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

Publication ,  Journal Article
Febbo, PG; Richie, JP; George, DJ; Loda, M; Manola, J; Shankar, S; Barnes, AS; Tempany, C; Catalona, W; Kantoff, PW; Oh, WK
Published in: Clin Cancer Res
July 15, 2005

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 stage T3 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.

Duke Scholars

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Published In

Clin Cancer Res

DOI

ISSN

1078-0432

Publication Date

July 15, 2005

Volume

11

Issue

14

Start / End Page

5233 / 5240

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Taxoids
  • Risk Assessment
  • RNA, Messenger
  • Prostatic Neoplasms
  • Prostatectomy
  • Prostate-Specific Antigen
  • Oncology & Carcinogenesis
  • Neoplasm Staging
  • Neoadjuvant Therapy
 

Citation

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Febbo, P. G., Richie, J. P., George, D. J., Loda, M., Manola, J., Shankar, S., … Oh, W. K. (2005). Neoadjuvant docetaxel before radical prostatectomy in patients with high-risk localized prostate cancer. Clin Cancer Res, 11(14), 5233–5240. https://doi.org/10.1158/1078-0432.CCR-05-0299
Febbo, Phillip G., Jerome P. Richie, Daniel J. George, Massimo Loda, Judith Manola, Sridhar Shankar, Agnieska Szot Barnes, et al. “Neoadjuvant docetaxel before radical prostatectomy in patients with high-risk localized prostate cancer.Clin Cancer Res 11, no. 14 (July 15, 2005): 5233–40. https://doi.org/10.1158/1078-0432.CCR-05-0299.
Febbo PG, Richie JP, George DJ, Loda M, Manola J, Shankar S, et al. Neoadjuvant docetaxel before radical prostatectomy in patients with high-risk localized prostate cancer. Clin Cancer Res. 2005 Jul 15;11(14):5233–40.
Febbo, Phillip G., et al. “Neoadjuvant docetaxel before radical prostatectomy in patients with high-risk localized prostate cancer.Clin Cancer Res, vol. 11, no. 14, July 2005, pp. 5233–40. Pubmed, doi:10.1158/1078-0432.CCR-05-0299.
Febbo PG, Richie JP, George DJ, Loda M, Manola J, Shankar S, Barnes AS, Tempany C, Catalona W, Kantoff PW, Oh WK. Neoadjuvant docetaxel before radical prostatectomy in patients with high-risk localized prostate cancer. Clin Cancer Res. 2005 Jul 15;11(14):5233–5240.

Published In

Clin Cancer Res

DOI

ISSN

1078-0432

Publication Date

July 15, 2005

Volume

11

Issue

14

Start / End Page

5233 / 5240

Location

United States

Related Subject Headings

  • Treatment Outcome
  • Taxoids
  • Risk Assessment
  • RNA, Messenger
  • Prostatic Neoplasms
  • Prostatectomy
  • Prostate-Specific Antigen
  • Oncology & Carcinogenesis
  • Neoplasm Staging
  • Neoadjuvant Therapy