- Understanding and managing neutropenia with NEUPOGEN®(filgrastim)

-Amgen Inc.

Introduction

As a patient about to undergo drug treatment for cancer, you are aware that chemotherapy may caused side effects. Fortunately, for the majority of patients, most of these side effects can be controlled and tolerated.

One of the most serious potential side effects of chemotherapy is neutropenia (a low white blood cell count). As the chemotherapy destroys your cancer cells, it may also destroy your white blood cells.

Neutropenia itself is not normally a danger to you. Over time, your body will replenish these destroyed white blood cells through regeneration of new cells in your bone marrow.

However, once neutropenia occurs, depending on your state of health, a delay and/or a reduction in the regular dose of your chemotherapy may be necessary to avoid potential problems. This may prevent your full cancer treatment to proceed as planned until your white blood count is restored.

For a small percentage of patients with neutropenia, an infection may develop, as not enough white blood cells are available to fight bacteria. These patients who develop febrile neutropenia (neutropenia plus a fever) must then be hospitalized and treated with intravenous antibiotics in an effort to eliminate the infection.

Today, as a result of advances in genetic engineering, neutropenia can be managed with the colony stimulating factor, NEUPOGEN®(filgrastim).

Through education, you can understand more about your drug treatment for cancer and its side effects. Information will allow you to become involved and to take a more active role in the decision-making process regarding your therapy if you choose. And, you will gain a better understanding of the treatment options which are available to you. Hopefully, by learning more about neutropenia and its management, you will gain a sense of control over your recovery, and will be more empowered to step forward to resume normal, healthy living.

What is chemotherapy?

Chemotherapy involves the use of drugs that help destroy cancer cells.

How does chemotherapy work?

Both normal healthy cells and cancer cells undergo a cycle of growth, rest, and division. Cancer cells, however, grow in an uncontrolled manner, and can spread from their site of origin.

Chemotherapy interrupts the cell cycle, and stops the cancer cells from growing. These drugs are especially effective at inhibiting the growth of rapidly dividing cells.

Unfortunately, chemotherapy is not very selective in its action, as normal cells that are rapidly growing may also be affected. Immediate side effects such as hair loss, sore mouth, nausea, and diarrhea, are the result of normal cells being disrupted. Delayed side effects can also occur.

The most important rapidly growing normal cells affected by chemotherapy are the blood cells. Neutrophils (white blood cells) in the blood circulation may be damaged or destroyed, thus causing a low white blood cell count reading in a laboratory blood test. As well, the bone marrow may be suppressed for a time by the effects of the chemotherapy from producing its usual number of replacement neutrophils.

What are neutrophils?

The neutrophil is the most common white blood cell (also known as leucocyte)in the blood, comprising 50-70% of circulating white blood cells.

Neutrophils live for less than a day in the blood, and so there is a continuous need to replace them. To meet this demand, the bone marrow, the soft centre part of most bones, produces approximately ten billion neutrophils every hour.

Why are neutrophils important?

In the healthy individual, neutrophils protect the body from developing infections by seeking out and engulfing the bacteria in the blood, and then destroying them.

If an infection occurs, the healthy person is usually able to get better, without the need of antibiotics or hospitalization, as the body responds by quickly producing many more neutrophils to help fight the bacteria. During a serious infection, neutrophils may live only for a couple of hours; normally, they live for approximately 8 - 10 hours.

However, if a patient has a low white blood cell count, for example, as a result of their chemotherapy, they have a greater chance of developing an infection and fever. Neutrophils may not be available in sufficient numbers to protect the patient should an infection develop, and the neutrophils may not be produced quickly enough to overcome the bacteria.

What is neutropenia?

Neutropenia means "a lack of neutrophils".

Neutropenia occurs when the bone marrow is not able to make enough neutrophils, or when the neutrophils are destroyed at a faster rate than they are produced. Anything which inhibits the bone marrow from producing white blood cells, or which destroys white blood cells in the blood or bone marrow, can cause neutropenia, for example, chemotherapy.

Blood cells damaged by chemotherapy include the platelets (which help to stop bleeding) and the white cells (which fight infection). The red cells (which carry oxygen to your body from the lungs) are not usually as affected.

The skin and mucous membranes (the outer linings of the body) are the first line of defense against infection. Needles, IV lines, and catheters can create opportunities for bacteria to enter the body through skin puncture. Chemotherapy and radiation can also damage mucous membranes.

Neutrophils are the second defense. But, if the person doesn't have enough neutrophils, infection may develop. The infections most often occur in the lungs, mouth and throat, sinuses, blood and skin. Painful mouth ulcers, gum infections, ear infections, and tooth disease are common.

What are the consequences of untreated neutropenia?

Neutropenia can range from mild to very serious. Chemotherapy is normally given to you in full dose as frequently as possible. Clinical studies have determined the most effective dose and duration of therapy for each drug to destroy the most cancer cells, while minimizing the side effects of treatment.

On the scheduled day of your chemotherapy, your white blood cell counts will be measured. If your physician sees that the counts are still low as a result of the previous treatment, he or she may need to discuss delaying your treatment, may prescribe a lower dose, and/or may prescribe a medication to raise the white blood cell counts.

In some cases, an infection may be severe and life-threatening. Therefore, if you develop neutropenia and fever, you may require hospitalization in order to receive intravenous antibiotics.

How is neutropenia managed?

New drugs in use today, known as supportive therapies, deal with the side effects of chemotherapy. One of the supportive therapies physicians are prescribing to help certain chemotherapy patients maintain an acceptable white blood cell count is NEUPOGENÒ (filigrastim).

What is NEUPOGEN®(filgrastim)?

NEUPOGEN®is the AMGEN Inc. Trademark for filgrastim, a glycoprotein (also known as human granulocyte colony stimulating factor, G-CSF).

NEUPOGEN® is very similar to the G-CSF which is naturally produced by the blood cells in your body, and it stimulates your bone marrow to produce neutrophils more quickly. With NEUPOGEN®, your white blood cell count returns to normal much sooner than it normally would after chemotherapy. This may allow you to maintain full doses of the most effective chemotherapy prescribed for you.

NEUPOGEN®is prescribed to be given as a daily injection following each course of chemotherapy. Your physician will take regular blood tests to determine how long you will receive NEUPOGEN®. For most people, it is between 7 and 14 days, but this is individualized for each person.

Generally, NEUPOGEN®is well tolerated. Some patients experience discomfort they describe as a dull ache in their bones. This bone pain is normal, and is usually relieved with an non-narcotic analgesic. Your physician, nurse, or pharmacist should be consulted on ways to relieve any discomfort.

What NEUPOGEN® is and isn't

When there are not enough white blood cells, the body's own colony stimulating factors, like G-CSF, tell the bone marrow to produce more. After chemotherapy, it can take your body a while to regenerate lost white blood cells.

NEUPOGEN®acting like a natural colony stimulating factor, causes the body to produce more white blood cells, specifically neutrophils. So, used after chemotherapy, it speeds up the return to a more normal white blood cell count.

Prior to the availability of NEUPOGEN®, the only way to deal with neutropenia was to delay chemotherapy treatment until the white blood cell count recovered, and/or to reduce the dose of chemotherapy given.

NEUPOGEN® is not a treatment for cancer. It works as a protection against infection during recovery from chemotherapy, which allows you to continue your treatment at the most effective dose and schedule designed to treat your cancer. You should discuss with your physician which treatment option is best for you.