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1.
Cancer Treat Rev ; 84: 101966, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32044644

RESUMO

Anti-angiogenic treatment is an important option that has changed the therapeutic landscape in various tumors, particularly in patients affected by renal cell carcinoma (RCC). Agents that block signaling pathways governing tumor angiogenesis have raised high expectations among clinicians. Vascular endothelial growth factor receptor-tyrosine kinase inhibitors (VEGFR-TKIs) comprise a heterogeneous class of drugs with distinct pharmacological profiles, including potency, selectivity, pharmacokinetics and drug-drug interactions. Among them, tivozanib is one of the last TKIs introduced in the clinical practice; this drug selectively targets VEGFRs, it is characterized by a favorable pharmacokinetics and safety profile and has been approved as first-line treatment for patients with metastatic RCC (mRCC). In this article, we describe the clinical pharmacology of selected VEGFR-TKIs used for the treatment of mRCC, highlighting the relevant differences; moreover we aim to define the main pharmacologic characteristics of these drug.


Assuntos
Inibidores da Angiogênese/farmacologia , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Inibidores de Proteínas Quinases/farmacologia , Receptores de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Inibidores da Angiogênese/efeitos adversos , Inibidores da Angiogênese/uso terapêutico , Anilidas/efeitos adversos , Anilidas/farmacologia , Anilidas/uso terapêutico , Axitinibe/efeitos adversos , Axitinibe/farmacologia , Axitinibe/uso terapêutico , Interações de Medicamentos , Humanos , Compostos de Fenilureia/efeitos adversos , Compostos de Fenilureia/farmacologia , Compostos de Fenilureia/uso terapêutico , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/uso terapêutico , Piridinas/efeitos adversos , Piridinas/farmacologia , Piridinas/uso terapêutico , Pirimidinas/efeitos adversos , Pirimidinas/farmacologia , Pirimidinas/uso terapêutico , Quinolinas/efeitos adversos , Quinolinas/farmacologia , Quinolinas/uso terapêutico , Sorafenibe/efeitos adversos , Sorafenibe/farmacologia , Sorafenibe/uso terapêutico , Sulfonamidas/efeitos adversos , Sulfonamidas/farmacologia , Sulfonamidas/uso terapêutico , Sunitinibe/efeitos adversos , Sunitinibe/farmacologia , Sunitinibe/uso terapêutico
2.
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
3.
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
4.
Cesk Slov Oftalmol ; 75(3): 138-144, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31779462

RESUMO

PURPOSE: To evaluate the safety and clinical efficacy of ranibizumab (Lucentis) in the treatment of choroidal neovascularization (CNV) caused by diseases other than age-related macular degeneration (AMD). PATIENTS: 21 patients with mean age 61  17.2 years (min 16, max 85) with CNV due to causes other than AMD, in particular pathological myopia (n=11), angioid streaks (n=3), central serous chorioretinopathy (n=2), North Carolina macular dystrophy (n=1), dominant familial drusen (n=1) and idiopathic CNV (n=3). METHODS: The patients were treated at the Ophthalmology Department of the University Hospital in Hradec Kralove with three monthly initial intravitreal injections of ranibizumab 0.5 mg with subsequent treatment regimen pro re nata (PRN). The best corrected visual acuity (BCVA) was evaluated on the ETDRS optotypes (Early Treatment Diabetic Retinopathy Study), central retinal thickness (CRT) was measured by optical coherent tomography (OCT) (Zeiss, Cirrus). These parameters were evaluated before start of the study and then at 1 (BCVA only), 4, 8, and 12 months during treatment. We also evaluated the possible occurrence of ocular and systemic side effects. RESULTS: Statistically significant improvement in the mean of BCVA score of 11.4 letters (p.


Assuntos
Inibidores da Angiogênese , Neovascularização de Coroide , Ranibizumab , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/uso terapêutico , Anticorpos Monoclonais Humanizados , Neovascularização de Coroide/tratamento farmacológico , Humanos , Injeções Intravítreas , Pessoa de Meia-Idade , Ranibizumab/uso terapêutico , Tomografia de Coerência Óptica , Resultado do Tratamento , Acuidade Visual , Adulto Jovem
5.
Invest Ophthalmol Vis Sci ; 60(14): 4632-4642, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31682714

RESUMO

Purpose: Targeting ß-adrenergic receptor signaling with propranolol has emerged as a potential candidate to counteract choroidal neovascularization (CNV). Little is known of its effect on macrophages, which play a critical role in CNV. We investigated the effect of propranolol on angiogenic response of mononuclear phagocytes (MPs). Methods: The angiogenic effect of propranolol was evaluated in laser-induced CNV model. Mice received intraperitoneal injections of propranolol (6 mg/kg/d) or vehicle. CNV area and inflammatory cells were determined respectively by using lectin staining and an anti-IBA-1 antibody on RPE/choroid flat mounts. Inflammatory gene expression was evaluated by quantitative (q) PCR analysis. Mechanisms of propranolol was studied in MP cell lines J774 and RAW264.7 and in primary peritoneal macrophages. Expression of pro- and antiangiogenic mediators was studied. In addition, effects of propranolol treatment of MPs was assessed on choroidal explant. Results: CNV was attenuated by propranolol and concomitantly associated with decreased inflammatory mediators IL-6 and TNFα, albeit with accumulation of (ß-adrenoceptor harboring) MPs in the CNV area. Conditioned media from MPs preincubated with propranolol exerted antiangiogenic effects. Treatment of J774 confirmed the attenuation of inflammatory response to propranolol and increased cleaved caspase-3 on choroidal explant. We found that propranolol increased pigment epithelium-derived factor (PEDF) expression in MPs. Trapping of PEDF with an antibody abrogated antiangiogenic effects of propranolol. PEDF was also detected in CNV-associated MPs. Conclusions: We hereby show that propranolol confers on MPs antiangiogenic properties by increasing PEDF expression, which complements its effects on vascular tissue resulting in inhibition of choroidal vasoproliferation in inflammatory conditions. The study supports possible use of propranolol as a therapeutic modality for CNV.


Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Inibidores da Angiogênese/uso terapêutico , Neovascularização de Coroide/prevenção & controle , Macrófagos Peritoneais/efeitos dos fármacos , Sistema Fagocitário Mononuclear/efeitos dos fármacos , Propranolol/uso terapêutico , Animais , Western Blotting , Caspase 3/metabolismo , Linhagem Celular , Neovascularização de Coroide/metabolismo , Neovascularização de Coroide/patologia , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Proteínas do Olho/metabolismo , Injeções Intraperitoneais , Interleucina-6/metabolismo , Macrófagos Peritoneais/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Sistema Fagocitário Mononuclear/metabolismo , Fatores de Crescimento Neural/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Epitélio Pigmentado da Retina/efeitos dos fármacos , Epitélio Pigmentado da Retina/metabolismo , Serpinas/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
6.
J Oncol Pharm Pract ; 25(8): 2049-2051, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31694494

RESUMO

Hemangioblastomas of central nervous system are rare and indolent. Twenty-five percent of cases are in association with von Hippel-Lindau disease. Surgery is the standard therapy but un-resectable or recurrent cases need radiation or systemic therapy. Defective von Hippel-Lindau tumor suppressor gene leads to vascular endothelial growth factor overexpression and enhance angiogenesis. Here we report a 19-year-old male, diagnosed at pediatric age, who had retinal and spinal cord hemangioblastomas. He was treated 34 months with bevacizumab, afterwards 12 months with thalidomide and tertiary therapy with pazopanib for 9 months which still goes on. In case of need, radiation and surgical procedures were performed. Vascular endothelial growth factor inhibition continuity is a good therapeutic option, which improves outcomes of von Hippel-Lindau-related hemangioblastomas.


Assuntos
Inibidores da Angiogênese/administração & dosagem , Hemangioblastoma/tratamento farmacológico , Doença de von Hippel-Lindau/complicações , Inibidores da Angiogênese/uso terapêutico , Hemangioblastoma/etiologia , Humanos , Masculino , Retina/patologia , Medula Espinal/patologia , Talidomida/administração & dosagem , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Adulto Jovem , Doença de von Hippel-Lindau/tratamento farmacológico
7.
J Cancer Res Clin Oncol ; 145(12): 3021-3036, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31617075

RESUMO

PURPOSE: In recent years, immune checkpoint blockade (ICB) therapies have shown good clinical responses in various solid cancers. However, a major challenge in the process of ICB treatment is when tumors do not have enough infiltrating T cells. Antiangiogenic drugs targeting vascular endothelial growth factor (VEGF) and its receptors have been approved for the treatment of various malignant solid tumors alone or in combination with other therapies. Our review mainly discusses the preclinical rationale and clinical efficacy of antiangiogenic and ICB combination therapy in urogenital tumors. METHODS: We reviewed relevant literature on preclinical research and clinical trial results regarding antiangiogenic and ICB combination therapy in urogenital tumors from PubMed. In addition, we searched ongoing clinical trials on ClinicalTrials.gov to collect information related to this specific topic. RESULTS: Antiangiogenesis therapy could enhance T cell recruitment and increase T cell infiltration into the tumor microenvironment by blocking VEGF-VEGF receptor 2 binding and downstream signaling pathways to normalize tumor blood vessels. The combination of ICB and antiangiogenesis therapy could improve antitumor activity according to subsequent preclinical experiments and several phase I/II/III clinical trials on urogenital tumors. CONCLUSION: Combined therapy has shown some antitumor efficacy in several urogenital tumors, such as metastatic renal cell carcinoma, metastatic urothelial and genitourinary tumors, endometrial carcinoma, ovarian cancer, and fallopian tube cancer. Combination therapy is a promising strategy that can be used to improve the therapeutic efficacy, and the identification of precise biomarkers of this combined therapy is the direction of future studies.


Assuntos
Inibidores da Angiogênese/farmacologia , Inibidores da Angiogênese/uso terapêutico , Neoplasias Urogenitais/tratamento farmacológico , Animais , Ensaios Clínicos como Assunto , Terapia Combinada/métodos , Humanos , Imunoterapia/métodos , Linfócitos T/efeitos dos fármacos , Microambiente Tumoral/efeitos dos fármacos
8.
Transplant Proc ; 51(9): 3092-3098, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31623898

RESUMO

Gastrointestinal bleeding after kidney transplantation is a complication that can occur from immunosuppressant use. We present a case of refractory small bowel bleeding treated successfully with thalidomide after multiple failed attempts of conventional treatment. A 65-year-old male patient with diabetic nephropathy underwent living donor kidney transplantation. The surgery was uneventful, however, he developed immunosuppressant-induced melena with unstable vital signs 11 days later. There were a total of 4 bleeding episodes until the 90th postoperative day, and he received a total of 290 units of red blood cell transfusion during this period. Endoscopic clipping, transarterial embolization, and 2 surgical interventions failed to stop the bleeding. A trial of thalidomide 100 mg per day finally stopped the bleeding and the patient was discharged on the 110th postoperative day with a functioning renal graft. This case shows that thalidomide can be a safe option to treat immunosuppressant-induced refractory gastrointestinal bleeding in the setting of kidney transplantation. Additionally, this is the first case that reports the survival of a renal graft after more than 3000 mL of transfusion.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Hemorragia Gastrointestinal/tratamento farmacológico , Transplante de Rim/efeitos adversos , Complicações Pós-Operatórias/tratamento farmacológico , Talidomida/uso terapêutico , Idoso , Humanos , Imunossupressores/efeitos adversos , Doadores Vivos , Masculino , Melena/imunologia , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Tacrolimo/efeitos adversos
9.
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
10.
Int J Nanomedicine ; 14: 7515-7531, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31571861

RESUMO

Background: Glioblastoma mutliforme is the most common and has the poorest prognosis of any malignant tumor of the central nervous system. Luteolin, the most abundant xanthone extracted from vegetables and medicinal plants, has been shown to have treatment effects in various cancer cell types. Luteolin is however, hydrophobic and has poor biocompatibility, which leads to low bioavailability. Patients and methods: In this study, folic acid modifiedpoly(ethylene glycol)-poly(e-caprolactone) (Fa-PEG-PCL) nano-micelles was used to encapsulate the luteolin, creating luteolin loaded PEG-PCL (Lut/Fa-PEG-PCL) micelles to treat glioma both in vitro and in vivo. Results: When compared with the free luteolin and Lut/MPEG-PCL, Lut/Fa-PEG-PCL induced a significant cell growth inhibition and more apoptosis of GL261 cells both in vitro and in vivo. The safety assessment also showed no obvious side effects were observed in mice which were administrated with free luteolin or Lut/MPEG-PCL and Lut/Fa-PEG-PCL. Conclusion: These results suggested Lut/Fa-PEG-PCL may be used as an excellent intravenously injectable formulation for the treatment and chemoprevention.


Assuntos
Sistemas de Liberação de Medicamentos , Ácido Fólico/química , Glioma/tratamento farmacológico , Luteolina/uso terapêutico , Nanopartículas/química , Inibidores da Angiogênese/farmacologia , Inibidores da Angiogênese/uso terapêutico , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Liberação Controlada de Fármacos , Glioma/irrigação sanguínea , Humanos , Luteolina/farmacocinética , Masculino , Camundongos Endogâmicos C57BL , Camundongos Nus , Micelas , Modelos Moleculares , Nanopartículas/ultraestrutura , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Poliésteres/química , Polietilenoglicóis/química , Antígeno Nuclear de Célula em Proliferação/metabolismo , Ratos Sprague-Dawley
11.
Cancer Sci ; 110(12): 3773-3787, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31578782

RESUMO

Vascular endothelial growth factor receptor 2 (VEGFR2) is highly expressed in tumor-associated endothelial cells, where it modulates tumor-promoting angiogenesis, and it is also found on the surface of tumor cells. Currently, there are no Ab therapeutics targeting VEGFR2 approved for the treatment of prostate cancer or leukemia. Therefore, development of novel efficacious anti-VEGFR2 Abs will benefit cancer patients. We used the Institute of Cellular and Organismic Biology human Ab library and affinity maturation to develop a fully human Ab, anti-VEGFR2-AF, which shows excellent VEGFR2 binding activity. Anti-VEGFR2-AF bound Ig-like domain 3 of VEGFR2 extracellular region to disrupt the interaction between VEGF-A and VEGFR2, neutralizing downstream signaling of the receptor. Moreover, anti-VEGFR2-AF inhibited capillary structure formation and exerted Ab-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity in vitro. We found that VEGFR2 is expressed in PC-3 human prostate cancer cell line and associated with malignancy and metastasis of human prostate cancer. In a PC-3 xenograft mouse model, treatment with anti-VEGFR2-AF repressed tumor growth and angiogenesis as effectively and safely as US FDA-approved anti-VEGFR2 therapeutic, ramucirumab. We also report for the first time that addition of anti-VEGFR2 Ab can enhance the efficacy of docetaxel in the treatment of a prostate cancer mouse model. In HL-60 human leukemia-xenografted mice, anti-VEGFR2-AF showed better efficacy than ramucirumab with prolonged survival and reduced metastasis of leukemia cells to ovaries and lymph nodes. Our findings suggest that anti-VEGFR2-AF has strong potential as a cancer therapy that could directly target VEGFR2-expressing tumor cells in addition to its anti-angiogenic action.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Leucemia/tratamento farmacológico , Neoplasias da Próstata/tratamento farmacológico , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Animais , Anticorpos/uso terapêutico , Linhagem Celular Tumoral , Epitopos de Linfócito B , Humanos , Masculino , Camundongos , Fosforilação , Fator A de Crescimento do Endotélio Vascular/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
12.
Middle East Afr J Ophthalmol ; 26(2): 117-119, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31543672

RESUMO

Vogt-Koyanagi-Harada (VKH) disease is a chronic, bilateral, granulomatous panuveitis associated with cutaneous, neurologic, and auditory manifestations. We report a 4-year-old Saudi boy who developed severe ocular complications by 5 years of age. He presented to King Khalid Eye Specialist Hospital at the age of 4 years and was previously operated on elsewhere for cataract with intraocular lens implantation in his right eye at the age of 3 years. He consecutively had iris capture and membrane formation around the intraocular lens. Examination revealed band keratopathy, posterior synechiae, and fundus depigmentation in both eyes with cataract formation in his left eye. At the age of 5.5 years, he developed subretinal neovascular membrane formation in the left eye. To the best of our knowledge, this patient is youngest VKH case that manifested most of the major complications at a young age as 5 years old.


Assuntos
Síndrome Uveomeningoencefálica/complicações , Inibidores da Angiogênese/uso terapêutico , Catarata/complicações , Extração de Catarata , Pré-Escolar , Neovascularização de Coroide/tratamento farmacológico , Neovascularização de Coroide/etiologia , Distrofias Hereditárias da Córnea/etiologia , Distrofias Hereditárias da Córnea/cirurgia , Angiofluoresceinografia , Hospitais Especializados , Humanos , Injeções Intravítreas , Implante de Lente Intraocular , Lentes Intraoculares , Masculino , Neovascularização Retiniana/diagnóstico , Neovascularização Retiniana/tratamento farmacológico , Neovascularização Retiniana/etiologia , Centros de Atenção Terciária , Síndrome Uveomeningoencefálica/diagnóstico , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Adulto Jovem
13.
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
14.
Chemotherapy ; 64(2): 110-114, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31533095

RESUMO

Patients who experience extramedullary relapses (EMR) of multiple myeloma (MM) have an adverse prognosis, also in this era of novel agents like proteasome inhibitors and immunomodulatory drugs. We describe the case of an MM patient with EMR at 2 different sites after allogeneic stem cell transplantation. EMR was refractory to bortezomib, anthracycline, and bendamustine, but the patient achieved long-term complete remission (4 years) with pomalidomide and dexamethasone. This supports the hypothesis that this could be due to the graft-versus-myeloma effect during therapy enhanced by pomalidomide.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Talidomida/análogos & derivados , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Imagem por Ressonância Magnética , Pessoa de Meia-Idade , Mieloma Múltiplo/terapia , Recidiva , Indução de Remissão , Talidomida/uso terapêutico , Transplante Homólogo
15.
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
16.
Ophthalmic Surg Lasers Imaging Retina ; 50(8): 485-491, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-31415694

RESUMO

BACKGROUND AND OBJECTIVE: Difficulty exists in the follow-up of proliferative macular telangiectasia type 2 (MacTel 2) cases after anti-vascular endothelial growth factor (VEGF) treatment due to staining in fluorescein angiography (FA) and alteration in retinal layers by optical coherence tomography (OCT). Herein, the authors report three cases in which OCT angiography (OCTA) could resolve this issue. PATIENTS AND METHODS: In this retrospective, observational case series, diagnosis of MacTel 2 was made based on clinical examination, FA, OCT, and OCTA at presentation. Regression of neovessels was monitored by OCT and OCTA. RESULTS: OCTA could delineate neovessels before treatment in all cases and facilitate differentiation between active and regressed lesions after treatment. Simultaneous OCT images were less easily appreciated due to altered retinal structure secondary to degenerative nature of the disease. CONCLUSION: OCTA could be the tool of choice to monitor neovascular response to anti-VEGF treatment in proliferative MacTel 2. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:485-491.].


Assuntos
Inibidores da Angiogênese/uso terapêutico , Técnicas de Diagnóstico Oftalmológico , Ranibizumab/uso terapêutico , Telangiectasia Retiniana , Idoso , Feminino , Angiofluoresceinografia/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Telangiectasia Retiniana/diagnóstico , Telangiectasia Retiniana/tratamento farmacológico , Vasos Retinianos/patologia , Estudos Retrospectivos , Tomografia de Coerência Óptica/métodos
17.
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
18.
BMC Cancer ; 19(1): 794, 2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31409302

RESUMO

BACKGROUND: PALETTE is a phase 3 trial that demonstrated single-agent activity of pazopanib in advanced soft tissue sarcomas (aSTS). We performed retrospective subgroup analyses to explore potential relationships between patient characteristics, prior lines of therapy, dose intensity, and dose modifications on safety and efficacy of pazopanib in aSTS. METHODS: PALETTE compared pazopanib with placebo in patients with aSTS (age ≥ 18 years) whose disease had progressed during or following prior chemotherapy. In these subgroup analyses, median progression-free survival (mPFS) among patients receiving pazopanib was the efficacy outcome of interest. Adverse events (AEs) were also compared within subgroups. All analyses were descriptive and exploratory. RESULTS: A total of 246 patients received pazopanib in the PALETTE study. The mPFS was longer in patients who had only 1 prior line versus 2+ prior lines of therapy (24.7 vs 18.9 weeks, respectively); AE rates were similar regardless of number of prior lines of therapy. The mPFS was similar in patients aged < 65 and ≥ 65 y (20.0 and 20.1 weeks, respectively). Although AEs leading to study discontinuation were higher in older patients (≥65 y, 30%; < 65 y, 17%), rates of dose reductions, dose interruptions, and serious AEs were similar between the 2 age groups. No reduction in mPFS was noted in patients requiring dose reductions or dose interruptions to manage toxicities. CONCLUSIONS: Longer mPFS was observed in patients receiving pazopanib following only 1 line of therapy. Additionally, mPFS with pazopanib was maintained regardless of patient age or dose modifications used to manage toxicity. TRIAL REGISTRATION: NCT00753688 , first posted September 16, 2008 (registered prospectively).


Assuntos
Inibidores da Angiogênese/uso terapêutico , Antineoplásicos/uso terapêutico , Pirimidinas/uso terapêutico , Sarcoma/diagnóstico , Sarcoma/tratamento farmacológico , Sulfonamidas/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/efeitos adversos , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Ensaios Clínicos Fase III como Assunto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Pirimidinas/administração & dosagem , Pirimidinas/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Retrospectivos , Sarcoma/mortalidade , Sulfonamidas/administração & dosagem , Sulfonamidas/efeitos adversos , Análise de Sobrevida , Resultado do Tratamento
20.
Future Oncol ; 15(22): 2571-2576, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31407939

RESUMO

Fruquintinib is a potent, highly selective and orally active inhibitor of VEGFR1, 2, 3 tyrosine kinases. It inhibits VEGF-induced VEGFR2 phosphorylation, endothelial cell proliferation and tubule formation. Currently, it has been approved for the treatment of metastatic colorectal cancer in patients who have failed at least two prior systemic antineoplastic therapies in China. However, it is not approved outside China, and there is another similar small molecular VEGFR multitarget drug approved in China, USA, Europe, etc. Here, we summarize the mechanism characteristics and clinical development of fruquintinib supporting its use in the treatment of metastastic colorectal cancer as well as explorations in other tumor types.


Assuntos
Benzofuranos/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neovascularização Patológica/tratamento farmacológico , Quinazolinas/uso terapêutico , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/genética , Inibidores da Angiogênese/uso terapêutico , Proliferação de Células/efeitos dos fármacos , China , Ensaios Clínicos como Assunto , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Europa (Continente) , Humanos , Metástase Neoplásica , Neovascularização Patológica/genética , Neovascularização Patológica/patologia , Fosforilação/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Fator A de Crescimento do Endotélio Vascular/genética
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