Efficacy and safety of trastuzumab
Jones, Robin L., Smith, Ian E.
Efficacy and safety of trastuzumab.
EXPERT OPINION ON DRUG SAFETY, 3 (4).
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The human epidermal growth factor receptor (HER) 2 is overexpressed in approximately 20-25% of human breast cancers and is an independent adverse prognostic factor. Targeted therapy directed against this receptor has been developed in the form of a humanised monoclonal antibody, trastuzumab. This antibody has shown activity as a single agent in metastatic breast cancer both prior to chemotherapy and in heavily pretreated patients. A pivotal Phase III trial has demonstrated that its use in combination with an anthracycline or paclitaxel results in a significant improvement in survival, time to progression, and response. This has recently been reinforced by another trial with docetaxel. The HER2 status of a tumour is a critical determinant of response to trastuzumab-based treatment. Those that express HER2 at the highest level on immunohistochemistry (IHC), 3+, derive more benefit from treatment with trastuzumab than those with overexpression at the 2+ level. Benefit correlates best with tumours that are positive on fluorescence in situ hybridisation for HER2, regardless of IHC status. Treatment with trastuzumab is generally well tolerated with a low incidence of adverse events. Some patients may experience fever, chills, dyspnoea and pain, particularly with the first administration. Unexpectedly, cardiac toxicity has developed in some patients treated with trastuzumab, and this has a higher incidence in those treated in combination with an anthracycline. 'Cross-talk' between the oestrogen receptor and HER2 pathway has stimulated interest in using trastuzumab in combination with endocrine therapy. Current clinical trials are investigating the role of this agent in the adjuvant setting.
|Item Type:||Review Article|
|Authors (ICR Faculty only):||Smith, Ian|
|All Authors:||Jones, Robin L., Smith, Ian E.|
|Uncontrolled Keywords:||Antibodies, Monoclonal / *adverse effects; *therapeutic use. Antineoplastic Agents / *adverse effects; *therapeutic use. Antineoplastic Combined Chemotherapy Protocols. Breast Neoplasms / *drug therapy; genetics. Female. Gene Amplification. Genes, erbB-2. Heart Diseases / chemically induced. Humans. Lung Diseases / chemically induced. Neoadjuvant Therapy. Receptor, erbB-2 / analysis Index Medicus 0 / Antibodies, Monoclonal. 0 / Antineoplastic Agents. 0 / trastuzumab. EC 188.8.131.52 / Receptor, erbB-2|
|Research teams:||Clinical Units > Breast Unit|
|Depositing User:||Ashley Cousins|
|Date Deposited:||28 Aug 2008 15:01|
|Last Modified:||31 Mar 2009 14:23|
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