New drugs and new combinations of drugs have recently shown promising clinical 
activity in hormone refractory prostate cancer. We studied the association of 
gefitinib with trastuzumab on the androgen-refractory prostate cancer cell line 
DU145 expressing both epidermal growth factor receptor (EGFR) and HER-2. Drug 
combinations with radiotherapy (RT) were considered along with the analysis of 
factors linked to cell proliferation and apoptosis. The antitumour effects of 
gefitinib were more pronounced than those observed with trastuzumab. In mice 
receiving the gefitinib-trastuzumab combination, reduction in tumour volume was 
inferior to that predicted by the observed impact of the agents alone. The 
presence of trastuzumab markedly attenuated the relative increase on p27 
expression and the Bax:Bcl2 ratio induced by gefitinib. The combination 
gefitinib-RT had similar antitumour effects as those predicted by the impact of 
the individual treatments, whereas the effect of the trastuzumab-RT combination 
was inferior to that predicted by the individual effects. The present data 
should be borne in mind when designing new clinical schedules for treatment of 
hormone-refractory prostate cancer including the use of HER inhibitors.