The incidence of human epidermal growth factor receptor 2 (HER2) protein 
overexpression and its prognostic value are not well characterized in patients 
with prostate cancer. A phase I study was designed to evaluate 
docetaxel/estramustine plus trastuzumab, a humanized monoclonal antibody that 
binds to the HER2 receptor, in patients with metastatic androgen-independent 
prostate cancer (AIPC). HER2 positivity was not required because safety was the 
primary endpoint. Patients received oral estramustine 280 mg three times daily 
(days 1 to 5); docetaxel, 70 mg/m(2) intravenously (day 2); and trastuzumab, 2 
mg/kg intravenously (days 2, 9, and 19), every 21 days until the disease 
progressed or toxicity became unacceptable. This regimen was well tolerated 
among the first 13 treated patients. Grade 4 neutropenia was seen in 10% of 
administered cycles. There were two episodes of febrile neutropenia and two 
thrombembolic events. Of the 13 patients evaluable for prostate-specific antigen 
(PSA) response, nine (69%) experienced a decrease in PSA level of >50%. Two 
(33%) of six patients with measurable disease had objective responses, and one 
complete response was seen on bone scan. Docetaxel/estramustine/trastuzumab 
appears to be a safe combination when used in the treatment of metastatic AIPC. 
The response data are too preliminary for speculation about the relative 
benefits of this 3-drug regimen compared with the combination of only docetaxel 
and estramustine in this clinical setting.