Antibody to the Her-2/neu gene product has been shown to inhibit the growth of 
breast cancer cells overexpressing Her-2/neu and to have clinical utility in 
treating breast cancer. We studied a recombinant, humanized anti-Her-2/neu 
antibody (Herceptin) in preclinical models of human prostate cancer. The 
androgen-dependent CWR22 and LNCaP human prostate cancer xenograft models and 
androgen-independent sublines of CWR22 were used. Her-2/neu staining of the 
parental, androgen-dependent, and androgen-independent CWR22 tumors and LNCaP 
tumors demonstrated variable Her-2/neu expression. Herceptin was administered 
i.p. at a dose of 20 mg/kg twice weekly after the xenograft had been 
established. No effect of Herceptin on tumor growth was observed in any of the 
androgen-independent tumors; however, significant growth inhibition was observed 
in both of the androgen-dependent xenograft models, CWR22 (68% growth inhibition 
at the completion of the experiment; P = 0.03 for trajectories of the average 
tumor volume of the groups) and LNCaP (89% growth inhibition; P = 0.002). There 
was a significant increase in prostate-specific antigen (PSA) index (ng PSA/ml 
serum/mm3 tumor) in Herceptin-treated androgen-dependent groups compared with 
control (CWR22, 18-fold relative to pretreatment value versus 1.0-fold, P = 
0.0001; LNCaP, 2.35-fold relative to pretreatment value versus 0.6-fold, P = 
0.001). When paclitaxel (6.25 mg/kg s.c., five times/week) was given to animals 
with androgen-dependent and -independent tumors, there was growth inhibition in 
each group. Paclitaxel and Herceptin cotreatment led to greater growth 
inhibition than was seen for the agents individually. Thus, in these prostate 
cancer model systems, Herceptin alone has clinical activity only in the 
androgen-dependent tumor and has at least an additive effect on growth, in 
combination with paclitaxel, in both androgen-dependent and androgen-independent 
tumors. Response to Herceptin did not correlate with the PSA levels, because the 
PSA index markedly increased in the Herceptin-treated group, whereas it remained 
constant in the control group. These results suggest the utility of Herceptin in 
the treatment of human prostate cancer.