Kidney Cancer: Avastin Dosing and Usage

Metastatic renal cell carcinoma (mRCC)
Avastin, in combination with interferon alfa, is indicated for the treatment of metastatic renal cell carcinoma.

Avastin dosing in metastatic renal cell carcinoma

In mRCC, Avastin is administered as a solution for intravenous (IV) infusion at the following dose and schedule[1]:

Tumor type Combination regimen Avastin dose Avastin schedule
mRCC* IFN 10 mg/kg IV Every 2 weeks

IFN=interferon alfa; MIU=million international units.
*10 mg/kg IV dose evaluated in mRCC in combination with IFN. AVOREN protocol allowed for IFN dose escalation (attaining a dose of 9 MIU within the first 2 weeks), reduction, or discontinuation. IFN was discontinued after 52 weeks or earlier.[3,14]  

  • 10 mg/kg IV every 2 weeks is the only dose of Avastin proven to increase progression-free survival and objective response rate in mRCC[1]

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 renal cell carcinoma

Patients were treated until disease progression or unacceptable toxicity.

Clinical benefits have been observed with Avastin given until disease progression or unacceptable toxicity[1,14]

  • Avastin was continued until disease progression or unacceptable toxicity in AVOREN, even if IFN was reduced or discontinued[1,14]

q2w=every 2 weeks.
An initial dose of less than 9 MIU was permitted as long as the recommended dose was reached within the first 2 weeks of treatment.[14]

  • IFN was discontinued after a maximum of 52 weeks, but Avastin was continued until disease progression or unacceptable toxicity[1,14]
  • In AVOREN, 31% (105/337) of patients in the Avastin plus IFN arm discontinued IFN after 52 weeks and received Avastin alone thereafter[1,14]
    49% (165/337) of patients in the Avastin plus IFN group received IFN dose reduction and 21% (71/337) discontinued IFN prior to 52 weeks[3]
  • Avastin was not dose reduced but was discontinued in 21% (71/337) of patients vs 6% (17/304) discontinuation of placebo in the placebo plus IFN group[3,14]

AVOREN protocol allowed for IFN dose escalation, reduction, or discontinuation[3,14]

An initial dose of less than 9 MIU was permitted as long as the recommended dose was reached within the first 2 weeks of treatment.[14]
After IFN held, per protocol.

IFN was discontinued in any patient with[3,14]

  • Grade 4 toxicity
  • Grade 3 toxicity that did not resolve to grade ≤1 within 4 weeks while IFN was held
  • Grade 3 toxicity after 2 dose modifications
  • 52 weeks of treatment

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

Inclusion of bevacizumab in National Comprehensive Cancer Network® (NCCN®) recommendations[15]

  • NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Kidney Cancer include bevacizumab plus IFN as a Category 1 first-line treatment option for patients with predominantly clear cell histology