Colorectal Cancer: Avastin Dosing and Usage

Metastatic colorectal cancer (MCRC)
Avastin, in combination with intravenous 5‑fluorouracil-based chemotherapy, is indicated for the first‑ or second‑line treatment of patients with metastatic colorectal cancer.

Avastin, in combination with fluoropyrimidine-irinotecan- or fluoropyrimidine-oxaliplatin-based chemotherapy, is indicated for the second-line treatment of patients with metastatic colorectal cancer who have progressed on a first-line Avastin-containing regimen.

Limitation of Use: Avastin is not indicated for adjuvant treatment of colon cancer.

Avastin dosing in metastatic colorectal cancer

Avastin has approved dosing for use with various chemotherapy regimens used in patients with MCRC[1]

In MCRC, Avastin is administered as a solution for intravenous (IV) infusion at the following doses and schedules[1]:

Tumor type Chemotherapy   Avastin dose Avastin schedule
MCRC IFL* (first-line Study 2107) 5 mg/kg IV Every 2 weeks
FOLFOX4 (second-line Study E3200) 10 mg/kg IV Every 2 weeks
Fluoropyrimidine-based chemotherapy in patients who had progressed on a first-line Avastin-containing regimen (first- through second-line TML§ study) 5 mg/kg IV Every 2 weeks
7.5 mg/kg IV Every 3 weeks

*5 mg/kg IV dose evaluated in first-line MCRC in combination with 5-fluorouracil (5-FU)/leucovorin (LV)/irinotecan (IFL).
10 mg/kg IV dose evaluated in second-line, Avastin-naive MCRC patients in combination with 5-FU/LV/oxaliplatin (FOLFOX4).
5 mg/kg IV every 2 weeks and 7.5 mg/kg IV every 3 weeks doses evaluated, in combination with fluoropyrimidine and either irinotecan- or oxaliplatin-containing chemotherapy, in MCRC patients who had progressed on a first-line Avastin-containing regimen.
§TML=Treatment through Multiple Lines (first and second line).

Boxed WARNINGS

  • Gastrointestinal (GI) perforation
    • Discontinue for gastrointestinal perforation
  • Surgery and wound healing complications
    • Withhold Avastin for at least 28 days prior to elective surgery. Do not administer Avastin for at least 28 days after surgery and until the wound is fully healed
    • Discontinue in patients with wound healing complications requiring medical intervention
  • Hemorrhage
    • Severe or fatal hemorrhage have occurred
    • Do not administer Avastin to patients with serious hemorrhage or recent history of hemoptysis
    • Discontinue for Grade 3-4 hemorrhage

Important treatment considerations—Women of childbearing potential

  • Avastin increases the risk of ovarian failure and may impair fertility. Inform females of reproductive potential of the risk of ovarian failure prior to the first dose of Avastin
  • Long-term effects of Avastin exposure on fertility are unknown
  • Patients should also use effective contraception during treatment and for 6 months following the last dose of Avastin
  • Nursing mothers should not breastfeed during treatment and for 6 months following their last dose of treatment
     

Duration of Avastin in metastatic colorectal cancer

For proven survival benefits in first and second line—start with Avastin, then continue beyond first progression[1,4]

||Oxaliplatin→irinotecan or irinotecan→oxaliplatin.

The FDA-approved Prescribing Information addresses the duration of Avastin treatment[1]:
Patients should continue treatment until disease progression or unacceptable toxicity.

Indications

Metastatic colorectal cancer (MCRC)
Avastin, in combination with intravenous 5‑fluorouracil-based chemotherapy, is indicated for the first‑ or second‑line treatment of patients with metastatic colorectal cancer.

Avastin, in combination with fluoropyrimidine-irinotecan- or fluoropyrimidine-oxaliplatin-based chemotherapy, is indicated for the second-line treatment of patients with metastatic colorectal cancer who have progressed on a first-line Avastin-containing regimen.

Limitation of Use: Avastin is not indicated for adjuvant treatment of colon cancer.

Important treatment considerations—dose modifications

No dose reductions for Avastin are recommended.

Dose modifications for adverse reactions

Adverse reaction Severity   Dose modification
Gastrointestinal perforation and fistulae
  • Gastrointestinal perforation, any grade
  • Tracheoesophageal fistula, any grade
  • Fistula, grade 4
  • Fistula formation involving any internal organ
Discontinue Avastin
Wound healing complications
  • Wound healing complications requiring medical intervention
  • Necrotizing fasciitis
Discontinue Avastin
Hemorrhage Grade 3 or 4 Discontinue Avastin
Recent history of hemoptysis of ½ teaspoon (2.5 mL) or more Withhold Avastin
Thromboembolic events
  • Arterial thromboembolism, severe
  • Venous thromboembolism, grade 4
Discontinue Avastin
Hypertension
  • Hypertensive crisis
  • Hypertensive encephalopathy
Discontinue Avastin
Hypertension, severe Withhold Avastin if not controlled with medical management; resume once controlled
Posterior reversible encephalopathy syndrome (PRES) Any Discontinue Avastin
Renal toxicity and proteinuria Nephrotic syndrome Discontinue Avastin
Proteinuria ≥2 g/24 h in absence of nephrotic syndrome Withhold Avastin until proteinuria <2 g/24 h
Infusion reaction Severe infusion reaction Discontinue Avastin
Clinically significant Interrupt infusion; resume at a decreased rate of infusion after symptoms resolve
Mild, clinically insignificant Decrease infusion rate
Congestive heart failure Any Discontinue Avastin

Boxed WARNINGS

  • Gastrointestinal (GI) perforation
    • Discontinue for gastrointestinal perforation
  • Surgery and wound healing complications
    • Withhold Avastin for at least 28 days prior to elective surgery. Do not administer Avastin for at least 28 days after surgery and until the wound is fully healed
    • Discontinue in patients with wound healing complications requiring medical intervention
  • Hemorrhage
    • Severe or fatal hemorrhage have occurred
    • Do not administer Avastin to patients with serious hemorrhage or recent history of hemoptysis
    • Discontinue for Grade 3-4 hemorrhage

Bevacizumab is the only FDA-approved biologic cancer therapy that is included as an option in National Comprehensive Cancer Network® (NCCN®) recommendations when continued through first- and second-line MCRC[7]

First-line MCRC   Second-line MCRC
Bevacizumab plus
• FOLFIRI
• FOLFOX
• IV 5-FU/LV
• FOLFOXIRI
Bevacizumab plus
• FOLFIRI
• FOLFOX

 

Bevacizumab continued through first- and second-line MCRC
Bevacizumab plus
• FOLFIRI
• FOLFOX
• CapeOX

FOLFIRI=5-FU/LV/irinotecan; FOLFOX=5-FU/LV/oxaliplatin; FOLFOXIRI=5-FU/LV/oxaliplatin/irinotecan; CapeOX=capecitabine/oxaliplatin.

Boxed WARNINGS

  • Gastrointestinal (GI) perforation
    • Discontinue for gastrointestinal perforation
  • Surgery and wound healing complications
    • Withhold Avastin for at least 28 days prior to elective surgery. Do not administer Avastin for at least 28 days after surgery and until the wound is fully healed
    • Discontinue in patients with wound healing complications requiring medical intervention
  • Hemorrhage
    • Severe or fatal hemorrhage have occurred
    • Do not administer Avastin to patients with serious hemorrhage or recent history of hemoptysis
    • Discontinue for Grade 3-4 hemorrhage