Intricacies of Bevacizumab-Induced Toxicities and Their Management

Gressett, Sarah M; Shah, Sachin

doi:10.1345/aph.1l426

Cited by 165 publications

(137 citation statements)

References 57 publications

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“…On the basis of cumulative adverse events observed in the expanded cohort of 1.6 mg/kg, the recommended phase II dose level of dalantercept as monotherapy is 1.2 mg/kg (75% of 1.6 mg/kg) every 3 weeks. In the present study, no clinically relevant hypertension, proteinuria, gastrointestinal perforations, or hemorrhage were observed, and thus the safety profile of dalantercept appears to be distinct from that of VEGF pathway inhibitors (32)(33)(34)(35). This result suggests that dalantercept potentially could be administered concurrently with a VEGF pathway inhibitor to achieve enhanced antiangiogenic effect.…”

Section: Discussionmentioning

confidence: 45%

Safety, Pharmacokinetics, Pharmacodynamics, and Antitumor Activity of Dalantercept, an Activin Receptor–like Kinase-1 Ligand Trap, in Patients with Advanced Cancer

Bendell

Gordon

Hurwitz

et al. 2014

Clinical Cancer Research

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Section: Discussionmentioning

confidence: 45%

Safety, Pharmacokinetics, Pharmacodynamics, and Antitumor Activity of Dalantercept, an Activin Receptor–like Kinase-1 Ligand Trap, in Patients with Advanced Cancer

Bendell

Gordon

Hurwitz

et al. 2014

Clinical Cancer Research

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“…One of the best studied agents is the monoclonal anti-VEGF antibody, bevacizumab. Toxicities associated with bevacizumab include neutropenia, with previously published reports indicating increased incidence of neutropenia in subjects assigned to the bevacizumab containing arms of phase 2 and 3 clinical trials [33,34] . Recently, two large prospective, randomized, phase 3 clinical trials evaluating use of bevacizumab in ovarian cancer were published.…”

Section: Discussionmentioning

confidence: 99%

Impact of chemotherapy-induced neutropenia on survival in patients with breast, ovarian and cervical cancer: a systematic review

Eskander

Tewari

2012

J Hemat Malig

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Background: Recent advances in chemotherapy administration, including targeted therapies and dose-dense scheduling have led to an increased incidence of neutropenia. Chemotherapy-induced neutropenia has been shown to be associated with improved treatment outcomes in various solid tumor types. We looked to summarize the relationship between chemotherapy-induced neutropenia and survival in patients with breast, ovarian and cervical cancer and describe future directions of research. Methodology/Principle findings:A comprehensive PUBMED literature search was conducted using the key words "solid tumor", "breast cancer", "ovarian cancer", "cervical cancer", "endometrial cancer", in combination with "chemotherapy", "neutropenia", "survival", "disease recurrence" and "prognosis". The search was also guided through a review of the reference lists of original and review articles. Published papers included in the review met the following criteria: patients with breast, ovarian, endometrial or cervical cancer treated with chemotherapy; prospective and retrospective studies, both randomized and cohort designs, evaluating impact of neutropenia or leukopenia on disease outcome. Eleven studies met the inclusion criteria. Sample size ranged from 103-750 subjects. The majority of included studies were conducted in breast cancer patients (7 of 11). No studies related to endometrial cancer were identified. Outcome measures included overall survival, progression free survival and distant disease free survival. All studies were retrospective in nature. Of the 11 identified studies, 9 suggested that the occurrence of chemotherapy-induced neutropenia was associated with improvement in oncologic outcome.Conclusions/Significance: Evaluation of the impact of chemotherapy-induced neutropenia on outcomes in patients with breast, ovarian and cervical cancer is warranted utilizing prospectively collected data from patients enrolled in clinical trials.

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“…Hemorrhage is one of the most severe toxicities associated with VEGFIs [46]. Bevacizumab has the highest frequency of bleeding, and although a pooled analysis of three randomized trials did not demonstrate a significantly higher incidence of grade 3-4 hemorrhage [47], numerous trials have individually reported higher incidences of bleeding [47].…”

Section: Hemorrhagementioning

confidence: 99%

“…Grade 3-4 hemorrhagic events with bevacizumab occur at a rate of 1.2%-4.6%. However, less severe bleeding occurs in up to 40% of patients [46,48]. The SMTKIs have so far been associated with a lower rate of bleeding, but events including fatal pulmonary and intracranial hemor- [49,50].…”

Section: Hemorrhagementioning

confidence: 99%

Noncardiac Vascular Toxicities of Vascular Endothelial Growth Factor Inhibitors in Advanced Cancer: A Review

et al. 2011

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Summary. The introduction of molecularly targeted anticancer therapies has brought the promise of longer survival times for select patients with cancers previously considered untreatable. However, it has also brought new toxicities that require understanding and management, sometimes for long periods of time. Vascular endothelial growth factor inhibitors are associated with a broad range of adverse effects, with vascular toxicity being particularly serious. This review focuses on the current understanding of the pathophysiology and mechanisms of macrovascular toxicities (hypertension, hemorrhage, and thromboembolism), their incidence and severity, the current clinical management, and implications in the advanced cancer setting. Movement of these agents into the early disease setting will alter the impact of these toxicities.Search Strategy and Selection Criteria. Information for this review was collected by searching PubMed/ Medline and American Society of Clinical Oncology abstract databases. The medical subject heading terms used included toxicity, hypertension, thromboembolism, hemorrhage, intestinal perforation, risk factors, pharmacokinetics, and metabolism, combined with free text search terms including, but not limited to, VEGF inhibitor*, bevacizumab, sunitinib, and sorafenib. Articles published in English before March 2010 were included, in addition to information from case reports and pharmaceutical agent package inserts. The Oncologist 2011;16:432-444

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Intricacies of Bevacizumab-Induced Toxicities and Their Management

Abstract: As bevacizumab is becoming widely used in general oncology practice, it is important to understand the toxicities that can arise and to develop practice guidelines for their management.

Cited by 165 publications

References 57 publications

Safety, Pharmacokinetics, Pharmacodynamics, and Antitumor Activity of Dalantercept, an Activin Receptor–like Kinase-1 Ligand Trap, in Patients with Advanced Cancer

Safety, Pharmacokinetics, Pharmacodynamics, and Antitumor Activity of Dalantercept, an Activin Receptor–like Kinase-1 Ligand Trap, in Patients with Advanced Cancer

Impact of chemotherapy-induced neutropenia on survival in patients with breast, ovarian and cervical cancer: a systematic review

Noncardiac Vascular Toxicities of Vascular Endothelial Growth Factor Inhibitors in Advanced Cancer: A Review

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