Avastin (bevacizumab) is a recombinant humanized monoclonal antibody produced in Chinese Hamster Ovary cells. It binds to vascular endothelial growth factor (VEGF) to inhibit angiogenesis and slow tumor growth. Avastin is approved to treat various cancers including colorectal, lung, kidney, and cervical cancers. Common side effects include hypertension, hemorrhage, gastrointestinal perforation, and wound healing complications. It has major drug interactions with deferiprone, vectibix, and thalidomide that can increase toxicity. Avastin is marketed by Genentech in the US and internationally by Roche and Chugai.

1. AVASTIN
TEAM 3

2. INTRODUCTION
BRAND NAME: Avastin
GENERIC NAME: Bevacizumab
Bevacizumab is produced in a Chinese Hamster Ovary mammalian cell expression system in a nutrient
medium containing the antibiotic gentamicin and has a molecular weight of approximately 149 kDa.
Half life : Approximately 20 days (range 11-50 days)
Approved by FDA:
First approved in February 26th, 2004 for the treatment of Metastatic Colorectal Cancer.
From then on, 9 more approvals have taken place.
The latest approval was in December 6, 2016 in which Avastin along with chemotherapy can be used for
a specific type of advanced ovarian cancer. [1]
Route of administration: Intravenous(IV)
Avastin is a recombinant humanized monoclonal antibody (Mab) used for the treatment of various types of
cancer.

3. Marketed by: Genentech in U.S
Chugai In Japan and
Roche in the rest of the world
INDICATIONS
 Glioblastoma (GBM)
 Metastatic colorectal cancer (MCRC)
 Non-squamous non-small cell lung cancer(NSCLC)
 Metastatic renal cell carcinoma (mRCC)
 Persistent, recurrent, or metastatic
cervical cancer (CC)
 Platinum-resistant recurrent epithelial ovarian,
fallopian tube or primary peritoneal cancer (prOC)
As it shows high efficacy across a number of cancers,
Avastin is considered the “gold standard” of treatment
for indications such as CRC. It is used along with
chemotherapy. [2]

4. MECHANISMOFACTION

5. VEGF: Vascular endothelial growth factor, a polypeptide that is structurally related to platelet-
derived growth factor (PDGF).
While expressed in normal tissues, Tumors release the VEGF protein in physiologically relevant
levels, causing nearby blood vessels to sprout new vessels — a process called angiogenesis. New
blood vessels feed the growth of the tumor while providing a "highway" for tumor cells to spread
to other parts of the body
VEGF also acts as a mitogen for vascular endothelial (vessel lining) cells, stimulating these cells
to divide and multiply.
VEGF:
◦ Promotes tumor vessel Survival
◦ Promotes tumor vessel permeability and
◦ Stimulates tumor vessel growth

6. Avastin is a therapeutic antibody that specifically binds to the VEGF protein — a potent source
of angiogenesis.
Avastin may block the tumor's ability to communicate with nearby blood vessels, preventing its
ability to grow and in response retardation of metastatic tumor growth occurs.
Specifically, Bevacizumab binds VEGF and prevents the interaction of VEGF to its receptors
(Flt-1 and KDR) on the surface of endothelial cells.
Abnormalities on the tumor vessel cause plasma
leakage from the vessels, creating high pressure inside
the tumor that may restrict anti cancer drug delivery.
Avastin
◦ Promotes regression of existing vessels
◦ Normalization of growing vessels
◦ Preventing vessel growth
◦ Abnormalities contributing to vessel permeability are closed

7. Drug interaction
Drug interaction classification
 Major
 Moderate
 Minor
1 alcohol/food interaction with Avastin (bevacizumab)
A total of 24 drugs are known to interact with Avastin (bevacizumab)
 5 major drug interactions
 19 moderate drug interactions
There are 7 disease interactions with Avastin (bevacizumab) which include:
 Fistula Formation (major interaction)
 Bevacizumab may cause fatal fistula formation involving tracheoesophageal, bronchopleural, biliary, vaginal, renal and
bladder sites.
 Permanently discontinue bevacizumab in patients with tracheoesophageal fistula or any Grade 4 fistula.
 Gastrointestinal Perforation (major interaction)
 Inhibitors of vascular endothelial growth factor receptors (VEGFR) (including Avastin) may cause gastrointestinal perforation
and fistulae.
 Avoid use of these agents in patients with ovarian cancer who have evidence of recto-sigmoid and permanently discontinue
these agents in patients with gastrointestinal perforation.
 Bleeding
 Hypertension
 Posterior Reversible Encephalopathy Syndrome
 Proteinuria
 Thromboembolic Disorders

8. Drug Indication Adverse effects due to
interaction
Signs and symptoms of drug interaction
Deferiprone Transfusional iron overload due
to thalassemia syndromes
Lower white blood cell count
Affect bone marrow function
Fever, chills, diarrhea, sore throat, muscle aches,
shortness of breath, blood in phlegm, weight loss, red
or inflamed skin, body sores, and pain or burning
during urination.
Vectibix Metastatic colorectal cancer
(chemotherapy drug)
Increased Mortality
Toxicity
Rash, dermatitis, diarrhea, dehydration, electrolyte
imbalances, mouth ulcers or sores, and pulmonary
embolism (blood clots in the lung)
Quadramet Relief of bone pain in patients
with multiple painful
osteoblastic skeletal
metastases
Affect bone marrow function
Lowers numbers of different
types of blood cells
develop anemia, bleeding
problems
 infections due to low blood cell
counts.
Develop paleness, fatigue, dizziness, fainting, unusual
bruising or bleeding, fever, chills, diarrhea, sore throat,
muscle aches, shortness of breath, blood in phlegm,
weight loss, red or inflamed skin, body sores, and pain
or burning during urination.
Sutent Gastrointestinal stromal tumor rare type of anemia caused by
blood clots forming in small blood
vessels
High blood pressure, diarrhea, loss of appetite,
dehydration, mouth sores, bleeding complications, and
infection.
Thalidomide Erythema nodosum leprosum
(ENL).
dangerous blood clots Chest pain, shortness of breath, difficulty breathing,
coughing up blood, sudden loss of vision, and/or pain,
redness or swelling in an arm or leg.

9. Newsreport
Avastin used to treat age-related macular degeneration, shows higher risk of glaucoma.
Avastin ("off-label" indication) used to treat an eye disease in premature infants, shows serious disabilities
such as cerebral palsy and hearing loss.
(https://www.drugs.com/answers/support-group/avastin/news/)
Rare adverse event - 65-year-old breast cancer patient was given a combination of capecitabine and
bevacizumab experienced hand-foot syndrome (i.e. loss of fingerprints).
(https://www.drugs.com/news/chemo-breast-cancer-erases-woman-s-fingerprints-56428.html)
Tecentriq-avastin combo shows promise in untreated advanced renal cell cancers.
(https://immuno-oncologynews.com/2017/02/21/tecentriq-avastin-combo-shows-promise-untreated-advanced-
renal-cell-cancers/)
Opdivo-avastin combo holds promise as metastatic renal cell carcinoma therapy.
(https://immuno-oncologynews.com/2017/04/04/opdivo-avastin-combo-metastatic-renal-cell/)
Roche’s Genentech filed a complaint over Amgen in Delaware District court on Feb 2017 infringing
Genentech patent.
(http://www.raps.org/Regulatory-Focus/News/2017/02/20/26890/Genentech-Files-Complaint-Over-
Amgen%E2%80%99s-Development-of-Avastin-Biosimilar/)

10. Sideeffects
Bevacizumab used for the treatment of angiogenesis.
Side effect- hypertension which may lead to posterior reversible encephalopathy syndrome, hemorrhage
and nasal septum perforation.
Avastin injection- for the treatment of macular degeneration
Side effects- increased risk of heart attack or stroke in diabetic patients.
Known risks –
 Retinal detachment
 Severe eye infection
 Bleeding
 Increased pressure in the eye
 Damage to the cornea or retina
 Cataract formation

11.  Bevacizumab for the treatment of breast cancer- a high degree of expression of VEGF mRNA and
protein in invasive ductal carcinoma, metastatic ductal carcinoma and comedo type ductal carcinoma
in situ , with relatively lower expression in lobular carcinoma.
Side effect- congestive heart failure
 Bevacizumab for colorectal cancer- it prolongs the survival when added to intravenous 5- fluorouracil
based chemotherapy in first line metastatic colorectal cancer treatment
Side effects – wound healing complications increased in patients who had undergone major surgery. (5)
Other side effects include – holes in the colon , internal bleeding
 Avastin for lung cancer- Avastin in combination with carboptalin and paclitaxel can be given to the
patients of advanced Non Squamous Non Small lung cancer (NSCLC) who have not received
chemotherapy for their advanced disease.
Side effects-
◦ GI perforation
◦ Wounds that don’t heal
◦ Serious bleeding

12. References
1. https://www.drugs.com/history/avastin.html
2. http://pdl.com/technology-products/commercialized-products/avastin-bevacizumab/
3. https://igeahub.com/2017/01/27/best-selling-oncology-drugs-2016/
4. https://www.avastin-hcp.com/about-avastin/dosing.html
5. https://www.avastin-hcp.com/about-avastin/proposed-moa.html
6. http://www.rxlist.com/script/main/art.asp?articlekey=5969
7. https://www.drugs.com/drug-interactions/bevacizumab,avastin.html
8. https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021825lbl.pdf
9. http://pi.amgen.com/~/media/amgen/repositorysites/pi-amgen-com/vectibix/vectibix_pi.ashx
10. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000150/WC500041751.pdf
11. https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/021938s13s17s18lbl.pdf
12. https://www.accessdata.fda.gov/drugsatfda_docs/label/1998/20785lbl.pdf
13. http://ascopubs.org/doi/abs/10.1200/JCO.2010.31.9129
14. https://link.springer.com/article/10.1007/s10549-010-0866-3
15. http://onlinelibrary.wiley.com/doi/10.1002/jso.20301/full

13. THANK YOU!