Neoadjuvant Docetaxel and Capecitabine in Patients With High Risk Prostate Cancer

Judah Friedman, Rodney L. Dunn, David Wood, Ulka Vaishampayan, Angela Wu, Deborah Bradley, James Montie, Fazlul H. Sarkar, Rajal B. Shah, Maha Hussain

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Purpose: Docetaxel is the most active cytotoxic agent in hormone refractory prostate cancer. Preclinically docetaxel increases expression of thymidine phosphorylase, an enzyme responsible for activation of capecitabine to 5-fluorouracil resulting in increased antitumor activity. We assessed activity and safety of neoadjuvant docetaxel and capecitabine in patients with high risk prostate cancer. Materials and Methods: Patients with either clinical stage greater than T2, prostate specific antigen 15 ng/ml or more, or Gleason sum 8 or greater received 3 to 6 cycles of docetaxel (36 mg/m2 intravenously on days 1, 8 and 15) and capecitabine (1,250 mg/m2 per day orally divided twice a day on days 5 to 18) every 28 days, followed by local therapy. The primary end point was rate of 50% or greater prostate specific antigen decrease. Correlative studies included qualitative changes in histology, tissue thymidine phosphorylase and survivin expression, and CK18Asp396 (serum apoptosis marker). Results: A total of 15 patients were treated, of whom 6 (40%) experienced a 50% or greater decrease in prostate specific antigen with infrequent diarrhea or hand-foot syndrome. Eleven patients underwent radical prostatectomy. There were no pathological complete responses and 4 patients demonstrated mild histological changes, including focal necrosis and vacuolated cytoplasm. While there was no discernable pattern of increased thymidine phosphorylase expression, 4 specimens showed decreased survivin expression, suggesting a possible mechanism for chemotherapy induced apoptosis. There was no correlation of prostate specific antigen response and survivin expression, and no increase in serum CK18Asp396. Conclusions: Neoadjuvant docetaxel and capecitabine is well tolerated but is not associated with significant pathological and prostate specific antigen responses.

Original languageEnglish (US)
Pages (from-to)911-916
Number of pages6
JournalJournal of Urology
Volume179
Issue number3
DOIs
StatePublished - Mar 1 2008
Externally publishedYes

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docetaxel
Prostate-Specific Antigen
Thymidine Phosphorylase
Prostatic Neoplasms
Hand-Foot Syndrome
Apoptosis
Enzyme Activation
Cytotoxins
Prostatectomy
Fluorouracil
Diarrhea
Histology
Cytoplasm
Necrosis
Biomarkers
Capecitabine
Hormones
Safety
Drug Therapy

Keywords

  • drug therapy
  • prostatic neoplasms

ASJC Scopus subject areas

  • Urology

Cite this

Friedman, J., Dunn, R. L., Wood, D., Vaishampayan, U., Wu, A., Bradley, D., ... Hussain, M. (2008). Neoadjuvant Docetaxel and Capecitabine in Patients With High Risk Prostate Cancer. Journal of Urology, 179(3), 911-916. https://doi.org/10.1016/j.juro.2007.10.064

Neoadjuvant Docetaxel and Capecitabine in Patients With High Risk Prostate Cancer. / Friedman, Judah; Dunn, Rodney L.; Wood, David; Vaishampayan, Ulka; Wu, Angela; Bradley, Deborah; Montie, James; Sarkar, Fazlul H.; Shah, Rajal B.; Hussain, Maha.

In: Journal of Urology, Vol. 179, No. 3, 01.03.2008, p. 911-916.

Research output: Contribution to journalArticle

Friedman, J, Dunn, RL, Wood, D, Vaishampayan, U, Wu, A, Bradley, D, Montie, J, Sarkar, FH, Shah, RB & Hussain, M 2008, 'Neoadjuvant Docetaxel and Capecitabine in Patients With High Risk Prostate Cancer', Journal of Urology, vol. 179, no. 3, pp. 911-916. https://doi.org/10.1016/j.juro.2007.10.064
Friedman J, Dunn RL, Wood D, Vaishampayan U, Wu A, Bradley D et al. Neoadjuvant Docetaxel and Capecitabine in Patients With High Risk Prostate Cancer. Journal of Urology. 2008 Mar 1;179(3):911-916. https://doi.org/10.1016/j.juro.2007.10.064
Friedman, Judah ; Dunn, Rodney L. ; Wood, David ; Vaishampayan, Ulka ; Wu, Angela ; Bradley, Deborah ; Montie, James ; Sarkar, Fazlul H. ; Shah, Rajal B. ; Hussain, Maha. / Neoadjuvant Docetaxel and Capecitabine in Patients With High Risk Prostate Cancer. In: Journal of Urology. 2008 ; Vol. 179, No. 3. pp. 911-916.
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abstract = "Purpose: Docetaxel is the most active cytotoxic agent in hormone refractory prostate cancer. Preclinically docetaxel increases expression of thymidine phosphorylase, an enzyme responsible for activation of capecitabine to 5-fluorouracil resulting in increased antitumor activity. We assessed activity and safety of neoadjuvant docetaxel and capecitabine in patients with high risk prostate cancer. Materials and Methods: Patients with either clinical stage greater than T2, prostate specific antigen 15 ng/ml or more, or Gleason sum 8 or greater received 3 to 6 cycles of docetaxel (36 mg/m2 intravenously on days 1, 8 and 15) and capecitabine (1,250 mg/m2 per day orally divided twice a day on days 5 to 18) every 28 days, followed by local therapy. The primary end point was rate of 50{\%} or greater prostate specific antigen decrease. Correlative studies included qualitative changes in histology, tissue thymidine phosphorylase and survivin expression, and CK18Asp396 (serum apoptosis marker). Results: A total of 15 patients were treated, of whom 6 (40{\%}) experienced a 50{\%} or greater decrease in prostate specific antigen with infrequent diarrhea or hand-foot syndrome. Eleven patients underwent radical prostatectomy. There were no pathological complete responses and 4 patients demonstrated mild histological changes, including focal necrosis and vacuolated cytoplasm. While there was no discernable pattern of increased thymidine phosphorylase expression, 4 specimens showed decreased survivin expression, suggesting a possible mechanism for chemotherapy induced apoptosis. There was no correlation of prostate specific antigen response and survivin expression, and no increase in serum CK18Asp396. Conclusions: Neoadjuvant docetaxel and capecitabine is well tolerated but is not associated with significant pathological and prostate specific antigen responses.",
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AU - Bradley, Deborah

AU - Montie, James

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N2 - Purpose: Docetaxel is the most active cytotoxic agent in hormone refractory prostate cancer. Preclinically docetaxel increases expression of thymidine phosphorylase, an enzyme responsible for activation of capecitabine to 5-fluorouracil resulting in increased antitumor activity. We assessed activity and safety of neoadjuvant docetaxel and capecitabine in patients with high risk prostate cancer. Materials and Methods: Patients with either clinical stage greater than T2, prostate specific antigen 15 ng/ml or more, or Gleason sum 8 or greater received 3 to 6 cycles of docetaxel (36 mg/m2 intravenously on days 1, 8 and 15) and capecitabine (1,250 mg/m2 per day orally divided twice a day on days 5 to 18) every 28 days, followed by local therapy. The primary end point was rate of 50% or greater prostate specific antigen decrease. Correlative studies included qualitative changes in histology, tissue thymidine phosphorylase and survivin expression, and CK18Asp396 (serum apoptosis marker). Results: A total of 15 patients were treated, of whom 6 (40%) experienced a 50% or greater decrease in prostate specific antigen with infrequent diarrhea or hand-foot syndrome. Eleven patients underwent radical prostatectomy. There were no pathological complete responses and 4 patients demonstrated mild histological changes, including focal necrosis and vacuolated cytoplasm. While there was no discernable pattern of increased thymidine phosphorylase expression, 4 specimens showed decreased survivin expression, suggesting a possible mechanism for chemotherapy induced apoptosis. There was no correlation of prostate specific antigen response and survivin expression, and no increase in serum CK18Asp396. Conclusions: Neoadjuvant docetaxel and capecitabine is well tolerated but is not associated with significant pathological and prostate specific antigen responses.

AB - Purpose: Docetaxel is the most active cytotoxic agent in hormone refractory prostate cancer. Preclinically docetaxel increases expression of thymidine phosphorylase, an enzyme responsible for activation of capecitabine to 5-fluorouracil resulting in increased antitumor activity. We assessed activity and safety of neoadjuvant docetaxel and capecitabine in patients with high risk prostate cancer. Materials and Methods: Patients with either clinical stage greater than T2, prostate specific antigen 15 ng/ml or more, or Gleason sum 8 or greater received 3 to 6 cycles of docetaxel (36 mg/m2 intravenously on days 1, 8 and 15) and capecitabine (1,250 mg/m2 per day orally divided twice a day on days 5 to 18) every 28 days, followed by local therapy. The primary end point was rate of 50% or greater prostate specific antigen decrease. Correlative studies included qualitative changes in histology, tissue thymidine phosphorylase and survivin expression, and CK18Asp396 (serum apoptosis marker). Results: A total of 15 patients were treated, of whom 6 (40%) experienced a 50% or greater decrease in prostate specific antigen with infrequent diarrhea or hand-foot syndrome. Eleven patients underwent radical prostatectomy. There were no pathological complete responses and 4 patients demonstrated mild histological changes, including focal necrosis and vacuolated cytoplasm. While there was no discernable pattern of increased thymidine phosphorylase expression, 4 specimens showed decreased survivin expression, suggesting a possible mechanism for chemotherapy induced apoptosis. There was no correlation of prostate specific antigen response and survivin expression, and no increase in serum CK18Asp396. Conclusions: Neoadjuvant docetaxel and capecitabine is well tolerated but is not associated with significant pathological and prostate specific antigen responses.

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