DOXIL is:

• A chemotherapy drug used to treat or control ovarian cancer cells in patients with recurrent ovarian cancer
• A different form of doxorubicin, a drug commonly used to treat cancer
• Surrounded by a coating that allows it to avoid being found and destroyed by the body's immune system

DOXIL is a reformulated version of doxorubicin. DOXIL takes the active agent doxorubicin and places it into a fat bubble called a liposome and another layer of hair-like strands made from methoxypolyethylene glycol—a type of rubber. This coating allows DOXIL to evade detection and destruction by the immune system, which increases the time the drug is in the body. The majority of the drug stays inside the liposome while in the blood (at least 90%). Therefore, DOXIL has more time to reach the tumor tissue, where the medication slowly leaks out. However, DOXIL may also affect normal tissue.

It is very important that you take an active role in your care. During the course of your DOXIL treatment, be sure to talk to your doctor or nurse about how you feel or any concerns you may have.

Administration
DOXIL is given by intravenous (IV) infusion, normally in the doctor's office or in a clinic. Your treatment will usually take approximately 1 hour although the first treatment may be longer. You will typically receive DOXIL treatments every 4 weeks for a minimum of 4 courses. However, speak with your doctor or nurse for your exact treatment schedule.

CA-125 is a protein (measured in a blood test) that is used as a potential indicator of ovarian cancer and effectiveness of treatment. It is not uncommon for CA-125 levels to increase during your treatment of ovarian cancer. A minimum of 4 courses is recommended because time to response in clinical trials was approximately 4 months. It is important for patients to complete the first 4 cycles of DOXIL therapy as long as they do not clinically progress, continue to tolerate treatment, and show no evidence of cardiotoxicity because clinical trials have shown this is the median time to response. Ask your doctor if you have questions or concerns about your CA-125 level.

Heart-Related Side Effects
The use of DOXIL may lead to heart-related side effects. In an important clinical study, these side effects were seen in 11% of patients treated with DOXIL.

Symptoms of heart-related side effects may include:

• Irregular heartbeat
• Shortness of breath
• Fatigue
• Ankle swelling

Due to the serious and possibly permanent effects of heart-related side effects, your doctor may monitor your heart function and will closely watch the total amount of DOXIL that you receive. Notify your doctor or nurse immediately if you experience any of the above symptoms.

Acute Infusion-Related Reactions
Infusion-related reactions were seen in up to 10% of patients treated with DOXIL, so you will be closely observed for reactions during your first infusion. If a reaction occurs, it usually happens during the first infusion. In most patients, infusion-related reactions can be managed by either slowing or stopping the treatment. In a Phase III ovarian cancer study, less than 1% of patients treated with DOXIL discontinued treatment due to infusion-related reactions. However, some reactions can be severe and may have serious consequences. A list of the most common infusion-related reactions is provided below. Please let your doctor or nurse know immediately if you experience any of these or other
symptoms during your treatment:

• Flushed feeling
• Dizziness or light-headedness
• Shortness of breath
• Chills
• Back pain
• Facial swelling
• Tightness in the chest or throat
• Headache

Changes in Blood Cell Counts
Chemotherapy treatments can lower blood cell counts, which can cause other unwanted effects:

• Reduced white blood cell counts (neutropenia) can lead to fever and infections
• Reduced red blood cell counts (anemia) can make you feel tired and fatigued
• Reduced platelet counts (thrombocytopenia) can lead to impaired blood clotting and prolonged bleeding

Changes in blood cell counts are generally moderate and reversible in patients treated with DOXIL. In some patients, severe reductions in blood cell counts may occur. Your doctor or nurse will typically check your blood cell counts regularly and may give you medication to bring low blood cell counts back up to the target range.

Skin-Related Reactions
You may experience a skin reaction called hand-foot syndrome (HFS), also called palmar-plantar erythrodysesthesia (PPE). It usually occurs on the palms of the hands and soles of the feet. It can also occur on other parts of the body where your clothes may be tight or where friction, pressure, rubbing, warmth, and/or sweating occur. You or a friend or family member should check regularly for signs of skin irritation and hand-foot syndrome. If you already have peripheral neuropathy (numbness or tingling in the hands and feet) from previous treatment or other conditions, you may not feel the symptoms easily.

Some common signs and symptoms of hand-foot syndrome include:

• Redness
• Rash
• Pain or tenderness
• Swelling
• Tingling, burning, or itching
• Flaking or peeling of the skin
• Small blisters or small sores

In most patients, the reaction is mild and improves in 1 to 2 weeks without a delay in therapy. However, hand-foot syndrome can be severe in some patients and may require either delaying or stopping therapy. At the first sign of any of these symptoms, please tell your doctor or nurse immediately. They may have suggestions to help you reduce the severity of hand-foot syndrome.

Because its frequency and severity are usually associated with the chemotherapy dose and/or schedule, hand-foot syndrome may be treated with a delay and/or reduction in therapy until the hand-foot syndrome is resolved. A delay or reduction in dose typically does not reduce the effectiveness of treatment.

Another skin-related reaction is stomatitis, a mouth irritation characterized by inflammation or sores. Stomatitis may be prevented with proper care of your mouth and by avoiding certain foods and beverages. Your doctor or nurse can provide you with guidelines to help prevent stomatitis. For example, you might be told to rinse your mouth daily with salt water.

Some common symptoms of stomatitis include:

• Mouth sores
• Dry, swollen tongue
• Pain or burning in the mouth
• Difficulty swallowing

Hair Loss
Hair loss, or alopecia, is typically mild with DOXIL therapy. When it does occur, the hair usually grows back after completion of therapy. In a clinical study, some hair loss occurred in 19.2% of patients.

Nausea and Vomiting
Nausea and vomiting are usually mild and may be prevented with medication.

Let your doctor or nurse know immediately if you are experiencing any of these symptoms.