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1.
Article in English | MEDLINE | ID: mdl-38701802

ABSTRACT

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.


Subject(s)
Bevacizumab , Carcinoma, Squamous Cell , Eye Neoplasms , Horse Diseases , Horses , Animals , Bevacizumab/therapeutic use , Bevacizumab/administration & dosage , Horse Diseases/drug therapy , Female , Carcinoma, Squamous Cell/veterinary , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/pathology , Carcinoma, Squamous Cell/surgery , Eye Neoplasms/veterinary , Eye Neoplasms/drug therapy , Eye Neoplasms/pathology , Eye Neoplasms/surgery , Angiogenesis Inhibitors/therapeutic use , Angiogenesis Inhibitors/administration & dosage , Corneal Stroma/drug effects , Corneal Stroma/pathology
2.
J Dev Orig Health Dis ; 15: e10, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38724487

ABSTRACT

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.


Subject(s)
Bevacizumab , Child Development , Retinopathy of Prematurity , Humans , Retinopathy of Prematurity/therapy , Retinopathy of Prematurity/physiopathology , Retinopathy of Prematurity/surgery , Male , Female , Bevacizumab/administration & dosage , Bevacizumab/therapeutic use , Child, Preschool , Cross-Sectional Studies , Child , Child Development/drug effects , Child Development/physiology , Infant, Newborn , Infant, Premature , Angiogenesis Inhibitors/administration & dosage , Angiogenesis Inhibitors/therapeutic use , Motor Skills/physiology , Intravitreal Injections
3.
Clin Adv Hematol Oncol ; 22 Suppl 4(5): 1-20, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38805297

ABSTRACT

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.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Colorectal Neoplasms , Neoplasm Metastasis , Patient Selection , Phenylurea Compounds , Pyridines , Trifluridine , Humans , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/pathology , Colorectal Neoplasms/mortality , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Pyridines/therapeutic use , Trifluridine/therapeutic use , Phenylurea Compounds/therapeutic use , Thymine/therapeutic use , Bevacizumab/therapeutic use , Pyrrolidines/therapeutic use , Drug Combinations , Uracil/analogs & derivatives , Uracil/therapeutic use
5.
Dermatol Online J ; 30(1)2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38762867

ABSTRACT

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.


Subject(s)
Bevacizumab , Carcinoma, Squamous Cell , Radiotherapy, Intensity-Modulated , Tonsillar Neoplasms , Humans , Bevacizumab/adverse effects , Bevacizumab/therapeutic use , Carcinoma, Squamous Cell/radiotherapy , Carcinoma, Squamous Cell/drug therapy , Radiotherapy, Intensity-Modulated/adverse effects , Tonsillar Neoplasms/radiotherapy , Tonsillar Neoplasms/drug therapy , Male , Osteonecrosis/chemically induced , Adenocarcinoma/drug therapy , Adenocarcinoma/radiotherapy , Rectal Neoplasms/drug therapy , Rectal Neoplasms/radiotherapy , Antineoplastic Agents, Immunological/adverse effects , Middle Aged , Jaw Diseases/chemically induced
6.
JCO Precis Oncol ; 8: e2300693, 2024 May.
Article in English | MEDLINE | ID: mdl-38754056

ABSTRACT

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.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Bevacizumab , Drug Resistance, Neoplasm , Indazoles , Ovarian Neoplasms , Piperidines , Humans , Female , Middle Aged , Ovarian Neoplasms/drug therapy , Aged , Bevacizumab/therapeutic use , Adult , Indazoles/therapeutic use , Aged, 80 and over , Piperidines/therapeutic use , Piperidines/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Cohort Studies
7.
Eur J Cancer ; 204: 114089, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38703618

ABSTRACT

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.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Sodium , Humans , Kidney Neoplasms/drug therapy , Kidney Neoplasms/blood , Kidney Neoplasms/pathology , Kidney Neoplasms/immunology , Male , Carcinoma, Renal Cell/drug therapy , Carcinoma, Renal Cell/blood , Carcinoma, Renal Cell/immunology , Carcinoma, Renal Cell/secondary , Carcinoma, Renal Cell/pathology , Female , Sodium/blood , Aged , Middle Aged , Immunotherapy/methods , Antibodies, Monoclonal, Humanized/therapeutic use , Bevacizumab/therapeutic use , Biomarkers, Tumor/blood , Immune Checkpoint Inhibitors/therapeutic use , Prognosis , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Sunitinib/therapeutic use , Carcinoma, Transitional Cell/drug therapy , Carcinoma, Transitional Cell/blood , Carcinoma, Transitional Cell/secondary , Carcinoma, Transitional Cell/immunology
8.
BMC Pediatr ; 24(1): 301, 2024 May 04.
Article in English | MEDLINE | ID: mdl-38704544

ABSTRACT

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.


Subject(s)
Angiogenesis Inhibitors , Bevacizumab , Fluorescein Angiography , Intravitreal Injections , Laser Coagulation , Retinal Neovascularization , Retinopathy of Prematurity , Humans , Bevacizumab/therapeutic use , Bevacizumab/administration & dosage , Infant, Newborn , Angiogenesis Inhibitors/therapeutic use , Angiogenesis Inhibitors/administration & dosage , Female , Laser Coagulation/methods , Retinal Neovascularization/etiology , Retinal Neovascularization/drug therapy , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Monoclonal, Humanized/administration & dosage , Combined Modality Therapy
9.
Medicine (Baltimore) ; 103(21): e38183, 2024 May 24.
Article in English | MEDLINE | ID: mdl-38788019

ABSTRACT

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.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Bayes Theorem , Bevacizumab , Drug Resistance, Neoplasm , Neoplasm Recurrence, Local , Network Meta-Analysis , Ovarian Neoplasms , Humans , Female , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/mortality , Bevacizumab/therapeutic use , Bevacizumab/administration & dosage , Neoplasm Recurrence, Local/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Randomized Controlled Trials as Topic , Nivolumab/therapeutic use , Nivolumab/administration & dosage , Progression-Free Survival , Clinical Trials, Phase III as Topic , Cyclobutanes/therapeutic use , Antineoplastic Agents/therapeutic use , Immunotherapy/methods , Molecular Targeted Therapy/methods , Carbolines , Heterocyclic Compounds, 4 or More Rings
10.
BMC Ophthalmol ; 24(1): 220, 2024 May 24.
Article in English | MEDLINE | ID: mdl-38790043

ABSTRACT

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.


Subject(s)
Angiogenesis Inhibitors , Bevacizumab , Gestational Age , Infant, Premature , Intravitreal Injections , Retinopathy of Prematurity , Humans , Retinopathy of Prematurity/drug therapy , Retinopathy of Prematurity/therapy , Retinopathy of Prematurity/diagnosis , Bevacizumab/administration & dosage , Bevacizumab/therapeutic use , Retrospective Studies , Infant, Newborn , Angiogenesis Inhibitors/administration & dosage , Angiogenesis Inhibitors/therapeutic use , Male , Female , Laser Coagulation/methods , Oxygen Inhalation Therapy/methods , Oxygen/therapeutic use , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Treatment Outcome
11.
ESMO Open ; 9(5): 103374, 2024 May.
Article in English | MEDLINE | ID: mdl-38744100

ABSTRACT

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.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Colorectal Neoplasms , Humans , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/pathology , Male , Female , Middle Aged , Aged , Prognosis , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Inflammation/drug therapy , Inflammation/blood , Irinotecan/therapeutic use , Irinotecan/pharmacology , Adult , Capecitabine/therapeutic use , Capecitabine/pharmacology , C-Reactive Protein/analysis , C-Reactive Protein/metabolism , Oxaloacetates , Bevacizumab/therapeutic use , Bevacizumab/pharmacology , Fluorouracil/therapeutic use , Fluorouracil/pharmacology , Biomarkers, Tumor/blood , Neoplasm Metastasis
13.
Am J Manag Care ; 30(2 Suppl): S31-S35, 2024 May.
Article in English | MEDLINE | ID: mdl-38701364

ABSTRACT

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.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Colorectal Neoplasms , Thymine , Trifluridine , Humans , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/pathology , Colorectal Neoplasms/genetics , Trifluridine/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bevacizumab/therapeutic use , Bevacizumab/administration & dosage , Pyridines/therapeutic use , Phenylurea Compounds/therapeutic use , Pyrrolidines/therapeutic use , Drug Combinations , Neoplasm Metastasis , Quality of Life
14.
PLoS One ; 19(4): e0298770, 2024.
Article in English | MEDLINE | ID: mdl-38687817

ABSTRACT

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.


Subject(s)
Antibodies, Monoclonal, Humanized , Antineoplastic Combined Chemotherapy Protocols , Bevacizumab , Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/drug therapy , Liver Neoplasms/pathology , Male , Female , Aged , Middle Aged , Bevacizumab/therapeutic use , Bevacizumab/administration & dosage , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Monoclonal, Humanized/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Adult , Aged, 80 and over , Treatment Outcome , Retrospective Studies
15.
J Neurooncol ; 168(1): 1-11, 2024 May.
Article in English | MEDLINE | ID: mdl-38619777

ABSTRACT

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.


Subject(s)
Bevacizumab , Necrosis , Radiation Injuries , Humans , Bevacizumab/therapeutic use , Radiation Injuries/etiology , Radiation Injuries/drug therapy , Radiation Injuries/pathology , Necrosis/etiology , Laser Therapy/methods , Central Nervous System Neoplasms/radiotherapy , Central Nervous System Neoplasms/drug therapy , Central Nervous System Neoplasms/therapy , Antineoplastic Agents, Immunological/therapeutic use , Antineoplastic Agents, Immunological/adverse effects , Angiogenesis Inhibitors/therapeutic use
16.
Invest Ophthalmol Vis Sci ; 65(4): 37, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38652648

ABSTRACT

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.


Subject(s)
Angiogenesis Inhibitors , Bevacizumab , Diabetic Retinopathy , Fibrosis , Intravitreal Injections , Vascular Endothelial Growth Factor A , Vitrectomy , Humans , Diabetic Retinopathy/metabolism , Diabetic Retinopathy/drug therapy , Diabetic Retinopathy/surgery , Angiogenesis Inhibitors/therapeutic use , Vascular Endothelial Growth Factor A/metabolism , Vascular Endothelial Growth Factor A/genetics , Bevacizumab/therapeutic use , Bevacizumab/pharmacology , Male , Female , Middle Aged , RNA, Messenger/genetics , RNA, Messenger/metabolism , Retinal Neovascularization/metabolism , Retinal Neovascularization/drug therapy , Aged , Preoperative Care , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Monoclonal, Humanized/pharmacology
17.
In Vivo ; 38(3): 1338-1350, 2024.
Article in English | MEDLINE | ID: mdl-38688599

ABSTRACT

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.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Bevacizumab , Drug Resistance, Neoplasm , Neoplasm Recurrence, Local , Ovarian Neoplasms , Humans , Bevacizumab/therapeutic use , Bevacizumab/administration & dosage , Bevacizumab/adverse effects , Female , Middle Aged , Ovarian Neoplasms/drug therapy , Ovarian Neoplasms/mortality , Ovarian Neoplasms/pathology , Aged , Neoplasm Recurrence, Local/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Adult , Treatment Outcome , Prognosis , Retrospective Studies , Carcinoma, Ovarian Epithelial/drug therapy , Carcinoma, Ovarian Epithelial/mortality , Platinum/therapeutic use , Antineoplastic Agents, Immunological/therapeutic use , Antineoplastic Agents, Immunological/adverse effects , Antineoplastic Agents, Immunological/administration & dosage
19.
J Gastroenterol ; 59(6): 515-525, 2024 06.
Article in English | MEDLINE | ID: mdl-38583112

ABSTRACT

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.


Subject(s)
Bevacizumab , Carcinoma, Hepatocellular , Esophageal and Gastric Varices , Hypertension, Portal , Liver Neoplasms , Phenylurea Compounds , Sorafenib , Humans , Hypertension, Portal/etiology , Male , Female , Retrospective Studies , Middle Aged , Aged , Risk Factors , Esophageal and Gastric Varices/etiology , Esophageal and Gastric Varices/epidemiology , Phenylurea Compounds/adverse effects , Phenylurea Compounds/administration & dosage , Phenylurea Compounds/therapeutic use , Sorafenib/adverse effects , Sorafenib/therapeutic use , Sorafenib/administration & dosage , Bevacizumab/administration & dosage , Bevacizumab/adverse effects , Bevacizumab/therapeutic use , Tomography, X-Ray Computed , Quinolines/therapeutic use , Quinolines/adverse effects , Quinolines/administration & dosage , Hepatic Encephalopathy/etiology , Hepatic Encephalopathy/epidemiology , Antineoplastic Agents/adverse effects , Antineoplastic Agents/administration & dosage , Adult , Aged, 80 and over , Gastrointestinal Hemorrhage/etiology , Gastrointestinal Hemorrhage/epidemiology , Incidence
20.
Front Immunol ; 15: 1354613, 2024.
Article in English | MEDLINE | ID: mdl-38617840

ABSTRACT

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.


Subject(s)
Antibodies, Monoclonal, Humanized , Colonic Neoplasms , Proto-Oncogene Proteins p21(ras) , Male , Humans , Bevacizumab/therapeutic use , Proto-Oncogene Proteins p21(ras)/genetics , Pathologic Complete Response , Colonic Neoplasms/drug therapy , Colonic Neoplasms/genetics , Platinum , Microsatellite Repeats , Tumor Microenvironment
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