Bevacizumab protects against sinusoidal obstruction syndrome and does not increase response rate in neoadjuvant XELOX/FOLFOX therapy of colorectal cancer liver metastases

Klinger, Markus; Eipeldauer, Sandra; Hacker, Stefan; Herberger, Beata; Tamandl, Dietmar; Dorfmeister, Marion; Koelblinger, Claus; Gruenberger, Birgit; Gruenberger, Thomas

doi:10.1016/j.ejso.2008.12.013

Cited by 146 publications

(90 citation statements)

References 31 publications

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“…Bevacizumab treatment has been shown to have a protective effect against oxaliplatin-induced sinusoidal injury (2,49,50). Our molecular observation could partially explain this clinical observation.…”

Section: Discussionsupporting

confidence: 73%

Gene Expression Profiling Provides Insights into Pathways of Oxaliplatin-Related Sinusoidal Obstruction Syndrome in Humans

Rubbia‐Brandt

Tauzin

Brézault

et al. 2011

Molecular Cancer Therapeutics

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Sinusoidal obstruction syndrome (SOS; formerly veno-occlusive disease) is a well-established complication of hematopoietic stem cell transplantation, pyrrolizidine alkaloid intoxication, and widely used chemotherapeutic agents such as oxaliplatin. It is associated with substantial morbidity and mortality. Pathogenesis of SOS in humans is poorly understood. To explore its molecular mechanisms, we used Affymetrix U133 Plus 2.0 microarrays to investigate the gene expression profile of 11 human livers with oxaliplatin-related SOS and compared it to 12 matched controls. Hierarchical clustering analysis showed that profiles from SOS and controls formed distinct clusters. To identify functional networks and gene ontologies, data were analyzed by the Ingenuity Pathway Analysis Tool. A total of 913 genes were differentially expressed in SOS: 613 being upregulated and 300 downregulated. Reverse transcriptase-PCR results showed excellent concordance with microarray data. Pathway analysis showed major gene upregulation in six pathways in SOS compared with controls: acute phase response (notably interleukin 6), coagulation system (Serpine1, THBD, and VWF), hepatic fibrosis/hepatic stellate cell activation (COL3a1, COL3a2, PDGF-A, TIMP1, and MMP2), and oxidative stress. Angiogenic factors (VEGF-C) and hypoxic factors (HIF1A) were upregulated. The most significant increase was seen in CCL20 mRNA. In conclusion, oxaliplatin-related SOS can be readily distinguished according to morphologic characteristics but also by a molecular signature. Global gene analysis provides new insights into mechanisms underlying chemotherapy-related hepatotoxicity in humans and potential targets relating to its diagnosis, prevention, and treatment. Activation of VEGF and coagulation (vWF) pathways could partially explain at a molecular level the clinical observations that bevacizumab and aspirin have a preventive effect in SOS.

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Section: Discussionsupporting

confidence: 73%

Gene Expression Profiling Provides Insights into Pathways of Oxaliplatin-Related Sinusoidal Obstruction Syndrome in Humans

Rubbia‐Brandt

Tauzin

Brézault

et al. 2011

Molecular Cancer Therapeutics

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“…In fact, recently, the introduction of cetu and beva to the standard chemotherapy has further improved survival. The safety of major hepatic resection in the setting of neo-adjuvant chemotherapy is crucial and still unknown when considering the use of these new "targeted molecules" (12)(13)(14)(15)(16). This case-control study did not show any deleterious consequences on outcomes after hepatic resection when cetu or beva were added to the standard chemotherapy regimen.…”

mentioning

confidence: 71%

“…14 influence of preoperative beva on complication after hepatic resection (13)(14)(15)(16). There were no differences in overall, severe, hepatic, and bleeding complications in group of patients treated with beva.…”

Section: A C C E P T E D Accepted Manuscriptmentioning

confidence: 99%

“…Preliminary results demonstrated that the addition bevacizumab or cetuximab to conventional chemotherapy may further increase the response rates (10)(11)(12). Few studies reported the outcome of liver resection after use of bevacizumab in combination with chemotherapy (13,14) and only two studies (15,16) reported the effect of bevacizumab on the non-tumorous liver. To our knowledge, no study has reported results with the use of cetuximab.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

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Targeted molecular therapies (cetuximab and bevacizumab) do not induce additional hepatotoxicity: Preliminary results of a case–control study

Pessaux

Panaro

Casnedi

et al. 2010

European Journal of Surgical Oncology (EJSO)

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“…(WHC), serious bleeding, arterial and venous thromboembolic events (ATE and VTE), renal toxicity and influences on liver parenchyma 5,[7][8][9][10][11][12][13] . Pharmacokinetic studies show that BV has a half-life of 20 days [range 11-50 days].…”

Section: A C C E P T E D Accepted Manuscriptmentioning

confidence: 99%

Review: Incidence and clinical significance of Bevacizumab-related non-surgical and surgical serious adverse events in metastatic colorectal cancer

Hompes

Ruers

2011

European Journal of Surgical Oncology (EJSO)

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To cite this version:Daphne Hompes, Theo Ruers. Review: Incidence and clinical significance of Bevacizumab-related non-surgical and surgical serious adverse events in metastatic colorectal cancer. EJSO -European Journal of Surgical Oncology, WB Saunders, 2011, 37 (9) This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. period of minimally 28 days should be respected before starting BV. Conclusion:Reported rates of BV-related SAE in relationship to surgery are low.

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Bevacizumab protects against sinusoidal obstruction syndrome and does not increase response rate in neoadjuvant XELOX/FOLFOX therapy of colorectal cancer liver metastases

Cited by 146 publications

References 31 publications

Gene Expression Profiling Provides Insights into Pathways of Oxaliplatin-Related Sinusoidal Obstruction Syndrome in Humans

Gene Expression Profiling Provides Insights into Pathways of Oxaliplatin-Related Sinusoidal Obstruction Syndrome in Humans

Targeted molecular therapies (cetuximab and bevacizumab) do not induce additional hepatotoxicity: Preliminary results of a case–control study

Review: Incidence and clinical significance of Bevacizumab-related non-surgical and surgical serious adverse events in metastatic colorectal cancer

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