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:
|Tumor type||Combination regimen||Avastin dose||Avastin schedule|
|mRCC*||IFN||10 mg/kg IV||Every 2 weeks|
IFN=interferon alfa; MIU=million international
*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
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.
- 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
- 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
- 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.
‡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||Dosage modification|
|Gastrointestinal perforation and fistulae|| ||Discontinue Avastin|
|Wound healing complications||Any||Withhold Avastin until adequate wound healing. The safety of resumption of Avastin after resolution of wound healing complications has not been established.|
|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|| ||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 greater than or equal to 2 grams per 24 hours in absence of nephrotic syndrome||Withhold Avastin until proteinuria less than 2 grams per 24 hours|
|Infusion-related reaction||Severe||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|