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1.
AAPS PharmSciTech ; 21(8): 291, 2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-33085055

RESUMO

Age-related macular degeneration, precisely neovascular form, is the leading cause of vision loss and the key treatment includes intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) agents. A method to increase local concentration of drug at posterior segment of the eye and to reduce the frequency of intravitreal injections is an unmet need. Resveratrol, a naturally occurring antioxidant and anti-inflammatory polyphenol, was loaded in PLGA polymeric nanoparticles to study their sustained release property and effectiveness in reducing expression of VEGF protein in vitro. Nanoparticles were characterized using FTIR, DSC, size, encapsulation efficiency, TEM, and in vitro drug release studies. Using MTT assay, the cytotoxicity of formulation was evaluated on ARPE-19 cells. The cellular uptake and VEGF expression levels were also evaluated in in vitro settings. The optimized formulation had a particle size of 102.7 nm with - 47.30 mV of zeta potential. Entrapment efficiency was found to be 65.21%. The cell viability results suggested compatibility of developed formulation. Cellular uptake and VEGF expression levels for the formulated nanoparticles specified that the developed formulation showed potential cellular uptake and had displayed anti-angiogenic property by inhibiting VEGF expression in vitro. The results showed successful development of resveratrol-loaded nanoparticles which may be used for neovascular AMD treatment alone or in combination with anti-VEGF agents.


Assuntos
Inibidores da Angiogênese/administração & dosagem , Antioxidantes/administração & dosagem , Nanopartículas , Resveratrol/administração & dosagem , Degeneração Macular Exsudativa/tratamento farmacológico , Inibidores da Angiogênese/farmacologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Humanos , Injeções Intravítreas , Polímeros/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Acuidade Visual
2.
J Fr Ophtalmol ; 43(10): 1047-1053, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33004191

RESUMO

Intravitreal anti-vascular epithelial growth factor (anti-VEGF) injections have revolutionised the treatment of macular diseases, but can be stressful for the patient. We surveyed 904 patients receiving injections at 5 centres in France regarding their feelings toward anti-VEGF injections. The mean age was 77.4 years, and the injections were performed mostly for age related macular degeneration (72%). Half of the patients had previously received>10 injections, 35.6% had received 3-10 injections, and 14.2% had received<3 injections. The mean (SD) stress score was 4.2 [on a scale from 1-10 (0=least stressful, 10=extremely stressful)]. Most patients (70%) reported low to moderate stress (score ≤5). The number of previous injections did not influence stress scores. Paradoxically, 61.2% of patients reported finding injections to be less stressful over time. Most patients found injections to be less traumatic than expected (64%) or just as they had anticipated (25%). Most patients (88%) were not bothered by the presence of other patients in the waiting room. Most patients (78.8%) preferred to be injected quickly before they had time to feel stressed about the procedure. Injections were generally well accepted; most patients would prefer to maintain their current schedule of injections and their current vision (55.7%), or would be willing to have more frequent injections for better vision (39.5%). Our results suggest that stress appears to be more related to the patient's psychological make-up than to the treatment experience or the number of injections received.


Assuntos
Inibidores da Angiogênese/administração & dosagem , Ansiedade/epidemiologia , Injeções Intravítreas/psicologia , Degeneração Macular/tratamento farmacológico , Satisfação do Paciente/estatística & dados numéricos , Estresse Psicológico/epidemiologia , Fator A de Crescimento do Endotélio Vascular/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/efeitos adversos , Ansiedade/etiologia , Feminino , França/epidemiologia , Humanos , Injeções Intravítreas/efeitos adversos , Degeneração Macular/epidemiologia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/psicologia , Estresse Psicológico/etiologia , Inquéritos e Questionários , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores
3.
J Fr Ophtalmol ; 43(10): 989-995, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33081995

RESUMO

PURPOSE: To report predictive factors for therapeutic response to anti-VEGF in patients with neovascular age-related macular degeneration (nAMD) in daily clinical practice in our patient population. METHODS: Retrospective cohort study including 56 patients (69 eyes) with nAMD treated with anti-VEGF, followed for at least two years between February 2012 and April 2018. Patients received three intravitreal anti-VEGF (bevacizumab) injections (loading dose) and were monitored and treated according to a PRN regimen. We analysed whether a gain in visual acuity of 15 or more ETDRS letters at the final visit was associated with demographic characteristics, presence of systemic comorbidities, fundus lesions or measurable improvement on Cirrus optical coherence tomography (OCT) between the first and last visit. RESULTS: After a mean follow-up of 15.5 months (4.7-27.8 interquartile range), central retinal thickness (CRT) (RR: 1.004; IC 95%: 1.001-1.007; P=0.011) and macular hemorrhage (RR: 0.30; IC 95%: 0.10-0.90, P=0.032) at baseline were found to be useful predictive factors for visual acuity improvement (≥15 letters) in patients treated for nAMD by anti-VEGF in a real world clinical setting. CONCLUSION: In the present series of patients with nAMD receiving a loading dose of bevacizumab and followed according to a PRN regimen for 24 months, the only predictable factors for a ≥15 letter gain in visual acuity were anatomical response as measured by OCT and macular hemorrhage at baseline.


Assuntos
Inibidores da Angiogênese/administração & dosagem , Bevacizumab/administração & dosagem , Degeneração Macular/tratamento farmacológico , Acuidade Visual , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/efeitos adversos , Bevacizumab/efeitos adversos , Biomarcadores Farmacológicos/análise , Feminino , Humanos , Injeções Intravítreas , Degeneração Macular/diagnóstico , Degeneração Macular/epidemiologia , Masculino , Neovascularização Patológica/diagnóstico , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/epidemiologia , Padrões de Prática Médica/estatística & dados numéricos , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Fator A de Crescimento do Endotélio Vascular/imunologia
4.
Clin Exp Ophthalmol ; 48(9): 1276-1285, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32902023

RESUMO

BACKGROUND: Clinical ophthalmological guidelines encourage the assessment of potential benefits and harms when deciding whether to perform elective ophthalmology procedures during the COVID-19 pandemic, in order to minimize the risk of disease transmission. METHOD: We performed probability calculations to estimate COVID-19 infection status and likelihood of disease transmission among neovascular age-related macular degeneration patients and health-care workers during anti-VEGF procedures, at various community prevalence levels of COVID-19. We then applied the expected burden of COVID-19 illness and death expressed through health-adjusted life-years (HALYs) lost. We compared these results to the expected disease burden of severe visual impairment if sight protecting anti-VEGF injections were not performed. RESULTS: Our calculations suggest a wide range of contexts where the benefits of treatment to prevent progression to severe visual impairment or blindness are greater than the expected harms to the patient and immediate health care team due to COVID-19. For example, with appropriate protective equipment the benefits of treatment outweigh harms when the chance of progression to severe visual impairment is >0.044% for all scenarios where COVID-19 prevalence was 1/1000, even when the attack rate in the clinical setting is very high (5-43%). CONCLUSION: Unless COVID-19 prevalence is very high, the reduced disease burden from avoiding visual impairment outweighs the expected HALYs lost from COVID-19 transmission. This finding is driven by the fact that HALYs lost when someone suffers severe visual impairment for 5 years are equivalent to nearly 400 moderate cases of infectious disease lasting 2 weeks each.


Assuntos
Inibidores da Angiogênese/efeitos adversos , Transmissão de Doença Infecciosa/estatística & dados numéricos , Degeneração Macular/tratamento farmacológico , Pandemias , Acuidade Visual , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/administração & dosagem , Comorbidade , Feminino , Humanos , Injeções Intravítreas/efeitos adversos , Degeneração Macular/epidemiologia , Masculino , Pessoa de Meia-Idade , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores
5.
Lancet Oncol ; 21(11): 1489-1499, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32966810

RESUMO

BACKGROUND: Surufatinib showed superior efficacy in extrapancreatic neuroendocrine tumours (NETs) in the phase 3 SANET-ep study. In SANET-p, we aimed to assess the efficacy and safety of surufatinib in patients with advanced pancreatic NETs. METHODS: SANET-p was a multicentre, randomised, double-blind, placebo-controlled, phase 3 study, done in 21 hospitals across China. Eligible patients were adults (aged 18 years or older) with progressive, advanced, well differentiated pancreatic NETs, Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and progression on up to two kinds of previous systemic regimens for advanced disease. Patients were randomly assigned (2:1) via an interactive web response system to receive 300 mg of surufatinib or placebo, taken orally once per day in consecutive 4-week treatment cycles until disease progression, intolerable toxicity, withdrawal of consent, poor compliance, use of other antitumour medication, pregnancy, loss to follow-up, or if the investigator deemed discontinuation in the patient's best interest. Randomisation was done centrally using stratified block randomisation (block size three), stratified by pathological grade, previous systemic antitumour treatment, and ECOG performance status score. Patients, investigators, research staff, and the sponsor study team were masked to treatment allocation. Crossover to surufatinib was permitted for patients in the placebo group with disease progression. The primary endpoint was investigator-assessed progression-free survival in the intention-to-treat population, which included all patients in randomisation. A pre-planned interim analysis was done at 70% of the predicted progression-free survival events. This study is registered at ClinicalTrials.gov, NCT02589821. FINDINGS: Between Feb 18, 2016, and Nov 11, 2019, of 264 patients who were screened, 172 (65%) patients were randomly assigned to receive surufatinib (n=113) or placebo (n=59). The median follow-up was 19·3 months (95% CI 9·3-19·4) in the surufatinib group and 11·1 months (5·7-35·9) in the placebo group. The median investigator-assessed progression-free survival was 10·9 months (7·5-13·8) for surufatinib versus 3·7 months (2·8-5·6) for placebo (hazard ratio 0·49, 95% CI 0·32-0·76; p=0·0011). The trial met the early stopping criteria at the interim analysis and was terminated on recommendation from the independent data monitoring committee. The most common grade 3 or worse treatment-related adverse events were hypertension (43 [38%] of 113 with surufatinib vs four [7%] of 59 with placebo), proteinuria (11 [10%] vs one [2%]), and hypertriglyceridaemia (eight [7%] vs none). Treatment-related serious adverse events were reported in 25 (22%) patients in the surufatinib group and four (7%) patients in the placebo group. There were three on-treatment deaths in the surufatinib group, including two deaths due to adverse events (gastrointestinal haemorrhage [possibly treatment-related] and cerebral haemorrhage [unlikely to be treatment-related]), and one death attributed to disease progression. One on-treatment death in the placebo group was attributed to disease progression. INTERPRETATION: Surufatinib significantly improves progression-free survival and has an acceptable safety profile in patients with progressive, advanced pancreatic NETs, and could be a potential treatment option in this patient population. FUNDING: Hutchison MediPharma.


Assuntos
Inibidores da Angiogênese/administração & dosagem , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Tumores Neuroendócrinos/tratamento farmacológico , Neoplasias Pancreáticas/tratamento farmacológico , Adulto , Idoso , Inibidores da Angiogênese/efeitos adversos , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , China/epidemiologia , Progressão da Doença , Método Duplo-Cego , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/classificação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Tumores Neuroendócrinos/epidemiologia , Tumores Neuroendócrinos/genética , Tumores Neuroendócrinos/patologia , Neoplasias Pancreáticas/epidemiologia , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Intervalo Livre de Progressão , Resultado do Tratamento
6.
Lancet Oncol ; 21(11): 1500-1512, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32966811

RESUMO

BACKGROUND: Therapeutic options for advanced neuroendocrine tumours (NETs) are limited. We investigated the efficacy and safety of surufatinib (HMPL-012, sulfatinib) in patients with extrapancreatic NETs. METHODS: SANET-ep was a randomised, double-blind, placebo-controlled, phase 3 trial undertaken at 24 hospitals across China. Patients (aged 18 years or older) with unresectable or metastatic, well differentiated, extrapancreatic NETs, with an Eastern Cooperative Oncology Group performance status of 0 or 1, and progression on no more than two types of previous systemic regimens were enrolled. Patients were centrally randomly assigned (2:1) using stratified block randomisation (block size 3) via an interactive web response system to receive oral surufatinib at 300 mg per day or matching placebo. Randomisation was stratified by tumour origin, pathological grade, and previous treatment. Patients, investigators, research staff and the sponsor study team were masked to treatment allocation. Crossover to the surufatinib group was allowed for patients in the placebo group at disease progression. The primary endpoint was investigator-assessed progression-free survival, which was analysed in the intention-to-treat population. A preplanned interim analysis was done at 70% of predicted progression-free survival events. This study was registered with ClinicalTrials.gov, NCT02588170. Follow-up is ongoing. FINDINGS: Between Dec 9, 2015, and March 31, 2019, 198 patients were randomly assigned to surufatinib (n=129) or placebo (n=69). Median follow-up was 13·8 months (95% CI 11·1-16·7) in the surufatinib group and 16·6 months (9·2-not calculable) in the placebo group. Investigator-assessed median progression-free survival was 9·2 months (95% CI 7·4-11·1) in the surufatinib group versus 3·8 months (3·7-5·7) in the placebo group (hazard ratio 0·33; 95% CI 0·22-0·50; p<0·0001). As the trial met the predefined criteria for early discontinuation of the study at the interim analysis, the study was terminated early, as recommended by the independent data monitoring committee. The most common treatment-related adverse events of grade 3 or worse were hypertension (47 [36%] of 129 patients in the surufatinib group vs nine [13%] of 68 patients in the placebo group) and proteinuria (25 [19%] vs zero). Treatment-related serious adverse events were reported in 32 (25%) of 129 patients in the surufatinib group and nine (13%) of 68 patients in the placebo group. Treatment-related deaths occurred in three patients in the surufatinib group (disseminated intravascular coagulation and hepatic encephalopathy, liver injury, and death with unknown reason) and one patient in the placebo group (cachexia and respiratory failure). INTERPRETATION: Progression-free survival was significantly longer in patients given surufatinib compared with patients given placebo, and surufatinib has a favourable benefit-to-risk profile in patients with progressive, advanced, well differentiated extrapancreatic NETs. Our results suggest that surufatinib might be a new treatment option for this population. FUNDING: Hutchison MediPharma.


Assuntos
Inibidores da Angiogênese/administração & dosagem , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Tumores Neuroendócrinos/tratamento farmacológico , Neoplasias Pancreáticas/tratamento farmacológico , Adulto , Idoso , Inibidores da Angiogênese/efeitos adversos , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , China/epidemiologia , Progressão da Doença , Método Duplo-Cego , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/classificação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Tumores Neuroendócrinos/epidemiologia , Tumores Neuroendócrinos/genética , Tumores Neuroendócrinos/patologia , Neoplasias Pancreáticas/epidemiologia , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Intervalo Livre de Progressão , Resultado do Tratamento
7.
Anticancer Res ; 40(9): 5285-5290, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32878818

RESUMO

BACKGROUND/AIM: Chemotherapy with additional bevacizumab is the standard treatment for primary and recurrent ovarian cancer. We aimed to investigate the clinical utility and safety of bevacizumab when used in combination with chemotherapy after disease progression. PATIENTS AND METHODS: This retrospective, observational study recruited patients treated for recurrent ovarian cancer from 2014 to 2016. We evaluated the effects of bevacizumab with chemotherapy in patients whose disease had progressed following treatment with bevacizumab. We assessed progression-free survival and adverse events. RESULTS: Thirty-three patients received post-progression treatment with bevacizumab. The median progression-free survival was 8.7 months (95% confidence interval=5.5-11). The progression-free survival was compared pre- and post-progression treatment, and was longer in platinum-resistant than platinum-sensitive cases after treatment (p=0.06). The most common non-hematological toxicity was proteinuria. The incidence of serious adverse events was low. CONCLUSION: Continuous administration of bevacizumab may be beneficial for ovarian cancer patients after disease progression.


Assuntos
Inibidores da Angiogênese/administração & dosagem , Antineoplásicos Imunológicos/administração & dosagem , Bevacizumab/administração & dosagem , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Adulto , Idoso , Progressão da Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Ovarianas/mortalidade , Prognóstico , Recidiva , Retratamento , Estudos Retrospectivos , Resultado do Tratamento
8.
Sci Rep ; 10(1): 14943, 2020 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-32913279

RESUMO

To evaluate the influence of fibrovascular pigment epithelial detachment (FVPED) on treatment outcomes in eyes with subretinal hemorrhage secondary to neovascular age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV). This retrospective study included 83 eyes diagnosed with fovea-involving submacular hemorrhage secondary to neovascular AMD or PCV. All the patients were treated with intravitreal anti-vascular endothelial growth factor. Eyes showing definite FVPED, which involves the subfoveal region, were included in the FVPED group. Eyes without subfoveal PED, shallow irregular PEDs, or serous/hemorrhagic PED were stratified to the non-FVPED group. The best-corrected visual acuity (BCVA) at diagnosis, at 3 months, at 12 months, and lesion re-activation after initial treatment were compared between the two groups. The mean size of hemorrhage was 8.6 ± 7.6 disc diameter areas. In the FVPED group, the mean logarithm of minimal angle of resolution BCVA was 1.11 ± 0.49 at diagnosis, 0.89 ± 0.58 at 3 months, and 1.05 ± 0.63 at 12 months. In the non-FVPED group, the values were 0.97 ± 0.56, 0.56 ± 0.55, and 0.45 ± 0.50, respectively. The BCVA at 3 months (P = 0.036) and at 12 months (P < 0.001) was significantly worse in the FVPED group than in the non-FVPED group. In addition, the incidence of lesion reactivation was greater in the FVPED group (83.3%) than in the non-FVPED group (38.5%) (P < 0.001). The presence of subfoveal FVPED was associated with a high incidence of lesion re-activation and poor treatment outcomes in eyes with subretinal hemorrhage. This result suggests that different treatment strategies are needed between eyes with and without FVPED.


Assuntos
Inibidores da Angiogênese/administração & dosagem , Neovascularização de Coroide/complicações , Descolamento Retiniano/patologia , Hemorragia Retiniana/patologia , Epitélio Pigmentado da Retina/patologia , Acuidade Visual/efeitos dos fármacos , Degeneração Macular Exsudativa/complicações , Idoso , Algoritmos , Inibidores da Angiogênese/efeitos adversos , Neovascularização de Coroide/tratamento farmacológico , Feminino , Angiofluoresceinografia , Humanos , Injeções Intravítreas , Masculino , Prognóstico , Descolamento Retiniano/etiologia , Hemorragia Retiniana/etiologia , Epitélio Pigmentado da Retina/efeitos dos fármacos , Estudos Retrospectivos , Resultado do Tratamento , Degeneração Macular Exsudativa/tratamento farmacológico
9.
Value Health ; 23(7): 928-935, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32762995

RESUMO

OBJECTIVES: Mappings to convert clinical measures to preference-based measures of health such as the EQ-5D-3L are sometimes required in cost-utility analyses. We developed mappings to convert best-corrected visual acuity (BCVA) to the EQ-5D-3L, the EQ-5D-3L with a vision bolt-on (EQ-5D V), and the Visual Functioning Questionnaire-Utility Index (VFQ-UI) in patients with macular edema caused by central retinal vein occlusion. METHODS: We used data from Lucentis, Eylea, Avastin in vein occlusion (LEAVO), which is a phase-3 randomized controlled trial comparing ranibizumab, aflibercept, and bevacizumab in 463 patients with observations at 6 time points. We estimated adjusted limited dependent variable mixture models consisting of 1 to 4 distributions (components) using BCVA in each eye, age, and sex to predict utility within the components and BCVA as a determinant of component membership. We compared model fit using mean error, mean absolute error, root mean square error, Akaike information criteria, Bayesian information criteria, and visual inspection of mean predicted and observed utilities and cumulative distribution functions. RESULTS: Mean utility scores were 0.82 for the EQ-5D-3L, 0.79 for the EQ-5D V, and 0.88 for the VFQ-UI. The best-fitting models for the EQ-5D and EQ-5D V had 2 components (with means of approximately 0.44 and 0.85), and the best-fitting model for VFQ-UI had 3 components (with means of approximately 0.95, 0.74, and 0.90). CONCLUSIONS: Models with multiple components better predict utility than those with single components. This article provides a valuable addition to the literature, in which previous mappings in visual acuity have been limited to linear regressions, resulting in unfounded assumptions about the distribution of the dependent variable.


Assuntos
Inibidores da Angiogênese/administração & dosagem , Edema Macular/tratamento farmacológico , Inquéritos e Questionários , Acuidade Visual/efeitos dos fármacos , Adulto , Idoso , Idoso de 80 Anos ou mais , Bevacizumab/administração & dosagem , Feminino , Humanos , Edema Macular/etiologia , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Preferência do Paciente , Qualidade de Vida , Ranibizumab/administração & dosagem , Receptores de Fatores de Crescimento do Endotélio Vascular/administração & dosagem , Proteínas Recombinantes de Fusão/administração & dosagem , Oclusão da Veia Retiniana/complicações , Adulto Jovem
10.
PLoS One ; 15(8): e0237330, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32780752

RESUMO

We investigated whether response to photodynamic therapy (PDT) with intravitreal aflibercept injection (IAI) for polypoidal choroidal vasculopathy (PCV) differs depending on fellow eye condition. A retrospective review was conducted for consecutive 60 eyes with PCV treated with PDT combined with IAI as well as 2-years of follow-up data. Fellow eyes were divided into 4 groups; Group 0: no drusen, Group 1; pachydrusen, Group 2; soft drusen, Group 3: PCV/fibrovascular scarring. Best-corrected visual acuity improved at 24-months irrespective of groups and there were no significant differences in visual improvement among treated eyes among the 4 groups. Within 2-years, 35 (58.3%) required the retreatment. The need for retreatment including additional injection and the combination therapy was significantly less in Group 1(12.5%) compared to the others (P = 0.0038) and mean number of additional IAI was also less in Group 1 compared to the others (P = 0.017). The retreatment-free period from the initial combination therapy was longest in Group 1 (23.6±1.1 months) (P = 0.0055, Group 0: 19.1±6.9, Group 2: 12.8±7.9, Group 3: 11.5±9.9). The need for retreatment was significantly different according to fellow-eye condition. Among PCV patients, pachydrusen in fellow eyes appear to be a predictive characteristic for a decreased treatment burden at 2 years.


Assuntos
Inibidores da Angiogênese/administração & dosagem , Neovascularização de Coroide/tratamento farmacológico , Fotoquimioterapia/métodos , Receptores de Fatores de Crescimento do Endotélio Vascular/administração & dosagem , Proteínas Recombinantes de Fusão/administração & dosagem , Drusas Retinianas/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Corioide/irrigação sanguínea , Corioide/diagnóstico por imagem , Corioide/efeitos dos fármacos , Neovascularização de Coroide/diagnóstico , Feminino , Seguimentos , Humanos , Injeções Intravítreas , Masculino , Pessoa de Meia-Idade , Drusas Retinianas/diagnóstico , Retratamento/estatística & dados numéricos , Estudos Retrospectivos , Fatores de Risco , Tomografia de Coerência Óptica , Resultado do Tratamento , Acuidade Visual
11.
Mayo Clin Proc ; 95(8): 1604-1612, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32753135

RESUMO

OBJECTIVE: To present our center's experience with a maintenance treatment algorithm for intravenous bevacizumab that allows for personalized therapy decisions. PATIENTS AND METHODS: We reviewed all patients treated with intravenous bevacizumab for hereditary hemorrhagic telangiectasia-related bleeding and/or high-output cardiac failure (HOCF) from January 1, 2013, to July 1, 2019, at the Mayo Clinic, Rochester, Minnesota. Data regarding subsequent bevacizumab dosing were abstracted. RESULTS: A total of 57 patients (n=40, 70.2% females) were identified with a median age of 65 (55 to 74; range, 37 to 89) years. High-cardiac output state was present in 21 patients (36.8%) and 10 (17.5%) were treated with intravenous bevacizumab primarily for HOCF. The median duration of follow-up after completion of the initial intravenous bevacizumab treatment was 25 (12.3 to 40.8; range, 0.1 to 65.4) months. A total of 20 (35.1%) patients with a median follow-up of 13.5 (range, 0 to 48.4) months required no maintenance dosing throughout the duration of follow-up. Among those who required subsequent maintenance doses, only a small fraction (8 patients; 14.0%) required regular maintenance doses every 4 to 8 weeks during follow-up whereas the majority of patients required intermittent "as-needed" doses at varying intervals. CONCLUSION: There is significant inter-individual variability in the need for maintenance intravenous bevacizumab when patients are followed using a predefined bevacizumab maintenance dosing treatment algorithm. The use of "as-needed" maintenance bevacizumab appears to be an effective strategy for management of hereditary hemorrhagic telangiectasia-related bleeding and HOCF.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Bevacizumab/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Hemorragia/tratamento farmacológico , Telangiectasia Hemorrágica Hereditária/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/administração & dosagem , Bevacizumab/administração & dosagem , Feminino , Insuficiência Cardíaca/etiologia , Hemorragia/etiologia , Humanos , Individualidade , Injeções Intravenosas , Masculino , Pessoa de Meia-Idade , Medicina de Precisão/métodos , Estudos Retrospectivos , Telangiectasia Hemorrágica Hereditária/complicações
12.
Sci Rep ; 10(1): 13248, 2020 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-32764619

RESUMO

The number of eye diseases treated with intravitreal injections is increasing. Obviously, an injection of fluid into the eye results in an increase of intraocular pressure (IOP), the main risk factor for glaucoma. However, the effect of these repeated IOP increases on the eye is unclear. Therefore, we performed a systematic review with meta-analyses. PubMed, Embase and Clinical Trials Registries were searched for articles investigating the relationship between intravitreal injections (anti-vascular endothelial growth factor [anti-VEGF] or steroids) and either IOP, retinal nerve fiber layer (RNFL)-thickness and glaucoma. Multiple meta-analyses were performed, combining data on intravitreal injection of anti-VEGF medication and dexamethasone implants. A total of 74 articles were eligible for meta-analyses. The short-term effect of an intravitreal injection of anti-VEGF showed a statistically significant increase in IOP. One day after injection of anti-VEGF, however, IOP was significantly lower than baseline. The long-term time-intervals showed no significant difference in IOP. After intravitreal injection of a dexamethasone implant, IOP was significantly higher than baseline 1 month post-injection. RNFL-thickness was significantly reduced 6 and 12 months post-injection of anti-VEGF, as well as at end of follow up. Caution is advised when using intravitreal medication, especially when treating patients with advanced glaucoma; in these cases, prophylactic IOP-lowering medication may be considered.


Assuntos
Inibidores da Angiogênese/administração & dosagem , Dexametasona/administração & dosagem , Glaucoma/tratamento farmacológico , Pressão Intraocular/efeitos dos fármacos , Fibras Nervosas/efeitos dos fármacos , Inibidores da Angiogênese/efeitos adversos , Dexametasona/efeitos adversos , Feminino , Humanos , Injeções Intravítreas , Masculino , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores
13.
Eur J Cancer ; 136: 195-203, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32712550

RESUMO

BACKGROUND: Sarcomatoid renal cell carcinoma (sRCC) represents a rare form of renal cell carcinoma marked by an aggressive biology, poor prognosis and little benefit from anti-angiogenic targeted therapy. More promising results come from the recent therapeutic strategy based on immune checkpoint inhibitor (ICI) combinations. MATERIALS AND METHODS: For this meta-analysis, we searched MEDLINE/PubMed, the Cochrane Library and American Society of Medical Oncology (ASCO) Meeting abstracts for phase II or III randomised clinical trials. Data extraction was conducted according to the Preferred Reporting Items for Systematic Review and Meta-Analysis statement. The hazard ratios (HRs) for progression-free survival (PFS) and overall survival (OS) with the relative 95% confidence intervals were extracted from studies. Summary HRs were calculated using random- or fixed-effects models, depending on the heterogeneity of the included studies. RESULTS: Four studies were selected for final analysis, including 467 patients (226 treated in with ICI combinations and 241 received sunitinib in the control arms). ICI-based combinations were associated with an improved PFS and OS compared with sunitinib, with a reduction of more than 40% of progression (HR = 0.56; p < 0.0001) and mortality (HR = 0.56; p = 0.001) risk. Moreover, ICI-based combinations are associated with a objective response rate (ORR) of more than 50% (versus 20% with sunitinib), corresponding to a doubled risk of achieving an ORR compared with controls (relative risk [RR] = 2.15; p < 0.00001). Finally, immunotherapy significantly increased the possibility to obtain complete responses (RR = 8.15, p = 0.0002) with an incidence of 11%. CONCLUSION: Our data support the efficacy of ICI-based combinations for sRCC therapy, redefining the first-line treatment.


Assuntos
Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Terapia Neoadjuvante/métodos , Inibidores da Angiogênese/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Ensaios Clínicos Fase II como Assunto/estatística & dados numéricos , Ensaios Clínicos Fase III como Assunto/estatística & dados numéricos , Humanos , Imunoterapia/métodos , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Terapia Neoadjuvante/estatística & dados numéricos , Intervalo Livre de Progressão , Inibidores de Proteínas Quinases/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Indução de Remissão , Análise de Sobrevida , Resultado do Tratamento
14.
J Fr Ophtalmol ; 43(8): 710-717, 2020 Oct.
Artigo em Francês | MEDLINE | ID: mdl-32653096

RESUMO

Initial management of diabetic macular edema (DME) is well-defined, but there is a lack of national or international consensus for patients who do not respond or respond only partially to these treatments. Several studies, mostly retrospective, have assessed medication switches, but currently, the literature contains no randomized studies. The goal of this article is to present an algorithm for switching medications, which can be proposed to DME patients treated with anti-VEGF agents, as defined by a group of French retina experts, supported by the existing literature on the subject. After initiation of an anti-VEGF treatment for DME, the response is usually assessed after 5 monthly injections. A partial anatomical response (reduction of central retinal thickness between 10 and 20%), seen in 30 to 40% of patients, is associated with a favorable visual prognosis according to randomized studies. Continuation of the anti-VEGF injections after the induction phase is thus possible. If the response remains incomplete after 3 additional anti-VEGF injections, a complete ophthalmologic examination should be performed, and a switch to another therapeutic class (corticosteroids) may be proposed in the absence of contraindications. If a complete non-response is seen initially (reduction of central retinal thickness<10%), the switch is proposed immediately after the induction phase.


Assuntos
Algoritmos , Retinopatia Diabética/tratamento farmacológico , Substituição de Medicamentos/normas , Edema Macular/tratamento farmacológico , Guias de Prática Clínica como Assunto , Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/efeitos adversos , Bevacizumab/administração & dosagem , Bevacizumab/efeitos adversos , Dexametasona/administração & dosagem , Dexametasona/efeitos adversos , Retinopatia Diabética/epidemiologia , Substituição de Medicamentos/métodos , Substituição de Medicamentos/estatística & dados numéricos , Humanos , Injeções Intravítreas , Edema Macular/epidemiologia , Ranibizumab/administração & dosagem , Ranibizumab/efeitos adversos , Estudos Retrospectivos
15.
Cochrane Database Syst Rev ; 7: CD009510, 2020 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-32633861

RESUMO

BACKGROUND: Branch retinal vein occlusion (BRVO) is one of the most commonly occurring retinal vascular abnormalities. The most common cause of visual loss in people with BRVO is macular oedema (MO). Grid or focal laser photocoagulation has been shown to reduce the risk of visual loss. Limitations to this treatment exist, however, and newer modalities may have equal or improved efficacy. Antiangiogenic therapy with anti-vascular endothelial growth factor (anti-VEGF) has recently been used successfully to treat MO resulting from a variety of causes. OBJECTIVES: To investigate the efficacy and gather evidence from randomised controlled trials (RCTs) on the potential harms of anti-vascular endothelial growth factor (VEGF) agents for the treatment of macular oedema (MO) secondary to branch retinal vein occlusion (BRVO). SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2019, Issue 6); MEDLINE Ovid; Embase Ovid; the ISRCTN registry; ClinicalTrials.gov; and the WHO ICTRP. The date of the last search was 12 June 2019. SELECTION CRITERIA: We included randomised controlled trials (RCTs) investigating BRVO. Eligible trials had to have at least six months' follow-up where anti-VEGF treatment was compared with another treatment, no treatment, or placebo. We excluded trials where combination treatments (anti-VEGF plus other treatments) were used; and trials that investigated the dose and duration of treatment without a comparison group (other treatment/no treatment/sham). DATA COLLECTION AND ANALYSIS: Two review authors independently extracted the data using standard methodological procedures expected by Cochrane. The primary outcome was the proportion of participants with an improvement from baseline in best-corrected visual acuity of greater than or equal to 15 letters (3 lines) on the Early Treatment in Diabetic Retinopathy Study (ETDRS) Chart at six months and 12 months of follow-up. The secondary outcomes were the proportion of participants who lost greater than or equal to 15 ETDRS letters (3 lines) and the mean visual acuity (VA) change at six and 12 months, as well as the change in central retinal thickness (CRT) on optical coherence tomography from baseline at six and 12 months. We also collected data on adverse events and quality of life (QoL). MAIN RESULTS: We found eight RCTs of 1631 participants that met the inclusion criteria after independent and duplicate review of the search results. These studies took place in Europe, North America, Eastern Mediterranean region and East Asia. Included participants were adults aged 18 or over with VA of 20/40 or worse. Studies varied by duration of disease but permitted previously treated eyes as long as there was sufficient treatment-free interval. All anti-VEGF agents (bevacizumab, ranibizumab and aflibercept) and steroids (triamcinolone and dexamethasone) were included. Overall, we judged the studies to be at moderate or unclear risk of bias. Four of the eight studies did not mask participants or outcome assessors, or both. One trial compared anti-VEGF to sham. At six months, eyes receiving anti-VEGF were significantly more likely to have a gain of 15 or more ETDRS letters (risk ratio (RR) 1.72, 95% confidence interval (CI) 1.19 to 2.49; 283 participants; moderate-certainty evidence). Mean VA was better in the anti-VEGF group at six months compared with control (mean difference (MD) 7.50 letters, 95% CI 5.29 to 9.71; 282 participants; moderate-certainty evidence). Anti-VEGF also proved more effective at reducing CRT at six months (MD -57.50 microns, 95% CI -108.63 to -6.37; 281 participants; lower CRT is better; moderate-certainty evidence). There was only very low-certainty evidence on adverse effects. There were no reports of endophthalmitis. Mean change in QoL (measured using the National Eye Institute Visual Functioning Questionnaire VFQ-25) was better in people treated with anti-VEGF compared with people treated with sham (MD 7.6 higher score, 95% CI 4.3 to 10.9; 281 participants; moderate-certainty evidence). Three RCTs compared anti-VEGF with macular laser (total participants = 473). The proportion of eyes gaining 15 or more letters was greater in the anti-VEGF group at six months (RR 2.09, 95% CI 1.44 to 3.05; 2 studies, 201 participants; moderate-certainty evidence). Mean VA in the anti-VEGF groups was better than the laser groups at six months (MD 9.63 letters, 95% CI 7.23 to 12.03; 3 studies, 473 participants; moderate-certainty evidence). There was a greater reduction in CRT in the anti-VEGF group compared with the laser group at six months (MD -147.47 microns, 95% CI -200.19 to -94.75; 2 studies, 201 participants; moderate-certainty evidence). There was only very low-certainty evidence on adverse events. There were no reports of endophthalmitis. QoL outcomes were not reported. Four studies compared anti-VEGF with intravitreal steroid (875 participants). The proportion of eyes gaining 15 or more ETDRS letters was greater in the anti-VEGF group at six months (RR 1.67, 95% CI 1.33 to 2.10; 2 studies, 330 participants; high-certainty evidence) and 12 months (RR 1.76, 95% CI 1.36 to 2.28; 1 study, 307 participants; high-certainty evidence). Mean VA was better in the anti-VEGF group at six months (MD 8.22 letters, 95% CI 5.69 to 10.76; 2 studies, 330 participants; high-certainty evidence) and 12 months (MD 9.15 letters, 95% CI 6.32 to 11.97; 2 studies, 343 participants; high-certainty evidence). Mean CRT also showed a greater reduction in the anti-VEGF arm at 12 months compared with intravitreal steroid (MD -26.92 microns, 95% CI -65.88 to 12.04; 2 studies, 343 participants; moderate-certainty evidence). People receiving anti-VEGF showed a greater improvement in QoL at 12 months compared to those receiving steroid (MD 3.10, 95% CI 0.22 to 5.98; 1 study, 307 participants; moderate-certainty evidence). Moderate-certainty evidence suggested increased risk of cataract and raised IOP with steroids. There was only very low-certainty evidence on APTC events. No cases of endophthalmitis were observed. AUTHORS' CONCLUSIONS: The available RCT evidence suggests that treatment of MO secondary to BRVO with anti-VEGF improves visual and anatomical outcomes at six and 12 months.


Assuntos
Inibidores da Angiogênese/administração & dosagem , Anticorpos Monoclonais Humanizados/administração & dosagem , Edema Macular/tratamento farmacológico , Oclusão da Veia Retiniana/complicações , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Inibidores da Angiogênese/efeitos adversos , Anticorpos Monoclonais Humanizados/efeitos adversos , Bevacizumab/administração & dosagem , Humanos , Injeções Intravítreas , Fotocoagulação a Laser , Terapia a Laser , Edema Macular/etiologia , Edema Macular/cirurgia , Ensaios Clínicos Controlados Aleatórios como Assunto , Ranibizumab/administração & dosagem , Receptores de Fatores de Crescimento do Endotélio Vascular/administração & dosagem , Proteínas Recombinantes de Fusão/administração & dosagem , Terapia de Salvação/métodos , Esteroides/administração & dosagem , Acuidade Visual/efeitos dos fármacos
16.
J Fr Ophtalmol ; 43(8): 761-769, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32622633

RESUMO

INTRODUCTION: To describe the one-year functional outcomes of treatment-naïve neovascular age-related macular degeneration (nAMD) treated with anti-VEGF agents at the Dijon University Hospital Ophthalmology Department. METHODS: Real-life interventional study including all treatment-naïve nAMD patients from January 2016 to December 2018 in the Ophthalmology Department of Dijon University Hospital. Data were retrospectively collected from the Fight Retinal Blindness! (FRB!) registry. At baseline, medical history, visual acuity (VA), type of lesion and activity on angiography and optical coherence tomography (OCT), and treatment were recorded. On follow-up, VA, lesion activity and treatment were recorded. RESULTS: Three-hundred twenty eyes of 259 patients were included, of which 65.6% were female and with a mean age of 80.1±11.1 years. Mean VA (standard deviation, SD) at baseline was 53.2 ETDRS letters (25.3). All patients received anti-VEGF injections, of which 164 eyes (51.2%), 152 eyes (47.5%) and 4 eyes (1.2%) were treated with aflibercept, ranibizumab and bevacizumab, respectively. A total of 198 eyes of 169 patients completed the 12-month follow-up, with a median (first quartile, third quartile) of 12 visits (10, 13). At one year (n=198), the overall mean VA gain [95% CI] was +3.3 ETDRS letters [0.7, 5.9] and 173 (87.4%) of the treated eyes did not lose 15 or more letters. We found no statistically significant difference in mean VA gain between aflibercept and ranibizumab. CONCLUSION: This real-world study confirmed the efficacy of anti-VEGF agents in nAMD and the feasibility of analyzing data in an international registry.


Assuntos
Inibidores da Angiogênese/administração & dosagem , Degeneração Macular/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/efeitos adversos , Bevacizumab/administração & dosagem , Bevacizumab/efeitos adversos , Cegueira/tratamento farmacológico , Cegueira/epidemiologia , Feminino , França/epidemiologia , Humanos , Injeções Intravítreas , Degeneração Macular/epidemiologia , Masculino , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/epidemiologia , Ranibizumab/administração & dosagem , Ranibizumab/efeitos adversos , Receptores de Fatores de Crescimento do Endotélio Vascular/administração & dosagem , Proteínas Recombinantes de Fusão/administração & dosagem , Proteínas Recombinantes de Fusão/efeitos adversos , Sistema de Registros , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Fator A de Crescimento do Endotélio Vascular/imunologia
17.
J Fr Ophtalmol ; 43(7): 618-625, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32473741

RESUMO

PURPOSE: To evaluate the efficacy of intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections (IVT) in diabetic macular edema (DME) in real-life practice using the Save Sight Registries (SSR). MATERIAL AND METHODS: We conducted an observational, single-centre, retrospective study in the department of ophthalmology of the Dijon University Hospital. We included treatment-naive patients who presented with DME between January 2016 and December 2017. Demographic and clinical data, follow-up visits, and treatments administered were entered into the SSR, an international online ophthalmic registry. Primary endpoints were the change in best-corrected visual acuity (BCVA) and central subfield thickness (CST) from baseline to 12 and 24 months. RESULTS: Fifty-eight eyes of 43 patients with a mean [standard deviation (SD)] age of 67.1 [9.5] years were included. Forty-one eyes completed 12 months of follow-up, and 17 eyes completed 24 months of follow up. Median [SD] baseline BCVA was 56.1 [22.9] ETDRS letters and the median [95% confidence interval (95% CI)] baseline CST was 447.9 [161.0] micrometers (µm). Median [95% CI] improvement in BCVA from baseline to months 12 and 24 were respectively, +5.6 [+0.5; +10.7] ETDRS letters and +7.7 [-2.8; +18.2] ETDRS letters. The median [95% CI] decrease in CST from baseline to months 12 and 24 were respectively, -110.9 [-154.5; -67.3] µm and -125.5 [-198.0; -53.0] µm. CONCLUSION: Our clinical practice can be evaluated easily with the SSR system. In real life, anti-VEGF IVT are an effective treatment for DME, which result in improved BCVA and decreased CST.


Assuntos
Bevacizumab/administração & dosagem , Retinopatia Diabética/tratamento farmacológico , Edema Macular/tratamento farmacológico , Centros Médicos Acadêmicos , Idoso , Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/efeitos adversos , Bevacizumab/efeitos adversos , Retinopatia Diabética/epidemiologia , Feminino , Seguimentos , França/epidemiologia , Humanos , Injeções Intravítreas , Edema Macular/epidemiologia , Masculino , Pessoa de Meia-Idade , Padrões de Prática Médica/estatística & dados numéricos , Sistema de Registros , Estudos Retrospectivos , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Fator A de Crescimento do Endotélio Vascular/imunologia
18.
Medicine (Baltimore) ; 99(21): e20222, 2020 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-32481293

RESUMO

BACKGROUND: The objective of this review and meta-analysis is to investigate the efficacy of conbercept and ranibizumab, combined with or without laser photocoagulation, in patients with macular edema secondary to retinal vein occlusion (RVO-ME). METHODS: Several databases have been used to identify relevant publications. After screening, a meta-analysis was conducted to compare conbercept and ranibizumab with the support of RevMan 5.3 (Cochrane Library Software, Oxford, UK). RESULTS: In this study, 9 randomized controlled trials and 6 retrospective trials were included with a total of 1180 patients. No significant difference was found in best corrected visual acuity (BCVA) or central macular thickness (CMT) in the baseline parameters [BCVA (weighted mean difference (WMD): -0.01; 95% confidence interval CI: -0.03 to 0.01; P = .17), CMT (WMD: 20.14; 95% CI: -26.70 to 66.97; P = .40). No significant differences were found in the improvements of BCVA and adverse events (AEs) between the 2 groups after injection of loading dosage [the 1st month BCVA (WMD: -0.01; 95% CI: -0.04 to 0.02; P = .54),the 3rd month BCVA (WMD: -0.02; 95% CI: --0.05 to 0.01; P = .23), the 6th month BCVA (WMD: -0.02; 95% CI: -0.05 to 0.01; P = .27), AEs (odds ratio: 0.84; 95% CI: 0.38 to 1.84; P = .66)]. However, there were significant differences between conbercept and ranibizumab treatment in terms of CMT [1st month CMT (WMD: -11.70; 95% CI: -19.71 to -3.68; P < .01), 3rd month CMT (WMD: -10.08; 95% CI: -15.62 to -4.53; P < .01), 6th month CMT (WMD: -15.83; 95% CI: -22.88 to -8.78; P < .01)] and the number of injections (WMD, -0.36; 95% CI: -0.68 to -0.04; P = .03). CONCLUSION: The current pooled evidence suggested that both therapies of intravitreal conbercept and intravitreal ranibizumab with or without laser photocoagulation are effective in vision function in RVO-ME patients, and confirmed that conbercept has advantages over ranibizumab in terms of CMT and the number of injections for treating RVO-ME. In addition, conbercept has the statistically same visual gains and safety as ranibizumab in RVO-ME patients. Longer-term follow-up surveys on the safety and effectiveness of these 2 treatment regimens are required.


Assuntos
Fotocoagulação/métodos , Edema Macular/tratamento farmacológico , Edema Macular/terapia , Oclusão da Veia Retiniana/complicações , Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/efeitos adversos , Inibidores da Angiogênese/uso terapêutico , Terapia Combinada/métodos , Humanos , Injeções Intravítreas , Edema Macular/diagnóstico por imagem , Ensaios Clínicos Controlados Aleatórios como Assunto , Ranibizumab/administração & dosagem , Ranibizumab/efeitos adversos , Ranibizumab/uso terapêutico , Proteínas Recombinantes de Fusão/administração & dosagem , Proteínas Recombinantes de Fusão/efeitos adversos , Proteínas Recombinantes de Fusão/uso terapêutico , Estudos Retrospectivos , Tomografia de Coerência Óptica , Acuidade Visual/efeitos dos fármacos
19.
Lancet Oncol ; 21(6): 808-820, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32502443

RESUMO

BACKGROUND: Dual blockade of PD-L1 and VEGF has enhanced anticancer immunity through multiple mechanisms and augmented antitumour activity in multiple malignancies. We aimed to assess the efficacy and safety of atezolizumab (anti-PD-L1) alone and combined with bevacizumab (anti-VEGF) in patients with unresectable hepatocellular carcinoma. METHODS: GO30140 is an open-label, multicentre, multiarm, phase 1b study that enrolled patients at 26 academic centres and community oncology practices in seven countries worldwide. The study included five cohorts, and the two hepatocellular carcinoma cohorts, groups A and F, are described here. Inclusion criteria for these two groups included age 18 years and older; histologically, cytologically, or clinically (per American Association for the Study of Liver Diseases criteria) confirmed unresectable hepatocellular carcinoma that was not amenable to curative treatment; no previous systemic treatment; and Eastern Cooperative Oncology Group performance status of 0 or 1. In group A, all patients received atezolizumab (1200 mg) and bevacizumab (15 mg/kg) intravenously every 3 weeks. In group F, patients were randomly assigned (1:1) to receive intravenous atezolizumab (1200 mg) plus intravenous bevacizumab (15 mg/kg) every 3 weeks or atezolizumab alone by interactive voice-web response system using permuted block randomisation (block size of two) and stratification factors of geographical region; macrovascular invasion, extrahepatic spread, or both; and baseline α-fetoprotein concentration. Primary endpoints were confirmed objective response rate in all patients who received the combination treatment for group A and progression-free survival in the intention-to-treat population in group F, both assessed by an independent review facility according to Response Evaluation Criteria in Solid Tumors version 1.1. In both groups, safety was assessed in all patients who received at least one dose of any study treatment. This study is registered with ClinicalTrials.gov, NCT02715531, and is closed to enrolment. FINDINGS: In group A, 104 patients were enrolled between July 20, 2016, and July 31, 2018, and received atezolizumab plus bevacizumab. With a median follow-up of 12·4 months (IQR 8·0-16·2), 37 (36%; 95% CI 26-46) of 104 patients had a confirmed objective response. The most common grade 3-4 treatment-related adverse events were hypertension (13 [13%]) and proteinuria (seven [7%]). Treatment-related serious adverse events occurred in 25 (24%) patients and treatment-related deaths in three (3%) patients (abnormal hepatic function, hepatic cirrhosis, and pneumonitis). In group F, 119 patients were enrolled and randomly assigned (60 to atezolizumab plus bevacizumab; 59 to atezolizumab monotherapy) between May 18, 2018, and March 7, 2019. With a median follow-up of 6·6 months (IQR 5·5-8·5) for the atezolizumab plus bevacizumab group and 6·7 months (4·2-8·2) for the atezolizumab monotherapy group, median progression-free survival was 5·6 months (95% CI 3·6-7·4) versus 3·4 months (1·9-5·2; hazard ratio 0·55; 80% CI 0·40-0·74; p=0·011). The most common grade 3-4 treatment-related adverse events in group F were hypertension (in three [5%] patients in the atezolizumab plus bevacizumab group; none in the atezolizumab monotherapy group) and proteinuria (in two [3%] patients in the atezolizumab plus bevacizumab group; none in the atezolizumab monotherapy group). Treatment-related serious adverse events occurred in seven (12%) patients in the atezolizumab plus bevacizumab group and two (3%) patients in the atezolizumab monotherapy group. There were no treatment-related deaths. INTERPRETATION: Our study shows longer progression-free survival with a combination of atezolizumab plus bevacizumab than with atezolizumab alone in patients with unresectable hepatocellular carcinoma not previously treated with systemic therapy. Therefore, atezolizumab plus bevacizumab might become a promising treatment option for these patients. This combination is being compared with standard-of-care sorafenib in a phase 3 trial. FUNDING: F Hoffmann-La Roche/Genentech.


Assuntos
Inibidores da Angiogênese/administração & dosagem , Anticorpos Monoclonais Humanizados/administração & dosagem , Antineoplásicos Imunológicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/administração & dosagem , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/efeitos adversos , Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab/efeitos adversos , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/patologia , Progressão da Doença , Feminino , Humanos , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Neovascularização Patológica , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , Intervalo Livre de Progressão , Receptores de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Receptores de Fatores de Crescimento do Endotélio Vascular/imunologia , Transdução de Sinais , Fatores de Tempo , Adulto Jovem
20.
J Cancer Res Clin Oncol ; 146(8): 2077-2087, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32561975

RESUMO

PURPOSE: Although biomarkers for patients with metastatic colorectal cancer exist, the benefit patients with RAS mutated tumors derive from established regimens is unclear. METHODS: Efficacy of therapeutic strategies available for RAS mutated patients (addition of chemotherapeutic agents and/or anti angiogenic agents) were investigated in fourteen randomized controlled phase III trials at trial level by meta-analysing individual study hazard ratios and 95% confidence intervals (95% CI) for overall survival (OS) and progression free survival (PFS). RESULTS: 6810 of 10,748 patients (63.3%) were available (48.5% RAS wildtype, 51.5% RAS mutated). Across all treatment lines, additional treatment efficacy (chemotherapy and/or anti angiogenic agents) was significantly smaller in RAS mutated compared to wildtype tumors for OS and PFS. In detail, patients with RAS mutated metastatic colorectal cancer derived significant benefit in PFS but not in OS by the addition of either chemotherapy or anti angiogenic agents to the respective comparator. In patients with RAS wildtype metastatic colorectal cancer, PFS and OS were improved by the addition of chemotherapy or anti angiogenic agent. CONCLUSION: The therapeutic benefit of additional substances is less distinct in patients with RAS mutated as compared to RAS wildtype metastatic colorectal cancer, especially with regard to OS.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Mutação , Proteínas ras/genética , Inibidores da Angiogênese/administração & dosagem , Ensaios Clínicos Fase III como Assunto , Genes ras , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
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