avastin side effects, avastin breast cancer, avastin fda, avastin ovarian cancer, avastin
lung cancer, avastin for brain tumors
November 18 2011
Avastin 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.

The following serious avastin side effects are summarized from its product label:

* Gastrointestinal Perforations
* Surgery and Wound Healing Complications
* Hemorrhage
* Non‑Gastrointestinal Fistula Formation
* Arterial Thromboembolic Events
* Hypertensive Crisis
* Reversible Posterior Leukoencephalopathy Syndrome
* Proteinuria

The most common side effects observed in Avastin patients at a rate > 10% and at least twice the control arm
rate, are epistaxis, headache, hypertension, rhinitis, proteinuria, taste alteration, dry skin, rectal hemorrhage,
lacrimation disorder, back pain and exfoliative dermatitis.

Across all studies, Avastin was discontinued in 8.4 to 21% of patients because of adverse avastin side effects.
For details and less common side effects, plesae, review its product label or consult with your medical doctor.

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.
Related Article: Avastin macular degeneration (AMD)
Genetech, Inc. Availability:  Prescription only  Date Approved by the FDA:   February 26, 2004

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. 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]

November 18, 2011

The government delivered a blow to some desperate patients on November 18, 2011 as it ruled the blockbuster
drug Avastin should no longer be used to treat advanced breast cancer. [BB1]

Avastin breast cancer
In 2008, against the recommendation of its advisors, the FDA approved Avastin for breast cancer through an
accelerated approval process, based on a study showing the drug stalled cancer growth by 5.5 months. But, in
four trials, they found no significant improvement of death rates and even no reduction has been experienced in
the progression of the disease. [CBS News.com, WebMD Health News, June 29, 2011] Consequently, the public
hearing on the Center for Drug Evaluation and Research’s  December 2010 proposal to withdraw approval of
the metastatic breast cancer indication for Avastin is now complete.  Following the closing of the docket, the
Center for Drug Evaluation and Research will await Commissioner Hamburg’s final decision on Avastin’s use for
metastatic breast cancer.  The Commissioner’s decision related to breast cancer will not affect Avastin’s
approved indications for use in colon cancer, lung cancer, kidney cancer, and brain cancer.  That is, regardless
of the final decision on metastatic breast cancer approval, Avastin will remain on the market. [Avastatin FDA
update; FDA website, 6/29/

However, according to CBS news, stripping the breast cancer indication for Avastin would not prevent doctors
from using it. But without FDA approval, insurers may refuse to pay Avastin's $8,000-a-month price tag. An
estimated 17,000 women now use the medicine for breast cancer. [CBS News.com, WebMD Health News, June
29, 2011] Anyway, Medicare will keep paying for the drug Avastin to fight
breast cancer even though an FDA
panel has recommended that Avastin no longer be sold as a treatment for breast cancer. [WebMD Health News,
July 1,

Reports 2-5 years ago
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] 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. Both Avastin and
Herceptin were developed jointly with Genentech Inc. and Roche. [5]

Avastin ovarian cancer (tumors)
Cancer of the ovary includes cancers that arise from celomic epithelium that invests the ovary during
development to form a capsule, germ cell cancers, cancers arising from the ovarian stroma, and a variety of
rare cancers of the ovary. Avastin currently, is not approved for ovarian cancer.  [Tate Thigpen, Design in
Clinical Trials of Ovarian Carcinoma, FDA website, August 2011] However, Avastin's active ingredient -
Bevacizumab was described to be effective in recurrent ovarian cancer in recent phase I and phase II trials. [A3]

In fact, according to the product label, Avastin may impair fertility. Female cynomolgus monkeys treated with 0.4
to 20 times the recommended human dose of Avastin exhibited arrested follicular development or absent
corpora lutea as well as dose‑related decreases in ovarian and uterine weights, endometrial proliferation, and
the number of menstrual cycles. However, Brown JV 3rd and co-workers at Hoag Cancer Center, Newport
Beach, CA, reported a tolerable hematologic toxicity and reasonable response obtained from a regimen
comprising paclitaxel, carboplatin, and bevacizumab in a study of 24 patients. [A1] Kudoh K et al at Nishisaitama-
Chuo National Hospital, Japan, also reported that combination therapy with bevacizumab and pegylated
liposomal doxorubicin was active and well tolerated for patients with recurrent ovarian cancers. [A2]

In a study of 15 patients treated with a total of 134 cycles of bevacizumab, researchers reported no perforation
observed and bevacizumab might be an efficient therapy option in the setting of heavily pre-treated ovarian
cancer. The most severe side effect in this group was fistula. [A4] [Note: a high rate of bowel perforations has
been reported in patients with ovarian cancer treated with bevacizumab.]

Avastin lung cancer
Recently,  the addition of bevacizumab to chemotherapy could be associated with better outcomes in patients
with advanced non-small cell lung cancer. And, the benefit is dependent on the drugs used in the chemotherapy
regimens. Lima AB et al at Universidade Estadual de Campinas, Brazil, reported that the addition of
bevacizumab to chemotherapy in patients with advanced non-small cell lung cancer prolongs overall survival,
progression-free survival and response rate. However, there was also a slight increase in side effects or toxicity
in bevacizumab group. [A5] Tassinari D and co-workers from City Hospital, Rimini, Italy reported similar results
when they dosed patients with non-squamous non-small cell lung cancer with bevacizumab-containing
regimens. They concluded "Adding bevacizumab to standard chemotherapy in the treatment of advanced,
chemotherapy-naive, non-squamous NSCLC seems to favor a modest improvement in the main outcomes, with
a significant worsening of the safety profile." [A6]

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

Avastin brain cancer
Desijardins A et al at Duke University Medical Center performed a phase 2 trial of combined protracted daily
temozolomide and biweekly bevacizumab for patients with recurrent glioblastoma who had previously received
radiation therapy and temozolomide. Glioblastoma multiforme is the most common and most aggressive
malignant primary brain tumor in humans. During the studies, some side effects were noticed. Two patients
discontinued therapy secondary to toxicity (prolonged thrombocytopenia and grade 4 pancreatitis). One patient
experienced grade 5 pneumonia. The study demonstrated that a regimen of combined daily temozolomide and
biweekly bevacizumab had some activity and was well tolerated. However, the results obtained in this study were
inferior to those observed in studies of bevacizumab monotherapy and of combined irinotecan and bevacizumab
therapy. [A7]

Chira C et al at Institut Curie, France, report a study of bevacizumab-based chemotherapy followed by whole-
brain radiation therapy for breast cancer patients with inoperable brain metastases or who refused surgery.
This is a retrospective study of seven metastatic breast cancer patients treated at the Institut Curie with at least
one course of bevacizumab-based chemotherapy before whole-brain radiation therapy, with a delay of ≤12
months between the two treatments. Toxicity was scored according to the common terminology criteria for
adverse side effects. Median age was 56 years. Median follow-up was 5.9 months. The median dose of
bevacizumab was 10 mg/kg. Median number of cycles bevacizumab-based chemotherapy was six. Different
chemotherapy regimens were used. Most common reported side-effects were nausea (n = 4), headache (n = 3),
vomiting (n = 1), and vertigo (n = 3). All patients had mild or moderate grade ≤2 neurologic toxicity. [A8]

Avastin 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.

This 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.
[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
A1 Brown JV 3rd, Micha JP, Rettenmaier MA, Abaid LN, Lopez KL, Goldstein BH. A pilot study evaluating a novel regimen
comprised of carboplatin, paclitaxel, and bevacizumab for advanced-stage ovarian carcinoma. Int J Gynecol Cancer. 2010 Oct;20(7):1132-6. A2.
Kudoh K, Takano M, Kouta H, Kikuchi R, Kita T, Miyamoto M, Watanabe A, Kato M, Goto T, Kikuchi Y. Effects of bevacizumab and pegylated
liposomal doxorubicin for the patients with recurrent or refractory ovarian cancers. Gynecol Oncol. 2011 Aug;122(2):233-7. [A3] Pietzner K, Richter R,
Chekerov R, Erol E, Oskay-Özcelik G, Lichtenegger W, Sehouli J.  Bevacizumab in Heavily Pre-treated and Platinum Resistant Ovarian Cancer: A
Retrospective Study of the North-Eastern German Society of Gynaecologic Oncology (NOGGO) Ovarian Cancer Study Group. Anticancer Res. 2011
Aug;31(8):2679-82. [A4] Pietzner K, Richter R, Chekerov R, Erol E, Oskay-Özcelik G, Lichtenegger W, Sehouli J. Bevacizumab in Heavily Pre-treated
and Platinum Resistant Ovarian Cancer: A Retrospective Study of the North-Eastern German Society of Gynaecologic Oncology (NOGGO) Ovarian
Cancer Study Group. Anticancer Res. 2011 Aug;31(8):2679-82. [A5] Lima AB, Macedo LT, Sasse AD. Addition of bevacizumab to chemotherapy in
advanced non-small cell lung cancer: a systematic review and meta-analysis. PLoS One. 2011;6(8):e22681. Epub 2011 Aug 2. [A6] Tassinari D, Sartori
S, Papi M, Drudi F, Castellani C, Carloni F, Tombesi P, Lazzari-Agli L. Bevacizumab in the Treatment of Advanced, Non-Squamous Non-Small Cell
Lung Cancer: An Evidence-Based Approach. Oncology. 2011 Jul 27;80(5-6):350-358. [A7] Desjardins A, Reardon DA, Coan A, Marcello J, Herndon JE
2nd, Bailey L, Peters KB, Friedman HS, Vredenburgh JJ. Bevacizumab and daily temozolomide for recurrent glioblastoma. Cancer. 2011 Jul 26. doi:
10.1002/cncr.26381  [A8] Chira C, Jacob J, Derhem N, Bollet MA, Campana F, Marchand V, Pierga JY, Fourquet A, Kirova YM. Preliminary experience
of whole-brain radiation therapy (WBRT) in breast cancer patients with brain metastases previously treated with bevacizumab-based chemotherapy. J
Neurooncol. 2011 Jun 5. [BB1]  
FDA revokes approval of Avastin for breast cancer, The Associated Press November 18,
2011, 10:14PM ET   
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