What is the recommended use and dosage of Bevacizumab (bevacizumab) in cancer treatment?

Recommended Use and Dosage of Bevacizumab in Cancer Treatment

Bevacizumab is indicated for multiple cancer types with specific dosages ranging from 5-15 mg/kg depending on cancer type and combination regimen, with mandatory intervals of at least 6 weeks between bevacizumab administration and elective surgery to prevent wound healing complications.

FDA-Approved Indications and Dosages

Metastatic Colorectal Cancer (mCRC)

• First-line or second-line treatment in combination with fluorouracil-based chemotherapy 1
• Dosage options:
  • 5 mg/kg intravenously every 2 weeks with bolus-IFL 1
  • 10 mg/kg intravenously every 2 weeks with FOLFOX4 1
  • 5 mg/kg intravenously every 2 weeks or 7.5 mg/kg intravenously every 3 weeks with fluoropyrimidine-irinotecan or fluoropyrimidine-oxaliplatin regimens for patients who progressed on first-line bevacizumab-containing regimen 1
• Not indicated for adjuvant treatment of colon cancer 1

Non-Small Cell Lung Cancer (NSCLC)

• First-line treatment for unresectable, locally advanced, recurrent or metastatic non-squamous NSCLC in combination with carboplatin and paclitaxel 1
• Dosage: 15 mg/kg intravenously every 3 weeks 1
• Restricted to patients with non-squamous histology due to risk of hemoptysis in squamous cell carcinoma 2

Other FDA-Approved Indications

• Recurrent glioblastoma: 10 mg/kg intravenously every 2 weeks 1
• Metastatic renal cell carcinoma: 10 mg/kg intravenously every 2 weeks with interferon alfa 1
• Persistent, recurrent, or metastatic cervical cancer: 15 mg/kg intravenously every 3 weeks with chemotherapy 1
• Platinum-resistant recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer: 10 mg/kg intravenously every 2 weeks or 15 mg/kg intravenously every 3 weeks depending on chemotherapy partner 1

Patient Selection and Contraindications

Patient Selection Criteria

• For mCRC: Appropriate for first-line or second-line treatment in combination with chemotherapy 2
• For NSCLC: Only for non-squamous histology with good performance status (ECOG 0-1) 2

Contraindications and Precautions

• Avoid in squamous cell NSCLC due to risk of severe hemoptysis 2
• Use with caution in patients with:
  • Recent history of hemoptysis (≥2.5 mL) 1
  • Brain metastases (though recent data suggest it may be safe in treated, stable brain metastases) 2
  • Risk of wound healing complications 2
  • Hypertension (requires monitoring and management) 1, 3

Surgical Considerations and Timing

• Withhold bevacizumab for at least 28 days prior to elective surgery 1
• Maintain an interval of at least 6 weeks (corresponding to 2 half-lives) between last bevacizumab dose and any elective surgery 2
• Delay reinitiation of bevacizumab for at least 6-8 weeks postoperatively 2
• Wound healing complications are more common if surgery is performed while on bevacizumab (13% vs 3.4% with chemotherapy alone) 2

Common Adverse Events and Management

• Hypertension: Monitor blood pressure regularly; may require antihypertensive therapy 1, 3
• Proteinuria: Monitor urine protein; withhold for proteinuria ≥2 g/24 hours 1
• Hemorrhage: Discontinue for severe bleeding (Grade 3-4) 1
• Arterial thromboembolic events: Discontinue for severe events 1
• Gastrointestinal perforations: Discontinue permanently 1
• Wound healing complications: Withhold until adequate healing 1, 2
• Infusion reactions: May require rate adjustment or discontinuation 1

Clinical Benefits and Limitations

Benefits

• In mCRC: Modest improvement in overall survival when added to chemotherapy (HR 0.85,95% CI 0.78-0.93) 2
• More effective with irinotecan-based regimens than with oxaliplatin-based regimens in mCRC 2
• In non-squamous NSCLC: Improved overall survival when added to carboplatin/paclitaxel (12.3 vs 10.3 months, HR 0.79) 2

Limitations

• Not recommended for perioperative treatment of resectable metastatic disease 2
• No evidence of efficacy in adjuvant setting for stage II and III colon cancer 2
• No evidence of "rebound effect" (accelerated recurrence) after discontinuation 2
• Should not be combined with EGFR inhibitors (cetuximab, panitumumab) in mCRC 2

Important Clinical Considerations

• Half-life is approximately 20 days 4
• Steady state is reached in approximately 100 days 4
• No dose adjustments required based on age, sex, or renal function 4
• Combination therapy involving both anti-EGFR and anti-VEGF agents is not recommended 2
• In NSCLC, bevacizumab should be continued until disease progression if tolerated 2

By following these evidence-based recommendations for bevacizumab use, clinicians can optimize treatment outcomes while minimizing risks for patients with various cancer types.