What is the recommended infusion protocol for bevacizumab (bevacizumab) in an adult patient with metastatic colorectal cancer receiving maintenance therapy?

Bevacizumab Infusion Protocol

Bevacizumab can be safely infused at a rate of 0.5 mg/kg/min, which translates to 5 mg/kg over 10 minutes or 7.5 mg/kg over 15 minutes, eliminating the need for the traditional 90-60-30 minute infusion sequence. 1

Standard Dosing for Metastatic Colorectal Cancer

First-Line Therapy

• Bevacizumab 5 mg/kg IV every 2 weeks when combined with FOLFIRI (irinotecan-based regimen) 1, 2
• Bevacizumab 7.5 mg/kg IV every 3 weeks when combined with CapeOX or mXELIRI (oxaliplatin-based regimens) 1
• Continue until disease progression or unacceptable toxicity 2, 3

Second-Line Therapy

• Bevacizumab 10 mg/kg IV every 2 weeks when combined with FOLFOX4 after progression on irinotecan-based therapy 3, 4

Rapid Infusion Protocol

The accelerated infusion rate of 0.5 mg/kg/min is now the standard of care and should be used from the first dose. 1

Practical Implementation

• 5 mg/kg dose: Infuse over 10 minutes 1, 5, 6, 7
• 7.5 mg/kg dose: Infuse over 15 minutes 1, 5, 6
• 10 mg/kg dose: Infuse over 20 minutes (extrapolated from the 0.5 mg/kg/min rate) 3, 4

Evidence Supporting Rapid Infusion

The traditional 90-60-30 minute infusion sequence was based on theoretical concerns about hypersensitivity reactions (HSRs) due to the <10% murine protein content. However, multiple studies have demonstrated that bevacizumab can be safely administered much faster:

• A prospective study of 370 patients receiving 2,311 doses at 5 mg/kg over 10 minutes found only 6 patients (1.6%) experienced minor, nonserious HSRs 7
• A study of 43 patients receiving 527 doses over 10 minutes reported only 2 grade 2 HSRs (both at 7.5 mg/kg), easily resolved with symptomatic treatment 6
• A prospective multicenter study using 30-minute initial infusion followed by 0.5 mg/kg/min reported zero HSRs in 23 patients 5

Timing Relative to Chemotherapy

• Administer bevacizumab on day 1 of each chemotherapy cycle, prior to chemotherapy infusion 1, 2
• For FOLFIRI regimens: Give bevacizumab first, then proceed with irinotecan, leucovorin, and 5-FU 1, 2
• For CapeOX regimens: Give bevacizumab first, then oxaliplatin, followed by oral capecitabine 1

Critical Safety Considerations

Absolute Contraindications to Infusion

• Do not administer within 28 days of major surgery due to wound-healing complications 3, 4
• Hold for gastrointestinal perforation, fistula formation, or serious bleeding 3, 4
• Discontinue permanently for arterial thromboembolic events (stroke, MI, TIA) 3, 4

Monitoring During Infusion

While HSRs are rare with bevacizumab (unlike cetuximab or panitumumab), monitor for:

• Hypotension, hypertension, or chest discomfort during the first 2-3 infusions 5, 6, 7
• If HSR occurs, stop infusion immediately and treat symptomatically; most reactions are grade 1-2 and resolve quickly 6, 7

Common Pitfalls to Avoid

Do not use the outdated 90-60-30 minute infusion sequence. This wastes nursing time and infusion chair resources without improving safety. 1, 7

Do not combine bevacizumab with anti-EGFR antibodies (cetuximab or panitumumab) plus chemotherapy—this triple combination increases toxicity without improving efficacy. 1

Do not continue bevacizumab beyond progression in second-line therapy. Unlike maintenance strategies in first-line, there is insufficient data to support bevacizumab continuation after progression on a bevacizumab-containing regimen. 1

Do not administer bevacizumab to patients ≥65 years without careful consideration of arterial thromboembolic risk, as this population has increased risk of stroke and other arterial events. 1, 8

Maintenance Therapy Considerations

• After initial combination therapy, bevacizumab can be continued with fluoropyrimidine alone (5-FU or capecitabine) as maintenance therapy 1
• Bevacizumab 5 mg/kg IV weekly when combined with single-agent capecitabine 1
• Maximum treatment duration in clinical trials was 96 weeks, though treatment typically continues until progression 3