Herceptin (trastuzumab)

• Herceptin is an intravenous drug that is part of a chemotherapy regimen that is used to prevent recurrence of breast cancer, and for the treatment breast cancer that has spread beyond the breast (metastasized).
• It belongs to a class of drugs called monoclonal antibodies. Other monoclonal antibodies include rituximab (Rituxan) and gemtuzumab ozogamicin (Mylotarg).
• A cancer cell has various receptors on its surface. Chemicals bind to these receptors and cause changes within the cancer cell. One of the receptors that occurs in about one-third of all breast cancers is called HER2. HER2 is known to control the growth and development of the cancer cells, and the production of new cancer cells. If HER2 receptors are present in large numbers on the cancer cells (often referred to as overexpression of HER2), then the cancer cells may multiply and grow quickly. Normally, the immune system produces antibodies that will detect and attack HER2 receptors to slow the growth of cancer cells; however, if HER2 is present in large numbers, the immune system may be unable to control HER2. Trastuzumab is a man-made antibody developed using molecular cloning and recombinant DNA technology. Trastuzumab is thought to block the HER2 receptors when there is overexpression, thereby blocking growth of the cancer.

What brand names are available for trastuzumab?

• Herceptin is the brand name available for trastuzumab in the US.

• Trastuzumab is used for preventing recurrence (adjuvant treatment) of HER2 overexpressing breast cancer.
• It also is used for treatment of metastatic breast cancer, metastatic gastric, or gastroesophageal junction adenocarcinoma among patients who overexpress HER2.
• It may be used alone or combined with other chemotherapy drugs.

BLACK BOX WARNING

• Trastuzumab can cause heart failure, especially when it is combined with cyclophosphamide and anthracycline-containing chemotherapy regimens. Left ventricular function should be monitored prior to and during treatment.
• It should be stopped in patients receiving adjuvant therapy, and withheld in patients with metastatic cancer if the function of the heart decreases significantly.

Herceptin (trasuzumab) side effects

Common side effects include:

• Diarrhea (25% of patients)
• A prickling or burning sensation in the skin (9% of patients)
• Either an upper respiratory or a catheter-related infection (26% of patients)
• Increased cough (26% of patients)
• Nausea and vomiting (23%-33% of patients)
• Rash (18% of patients)
• infusion-related side effects including mild to moderate chills and/or fever (40% of patients)
• Insomnia
• Weight loss
• Stomatitis
• Shortness of breath
• Distortion of taste
• Fatigue
• Pain
• Cough
• Dizziness

Other side effects include:

• Bone pain
• Joint pain
• Muscle pain
• Increased heart rate
• Body swelling (edema)
• Acne
• Headache

Possible serious side effects include:

• Heart failure
• Pulmonary toxicity
• Serious allergic reactions
• Fetal toxicity
• Decreased red and/or white blood cells,
• Herpes simplex infections
• Urinary tract infections
• Depression
• Neutropenia
• Anemia
• Leukopenia
• Sepsis
• Glomerulonephritis

Trastuzumab can cause serious and fatal infusion reactions and pulmonary toxicity. Symptoms usually occur during treatment or within 24 hours of treatment. The infusion should be interrupted if patients develop shortness of breath or significant reduction in blood pressure, and patients should be monitored until symptoms completely resolve.

Trastuzumab should be stopped if any of the following occurs:

• Anaphylaxis
• Angioedema
• Interstitial pneumonia
• Acute respiratory distress syndrome

Use of trastuzumab during pregnancy can cause oligohydramnios and oligohydramnios sequence, manifesting as pulmonary hypoplasia, skeletal abnormalities, and death of the baby.

• Trastuzumab or Herceptin can cause fetal harm when administered to pregnant women and should not be administered during pregnancy.
• It is not known whether trastuzumab is excreted in human milk. Nursing mothers should decide whether to stop nursing or discontinue the drug.
• Use of trastuzumab during pregnancy can cause oligohydramnios and oligohydramnios sequence, manifesting as pulmonary hypoplasia, skeletal abnormalities, and death of the baby.

• Paclitaxel may increase blood levels of trastuzumab.

• Trastuzumab is administered by intravenous infusion over 30 to 90 minutes.

Herceptin for adjuvant treatment

• The recommended dose of trastuzumab during and following paclitaxel (Taxol), docetaxel (Taxotere), or docetaxel/carboplatin (Paraplatin) treatment is 4 mg per kilogram of body weight followed by a weekly dose of 2 mg per kilogram of body weight for 12 weeks or 18 weeks.
• When it is used alone the dose is 8 mg/kg initially followed by 6 mg/kg every 3 weeks.

Herceptin for Metastatic breast cancer treatment

• Trastuzumab 4 mg/kg is administered alone or in combination with paclitaxel followed by once weekly doses of 2 mg/kg until there is disease progression.

Herceptin Metastatic Gastric Cancer

• The initial dose of trastuzumab is 8 mg/kg then 6 mg/kg every 3 weeks until there is disease progression.

What preparations of trastuzumab are available?

• Trastuzumab is available as a powder in a vial containing 440 mg of the drug. It must be mixed with a liquid before intravenous injection.

How should I keep it stored?

• Trastuzumab should be stored at 2 C to 8 C (36F to 46 F), and should not be frozen.

When was XYZ approved by the FDA?

• Trastuzumab was approved by the FDA in 1998.