 to 2.14) and severe NDI (aOR 1.14; 95% CI 0.76 to 1.70) did not differ between groups. Odds of death (aOR 2.54 [95% CI 1.42 to 4.55]; P = .002), a cognitive score <85 (aOR 1.78 [95% CI 1.09 to 2.91]; P = .02), and a Gross Motor Functional Classification Scale level ≥2 (aOR 1.73 [95% CI 1.04 to 2.88]; P = .04) were significantly higher with bevacizumab therapy. CONCLUSIONS: In this multicenter cohort of preterm infants, ROP treatment modality was not associated with differences in death or NDI, but the bevacizumab group had higher mortality and poor cognitive outcomes in early childhood. These data reveal the need for a rigorous appraisal of ROP therapy.


Assuntos
Bevacizumab/uso terapêutico , Desenvolvimento Infantil/efeitos dos fármacos , Desenvolvimento Infantil/fisiologia , Recém-Nascido Prematuro/crescimento & desenvolvimento , Retinopatia da Prematuridade/tratamento farmacológico , Retinopatia da Prematuridade/cirurgia , Adulto , Inibidores da Angiogênese/uso terapêutico , Estudos de Coortes , Feminino , Humanos , Recém-Nascido , Masculino , Transtornos do Neurodesenvolvimento/mortalidade , Transtornos do Neurodesenvolvimento/prevenção & controle , Estudos Prospectivos , Retinopatia da Prematuridade/mortalidade , Estudos Retrospectivos
15.
Ceska Slov Farm ; 68(2): 43-47, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31331174

RESUMO

Targeted therapy is a significant benefit in the treatment of cancer patients. Bevacizumab improves overall survival (OS) and progression free survival (PFS) in the treatment of metastatic colorectal cancer (mCRC). The clinical effectiveness of bevacizumab is similar to its efficacy in randomised controlled trials. However, the costs of bevacizumab treatment as well as other agents of targeted treatment are discussed between the health care payers, the regulatory authorities and the members of professional societies. Biomarkers of bevacizumab treatment helpful in the selection of eligible groups of patients are still missing. This review focuses on current bevacizumab therapy of mCRC from the pharmacoeconomic perspective. The cost per a 14-day bevacizumab treatment cycle is approximately 31,000 CZK in the Czech Republic. External published pharmacoeconomics analyses have no clear conclusions. Their results are usually expressed as the cost per QALY gained in comparison with a comparator. They differ according to the economic situation of the particular countries. The pharmacoeconomic results have to be confirmed in the real clinical practice, and then the decision should be reassessed by using the uniform methodology, e.g. the Health Technology Assessment (HTA).


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Bevacizumab/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Anticorpos Monoclonais , Neoplasias Colorretais/patologia , Análise Custo-Benefício , República Tcheca , Humanos , Metástase Neoplásica/tratamento farmacológico , Anos de Vida Ajustados por Qualidade de Vida
16.
J Cancer Res Clin Oncol ; 145(10): 2555-2564, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31350622

RESUMO

PURPOSE: Previously, the combination of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) and bevacizumab (BEV) was investigated. A subgroup analysis of the IMpower150 trial, which investigated the combination of atezolizumab, carboplatin, paclitaxel, and bevacizumab (ABCP), demonstrated the benefit of ABCP in patients harboring EGFR mutations. This study aims to assess the prognostic significance of the qualification for BEV use and the proportion of patients who potentially benefit from BEV-containing combination therapy before and after initial EGFR-TKI treatment. METHODS: We retrospectively analyzed the data of 297 patients with advanced or recurrent non-squamous non-small cell lung cancer (NSCLC) harboring EGFR mutations who had received EGFR-TKIs. We performed statistical analyses using the Kaplan-Meier method and the Cox regression adjusted for risk factors. RESULTS: Of the 297 patients, 203 (68%) were eligible to receive BEV ("BEV fit") at the time of EGFR-TKI initiation. Among the "BEV unfit" patients at baseline (n = 70), 14 (20%) became eligible to receive ABCP ("ABCP fit") at the time of EGFR-TKI failure. The median overall survival (OS) of the "BEV fit" and "BEV unfit" patients was 26.2 [95% confidence interval (CI) 23.7-31.2] and 19.1 (95% CI 15.0-25.1) months, respectively (P < 0.001). The multivariate analysis revealed a marked correlation between survival and the qualification for BEV use. CONCLUSIONS: The qualification for BEV use at baseline is independently related to the OS. Some patients harboring EGFR mutations, including those who were "BEV unfit" at baseline, could be eligible for the ABCP regimen after EGFR-TKI treatment.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Mutação , Adulto , Idoso , Idoso de 80 Anos ou mais , Bevacizumab/farmacologia , Bevacizumab/uso terapêutico , Biomarcadores Tumorais , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Receptores ErbB/genética , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Estudos Retrospectivos , Resultado do Tratamento
17.
Acta Gastroenterol Belg ; 82(2): 322-325, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31314196

RESUMO

Colorectal cancer is one of the most frequently diagnosed malignancies worldwide. One of the most important developments in the management of metastatic colorectal cancer is targeted therapy. Bevacizumab, a monoclonal antibody inhibiting VEGF induced angiogenesis, has been accepted as safe and efficient in the treatment of metastatic colorectal cancer for more than a decade. Addition of bevacizumab to fluorouracil-based chemotherapy is also associated with severe adverse events. We present a case of bevacizumab-induced bowel ischaemia associated with gastrointestinal haemorrhage.


Assuntos
Inibidores da Angiogênese/efeitos adversos , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos Imunológicos/efeitos adversos , Bevacizumab/efeitos adversos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Metástase Neoplásica/tratamento farmacológico , Inibidores da Angiogênese/uso terapêutico , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab/uso terapêutico , Hemorragia Gastrointestinal , Humanos
18.
Expert Opin Pharmacother ; 20(14): 1767-1775, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31314604

RESUMO

Introduction: The liver is the most common metastatic site in colorectal cancer with more than half the patients developing a liver metastasis either at the time of their diagnosis (synchronous) or later (metachronous). Surgical resection remains the principal curative approach that offers significant survival improvements. However, upfront surgery is only possible in about 10-20% of patients at the time of diagnosis, making the consideration of other treatment modalities essential. Areas covered: In this review, the authors provide an overview of the standard approaches for the initial management of patients with colorectal cancer with liver metastases. They then provide an up-to-date discussion of first-line systemic chemotherapy/targeted therapy options in the contexts of initially resectable and unresectable disease and review toxicities and complications following these options. Expert opinion: Advances in chemotherapeutic agents and biological targeted therapies have improved the prognosis of colorectal cancer with liver metastases. However, there is still no 'single best approach', making further trials necessary to provide more evidence.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Hepáticas/patologia , Antineoplásicos/efeitos adversos , Bevacizumab/efeitos adversos , Bevacizumab/uso terapêutico , Neoplasias Colorretais/patologia , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Instabilidade de Microssatélites , Terapia Neoadjuvante , Prognóstico
19.
BMC Cancer ; 19(1): 687, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31307428

RESUMO

BACKGROUND: In a prospective study with long-term follow-up, we analyzed circulating T cell subsets in patients with metastatic colorectal cancer (mCRC) in the context of primary tumor sidedness, KRAS status, and clinical outcome. Our primary goal was to investigate whether baseline levels of circulating T cell subsets serve as a potential biomarker of clinical outcome of mCRC patients treated with an anti-VEGF-based regimen. METHODS: The study group consisted of 36 patients with colorectal adenocarcinoma who started first-line chemotherapy with bevacizumab for metastatic disease. We quantified T cell subsets including Tregs and CD8+ T cells in the peripheral blood prior to therapy initiation. Clinical outcome was evaluated as progression-free survival (PFS), overall survival (OS), and objective response rate (ORR). RESULTS: 1) mCRC patients with KRAS wt tumors had higher proportions of circulating CD8+ cytotoxic T cells among all T cells but also higher measures of T regulatory (Treg) cells such as absolute count and a higher proportion of Tregs in the CD4+ subset. 2) A low proportion of circulating Tregs among CD4+ cells, and a high CD8:Treg ratio at initiation of VEGF-targeting therapy, were associated with favorable clinical outcome. 3) In a subset of patients with primarily right-sided mCRC, superior PFS and OS were observed when the CD8:Treg ratio was high. CONCLUSIONS: The baseline level of circulating immune cells predicts clinical outcome of 1st-line treatment with the anti-VEGF angio/immunomodulatory agent bevacizumab. Circulating immune biomarkers, namely the CD8:Treg ratio, identified patients in the right-sided mCRC subgroup with favorable outcome following treatment with 1st-line anti-VEGF treatment.


Assuntos
Adenocarcinoma/tratamento farmacológico , Inibidores da Angiogênese/uso terapêutico , Bevacizumab/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Metástase Neoplásica/tratamento farmacológico , Linfócitos T Citotóxicos/metabolismo , Linfócitos T Reguladores/metabolismo , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Adenocarcinoma/sangue , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/administração & dosagem , Bevacizumab/administração & dosagem , Biomarcadores Tumorais/metabolismo , Neoplasias Colorretais/sangue , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Feminino , Seguimentos , Humanos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Estudos Prospectivos , Proteínas Proto-Oncogênicas p21(ras)/análise , Taxa de Sobrevida
20.
Drugs ; 79(11): 1231-1239, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31267481

RESUMO

For more than 20 years, the combination of a platinum agent and a taxane has served as the primary chemotherapy strategy for epithelial ovarian cancer. Alternative approaches employing these drugs (intraperitoneal drug delivery, neoadjuvant therapy) have favorably impacted outcomes in selected patient populations. Multiple single agent and combination therapy strategies have been delivered in the second-line (or later) setting with the goal to prolong survival and optimize quality-of-life. The anti-angiogenic agent bevacizumab has been shown to be clinically active when added to chemotherapy and delivered as a "maintenance" strategy in the front-line, platinum-sensitive recurrent and platinum-resistant settings. Several poly-(ADP-ribose) polymerase (PARP) inhibitors are currently utilized as single-agent "second-line" treatment options or in the maintenance setting. Recent clinical research efforts in ovarian cancer have focused on the potential role of checkpoint inhibitors used alone or in combination with PARP inhibitors or anti-angiogenic agents.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Epitelial do Ovário/tratamento farmacológico , Inibidores da Angiogênese/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/uso terapêutico , Hidrocarbonetos Aromáticos com Pontes/uso terapêutico , Carboplatina/uso terapêutico , Cisplatino/uso terapêutico , Sistemas de Liberação de Medicamentos/métodos , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Terapia Neoadjuvante , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Poli(ADP-Ribose) Polimerases/metabolismo , Taxoides/uso terapêutico
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