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1.
Anticancer Res ; 42(4): 1905-1910, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35347009

RESUMO

AIM: The present study evaluated the efficacy and safety of ramucirumab (RAM) in clinical practice as post-treatment, following atezolizumab plus bevacizumab (Atz/Bev) for advanced hepatocellular carcinoma (HCC) with alpha-fetoprotein (AFP) levels of ≥400 ng/ml. PATIENTS AND METHODS: Of the 77 patients treated with Atz/Bev at our institution, 13 patients for whom RAM was introduced as post-treatment following Atz/Bev were enrolled in this retrospective study. There were 9 patients (69.2%) with Child-Pugh A and 11 patients (84.6%) for whom RAM was initiated as 3rd- or later-line therapy. The median AFP level was 2259 ng/ml. RESULTS: The objective response rate by Response Evaluation Criteria in Solid Tumours at 6 weeks was 15.4%, and the disease control rate was 69.2%. The median time to progression was 3.0 months; AFP level decreased at 2 weeks in 11 patients (84.6%) and at 6 weeks in seven patients (53.8%). The most common adverse events (AEs) within 6 weeks were ascites, peripheral oedema, and proteinuria, while grade 3 AEs occurred in six patients (46.2%). Albumin-bilirubin scores at both 4 and 6 weeks were significantly worse than those at baseline. CONCLUSION: In HCC patients with AFP levels of ≥400 ng/mL, RAM after Atz/Bev is expected to be an effective treatment option. Careful attention should be paid to the development of AEs and deterioration of liver function, especially when RAM is used as 3rd- or later-line therapy. Additional studies are needed to confirm the efficacy and safety of RAM as 2nd-line treatment after Atz/Bev in Child-Pugh A patients.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Anticorpos Monoclonais Humanizados , Bevacizumab/efeitos adversos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Estudos Retrospectivos
3.
Biomed Res Int ; 2022: 2317181, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35480138

RESUMO

Objective: To evaluate the efficacy of bevacizumab and gemcitabine in combination with cisplatin in the treatment of esophageal cancer and the effect on the incidence of adverse reactions. Methods: A total of 100 esophageal cancer patients admitted to our hospital from March 2019 to March 2021 were identified as research subjects and randomized into the control group and the study group, with 50 cases in each group. The control group was treated with gemcitabine combined with cisplatin, and the study group was treated with the triple therapy of bevacizumab, gemcitabine, and cisplatin. The treatment efficiency and the incidence of adverse reactions were compared between the two groups of patients. Results: The total treatment efficiency in the study group was 86%, which was significantly higher than that of 66% in the control group (P < 0.05). After treatment, the levels of vascular endothelial growth factor (VEGF), Cyfra21-1, and C-met were reduced in both groups, with significantly lower levels in the study group than in the control group (P < 0.05). The incidence of all CTCAE, ototoxicity, and nephrotoxicity was comparable between the two groups (P > 0.05). The survival rates of patients in the study group were 88% and 54% at 1 and 2 years after treatment, which were significantly higher than that of 68% and 32% in the control group (P < 0.05). Conclusion: The clinical efficiency of bevacizumab and gemcitabine combined with cisplatin in the treatment of esophageal cancer is remarkable, which improves the survival of patients, and is worthy of clinical promotion and application.


Assuntos
Neoplasias Esofágicas , Neoplasias Pulmonares , Anticorpos Monoclonais Humanizados/uso terapêutico , Antígenos de Neoplasias , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab/efeitos adversos , Cisplatino/uso terapêutico , Desoxicitidina/análogos & derivados , Neoplasias Esofágicas/tratamento farmacológico , Humanos , Incidência , Queratina-19 , Neoplasias Pulmonares/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular
4.
J Immunol Res ; 2022: 6004047, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35465351

RESUMO

This study is aimed at assessing the efficacy and safety of antivascular endothelial growth factor (anti-VEGF) inhibitors in treating age-related macular degeneration (AMD). PubMed, Embase, and Cochrane library were searched. Weighted mean difference (WMD) and relative risk (RR) with 95% confidence interval (CI) were applied to assess outcomes. Eighteen randomized controlled trials involved 8,847 neovascular AMD patients were selected for the meta-analysis. Pegaptanib (WMD: 6.70; P < 0.001) and ranibizumab (WMD: 17.80; P < 0.001) were associated with greater BCVA changes than control after 1 year. Bevacizumab was linked with less changes in central macular thickness after 1 year compared to control (WMD: -38.50; P < 0.001), but more changes compared to ranibizumab (WMD: 10.69; P = 0.024). The incidence of gain of 15 or more letter visual acuity after 1 year was increased when compared with bevacizumab versus control (RR: 7.80; P = 0.001), pegaptanib versus control (RR: 2.83; P = 0.015), and ranibizumab versus control (RR: 3.92; P = 0.003). Moreover, ranibizumab was associated with more BCVA changes and an increased incidence of gain of 15 or more letter visual acuity after 2 years compared with control (RR: 5.77; P < 0.001). This study found that most anti-VEGF inhibitors provided better efficacy than non-anti-VEGF intervention, and the treatment effectiveness among various anti-VEGF agents was equally effective.


Assuntos
Ranibizumab , Degeneração Macular Exsudativa , Inibidores da Angiogênese/efeitos adversos , Anticorpos Monoclonais , Bevacizumab/efeitos adversos , Fatores de Crescimento Endotelial , Humanos , Injeções Intravítreas , Ensaios Clínicos Controlados Aleatórios como Assunto , Ranibizumab/efeitos adversos , Fator A de Crescimento do Endotélio Vascular , Acuidade Visual , Degeneração Macular Exsudativa/tratamento farmacológico
5.
Eur J Cancer ; 167: 23-31, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35366570

RESUMO

BACKGROUND: We performed a pooled analysis of TRIBE and TRIBE2 studies to assess the efficacy and safety of the intensification of upfront chemotherapy backbone - from doublets to the triplet FOLFOXIRI - in combination with bevacizumab (bev) in patients with early-onset metastatic colorectal cancer (EO-mCRC; aged <50 years) and to explore whether EO-mCRCs have a peculiar tumour genomic profiling. MATERIALS AND METHODS: Subgroup analyses according to age (<50 versus ≥50 years) and treatment (FOLFOXIRI/bev versus doublets/bev) were carried out for rates of any grade and grade ≥3 (≥G3) overall and singular adverse events, progression-free survival (PFS), overall survival (OS) and objective response rate (ORR). Tumour genomic profiling was obtained using a DNA-based next-generation sequencing platform. RESULTS: Of 1187 patients included, 194 (16%) patients were aged <50 years. Females were more frequently diagnosed with EO-mCRC (P = 0.04). Patients aged <50 years showed a lower risk of ≥G3 neutropenia (P = 0.07), diarrhoea (P = 0.04), asthenia (P = 0.008) and a higher risk of any grade nausea (P < 0.01) and vomiting (P < 0.01). Patients receiving FOLFOXIRI/bev more frequently experienced ≥G3 chemotherapy-related adverse events respect to doublets/bev, regardless of age (Pinteraction = 0.60). FOLFOXIRI/bev was associated to a lower incidence of neutropenia (P = 0.04) and asthenia (P = 0.01) in patients <50 years old, than those aged ≥50 years. PFS, OS and ORR did not differ according to age (PFS P = 0.81, OS P = 0.44, ORR P = 0.50) and no interaction between age and the benefit from the intensification of upfront chemotherapy was observed (PFS Pinteraction = 0.72, OS Pinteraction = 0.54, ORR Pinteraction = 0.65). Genomic profiling was assessed in 296 patients, showing an enrichment of FBXW7 and POLE mutations in EO-mCRC. CONCLUSIONS: Upfront FOLFOXIRI/bev shows a favourable efficacy/safety balance in EO-mCRC. TRIAL REGISTRATION: Clinicaltrials.gov Identifiers NCT00719797, NCT0233-9116.


Assuntos
Neoplasias Colorretais , Neutropenia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Astenia/induzido quimicamente , Bevacizumab/efeitos adversos , Camptotecina/análogos & derivados , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Feminino , Fluoruracila/efeitos adversos , Humanos , Leucovorina/efeitos adversos , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Compostos Organoplatínicos
6.
Oncologist ; 27(4): 292-298, 2022 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-35380713

RESUMO

BACKGROUND: Combination irinotecan and cetuximab is approved for irinotecan-refractory metastatic colorectal cancer (mCRC). It is unknown if adding bevacizumab improves outcomes. PATIENTS AND METHODS: In this multicenter, randomized, double-blind, placebo-controlled phase II trial, patients with irinotecan-refractory RAS-wildtype mCRC and no prior anti-EGFR therapy were randomized to cetuximab 500 mg/m2, bevacizumab 5 mg/kg, and irinotecan 180 mg/m2 (or previously tolerated dose) (CBI) versus cetuximab, irinotecan, and placebo (CI) every 2 weeks until disease progression or intolerable toxicity. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR), and adverse events (AEs). RESULTS: The study closed early after the accrual of 36 out of a planned 120 patients due to changes in funding. Nineteen patients were randomized to CBI and 17 to CI. Baseline characteristics were similar between arms. Median PFS was 9.7 versus 5.5 months for CBI and CI, respectively (1-sided log-rank P = .38; adjusted hazard ratio [HR] = 0.64; 95% confidence interval [CI], 0.25-1.66). Median OS was 19.7 versus 10.2 months for CBI and CI (1-sided log-rank P = .02; adjusted HR = 0.41; 95% CI, 0.15-1.09). ORR was 36.8% for CBI versus 11.8% for CI (P = .13). Grade 3 or higher AEs occurred in 47% of patients receiving CBI versus 35% for CI (P = .46). CONCLUSION: In this prematurely discontinued trial, there was no significant difference in the primary endpoint of PFS between CBI and CI. There was a statistically significant improvement in OS in favor of CBI compared with CI. Further investigation of CBI for the treatment of irinotecan-refractory mCRC is warranted.Clinical Trial Registration: NCT02292758.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Colorretais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab/efeitos adversos , Camptotecina/efeitos adversos , Cetuximab/efeitos adversos , Neoplasias Colorretais/patologia , Fluoruracila , Humanos , Irinotecano/uso terapêutico
8.
J Neurooncol ; 157(2): 355-364, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35239111

RESUMO

INTRODUCTION: At least half of children with low-grade glioma (LGG) treated with first line chemotherapy experience a relapse/progression and may therefore need a second-line chemotherapy. Irinotecan-bevacizumab has been recommended in this setting in France after encouraging results of pilot studies. We performed a retrospective analysis to define the efficacy, toxicity and predictors for response to the combination on a larger cohort. METHODS: We reviewed the files from children < 19 years of age with progressive or refractory LGG treated between 2009 and 2016 in 7 French centers with this combination. RESULTS: 72 patients (median age 7.8 years [range 1-19]) received a median of 16 courses (range 3-30). The median duration of treatment was 9 months (range 1.4-16.2). 96% of patients experienced at least disease stabilization. The 6-month and 2-year progression-free survivals (PFS) were 91.7% [IC 95% 85.5-98.3] and 38.2% [IC 95% 28.2-51.8] respectively. No progression occurred after treatment in 18 patients with a median follow-up of 35.6 months (range 7.6-75.9 months). Younger patients had a worse PFS (p = 0.005). Prior chemoresistance, NF1 status, duration of treatment, histopathology or radiologic response did not predict response. The most frequent toxicities related to bevacizumab included grades 1-2 proteinuria in 21, epistaxis in 10, fatigue in 12 and hypertension in 8 while gastro-intestinal toxicity was the most frequent side effect related to irinotecan. CONCLUSIONS: Bevacizumab-irinotecan has the potential of disease control clinically and radiographically in children with recurrent LGG whatever their previous characteristics; in many cases however these responses are not sustained, especially in younger children.


Assuntos
Neoplasias Encefálicas , Glioma , Adolescente , Adulto , Anticorpos Monoclonais Humanizados/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab/efeitos adversos , Neoplasias Encefálicas/patologia , Camptotecina/efeitos adversos , Criança , Pré-Escolar , Glioma/tratamento farmacológico , Glioma/patologia , Humanos , Lactente , Irinotecano , Recidiva Local de Neoplasia/patologia , Estudos Retrospectivos , Adulto Jovem
10.
Pak J Pharm Sci ; 35(1(Special)): 381-386, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35236652

RESUMO

To evaluate the efficacy and safety of bevacizumab combined with chemotherapy in the treatment of advanced colorectal cancer and the effect on its adverse reactions, 100 patients with advanced colorectal cancer admitted to our hospital from March 2019 to March 2021 were identified as study subjects and were randomly divided into a control group and an experimental group, with 50 cases in each group. The control group was treated with chemotherapy, and the experimental group was given a combination of bevacizumab with chemotherapy. The treatment efficacy, safety, and incidence of adverse reactions in both groups were analyzed and compared. The effectiveness and disease control rate of the experimental group were 50% and 96%, which were significantly higher than those of 26% and 80% in the control group (P<0.05). After treatment, the experimental group exhibited a significantly lower serum vascular endothelial growth factor level and heat shock protein 90α (HSP90α) level compared with that of the control group (P<0.05). Markedly higher apoptosis index of tumor cells was observed in the experimental group than in the control group (P<0.05). The incidence of adverse reactions was 8% in the experimental group, which was significantly lower than that of 28% in the control group (P<0.05). The post-treatment quality of life scores in the experimental group exceeded that in the control group (P<0.05). Bevacizumab combined with chemotherapy for advanced colorectal cancer boosts treatment efficiency, promotes apoptosis of tumor cells, down regulates HSP90α level and enhances patients' quality of life with high safety, which is worthy of clinical promotion and application.


Assuntos
Antineoplásicos/uso terapêutico , Bevacizumab/uso terapêutico , Capecitabina/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Oxaliplatina/uso terapêutico , Antineoplásicos/administração & dosagem , Bevacizumab/administração & dosagem , Bevacizumab/efeitos adversos , Capecitabina/administração & dosagem , Capecitabina/efeitos adversos , Feminino , Humanos , Masculino , Oxaliplatina/administração & dosagem , Oxaliplatina/efeitos adversos
11.
BMC Cancer ; 22(1): 346, 2022 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-35354431

RESUMO

BACKGROUND: In women with newly diagnosed ovarian cancer, bevacizumab and poly (ADP-ribose) polymerase inhibitors (PARPi) exhibit improved progression-free survival (PFS) when administered concurrent with chemotherapy and/or maintenance therapy, but no study has directly compared their effects. Therefore, this study aimed to compare the efficacy and safety of bevacizumab and PARPi in women with newly diagnosed ovarian cancer using a network meta-analysis. METHODS: PubMed, Medline, and Embase databases were searched, and five randomized trials assessing PFS in women with newly diagnosed ovarian cancer treated with either bevacizumab, PARPi, or placebo or no additional agent (controls) were identified. PFS was compared in the overall population with ovarian cancer, women with a BRCA1/2 mutation (BRCAm) and women with homologous-recombination deficiency (HRD). Adverse events (grade ≥ 3) were compared in all populations of the included studies. RESULTS: PARPi improved PFS significantly more than bevacizumab in women with a BRCAm (HR 0.47; 95% CI 0.36-0.60) and with HRD (HR 0.66; 95% CI 0.50-0.87). However, in the overall population with ovarian cancer, no significant difference in PFS was observed between women treated with PARPi and those treated with bevacizumab. PARPi exhibited the highest surface under the cumulative ranking probabilities value as the most effective treatment for PFS (PARPi vs. bevacizumab: 98% vs. 52% in the overall population with ovarian cancer; 100% vs. 50% in women with BRCAm; 100% vs. 50% in women with HRD). For adverse events, the risk of all treatments was similar. However, PARPi had a higher adverse risk than the control group (relative risk 2.14; 95% CI 1.40-3.26). CONCLUSIONS: In women with newly diagnosed ovarian cancer, PARPi might be more effective in terms of PFS compared to bevacizumab. The risk of serious adverse events was similar for PARPi and bevacizumab.


Assuntos
Neoplasias Ovarianas , Inibidores de Poli(ADP-Ribose) Polimerases , Bevacizumab/efeitos adversos , Carcinoma Epitelial do Ovário/tratamento farmacológico , Feminino , Humanos , Metanálise em Rede , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Inibidores de Poli(ADP-Ribose) Polimerases/efeitos adversos
12.
Future Oncol ; 18(13): 1651-1664, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35129371

RESUMO

Aim: To review the efficacy and safety of regimens containing anti-PD-1/PD-L1 and bevacizumab for patients with advanced nonsquamous, non-small-cell lung cancer. Methods: Sixteen eligible trials were assessed. Clinical outcomes and adverse events were integrated. Subgroup analysis was conducted according to PD-L1 expression and liver metastases. Results: For the PD-L1 high population, a PD-1 inhibitor plus platinum-doublet provided significant progression-free survival (PFS) benefit versus bevacizumab. While for patients harboring PD-L1 <50%, anti-PD-1/PD-L1-containing regimens performed comparably to bevacizumab. With regard to the liver metastatic population, there existed a trend that anti-PD-1 plus chemotherapy brought about PFS benefits. Conclusion: The preference for chemoimmunotherapy lacks sufficient evidence in patients harboring PD-L1 <50%. Direct head-to-head clinical trials are warranted to identify optimal therapeutic regimens for specific patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Antígeno B7-H1/metabolismo , Bevacizumab/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Neoplasias Pulmonares/patologia , Metanálise em Rede
13.
Eur J Drug Metab Pharmacokinet ; 47(3): 309-317, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35112328

RESUMO

BACKGROUND AND OBJECTIVE: LY01008 had been identified as being highly similar to the bevacizumab reference product in the pharmacy and pharmacology terms. The primary objective of this study was to compare the pharmacokinetic characteristics of the biosimilar candidate LY01008 with that of the bevacizumab (Avastin®) reference product after a single intravenous infusion in healthy Chinese adults. The secondary objective was to compare the safety and immunogenicity of LY01008 with those of bevacizumab. METHODS: In this double-blind, parallel-group, phase I study, 102 male subjects aged 18-45 years were randomized 1:1 to receive a single intravenous infusion of 3 mg/kg LY01008 or bevacizumab. Before the pivotal section, 12 healthy male subjects receiving a single intravenous (IV) infusion of 0.5 mg/kg or 1.5 mg/kg LY01008 were screened to verify the safety and tolerability of LY01008. Primary endpoints included the area under the concentration-time curve (AUC) from time zero to the last quantifiable time point (AUC0-t), AUC from time zero to the infinity time (AUC0-inf), and maximum plasma concentration (Cmax). RESULTS: The geometric mean ratios (GMRs) (90% confidence intervals, CIs) of AUC0-t, AUC0-inf, and Cmax of LY01008 to bevacizumab were 87.62% (82.91%, 92.61%), 87.27% (82.46%, 92.35%), and 96.45% (91.37%, 101.81%), respectively, in the pivotal section, which were within the prespecified equivalence margin of 80.00-125.00%. LY01008 and bevacizumab administered as a single 3 mg/kg intravenous dose were comparably well tolerated. No new or unexpected adverse events were observed. Nine subjects had antidrug antibodies (ADAs) (5 in the LY01008 group and 4 in the bevacizumab group) after dosing. No neutralizing antibody (Nab) was detected. CONCLUSION: LY01008, a recombinant humanized monoclonal antibody (mAb) against vascular endothelial growth factor (VEGF), displayed pharmacokinetic similarity to bevacizumab, and good safety and tolerability profiles. The data from this trial provide fundamental information for further development. TRIAL REGISTRATION: Clinical trial registration ID: CTR20170191.


Assuntos
Medicamentos Biossimilares , Fator A de Crescimento do Endotélio Vascular , Adulto , Área Sob a Curva , Bevacizumab/efeitos adversos , Bevacizumab/farmacocinética , Medicamentos Biossimilares/efeitos adversos , China , Método Duplo-Cego , Feminino , Voluntários Saudáveis , Humanos , Masculino , Equivalência Terapêutica
14.
Oncol Res Treat ; 45(5): 281-290, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35114663

RESUMO

BACKGROUND: A previous meta-analysis suggested that use of bevacizumab is associated with an increased risk of infection in cancer patients. With the continuous accumulation of evidence in non-small-cell lung cancer (NSCLC), we performed a new, focused meta-analysis of randomized controlled trials (RCTs) to quantify the relative risk (RR) and incidence of infectious complications in those individuals treated with bevacizumab. METHODS: Electronic databases were searched, including PubMed, Embase, and Cochrane databases. Eligible studies were prospective randomized clinical trials of NSCLC patients treated with bevacizumab with toxicity data on infectious complications. RR, overall incidence rates, and 95% confidence intervals (CI) were calculated using fixed- or random-effects models, depending on the heterogeneity of the included studies. RESULTS: A total of 4,545 patients from 14 prospective RCTs were included in the meta-analysis. Treatment with bevacizumab was not associated with an increased risk of all-grade (RR 1.12, 95% CI: 0.84-1.49) or high-grade (RR 1.11, 95% CI: 0.86-1.41) infections, respectively. The summary incidences of all-grade and high-grade infections in patients receiving bevacizumab in the treatment group were 16.4% (95% CI: 15.7-17.2%) and 4.3% (95% CI: 3.0-6.1%), respectively. CONCLUSIONS: The use of bevacizumab is not associated with a significantly higher risk of infections in NSCLC patients. These data provide reassurance regarding the risk of infection in patients with NSCLC receiving bevacizumab.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Inibidores da Angiogênese/efeitos adversos , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Bevacizumab/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Humanos , Incidência , Neoplasias Pulmonares/tratamento farmacológico
15.
Eur J Gastroenterol Hepatol ; 34(6): 698-706, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35170529

RESUMO

OBJECTIVE: To investigate whether neutrophil-to-lymphocyte ratio (NLR) can predict outcomes in patients with unresectable hepatocellular carcinoma (HCC) treated with atezolizumab plus bevacizumab (Atez/Bev). METHODS: A total of 249 patients with unresectable HCC treated with Atez/Bev were included. We analyzed survival and discontinuation of this therapy in this cohort. RESULTS: Cumulative overall survival at 2, 4, 6, and 8 months was 97.6%, 94.9%, 88.9%, and 82.8%, respectively. Cumulative overall survival differed significantly between patients with low (<3.0) versus high (≥3.0) NLR (P = 0.001). Conversely, cumulative progression-free survival did not differ between patients with low versus high NLR. The distribution of response was 1.5% for complete response, 17.1% for partial response, 60.5% for stable disease, and 21.0% for progressive disease. Responses were not different between patients with low and high NLR. Regarding adverse events, immune-related liver injury of any grade and grade of at least 3, decreased appetite of any grade, grade of at least 3 proteinuria, and other adverse events of any grade differed significantly between patients with low and high NLR. There were 56, 18, and 2 patients who discontinued Atez/Bev therapy due to progression of disease, adverse event, and other reasons, respectively. The cumulative discontinuation rate for Atez/Bev therapy due to adverse events differed significantly between patients with low versus high NLR (P = 0.022). Cox proportional hazards modeling analysis with inverse probability weighting showed that NLR of at least 3.0 was significantly associated with overall survival (hazard ratio, 3.369; 95% confidence interval, 1.024-11.080). CONCLUSIONS: NLR can predict outcomes in patients with unresectable HCC treated with Atez/Bev.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Anticorpos Monoclonais Humanizados , Bevacizumab/efeitos adversos , Carcinoma Hepatocelular/patologia , Humanos , Neoplasias Hepáticas/patologia , Linfócitos , Neutrófilos/patologia
16.
JAMA Netw Open ; 5(2): e2149040, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-35179586

RESUMO

Importance: Cotargeting vascular endothelial growth factor and programmed cell death 1 or programmed cell death ligand 1 may produce anticancer activity in refractory metastatic colorectal cancer (mCRC). The clinical benefit of atezolizumab combined with chemotherapy and bevacizumab remains unclear for the treatment of mCRC. Objectives: To assess whether the addition of atezolizumab to capecitabine and bevacizumab therapy improves progression-free survival (PFS) among patients with refractory mCRC and to perform exploratory analyses among patients with microsatellite-stable (MSS) disease and liver metastasis. Design, Setting, and Participants: This double-blind phase 2 randomized clinical trial enrolled 133 patients between September 25, 2017, and June 28, 2018 (median duration of follow-up for PFS, 20.9 months), with data cutoff on May 4, 2020. The study was conducted at multiple centers through the Academic and Community Cancer Research United network. Adult patients with mCRC who experienced disease progression while receiving fluoropyrimidine, oxaliplatin, irinotecan, bevacizumab, and anti-epidermal growth factor receptor antibody therapy (if the patient had a RAS wild-type tumor) were included. Interventions: Patients were randomized (2:1) to receive capecitabine (850 or 1000 mg/m2) twice daily on days 1 to 14 and bevacizumab (7.5 mg/kg) on day 1 plus either atezolizumab (1200 mg; investigational group) or placebo (placebo group) on day 1 of each 21-day cycle. Main Outcomes and Measures: The primary end point was PFS; 110 events were required to detect a hazard ratio (HR) of 0.65 with 80% power (1-sided α = .10). Secondary end points were objective response rate, overall survival (OS), and toxic effects. Results: Of 133 randomized patients, 128 individuals (median age, 58.0 years [IQR, 51.0-65.0 years]; 77 men [60.2%]) were assessed for efficacy (82 in the investigational group and 46 in the placebo group). Overall, 15 patients (11.7%) self-identified as African American or Black, 8 (6.3%) as Asian, 1 (0.8%) as Pacific Islander, 101 (78.9%) as White, 1 (0.8%) as multiple races (Asian, Native Hawaiian/Pacific Islander, and White), and 2 (1.6%) as unknown race or unsure of race. Microsatellite-stable disease was present in 110 patients (69 in the investigational group and 41 in the placebo group). Median PFS was 4.4 months (95% CI, 4.1-6.4 months) in the investigational group and 3.6 months (95% CI, 2.2-6.2 months) in the placebo group (1-sided log-rank P = .07, a statistically significant result; HR, 0.75; 95% CI, 0.52-1.09). Among patients with MSS and proficient mismatch repair, the HR for PFS was 0.66 (95% CI, 0.44-0.99). The most common grade 3 or higher treatment-related adverse events in the investigational vs placebo groups were hypertension (6 patients [7.0%] vs 2 patients [4.3%]), diarrhea (6 patients [7.0%] vs 2 patients [4.3%]), and hand-foot syndrome (6 patients [7.0%] vs 2 patients [4.3%]). One treatment-related death occurred in the investigational group. In the investigational group, the response rate was higher among patients without liver metastasis (3 of 13 individuals [23.1%]) vs with liver metastasis (4 of 69 individuals [5.8%]). The benefit of atezolizumab for PFS and OS was greater among patients without vs with liver metastasis (primary analysis of PFS: HR, 0.63 [95% CI, 0.27-1.47] vs 0.77 [95% CI, 0.51-1.17]; OS: HR, 0.33 [95% CI, 0.11-1.02] vs 1.14 [95% CI, 0.72-1.81]). Conclusions and Relevance: In this randomized clinical trial, the addition of atezolizumab to capecitabine and bevacizumab therapy provided limited (ie, not clinically meaningful) clinical benefit. Patients with MSS and proficient mismatch repair tumors and those without liver metastasis benefited more from dual inhibition of the vascular endothelial growth factor and programmed cell death 1 or programmed cell death ligand 1 pathways. Trial Registration: ClinicalTrials.gov Identifier: NCT02873195.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/uso terapêutico , Bevacizumab/uso terapêutico , Capecitabina/uso terapêutico , Neoplasias Colorretais , Idoso , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/administração & dosagem , Bevacizumab/efeitos adversos , Capecitabina/administração & dosagem , Capecitabina/efeitos adversos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão
17.
Clin J Gastroenterol ; 15(2): 451-459, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35179703

RESUMO

We report two cases of rapid progression of esophageal varices after atezolizumab-bevacizumab treatment for hepatocellular carcinoma (HCC). Case 1: a man in his 60s with hepatitis C-related liver cirrhosis after viral eradication by direct acting antiviral. He was diagnosed with HCC 8 years previously. He had undergone surgical resection 4 times, radio-frequency ablation (RFA) several times, and transcatheter arterial chemoembolization (TACE). However, HCC progressed and could not be controlled by locoregional treatment. Systemic chemotherapy was, therefore, selected. Atezolizumab-bevacizumab was administered after lenvatinib and sorafenib failure. Before starting treatment, his liver function was preserved (Child-Pugh score 5 and class A). His alpha fetoprotein and des-gamma-carboxyprothrombin levels were 3.6 ng/mL and 443 mAU/mL, respectively. Esophagogastroduodenoscopy showed no remarkable esophageal varices before atezolizumab-bevacizumab treatment. Nine months after the initiation of atezolizumab-bevacizumab, the patient was admitted for hematemesis from esophageal varices. The disease control of HCC was classified as stable disease (SD) for the liver and lung metastases, and partial response for the lymph node metastases. Neither AST nor ALT was markedly elevated in the clinical course. Endoscopic variceal ligation (EVL) for the spurting point of large esophageal varices with red wale signs was able to successfully achieve hemostasis. Atezolizumab-bevacizumab was stopped and additional EVL eradicated the esophageal varices. However, the post-banding ulcer was prolonged in comparison to usual cases. Case 2: a man in his 60s with hepatitis C-related liver cirrhosis after viral eradication by direct acting antiviral therapy. He was diagnosed with HCC 6 years previously. He had received RFA 2 times and TACE 7 times. Atezolizumab-bevacizumab was administered after lenvatinib failure. The disease control of HCC was classified as SD; however, the esophageal varices ruptured after 15 courses of atezolizumab-bevacizumab. Neither AST nor ALT were markedly elevated in the clinical course. The esophageal varices of these patients did not require treatment before atezolizumab-bevacizumab; however, they rapidly worsened and ruptured during atezolizumab-bevacizumab treatment. Although rare, similar cases with rapid progression of portal hypertension after atezolizumab-bevacizumab have been reported. We should pay attention to the worsening of esophageal varices during atezolizumab-bevacizumab treatment and poor wound healing after EVL.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Varizes Esofágicas e Gástricas , Hepatite C Crônica , Neoplasias Hepáticas , Anticorpos Monoclonais Humanizados , Antivirais/uso terapêutico , Bevacizumab/efeitos adversos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Varizes Esofágicas e Gástricas/etiologia , Hepatite C Crônica/tratamento farmacológico , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Masculino
18.
Anticancer Res ; 42(3): 1403-1412, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35220233

RESUMO

BACKGROUND/AIM: Atezolizumab plus bevacizumab therapy is the new standard treatment option for advanced hepatocellular carcinoma (HCC). The clinical details and sequential course after atezolizumab plus bevacizumab therapy remain to be determined. PATIENTS AND METHODS: Thirty-four consecutive patients who received atezolizumab plus bevacizumab therapy were evaluated. Their clinical outcomes were assessed according to liver function classified by modified albumin-bilirubin (ALBI) grade 1 and 2a (1/2a) versus 2b and treatment line (first-line versus second- or later-line). Furthermore, the treatment sequence after atezolizumab plus bevacizumab therapy was also assessed. RESULTS: The objective response and disease control rates were 15.6% and 93.8%, respectively. The median proportions of ALBI scores at 1, 2, and 3 months relative to the baseline scores were 0.94, 0.97, and 0.93, respectively. The median proportions of α-fetoprotein (AFP) scores at 1, 2, and 3 months relative to the baseline scores were 0.98, 1.12, and 1.83, respectively. There were no significant differences in the changes in the proportions of AFP and ALBI scores according to both liver function and treatment line. Twelve patients were administered lenvatinib treatment after the failure of atezolizumab plus bevacizumab therapy. The proportions of AFP and ALBI scores at 1 month relative to the baseline scores were 0.55 and 0.81, respectively. CONCLUSION: Atezolizumab plus bevacizumab therapy can be effective for advanced HCC irrespective of the patients' liver function and treatment line. Lenvatinib administration after atezolizumab plus bevacizumab therapy can be effective, although special attention should be paid to the deterioration of liver function.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab/efeitos adversos , Bilirrubina/sangue , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/patologia , Feminino , Humanos , Testes de Função Hepática , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Compostos de Fenilureia/uso terapêutico , Quinolinas/uso terapêutico , Estudos Retrospectivos , Albumina Sérica Humana/metabolismo , Fatores de Tempo , Resultado do Tratamento , alfa-Fetoproteínas/metabolismo
19.
BMC Cancer ; 22(1): 129, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-35105329

RESUMO

BACKGROUND: BCD-021 is a bevacizumab biosimilar which was shown to be equivalent to reference bevacizumab in a wide panel of physicochemical studies as well as preclinical studies in vitro and in vivo. International multicenter phase III clinical trial was conducted to compare efficacy and safety of BCD-021 and reference bevacizumab in combination with paclitaxel and carboplatin in a first-line treatment of inoperable or advanced non-squamous non-small-cell lung cancer (NSCLC). METHODS: Patients with no previous treatment for advanced non-squamous NSCLC were randomly assigned 3:2 to BCD-021 or reference bevacizumab and were treated with bevacizumab + paclitaxel + carboplatin. Therapy continued for 6 cycles (every 3 weeks), until progression of the disease or unbearable toxicity. The primary study endpoint was the overall response rate. The study goal was to prove the equivalent efficacy of BCD-021 and reference bevacizumab. Equivalence margins for 95% CI for the difference in the overall response rates were set at [-18%; 18%], for 90% CI for the ratio of overall response rate were set at [67%; 150%]. RESULTS: In total 357 patients were enrolled in the study, 212 in the BCD-021 group and 145 in the reference bevacizumab group. The ORR was 34.63% in the BCD-022 group and 33.82% in the reference bevacizumab group. Limits of 95% CI for the difference in overall response rates between the groups were [-9.47%; 11.09%]. Limits of 90% CI for the ratio of overall response rate between the groups were [79.6%; 131.73%]. For both approaches CI lied within predetermined equivalence margins. Profile of adverse events (AEs) was similar between the groups (any AEs were reported in 86.89% of patients in BCD-021 group and 89.05% of patients in reference group). No unexpected adverse reactions were reported throughout the study. No statistically significant differences regarding anti-drug antibody occurrence rate was found between BCD-022 (n=4; 1.96%) and comparator (n=5; 3.65%). Both drug products showed low occurrence rate and short life of anti-bevacizumab antibodies. Pharmacokinetics assessment after 1st and 6th study drug injection also demonstrated equivalent PK parameters by all outcome measures. CONCLUSIONS: Thus, the results of this study demonstrated therapeutic equivalence of bevacizumab biosimilar BCD-021 and referent bevacizumab drug. TRIAL REGISTRATION: The trial was registered with ClinicalTrials.gov (Study Number NCT01763645, date of registration 09/01/2013).


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab/efeitos adversos , Medicamentos Biossimilares/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Adolescente , Adulto , Idoso , Carboplatina , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/tratamento farmacológico , Paclitaxel , Federação Russa , Equivalência Terapêutica , Resultado do Tratamento , Ucrânia , Adulto Jovem
20.
J Fr Ophtalmol ; 45(4): 405-412, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35093263

RESUMO

PURPOSE: To determine the effect of two distinct intravitreal injection (IVI) techniques on the frequency of vitreous reflux (VR) and on treatment response at cumulative dosages in neovascular age-related macular degeneration (nAMD) patients. PATIENTS AND METHODS: Ninety-three eyes of 93 nAMD patients were included in the study. IVI was performed in 47 eyes using the straight technique (ST) and 46 eyes with the tunneled technique (TT). Patients received three loading doses of intravitreal bevacizumab, and substantial VR was noted for each IVI. Central (CMT), 1mm (MT1), and 3mm (MT3) macular thicknesses were measured before and after treatment. VR frequency and treatment response were compared in both groups, and correlation analysis was performed. RESULTS: Post-treatment VR was seen in 91 of 141 IVI with the ST and 33 of 138 IVI with the TT. The decrease in CMT, MT1, and MT3 after treatment with the ST was 121.4±92.5µm, 65.3±50.6µm, 28.8±30.8µm, respectively, and with the TT was 114.0±97.5µm, 67.8±72.6µm, and 27.1±31.4µm, respectively. The ST substantially increased the rate of VR compared to the TT (P<0.001), whereas the decrease in CMT, MT1, and MT3 did not vary significantly (P>0.05). There was no correlation between VR rate and decreases in CMT, MT1, or MT3 (P>0.05). CONCLUSIONS: According to our findings, the ST resulted in a higher frequency of VR than the TT, but VR did not affect the treatment response, despite multiple doses. Complication rates were negligible with both approaches. As a result, it appears that practitioners may use either IVI approach.


Assuntos
Inibidores da Angiogênese , Degeneração Macular Exsudativa , Bevacizumab/efeitos adversos , Seguimentos , Humanos , Injeções Intravítreas , Ranibizumab , Estudos Retrospectivos , Resultado do Tratamento , Fator A de Crescimento do Endotélio Vascular , Acuidade Visual , Degeneração Macular Exsudativa/tratamento farmacológico
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