Bevacizumab

Kazazi-Hyseni, Filis; Beijnen, Jos H.; Schellens, Jan H.M.

doi:10.1634/theoncologist.2009-0317

Cited by 227 publications

(183 citation statements)

References 39 publications

(49 reference statements)

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“…Bevacizumab inhibits VEGF-induced proliferation of endothelial cells [25]. The clearance of bevacizumab is a complex process which depends on several factors, namely on body weight, gender, serum albumin, alkaline phosphatase (ALP), and serum aspartate aminotransferase (AST) [26,27]. In our previous mice experiments [17] all mice were 20 gram male C57Bl/6 mice.…”

Section: Discussionmentioning

confidence: 99%

Modeling of Tumor Growth Incorporating the Effects of Necrosis and the Effect of Bevacizumab

2017

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Tumor growth models are important to create an engineering background for cancer treatment either by using the models for simulations and evaluation of treatment protocols or, if combined with control engineering, by designing treatment protocols. A well-defined tumor growth model must describe the physiological processes and the measurements as well. Growing tumors are composed of dead tumor cells (forming the necrotic part) and living, proliferating tumor cells (forming the proliferating part); when tumor volume is measured, these parts are measured together. Most of the known tumor growth models do not consider the modeling of the necrotic part. Starting from a minimal model of the tumor growth under bevacizumab treatment, the aim of the current research is to extend it incorporating the volume and dynamics of the necrotic part and the pharmacodynamics and mixed-order pharmacokinetics of the applied drug. The extended model is validated using measurements with mice as hosts, colon adenocarcinoma as tumor, and bevacizumab as the drug used for treatment. The results show that the extended model can describe the important physiological phenomena and shows a good fit to the average of the measurements.

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Section: Discussionmentioning

confidence: 99%

Modeling of Tumor Growth Incorporating the Effects of Necrosis and the Effect of Bevacizumab

2017

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“…The difference in survival seems to be mainly related to the increased toxicity attributable to bevacizumab treatment. Bevacizumab is known to cause several typical side effects (25), including arterial hypertension, proteinuria, bleeding, and thrombosis; these side effects also have been reported in HCC trials (12)(13)(14)(15). Our main concern during the design of this protocol was the potentially increased variceal bleeding risk due to bevacizumab; this is a lifethreatening complication of advancedstage liver disease, with a particularly dismal outcome (26).…”

Section: Vascular and Interventional Radiology: Hepatocellular Carcinmentioning

confidence: 96%

Hepatocellular Carcinoma: A Phase II Randomized Controlled Double-Blind Trial of Transarterial Chemoembolization in Combination with Biweekly Intravenous Administration of Bevacizumab or a Placebo

Pinter¹,

Ulbrich²,

Sieghart³

et al. 2015

Radiology

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).q RSNA, 2015 Purpose:To investigate the efficacy and safety of conventional transarterial chemoembolization (TACE) (cTACE) in combination with bevacizumab or a placebo in patients with hepatocellular carcinoma (HCC) in a randomized controlled double-blind phase II trial. Materials and Methods:This study was approved by the institutional review board, and written informed consent was obtained prior to inclusion. A total of 40 patients (20 patients per group, all 18 years or older) with histologically confirmed early-or intermediate-stage HCC and Child-Pugh class A or B cirrhosis were scheduled for inclusion. The primary endpoint was radiologic progression at 12 months according to European Association for the Study of the Liver criteria. Secondary endpoints were safety and overall survival (OS). Patients underwent cTACE with doxorubicin and intravenous administration of a placebo (cTACE-C) or bevacizumab (cTACE-B) (5 mg per kilogram of body weight) every 2 weeks for 52 weeks. After the first TACE procedure, TACE was repeated twice in 4-week intervals if indicated and technically feasible and on demand thereafter. Statistical analyses were performed with statistical software. P , .05 indicated a significant difference. Results:Thirty-two patients were recruited between January 2006 and December 2009 (29 male, three female; mean age, 61 years 6 8 [standard deviation]; Barcelona Clinic Liver Cancer stage A, n = 4; Barcelona Clinic Liver Cancer stage B, n = 28; predominant cause, alcohol [n = 15]; Child-Pugh class A disease, n = 22; Child-Pugh class B disease, n = 10; 16 patients received bevacizumab; 16 patients received a placebo). Patients underwent a median of three TACE cycles and received 13 infusions of bevacizumab versus 11 infusions of the placebo before the trial was stopped prematurely for safety reasons. Severe (grade 3-5) septic (n = 8 vs n = 3) and vascular (n = 9 vs n = 0) side effects were observed almost exclusively in the cTACE-B group. Median survival was worse in the cTACE-B group than in the cTACE-C group (5.3 vs 13.7 months; hazard ratio [HR], 1.7; 95% confidence interval [CI]: 0.8, 3.6; P = .195) and reached significance in patients with Child-Pugh class A cirrhosis (7.3 vs 26.5 months; HR, 2.6; 95% CI: 1.0, 6.6; P = .049). The primary endpoint was not met, since there was no difference in radiologic response between the groups at 3, 6, or 12 months. Conclusion:No improvement in radiologic tumor response or OS was observed in patients with HCC who received cTACE and bevacizumab, but severe and even lethal septic and vascular side effects occurred. Thus, bevacizumab cannot be recommended as an adjuvant treatment to cTACE.q RSNA, 2015

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“…An example of this class of agents is bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor. This agent showed a significant antitumor effect in patients with advanced colorectal cancer, non-small cell lung cancer, and metastatic breast cancer when combined with standard cytotoxic chemotherapy, but was not effective as a monotherapy (Kazazi-Hyseni et al 2010). Although its mechanisms of action have not been fully defined and may vary among different tumor types, one of the potent mechanisms of bevacizumab is the normalization of the tumor vasculature and the improvement of chemotherapy delivery to the tumor (Ellis and Hicklin 2008).…”

Section: Classification Of Targeted Agents For Clinical Developmentmentioning

confidence: 99%

Clinical Classification of Targeted Agents Used for Anticancer Treatment

Sekine

Takiguchi

2013

Tohoku J. Exp. Med.

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The introduction of targeted agents has resulted in a breakthrough in advanced cancer treatment. We propose a new classification for these agents to evaluate them in appropriate clinical trials according to agent class. Class I agents that inhibit driver oncogene activities result in massive and rapid tumor shrinkage, with response rates as high as 70% when administered to patients with appropriate targets. These agents can be evaluated in single-arm phase II trials with response rate as the primary endpoint. Class II agents inhibit one oncogene that is partially responsible for accelerating tumor cell proliferation. Their clinical features include synergism with cytotoxic agents and moderate single-agent activity, as shown by response rates of between 10% and 30%. Randomized phase II trials in patients with over-expressed targets are appropriate for the evaluation of these agents. Class III agents inhibit proliferation regulators that are not always oncogenic. Their clinical activity is unique, as they confer a survival benefit on patients with a minimum tumor shrinkage effect. Class IV agents target environmental molecules that act on normal cells surrounding tumor cells, such as the endothelial cells that form vessels. Placebo-controlled randomized phase II trials are required to identify the clinical activities of both class III and IV agents. Class V agents act by enhancing anti-tumor immunity. Immune-related response criteria should aid the evaluation of these agents. We believe that this classification for targeted agents should facilitate their further clinical development.

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Bevacizumab

Cited by 227 publications

References 39 publications

Modeling of Tumor Growth Incorporating the Effects of Necrosis and the Effect of Bevacizumab

Modeling of Tumor Growth Incorporating the Effects of Necrosis and the Effect of Bevacizumab

Hepatocellular Carcinoma: A Phase II Randomized Controlled Double-Blind Trial of Transarterial Chemoembolization in Combination with Biweekly Intravenous Administration of Bevacizumab or a Placebo

Clinical Classification of Targeted Agents Used for Anticancer Treatment

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