Neoadjuvant mitoxantrone and docetaxel for high-risk localized prostate cancer

Mark Garzotto, Anne Myrthue, Celestia S. Higano, Tomasz (Tom) Beer

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Purpose: Currently available treatment modalities for high-risk clinically localized prostate cancer have limited chances of achieving complete tumor elimination because of either inadequate local or metastatic tumor eradication. The goal of this phase I/II study is to evaluate the safety and efficacy of neoadjuvant docetaxel and mitoxantrone before prostatectomy. Materials and Methods: A total of 22 men with high-risk clinically localized prostate cancer underwent weekly treatment with docetaxel (35 mg/m2), with increasing doses of mitoxantrone (2-5 mg/m2) for a 12 of 16-week treatment cycle before prostatectomy. Testosterone and prostate-specific antigen (PSA) measurements were made before and after chemotherapy. Results: The maximally tolerated dose for mitoxantrone was 4 mg/m2, and the primary toxicity was neutropenia. Testosterone levels were maintained throughout treatment. PSA reductions were observed in 95% of patients, with a median reduction of 41%. The surgery was well tolerated after chemotherapy, without any major complications. Negative surgical margins were attained in 76% of patients. Conclusions: Administration of multi-agent chemotherapy before prostatectomy was safe in this population. This regimen appeared to have antineoplastic activity as evidenced by PSA reductions in the absence of significant testosterone changes. The benefit of chemotherapy for improving surgical margin rates could not be determined outside of a phase III trial because the effect of patient or surgeon factors could not be dissected from the potential effect of neoadjuvant therapy. Continued study of novel agents in the neoadjuvant setting is warranted because this approach allows for the rapid identification of active agents and for molecular investigation into the mechanism of drug activity.

Original languageEnglish (US)
Pages (from-to)254-259
Number of pages6
JournalUrologic Oncology: Seminars and Original Investigations
Volume24
Issue number3
DOIs
StatePublished - May 2006

Fingerprint

docetaxel
Mitoxantrone
Prostatic Neoplasms
Prostate-Specific Antigen
Prostatectomy
Testosterone
Drug Therapy
Neoadjuvant Therapy
Maximum Tolerated Dose
Therapeutics
Neutropenia
Antineoplastic Agents
Neoplasms
Safety
Pharmaceutical Preparations
Population

Keywords

  • Advanced prostate cancer
  • Chemotherapy
  • Docetaxel
  • Mitoxantrone
  • Neoadjuvant

ASJC Scopus subject areas

  • Oncology
  • Urology

Cite this

Neoadjuvant mitoxantrone and docetaxel for high-risk localized prostate cancer. / Garzotto, Mark; Myrthue, Anne; Higano, Celestia S.; Beer, Tomasz (Tom).

In: Urologic Oncology: Seminars and Original Investigations, Vol. 24, No. 3, 05.2006, p. 254-259.

Research output: Contribution to journalArticle

@article{6f58ea9e76ee406b837474a02cac6c24,
title = "Neoadjuvant mitoxantrone and docetaxel for high-risk localized prostate cancer",
abstract = "Purpose: Currently available treatment modalities for high-risk clinically localized prostate cancer have limited chances of achieving complete tumor elimination because of either inadequate local or metastatic tumor eradication. The goal of this phase I/II study is to evaluate the safety and efficacy of neoadjuvant docetaxel and mitoxantrone before prostatectomy. Materials and Methods: A total of 22 men with high-risk clinically localized prostate cancer underwent weekly treatment with docetaxel (35 mg/m2), with increasing doses of mitoxantrone (2-5 mg/m2) for a 12 of 16-week treatment cycle before prostatectomy. Testosterone and prostate-specific antigen (PSA) measurements were made before and after chemotherapy. Results: The maximally tolerated dose for mitoxantrone was 4 mg/m2, and the primary toxicity was neutropenia. Testosterone levels were maintained throughout treatment. PSA reductions were observed in 95{\%} of patients, with a median reduction of 41{\%}. The surgery was well tolerated after chemotherapy, without any major complications. Negative surgical margins were attained in 76{\%} of patients. Conclusions: Administration of multi-agent chemotherapy before prostatectomy was safe in this population. This regimen appeared to have antineoplastic activity as evidenced by PSA reductions in the absence of significant testosterone changes. The benefit of chemotherapy for improving surgical margin rates could not be determined outside of a phase III trial because the effect of patient or surgeon factors could not be dissected from the potential effect of neoadjuvant therapy. Continued study of novel agents in the neoadjuvant setting is warranted because this approach allows for the rapid identification of active agents and for molecular investigation into the mechanism of drug activity.",
keywords = "Advanced prostate cancer, Chemotherapy, Docetaxel, Mitoxantrone, Neoadjuvant",
author = "Mark Garzotto and Anne Myrthue and Higano, {Celestia S.} and Beer, {Tomasz (Tom)}",
year = "2006",
month = "5",
doi = "10.1016/j.urolonc.2005.11.034",
language = "English (US)",
volume = "24",
pages = "254--259",
journal = "Urologic Oncology: Seminars and Original Investigations",
issn = "1078-1439",
publisher = "Elsevier Inc.",
number = "3",

}

TY - JOUR

T1 - Neoadjuvant mitoxantrone and docetaxel for high-risk localized prostate cancer

AU - Garzotto, Mark

AU - Myrthue, Anne

AU - Higano, Celestia S.

AU - Beer, Tomasz (Tom)

PY - 2006/5

Y1 - 2006/5

N2 - Purpose: Currently available treatment modalities for high-risk clinically localized prostate cancer have limited chances of achieving complete tumor elimination because of either inadequate local or metastatic tumor eradication. The goal of this phase I/II study is to evaluate the safety and efficacy of neoadjuvant docetaxel and mitoxantrone before prostatectomy. Materials and Methods: A total of 22 men with high-risk clinically localized prostate cancer underwent weekly treatment with docetaxel (35 mg/m2), with increasing doses of mitoxantrone (2-5 mg/m2) for a 12 of 16-week treatment cycle before prostatectomy. Testosterone and prostate-specific antigen (PSA) measurements were made before and after chemotherapy. Results: The maximally tolerated dose for mitoxantrone was 4 mg/m2, and the primary toxicity was neutropenia. Testosterone levels were maintained throughout treatment. PSA reductions were observed in 95% of patients, with a median reduction of 41%. The surgery was well tolerated after chemotherapy, without any major complications. Negative surgical margins were attained in 76% of patients. Conclusions: Administration of multi-agent chemotherapy before prostatectomy was safe in this population. This regimen appeared to have antineoplastic activity as evidenced by PSA reductions in the absence of significant testosterone changes. The benefit of chemotherapy for improving surgical margin rates could not be determined outside of a phase III trial because the effect of patient or surgeon factors could not be dissected from the potential effect of neoadjuvant therapy. Continued study of novel agents in the neoadjuvant setting is warranted because this approach allows for the rapid identification of active agents and for molecular investigation into the mechanism of drug activity.

AB - Purpose: Currently available treatment modalities for high-risk clinically localized prostate cancer have limited chances of achieving complete tumor elimination because of either inadequate local or metastatic tumor eradication. The goal of this phase I/II study is to evaluate the safety and efficacy of neoadjuvant docetaxel and mitoxantrone before prostatectomy. Materials and Methods: A total of 22 men with high-risk clinically localized prostate cancer underwent weekly treatment with docetaxel (35 mg/m2), with increasing doses of mitoxantrone (2-5 mg/m2) for a 12 of 16-week treatment cycle before prostatectomy. Testosterone and prostate-specific antigen (PSA) measurements were made before and after chemotherapy. Results: The maximally tolerated dose for mitoxantrone was 4 mg/m2, and the primary toxicity was neutropenia. Testosterone levels were maintained throughout treatment. PSA reductions were observed in 95% of patients, with a median reduction of 41%. The surgery was well tolerated after chemotherapy, without any major complications. Negative surgical margins were attained in 76% of patients. Conclusions: Administration of multi-agent chemotherapy before prostatectomy was safe in this population. This regimen appeared to have antineoplastic activity as evidenced by PSA reductions in the absence of significant testosterone changes. The benefit of chemotherapy for improving surgical margin rates could not be determined outside of a phase III trial because the effect of patient or surgeon factors could not be dissected from the potential effect of neoadjuvant therapy. Continued study of novel agents in the neoadjuvant setting is warranted because this approach allows for the rapid identification of active agents and for molecular investigation into the mechanism of drug activity.

KW - Advanced prostate cancer

KW - Chemotherapy

KW - Docetaxel

KW - Mitoxantrone

KW - Neoadjuvant

UR - http://www.scopus.com/inward/record.url?scp=33646173163&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33646173163&partnerID=8YFLogxK

U2 - 10.1016/j.urolonc.2005.11.034

DO - 10.1016/j.urolonc.2005.11.034

M3 - Article

VL - 24

SP - 254

EP - 259

JO - Urologic Oncology: Seminars and Original Investigations

JF - Urologic Oncology: Seminars and Original Investigations

SN - 1078-1439

IS - 3

ER -