Neoadjuvant docetaxel before radical prostatectomy in patients with high-risk localized prostate cancer

Phillip G. Febbo, Jerome P. Richie, Daniel J. George, Massimo Loda, Judith Manola, Sridhar Shankar, Agnieska Szot Barnes, Clare Tempany, William Catalona, Philip W. Kantoff, William K. Oh

Research output: Contribution to journalArticle

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Abstract

Purpose: To determine the clinical, pathologic, and molecular effects of neoadjuvant docetaxel chemotherapy in high-risk localized prostate cancer. Experimental Design: Patients with biopsy Gleason scores of 8 to 10, serum prostate-specific antigen levels >20 ng/mL, and/or clinical stageT 3 disease received weekly docetaxel (36 mg/m2) for 6 months, followed by radical prostatectomy, and were monitored with weekly visits, serum prostate-specific antigen measurements, and endorectal magnetic resonance imaging (MRI). Frozen tumor specimens were collected for microarray analysis. Results: The 19 patients enrolled received 82% of the planned chemotherapy. Toxicity was mild to moderate; fatigue and taste disturbance were common. Prostate-specific antigen declines of >50% were seen in 11 of 19 patients (58%; 95% confidence interval, 33-80%) and endorectal MRI showed maximum tumor volume reduction of at least 25% in 13 of 19 patients (68%; 95% confidence interval, 47-85%) and at least 50% in 4 patients (21%; 95% confidence interval, 6-46%). Sixteen patients completed chemotherapy and had radical prostatectomy; none achieved pathologic complete response. Microarray analysis identified coordinate up-regulation of genes involved in androgen metabolism associated with docetaxel therapy. Specifically, RNA expression for genes that decrease cellular levels of bioactive androgens was coordinately increased in response to chemotherapy. Conclusions: Neoadjuvant docetaxel administered for 6 months before radical prostatectomy is feasible, well tolerated, and often results in prostate-specific antigen declines of >50% and decreased tumor volume on endorectal MRI. No pathologic; complete responses were observed. Altered androgen metabolism may partially account for the noted declines in prostate-specific antigen and be a mechanism for chemotherapy resistance.

Original languageEnglish (US)
Pages (from-to)5233-5240
Number of pages8
JournalClinical Cancer Research
Volume11
Issue number14
DOIs
StatePublished - Jul 15 2005

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docetaxel
Prostatectomy
Prostate-Specific Antigen
Prostatic Neoplasms
Drug Therapy
Androgens
Magnetic Resonance Imaging
Confidence Intervals
Microarray Analysis
Tumor Burden
Neoplasm Grading
Serum
Fatigue
Research Design
Up-Regulation
RNA
Biopsy
Gene Expression

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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Neoadjuvant docetaxel before radical prostatectomy in patients with high-risk localized prostate cancer. / Febbo, Phillip G.; Richie, Jerome P.; George, Daniel J.; Loda, Massimo; Manola, Judith; Shankar, Sridhar; Barnes, Agnieska Szot; Tempany, Clare; Catalona, William; Kantoff, Philip W.; Oh, William K.

In: Clinical Cancer Research, Vol. 11, No. 14, 15.07.2005, p. 5233-5240.

Research output: Contribution to journalArticle

Febbo, PG, Richie, JP, George, DJ, Loda, M, Manola, J, Shankar, S, Barnes, AS, Tempany, C, Catalona, W, Kantoff, PW & Oh, WK 2005, 'Neoadjuvant docetaxel before radical prostatectomy in patients with high-risk localized prostate cancer', Clinical Cancer Research, vol. 11, no. 14, pp. 5233-5240. https://doi.org/10.1158/1078-0432.CCR-05-0299
Febbo, Phillip G. ; Richie, Jerome P. ; George, Daniel J. ; Loda, Massimo ; Manola, Judith ; Shankar, Sridhar ; Barnes, Agnieska Szot ; Tempany, Clare ; Catalona, William ; Kantoff, Philip W. ; Oh, William K. / Neoadjuvant docetaxel before radical prostatectomy in patients with high-risk localized prostate cancer. In: Clinical Cancer Research. 2005 ; Vol. 11, No. 14. pp. 5233-5240.
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abstract = "Purpose: To determine the clinical, pathologic, and molecular effects of neoadjuvant docetaxel chemotherapy in high-risk localized prostate cancer. Experimental Design: Patients with biopsy Gleason scores of 8 to 10, serum prostate-specific antigen levels >20 ng/mL, and/or clinical stageT 3 disease received weekly docetaxel (36 mg/m2) for 6 months, followed by radical prostatectomy, and were monitored with weekly visits, serum prostate-specific antigen measurements, and endorectal magnetic resonance imaging (MRI). Frozen tumor specimens were collected for microarray analysis. Results: The 19 patients enrolled received 82{\%} of the planned chemotherapy. Toxicity was mild to moderate; fatigue and taste disturbance were common. Prostate-specific antigen declines of >50{\%} were seen in 11 of 19 patients (58{\%}; 95{\%} confidence interval, 33-80{\%}) and endorectal MRI showed maximum tumor volume reduction of at least 25{\%} in 13 of 19 patients (68{\%}; 95{\%} confidence interval, 47-85{\%}) and at least 50{\%} in 4 patients (21{\%}; 95{\%} confidence interval, 6-46{\%}). Sixteen patients completed chemotherapy and had radical prostatectomy; none achieved pathologic complete response. Microarray analysis identified coordinate up-regulation of genes involved in androgen metabolism associated with docetaxel therapy. Specifically, RNA expression for genes that decrease cellular levels of bioactive androgens was coordinately increased in response to chemotherapy. Conclusions: Neoadjuvant docetaxel administered for 6 months before radical prostatectomy is feasible, well tolerated, and often results in prostate-specific antigen declines of >50{\%} and decreased tumor volume on endorectal MRI. No pathologic; complete responses were observed. Altered androgen metabolism may partially account for the noted declines in prostate-specific antigen and be a mechanism for chemotherapy resistance.",
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T1 - Neoadjuvant docetaxel before radical prostatectomy in patients with high-risk localized prostate cancer

AU - Febbo, Phillip G.

AU - Richie, Jerome P.

AU - George, Daniel J.

AU - Loda, Massimo

AU - Manola, Judith

AU - Shankar, Sridhar

AU - Barnes, Agnieska Szot

AU - Tempany, Clare

AU - Catalona, William

AU - Kantoff, Philip W.

AU - Oh, William K.

PY - 2005/7/15

Y1 - 2005/7/15

N2 - Purpose: To determine the clinical, pathologic, and molecular effects of neoadjuvant docetaxel chemotherapy in high-risk localized prostate cancer. Experimental Design: Patients with biopsy Gleason scores of 8 to 10, serum prostate-specific antigen levels >20 ng/mL, and/or clinical stageT 3 disease received weekly docetaxel (36 mg/m2) for 6 months, followed by radical prostatectomy, and were monitored with weekly visits, serum prostate-specific antigen measurements, and endorectal magnetic resonance imaging (MRI). Frozen tumor specimens were collected for microarray analysis. Results: The 19 patients enrolled received 82% of the planned chemotherapy. Toxicity was mild to moderate; fatigue and taste disturbance were common. Prostate-specific antigen declines of >50% were seen in 11 of 19 patients (58%; 95% confidence interval, 33-80%) and endorectal MRI showed maximum tumor volume reduction of at least 25% in 13 of 19 patients (68%; 95% confidence interval, 47-85%) and at least 50% in 4 patients (21%; 95% confidence interval, 6-46%). Sixteen patients completed chemotherapy and had radical prostatectomy; none achieved pathologic complete response. Microarray analysis identified coordinate up-regulation of genes involved in androgen metabolism associated with docetaxel therapy. Specifically, RNA expression for genes that decrease cellular levels of bioactive androgens was coordinately increased in response to chemotherapy. Conclusions: Neoadjuvant docetaxel administered for 6 months before radical prostatectomy is feasible, well tolerated, and often results in prostate-specific antigen declines of >50% and decreased tumor volume on endorectal MRI. No pathologic; complete responses were observed. Altered androgen metabolism may partially account for the noted declines in prostate-specific antigen and be a mechanism for chemotherapy resistance.

AB - Purpose: To determine the clinical, pathologic, and molecular effects of neoadjuvant docetaxel chemotherapy in high-risk localized prostate cancer. Experimental Design: Patients with biopsy Gleason scores of 8 to 10, serum prostate-specific antigen levels >20 ng/mL, and/or clinical stageT 3 disease received weekly docetaxel (36 mg/m2) for 6 months, followed by radical prostatectomy, and were monitored with weekly visits, serum prostate-specific antigen measurements, and endorectal magnetic resonance imaging (MRI). Frozen tumor specimens were collected for microarray analysis. Results: The 19 patients enrolled received 82% of the planned chemotherapy. Toxicity was mild to moderate; fatigue and taste disturbance were common. Prostate-specific antigen declines of >50% were seen in 11 of 19 patients (58%; 95% confidence interval, 33-80%) and endorectal MRI showed maximum tumor volume reduction of at least 25% in 13 of 19 patients (68%; 95% confidence interval, 47-85%) and at least 50% in 4 patients (21%; 95% confidence interval, 6-46%). Sixteen patients completed chemotherapy and had radical prostatectomy; none achieved pathologic complete response. Microarray analysis identified coordinate up-regulation of genes involved in androgen metabolism associated with docetaxel therapy. Specifically, RNA expression for genes that decrease cellular levels of bioactive androgens was coordinately increased in response to chemotherapy. Conclusions: Neoadjuvant docetaxel administered for 6 months before radical prostatectomy is feasible, well tolerated, and often results in prostate-specific antigen declines of >50% and decreased tumor volume on endorectal MRI. No pathologic; complete responses were observed. Altered androgen metabolism may partially account for the noted declines in prostate-specific antigen and be a mechanism for chemotherapy resistance.

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