AVASTN®

AVASTIN®(Bevacizumab)
Lobna AL Juffali.

Overview
Avastin is the first angiogenesis inhibitor approved in the U.S. FDA approved 2/26/04. AVASTIN®(Bevacizumab) is a recombinant humanized monoclonal IgG1 antibody. Has shown promising preclinical and clinical activity against metastatic colorectal cancer, particularly in combination with chemotherapy.

Bevacizumab (beh va KIZ you mab) is produced in a Chinese Hamster Ovary mammalian cell expression system in a nutrient medium containing the antibiotic gentamicn and has a molecular weight of approximately 149 kiloDaltons.

Mechanism of action
Bevacizumab binds to (Flt-1 and KDR)
receptors on the surface of endothelial
cells. The interaction leads to Inhibition
of the biological activity of vascular
endothelial growth factor (VEGF). The
VEGF receptor is over expressed on the
endothelium of tumor vasculature and is
rarely expressed on the endothelium of
normal tissue vessels. Binding and
inhibiting VEGF interferes with a tumor
cell’s ability to make new blood vessels.
Inhibiting blood vessel formation
impairs the tumor cell’s ability to
survive due to lack of oxygen and
nutrients and build up of waste products.

Place in Therapy:
Bevacizumab is not itself directly
cytotoxic but is used in conjunction with
cytotoxic agents; in combination with a
5-fluorouracil–based
chemotherapy,
which is approved for first line treatment
of patients with metastatic carcinoma of
the colon and rectum.
Ongoing
investigations
include
treatment of metastatic renal cell cancer,

breast cancer, non-small cell lung
cancer, prostate cancer, and age-related
macular degeneration. Some potentially
serious adverse effects of bevacizumab
(eg, hypertension, thrombosis, bleeding)
may limit its clinical use.
Bevacizumab as a Single Agent
The efficacy of Bevacizumab as a single
agent in colorectal cancer has not been
established.

Pharmacokinetics
The pharmacokinetic profile of
Bevacizumab was assessed using an
assay that measures total serum
Bevacizumab concentrations (i.e., the
assay did not distinguish between free
drug and the drug bound to VEGF
ligand). Based on a population
pharmacokinetic analysis of 491 patients
who received 1 to 20 mg/kg of
Bevacizumab weekly, every 2 weeks, or
every 3weeks, followed a liner kinetic.
The estimated half-life of Bevacizumab

Lobna AL Juffali©

AVASTN®
was approximately 20 days (range 11-50
days)....

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