Phase 1/2 study of preoperative docetaxel and mitoxantrone for high-risk prostate cancer

Mark Garzotto, Celestia S. Higano, Catherine O'Brien, Brooks L S Rademacher, Nicole Janeba, Ladan Fazli, Paul H. Lange, Stephen Lieberman, Tomasz (Tom) Beer

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

BACKGROUND: A study was conducted to determine the 5-year recurrence-free survival in patients with high-risk prostate cancer after neoadjuvant combination chemotherapy followed by surgery. Secondary endpoints included safety, pathologic effects of chemotherapy, and predictors of disease recurrence. METHODS: Fifty-seven patients were enrolled in a phase 1/2 study of weekly docetaxel 35 mg/m2 and escalating mitoxantrone to 4 mg/m2 before prostatectomy. Patients were treated with 16 weeks of chemotherapy administered weekly on a 3 of every 4 week schedule. A tissue microarray, constructed from the prostatectomy specimens, served to facilitate the exploratory evaluation of biomarkers. The primary endpoint was recurrence-free survival. Disease recurrence was defined as a confirmed serum prostate-specific antigen (PSA) >0.4 ng/mL. RESULTS: Of the 57 patients, 54 received 4 cycles of docetaxel and mitoxantrone before radical prostatectomy. Grade 4 toxicities were limited to leukopenia, neutropenia, and hyperglycemia. Serum testosterone levels remained stable after chemotherapy. Negative surgical margins were attained in 67% of cases. Lymph node involvement was detected in 18.5% of cases. With a median follow-up of 63 months, 27 of 57 (47.4%) patients recurred. The Kaplan-Meier recurrence-free survival at 2 years was 65.5% (95% confidence interval [CI], 53.0%-78.0%) and was 49.8% at 5 years (95% CI, 35.5%-64.1%). Pretreatment serum PSA, lymph node involvement, and postchemotherapy tissue vascular endothelial growth factor expression were independent predictors of early recurrence. CONCLUSIONS: Preoperative chemotherapy with docetaxel and mitoxantrone is feasible. Approximately half of the high-risk patients remain free of disease recurrence at 5 years, and clinical and molecular predictors of early recurrence were identified.

Original languageEnglish (US)
Pages (from-to)1699-1708
Number of pages10
JournalCancer
Volume116
Issue number7
DOIs
StatePublished - Apr 1 2010

Fingerprint

docetaxel
Mitoxantrone
Prostatic Neoplasms
Recurrence
Prostatectomy
Drug Therapy
Prostate-Specific Antigen
Survival
Lymph Nodes
Serum
Confidence Intervals
Leukopenia
Combination Drug Therapy
Neutropenia
Hyperglycemia
Vascular Endothelial Growth Factor A
Testosterone

Keywords

  • Chemotherapy before prostatectomy
  • Docetaxel
  • Mitoxantrone
  • Neoadjuvant chemotherapy
  • Prostate cancer

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Garzotto, M., Higano, C. S., O'Brien, C., Rademacher, B. L. S., Janeba, N., Fazli, L., ... Beer, T. T. (2010). Phase 1/2 study of preoperative docetaxel and mitoxantrone for high-risk prostate cancer. Cancer, 116(7), 1699-1708. https://doi.org/10.1002/cncr.24960

Phase 1/2 study of preoperative docetaxel and mitoxantrone for high-risk prostate cancer. / Garzotto, Mark; Higano, Celestia S.; O'Brien, Catherine; Rademacher, Brooks L S; Janeba, Nicole; Fazli, Ladan; Lange, Paul H.; Lieberman, Stephen; Beer, Tomasz (Tom).

In: Cancer, Vol. 116, No. 7, 01.04.2010, p. 1699-1708.

Research output: Contribution to journalArticle

Garzotto, M, Higano, CS, O'Brien, C, Rademacher, BLS, Janeba, N, Fazli, L, Lange, PH, Lieberman, S & Beer, TT 2010, 'Phase 1/2 study of preoperative docetaxel and mitoxantrone for high-risk prostate cancer', Cancer, vol. 116, no. 7, pp. 1699-1708. https://doi.org/10.1002/cncr.24960
Garzotto M, Higano CS, O'Brien C, Rademacher BLS, Janeba N, Fazli L et al. Phase 1/2 study of preoperative docetaxel and mitoxantrone for high-risk prostate cancer. Cancer. 2010 Apr 1;116(7):1699-1708. https://doi.org/10.1002/cncr.24960
Garzotto, Mark ; Higano, Celestia S. ; O'Brien, Catherine ; Rademacher, Brooks L S ; Janeba, Nicole ; Fazli, Ladan ; Lange, Paul H. ; Lieberman, Stephen ; Beer, Tomasz (Tom). / Phase 1/2 study of preoperative docetaxel and mitoxantrone for high-risk prostate cancer. In: Cancer. 2010 ; Vol. 116, No. 7. pp. 1699-1708.
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abstract = "BACKGROUND: A study was conducted to determine the 5-year recurrence-free survival in patients with high-risk prostate cancer after neoadjuvant combination chemotherapy followed by surgery. Secondary endpoints included safety, pathologic effects of chemotherapy, and predictors of disease recurrence. METHODS: Fifty-seven patients were enrolled in a phase 1/2 study of weekly docetaxel 35 mg/m2 and escalating mitoxantrone to 4 mg/m2 before prostatectomy. Patients were treated with 16 weeks of chemotherapy administered weekly on a 3 of every 4 week schedule. A tissue microarray, constructed from the prostatectomy specimens, served to facilitate the exploratory evaluation of biomarkers. The primary endpoint was recurrence-free survival. Disease recurrence was defined as a confirmed serum prostate-specific antigen (PSA) >0.4 ng/mL. RESULTS: Of the 57 patients, 54 received 4 cycles of docetaxel and mitoxantrone before radical prostatectomy. Grade 4 toxicities were limited to leukopenia, neutropenia, and hyperglycemia. Serum testosterone levels remained stable after chemotherapy. Negative surgical margins were attained in 67{\%} of cases. Lymph node involvement was detected in 18.5{\%} of cases. With a median follow-up of 63 months, 27 of 57 (47.4{\%}) patients recurred. The Kaplan-Meier recurrence-free survival at 2 years was 65.5{\%} (95{\%} confidence interval [CI], 53.0{\%}-78.0{\%}) and was 49.8{\%} at 5 years (95{\%} CI, 35.5{\%}-64.1{\%}). Pretreatment serum PSA, lymph node involvement, and postchemotherapy tissue vascular endothelial growth factor expression were independent predictors of early recurrence. CONCLUSIONS: Preoperative chemotherapy with docetaxel and mitoxantrone is feasible. Approximately half of the high-risk patients remain free of disease recurrence at 5 years, and clinical and molecular predictors of early recurrence were identified.",
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AU - Higano, Celestia S.

AU - O'Brien, Catherine

AU - Rademacher, Brooks L S

AU - Janeba, Nicole

AU - Fazli, Ladan

AU - Lange, Paul H.

AU - Lieberman, Stephen

AU - Beer, Tomasz (Tom)

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N2 - BACKGROUND: A study was conducted to determine the 5-year recurrence-free survival in patients with high-risk prostate cancer after neoadjuvant combination chemotherapy followed by surgery. Secondary endpoints included safety, pathologic effects of chemotherapy, and predictors of disease recurrence. METHODS: Fifty-seven patients were enrolled in a phase 1/2 study of weekly docetaxel 35 mg/m2 and escalating mitoxantrone to 4 mg/m2 before prostatectomy. Patients were treated with 16 weeks of chemotherapy administered weekly on a 3 of every 4 week schedule. A tissue microarray, constructed from the prostatectomy specimens, served to facilitate the exploratory evaluation of biomarkers. The primary endpoint was recurrence-free survival. Disease recurrence was defined as a confirmed serum prostate-specific antigen (PSA) >0.4 ng/mL. RESULTS: Of the 57 patients, 54 received 4 cycles of docetaxel and mitoxantrone before radical prostatectomy. Grade 4 toxicities were limited to leukopenia, neutropenia, and hyperglycemia. Serum testosterone levels remained stable after chemotherapy. Negative surgical margins were attained in 67% of cases. Lymph node involvement was detected in 18.5% of cases. With a median follow-up of 63 months, 27 of 57 (47.4%) patients recurred. The Kaplan-Meier recurrence-free survival at 2 years was 65.5% (95% confidence interval [CI], 53.0%-78.0%) and was 49.8% at 5 years (95% CI, 35.5%-64.1%). Pretreatment serum PSA, lymph node involvement, and postchemotherapy tissue vascular endothelial growth factor expression were independent predictors of early recurrence. CONCLUSIONS: Preoperative chemotherapy with docetaxel and mitoxantrone is feasible. Approximately half of the high-risk patients remain free of disease recurrence at 5 years, and clinical and molecular predictors of early recurrence were identified.

AB - BACKGROUND: A study was conducted to determine the 5-year recurrence-free survival in patients with high-risk prostate cancer after neoadjuvant combination chemotherapy followed by surgery. Secondary endpoints included safety, pathologic effects of chemotherapy, and predictors of disease recurrence. METHODS: Fifty-seven patients were enrolled in a phase 1/2 study of weekly docetaxel 35 mg/m2 and escalating mitoxantrone to 4 mg/m2 before prostatectomy. Patients were treated with 16 weeks of chemotherapy administered weekly on a 3 of every 4 week schedule. A tissue microarray, constructed from the prostatectomy specimens, served to facilitate the exploratory evaluation of biomarkers. The primary endpoint was recurrence-free survival. Disease recurrence was defined as a confirmed serum prostate-specific antigen (PSA) >0.4 ng/mL. RESULTS: Of the 57 patients, 54 received 4 cycles of docetaxel and mitoxantrone before radical prostatectomy. Grade 4 toxicities were limited to leukopenia, neutropenia, and hyperglycemia. Serum testosterone levels remained stable after chemotherapy. Negative surgical margins were attained in 67% of cases. Lymph node involvement was detected in 18.5% of cases. With a median follow-up of 63 months, 27 of 57 (47.4%) patients recurred. The Kaplan-Meier recurrence-free survival at 2 years was 65.5% (95% confidence interval [CI], 53.0%-78.0%) and was 49.8% at 5 years (95% CI, 35.5%-64.1%). Pretreatment serum PSA, lymph node involvement, and postchemotherapy tissue vascular endothelial growth factor expression were independent predictors of early recurrence. CONCLUSIONS: Preoperative chemotherapy with docetaxel and mitoxantrone is feasible. Approximately half of the high-risk patients remain free of disease recurrence at 5 years, and clinical and molecular predictors of early recurrence were identified.

KW - Chemotherapy before prostatectomy

KW - Docetaxel

KW - Mitoxantrone

KW - Neoadjuvant chemotherapy

KW - Prostate cancer

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