No

Monoclonal Antibody

Single agent for the treatment of patients with metastatic breast cancer whose tumors overexpress the HER2/neu protein and who have received one or more chemotherapy regimens for their metastatic disease

Combination therapy with paclitaxel for the treatment of patients with metastatic breast cancer whose tumors overexpress the HER2/neu protein and who have not received chemotherapy for their metastatic disease

Note: HER2/neu protein overexpression or amplification has been noted in ovarian, gastric, colorectal, endometrial, lung, bladder, prostate, and salivary gland tumors. It is not yet known whether trastuzumab may be effective in these other carcinomas which overexpress HER2/neu protein.

B

It is not known whether trastuzumab is secreted in human milk; because many immunoglobulins are secreted in milk, and the potential for serious adverse reactions exists, patients should discontinue nursing during treatment and for 6 months after the last dose

Congestive heart failure associated with trastuzumab may be severe and has been associated with disabling cardiac failure, death, mural thrombus, and stroke. Left ventricular function should be evaluated in all patients prior to and during treatment with trastuzumab. Discontinuation should be strongly considered in patients who develop a clinically significant decrease in ejection fraction during therapy. Combination therapy which includes anthracyclines and cyclophosphamide increases the incidence and severity of cardiac dysfunction. Extreme caution should be used when treating patients with pre-existing cardiac disease or dysfunction, and in patients with previous exposure to anthracyclines. Advanced age may also predispose to cardiac toxicity. Use with caution in patients with known hypersensitivity to trastuzumab, Chinese hamster ovary cell preparations or any component of this product.

>10%:

Central nervous system: Pain (47%), fever (36%), chills (32%), headache (26%)

Dermatologic: Rash (18%)

Neuromuscular & skeletal: Weakness (42%), back pain (22%)

Gastrointestinal: Nausea (33%), diarrhea (25%), vomiting (23%), abdominal pain (22%), anorexia (14%)

Respiratory: Cough (26%), dyspnea (22%), rhinitis (14%), pharyngitis (12%)

Miscellaneous: Infection (20%)

1% to 10%:

Cardiovascular: Peripheral edema (10%), congestive heart failure (7%), tachycardia (5%)

Central nervous system: Insomnia (14%), dizziness (13%), paresthesia (9%), depression (6%), peripheral neuritis (2%), neuropathy (1%)

Dermatologic: Herpes simplex (2%), acne (2%)

Gastrointestinal: Nausea and vomiting (8%)

Genitourinary: Urinary tract infection (5%)

Hematologic: Anemia (4%), leukopenia (3%)

Neuromuscular & skeletal: Bone pain (7%), arthralgia (6%)

Respiratory: Sinusitis (9%)

Miscellaneous: Flu syndrome (10%), accidental injury (6%), allergic reaction (3%)

<1%: Anaphylaxis, respiratory distress, adult respiratory distress syndrome (ARDS), severe infusion reaction, vascular thrombosis, pericardial effusion, cardiac arrest, hypotension, hemorrhage, shock, arrhythmia, syncope, cellulitis, hypothyroidism, gastroenteritis, hematemesis, ileus, intestinal obstruction, colitis, esophageal ulcer, stomatitis, pancreatitis, pancytopenia, acute leukemia, coagulopathy, lymphangitis, ascites, hydrocephalus, hepatic failure, hepatitis, amblyopia, deafness, anaphylactoid reaction, radiation injury

There is no experience with overdosage in human trials; single doses >500 mg have not been tested

Increased effect: Paclitaxel may result in a decrease in clearance of trastuzumab, increasing serum concentrations

Store intact vials under refrigeration (2°C to 8°C/36°F to 46°F) prior to reconstitution. Reconstituted each vial with 20 mL of bacteriostatic sterile water for injection. Do not shake. This solution results in a concentration of 21 mg/mL and is stable for 28 days from the date of reconstitution under refrigeration. If the patient has a known hypersensitivity to benzyl alcohol, trastuzumab may be reconstituted with sterile water for injection which must be used immediately.

Trastuzumab is a monoclonal antibody which binds to the extracellular domain of the human epidermal growth factor receptor 2 protein (HER2); it mediates antibody-dependent cellular cytotoxicity against cells which overproduce HER2

Distribution: V_d: 44 mL/kg

Half-life: Mean: 5.8 days (range: 1-32 days)

I.V. infusion:

Initial loading dose: 4 mg/kg intravenous infusion over 90 minutes

Maintenance dose: 2 mg/kg intravenous infusion over 90 minutes (can be administered over 30 minutes if prior infusions are well tolerated) weekly until disease progression

Dosing adjustment in renal impairment: Data suggest that the disposition of trastuzumab is not altered based on age or serum creatinine (up to 2 mg/dL); however, no formal interaction studies have been performed

Dosing adjustment in hepatic impairment: No data is currently available

Signs and symptoms of cardiac dysfunction

Insomnia and dizziness are common; may cause depression

None noted

No information available to require special precautions

Stomatitis occurs in <1% of patients

This medication can only be administered by infusion. Report immediately any adverse reactions during infusion (eg, chills, fever, headache, backache, or nausea/vomiting) so appropriate medication can be administered. You will be susceptible to infection (avoid crowds or exposure to persons with infections or contagious diseases). You may experience dizziness or weakness (use caution when driving or engaging in tasks requiring alertness until response to drug is known); nausea or vomiting (small frequent meals, frequent mouth care, chewing gum, or sucking lozenges may help); diarrhea (boiled milk, yogurt, or buttermilk may help); or headache, back or joint pain (mild analgesics may offer relief). Report persistent gastrointestinal effects; sore throat, runny nose, or difficulty breathing; chest pain, irregular heartbeat, palpitations, swelling of extremities, or unusual weight gain; muscle or joint weakness, numbness, or pain; skin rash or irritation; itching or pain on urination; unhealed sores, white plaques in mouth or genital area, unusual bruising or bleeding; or other unusual effects related to this medication. Breast-feeding precautions: Breast-feeding is not recommended.

Injection: Vial, 440 mg, with vial of bacteriostatic water for injection

Baselga J, Norton L, Albanell J, et al, "Recombinant Humanized Anti-HER2 Antibody (Herceptin™) Enhances the Antitumor Activity of Paclitaxel and Doxorubicin Against HER2/neu Overexpressing Human Breast Cancer Xenografts," Cancer Res, 1998, 58(13):2825-31.

Pegram MD, Lipton A, Hayes DF, et al, "Phase II Study of Receptor-Enhanced Chemosensitivity Using Recombinant Humanized Anti-p185 HER2/neu Monoclonal Antibody Plus Cisplatin in Patients With HER2/neu-Overexpressing Metastatic Breast Cancer Refractory to Chemotherapy Treatment," J Clin Oncol, 1998, 16(8):2659-71.