Phase I Study of Weekly Mitoxantrone and Docetaxel before Prostatectomy in Patients with High-Risk Localized Prostate Cancer

Tomasz (Tom) Beer, Mark Garzotto, Bruce A. Lowe, William J. Ellis, Michelle A. Montalto, Paul H. Lange, Celestia S. Higano

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Purpose: The purpose is to determine the dose-limiting toxicity (DLT) and maximum-tolerated dose (MTD) of mitoxantrone and docetaxel administered weekly before prostatectomy in men with localized prostate cancer at high risk for recurrence. Experimental Design: Twenty-two patients were treated with four cycles of docetaxel 35 mg/m2 and increasing doses of mitoxantrone starting at 2 mg/m2 repeated weekly for 3 weeks of a 4-week cycle before prostatectomy. The MTD was defined as that dose at which fewer than one-third of patients experienced a DLT (≥grade 4 hematological or ≥grade 3 nonhematological toxicity). Changes in serum prostate-specific antigen and serum testosterone, and pathological outcome with surgery were secondary endpoints. Results: The MTD for mitoxantrone in combination with this dose of docetaxel was 4 mg/m2. Neutropenia was the DLT for the combination. Ten of 12 patients treated at the MTD completed the planned 16 weeks of chemotherapy, whereas 2 discontinued therapy early because of toxicity. The median reduction in PSA was 41% (range, 4-88%). Serum testosterone levels remained constant postchemotherapy. Conclusions: In this patient population, the planned Phase II regimen is 4 mg/m2 mitoxantrone and 35 mg/m 2 docetaxel weekly for 3 of every 4 weeks. Delivery of this regimen before prostatectomy is feasible with acceptable toxicity. Additional studies are needed to determine whether this combined modality approach will reduce cancer recurrence rates in this high-risk population. Because extent of disease and exposure to prior therapy may impact treatment tolerance these safety data may not be applicable to patients with advanced prostate cancer.

Original languageEnglish (US)
Pages (from-to)1306-1311
Number of pages6
JournalClinical Cancer Research
Volume10
Issue number4
DOIs
StatePublished - Feb 15 2004

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docetaxel
Mitoxantrone
Prostatectomy
Maximum Tolerated Dose
Prostatic Neoplasms
Testosterone
Serum
Recurrence
Prostate-Specific Antigen
Neutropenia
Population
Research Design
Therapeutics
Safety
Drug Therapy

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Phase I Study of Weekly Mitoxantrone and Docetaxel before Prostatectomy in Patients with High-Risk Localized Prostate Cancer. / Beer, Tomasz (Tom); Garzotto, Mark; Lowe, Bruce A.; Ellis, William J.; Montalto, Michelle A.; Lange, Paul H.; Higano, Celestia S.

In: Clinical Cancer Research, Vol. 10, No. 4, 15.02.2004, p. 1306-1311.

Research output: Contribution to journalArticle

Beer, Tomasz (Tom) ; Garzotto, Mark ; Lowe, Bruce A. ; Ellis, William J. ; Montalto, Michelle A. ; Lange, Paul H. ; Higano, Celestia S. / Phase I Study of Weekly Mitoxantrone and Docetaxel before Prostatectomy in Patients with High-Risk Localized Prostate Cancer. In: Clinical Cancer Research. 2004 ; Vol. 10, No. 4. pp. 1306-1311.
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abstract = "Purpose: The purpose is to determine the dose-limiting toxicity (DLT) and maximum-tolerated dose (MTD) of mitoxantrone and docetaxel administered weekly before prostatectomy in men with localized prostate cancer at high risk for recurrence. Experimental Design: Twenty-two patients were treated with four cycles of docetaxel 35 mg/m2 and increasing doses of mitoxantrone starting at 2 mg/m2 repeated weekly for 3 weeks of a 4-week cycle before prostatectomy. The MTD was defined as that dose at which fewer than one-third of patients experienced a DLT (≥grade 4 hematological or ≥grade 3 nonhematological toxicity). Changes in serum prostate-specific antigen and serum testosterone, and pathological outcome with surgery were secondary endpoints. Results: The MTD for mitoxantrone in combination with this dose of docetaxel was 4 mg/m2. Neutropenia was the DLT for the combination. Ten of 12 patients treated at the MTD completed the planned 16 weeks of chemotherapy, whereas 2 discontinued therapy early because of toxicity. The median reduction in PSA was 41{\%} (range, 4-88{\%}). Serum testosterone levels remained constant postchemotherapy. Conclusions: In this patient population, the planned Phase II regimen is 4 mg/m2 mitoxantrone and 35 mg/m 2 docetaxel weekly for 3 of every 4 weeks. Delivery of this regimen before prostatectomy is feasible with acceptable toxicity. Additional studies are needed to determine whether this combined modality approach will reduce cancer recurrence rates in this high-risk population. Because extent of disease and exposure to prior therapy may impact treatment tolerance these safety data may not be applicable to patients with advanced prostate cancer.",
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