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1.
Artigo em Inglês | MEDLINE | ID: mdl-38701802

RESUMO

A 17-year-old Appaloosa mare was referred for evaluation of presumed refractory keratitis of the left eye. Gross examination revealed ocular discomfort and corneal neovascularization with a nasal focal opacification affecting approximately 40% of the corneal surface. On ophthalmic examination, extensive subepithelial to mid-stromal vascular branching accompanied by a homogeneous white, dense opacification, which affected up to 80% of the total corneal thickness, were apparent. Signs of concurrent uveitis were absent. Deep-stromal lamellar keratectomy with a conjunctival pedicle graft was performed under general anesthesia. Histopathology confirmed a poorly differentiated corneal stromal invasive squamous cell carcinoma (SI-SCC) with neoplastic cell extension to the surgical margins. Postoperatively, 4 topical mitomycin C 0.04% chemotherapy cycles combined with oral firocoxib therapy were initiated. Seven months after surgery, regrowth of the SI-SCC was clinically suspected. A total volume of 1 ml bevacizumab 2.5% was administered in the standing sedated horse via 3 mid-stromal corneal injections. Four weeks later, intrastromal bevacizumab injections (ISBIs) were repeated, however, this time the solution was injected directly into the main corneal vessel branches.Seven weeks after the second ISBIs, the left eye was comfortable and significant remission of corneal vascularization and opacity was recognized. No recurrence has been noted for a follow-up period of more than 53 months.Equine SI-SCC usually has a very poor prognosis for globe maintenance. To the authors' knowledge this is the first report of well-tolerated intrastromal antivascular endothelial growth factor adjunctive therapy with bevazicumab 2.5% and SI-SCC resolution after a multimodal treatment approach.


Assuntos
Bevacizumab , Carcinoma de Células Escamosas , Neoplasias Oculares , Doenças dos Cavalos , Cavalos , Animais , Bevacizumab/uso terapêutico , Bevacizumab/administração & dosagem , Doenças dos Cavalos/tratamento farmacológico , Feminino , Carcinoma de Células Escamosas/veterinária , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Neoplasias Oculares/veterinária , Neoplasias Oculares/tratamento farmacológico , Neoplasias Oculares/patologia , Neoplasias Oculares/cirurgia , Inibidores da Angiogênese/uso terapêutico , Inibidores da Angiogênese/administração & dosagem , Substância Própria/efeitos dos fármacos , Substância Própria/patologia
2.
J Dev Orig Health Dis ; 15: e10, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38724487

RESUMO

Premature infants have a risk of neurodevelopmental deficits. Little is known, however, about how retinopathy of prematurity (ROP) affects visual motor integration (VMI), which is necessary for both fine motor skills and further school abilities. Due to the systemic escape of bevacizumab in the treatment of ROP, concerns regarding the long-term neurodevelopmental effect of the drug have arisen. The aim is to evaluate VMI and motor development long-term outcomes after intravitreal bevacizumab (IVB) injection and laser treatment for ROP. Two groups of premature children were included: Bevacizumab group - 16 premature children who received IVB treatment and laser group - 23 premature children who underwent laser photocoagulation treatment in this single center cross-sectional study. At 2-6 years of age, VMI (Beery-Buktenica Developmental Test), motor development (Peabody Developmental Motor Scales-2), visual acuity, and refractive status were assessed. The incidence of abnormal visual function was significantly higher in bevacizumab group than in laser group (p = 0.022). The incidence of abnormal VMI skill was significantly higher in bevacizumab group than in laser group (p = 0.024). Incidences of abnormal gross, fine, and total motor skills were significantly higher in bevacizumab group compared to laser group (p < 0.05). Premature children who received bevacizumab for ROP demonstrated significantly lower VMI and motor development features than those with laser treatment at preschool age. Although our results suggest the relevance of bevacizumab injection in impaired VMI and motor development outcomes, general level of sickness rather than treatment might be the cause of delayed motor development.


Assuntos
Bevacizumab , Desenvolvimento Infantil , Retinopatia da Prematuridade , Humanos , Retinopatia da Prematuridade/terapia , Retinopatia da Prematuridade/fisiopatologia , Retinopatia da Prematuridade/cirurgia , Masculino , Feminino , Bevacizumab/administração & dosagem , Bevacizumab/uso terapêutico , Pré-Escolar , Estudos Transversais , Criança , Desenvolvimento Infantil/efeitos dos fármacos , Desenvolvimento Infantil/fisiologia , Recém-Nascido , Recém-Nascido Prematuro , Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/uso terapêutico , Destreza Motora/fisiologia , Injeções Intravítreas
3.
Clin Adv Hematol Oncol ; 22 Suppl 4(5): 1-20, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38805297

RESUMO

The systemic treatment options for patients with metastatic colorectal cancer have recently expanded with the US Food and Drug Administration approval of fruquintinib being added to previously approved trifluridine/tipiracil with or without bevacizumab and regorafenib. These therapies are recommended for use based on the initial clinical trials that focused on their safety and efficacy in extending overall survival of patients with refractory metastatic disease, as well as later studies, including the ReDOS study that confirmed the dose-escalation strategy of regorafenib to be key in optimizing duration of therapy and preventing side effects. Although more research is needed on how to sequence third-line therapies, data from real-world studies showed that switching from regorafenib to trifluridine/tipiracil with or without bevacizumab allowed patients to have a chemotherapy-free break and led to improved survival, suggesting that there may be a benefit for using regorafenib first. Current treatment guidelines state that each therapy can be given before or after the others. Generally, sequencing considerations in the refractory setting include multiple variables such as tumor characteristics, toxicities, factors that are important to the patient, response to prior lines of therapy, and extent of disease.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Colorretais , Metástase Neoplásica , Seleção de Pacientes , Compostos de Fenilureia , Piridinas , Trifluridina , Humanos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Neoplasias Colorretais/mortalidade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Piridinas/uso terapêutico , Trifluridina/uso terapêutico , Compostos de Fenilureia/uso terapêutico , Timina/uso terapêutico , Bevacizumab/uso terapêutico , Pirrolidinas/uso terapêutico , Combinação de Medicamentos , Uracila/análogos & derivados , Uracila/uso terapêutico
5.
Dermatol Online J ; 30(1)2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38762867

RESUMO

Osteonecrosis of the jaw is a recognized complication associated with bevacizumab. Here, we present a patient with squamous cell carcinoma of the tonsil who experienced minimal skin fibrosis following intensity-modulated radiation therapy. Subsequently, the patient developed rectal adenocarcinoma and encountered osteonecrosis of the jaw after receiving two cycles of bevacizumab. Close monitoring, accompanied by thorough examination to detect early signs of osteonecrosis of the jaw, should be considered for patients who have undergone radiation therapy in the head and neck region and are receiving bevacizumab or other medications known to be associated with osteonecrosis of the jaw.


Assuntos
Bevacizumab , Carcinoma de Células Escamosas , Radioterapia de Intensidade Modulada , Neoplasias Tonsilares , Humanos , Bevacizumab/efeitos adversos , Bevacizumab/uso terapêutico , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/tratamento farmacológico , Radioterapia de Intensidade Modulada/efeitos adversos , Neoplasias Tonsilares/radioterapia , Neoplasias Tonsilares/tratamento farmacológico , Masculino , Osteonecrose/induzido quimicamente , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/radioterapia , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/radioterapia , Antineoplásicos Imunológicos/efeitos adversos , Pessoa de Meia-Idade , Doenças Maxilomandibulares/induzido quimicamente
6.
JCO Precis Oncol ; 8: e2300693, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38754056

RESUMO

PURPOSE: To report the results of OPAL (ClinicalTrials.gov identifier: NCT03574779) cohort A, a single-arm substudy of niraparib plus dostarlimab and bevacizumab for the treatment of advanced, platinum-resistant ovarian cancer (PROC). METHODS: Participants with PROC who received 1-2 previous lines of therapy were treated with niraparib (200 or 300 mg once daily), dostarlimab (500 mg once every 3 weeks for four 21-day cycles, followed by 1,000 mg once every 6 weeks), and bevacizumab (15 mg/kg once every 3 weeks). The primary end point was investigator-assessed objective response rate (ORR) per RECIST v1.1. Safety was also assessed. Exploratory biomarker end points included evaluation of changes in the tumor molecular profile and microenvironment using baseline and on-treatment tumor samples. RESULTS: Of 41 enrolled participants (median age, 66.0 years [range, 37-83 years]), 9.8% had tumors that were BRCA-mutated, 19.5% were homologous recombination (HR)-deficient, and 17.1% were HR repair (HRR)-mutated. As of the cutoff date, all participants discontinued treatment. The ORR was 17.1% (80% CI, 9.8 to 27.0), including one complete response (2.4%); the disease control rate was 73.2% (80% CI, 62.3 to 82.2). Two participants withdrew before first postbaseline scan because of adverse events (AEs). Grade ≥3 treatment-emergent AEs were reported in 92.7% of participants, with the most common being hypertension (26.8%). Response was not correlated with BRCA, HRR, HR deficiency (HRD), or PD-L1 status. Changes suggesting immune activation were observed in on-treatment samples after triplet therapy. CONCLUSION: Results demonstrated modest activity of niraparib, dostarlimab, and bevacizumab in participants with PROC, many of whom had prognostic factors for poor treatment response. Most participants with response were bevacizumab-naïve. No association was found with HRD, BRCA, or PD-L1 status. AEs were consistent with previous monotherapy reports, except that hypertension was reported more frequently.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Bevacizumab , Resistencia a Medicamentos Antineoplásicos , Indazóis , Neoplasias Ovarianas , Piperidinas , Humanos , Feminino , Pessoa de Meia-Idade , Neoplasias Ovarianas/tratamento farmacológico , Idoso , Bevacizumab/uso terapêutico , Adulto , Indazóis/uso terapêutico , Idoso de 80 Anos ou mais , Piperidinas/uso terapêutico , Piperidinas/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Estudos de Coortes
7.
Eur J Cancer ; 204: 114089, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38703618

RESUMO

OBJECTIVES: The development of reliable biomarkers for the prediction of immune checkpoint inhibition (ICI) response in patients with metastatic renal cell carcinoma (mRCC) and urothelial carcinoma (mUC) remains an unresolved challenge. Conventional ICI biomarkers typically focus on tumor-related factors such as PD-L1 expression. However, a comprehensive evaluation of the predictive value of serum electrolyte levels, a so far widely unexplored area, is still pending. METHODS: We conducted a post-hoc analysis of baseline sodium, potassium, chloride, magnesium and calcium levels in two independent phase 3 clinical trials: IMvigor211 for mUC comparing atezolizumab to chemotherapy, and IMmotion151 for mRCC comparing atezolizumab+bevacizumab to sunitinib. This analysis aimed to evaluate the prognostic and predictive value of these electrolyte levels in these clinical settings. A total of 1787 patients (IMvigor211 n = 901; IMmotion151 n = 886) were analyzed. RESULTS: We found a linear correlation of baseline serum sodium and chloride with prognosis across both trials, which was not found for potassium, magnesium and calcium. In multivariate analysis, the prognostic capacity of sodium was limited to patients receiving ICI as compared to the control group. Interestingly, in both studies, the chance of achieving an objective response was highest in the patient subgroup with high baseline serum sodium levels of > 140 mmol/L (IMmotion151: Complete response in 17.9% versus 2.0% in patients with mRCC with baseline sodium < 135 mmol/L). Serum sodium outperformed tumor PD-L1 expression as a predictor for immunotherapy efficacy. CONCLUSIONS: Patients exhibiting elevated serum sodium levels derive the greatest benefit from immunotherapy, suggesting that baseline serum concentration could serve as a valuable and cost-effective predictive biomarker for immunotherapy across entities.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Sódio , Humanos , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/sangue , Neoplasias Renais/patologia , Neoplasias Renais/imunologia , Masculino , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/sangue , Carcinoma de Células Renais/imunologia , Carcinoma de Células Renais/secundário , Carcinoma de Células Renais/patologia , Feminino , Sódio/sangue , Idoso , Pessoa de Meia-Idade , Imunoterapia/métodos , Anticorpos Monoclonais Humanizados/uso terapêutico , Bevacizumab/uso terapêutico , Biomarcadores Tumorais/sangue , Inibidores de Checkpoint Imunológico/uso terapêutico , Prognóstico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Sunitinibe/uso terapêutico , Carcinoma de Células de Transição/tratamento farmacológico , Carcinoma de Células de Transição/sangue , Carcinoma de Células de Transição/secundário , Carcinoma de Células de Transição/imunologia
8.
BMC Pediatr ; 24(1): 301, 2024 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-38704544

RESUMO

BACKGROUND: We present a patient with retinopathy of prematurity (ROP) who developed worsening plus disease after complete regression of stage 3 ROP. The use of fundus fluorescein angiography (FFA) aided the visualization of occult neovascularization that caused the disease progression. CASE PRESENTATION: The patient was at high risk for ROP due to low birth weight of 690 g and gestational age of 25 weeks. After the diagnosis of stage 3 ROP in zone I without plus disease, she was treated initially with bilateral intravitreal bevacizumab (IVB) and followed by laser photocoagulation 5 weeks later. Despite the resolution of ROP stage, the plus disease worsened. Neither systemic risk factors nor skip laser areas were observed. Hence, FFA was performed and subsequently identified occult neovascularization with active leakage. Additional IVB and laser treatment in the capillary dropout area inside vascularized retina were added. The plus disease improved but mild arteriolar tortuosity persisted. CONCLUSIONS: Worsening of plus disease after completion of laser ablation and IVB with complete regression of stage 3 ROP is rare. Systemic risk factors such as continuous oxygen therapy and cardiovascular disease should be ruled out. FFA aided in identifying occult neovascularization and prompted further treatment.


Assuntos
Inibidores da Angiogênese , Bevacizumab , Angiofluoresceinografia , Injeções Intravítreas , Fotocoagulação a Laser , Neovascularização Retiniana , Retinopatia da Prematuridade , Humanos , Bevacizumab/uso terapêutico , Bevacizumab/administração & dosagem , Recém-Nascido , Inibidores da Angiogênese/uso terapêutico , Inibidores da Angiogênese/administração & dosagem , Feminino , Fotocoagulação a Laser/métodos , Neovascularização Retiniana/etiologia , Neovascularização Retiniana/tratamento farmacológico , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Terapia Combinada
9.
Medicine (Baltimore) ; 103(21): e38183, 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38788019

RESUMO

BACKGROUND: We aimed to compare 7 newer immunotherapies and targeted therapies for platinum-resistant relapsed ovarian cancer. METHODS: We conducted a comprehensive search of PubMed, EMBASE, and Cochrane Library electronic databases for phase III trials involving platinum-resistant recurrent ovarian cancer (PRrOC) patients treated with immunotherapy or targeted therapy in combination with chemotherapy. The quality of the included trials was assessed using the GRADE method. The primary outcome of comparison was progression-free survival, and secondary outcomes included overall survival and safety. RESULTS: This analysis included 7 randomized phase III controlled trials, encompassing 2485 PRrOC patients. Combining bevacizumab plus chemotherapy and lurbinectedin demonstrated statistically significant differences in progression-free survival compared to all other regimens of interest. However, no statistically significant differences were observed in the overall survival. Nivolumab and mirvetuximab exhibited fewer serious adverse events than the other regimens of interest. CONCLUSIONS: Our findings indicate that bevacizumab combined with chemotherapy and lurbinectedin monotherapy has significant efficacy in patients with PRrOC. For patients with PRrOC who have exhausted treatment options, nivolumab and mirvetuximab may be considered as alternatives because of their better safety profiles.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Teorema de Bayes , Bevacizumab , Resistencia a Medicamentos Antineoplásicos , Recidiva Local de Neoplasia , Metanálise em Rede , Neoplasias Ovarianas , Humanos , Feminino , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/mortalidade , Bevacizumab/uso terapêutico , Bevacizumab/administração & dosagem , Recidiva Local de Neoplasia/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Nivolumabe/uso terapêutico , Nivolumabe/administração & dosagem , Intervalo Livre de Progressão , Ensaios Clínicos Fase III como Assunto , Ciclobutanos/uso terapêutico , Antineoplásicos/uso terapêutico , Imunoterapia/métodos , Terapia de Alvo Molecular/métodos , Carbolinas , Compostos Heterocíclicos de 4 ou mais Anéis
10.
BMC Ophthalmol ; 24(1): 220, 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38790043

RESUMO

BACKGROUND: Retinopathy of prematurity (ROP) is a disease that affects preterm infants born younger than 30 weeks of gestation. The pathophysiology of ROP involves an initial vaso-obliterative phase followed by vaso-proliferative phase that leads to disease progression. The use of supplemental oxygen during the vaso-proliferative phase of ROP has been associated with reduced disease progression, but how this impacts the need for ROP treatment is unclear. The goal of this study was to compare the rate of laser or intravitreal bevacizumab after implementation of a new supplemental oxygen therapy protocol in preterm infants with stage 2 ROP. METHODS: This is a retrospective chart review of preterm infants diagnosed with stage 2 ROP at Riley Hospital for Children between 1/2017 and 12/2022. Patients diagnosed between 1/2017 and 6/2020 were classified as Cohort A, preprotocol implementation. Patients diagnosed from 8/2020 to 12/2022 were classified as Cohort B, postprotocol implementation. In Cohort A, oxygen saturation was kept at 91-95% through the entire hospitalization. In Cohort B, oxygen saturation was increased to 97-99% as soon as Stage 2 ROP was diagnosed. Statistical analyses were performed using chi-square and Student's T test, followed by multivariate analyses to determine the impact of the oxygen protocol on the need for ROP treatment. RESULTS: A total of 211 patients were diagnosed with stage 2 ROP between 1/2017 and 12/2022. Of those patients, 122 were before protocol implementation therapy (Cohort A), and 89 were after implementation of supplemental oxygen protocol (Cohort B). Gestational age was slightly higher in Cohort B (Cohort A 25.3 ± 1.9, Cohort B 25.8 ± 1.84, p = 0.04). There was no difference in birth weight, NEC, BPD, or survival. Cohort B had lesser need for invasive mechanical ventilation and higher days on CPAP during hospitalization. Notably, Cohort A had 67 (55%) patients treated with laser photocoagulation or intravitreal bevacizumab versus 20 (22%) patients in Cohort B (OR 0.19, 0.08-0.40). CONCLUSION: The need for laser photocoagulation or intravitreal bevacizumab was significantly decreased in high-risk patients treated with the supplemental oxygen protocol. This result supports the idea that targeted supplemental oxygen therapy to keep saturations between 97 and 99% can reduce disease progression in infants with stage 2 ROP and potentially decrease the burden of additional procedures.


Assuntos
Inibidores da Angiogênese , Bevacizumab , Idade Gestacional , Recém-Nascido Prematuro , Injeções Intravítreas , Retinopatia da Prematuridade , Humanos , Retinopatia da Prematuridade/tratamento farmacológico , Retinopatia da Prematuridade/terapia , Retinopatia da Prematuridade/diagnóstico , Bevacizumab/administração & dosagem , Bevacizumab/uso terapêutico , Estudos Retrospectivos , Recém-Nascido , Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/uso terapêutico , Masculino , Feminino , Fotocoagulação a Laser/métodos , Oxigenoterapia/métodos , Oxigênio/uso terapêutico , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Resultado do Tratamento
11.
ESMO Open ; 9(5): 103374, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38744100

RESUMO

BACKGROUND: The inflammation-based modified Glasgow Prognostic Score (mGPS) combines serum levels of C-reactive protein and albumin and was shown to predict survival in advanced cancer. We aimed to elucidate the prognostic impact of mGPS on survival as well as its predictive value when combined with gender in unselected metastatic colorectal cancer (mCRC) patients receiving first-line chemotherapy in the randomized phase III XELAVIRI trial. PATIENTS AND METHODS: In XELAVIRI, mCRC patients were treated with either fluoropyrimidine/bevacizumab followed by additional irinotecan at first progression (sequential treatment arm; Arm A) or upfront combination of fluoropyrimidine/bevacizumab/irinotecan (intensive treatment arm; Arm B). In the present post hoc analysis, survival was evaluated with respect to the assorted mGPS categories 0, 1 or 2. Interaction between mGPS and gender was analyzed. RESULTS: Out of 421 mCRC patients treated in XELAVIRI, 362 [119 women (32.9%) and 243 men (67.1%)] were assessable. For the entire study population a significant association between mGPS and overall survival (OS) was observed [mGPS = 0: median 28.9 months, 95% confidence interval (CI) 25.9-33.6 months; mGPS = 1: median 21.4 months, 95% CI 17.6-26.1 months; mGPS = 2: median 16.8 months, 95% CI 14.3-21.2 months; P < 0.00001]. Similar results were found when comparing progression-free survival between groups. The effect of mGPS on survival did not depend on the applied treatment regimen (P = 0.21). In female patients, a trend towards longer OS was observed in Arm A versus Arm B, with this effect being clearly more pronounced in the mGPS cohort 0 (41.6 versus 25.5 months; P = 0.056). By contrast, median OS was longer in male patients with an mGPS of 1-2 treated in Arm B versus Arm A (20.8 versus 17.4 months; P = 0.022). CONCLUSION: We demonstrate the role of mGPS as an independent predictor of OS regardless of the treatment regimen in mCRC patients receiving first-line treatment. mGPS may help identify gender-specific subgroups that benefit more or less from upfront intensive therapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Colorretais , Humanos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Prognóstico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Inflamação/tratamento farmacológico , Inflamação/sangue , Irinotecano/uso terapêutico , Irinotecano/farmacologia , Adulto , Capecitabina/uso terapêutico , Capecitabina/farmacologia , Proteína C-Reativa/análise , Proteína C-Reativa/metabolismo , Oxaloacetatos , Bevacizumab/uso terapêutico , Bevacizumab/farmacologia , Fluoruracila/uso terapêutico , Fluoruracila/farmacologia , Biomarcadores Tumorais/sangue , Metástase Neoplásica
13.
Am J Manag Care ; 30(2 Suppl): S31-S35, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38701364

RESUMO

Numerous advances in the standard of care for metastatic colorectal cancer (mCRC), including the approval of several new treatments indicated for treatment in the third line or later (3L+), have been made, yet data and appropriate guidance on the optimal sequencing and treatment strategies for these lines of therapy are lacking. Four treatments-regorafenib, trifluridine/tipiracil alone or with bevacizumab, and fruquintinib-are FDA-approved and recommended by the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for the treatment of mCRC in the 3L+. When considering sequencing of treatment options for patients in the 3L+, the goal of treatment is to improve survival, but also maintain quality of life, a goal that requires consideration of relative efficacy and cumulative toxicity such as persistent myelosuppression.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Colorretais , Timina , Trifluridina , Humanos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Neoplasias Colorretais/genética , Trifluridina/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/uso terapêutico , Bevacizumab/administração & dosagem , Piridinas/uso terapêutico , Compostos de Fenilureia/uso terapêutico , Pirrolidinas/uso terapêutico , Combinação de Medicamentos , Metástase Neoplásica , Qualidade de Vida
14.
PLoS One ; 19(4): e0298770, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38687817

RESUMO

AIM: To clarify the efficacy of atezolizumab (ATZ) plus bevacizumab (BEV) as the second-line therapy for patients with unresectable hepatocellular carcinoma (HCC). METHODS: The subjects were 82 patients with HCC receiving ATZ/BEV, including 33 patients with previous therapies with molecular-targeted agents (MTA). Therapeutic efficacy was evaluated using contrast-enhanced CT according to the mRECIST. RESULTS: The Child-Pugh scores were 5, 6,7 and 8 in 40, 35, 5 and 2 patients, respectively, and the extents of HCC progression were BCLC stage A, B and C in 3, 31 and 48 patients, respectively. Early therapeutic efficacy was evaluated in 67 patients, and percentages of patients achieving CR/PR/SD/PD until 12 weeks were 3.0%/29.9%/49.3%/17.9%, respectively, indicating ORR of 32.8% and DCR of 82.1%, The ORR was higher in MTA-naïve patients (40.5%) than in those after discontinuation of lenvatinib due to PD (7.7%, P = 0.0410), while the DCR was equivalent between both patients (83.3% vs 80.0%, P = 0.1184), and the multivariate analysis revealed previous MTA therapies with lenvatinib alone as a factor to deteriorate the ORR (HR of 4.846 (P = 0.0619)). The OS rates at 24 and 48 weeks were 86% and 72%, respectively, and the rates did not differ between MTA-naïve and MTA-experienced patients. Multivariate analyses revealed that achievement of CR, PR or SD and peripheral neutrophil/lymphocyte ratio were associated with a favorable outcome (HR of 0.124, P<0.0001 and 0.351, P = 0.0303). CONCLUSIONS: ATZ/BEV merits consideration even for MTA-experienced patients, since the OS was equivalent to those in MTA-naïve patients despite of an unfavorable early therapeutic efficacy.


Assuntos
Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Bevacizumab , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Bevacizumab/uso terapêutico , Bevacizumab/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Adulto , Idoso de 80 Anos ou mais , Resultado do Tratamento , Estudos Retrospectivos
15.
J Neurooncol ; 168(1): 1-11, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38619777

RESUMO

PURPOSE: Radiation necrosis (RN) is a local inflammatory reaction that arises in response to radiation injury and may cause significant morbidity. This study aims to evaluate and compare the efficacy of bevacizumab and laser interstitial thermal therapy (LITT) in treating RN in patients with previously radiated central nervous system (CNS) neoplasms. METHODS: PubMed, Cochrane, Scopus, and EMBASE databases were screened. Studies of patients with radiation necrosis from primary or secondary brain tumors were included. Indirect meta-analysis with random-effect modeling was performed to compare clinical and radiological outcomes. RESULTS: Twenty-four studies were included with 210 patients in the bevacizumab group and 337 patients in the LITT group. Bevacizumab demonstrated symptomatic improvement/stability in 87.7% of cases, radiological improvement/stability in 86.2%, and steroid wean-off in 45%. LITT exhibited symptomatic improvement/stability in 71.2%, radiological improvement/stability in 64.7%, and steroid wean-off in 62.4%. Comparative analysis revealed statistically significant differences favoring bevacizumab in symptomatic improvement/stability (p = 0.02), while no significant differences were observed in radiological improvement/stability (p = 0.27) or steroid wean-off (p = 0.90). The rates of adverse reactions were 11.2% for bevacizumab and 14.9% for LITT (p = 0.66), with the majority being grade 2 or lower (72.2% for bevacizumab and 62.5% for LITT). CONCLUSION: Both bevacizumab and LITT exhibited favorable clinical and radiological outcomes in managing RN. Bevacizumab was found to be associated with better symptomatic control compared to LITT. Patient-, diagnosis- and lesion-related factors should be considered when choosing the ideal treatment modality for RN to enhance overall patient outcomes.


Assuntos
Bevacizumab , Necrose , Lesões por Radiação , Humanos , Bevacizumab/uso terapêutico , Lesões por Radiação/etiologia , Lesões por Radiação/tratamento farmacológico , Lesões por Radiação/patologia , Necrose/etiologia , Terapia a Laser/métodos , Neoplasias do Sistema Nervoso Central/radioterapia , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Neoplasias do Sistema Nervoso Central/terapia , Antineoplásicos Imunológicos/uso terapêutico , Antineoplásicos Imunológicos/efeitos adversos , Inibidores da Angiogênese/uso terapêutico
16.
Invest Ophthalmol Vis Sci ; 65(4): 37, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38652648

RESUMO

Purpose: Adjuvant, pre-operative intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections have been used to reduce peri-operative bleeding in eyes undergoing pars-plana vitrectomy for complications of proliferative diabetic retinopathy (PDR). To address the concern over their potential off-target effects of progressive fibrous contraction, we sought to dissect the transcriptional changes in the surgically extracted fibrovascular membranes (FVMs). Methods: We analyzed surgically extracted FVMs from 10 eyes: 4 eyes pretreated with intravitreal bevacizumab (IVB) and 6 untreated eyes. FVMs were digested into single cells, mRNA was extracted from endothelial cell-enriched (microbead selection with CD31) and non-endothelial cell compartments, followed by RT-qPCR quantification. We then compared the relative expression of genes involved in angiogenesis, endothelial cell integrity, and myofibroblastic processes between treated and untreated FVMs. Results: Endothelial cells from IVB pretreated FVMs showed significant reduction of VEGFA, VEGF receptors (FLT1 and KDR), and angiopoietin 2 expression as well as increased vascular endothelial cadherin and endothelin, suggesting reduced angiogenesis and enhanced vascular integrity. The non-endothelial cell fraction showed decreased expression of VEGFA and fibronectin, without significant difference in the expression of other profibrotic factors. Conclusions: Our findings confirm that adjuvant pre-operative IVB decreased fibronectin and increase endothelin-1 expression without affecting other profibrotic gene expression, uncovering an important interaction between IVB and endothelin-1 that deserves further study.


Assuntos
Inibidores da Angiogênese , Bevacizumab , Retinopatia Diabética , Fibrose , Injeções Intravítreas , Fator A de Crescimento do Endotélio Vascular , Vitrectomia , Humanos , Retinopatia Diabética/metabolismo , Retinopatia Diabética/tratamento farmacológico , Retinopatia Diabética/cirurgia , Inibidores da Angiogênese/uso terapêutico , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Bevacizumab/uso terapêutico , Bevacizumab/farmacologia , Masculino , Feminino , Pessoa de Meia-Idade , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Neovascularização Retiniana/metabolismo , Neovascularização Retiniana/tratamento farmacológico , Idoso , Cuidados Pré-Operatórios , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/farmacologia
17.
In Vivo ; 38(3): 1338-1350, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38688599

RESUMO

BACKGROUND/AIM: Over the past several decades, new anti-cancer drugs have been developed for the treatment of epithelial ovarian cancer. The development of drugs has led to changes in improving the prognosis of ovarian cancer patients. One of these drugs, bevacizumab, is used for advanced or recurrent ovarian cancer. In this study, we aimed to evaluate survival improvement in patients with platinum-resistant relapsed epithelial ovarian cancer (PR-ROC) after introduction of bevacizumab in real world experience. PATIENTS AND METHODS: We retrospectively divided patients with PR-ROC into two groups: bevacizumab plus chemotherapy (BEV-CT group) and chemotherapy alone (CT group). Progression-free survival (PFS), the primary endpoint, between two groups was compared to evaluate whether survival outcomes were improved. In addition, overall survival (OS) was also compared. RESULTS: A total of 154 patients were included in the study: 57 and 97 patients in the BEV-CT and CT groups, respectively. OS was significantly longer in the BEV-CT group than in the CT group. The use of bevacizumab was identified as a favorable prognostic factor for OS. In a subgroup analysis confined to second-line chemotherapy, PFS and OS were statistically different between groups. More patients in the CT group suffered hematologic adverse events of grade 3 or above than patients in the BEV-CT group. CONCLUSION: In a real-world clinical setting, introduction of bevacizumab led to improvement of OS in patients with PR-ROC with a tolerable toxicity.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Bevacizumab , Resistencia a Medicamentos Antineoplásicos , Recidiva Local de Neoplasia , Neoplasias Ovarianas , Humanos , Bevacizumab/uso terapêutico , Bevacizumab/administração & dosagem , Bevacizumab/efeitos adversos , Feminino , Pessoa de Meia-Idade , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Idoso , Recidiva Local de Neoplasia/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Adulto , Resultado do Tratamento , Prognóstico , Estudos Retrospectivos , Carcinoma Epitelial do Ovário/tratamento farmacológico , Carcinoma Epitelial do Ovário/mortalidade , Platina/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Antineoplásicos Imunológicos/efeitos adversos , Antineoplásicos Imunológicos/administração & dosagem
19.
J Gastroenterol ; 59(6): 515-525, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38583112

RESUMO

BACKGROUND: During systemic therapy, the management of portal hypertension (PH)-related complications is vital. This study aimed to clarify factors associated with the incidence and exacerbation of PH-related complications, including the usefulness of contrast-enhanced computed tomography (CECT) in the management of PH-related complications during systemic therapy. METHODS: A total of 669 patients who received systemic therapy as first-line treatment (443 patients for sorafenib, 131 for lenvatinib, and 90 for atezolizumab/bevacizumab [ATZ/BEV]) were enrolled in this retrospective study. Additionally, the lower esophageal intramural vessel diameters (EIV) on CECT and endoscopic findings in 358 patients were compared. RESULTS: The cutoff values of the EIV diameter on CECT were 3.1 mm for small, 5.1 mm for medium, and 7.6 mm for large varices, demonstrating high concordance with the endoscopic findings. esophageal varices (EV) bleeding predictors include EIV ≥ 3.1 mm and portal vein tumor thrombosis (PVTT). In patients without EV before systemic therapy, factors associated with EV exacerbation after 3 months were EIV ≥ 1.9 mm and ATZ/BEV use. Predictors of hepatic encephalopathy (HE) include the ammonia level or portosystemic shunt diameter ≥ 6.8 mm. The incidence of HE within 2 weeks was significantly higher (18%) in patients with an ammonia level ≥ 73 µmol/L and a portosystemic shunt ≥ 6.8 mm. The exacerbating factors for ascites after 3 months were PVTT and low albumin levels. CONCLUSIONS: Careful management is warranted for patients with risk factors for exacerbation of PH-related complications; moreover, the effective use of CECT is clinically important.


Assuntos
Bevacizumab , Carcinoma Hepatocelular , Varizes Esofágicas e Gástricas , Hipertensão Portal , Neoplasias Hepáticas , Compostos de Fenilureia , Sorafenibe , Humanos , Hipertensão Portal/etiologia , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Fatores de Risco , Varizes Esofágicas e Gástricas/etiologia , Varizes Esofágicas e Gástricas/epidemiologia , Compostos de Fenilureia/efeitos adversos , Compostos de Fenilureia/administração & dosagem , Compostos de Fenilureia/uso terapêutico , Sorafenibe/efeitos adversos , Sorafenibe/uso terapêutico , Sorafenibe/administração & dosagem , Bevacizumab/administração & dosagem , Bevacizumab/efeitos adversos , Bevacizumab/uso terapêutico , Tomografia Computadorizada por Raios X , Quinolinas/uso terapêutico , Quinolinas/efeitos adversos , Quinolinas/administração & dosagem , Encefalopatia Hepática/etiologia , Encefalopatia Hepática/epidemiologia , Antineoplásicos/efeitos adversos , Antineoplásicos/administração & dosagem , Adulto , Idoso de 80 Anos ou mais , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/epidemiologia , Incidência
20.
Front Immunol ; 15: 1354613, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38617840

RESUMO

Metastatic colon cancer remains an incurable disease, and it is difficult for existing treatments to achieve the desired clinical outcome, especially for colon cancer patients who have received first-line treatment. Although immune checkpoint inhibitors (ICIs) have demonstrated durable clinical efficacy in a variety of solid tumors, their response requires an inflammatory tumor microenvironment. However, microsatellite-stable (MSS) colon cancer, which accounts for the majority of colorectal cancers, is a cold tumor that does not respond well to ICIs. Combination regimens open the door to the utility of ICIs in cold tumors. Although combination therapies have shown their advantage even for MSS colon cancer, it remains unclear whether combination therapies show their advantage in patients with pretreated metastatic colon cancer. We report a patient who has achieved complete remission and good tolerance with sintilimab plus bevacizumab and platinum-based chemotherapy after postoperative recurrence. The patient had KRAS mutation and MSS-type colon cancer, and his PD-1+CD8+ and CD3-CD19-CD14+CD16-HLA-DR were both positive. He has achieved a progression-free survival of 43 months and is still being followed up at our center. The above results suggest that this therapeutic regimen is a promising treatment modality for the management of pretreated, MSS-type and KRAS-mutated metastatic colorectal cancer although its application to the general public still needs to be validated in clinical trials.


Assuntos
Anticorpos Monoclonais Humanizados , Neoplasias do Colo , Proteínas Proto-Oncogênicas p21(ras) , Masculino , Humanos , Bevacizumab/uso terapêutico , Proteínas Proto-Oncogênicas p21(ras)/genética , Resposta Patológica Completa , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/genética , Platina , Repetições de Microssatélites , Microambiente Tumoral
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