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Avastin Review Article

 

treatment of cancerAvastin (Generic Name: Bevacizumab) is the first drug that belongs to a new class of medications that are used for the treatment of cancer by compromising blood supply. It was the first marketed angiogenesis inhibitor and is a humanized monoclonal antibody. It is deemed to inhibit angiogenesis which is the development of new blood vessels that provide blood, oxygen, and other nutrients to the tumor and tolerate its growth and metastasis to other parts of the body. Moreover, this drug may impede the growth of the tumor by stimulating the blood vessels to shrivel away from the tumor. It does so by targeting and holding back the function of vascular endothelial growth factor (VEGF) which is a natural protein that stimulates new blood cell formation. Bevacizumab is usually prescribed for Colorectal, Lung, and Breast Cancer. Side effects may include hypertension, risk of bleeding, perforation in bowel, stomach, and intestines.

AVASTIN (Bevacizumab) is first FDA Approved Medication to Inhibit Nutrient Supply to Cancer Tumors.

Cancer, a scary and potentially life-threatening diagnosis, has proven to be a very difficult battle for patients, their families and friends, doctors, and scientists alike. Research trials have revealed a new type of medication aimed at fighting cancer at its source. Continue reading...


Cancer, what it is and how does it progresses?

Cancer is an uncontrolled growth of cells within our bodies. This increased growth is usually due to a lack of normal growth control over the cells. These cells quickly and erratically grow and mutate, becoming useless to proper functioning within our bodies. (5,8)

As these cells form and mutate in one area, they create tumors. Our bodies supply the nutrients needed for these tumors to further grow. While developing, the tumors create blood vessels so that they can receive a direct blood supply. If these tumors are malignant (cancerous) they may invade and damage nearby tissues and organs. Malignant tumors can also shed cancer cells that travel throughout the body. These cells may or may not live long enough to adhere to another area within the body. If they do, these cells are able to invade tissues and create more tumors. This is known as metastasis, the term used to describe how cancer spreads. The same cycle begins again; tumor growth, damage to nearby tissues and organs, possible metastasis which leads to further and more severe health issues. (5,8)

How can AVASTIN Help Fight Against Cancer?

Avastin is classified as an antineoplastic and monoclonal antibody. An antineoplastic medication prevents the growth of new cells. Although these types of medications are also harmful to the body’s cells, they are more harmful to those the cells that are dividing, such as cancer cells, than the regular ones. Keep in mind, the body only reproduces (divides into) new cells on an as-needed basis; whereas, cancer cells are continuously multiplying and dividing. The second term, monoclonal antibody, is used to identify medications created as B lymphocyte clones. B lymphocytes are naturally created in our bone marrow. They produce antibodies and assist with our body’s immune responses.6

How does Avastin inhibit tumor growth?

Avastin binds to the vascular endothelial growth factor (VEGF). VEGF stimulates the production of cells lining the blood vessels and fuels the creation of capillaries. Tumors direct new capillary growth to themselves so that they receive a nonstop supply of blood, imperative for the tumor’s growth. When Avastin binds to VEGF, it inhibits any further vessel and capillary creation. By cutting off the tumor’s nutrient and blood supply, it is believed that Avastin slows down the tumors from growing and metastasizing, thus slowing the disease progression. (1,2,3,6,7)

AvastinFigure 2. Illustration demonstrates the effects of Avastin on the capillary blood supply to the tumor. The red demonstrates the patient’s blood supply to the tumor over a period of time while taking Avastin. (From Genetech: VEGF, Ang––iogenesis and Cancer.

What types of Cancer does Avastin work against?

Avastin may be used either as monotherapy (by itself) or as an adjuvant therapy (given in addition to other medications) depending on the type of cancer:
1. Metastatic colon or rectal carcinomas;
2. Metastatic human epidermal growth factor receptor 2-negative breast cancer;
3. Unresectable, locally advanced, recurrent or metastatic nonsquamous, non-small cell lung cancer;
4. Glioblastoma;
5. Metastatic renal cell cancer tumors


Dosage for Indications

Avastin is supplied as an injection solution (for IV infusion or Injection) and comes in 25 mg/ml concentrate. All dosages are for Adults only:
Metastatic colon or rectal carcinomas (first or second line treatment)
• 5 mg/kg once every 2 weeks with bolus IFL (Irinotecan, fluorouracil, and Leucovorin)
• If used in combination with IV FOLFOX-4 (fluorouracil, leucovorin, and oxaliplatin) dosage is 10 mg/kg every 2 weeks
• Continue medication until disease progression is detected
Metastatic HER2-negative breast cancer (for those who have not received chemotherapy)
• Used in combination with Paclitaxel
• 10mg/kg as an IV infusion every 2 weeks
Nonsquamous non-small-cell lung cancer (first line treatment)
• Used in combination with Carboplatin/Paclitaxel
• 15 mg/kg as an IV infusion every 3 weeks
Glioblastoma (treat with progressive disease following previous therapy)
• 10 mg/kg as an IV infusion every 2 weeks
Metastatic renal cell carcinoma
• Used in combination with Interferon Alfa
• 10mg/kg as IV injection every 2 weeks

Contraindications/Precautions:
Risk cannot be ruled out for pregnancy; fetal harm may occur. Avastin is contraindicated within 28 days before or after major surgery. Those with cardiovascular disease taking Avastin have not been adequately studied. The elderly population tends to have more severe side effects. Medication has not been evaluated on children. Females with reproductive potential may be at risk of ovarian failure with Avastin. (2,7)

Special Concerns
Gastrointestinal (GI) perforations range from 0.3% - 2.4%, some have been fatal. Discontinue if patient has GI perforation. Discontinue if wounds are not healing or surgical sites are no longer remaining intact. Severe and fatal bleeding has been associated with Avastin; if you are bleeding or recently have coughed up blood, do not take Avastin. There is a risk of stroke, cerebral infarction, heart attack, transient ischemic attacks, angina (chest pain), and fatal arterial blood clotting events in those also receiving chemotherapy. There is a higher risk among those with blood clotting problems before receiving Avastin and those 65 years and older. (2,7)

Side effects
The most common side effects include back pain, dry skin, upper respiratory tract infections, weakness or energy loss, breathing difficulty, headaches, high blood pressure, nausea and vomiting, rectal hemorrhage, abdominal pain, diarrhea.

The most serious side effects include congestive heart failure, GI perforation, surgery and wound healing complications, serious and non-serious bleeding episodes, clotting events, hypertensive crisis, nephritic syndrome, and possible fistula formation. (2,7)

Drug interactions
When taking Avastin with Paclitaxel and Carboplatin, decrease Paclitaxel exposure after four treatment cycles. (7)

References

1. Amini A, Moghaddaam SM, Morris DL, Pourgholami MH. Utility of vascular endothelial growth factor inhibitors in the treatment of ovarian cancer: from concept to application. Journal of Oncology. 2012; 2012:540791.

2. Food and Drug Administration (FDA). Updated June 29, 2011. Accessed October 7, 2011.

3. Gerber HP, Ferrara N. Pharmacology and Pharmacodynamics of Bevacizumab as Monotherapy or in Combination with Cytotoxic Therapy in Preclinical Studies. Cancer Res. 2005 February 1;65(3):671-80.

4. Giantonio BJ, Catalano PJ, Meropol NJ, et al. Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: results from the eastern cooperative oncology group study E3200. Journal of Clinical Oncology. 2007 April 25;12:1539-44.

5. Mayoclinic. Accessed October 7, 2011.

6. Mosby’s Dictionary of Medicine, Nursing, and Health Professions. 8th ed. St. Loius, MO: Mosby, Inc; 2009.

7. Spratto GR, Woods AL. Delmar Nurse’s Drug Handbook. 2012 ed. Canada: Delmar, Cengage Learning; 2012.

8. The Merck Manual of Diagnosis and Therapy. 19th ed. Whitehouse Station, NJ: Merck Sharp and Dohme Corp; 2011.


 

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