Tuesday, July 20, 2010

Erbitux

Generic Name: Cetuximab
Other Name: C225

Drug Type:

Erbitux is a targeted therapy. It is classified as a "monoclonal antibody" and "signal transduction inhibitor" by binding to epidermal growth factor receptors (EGFR). (For more detail, see "How Erbitux Works" section below.)

What Erbitux Is Used For:

Erbitux is used to treat metastatic colorectal cancer (cancer spread beyond the colon or rectum) that over-expresses the epidermal growth factor receptor (EGFR).
Approved for the treatment of squamous cell carcinoma of the head and neck.
Note: If a drug has been approved for one use, physicians may elect to use this same drug for other problems if they believe it may be helpful.

How Erbitux Is Given:

By intravenous (IV) infusion.
The amount of cetuxumab that you will receive depends on many factors, including your height and weight, your general health or other health problems, and the type of cancer or condition being treated. Your doctor will determine your dose and schedule.
Erbitux Side Effects:

Important things to remember about the side effects of cetuxumab include:

Most people do not experience all of the side effects listed.
Side effects are often predictable in terms of their onset and duration.
Side effects are almost always reversible and will go away after treatment is complete.
There are many options to help minimize or prevent side effects.
There is no relationship between the presence or severity of side effects and the effectiveness of Erbitux.
The following side effects are common (occurring in greater than 30%) for patients taking Erbitux:

Rash (acne-like)
Generalized weakness, malaise
Fever
Low magnesium level (see blood test abnormalities)
These side effects are less common side effects (occurring in about 10-29%) of patients receiving Erbitux:

Nausea and vomiting
Diarrhea
Constipation
Poor appetite
Headache
Abdominal pain
Nail disorder - inflammation of the skin surrounding a fingernail or toenail
Mouth sores
Swelling
Difficulty sleeping
Itching
Low red blood cell count (Anemia)
Cough
Infusion reactions (chills, fever, shortness of breath) have been experienced with this infusion - rarely, this reaction can be severe with difficulty breathing, itching, low blood pressure. Pre-medication is given prior to infusion as a precaution.

Not all side effects are listed above. Some that are rare (occurring in less than 10% of patients) are not listed here. However, you should always inform your health care provider if you experience any unusual symptoms.

When To Contact Your Doctor or Health Care Provider:

Seek emergency help immediately and notify your health care provider, it you experience the following symptoms:

Shortness of breath, wheezing, difficulty breathing, closing up of the throat, swelling of facial features, hives (possible allergic reaction).
The following symptoms require medical attention, but are not an emergency. Contact your health care provider within 24 hours of noticing any of the following:

Nausea (interferes with ability to eat and unrelieved with prescribed Erbitux).
Vomiting (vomiting more than 4-5 times in a 24 hour period).
Diarrhea (4-6 episodes in a 24-hour period).
Extreme fatigue (unable to carry on self-care activities).
Mouth sores (painful redness, swelling or ulcers).
Constipation unrelieved by laxative use.
Swelling of the feet or ankles. Sudden weight gain.
Unable to eat or drink for 24 hours or have signs of dehydration: tiredness, thirst, dry mouth, dark and decrease amount of urine, or dizziness.
Always inform your health care provider if you experience any unusual symptoms.

Erbitux Precautions:

Before starting Erbitux treatment, make sure you tell your doctor about any other medications you are taking (including prescription, over-the-counter, vitamins, herbal remedies, etc.). Do not take aspirin, or products containing aspirin unless your doctor specifically permits this.
Do not receive any kind of immunization or vaccination without your doctor's approval while taking Erbitux.
Inform your health care professional if you are pregnant or may be pregnant prior to starting this treatment. Pregnancy category C (use in pregnancy only when benefit to the mother outweighs risk to the fetus).
For both men and women: Do not conceive a child (get pregnant) while taking Erbitux. Barrier methods of contraception, such as condoms, are recommended. Discuss with your doctor when you may safely become pregnant or conceive a child after therapy.
Do not breast feed while taking Erbitux and for 60 days following the last dose.
Erbitux Self Care Tips:

Drink at least two to three quarts of fluid every 24 hours, unless you are instructed otherwise.
Wash your hands often.
You may be at risk of infection report fever or any other signs of infection immediately to your health care provider.
To help treat/prevent mouth sores, use a soft toothbrush, and rinse three times a day with 1/2 to 1 teaspoon of baking soda and/or 1/2 to 1 teaspoon of salt mixed with 8 ounces of water.
Erbitux causes little nausea. But if you should experience nausea, take anti-nausea medications as prescribed by your doctor, and eat small frequent meals. Sucking on lozenges and chewing gum may also help.
Keep your bowels moving. Your health care provider may prescribe a stool softener to help prevent constipation that may be caused by Erbitux.
An acne-like rash is a common side effect of Erbitux. If you are experiencing this side effect make sure your health care professional is aware, so they can assess the severity and offer suggestions for management.
Avoid sun exposure. Wear SPF 15 (or higher) sunblock and protective clothing.
In general, drinking alcoholic beverages should be kept to a minimum or avoided completely. You should discuss this with your doctor.
Get plenty of rest.
Maintain good nutrition.
If you experience symptoms or side effects, be sure to discuss them with your health care team. They can prescribe medications and/or offer other suggestions that are effective in managing such problems.
Acetaminophen or ibuprophen may help relieve discomfort from fever, headache and/or generalized aches and pains. However, be sure to talk with your doctor before taking it.
Monitoring and Testing While Taking Erbitux:

You will be checked regularly by your health care professional while you are taking Erbitux, to monitor side effects and check your response to therapy. Periodic blood work to monitor your complete blood count (CBC), electrolyte levels as well as the function of other organs (such as your kidneys and liver) will also be ordered by your doctor.

How Erbitux Works:

About Targeted Therapy

Targeted therapy is the result of about 100 years of research dedicated to understanding the differences between cancer cells and normal cells. To date, cancer treatment has focused primarily on killing rapidly dividing cells because one feature of cancer cells is that they divide rapidly. Unfortunately, some of our normal cells divide rapidly too, causing multiple side effects.

Targeted therapy is about identifying other features of cancer cells. Scientists look for specific differences in the cancer cells and the normal cells. This information is used to create a targeted therapy to attack the cancer cells without damaging the normal cells, thus leading to fewer side effects. Each type of targeted therapy works a little bit differently but all interfere with the ability of the cancer cell to grow, divide, repair and/or communicate with other cells. Modern targeted therapy types include the use of monoclonal antibodies and anti-angiogenesis drugs, both of which are described in greater depth here.

The different types of targeted therapies are defined in three broad categories. Some targeted therapies focus on the internal components and function of the cancer cell. The targeted therapies use small molecules that can get into the cell and disrupt the function of the cells, causing them to die. There are several types of targeted therapy that focus on the inner parts of the cells. Other targeted therapies target receptors that are on the outside of the cell. Therapies that target receptors are also known as monoclonal antibodies. Anti-angiogenesis drugs target the blood vessels that supply oxygen to the cells, ultimately causing the cells to starve.

Researchers agree that targeted therapies are not a replacement for traditional therapies. Targeted therapies involve production of components such as monoclonal antibodies or anti-angiogenesis drugs may best be used in the short term, combination with traditional therapies. More research is needed to identify which cancers may be best treated with targeted therapies such as monoclonal antibodies or anti-angiogenesis drugs and to identify additional targets for more types of cancer.

Using Monoclonal Antibodies as Targeted Therapy

Monoclonal antibodies are a relatively new type of "targeted" cancer therapy. Antibodies are part of the immune system. Normally, the body creates antibodies in response to an antigen (such as a protein in a germ) entering the body. The antibodies attach to the antigen in order to mark the antigen for destruction by the body's immune system. In the laboratory, scientists analyze specific antigens on the surface of cancer cells (target) to determine a protein to match the antigen. Then, using protein from animals and humans, scientists work to create a special antibody that will attach to the target antigen. An antibody will attach to a matching antigen like a key fits a lock. This technology allows treatment to target specific cells, causing less toxicity to healthy cells. Monoclonal antibody therapy can be done only for cancers in which antigens (and the respective antibodies) have been identified.

Erbitux is a targeted therapy that targets and binds to the epidermal growth factor receptors (EGFR) on the surface of the cell. EGFR is found on the surface of many normal and cancer cells. By binding to these receptors, Erbitux blocks an important pathway that promotes cell division this results in inhibition of cell growth and apoptosis (cell suicide).

Note: We strongly encourage you to talk with your health care professional about your specific medical condition and treatments. The information contained in this website is meant to be helpful and educational, but is not a substitute for medical advice.

Erbitux

ERBITUX


Erbitux (cetuximab)


Company: Imclone, Bristol-Myers Squibb
Approval Status: Approved February 2004
Treatment for: Colorectal Cancer
Areas: Gastroenterology; Oncology

| General Information | Clinical Results | Side Effects | Mechanism of Action | Literature References | Additional Information |


General Information

Erbitux (cetuximab) for injection is a monoclonal antibodyt hat targets and inhibits epidermal growth factor receptor (EGFr). EGFr is over-expressed in more than 35% of all solid malignant tumors. It is used alone or combination with other therapies for the treatment of colorectal cancer.

Erbitux is indicated, in combination with irinotecan, for the treatment of EGFR-expressing, metastatic colorectal cancer in patients who are refractory to irinotecan-based chemotherapy. In addition, it is also approved for use as a single agent in the treatment of patients with EGFR-expressing, metastatic colorectal cancer who are intolerant to irinotecan-based chemotherapy.

The recommended dosage of Erbitux is 400 mg/m2 as an initial loading dose, administered as a 120-minute IV infusion. The recommended weekly maintenance dose is 250 mg/m2 infused over 60 minutes.




Clinical Results

FDA approval of Erbitux was based on three separate clinical trials on subjects with EGFR-expressing metastatic colorectal cancer, whose disease had progressed after receiving an irinotecan-containing regimen.

A randomized, controlled trial enrolling 329 subjects investigated Erbitux both as a monotherapy and in combination with irinotecan. Subjects received Erbitux plus irinotecan or Erbitux monotherapy, administered as a 400 mg/m2 initial dose, followed by 250 mg/m2 weekly until disease progression or unacceptable toxicity. Eighty-eight percent of subjects had baseline Karnofsky Performance Status of 80 or higher. Fifty-eight percent of subjects had colon cancer and 40% rectal cancer with two-thirds of them having previously failed oxaliplatin treatment. Data showed that the median duration of response in the overall population was 5.7 months in the combination arm and 4.2 months in the monotherapy arm. Analysis showed that subjects randomized to Erbitux and irinotecan demonstrated a significantly longer median time to disease progression compared with Erbitux alone.

An open-label, single-arm trial enrolling 138 subjects investigated Erbitux in combination with irinotecan. Subjects received a 20-mg test dose of Erbitux on day 1, followed by a 400-mg/m2 initial dose, and 250 mg/m2 weekly until disease progression or unacceptable toxicity. Seventy-four subjects had documented progression to irinotecan. Results demonstrated an overall response rate of 15% for the overall population and 12% for the irinotecan-failure population. The median durations of response were 6.5 and 6.7 months, respectively. In a third trial, Erbitux was studied as a single agent in a open-label, single-arm study enrolling 57 subjects. Results showed an overall response rate of 9% for the all-treated group and 14% for the irinotecan-failure group. The median times to progression were 1.4 and 1.3 months, respectively. The median duration of response was 4.2 months for both groups.