Generic Name

Bevacizumab

Mechanism

• VEGF‑A inhibition – Binds circulating VEGF‑A and placental growth factor‑1 (PlGF‑1), preventing interaction with VEGF receptors on endothelial cells.
• Arrest of endothelial growth – Blocks downstream PI3K/Akt and MAPK signaling, leading to impaired endothelial cell proliferation, migration, and capillary tube formation.
• Tumor vessel normalization – Reduces leaky vasculature, improves drug delivery, and induces apoptosis in tumor micro‑environment.

Pharmacokinetics

| Excretion | Mainly renal ( *Key point:* Steady‑state trough concentration is achieved by week 4; exposure correlates with tumor response.

Indications

• Colorectal cancer – Metastatic, refractory to 5‑FU, with or without irinotecan or oxaliplatin.
• Non‑small cell lung cancer (NSCLC) – Metastatic refractory to platinum‑based therapy.
• Renal cell carcinoma (RCC) – Metastatic disease after cytokine therapy.
• Glioblastoma multiforme (GBM) – Recurrent.
• Choroidal neovascularization (CNV) – Age‑related macular degeneration (off‑label, retinal form).
• Breast cancer – Recurrent metastatic disease (limited evidence).
• Melanoma – Recurrent metastatic disease (limited evidence).

*Note:* FDA labeling is *limited to colon, lung, and RCC*; other indications are supported by evidence‑based guidelines and compassionate use.

Contraindications

• Active bleeding (e.g., GI ulcer, cerebral hemorrhage) – contraindicated.
• Arterial thromboembolic disease (stroke, MI, PEA) in the past 3 months.
• Pregnancy – Category X; teratogenic.
• Hypersensitivity to bevacizumab or murine components.
• Peptic ulcer disease – Uncontrolled.
• Severe hypertension (≥140/90 mmHg) unresponsive to therapy.
• Recent severe cardiovascular event (≥3 months).
• Poor wound healing and surgery – avoid for 4 weeks post‑treatment.

*Warnings* include:
• Hypertension – Can develop within 2 weeks; treat aggressively.
• Proteinuria/renal dysfunction – Urine protein/creatinine ratio >0.5 g/24 h warrants dose interruption.
• Bleeding/Tissue necrosis – Monitor for GI perforation, GI bleeding, and wound issues.
• Conjunctional (ocular) risk – Rare but possible ocular toxicity.

Dosing

• Colorectal: 7.5 mg/kg IV over 90 min q2w (or 5 mg/kg if renal impairment >3 mL/min/1.73 m²).
• Lung: 5 mg/kg IV q2w (± combination).
• RCC: 7.5 mg/kg IV q2w.
• Glioblastoma: 10 mg/kg IV q2w (dose‑escalation studies).
• General: 15 mg/second IV infusion; 7–8 hours total infusion time.
• Premedication: Antihistamine, antihyperlipidemic; avoid NSAIDs pre‑infusion.

Adverse Effects

Common (≥15 %):
• Hypertension (≈20 %)
• Proteinuria (≈8 %)
• Fatigue
• Nausea, vomiting
• Diarrhea (5–10 %)
• Arthralgia, myalgia

Serious (≤5 %):
• GI perforation (≈1 %)
• Severe hemorrhage (≥3 %)
• Ischemic events: MI, stroke, TIA
• Arteriovenous thrombosis
• Severe wound healing complications
• Hypersensitivity/infusion reactions (anaphylaxis)

Incidence: Reported in phase III trials; numbers vary by indication.

Monitoring

| Urine protein/creatinine ratio | Every 2 weeks | 180/110 mmHg; treat with antihypertensives.
• Dose delay for proteinuria >2 g/24 h or renal dysfunction.
• Permanent discontinuation for GI perforation, uncontrolled bleeding.

Clinical Pearls

• Early hypertension is a biomarker for response; however, aggressive BP control maintains tolerability.
• Proteinuria >0.5 g/24 h warrants dose hold; consider switching to 2 g/24 h before resume.
• Concomitant use with corticosteroids reduces infusion reaction risk; avoid NSAIDs that impair healing.
• Tumor vascular normalization can improve chemotherapy delivery; consider scheduling bevacizumab 24 h before cytotoxics.
• Pregnancy prevention: Mandatory until no pregnancy detectable; patients on long‑term therapy should use effective contraception.
• Rechallenge after discontinuation is feasible; evaluate for previous adverse events and tumor progression.
• Drug interactions minimal; but caution with anticoagulants – risk of bleeding ↑.
• Bioavailability: Not oral; no subcutaneous formulation approved.
• Vascular events: Monitor for arrhythmias in patients with pre‑existing coronary artery disease; consider cardiology consultation pre‑treatment.

*Reference:* National Comprehensive Cancer Network (NCCN) Guidelines, 2025; FDA label, 2023.