A phase II study of paclitaxel poliglumex in combination with transdermal estradiol for the treatment of metastatic castration-resistant prostate cancer after docetaxel chemotherapy

Tomasz (Tom) Beer, Charles Ryan, Joshi Alumkal, Christopher Ryan, Janine Sun, Kristine M. Eilers

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    31 Citations (Scopus)

    Abstract

    Taxanes remain the only agents to extend survival in castration-resistant metastatic prostate cancer, but their impact on the natural history of this disease is modest. We sought to test the hypothesis that increased delivery of taxane chemotherapy to the tumor through the use of a macromolecular polymer-drug conjugate of paclitaxel modulated by estradiol could extend the utility of this class of drugs. Patients with metastatic adenocarcinoma of the prostate who progressed despite standard hormonal therapy and after docetaxel-containing chemotherapy were treated with transdermal estradiol (0.2mg/24h) for 4 weeks followed by the same dose of transdermal estradiol and paclitaxel poliglumex (PPX; 150mg/m2 intravenous) every 28 days. The primary objective was to determine the level of activity of the regimen measured using a fraction of patients who experienced a confirmed decline in serum prostate-specific antigen (PSA) of 50% or more. A two-stage phase II study designed to identify a response rate of ≥25% required three responders among 21 patients in the first stage. Twenty-one patients who received a median of two earlier chemotherapy regimens were enrolled in the trial between March 2007 and May 2008. During the estradiol-only treatment phase, no patient had a PSA decline in excess of 50% and lesser PSA declines that ranged from 8.8 to 34.1% were seen in five patients. No patients achieved a ≥50% PSA decline following the addition of PPX and there were no responses in measurable disease. The median time to progression was 4 weeks. In conclusion, this regimen of low-dose transdermal estradiol induction followed by PPX does not have activity in taxane pretreated patients with castration-resistant prostate cancer.

    Original languageEnglish (US)
    Pages (from-to)433-438
    Number of pages6
    JournalAnti-Cancer Drugs
    Volume21
    Issue number4
    DOIs
    StatePublished - Apr 2010

    Fingerprint

    docetaxel
    Castration
    Estradiol
    Prostatic Neoplasms
    Drug Therapy
    Prostate-Specific Antigen
    Therapeutics
    Taxoids
    paclitaxel poliglumex
    Paclitaxel
    Pharmaceutical Preparations

    Keywords

    • Paclitaxel poliglumex
    • Prostate cancer
    • Transdermal estradiol

    ASJC Scopus subject areas

    • Pharmacology
    • Pharmacology (medical)
    • Cancer Research
    • Oncology

    Cite this

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    title = "A phase II study of paclitaxel poliglumex in combination with transdermal estradiol for the treatment of metastatic castration-resistant prostate cancer after docetaxel chemotherapy",
    abstract = "Taxanes remain the only agents to extend survival in castration-resistant metastatic prostate cancer, but their impact on the natural history of this disease is modest. We sought to test the hypothesis that increased delivery of taxane chemotherapy to the tumor through the use of a macromolecular polymer-drug conjugate of paclitaxel modulated by estradiol could extend the utility of this class of drugs. Patients with metastatic adenocarcinoma of the prostate who progressed despite standard hormonal therapy and after docetaxel-containing chemotherapy were treated with transdermal estradiol (0.2mg/24h) for 4 weeks followed by the same dose of transdermal estradiol and paclitaxel poliglumex (PPX; 150mg/m2 intravenous) every 28 days. The primary objective was to determine the level of activity of the regimen measured using a fraction of patients who experienced a confirmed decline in serum prostate-specific antigen (PSA) of 50{\%} or more. A two-stage phase II study designed to identify a response rate of ≥25{\%} required three responders among 21 patients in the first stage. Twenty-one patients who received a median of two earlier chemotherapy regimens were enrolled in the trial between March 2007 and May 2008. During the estradiol-only treatment phase, no patient had a PSA decline in excess of 50{\%} and lesser PSA declines that ranged from 8.8 to 34.1{\%} were seen in five patients. No patients achieved a ≥50{\%} PSA decline following the addition of PPX and there were no responses in measurable disease. The median time to progression was 4 weeks. In conclusion, this regimen of low-dose transdermal estradiol induction followed by PPX does not have activity in taxane pretreated patients with castration-resistant prostate cancer.",
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    AU - Ryan, Christopher

    AU - Sun, Janine

    AU - Eilers, Kristine M.

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    AB - Taxanes remain the only agents to extend survival in castration-resistant metastatic prostate cancer, but their impact on the natural history of this disease is modest. We sought to test the hypothesis that increased delivery of taxane chemotherapy to the tumor through the use of a macromolecular polymer-drug conjugate of paclitaxel modulated by estradiol could extend the utility of this class of drugs. Patients with metastatic adenocarcinoma of the prostate who progressed despite standard hormonal therapy and after docetaxel-containing chemotherapy were treated with transdermal estradiol (0.2mg/24h) for 4 weeks followed by the same dose of transdermal estradiol and paclitaxel poliglumex (PPX; 150mg/m2 intravenous) every 28 days. The primary objective was to determine the level of activity of the regimen measured using a fraction of patients who experienced a confirmed decline in serum prostate-specific antigen (PSA) of 50% or more. A two-stage phase II study designed to identify a response rate of ≥25% required three responders among 21 patients in the first stage. Twenty-one patients who received a median of two earlier chemotherapy regimens were enrolled in the trial between March 2007 and May 2008. During the estradiol-only treatment phase, no patient had a PSA decline in excess of 50% and lesser PSA declines that ranged from 8.8 to 34.1% were seen in five patients. No patients achieved a ≥50% PSA decline following the addition of PPX and there were no responses in measurable disease. The median time to progression was 4 weeks. In conclusion, this regimen of low-dose transdermal estradiol induction followed by PPX does not have activity in taxane pretreated patients with castration-resistant prostate cancer.

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