Trastuzumab.
Trastuzumab is a recombinant humanised monoclonal antibody specific for the growth factor receptor p185(HER2) (HER2) which is overexpressed in 25 to 30% of breast cancer tumours. The drug inhibits the growth of human breast cancer cells overexpressing HER2 in vitro and in vivo. It shows additive antitumour activity in vitro and in vivo when administered with paclitaxel, doxorubicin, various cytokines or tamoxifen. In patients with metastatic breast cancer whose tumours overexpressed HER2, trastuzumab (4 mg/kg loading dose then 2 mg/kg/week by intravenous infusion) produced objective responses in 21% of 213 patients. A further 7% of patients had minor responses and 30% had stable disease. Combination therapy with trastuzumab and either paclitaxel or doxorubicin (or epirubicin) plus cyclophosphamide produced a higher response rate (49%), longer median time to disease progression (7.6 months), a higher one-year survival rate (78%) and significantly increased median overall survival (25.4 months) than antineoplastic agents alone (response rate 32%, time to disease progression 4.6 months, one-year survival rate 67% and overall survival 20.3 months) in a phase III study in 469 patients. Trastuzumab is generally well tolerated. Chills, fever, nausea, vomiting, weakness and headache were among the most common adverse events in clinical trials and occurred in 40 to 50% of patients during the first infusion of the drug. Cardiac dysfunction was the most serious adverse event reported and was more common in patients receiving trastuzumab plus antineoplastic therapy than in those receiving trastuzumab alone.
Perry
C M
CM
Adis International Limited, Auckland, New Zealand. demail@adis.co.nz
Wiseman
L R
LR