trastuzumab


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trastuzumab

 [tras-tuz´u-mab]
a monoclonal antibody that binds to a protein overexpressed in some breast cancers; used as an antineoplastic agent in treatment of metastatic breast cancer with such overexpression.

trastuzumab

Pharmacologic class: Recombinant DNA-derived monoclonal antibody

Therapeutic class: Antineoplastic

Pregnancy risk category B

FDA Box Warning

Drug can result in subclinical and clinical cardiac failure manifesting as congestive heart failure and decreased left ventricular ejection fraction.

Incidence and severity of left ventricular dysfunction were highest in patients who received trastuzumab concurrently with anthracycline-containing chemotherapy regimens.

Discontinue trastuzumab in patients receiving adjuvant therapy and strongly consider discontinuing in patients with metastatic breast cancer who develop clinically significant decrease in left ventricular function.

Monitor patients for decreased left ventricular function before starting trastuzumab and frequently during and after treatment. Monitor more frequently if drug is withheld in patients who develop significant left ventricular dysfunction.

Serious infusion reactions, some fatal, and pulmonary toxicity have occurred. In most cases, signs and symptoms occurred during or within 24 hours of administration. Interrupt infusion for patients experiencing dyspnea or clinically significant hypotension.

Discontinue drug for infusion reactions manifesting as anaphylaxis, angioedema, interstitial pneumonitis, or acute respiratory distress syndrome.

Exacerbation of chemotherapy-induced neutropenia has also occurred.

Action

Selectively binds to human epidermal growth factor receptor 2 (HER2), inhibiting proliferation of human tumor cells that overexpress HER2

Availability

Lyophilized powder: 440-mg vial (each vial contains 20 ml bacteriostatic water for injection, 1.1% benzyl alcohol)

Indications and dosages

Metastatic breast cancer in patients whose tumors overexpress HER2

Adults: As monotherapy, loading dose of 4 mg/kg I.V. infusion over 90 minutes, followed by weekly maintenance dose of 2 mg/kg I.V. infusion given over 30 minutes if loading dose was tolerated. Don't give by I.V. push.

Contraindications

None

Precautions

Use cautiously in:
• hypersensitivity to Chinese hamster ovary cell protein or to benzyl alcohol
• cardiac disease, anemia, leukopenia
• elderly patients
• pregnant or breastfeeding patients
• children younger than age 18 (safety and efficacy not established).

Administration

• Be aware that baseline left ventricular ejection fraction (LVEF) measurement should be performed immediately before starting drug.
• Follow facility policy for handling, administering, and disposal of carcinogenic, mutagenic, and teratogenic agents.
• Give antiemetic, as prescribed, before administering trastuzumab.

Administer by I.V. infusion only. Don't give by I.V. push or bolus.
• To reconstitute, add 20 ml of bacteriostatic water for injection to vial, pointing diluent stream at lyophilized cake. Swirl vial gently; don't shake. Withdraw prescribed dose and add it to 250 ml of normal saline solution. (Don't use dextrose 5% in water.)
• Infuse loading dose I.V. over 90 minutes. Infuse weekly doses I.V. over 30 minutes.
• Immediately after reconstituting, write a date that is 28 days from reconstitution date in the space after "Do not use after" on vial label.
• If patient has benzyl alcohol hypersensitivity, reconstitute with sterile water for injection. Use immediately after reconstitution; discard unused portion.

Never administer intrathecally; doing so causes death.
• Know that for patient who hasn't previously received chemotherapy for metastatic disease, drug is given at same dosage but in combination with paclitaxel.

Adverse reactions

CNS: dizziness, headache, depression, paresthesia, insomnia, ataxia, confusion, manic reaction, seizures

CV: peripheral edema, hypotension, tachycardia, syncope, arrhythmias, shock, pericardial effusion, vascular thrombosis, heart failure, cardiotoxicity, cardiac arrest, cardiomyopathy

EENT: amblyopia, hearing loss

GI: nausea, vomiting, diarrhea, gastroenteritis, hematemesis, colitis, esophageal ulcer, stomatitis, ileus, anorexia, intestinal obstruction, pancreatitis

GU: urinary tract infection, hematuria, hemorrhagic cystitis, hydronephrosis, pyelonephritis, renal failure

Hematologic: coagulation disorder, pancytopenia, leukemia, exacerbation of chemotherapy-induced neutropenia

Hepatic: ascites, hepatitis, hepatic failure

Metabolic: hypothyroidism, hypercalcemia, hyponatremia

Musculoskeletal: back, bone, or joint pain; myopathy; fractures; bone necrosis

Respiratory: upper respiratory infection, dyspnea, pulmonary toxicity (dyspnea, interstitial pneumonitis, pulmonary infiltrates, pleural effusions, noncardiogenic pulmonary edema, pulmonary insufficiency and hypoxia, acute respiratory distress syndrome, pulmonary fibrosis)

Skin: cellulitis, rash, acne, herpes simplex, herpes zoster, skin ulcers

Other: weight loss, edema, infection, fever, chills, flulike syndrome, lymphangitis, hypersensitivity reactions including anaphylaxis, infusion reaction

Interactions

Drug-drug. Anthracyclines, cyclophosphamide: cardiotoxicity

Patient monitoring

Monitor closely for signs and symptoms of infusion reaction (including respiratory distress). Halt infusion if these occur.
• Monitor vital signs, especially for hypotension and bradycardia.

Use with extreme caution in patients with cardiac dysfunction. Assess cardiovascular status carefully; stay alert for heart failure, cardiomyopathy, and peripheral edema.
• Assess neurologic status for depression and paresthesia.
• Monitor respiratory status. Report increased dyspnea or flulike symptoms.
• Watch closely for signs and symptoms of infection, including herpes simplex.
• Monitor electrolyte levels and CBC with white cell differential.
• Monitor LVEF measurement every 3 months during and at completion of therapy; measure LVEF at 4-week intervals if drug is withheld for significant left ventricular cardiac dysfunction. Continue LVEF measurement every 6 months for at least 2 years after completion of therapy.

Patient teaching

Instruct patient to immediately report difficulty breathing, flulike symptoms, and fever, chills, and other signs and symptoms of infection.

Advise patient to monitor weight. Tell him to report sudden weight gain as well as swelling and other signs and symptoms of heart failure.

Instruct patient to immediately report abdominal pain, change in bowel habits, yellowing of skin or eyes, and easy bruising or bleeding.
• Tell patient drug may cause depression. Advise him (or significant other as appropriate) to contact prescriber if this occurs.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs mentioned above.

trastuzumab

/tras·tuz·u·mab/ (tras-tuz´u-mab) a monoclonal antibody that binds to a protein overexpressed in some breast cancers; used as an antineoplastic in the treatment of metastatic breast cancer with such overexpression.

trastuzumab

(trăs-to͞o′zə-măb′)
n.
A humanized monoclonal antibody used intravenously to treat certain types of breast cancer and gastric cancer.

trastuzumab

a miscellaneous antineoplastic.
indications It is used in the treatment of metastatic breast cancer with the overexpression of HER2.
contraindications Factors that prohibit its use include known hypersensitivity to this drug or to Chinese hamster ovary cell protein.
adverse effects Life-threatening effects are tachycardia, congestive heart failure, and leukopenia. Other adverse reactions include depression, insomnia, neuropathy, peripheral neuritis, acne, herpes simplex, nausea, vomiting, anorexia, diarrhea, anemia, arthralgia, bone pain, edema, peripheral edema, cough, dyspnea, pharyngitis, rhinitis, and sinusitis. Common side effects include dizziness, numbness, paresthesias, rash, and flulike syndrome (fever, headache, chills).

trastuzumab

Herceptin® Oncology A bioengineered monoclonal antibody used to manage Pts with breast CA who overexpress HER2, which transmits growth signals to breast CA cells. See HER2.

trastuzumab

A monoclonal antibody drug used to treat breast cancers that over-express the HER2 growth factor receptor. Trastuzumab blocks the receptors on cancer cells thus preventing the growth factor from promoting reproduction and growth of the cancer cells. In May 2005 it was announced that an international trial called Hera involving 5000 women in 39 countries had shown a 46 percent reduction in the risk of recurrence of the early stages of this kind of cancer by the use of trastuzumab. The drug is being tested on a range of other cancers. A brand name is Herceptin.
References in periodicals archive ?
Marketing applications for trastuzumab emtansine (T-DM1), the most advanced compound using ImmunoGen's TAP technology, are under review in the US and Europe.
Developed by Genentech, trastuzumab was approved by FDA to be used in the clinic in September 1998 under the trade name of Herceptin, a major product of Roche.
The results of BOLERO-1, a Phase III, randomized, double-blind, placebo-controlled multicenter trial of 719 patients with HER2+ locally advanced or metastatic breast cancer, showed that the median PFS with everolimus plus trastuzumab and paclitaxel was 15.
The risk of developing new-onset heart failure or left ventricular dysfunction during 1 year on trastuzumab (Herceptin) was 65% lower in 30 breast cancer patients who were incidentally on a beta-blocker at the start of the monoclonal antibody therapy than in 167 other breast cancer patients who were not, Thomas B.
These findings imply that any positive test result maybe predictive of benefit from trastuzumab therapy in the adjuvant setting.
In the trial, researchers randomly assigned 137 women to treatment with either trastuzumab plus the chemotherapy drug docetaxel, or T-DM1.
In contrast to the clear evidence of irreversible ultrastructural change in cardiac muscle caused by the anthracyclines, biopsy studies in individuals exposed to trastuzumab show no abnormalities.
Trastuzumab can cause cardiotoxic effects--including left ventricular (LV) cardiac dysfunction, dysrhythmias, hypertension, cardiac failure, cardiomyopathy, and death--with reported incidence rates ranging from 2.
Trastuzumab (Herceptin), a targeted monoclonal antibody, was initially approved in 1998 for use in HER2-positive metastatic breast cancer as a first line therapy in combination with paclitaxel and as a single agent in second- and third-line therapy.
We are very pleased that the FDA has granted trastuzumab emtansine a Priority Review, as we know people with HER2-positive metastatic breast cancer still need new treatment options," said Hal Barron, M.
In the CHER-LOB study, 121 patients with HER-2 positive breast cancer were randomly assigned to treatment with neoadjuvant chemotherapy plus trastuzumab, lapatinib, or both trastuzumab and lapatinib.
Contract notice: Trastuzumab Dose Banded Medicines.