Response of prostate cancer to anti-Her-2/neu antibody in androgen-dependent and -independent human xenograft models

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 utili ty 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 mode ls 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 h ad been established. No effect of Herceptin on tumor growth was observed in any of the androgen-independent tumors; however, significant growth inhibi tion was observed in both of the androgen-dependent xenograft models, CWR22 (68% growth inhibition at the completion of the experiment; P = 0.03 for t rajectories of the average tumor volume of the groups) and LNCaP (89% growt h inhibition; P = 0.002). There was a significant increase in prostate-spec ific antigen (PSA) index (ng PSA/ml serum/mm(3) tumor) in Herceptin-treated androgen-dependent groups compared with control (CWR22, 18-fold relative t o 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 m g/kg s.c., five times/week) was given to animals with androgen-dependent an d -independent tumors, there was growth inhibition in each group. Paclitaxe l 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 paclitax el, in both androgen-dependent and androgen-independent tumors. Response to Herceptin did not correlate with the PSA levels, because the PSA index mar kedly increased in the Herceptin-treated group, whereas it remained constan t in the control group. These results suggest the utility of Herceptin in t he treatment of human prostate cancer.