BACKGROUND: Overexpression of the HER-2/neu oncoprotein has been reported to 
occur in </= 60% of patients with prostate carcinoma and to correlate with 
shortened survival. Trastuzumab is a humanized monoclonal antibody to the HER-2 
receptor and has activity against HER-2-positive breast carcinoma, more so when 
combined with a taxane. The authors screened for HER-2 overexpression in 
patients developing hormone-refractory prostate carcinoma (HRPC) and conducted a 
Phase II trial of trastuzumab plus docetaxel in HER-2-positive patients.
METHODS: Paraffin-embedded tumor specimens from potentially eligible patients 
were screened for HER-2 expression by immunohistochemistry (IHC) and/or 
amplification by fluorescent in situ hybridization (FISH). Shed HER-2 was also 
assessed by enzyme-linked immunoradsorbent assay (ELISA). Patients with 
HER-2-positive tumor specimens (IHC 2+ or 3+ or FISH ratio > 2) were initially 
randomized to receive either single-agent trastuzumab or docetaxel. After two 
treatment cycles, nonresponding patients received the trastuzumab/docetaxel 
combination. Treatment was comprised of 30 mg/m(2) of docetaxel weekly for 6 
weeks followed by a 2-week break and 4 mg/kg of trastuzumab intravenously during 
Week 1 then 2 mg/kg per week thereafter. The cycle length was 8 weeks.
RESULTS: One hundred patients with HPRC were screened. IHC results were as 
follows: 3+ (n = 1), 2+ (n = 6), 1+ (n = 26), 0 (n = 39), and insufficient 
tissue specimen/not tested (n = 28). Only 3 of 37 patients had elevated shed 
HER-2 by ELISA (> 15 mg/mL). None overexpressed HER-2 by IHC. FISH amplification 
was found in 0 of 34 tissue samples. Of seven patients with IHC 3+ or 2+, four 
were tested by ELISA and two by FISH. None were abnormal. Age and Gleason score 
did not correlate with IHC status. Of the seven patients eligible for the Phase 
II study, only four agreed to participate. The trial was thus closed for 
nonfeasibility (the overall HER-2 positivity rate was < 20%). No patient 
responded to trastuzumab alone. The median survival was not reached and the 
median progression-free survival was 7 months.
CONCLUSIONS: HER-2 overexpression by IHC in archival prostate carcinoma 
specimens was infrequent. There was no apparent correlation among IHC, ELISA, 
and FISH, although the sample size was limited. Conclusions regarding the 
predictive value of HER-2 status on outcome after trastuzumab-based therapy were 
not reached and were only drawn after larger-scale screening efforts. The 
authors estimated that 1000 patients need to be screened to complete accrual to 
a 40-patient efficacy trial.