Avastin

Avastin Side Effects, Warnings and mechanism
January 2007

WHAT IS AVASTIN? Avastin-first line treatment for patients with
metastatic colorectal cancer- is a genetically engineered version of a
mouse antibody that contains both human and mouse components.
(Antibodies are substances produced by the body's immune system
to fight foreign substances.) It is the first product to be approved
that works by preventing the formation of new blood vessels, i.e.
angiogenesis. Avastin was shown to extend patients' lives by about
five months when given intravenously as a combination treatment
along with standard chemotherapy drugs for colon cancer (the "Saltz
regimen" also known as IFL). IFL treatment includes ironotecan,
5-fluorouracil (5FU) and leucovorin. [3]

Is Avastin a cure for metastatic colorectal cancer? Avastin will not
cure metastatic colorectal cancer. In clinical trials there was longer
survival and tumor control in patients who received the combination
of IFL plus Avastin than among those who received IFL without
Avastin. Overall, patients given Avastin survived about five months
longer. In addition, the average time before tumors restarted
growing or new tumors appeared was four months longer than
patients who did not receive Avastin.

MECHANISM This new monoclonal antibody is believed to work by
targeting and inhibiting the function of a natural protein called
"vascular endothelial growth factor" (VEGF) that stimulates new
blood vessel formation. When VEGF is targeted and bound to
Avastin, it cannot stimulate the growth of blood vessels, thus
denying tumors blood, oxygen and other nutrients needed for
growth. Angiogenesis inhibitors such as Avastin have been studied,
first in the laboratory and then in patients, for three decades with
the hope they might prevent the growth of cancer. This is the first
such product that has been proven to delay tumor growth and more
importantly, significantly extend the lives of patients. [3]

Avastin is given intravenously (into a vein) every 14 days.

STATISTICS Colorectal cancer is the third most common cancer in
the U.S. and,is the second leading cause of cancer-related death.
Colorectal cancer is also one of the most commonly diagnosed
cancers in the U.S.; approximately 147,500 new cases were
diagnosed in 2003.

SAFETY AND EFFICACY The safety and efficacy of Avastin was
primarily shown in a randomized, double-blind clinical trial of more
than 800 patients with metastatic colorectal cancer designed to find
out whether Avastin extended the lives of patients. Overall, patients
given Avastin in combination with IFL survived about five months
longer and the average time before tumors started regrowing or new
tumors appeared was four months longer than patients receiving IFL
alone. The overall response rate to the treatment was 45%
compared to 35% for the control arm of the trial.

Special Warning(s) with Avastin: Avastin may cause
gastrointestinal perforation (holes in the stomach, intestines or
colon) requiring surgery to repair. Avastin may impair wound healing
or cause wounds to open up. Avastin should not be started for at
least 28 days following major surgery and full wound healing, and
should be stopped before a scheduled surgery.
Some patients with non-small cell lung cancer (for which Avastin is
not approved) treated with chemotherapy and Avastin had bleeding
from the lung tumor, spitting up of blood, leading to death. Avastin
may cause a severe increase in blood pressure so patients receiving
Avastin should have their blood pressure checked regularly. Avastin
may cause proteinuria (protein in the urine, a sign of kidney
damage). Avastin may cause congestive heart failure (failure of the
heart to pump blood well).

Avastin may cause severe infusion reactions such as trouble
breathing during the first or later doses.

SIDE-EFFECTS Serious, but uncommon, side-effects of Avastin
include formation of holes in the colon (gastrointestinal perforation)
generally requiring surgery and sometimes leading to
intra-abdominal infections, impaired wound healing, and bleeding
from the lungs or internally. Other, more common, side-effects are
high blood pressure, tiredness, blood clots, diarrhea, decreased
white blood cells (lowering immunity to diseases) headache, appetite
loss and mouth sores.

Future Indications of Avastin?, Combination of Avastin with other
drugs for other diseases. [December 2006]
The interim results of a late-stage trial showed that Avastin was
successful when used with chemotherapy in untreated breast cancer
which has spread to other parts of the body. [1]

Avastin combined with Tarceva provides promising activity in
recurrent non-small cell lung cancer. [2]

A Phase II study, which investigated the first-line treatment of
HER2-positive advanced breast cancer, showed that more than half
of the patients showed a complete or partial response to treatment
of a combination of Herceptin and Avastin. In addition, the study also
showed that the safety profile of this drug combo was acceptable
and lacked the typical chemotherapy-related side effects. [4]

This combination fights the tumor by blocking the HER2 protein that
gives the cancer instructions to grow and by starving the cancer of
its blood supply. This combination caused tumors to shrink in more
than half of the 37 patients participating in the study. [6]

An interim analysis suggested that a combination of Avastin and
Xeloda might offer clinical benefits to metastatic breast cancer
patients with no prior treatment history, boosting hopes Avastin
could gain U.S. approval for treating the disease.

Breast cancer is the most common cancer among women. About
212,920 women in the United States will be found to have invasive
breast cancer in 2006 and about 40,970 women will die from the
disease this year. [5]

Both Avastin and Herceptin were developed jointly with Genentech
Inc. and Roche. [5]

Xeloda (capecitabine)is the only FDA-approved oral chemotherapy for
both metastatic breast cancer and adjuvant and metastatic colorectal
cancer. Xeloda is transformed by thymidine phosphorylase to 5-FU, a
cytotoxic (cell-killing) drug in the body. Because many cancers have
higher levels of TP than does normal tissue, more 5-FU is delivered to
the tumor than to other tissue. [7]

Use of Avastin in Age-related macular degeneration (AMD)
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Reference
[1] Roche's Avastin Works in Third Type of Cancer, Reuters, April 15, 2005[2]
Herbst R et al, Phase I/II Trial Evaluating the Anti-Vascular Endothelial Growth
Factor Monclonal Antibody Bevacizumab in Combination With the
HER-1/Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Erlotinib for
Patients With Recurrent Non-Small-Cell Lung Cancer, Journal of Clinical
Oncology, 2005; 23:2544-2555. [3] FDA News P04-23 "FDA Approves First
Angiogenesis Inhibitor to Treat Colorectal Cancer", February 26, 2004 [4]
UPDATE 1-Roche 2-drug combo treats breast cancer in trial Reuters Mon Dec
18, 2006 [5] Xeloda(R) Plus Avastin(R) Combination May Produce Clinical
Benefit in Patients with Advanced Breast Cancer PRNewswise December 18,
2006 - 5:07 AM [6] Roche drug combo shows promise in breast cancer DOW
JONES NEWSWIRES December 18, 2006 [7] Xeloda(R) Plus Avastin(R)
Combination May Produce Clinical Benefit In Patients With Advanced Breast
Cancer Medical News Today 16 Dec 2006

What are monoclonal antibodies? Antibodies are substances produced by the
immune system in response to foreign substances such as bacteria, viruses or
toxins). They are the body's natural defense mechanism against infection, as
they help to destroy these foreign substances. Monoclonal antibodies are
antibodies produced in a laboratory to target a very specific part of the foreign
substance (antigen). Because of their precision, it is expected that they may
be more effective than standard chemotherapy with fewer side effects.

What are angiogenesis inhibitors? Angiogenesis inhibitors prevent the
formation of new blood vessels, including those that surround and supply
cancer cells, with the oxygen and nutrients they need to survive and grow. By
taking away the blood supply, angiogenesis inhibitors may reduce tumor cell
growth and cause cancerous tumors to grow more slowly or to become smaller.

For more detailed information about Avastin or other questions, ask your
health care provider or pharmacist. This article can be used only as a
reference. Publisher does not guarantee its accuracy. ALL RIGHTS RESERVED
2008 zhion. DO NOT COPY NOR TRANSFER THIS ARTICLE TO OTHER
WEBSITES NOR BLOGS.

Avastin Brand Name: Avastin, Active Ingredient:   bevacizumab Strength(s): 100mg/4mL, 400 mg/16 mL,
Dosage Form(s):   Injectable Company Name:    Genetech, Inc. Availability: Prescription only Date
Approved by the FDA:   February 26, 2004

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