How is bevacizumab administered, what are the recommended doses for various cancers, and what contraindications and safety considerations should be taken into account?

Bevacizumab Administration and Dosing

Bevacizumab is administered as an intravenous infusion with cancer-specific dosing ranging from 5-15 mg/kg every 2-3 weeks, and must be withheld for at least 28 days before elective surgery and until adequate wound healing after major surgery. 1

Administration Method

Bevacizumab is given as an intravenous infusion after dilution. 1 While traditional recommendations suggest the first infusion last 90 minutes, the second 60 minutes, and subsequent infusions 30 minutes 2, more recent evidence demonstrates that rapid administration is both safe and practical:

• Bevacizumab may be safely administered at a rate of 0.5 mg/kg/min (5 mg/kg over 10 minutes and 7.5 mg/kg over 15 minutes). 2
• A 30-minute initial infusion followed by subsequent infusions at 0.5 mg/kg/min has been shown to be safe and efficacious for colorectal cancer, with no hypersensitivity reactions observed. 3
• The rapid infusion approach limits patient confinement time and reduces healthcare resource utilization without compromising safety. 4

Cancer-Specific Dosing Regimens

Metastatic Colorectal Cancer

For first-line treatment, bevacizumab 5 mg/kg every 2 weeks is administered with bolus-IFL, or 10 mg/kg every 2 weeks with FOLFOX4. 1 Alternative regimens include:

• 5 mg/kg every 2 weeks or 7.5 mg/kg every 3 weeks with fluoropyrimidine-irinotecan- or fluoropyrimidine-oxaliplatin-based chemotherapy. 1
• With FOLFOXIRI: 5 mg/kg IV on day 1, repeated every 2 weeks. 2
• With capecitabine-based regimens: 7.5 mg/kg IV on day 1, repeated every 3 weeks. 2
• With trifluridine/tipiracil: 5 mg/kg IV on day 1, repeated every 14 days. 2

For second-line treatment after progression on a first-line bevacizumab-containing regimen, use 5 mg/kg every 2 weeks or 7.5 mg/kg every 3 weeks with fluoropyrimidine-based chemotherapy. 1 The efficacy of bevacizumab plus FOLFOX4 in second-line treatment demonstrated significantly longer overall survival and higher objective response rates compared to FOLFOX4 alone. 5

Non-Small Cell Lung Cancer

For first-line treatment of unresectable, locally advanced, recurrent or metastatic non-squamous NSCLC, administer 15 mg/kg every 3 weeks with carboplatin and paclitaxel. 1

Glioblastoma

For recurrent glioblastoma in adults, administer 10 mg/kg every 2 weeks. 1

Renal Cell Carcinoma

For metastatic renal cell carcinoma, administer 10 mg/kg every 2 weeks in combination with interferon alfa. 1

Cervical Cancer

For persistent, recurrent, or metastatic cervical cancer, administer 15 mg/kg every 3 weeks with paclitaxel and cisplatin, or paclitaxel and topotecan. 1

Ovarian Cancer

For platinum-resistant recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, administer:

• 10 mg/kg every 2 weeks with paclitaxel, pegylated liposomal doxorubicin, or topotecan given weekly. 1
• 15 mg/kg every 3 weeks with topotecan given every 3 weeks. 1

Hereditary Hemorrhagic Telangiectasia (HHT)

For moderate to severe HHT-related gastrointestinal bleeding, IV bevacizumab is given as induction at 5 mg/kg every 2 weeks for 4-6 doses, followed by maintenance dosing (5 mg/kg every 1-3 months is an option). 2 This regimen demonstrated a mean hemoglobin improvement of 3.2 g/dL, an 82% reduction in red cell transfusions, and a 70% reduction in iron infusions. 2

Critical Contraindications and Safety Monitoring

Absolute Contraindications

Discontinue bevacizumab immediately for:

• Gastrointestinal perforation, tracheoesophageal fistula, or grade 4 fistula. 1
• Grade 3-4 hemorrhage or recent hemoptysis. 1
• Severe arterial thromboembolic events. 1
• Grade 4 venous thromboembolic events. 1
• Hypertensive crisis or hypertensive encephalopathy. 1
• Posterior reversible encephalopathy syndrome (PRES). 1
• Nephrotic syndrome. 1
• Congestive heart failure. 1
• Wound healing complications of necrotizing fasciitis. 1

Surgical Considerations

Withhold bevacizumab for at least 28 days prior to elective surgery. 1 Do not administer bevacizumab for at least 28 days following major surgery and until adequate wound healing is established. 1 The safety of resuming bevacizumab after resolution of wound healing complications has not been established. 1

Required Monitoring

Monitor patients receiving bevacizumab for:

• Blood pressure at each visit; withhold if hypertension is not medically controlled and resume once controlled. 1
• Urine protein regularly; withhold until proteinuria is less than 2 grams. 1
• Signs of infection, delayed wound healing, and venous thromboembolism. 2
• Gastrointestinal perforation, bleeding, and thromboembolism, especially in patients with predisposing conditions. 6

Special Populations

Bevacizumab is contraindicated in patients with recent thrombosis; relative contraindications include atrial fibrillation or known thrombophilia. 2

Advise females of reproductive potential to use effective contraception during treatment and for 6 months after the last dose, as bevacizumab may cause fetal harm. 1 Advise females not to breastfeed during treatment. 1 Counsel females about the potential risk of ovarian failure. 1

Important Limitations

Bevacizumab is NOT indicated for adjuvant treatment of colon cancer. 1 The use of bevacizumab with irinotecan in the adjuvant setting should be avoided outside clinical trials. 7