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

David B. Agus, Howard I. Scher, Brian Higgins, William D. Fox, Glenn Heller, Melissa Fazzari, Carlos Cordon-Cardo, David W. Golde

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)4761-4764
Number of pages4
JournalCancer Research
Volume59
Issue number19
StatePublished - Oct 1 1999
Externally publishedYes

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Heterografts
Androgens
Prostatic Neoplasms
Antibodies
Prostate-Specific Antigen
Growth
Neoplasms
Paclitaxel
Breast Neoplasms
erbB-2 Genes
Trastuzumab
Tumor Burden
Staining and Labeling
Control Groups

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Agus, D. B., Scher, H. I., Higgins, B., Fox, W. D., Heller, G., Fazzari, M., ... Golde, D. W. (1999). Response of prostate cancer to anti-Her-2/neu antibody in androgen- dependent and -independent human xenograft models. Cancer Research, 59(19), 4761-4764.

Response of prostate cancer to anti-Her-2/neu antibody in androgen- dependent and -independent human xenograft models. / Agus, David B.; Scher, Howard I.; Higgins, Brian; Fox, William D.; Heller, Glenn; Fazzari, Melissa; Cordon-Cardo, Carlos; Golde, David W.

In: Cancer Research, Vol. 59, No. 19, 01.10.1999, p. 4761-4764.

Research output: Contribution to journalArticle

Agus, DB, Scher, HI, Higgins, B, Fox, WD, Heller, G, Fazzari, M, Cordon-Cardo, C & Golde, DW 1999, 'Response of prostate cancer to anti-Her-2/neu antibody in androgen- dependent and -independent human xenograft models', Cancer Research, vol. 59, no. 19, pp. 4761-4764.
Agus, David B. ; Scher, Howard I. ; Higgins, Brian ; Fox, William D. ; Heller, Glenn ; Fazzari, Melissa ; Cordon-Cardo, Carlos ; Golde, David W. / Response of prostate cancer to anti-Her-2/neu antibody in androgen- dependent and -independent human xenograft models. In: Cancer Research. 1999 ; Vol. 59, No. 19. pp. 4761-4764.
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abstract = "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.",
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AU - Scher, Howard I.

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AU - Fazzari, Melissa

AU - Cordon-Cardo, Carlos

AU - Golde, David W.

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N2 - 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.

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