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Recurrent Glioblastoma: Avastin Dosing and Usage

Recurrent glioblastoma (GBM)
Avastin is indicated for the treatment of recurrent glioblastoma in adults.

Avastin dosing in recurrent glioblastoma

In recurrent glioblastoma (rGBM), Avastin is administered as a solution for intravenous (IV) infusion at the following dosage[1]

Tumor type Avastin dose Avastin schedule
rGBM* 10 mg/kg IV Every 2 weeks

*10 mg/kg dose evaluated for rGBM.

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 rGBM

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

Important treatment considerations—dose modifications[1]

No dose reductions for Avastin are recommended.

Dose Modifications for Adverse Reactions 

Adverse reaction Severity Dosage 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 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
  • 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 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
Select NCCN Guidelines
Inclusion of bevacizumab in National Comprehensive Cancer Network® (NCCN®) recommendations
Bevacizumab as a single agent or in combination with chemotherapy is included in NCCN recommendations for recurrent glioblastoma.[27]

The NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. 

Indication

Recurrent glioblastoma (GBM)

Avastin is indicated for the treatment of recurrent glioblastoma in adults.

Serious adverse reactions (Warnings and Precautions)

  • Serious and sometimes fatal adverse reactions with increased incidence in the Avastin-treated arm vs chemotherapy arm included:
    • Gastrointestinal (GI) perforation ranged from 0.3% to 3% of patients across clinical studies
    • Non-GI fistulae (<1% to 1.8%, highest in patients with cervical cancer)
    • Arterial thromboembolic events (Grade ≥3, 5%, highest in patients with GBM)
    • The incidence of wound healing and surgical complications, including serious and fatal complications, is increased in Avastin-treated patients
    • Hemorrhage (Grade 3–5) ranged from 0.4% to 7% of patients across clinical studies
    • Renal injury and proteinuria
      • Grade 3–4 proteinuria ranged from 0.7% to 7% in clinical studies
      • Nephrotic syndrome (<1%)
  • Additional serious adverse reactions with increased incidence in the Avastin-treated arm vs chemotherapy arm included:
    • Venous thromboembolism (Grade ≥3, 11% seen in GOG-0240)
    • Hypertension (Grade 3–4, 5%–18%)
    • Posterior reversible encephalopathy syndrome (PRES) (<0.5%)
    • Congestive heart failure (CHF): Grade ≥3 left ventricular dysfunction (1%)
  • Infusion-related reactions with the first dose of Avastin occurred in <3% of patients, and severe reactions occurred in 0.4% of patients
  • Avoid use in patients with ovarian cancer who have evidence of recto-sigmoid involvement by pelvic examination or bowel involvement on CT scan or clinical symptoms of bowel obstruction
  • Inform females of reproductive potential of the risk of ovarian failure prior to initiating treatment with Avastin
  • An evaluation for the presence of varices is recommended within 6 months of initiation of Avastin in patients with HCC

Pregnancy warning

  • Based on the mechanism of action and animal studies, Avastin may cause fetal harm
  • Advise female patients that Avastin may cause fetal harm, and to inform their healthcare provider of a known or suspected pregnancy
  • Advise females of reproductive potential to use effective contraception during treatment with Avastin and for 6 months after the last dose of Avastin
  • Advise nursing women not to breastfeed during treatment with Avastin and for 6 months following their last dose of treatment
  • Avastin may impair fertility

Most common adverse reactions

  • Across studies, the most common adverse reactions observed in Avastin patients at a rate >10% were:
    • Epistaxis
    • Headache
    • Hypertension
    • Rhinitis
    • Proteinuria
    • Taste alteration
    • Dry skin
    • Hemorrhage
    • Lacrimation disorder
    • Back pain
    • Exfoliative dermatitis

  • Across all studies, Avastin was discontinued in 8% to 22% of patients because of adverse reactions

Indication-specific adverse reactions

  • In rGBM Study EORTC 26101, the incidence of Grade 3–4 VTE was 5% in patients receiving Avastin with chemotherapy compared to 2% in patients receiving chemotherapy alone. In this study, 22% of patients discontinued treatment in the Avastin with lomustine arm due to adverse reactions compared with 10% of patients in the lomustine arm. In patients receiving Avastin with lomustine, the adverse reaction profile was similar to that observed in other approved indications

You may report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch.
You may also report side effects to Genentech at (888) 835-2555.

Please see full Prescribing Information for additional important safety information.

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