Uses
Trastuzumab is used to treat breast cancer. It is effective against tumors that overexpress the HER2/neu protien. As part of chemotherapy regimen for adjuvant treatment of lymph-node positive, HER2/neu positive cancer.
General Description
Trastuzumab (Herceptin, humanized) is an MAb engineeredfrom the human epidermal growth factor receptor type 2(HER2) protein. This MAb is a human–murine immunoglobulin.It contains human structural domains (framework) andthe CDR of a murine antibody (4D5) that binds specifically toHER2. IgG1 κ is the type structure, and the antibody is monoclonal.The protein inhibits the proliferation of human tumorcells that overexpress HER2.
Trastuzumab is indicated for use as a single agent for thetreatment of patients with metastatic breast cancer whose tumorsoverexpress the HER2 protein and who have not receivedchemotherapy for their metastatic disease.
The HER2 proto-oncogene encodes a transmembrane receptorprotein of 185 kDa that is structurally related to theepidermal growth factor receptor HER2. Overexpression ofthis protein is observed in 25% to 30% of primary breastcancers. Trastuzumab binds with high affinity to the extracellulardomain of HER2. It inhibits the proliferation ofhuman tumor cells that overexpress HER2. Trastuzumabalso mediates the process of antibody-mediated cellular cytotoxicity(ADCC). This process, leading to cell death, ispreferentially exerted on HER2-overexpressing cancer cellsover those that do not overexpress HER2.
Clinical Use
Humanized monoclonal antibody that
binds selectively to the epidermal growth
factor receptor 2 (HER2) protein. Used in
treating some breast carcinomas that
overexpress HER2.
Drug interactions
Potentially hazardous interactions with other drugs
Antipsychotics: avoid with clozapine - increased risk
of agranulocytosis.
Cytotoxics: possible increased risk of cardiotoxicity
with daunorubicin, doxorubicin, epirubicin and
idarubicin - avoid for up to 28 weeks after stopping
trastuzumab.
Vaccines: risk of generalised infections with live
vaccines - avoid.
Metabolism
Trastuzumab is most likely removed by opsonisation via
the reticuloendothelial system.
