Compound Name:TrastuzumabMolecular Target:c-erbB2/HER2Molecular Structure:humanized receptor antagonistLicensed Indication:HER2 overexpressing breast cancerManufacturer and/or Distributor:GenentechInitial FDA Approval1998SummaryTrastuzumab (Herceptin) is a humanized recombinant IgG1k monoclonal antibody targeted at the extracellular domain (Subdomain II) of the human epidermal growth factor receptor 2 protein (HER2, also known as Neu, c-erbB2, CD340 or p185). HER2 is a transmembrane receptor protein, which is overexpressed in some malignancies, including about 25% of breast cancers and perhaps a somewhat smaller percentage of gastric carcinomas. Trastuzumab is administered by intravenous infusion every 1 or 3 weeks, depending on the indication. Herceptin was FDA approved for the treatment of HER2-positive breast cancer in 1998. In combination with chemotherapy for treatment of metastatic disease, trastuzumab has been reported to prolong survival. Adding trastuzumab to chemotherapy significantly improved the overall and disease-free survival of a combined 4046 patients with early HER2-positive breast cancer. It can also be used as adjuvant treatment, where it has been shown to prolong disease-free survival. In 2010, an indication was added for HER2-positive, metastatic, gastric or gastroesophageal junction adenocarcinoma, where an improvement in survival was found. Significant safety concerns are cardiac and pulmonary toxicity, infusion reactions, neutropenia, and embryo-fetal toxicity. Trastuzumab is being studied for possible use in other cancers, including lung, other GI, and genitourinary.References

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