Introduction
Bevacizumab is a recombinant humanized monoclonal IgG1 antibody that specifically binds to and neutralizes vascular endothelial growth factor (VEGF), preventing its interaction with VEGF receptors. It was first approved by the FDA in 2004 and represents a cornerstone of antiangiogenic therapy in oncology. Bevacizumab is marketed under the brand name Avastin® and has revolutionized the treatment of multiple solid tumors by targeting tumor vasculature.
Mechanism of Action
Bevacizumab exerts its therapeutic effects by binding to VEGF-A, a key cytokine that promotes angiogenesis—the formation of new blood vessels. By sequestering VEGF-A, bevacizumab prevents its interaction with VEGF receptors (VEGFR-1 and VEGFR-2) on endothelial cells. This inhibition leads to:
- Regression of existing tumor vasculature
- Normalization of remaining tumor vasculature
- Inhibition of new blood vessel formation
- Reduced vascular permeability
- Ultimately, suppression of tumor growth and metastasis
The drug's antiangiogenic effects create an "anti-tumor" environment by starving tumors of oxygen and nutrients while improving delivery of concomitant chemotherapy agents through vascular normalization.
Indications
FDA-approved indications include:
- Metastatic colorectal cancer (first- or second-line in combination with chemotherapy)
- Non-squamous non-small cell lung cancer (with carboplatin and paclitaxel)
- Recurrent glioblastoma (as single agent)
- Metastatic renal cell carcinoma (with interferon alfa)
- Cervical cancer (with paclitaxel and cisplatin or paclitaxel and topotecan)
- Epithelial ovarian, fallopian tube, or primary peritoneal cancer:
- First-line treatment (with carboplatin and paclitaxel) - Platinum-sensitive recurrent disease (with carboplatin and gemcitabine) - Platinum-resistant recurrent disease (with paclitaxel, pegylated liposomal doxorubicin, or topotecan)
Additional off-label uses are supported by clinical evidence in various malignancies.
Dosage and Administration
Standard dosing:- 5-15 mg/kg IV every 2-3 weeks depending on indication and regimen
- Typically administered as a 30-90 minute IV infusion following chemotherapy
- Colorectal cancer: 5-10 mg/kg every 2 weeks
- NSCLC: 15 mg/kg every 3 weeks
- Glioblastoma: 10 mg/kg every 2 weeks
- Renal cell carcinoma: 10 mg/kg every 2 weeks
- Ovarian cancer: 15 mg/kg every 3 weeks or 10 mg/kg every 2 weeks
- Renal impairment: No dosage adjustment required
- Hepatic impairment: No specific recommendations; use with caution
- Elderly: Increased risk of arterial thromboembolic events
- Pediatrics: Safety and effectiveness not established
Pharmacokinetics
Absorption: Administered intravenously only, resulting in complete bioavailability Distribution: Limited extravascular distribution; volume of distribution approximates plasma volume (2.9-4.7 L) Metabolism: Cleared via proteolytic degradation throughout the body, similar to endogenous IgG Elimination: Half-life approximately 20 days (range 11-50 days); clearance affected by body weight, gender, and tumor burden Steady-state: Achieved after approximately 3 cycles (84 days)Contraindications
- Hypersensitivity to bevacizumab or any component of the formulation
- Recent history of hemoptysis (≥1/2 teaspoon of red blood)
- Major surgery within 28 days prior to initiation
- Anticipated major surgical procedure during treatment
- Recent history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess
Warnings and Precautions
Boxed Warning:- Gastrointestinal perforations
- Surgery and wound healing complications
- Hemorrhage
- Arterial thromboembolic events (MI, CVA, TIA)
- Hypertension (may require antihypertensive therapy)
- Posterior reversible encephalopathy syndrome (PRES)
- Renal injury and proteinuria
- Infusion reactions
- Ovarian failure and fertility implications
- Congestive heart failure
- Embryo-fetal toxicity
Drug Interactions
- Sunitinib: Increased risk of microangiopathic hemolytic anemia
- Anthracyclines: Potential increased risk of cardiotoxicity
- NSAIDs: May increase risk of gastrointestinal perforation
- Anticoagulants: May increase bleeding risk
- CYP450 substrates: No expected interactions
Adverse Effects
Very common (≥10%):- Hypertension (up to 34%)
- Fatigue (33%)
- Diarrhea (21%)
- Anorexia (19%)
- Nausea (16%)
- Vomiting (12%)
- Proteinuria (11%)
- Gastrointestinal perforation (1.4-2.4%)
- Hemorrhage (2.4-5%)
- Arterial thromboembolism (2.6-4.4%)
- Wound healing complications (1.7-3.4%)
- Reversible posterior leukoencephalopathy syndrome (0.5%)
- Neutropenia and infection
Monitoring Parameters
Prior to initiation:- Baseline blood pressure
- Urinalysis for proteinuria
- Surgical history and planned procedures
- coagulation parameters
- Blood pressure every 2-3 weeks
- Urine protein:creatinine ratio periodically
- Complete blood count with differential
- Signs/symptoms of GI perforation, hemorrhage, thrombosis
- Neurologic assessment for PRES
- Wound healing status
- Cardiac function in patients with risk factors
- Renal function
- ovarian function in premenopausal women
Patient Education
- Report any signs of bleeding, severe headaches, visual changes, or abdominal pain immediately
- Inform all healthcare providers about bevacizumab treatment before any surgical procedures
- Use effective contraception during and for 6 months after treatment
- Monitor blood pressure regularly as directed
- Report symptoms of infection, wound complications, or delayed healing
- Understand potential risks and benefits of therapy
- Do not receive live vaccines during treatment
References
1. FDA Prescribing Information: Avastin (bevacizumab) 2. National Comprehensive Cancer Network (NCCN) Guidelines 3. Giantonio BJ, et al. J Clin Oncol. 2007;25(12):1539-1544 4. Sandler A, et al. N Engl J Med. 2006;355(24):2542-2550 5. Friedman HS, et al. J Clin Oncol. 2009;27(28):4733-4740 6. Burger RA, et al. N Engl J Med. 2011;365(26):2473-2483 7. Escudier B, et al. J Clin Oncol. 2010;28(13):2144-2150 8. Tewari KS, et al. N Engl J Med. 2017;376(11):1019-1029
This monograph is for educational purposes only and should not replace clinical judgment. Always consult current prescribing information and clinical guidelines.