Bevacizumab (Antineoplastic)

Publication Details



Bevacizumab is a humanized monoclonal antibody to human vascular endothelial growth factor (VEGF) and an anti-angiogenesis agent used in the therapy of colorectal, ovarian, renal and brain cancers. Bevacizumab has not been linked to serum enzyme elevations during therapy or to idiosyncratic acute liver injury. Bevacizumab may be partially protective against the vascular hepatic damage caused by other chemotherapeutic agents.


Bevacizumab (be” va siz’ ue mab) is a recombinant humanized monoclonal IgG1 antibody which is directed at and binds avidly to circulating vascular endothelial growth factor (VEGF). Receptors for VEGF (Flt-1 and KDR) are present on endothelial cells, and the engagement of VEGF with these receptors promotes angiogenesis. Inhibition of VEGF decreases formation of new blood vessels, which plays an important role in growth and spread of cancer cells. When used in combination with other antineoplastic agents, bevacizumab has been shown to extend both recurrence-free as well as overall patient survival in several forms of advanced cancer. Bevacizumab was approved in the United States in 2004 for use in metastatic colon cancer. Indications were subsequently extended to selected forms of non-small cell lung cancer, breast and renal cancer and glioblastoma. However, the indication for use in breast cancer was withdrawn in 2011 because of lack of evidence that bevacizumab extended overall patient survival. Bevacizumab is available vials of 100 or 400 mg (25 mg/mL) under the brand name Avastin. The typical dose is 5 to 10 mg/kg intravenously every 2 weeks or 7.5 to 15 mg every three weeks, usually in combination with other antineoplastic agents. Bevacizumab should be administered only by physicians with experience in using antineoplastic agents and managing their major complications. Bevacizumab has significant adverse side effects. Common adverse events include epistaxis, headache, dizziness, fatigue, hypertension, rhinitis, dry skin, back pain, excessive bleeding and skin rash. Rare complications include bowel, stomach or nasal septum perforation, poor wound healing, hemorrhage, thrombosis, renal dysfunction and ovarian failure.


In large clinical trials, serum aminotransferase elevations were no more frequent in patients receiving bevacizumab than in those on placebo or receiving comparator agents. Subsequent to its approval and general use, bevacizumab has not been implicated in cases of idiosyncratic adult liver injury. Bevacizumab is generally given with other potent antineoplastic agents and to patients with hepatic metastases which makes it difficult to attribute serum enzyme elevations or clinically apparent liver injury to a specific agent being used. Nevertheless, significant liver injury from bevacizumab must be quite rare, if it occurs at all.

Because bevacizumab inhibits angiogenesis, it has the potential to inhibit hepatic regeneration and wound healing after hepatic surgery. However, when used in conjunction with other antineoplastic agents before resection for colorectal hepatic metastases, bevacizumab has been associated with less hepatic toxicity from the other antineoplastic agents (such as oxaliplatin, fluorouracil and irinotecan) and has not been associated with an increase in perioperative complications or operative mortality. Thus, inhibition of angiogenesis by bevacizumab may be beneficial in ameliorating the hepatic vascular injury caused by other antineoplastic agents. Indeed, bevacizumab has been reported to decrease the frequency of sinusoidal obstruction syndrome in patients receiving chemotherapy for colorectal liver metasstases.

Likelihood score: E (unlikely cause of clinically apparent liver injury).

Mechanism of Injury

The mechanism by which bevacizumab might cause liver injury is unclear. It is a recombinant protein and unlikely to be inherently hepatoxic, being metabolized to small polypeptides or amino acids by many cells and having no effect on activity of drug metabolizing enzymes or hepatic transporter molecules. Because it is an inhibitor of angiogenesis, it might be benefical in ameliorating hepatic vascular injury caused by other antigenoplastic agents.

Drug Class: Antineoplastic Agents, Monoclonal Antibodies

See also: Macular Degeneration Agents



Bevacizumab – Avastin®


Antineoplastic Agents


Product labeling at DailyMed, National Library of Medicine, NIH



References updated: 26 September 2017

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    (Among 106 patients with metastatic colorectal cancer undergoing preoperative chemotherapy before hepatic resection, bevacizumab therapy [n=50] was associated with less sinusoidal dilatation [both frequency and severity], but rates of steatosis, fibrosis and tumor response were similar in the two groups).
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    (Systematic review of literature on chemotherapy induced liver injury in patients with colorectal cancer; oxaliplatin regimens are associated with a higher rate of sinusoidal injury [17% vs 6%] but not steatosis [11.5% vs 9.8%], and rates are reduced by concurrent bevacizumab therapy).
  • Noguchi Y, Tsurushima M, Tamura Y, Aoyama K, Tokuyama Y, Uchiyama K, Shimizu Y. [A case of hepatitis B virus reactivation in a patient with prior resolved hepatitis B infection during bevacizumab plus FOLFIRI treatment]. Gan To Kagaku Ryoho 2013; 40: 1561-3. Japanese. [PubMed: 24231716]
    (Abstract: 74 year old man with metastatic colorectal cancer who had anti-HBc without HBsAg in serum developed reactivation of hepatitis B 42 days after the 21st cycle of bevacizumab and FOLFIRI with HBsAg, HBeAg and high levels of HBV DNA progressing to acute liver failure and death).
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    (Retrospective analysis of 151 patients with colorectal cancer and hepatic metastases; some degree of sinusoidal obstruction syndrome occurred in 60 of 67 [90%] of those who received oxaliplatin and fluorouracil alone and was severe in 37 [55%], but arose in only 6 of 10 [60%] who also received bevacizumab and was severe in only 1 [10%]).
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