Routine proteinuria monitoring for bevacizumab in patients with gynecologic malignancies

Lee, Catherine S.; Alwan, Laura; Sun, Xiaocui; McLean, K.; Urban, Renata R.

doi:10.1177/1078155215609987

Cited by 9 publications

(7 citation statements)

References 13 publications

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“…Ang-2 and VEGF may be involved in promoting the integrity of glomerular endothelia (34)(35)(36). Altered glomerular permeability with leakage of large proteins into the urine appears to be a direct result of VEGF-A and Ang-2 inhibition.…”

Section: Discussionmentioning

confidence: 99%

First-in-Human Phase I Study of Single-agent Vanucizumab, A First-in-Class Bispecific Anti-Angiopoietin-2/Anti-VEGF-A Antibody, in Adult Patients with Advanced Solid Tumors

Hidalgo

Martinez-García

Tourneau

et al. 2018

Clinical Cancer Research

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Vanucizumab is an investigational antiangiogenic, first-in-class, bispecific mAb targeting VEGF-A and angiopoietin-2 (Ang-2). This first-in-human study evaluated the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of vanucizumab in adults with advanced solid tumors refractory to standard therapies. Patients received escalating biweekly (3-30 mg/kg) or weekly (10-30 mg/kg) intravenous doses guided by a Bayesian logistic regression model with overdose control. Forty-two patients were treated. One dose-limiting toxicity, a fatal pulmonary hemorrhage from a large centrally located mediastinal mass judged possibly related to vanucizumab, occurred with the 19 mg/kg biweekly dose. Arterial hypertension (59.5%), asthenia (42.9%), and headache (31%) were the most common toxicities. Seventeen (41%) patients experienced treatment-related grade ≥3 toxicities. Toxicity was generally higher with weekly than biweekly dosing. A MTD of vanucizumab was not reached in either schedule. Pharmacokinetics were dose-linear with an elimination half-life of 6-9 days. All patients had reduced plasma levels of free VEGF-A and Ang-2; most had reductions in K (measured by dynamic contrast-enhanced MRI). Two patients (renal cell and colon cancer) treated with 30 mg/kg achieved confirmed partial responses. Ten patients were without disease progression for ≥6 months. A flat-fixed 2,000 mg biweekly dose (phamacokinetically equivalent to 30 mg/kg biweekly) was recommended for further investigation. Biweekly vanucizumab had an acceptable safety and tolerability profile consistent with single-agent use of selective inhibitors of the VEGF-A and Ang/Tie2 pathway. Vanucizumab modulated its angiogenic targets, impacted tumor vascularity, and demonstrated encouraging antitumor activity in this heterogeneous population. .

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Section: Discussionmentioning

confidence: 99%

First-in-Human Phase I Study of Single-agent Vanucizumab, A First-in-Class Bispecific Anti-Angiopoietin-2/Anti-VEGF-A Antibody, in Adult Patients with Advanced Solid Tumors

Hidalgo

Martinez-García

Tourneau

et al. 2018

Clinical Cancer Research

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“…It was concluded that monitoring the UP to creatinine ratio may not be necessary with every dose of bevacizumab due to the low prevalence of proteinuria, similar to the results of our analysis. 12…”

Section: Discussionmentioning

confidence: 99%

“…found no identifiable risk factors among this patient population that would predispose certain patients to the development of proteinuria during bevacizumab therapy. 12…”

Section: Discussionmentioning

confidence: 99%

Assessment of extended urine protein monitoring frequency in patients receiving bevacizumab

Schiffer

Zukovic

Hall

et al. 2020

J Oncol Pharm Pract

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Purpose Proteinuria monitoring is required for patients receiving bevacizumab. Nonetheless, the frequency of monitoring is not specified in the package insert. A 2014 quality improvement study performed at Yale New Haven Health System (YNHHS) found that proteinuria occurred in 15% (all grade) of the 162 patients evaluated. These results led to decreasing the frequency of proteinuria monitoring from every treatment to every other treatment. The objective of this study is to assess the safety of the extended interval for urine protein (UP) monitoring. Methods Patients receiving at least four bevacizumab treatments at YNHHS from January to June 2017 were randomly selected and retrospectively reviewed. The following data were collected: baseline patient characteristics, comorbidities, medication history, and proteinuria monitoring. The grade, prevalence and management of proteinuria were evaluated. The minimum necessary sample size was determined to be 384 treatments to achieve a 95% confidence interval. Results Fifty-five patients and 388 bevacizumab treatments were evaluated. Urine protein was assessed in 52.5% of treatments. The incidence of proteinuria among patients was 7.2% (grade 2) and 0% (grade 3). Cumulative dose and the number of total bevacizumab doses did not affect the timing for onset or severity of proteinuria. Two patients with UP ≥ 2+ were further monitored using a 24-h urine collection test with negative results. No treatments were held due to proteinuria. Conclusion Monitoring proteinuria every other treatment does not increase the frequency of adverse events. Urine protein is now monitored prior to every third bevacizumab treatment, reducing unnecessary labs and chair time.

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“…Bevacizumab leads to vasoconstriction and hypertension by inhibiting VEGF. Secondly, inhibition by VEGF of the kidney can induce occurrence of renal thrombotic microangiopathy and aggravation of hypertension (16). Lastly, it has also been noted that VEGF was overexpressed in patients with myocardial infarction (17) or cardiac pressure overload (18).…”

Section: Discussionmentioning

confidence: 99%

Severe Cardiotoxicity in a Patient with Colorectal Cancer Treated with Bevacizumab

Chen

et al. 2017

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Routine proteinuria monitoring for bevacizumab in patients with gynecologic malignancies

Cited by 9 publications

References 13 publications

First-in-Human Phase I Study of Single-agent Vanucizumab, A First-in-Class Bispecific Anti-Angiopoietin-2/Anti-VEGF-A Antibody, in Adult Patients with Advanced Solid Tumors

First-in-Human Phase I Study of Single-agent Vanucizumab, A First-in-Class Bispecific Anti-Angiopoietin-2/Anti-VEGF-A Antibody, in Adult Patients with Advanced Solid Tumors

Assessment of extended urine protein monitoring frequency in patients receiving bevacizumab

Severe Cardiotoxicity in a Patient with Colorectal Cancer Treated with Bevacizumab

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