Trastuzumab Plus Docetaxel in HER-2/neu-Positive Prostate Carcinoma: Final Results from the California Cancer Consortium Screening and Phase II Trial

Primo N Lara, Karen Giselle Chee, Jeff Longmate, Christopher Ruel, Frederick J Meyers, Carl R. Gray, Regina F Gandour-Edwards, Paul H. Gumerlock, Przemyslaw Twardowski, James H. Doroshow, David R Gandara

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)2125-2131
Number of pages7
JournalCancer
Volume100
Issue number10
DOIs
StatePublished - May 15 2004

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docetaxel
Early Detection of Cancer
Prostate
Carcinoma
Immunohistochemistry
Fluorescence In Situ Hybridization
Enzymes
Trastuzumab

Keywords

  • Docetaxel
  • HER-2/neu
  • Hormone-refractory prostate carcinoma
  • Trastuzumab

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Trastuzumab Plus Docetaxel in HER-2/neu-Positive Prostate Carcinoma : Final Results from the California Cancer Consortium Screening and Phase II Trial. / Lara, Primo N; Chee, Karen Giselle; Longmate, Jeff; Ruel, Christopher; Meyers, Frederick J; Gray, Carl R.; Gandour-Edwards, Regina F; Gumerlock, Paul H.; Twardowski, Przemyslaw; Doroshow, James H.; Gandara, David R.

In: Cancer, Vol. 100, No. 10, 15.05.2004, p. 2125-2131.

Research output: Contribution to journalArticle

Lara, Primo N ; Chee, Karen Giselle ; Longmate, Jeff ; Ruel, Christopher ; Meyers, Frederick J ; Gray, Carl R. ; Gandour-Edwards, Regina F ; Gumerlock, Paul H. ; Twardowski, Przemyslaw ; Doroshow, James H. ; Gandara, David R. / Trastuzumab Plus Docetaxel in HER-2/neu-Positive Prostate Carcinoma : Final Results from the California Cancer Consortium Screening and Phase II Trial. In: Cancer. 2004 ; Vol. 100, No. 10. pp. 2125-2131.
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title = "Trastuzumab Plus Docetaxel in HER-2/neu-Positive Prostate Carcinoma: Final Results from the California Cancer Consortium Screening and Phase II Trial",
abstract = "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.",
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author = "Lara, {Primo N} and Chee, {Karen Giselle} and Jeff Longmate and Christopher Ruel and Meyers, {Frederick J} and Gray, {Carl R.} and Gandour-Edwards, {Regina F} and Gumerlock, {Paul H.} and Przemyslaw Twardowski and Doroshow, {James H.} and Gandara, {David R}",
year = "2004",
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TY - JOUR

T1 - Trastuzumab Plus Docetaxel in HER-2/neu-Positive Prostate Carcinoma

T2 - Final Results from the California Cancer Consortium Screening and Phase II Trial

AU - Lara, Primo N

AU - Chee, Karen Giselle

AU - Longmate, Jeff

AU - Ruel, Christopher

AU - Meyers, Frederick J

AU - Gray, Carl R.

AU - Gandour-Edwards, Regina F

AU - Gumerlock, Paul H.

AU - Twardowski, Przemyslaw

AU - Doroshow, James H.

AU - Gandara, David R

PY - 2004/5/15

Y1 - 2004/5/15

N2 - 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.

AB - 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.

KW - Docetaxel

KW - HER-2/neu

KW - Hormone-refractory prostate carcinoma

KW - Trastuzumab

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