Isquemia anastomótica por bevacizumab. Casos clínicos

Objetivo: Presentar dos casos de isquemia anastomótica tardía por bevacizumab y compararlo con la literatura actual. Casos clínicos: Se exponen dos pacientes con cáncer de recto metastásico, con manejo neoadyuvante, quirúrgico y adyuvancia que incluye bevacizumab, que presentan complicaciones isquémicas anastomóticas, evidenciadas con endoscopia, imágenes más biopsias dirigidas, resolviéndose en forma quirúrgica y biopsiando sitios perianastomóticos con cambios isquémicos. Discusión: Existe evidencia en la literatura que reporta isquemias y filtraciones anastomóticas tardías con el uso de bevacizumab. Parece prudente considerar y sospechar en forma oportuna esta complicación, especialmente, en pacientes con factores de riesgo. Conclusiones: Se debe considerar eventos isquémicos en territorios quirúrgicos, al uso de Bevacizumab. Mayor hincapié en pacientes con factores de riesgo como malnutrición, irradiación o sexo masculino. Considerar estudio dirigido anastomótico previo al inicio de bevacizumab. Dar relevancia a los tiempos de suspensión y reinicio de bevacizumab para evaluación de posibles complicaciones isquémicas.

Objective: To present two cases of late anastotomotic breakdown by bevacizumab and compare it with the current literature. Case report: Two patients with metastatic rectal cancer, with neoadjuvant, surgical and adjuvant management including bevacizumab, presenting anastomotic ischemic complications, evidenced with endoscopy, images and directed biopsies, surgically resolved and taking biopsy of perianastomotic sites with ischemic changes. Discussion: There is evidence in the literature reporting late anastomotic ischemia and leaks with the use of bevacizumab. It seems prudent to consider and suspect this complication in a timely manner, especially in patients with risk factors. Conclusions: Ischemic events in surgical territories should be considered when using bevacizumab. Greater emphasis on patients with risk factors such as malnutrition, irradiation or male sex. Anastomotic-directed study prior to initiation of bevacizumab should be considered. To highlight bevacizumab suspension and restart times for the evaluation of possible ischemic complications.

Case analysis of abnormal increase in blood glucose after targeted combination chemotherapy in a patient with colon cancer / 药物流行病学杂志

This article introduced a case of colon cancer patient who developed abdominal pain with nausea and vomiting after two cycles of using bevacizumab combined with fluorouracil.The perfect examination founded that the blood sugar rose abnormally to 40 mmol·L-1,the pH of blood gas was 7.24,the actual bicarbonate was 4 mmol·L-1,ketone body 3+,and urine sugar 3+.It was judged as mild diabetes ketoacidosis.After a large amount of fluid infusion,insulin treatment,and dual insulin treatment,The patient's blood gas analysis,ketone bodies,and urine sugar have all been normal,and their fasting blood sugar is controlled at 8.6 mmol·L1.The patient's condition was stable while long term use of insulin aspart was necessary.According to the association evaluation method of the National ADR Monitoring Center,the author evaluated the association of diabetes ketoacidosis,and assessed that diabetes ketoacidosis"may"be caused by the combined use of bevacizumab and fluorouracil.Through consulting domestic and foreign literature,the author analyzed and summarized tumor related glucose metabolism abnormalities,realized that abnormal blood glucose caused by chemotherapy drugs or chemotherapy adjuvant drugs can not be ignored,especially in tumor patients with diabetes history or pre diabetes.Hope the analysis can provide a certain reference for similar reactions.

Cost-utility analysis of bevacizumab combined with erlotinib in the first-line treatment of advanced EGFR mutant non-squamous NSCLC / 中国药房

OBJECTIVE To evaluate the cost-effectiveness of bevacizumab combined with erlotinib in the first-line treatment of advanced EGFR mutant non-squamous non-small cell lung cancer （NSCLC） from the perspective of China’s health system. METHODS A dynamic Markov model was established based on BEVERLY study data， with a cycle of 3 weeks， a research deadline until 99% of patients die， and an annual discount rate of 5%. The model outputs were total cost， quality-adjusted life year （QALY）， and incremental cost-effectiveness ratio （ICER）. Taking 3 times China’s per capita gross domestic product （GDP） in 2023 as the willingness-to-pay （WTP） threshold， the cost-utility analysis was used to evaluate the cost-effectiveness of bevacizumab combined with erlotinib （observation group） versus erlotinib alone （control group） in the first-line treatment of advanced EGFR mutant non-squamous NSCLC， and the single factor sensitivity analysis and probability sensitivity analysis were used to verify the robustness of the basic analysis results. RESULTS The results of the basic analysis showed that compared with the erlotinib therapy plan， ICER of bevacizumab combined with erlotinib was 1 452 243.01 yuan/QALY， which was more than 3 times China’s per capita GDP in 2023 （268 074 yuan/QALY） as the WTP threshold， indicating that bevacizumab combined with erlotinib was not cost-effective. The results of single factor sensitivity analysis showed that the cost of bevacizumab， the utility value of progression-free survival and progressed disease status had a great influence on the results. The results of probability sensitivity analysis showed that when the WTP threshold was 1 740 000 yuan/QALY， the probability of cost-effective of bevacizumab combined with erlotinib plan was 50%. CONCLUSIONS Compared with erlotinib alone， bevacizumab combined with erlotinib is not cost-effective in the first-line treatment of advanced EGFR mutant non-squamous NSCLC， when using 3 times China’s per capita GDP in 2023 as the WTP threshold.

Cost-utility analysis of bevacizumab combined with erlotinib in the first-line treatment of advanced EGFR mutant non-squamous NSCLC / 中国药房

OBJECTIVE To evaluate the cost-effectiveness of bevacizumab combined with erlotinib in the first-line treatment of advanced EGFR mutant non-squamous non-small cell lung cancer （NSCLC） from the perspective of China’s health system. METHODS A dynamic Markov model was established based on BEVERLY study data， with a cycle of 3 weeks， a research deadline until 99% of patients die， and an annual discount rate of 5%. The model outputs were total cost， quality-adjusted life year （QALY）， and incremental cost-effectiveness ratio （ICER）. Taking 3 times China’s per capita gross domestic product （GDP） in 2023 as the willingness-to-pay （WTP） threshold， the cost-utility analysis was used to evaluate the cost-effectiveness of bevacizumab combined with erlotinib （observation group） versus erlotinib alone （control group） in the first-line treatment of advanced EGFR mutant non-squamous NSCLC， and the single factor sensitivity analysis and probability sensitivity analysis were used to verify the robustness of the basic analysis results. RESULTS The results of the basic analysis showed that compared with the erlotinib therapy plan， ICER of bevacizumab combined with erlotinib was 1 452 243.01 yuan/QALY， which was more than 3 times China’s per capita GDP in 2023 （268 074 yuan/QALY） as the WTP threshold， indicating that bevacizumab combined with erlotinib was not cost-effective. The results of single factor sensitivity analysis showed that the cost of bevacizumab， the utility value of progression-free survival and progressed disease status had a great influence on the results. The results of probability sensitivity analysis showed that when the WTP threshold was 1 740 000 yuan/QALY， the probability of cost-effective of bevacizumab combined with erlotinib plan was 50%. CONCLUSIONS Compared with erlotinib alone， bevacizumab combined with erlotinib is not cost-effective in the first-line treatment of advanced EGFR mutant non-squamous NSCLC， when using 3 times China’s per capita GDP in 2023 as the WTP threshold.

Rare and severe adverse reaction diabetic ketoacidosis induced by bevacizumab：one case report / 中国药房

OBJECTIVE To provide reference for the safe use of bevacizumab in cancer patients. METHODS The diagnosis and treatment of a 65-year-old female lung adenocarcinoma patient with diabetic ketoacidosis （DKA） induced by bevacizumab was retrospectively analyzed， and the possible mechanisms and causes were analyzed based on literature review. RESULTS & CONCLUSIONS The diagnosis and treatment process of patients were analyzed， and DKA caused by other drugs and disease factors were excluded. DKA was considered to be caused by the use of bevacizumab according to Naranjo’s ADR evaluation scale； the acidosis of the patient improved rapidly after one hemodialysis treatment. DKA caused by bevacizumab is rare in clinic， clinicians should be aware that bevacizumab may affect pancreatic function and induce DKA， and early detection and treatment should be achieved to improve the prognosis.

Retrospective analysis of adverse drug reactions of bevacizumab biosimilar and original drug in our hospital / 中国药房

OBJECTIVE To analyze the occurrence of adverse drug reactions （ADR） between bevacizumab biosimilars and original drugs， and to provide data support for rational use of drugs in clinical. METHODS ADR reports of bevacizumab biosimilars and original drugs reported by Jiangsu Cancer Hospital from January to December 2022 were retrospectively analyzed. RESULTS A total of 6 818 patients were treated with bevacizumab， and 136 ADR patients were reported. The incidence of ADR caused by bevacizumab biosimilars was higher than original drugs （2.18% vs. 0.71%， P＝0.004）. In ADR reports， the main treatment plan was bevacizumab combined with other tumor drugs （129 patients）； 118 patients were cured and improved； there were 108 general reports and 28 serious reports； the main system/organ involved in ADR was the cardiovascular system； there were no statistical significance in the incidence rates of hypertension/blood pressure increase， leukocyte/platelet decrease， diarrhea and fever caused by bevacizumab biosimilars and original drugs. CONCLUSIONS The incidence of ADR related to bevacizumab biosimilars is significantly higher than that of the original drugs， but there is no significant difference in the clinical manifestation of ADR. Clinicians can use bevacizumab biosimilars or original drugs based on the willingness of patients and their families.

Evaluation of efficacy and safety of Sintilimab+Bevacizumab combined with PP regime in patients with advanced non-squamous non-small cell lung cancer / 中国药师

Objective To investigate the clinical efficacy and safety of the combination PP(Pemetrexed+Cisplatin)regimen of sindilizumab(Sintilimab)+bevacizumab(Bevacizumab)in advanced non-squamous non-small cell lung cancer(NSCLC)with disease progression after treatment with epidermal growth factor receptor(EGFR)tyrosine kinase inhibitors.Methods Patients with advanced non-squamous NSCLC with disease progression after receiving EGFR tyrosine kinase inhibitor treatment from January 2019 to January 2022 were retrospectively selected from The Third Affiliated Hospital of Zhejiang University of Traditional Chinese Medicine.According to the different treatment modalities,patients were divided into the pemetrexed+cisplatin treatment group(Chemotherapy)group and the pemetrexed+cisplatin+si ndilizumab+bevacizumab treatment(Sintilimab+Bevacizumab)group.Progression-free survival(PFS),overall survival(OS),objective response rate(ORR)and disease control rate(DCR)were compared between the two groups and the occurrence of adverse reactions was assessed.Results A total of 107 patients were enrolled in the study,53 in the Sintilimab+Bevacizumab group and 54 in the Chemotherapy group.The median PFS and median OS were significantly higher in the Sintilimab+Bevacizumab group than in the Chemotherapy group(P＜0.05).The median PFS and median OS in the Sintilimab+Bevacizumab group were significantly higher than in the Chemotherapy group.Bevacizumab group had no statistically significant difference in ORR with Chemotherapy group(P＞0.05),while DCR was significantly higher than Chemotherapy group(P＜0.05).The main adverse reactions were similar in both groups with the most common adverse events being anemia and neutrophils decrease.Conclusion Sintilimab+Bevacizumab combined with PP regimen treatment improved DCR and prolonged PFS and OS in patients with advanced non-squamous NSCLC whose disease progressed after EGFR tyrosine kinase inhibitor treatment.

Preoperative co-application of bevacizumab and tissue plasminogen activator in vitrectomy for proliferative diabetic retinopathy

ABSTRACT Purpose: To investigate the clinical benefits of the co-application of bevacizumab and tissue plasminogen activator as adjuncts in the surgical treatment of proliferative diabetic retinopathy. Methods: Patients who underwent vitrectomy for proliferative dia-betic retinopathy complications were preoperatively given in-travitreal injection with either bevacizumab and tissue plasminogen activator (Group 1) or bevacizumab alone (Group 2). Primary outcomes were surgery time and number of intraoperative iatrogenic retinal breaks. Secondary outcomes included changes in the best-corrected visual acuity and postoperative complications at 3 months postoperatively. Results: The mean surgery time in Group 1 (52.95 ± 5.90 min) was significantly shorter than that in Group 2 (79.61 ± 12.63 min) (p<0.001). The mean number of iatrogenic retinal breaks was 0.50 ± 0.59 (0-2) in Group 1 and 2.00 ± 0.83 (0-3) in Group 2 (p<0.001). The best-corrected visual acuity significantly improved in both groups (p<0.001). One eye in each group developed retinal detachment. Conclusion: Preoperative co-application of bevacizumab and tissue plasminogen activator as adjuncts in the surgical treatment of proliferative diabetic retinopathy shortens the surgery time and reduces the number of intraoperative iatrogenic retinal breaks.

Effectiveness of treatment of exudative age-related macular degeneration with anti-vascular endothelial growth factor drugs / Efetividade do tratamento da doença macular relacionada à idade exsudativa com drogas antifactor de crescimento endotelial vascular

ABSTRACT Objective: To characterize the effectiveness of anti-vascular endothelial growth factor drugs in exudative age-related macular degeneration. Methods: Retrospective longitudinal study of 54 patients with age-related macular degeneration receiving bevacizumab or aflibercept. Demographic data, visual acuity, and central retinal thickness measurements were collected. Improvement/stability of visual acuity and reduction in retinal thickness configured satisfactory responses. Results: Among the 60 eyes studied, there was no difference (p = 0.262) in satisfactory response when using bevacizumab (48.5%) or aflibercept (63.0%). Snellen's visual acuity, letter gain, and retinal thickness showed improvement or maintenance in 55.0%, 32.8%, and 78.3% of cases, respectively. The percentage of improvement/maintenance was higher in eyes with an initial visual acuity of < Snellen 20/400 (70.0% versus 40.0%; p = 0.002). Conclusion: A higher percentage of improvement/stabilization of visual acuity and macular thickness was observed in patients with age-related macular degeneration, with better response in patients with visual acuity worse than Snellen 20/400.

RESUMO Objetivo: Caracterizar a efetividade de medicamentos antifactor de crescimento endotelial vascular na degeneração macular relacionada à idade exsudativa. Métodos: Estudo longitudinal retrospectivo em 54 pacientes com degeneração macular relacionada à idade que usaram bevacizumab ou aflibercept. Foram coletados dados demográficos, da acuidade visual e da espessura central da retina. Melhora/estabilidade da acuidade visual e redução da espessura configuraram respostas satisfatórias. Resultados: Entre 60 olhos estudados, não houve diferença (p = 0,262) de acordo com o uso de bevacizumab (48,5%) ou aflibercept (63,0%). Acuidade visual segundo Snellen, ganho de letras e espessura retiniana demonstraram melhora ou estabilidade em 55,0%, 32,8% e 78,3% dos casos, respectivamente. Entre os olhos com acuidade visual inicial < 20/400, o percentual de melhora/estabilidade foi superior (70,0% versus 40,0%; p = 0,002). Conclusão: Em pacientes com degeneração macular relacionada à idade, foi percebida uma maior proporção de melhora ou estabilização da acuidade visual e espessura macular, com melhor resposta entre os pacientes com visão pior que 20/400.

Refractive profile of children treated with intravitreal bevacizumab for retinopathy of prematurity

Purpose: To study the refractive profile of children after they received intravitreal injection of bevacizumab for retinopathy of prematurity (ROP). Methods: The study was conducted at a tertiary eye care hospital in South India. ROP patients of more than 1 year of age, presenting to the Pediatric Ophthalmology Clinic and Retina Clinic and having history of treatment for type ? ROP with intravitreal bevacizumab (IVB) or intravitreal bevacizumab and laser photocoagulation were included in the study. Cycloplegic refraction was done, and the refractive status was evaluated. The refractive status of age?matched, full?term children with uneventful perinatal and neonatal history was also recorded and compared to the study group. Results: Among 134 eyes of 67 study subjects, the major refractive error was myopia in 93 eyes (69.4%; spherical equivalent [SE] = ?2.89 ± 3.1, range = ?11.5 to ?0.5 D). There were 75 eyes (56%) with low?to?moderate myopia; high myopia was seen in 13.4%, emmetropia in 18.7%, and hypermetropia in 11.9% of eyes. The majority of them (87%) had with?the?rule (WTR) astigmatism. In 134 eyes, the SE was ?1.78 ± 3.2 (range = ?11.5 to 4 D); the SE of the 75 eyes with low?to?moderate myopia was ?1.53 ± 1.2 (range = ?0.50 to ?5 D). In the control group, the majority had emmetropia (91.8%). There was no significant association between the age at which IVB had been injected and the development of refractive errors (P = 0.078). The prevalence of low?to?moderate myopia was more than high myopia in patients with zone ? and zone ? ROP before treatment (60.0% and 54.5%, respectively). Conclusion: Myopia was the major refractive error seen in post?IVB pediatric patients. WTR astigmatism was more commonly seen. The age at which IVB injection had been given had no effect on the development of refractive errors

Bevacizumab effect on viability of free groin flaps in rats / Efeito do bevacizumabe na viabilidade de retalho inguinal livre em ratos

Introduction: Bevacizumab is among the most frequently used drugs in cancer treatment. There is evidence that some anti-angiogenic drugs reduce flap survival, but it is unclear whether this applies to Bevacizumab. We investigated the effect of Bevacizumab on the viability of free flaps in rats. Methods: The animals were randomly assigned to one of three groups. The Graft group received intravascular saline and was submitted to a full-thickness skin graft. The Flap-Saline and the Flap- BVZ groups underwent a free groin flap after receiving, respectively, intravascular saline solution or intravascular administration of Bevacizumab. Results: The Graft group showed a lower percentage of the viable area (22.81%) relative to the Flap- Saline (83.98%; p<0.0001) and the Flap-BVZ groups (60.50%; p=0.0048). The lowest vascular pedicle patency was observed in the Flap-BVZ group, but the difference relative to the Flap-Saline was not significant (arteries, p=0.0867; veins, p=0.9999). A significant difference was observed in the occurrence of necrosis (p=0.0010), which was higher in the histological samples of the Graft (87.50%) and the Flap- BVZ (60.00%) relative to the Flap-Saline Group (0%). Inflammation occurred less frequently in the Flap-Saline (33.33%) compared to the Graft (87.5%) and Flap- BVZ group (70.00%), but the difference did not reach significance (p=0.0588). No significant differences emerged in the occurrence of hemorrhage or intraluminal thrombosis. Conclusion: The increase in inflammation, decrease in patency and reduction of viable area, though not significant, are in line with the histological analysis and call for further research on the potential adverse effects of the drug.

Introdução: Bevacizumabe é um dos fármacos mais utilizados no tratamento do câncer. Existem evidências de que drogas antiangiogênicas reduzem a taxa de sobrevivência dos retalhos, porém não está claro se isso se aplica ao bevacizumabe. Investigamos o efeito de bevacizumabe na viabilidade de retalhos livres em ratos. Método: Os animais foram randomizados em três grupos. O grupo Enxerto recebeu injeção intravenosa de soro fisiológico 0,9% (SF 0,9%) e foi submetido a uma enxertia de pele total. Os grupos Retalho-SF e Retalho-BVZ foram submetidos a retalhos inguinais livres e receberam injeções intravenosas, respectivamente, de SF 0,9% e Bevacizumabe. Resultados: O grupo Enxerto apresentou menor percentual de área de retalho viável (22,81%) em relação ao grupo Retalho-SF (83,98%; p<0,0001) e Retalho-BVZ (60,50%; p=0,0048). Os pedículos do grupo Retalho-BVZ apresentaram menor patência, mas a diferença em relação ao grupo Retalho-SF não foi significante (artérias, p=0,0867; veias, p=0,9999). A ocorrência de necrose foi significativamente maior nos grupos Enxerto (87,50%) e Retalho-BVZ (60,00%) em relação ao grupo Retalho-SF (0%) (p=0,0010). A ocorrência de inflamação foi menor no grupo Retalho-SF (33,33%) em relação aos grupos Enxerto (87,5%) e Retalho-BVZ (70,00%), porém essa análise não atingiu significância (p=0,0588). Não houve diferenças significantes na ocorrência de hemorragia ou trombose intraluminal entre os grupos. Conclusão: O aumento da inflamação, redução da patência e das áreas viáveis dos retalhos, apesar de não significantes, corroboram com efeitos deletérios do bevacizumabe evidenciados na análise histológica e demandam futuros estudos dos potenciais efeitos adversos da droga.

Efficacy and safety analysis of intravitreal bio-similar products of bevacizumab in patients with macular edema because of retinal diseases

Purpose: The purpose of this study was to evaluate retrospectively the efficacy and safety profile of intravitreal injection of bevacizumab bio?similar product Zybev(Z) for macular edema because of retinal diseases. Methods: A retrospective analysis was conducted on patients with macular edema because of retinal diseases, who had been administered intravitreal injections of bio?similar bevacizumab at a tertiary eye care center. Changes in the retinal thickness and visual acuity were evaluated to judge the efficacy, and adverse events were noted for the safety profile over a period of 6 weeks. Results: A total of 104 patients were included in the study. The mean age of the patients was 53 ± 13.5 years. The mean pre?injection best corrected visual acuity (BCVA) was 1.32 ± 0.70 log minimum angle of resolution (logMAR) with a central subfield thickness (CST) of 429.26 ± 204.30 ?m, and the post?injection BCVA at 6 weeks was 1.13 ± 0.71 logMAR with a CST of 302.26 ± 104.50 ?m; this change was statistically significant (P < 0.05) for all groups. The mean average cube thickness (?m) decreased from 11.85 ± 1.96 pre?injection to 10.52 ± 1.75 post?injection, and the mean average cube volume (mm3) decreased from 329.30 ± 54.35 to 302.23 ± 49.56 (P < 0.05). During the follow?up period after injection, no patient had inflammation, endophthalmitis, an increase in intra?ocular pressure, or systemic side effects. Conclusion: This short?term retrospective analysis provides evidence regarding the efficacy and safety of intravitreal injection of bio?similar products of bevacizumab for the treatment of macular edema because of retinal diseases

Staphylococcus hominis: a rare cause of endophthalmitis / Staphylococcus hominis: uma causa rara de endoftalmite

ABSTRACT Staphylococcus hominis (S. hominis) is a coagulase-negative Staphylococci and an infrequent cause of endophthalmitis. Due to its ability to produce biofilm, especially in diabetic patients, strains may acquire antibiotic resistance. We present two cases of S. hominis endophthalmitis, one with acute endophthalmitis after intravitreal bevacizumab injection and one with chronic endophthalmitis following undiagnosed penetrating ocular trauma. Although there are only four published S. hominis endophthalmitis cases in the literature, to the best of our knowledge, there has been no previously published case after intravitreal bevacizumab.

RESUMO Staphylococcus hominis (S. hominis) é um estafilococo coagulase-negativo e uma causa pouco frequente de endoftalmite. Devido à sua capacidade de produzir biofilme, especialmente em pacientes diabéticos, cepas dessa bactéria podem adquirir resistência a antibióticos. Este relato apresenta dois casos de endoftalmite por S. hominis: um de endoftalmite aguda após injeção intravítrea de bevacizumabe e outro de endoftalmite crônica após trauma ocular penetrante não diagnosticado. Embora existam apenas quatro casos de endoftalmite por S. hominis publicados na literatura, até onde sabemos não houve nenhum caso publicado anteriormente após bevacizumabe intravítreo.

Prospective evaluation of the effectiveness of combined treatment of macular edema secondary to retinal vein occlusion with intravitreal bevacizumab and dexamethasone implants / Estudo intervencionista prospectivo para avaliar a eficácia da associação do bevacizumabe intravítreo ao implante de dexametasona para edema macular secundário à oclusão da veia retiniana

ABSTRACT Purpose: To evaluate the effectiveness of in­­­travitreal bevacizumab injections following a single dexamethasone implant in the treatment of macular edema secondary to branch and central retinal vein occlusion. Methods: This was a prospective interventional non-comparative study, 44 eyes of patients with naïve macular edema related to branch and central retinal vein occlusion were treated with a dexamethasone implant. Patients were followed-up at four-week intervals from the second to the sixth month. If persistent or recurrent macular edema occurred during this period, the patient was treated with intravitreal bevacizumab injections on an as-needed basis. The outcome measures were best-corrected visual acuity and central macular thickness changes. Results: The mean best-corrected visual acuity changed from 0.97 ± 0.33 LogMAR at baseline to 0.54 ± 0.40 at the six-month post-implant examination (p<0.00001). Improvement ≥3 Snellen lines were seen in 20 eyes (45.54%). The mean central macular thickness at baseline was 670.25 ± 209.9 microns. This had decreased to 317.43 ± 112.68 microns at the six-month follow-up (p<0.00001). The mean number of intravitreal bevacizumab injections received in the six months post-implant was 2.32. The mean time from dexamethasone implant to first anti-VEGF injection was 3.45 months. Conclusions: Intravitreal bevacizumab injections following a single dexamethasone implant were found to improve best-corrected visual acuity and central macular thickness in patients with macular edema due to branch and central retinal vein occlusion at six months, with few intravitreal injections required.

RESUMO Objetivo: Avaliar a eficácia da combinação de in­jeções intravítreas de bevacizumabe em olhos com edema macular secundário à oclusão de ramo e da veia central da retina após um único implante de dexametasona. Métodos: Foi realizado um estudo prospectivo intervencionista não comparativo com 44 olhos de pacientes com edema macular relacionado à oclusão de ramo e veia central da retina, sem tratamento prévio e tratados com um único implante de dexametasona, que foram acompanhados em intervalos de quatro semanas do segundo ao sexto mês. Se fosse constatado edema macular persistente ou recorrente durante esse período, os pacientes eram tratados com injeções intravítreas de bevacizumabe em um regime ajustado conforme a necessidade. Foram estudadas a melhor acuidade visual corrigida e alterações da espessura macular central. Resultados: A média da melhor acuidade visual corrigida mudou de 0,97 ± 0,33 LogMAR iniciais para 0,54 ± 0,40 no exame de 6 meses (p<0,00001). Vinte olhos (45,54%) melhoraram 3 linhas de Snellen ou mais. A média da espessura macular central inicial foi de 670,25 ± 209,9 μm e diminuiu para 317,43 ± 112,68 μm na visita de 6 meses (p<0,00001). O número médio de injeções intravítreas de bevacizumabe em 6 meses foi de 2,32 e o tempo médio entre o implante de dexametasona e a primeira injeção de anti-VEGF foi de 3,45 meses. Conclusão: Injeções intravítreas de bevacizumabe após um único implante de dexametasona podem proporcionar um aumento da melhor acuidade visual corrigida e diminuição da espessura macular central aos 6 meses em pacientes com edema macular devido à oclusão de ramo e da veia central da retina, com poucas injeções intravítreas.

99mTc-HYNIC/Cy7-Fab(Bevacizumab): su empleo como agente de imagen en mieloma múltiple / 99mTc-HYNIC/Cy7-Fab(Bevacizumab): its use as an imaging agent in Multiple Myeloma / 99mTc-HYNIC/Cy7-Fab (Bevacizumab): seu uso como agente de imagem em mieloma múltiplo

Introducción: el mieloma múltiple es un trastorno hematológico maligno y el segundo cáncer de la sangre más frecuente. El proceso de la angiogénesis tumoral es fundamental para el crecimiento y metástasis de muchos tipos de tumores, incluido en mieloma múltiple. Se sabe que la sobreexpresión del factor de crecimiento endothelial vascular se encuentra asociado a un mal pronóstico en esta patología, representando un blanco clave para la terapia anti-angiogénica en mieloma múltiple. El anticuerpo monoclonal Bevacizumab es capaz de unirse con gran afinidad al factor de crecimiento endothelial vascular bloqueando su acción. Objetivo: evaluar el Fab(Bevacizumab) marcado con 99mTc o Cy7 como potenciales agentes de imagen moleculares de la expresión de factor de crecimiento endothelial vascular en mieloma múltiple. Material y métodos: la expresión de factor de crecimiento endothelial vascular fue analizada mediante citometría de flujo en la línea celular huaman de mieloma múltiple, la MM1S. Fab(Bevacizumab) fue producido mediante digestión de Bevacizumab con papaína, conjugado a NHS-HYNIC-Tfa y radiomarcado con 99mTc. Se realizaron estudios de biodistribución y de tomografía computarizada por emisión del fotón simple. A su vez, Fab(Bevacizumab) fue marcado con Cy7 para obtener imágenes de fluorescencia in vivo hasta 96 horas. Resultados: el análisis por citometría de flujo en la línea celular MM1S reveló que la expresión de factor de crecimiento endothelial vascular es predominantemente intracelular. Los estudios de biodistribución y SPECT/CT del complejo 99mTc-HYNIC-Fab(Bevacizumab) mostraron una rápida eliminación sanguínea y una significativa captación a nivel renal y tumoral. Las imágenes por fluorescencia empleando Cy7-Fab(Bevacizumab) permitieron la visualización tumoral hasta 96 h p.i. Conclusiones: logramos visualizar la expresión de factor de crecimiento endothelial vascular in vivo en mieloma múltiple mediante el empleo del fragmento Fab del anticuerpo anti-VEGF (Bevacizumab) marcado con 99mTc y Cy7. Estos nuevos agentes de imagen molecular podrían ser empleados potencialmente en el ámbito clínico para la estadificación y el seguimiento de pacientes con mieloma múltiple, mediante la visualización radioactiva in vivo de la expresión de factor de crecimiento endothelial vascular en todo el cuerpo. La imagen óptica de estos trazadores mejoraría el muestreo tumoral y podría guiar la extirpación quirúrgica.

Introduction: Multiple myeloma is a hematologic malignancy and the second most common blood cancer. The process of tumor angiogenesis is central to the growth and metastasis of many types of tumors, including multiple myeloma. Overexpression of vascular endothelial growth factor is known to be associated with poor prognosis in this pathology, representing a key target for anti-angiogenic therapy in multiple myeloma. The monoclonal antibody Bevacizumab is able to bind with high affinity to vascular endothelial growth factor blocking its action. Objective: to evaluate 99mTc- or Cy7-labeled Fab(Bevacizumab) as potential molecular imaging agents of vascular endothelial growth factor expression in multiple myeloma. Methods: Vascular endothelial growth factor expression was analyzed by flow cytometry in the multiple myeloma huaman cell line, MM1S. Fab(Bevacizumab) was produced by digestion of Bevacizumab with papain, conjugated to NHS-HYNIC-Tfa and radiolabeled with 99mTc. Biodistribution and single photon emission computed tomography studies were performed. In turn, Fab(Bevacizumab) was labeled with Cy7 to obtain in vivo fluorescence images up to 96 hours. Results: Flow cytometry analysis in the MM1S cell line revealed that vascular endothelial growth factor expression is predominantly intracellular. Biodistribution and SPECT/CT studies of the 99mTc-HYNIC-Fab(Bevacizumab) complex showed rapid blood clearance and significant renal and tumor uptake. Fluorescence imaging using Cy7-Fab(Bevacizumab) allowed tumor visualization up to 96 h p.i. Conclusions: we were able to visualize vascular endothelial growth factor expression in vivo in multiple myeloma using the Fab fragment of the anti-VEGF antibody (Bevacizumab) labeled with 99mTc and Cy7. These new molecular imaging agents could potentially be employed in the clinical setting for staging and monitoring of patients with multiple myeloma by in vivo radioactive visualization of vascular endothelial growth factor expression throughout the body. Optical imaging of these tracers would improve tumor sampling and could guide surgical excision.

Introdução: O mieloma múltiplo é uma malignidade hematológica e o segundo câncer de sangue mais comum. O processo de angiogênese tumoral é fundamental para o crescimento e a metástase de muitos tipos de tumores, incluindo o mieloma múltiplo. Sabe-se que a superexpressão do fator de crescimento endotelial vascular está associada a um prognóstico ruim no mieloma múltiplo, representando um alvo importante para a terapia antiangiogênica no mieloma múltiplo. O anticorpo monoclonal Bevacizumab é capaz de se ligar com alta afinidade ao fator de crescimento endotelial vascular e bloquear sua ação. Objetivo: avaliar o Fab(Bevacizumab) marcado com 99mTc ou Cy7 como possíveis agentes de imagem molecular da expressão do fator de crescimento endotelial vascular no mieloma múltiplo. Métodos: A expressão do fator de crescimento endotelial vascular foi analisada por citometria de fluxo na linha celular de mieloma múltiplo MM1S. O Fab(Bevacizumab) foi produzido pela digestão do Bevacizumab com papaína, conjugado com NHS-HYNIC-Tfa e radiomarcado com 99mTc. Foram realizados estudos de biodistribuição e tomografia computadorizada por emissão de fóton único. Por sua vez, o Fab(Bevacizumab) foi marcado com Cy7 para geração de imagens de fluorescência in vivo por até 96 horas. Resultados: A análise de citometria de fluxo na linha celular MM1S revelou que a expressão do fator de crescimento endotelial vascular é predominantemente intracelular. Os estudos de biodistribuição e SPECT/CT do complexo 99mTc-HYNIC-Fab(Bevacizumab) mostraram uma rápida depuração sanguínea e uma captação renal e tumoral significativa. A imagem de fluorescência usando Cy7-Fab(Bevacizumab) permitiu a visualização do tumor até 96 horas p.i. Conclusões: Conseguimos visualizar a expressão do fator de crescimento endotelial vascular in vivo no mieloma múltiplo usando o fragmento Fab do anticorpo anti-VEGF (Bevacizumab) marcado com 99mTc e Cy7. Esses novos agentes de imagem molecular poderiam ser usados no cenário clínico para o estadiamento e o monitoramento de pacientes com mieloma múltiplo, visualizando radioativamente a expressão do fator de crescimento endotelial vascular in vivo em todo o corpo. A geração de imagens ópticas desses traçadores melhoraria a amostragem do tumor e poderia orientar a excisão cirúrgica.

Clinical efficacy of paclitaxel and carboplatin with versus without bevacizumab in treatment of advanced non-small cell lung cancer: A systematic review and meta-analysis / 中国胸心血管外科临床杂志

@#Objective    To systematically evaluate the clinical efficacy and adverse reactions of paclitaxel and carboplatin with or without bevacizumab in the treatment of non-small cell lung cancer (NSCLC). Methods    The databases including PubMed, The Cochrane Library, EMbase, CNKI, Wanfang Data, VIP and CBM were searched from inception to October 2022 to collect randomized controlled trials of the clinical efficacy of paclitaxel and carboplatin with or without bevacizumab for the treatment of NSCLC. RevMan 5.4 software was used for meta-analysis. Results    Eight randomized controlled trials were enrolled, involving a total of 1 724 patients. Meta-analysis showed that for the treatment of NSCLC, the disease control rate, overall response rate, 1-year survival rate, and 2-year survival rate were higher in the trial group (paclitaxel and carboplatin combined with bevacizumab) than those in the control group (paclitaxel and carboplatin) (P<0.05); however, the incidences of the adverse reactions, such as leukopenia, hemorrhage, proteinuria and hypertension, etc, were higher in the trial group than those in the control group (P<0.05). There were no statistical differences between the trial group and the control group in the incidences of fatigue, thrombocytopenia, neutropenia or hyponatremia, etc (P>0.05). In addition, the median progression-free survival and overall survival were longer in the trial  group than those in the control group. Conclusion    For the treatment of NSCLC, paclitaxel and carboplatin combined with bevacizumab is superior in terms of disease control, overall response and prolonging patient survival, etc, but will be associated with more adverse reactions.

Initial Treatment of Aumolertinib in Combination with Bevacizumab for Advanced NSCLC with Primary EGFR T790M Mutation: A Report of Three Cases and Literature Review / 中国肺癌杂志

With the development of sequencing technology, the detection rate of non-small cell lung cancer (NSCLC) with primary epidermal growth factor receptor (EGFR) T790M mutation is increasing. However, the first-line treatment for primary EGFR T790M-mutated NSCLC still lacks standard recommendations. Here, we reported three advanced NSCLC cases with EGFR-activating mutation and primary T790M mutation. The patients were initially treated with Aumolertinib combination with Bevacizumab; among which, one case was discontinued Bevacizumab due to bleeding risk after treatment for three months. Treatment was switched to Osimertinib after ten months of treatment. Another case switched to Osimertinib and discontinued Bevacizumab after thirteen months of treatment. The best effect response in all three cases was partial response (PR) after initial treatment. Two cases progressed after first-line treatment and progression-free survival (PFS) was eleven months and seven months respectively. The other one patient had persistent response after treatment, and the treatment duration has reached nineteen months. Two cases had multiple brain metastases before administration and the best response to intracranial lesions was PR. The intracranial PFS was fourteen months and not reached (16+ months), respectively. There were no new adverse events (AEs), and no AEs of grade three or above were reported. In addition, we summarized the research progress of Osimertinib in the treatment of NSCLC with primary EGFR T790M mutation. In conclusion, Aumolertinib combined with Bevacizumab in the treatment of advanced NSCLC with primary EGFR T790M mutation has a high objective response rate (ORR) and control ability of intracranial lesions, which can be used as one of the initial options for first-line advanced NSCLC with primary EGFR T790M mutation.
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Clinical efficacy and pharmacoeconomic evaluation of bevacizumab or cetuximab combined with chemotherapy in the treatment of advanced colorectal cancer / 中国医师进修杂志

Objective:To compare the clinical efficacy and pharmacoeconomic evaluation of bevacizumab or cetuximab combined with chemotherapy in the treatment of advanced colorectal cancer.Methods:The clinical data of 68 patients with advanced colorectal cancer from January 2018 to December 2020 in Baotou Tumor Hospital were retrospectively analyzed. Among them, 40 patients with treated with bevacizumab combined with chemotherapy (bevacizumab group), 28 patients were treated with cetuximab combined with chemotherapy (cetuximab group), and the chemotherapy of two group was FOLFOX/FOLFIRI program. The short-term clinical efficacy, adverse reactions and pharmacoeconomic evaluation result were compared between two groups.Results:There were no statistical differences in effective rate and disease control rate between bevacizumab group and cetuximab group: 30.00% (12/40) vs. 28.57% (8/28) and 67.5% (27/40) vs. 60.71% (17/28), P>0.05. The incidence of Ⅲ to Ⅳ grade erythra in bevacizumab group was significantly lower than that in cetuximab group: 2.50% (1/40) vs. 71.43% (20/28), and there was statistical difference ( P<0.01); there were no statistical differences in the incidences of Ⅲ to Ⅳ grade bone marrow suppression, nausea vomiting, hepatic functional lesion and diarrhea between two groups ( P>0.05). The pharmacoeconomic evaluation result showed that the cost of monoclonal antibody and total cost in bevacizumab group were significantly lower than those in cetuximab group: (9 009 ± 1 500) yuan vs. (27 840 ± 2 202) yuan and (11 242 ± 1 731) yuan vs. (29 867 ± 3 002) yuan, and there were statistical differences ( P<0.01); the cost-effectiveness ratio in bevacizumab group was 37 473.3, and it in cetuximab group was 104 430.1, the incremental cost-effectiveness ratio of two programs was 11 640.6. Conclusions:In the treatment of advanced colorectal cancer, the efficacy of bevacizumab combined with chemotherapy is similar to that of cetuximab combined with chemotherapy, but bevacizumab combined with chemotherapy has lower costs and fewer adverse reactions, so bevacizumab is more economical and applicable.

A comparative study on the efficacy and adverse reactions of nituzumab and bevacizumab combined with synchronous ra-diotherapy and chemotherapy in the treatment of locally advanced cervical cancer / 实用肿瘤学杂志

Objective The objective of this study was to compare the short-term efficacy and adverse reactions of nituzum-ab combined with synchronous radiotherapy and chemotherapy and bevacizumab combined with synchronous radiotherapy and chemo-therapy in the treatment of locally advanced cervical cancer.Methods A total of 100 locally advanced cervical cancer patients with pathological type of squamous cell carcinoma were collected from 1 September 2020 to 31 December 2021.They were divided into a control group(synchronous radiotherapy and chemotherapy group),a nituzumab group(nituzumab combined synchronous radiotherapy group)and a bevacizumab group(bevacizumab combined synchronous radiotherapy and chemotherapy group).The total effective rate of short-term treatment,changes in tumor volume before and after treatment,serum squamous cell carcinoma antigen(SCC)levels be-fore and after treatment,and adverse reactions after treatment were compared among patients of the three groups.Results The short-term total effective rates of the Nitro group,Bevar group and control group were 90.3％,87.2％and 60.0％,respectively.The total effective rates of the Nitro and Bevar groups were significantly higher than those of the control group,and the differences were statisti-cally significant(P＜0.001).There was no statistically significant difference in the total effective rates of the Nitro and Bevar groups(P＞0.05);The degree of tumor volume reduction and SCC reduction in the Nituo group and Bevac group after treatment was higher than those in the control group(P＜0.05),and there was no statistically significant difference between the two groups(P＞0.05).The incidence of hypertension in the Bevar group was 33.4％,significantly higher than that in the control group(10.0％)and the Ni-tro group(12.9％)(P＜0.05).There was no statistically significant difference in the incidence of hypertension between the Nito group and the control group(P＞0.05);There was no statistically significant difference in the incidence of adverse reactions among the three groups except hypertension(P＞0.05).Conclusion Nituzumab combined with synchronous radiotherapy and chemothera-py,as well as bevacizumab combined with synchronous radiotherapy and chemotherapy,can improve the short-term efficacy of locally advanced cervical cancer,effectively reduce tumor volume and inhibit the expression of tumor markers,both of which are superior to synchronous radiotherapy and chemotherapy alone.Compared to bevacizumab,nituzumab has fewer adverse reactions.For patients with locally advanced cervical cancer,the combination of nituzumab and concurrent radiotherapy and chemotherapy is more reliable in terms of safety.

Efficacy and safety of bevacizumab biosimilars versus original drugs for patients with metastatic colorectal cancer:a Meta-analysis / 药物流行病学杂志

Objective To systematically review the efficacy and safety of bevacizumab biosimilars versus original drugs in treatment of metastatic colorectal cancer.Methods PubMed,Embase,Cochrane Library,CNKI,WanFang Data,VIP and SinoMed databases were electronically searched to collect the randomized controlled trials(RCTs)of bevacizumab biosimilar in patients with metastatic colorectal cancer from inception to June 18,2023.Two reviewers independently screened the literature,extracted data,and assessed the risk of bias of the included studies,and a meta-analysis was conducted using Stata 17.0 software.Results A total of 4 RCTs involving 1 052 patients were included.The results of meta-analysis showed that no significant difference was found in overall response rate(RD=﹣0.01,95%CI ﹣0.06 to 0.05,P=0.86),progression free survival(HR=1.00,95%CI 0.91 to 1.09,P=0.94),the total incidence of adverse drug reactions(RR=1.05,95%CI 0.85 to 1.31,P=0.91)and the incidence of severe adverse events(RR=0.886,95%CI 0.377 to 2.081,P=0.60)between bevacizumab biosimilars group and original drugs group.Conclusion The current evidence shows that bevacizumab biosimilar is equivalent to original drugs in treatment of metastatic colorectal cancer.Due to limited quality and quantity of the included studies,more high quality studies are required to verify the above conclusions.