High-dose weekly oral calcitriol in patients with a rising PSA after prostatectomy or radiation for prostate carcinoma

Tomasz (Tom) Beer, Dianne Lemmon, Bruce A. Lowe, W. David Henner

    Research output: Contribution to journalArticle

    101 Citations (Scopus)

    Abstract

    BACKGROUND. In preclinical systems, calcitriol, the natural vitamin D receptor (VDR) ligand, has been found to demonstrate antiproliferative effects, although concentrations > 1 nM are required. Unlike daily dosing, weekly administration of oral calcitriol can safely achieve such blood calcitriol concentrations. This study sought to define the long-term toxicity of this regimen and measure its effect on serum prostate specific antigen (PSA) levels in patients with hormone-naïve prostate carcinoma. METHODS. Patients with a rising serum PSA after prostatectomy and/or radiation and no prior systemic therapy for prostate carcinoma recurrence maintained a reduced calcium diet and received calcitriol 0.5 μg/kg orally once each week until a maximum of a four-fold increase in the PSA. RESULTS. Twenty-two patients received treatment for a median of 10 months (range, 2-25+ months). Treatment was well tolerated with no Grade ≥ 3 toxicity and no hypercalcemia or renal calculi. No patient had a PSA response (50% reduction confirmed 4 weeks later). Three patients (14%, 95% CI 0-28%) had confirmed reductions in the PSA ranging from 10% to 47%. Statistically significant increases in the PSA doubling time (PSADT) were seen in three additional patients and no patient had a shorter PSADT after starting treatment. For the entire study population, the median PSADT increased from 7.8 months to 10.3 months (P = 0.03 by Wilcoxon signed rank test). CONCLUSIONS. Weekly high-dose calcitriol was found to be safe. The primary efficacy endpoint of 50% reduction in the serum PSA was not achieved with this therapy. Randomized studies are needed to further examine the impact of this therapy on prostate carcinoma progression.

    Original languageEnglish (US)
    Pages (from-to)1217-1224
    Number of pages8
    JournalCancer
    Volume97
    Issue number5
    DOIs
    StatePublished - Mar 1 2003

    Fingerprint

    Calcitriol
    Prostate-Specific Antigen
    Prostatectomy
    Prostate
    Radiation
    Carcinoma
    Therapeutics
    Serum
    Calcitriol Receptors
    Kidney Calculi
    Hypercalcemia
    Nonparametric Statistics
    Oral Administration
    Hormones
    Diet
    Ligands
    Calcium
    Recurrence
    Population

    Keywords

    • 1α,25-dihydroxycholecalciferol
    • 1,25-dihydroxyvitamin D
    • Calcitriol
    • Clinical trial
    • Phase II
    • Prostate carcinoma
    • Prostate specific antigen (PSA)
    • Vitamin D

    ASJC Scopus subject areas

    • Cancer Research
    • Oncology

    Cite this

    High-dose weekly oral calcitriol in patients with a rising PSA after prostatectomy or radiation for prostate carcinoma. / Beer, Tomasz (Tom); Lemmon, Dianne; Lowe, Bruce A.; Henner, W. David.

    In: Cancer, Vol. 97, No. 5, 01.03.2003, p. 1217-1224.

    Research output: Contribution to journalArticle

    Beer, Tomasz (Tom) ; Lemmon, Dianne ; Lowe, Bruce A. ; Henner, W. David. / High-dose weekly oral calcitriol in patients with a rising PSA after prostatectomy or radiation for prostate carcinoma. In: Cancer. 2003 ; Vol. 97, No. 5. pp. 1217-1224.
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    abstract = "BACKGROUND. In preclinical systems, calcitriol, the natural vitamin D receptor (VDR) ligand, has been found to demonstrate antiproliferative effects, although concentrations > 1 nM are required. Unlike daily dosing, weekly administration of oral calcitriol can safely achieve such blood calcitriol concentrations. This study sought to define the long-term toxicity of this regimen and measure its effect on serum prostate specific antigen (PSA) levels in patients with hormone-na{\"i}ve prostate carcinoma. METHODS. Patients with a rising serum PSA after prostatectomy and/or radiation and no prior systemic therapy for prostate carcinoma recurrence maintained a reduced calcium diet and received calcitriol 0.5 μg/kg orally once each week until a maximum of a four-fold increase in the PSA. RESULTS. Twenty-two patients received treatment for a median of 10 months (range, 2-25+ months). Treatment was well tolerated with no Grade ≥ 3 toxicity and no hypercalcemia or renal calculi. No patient had a PSA response (50{\%} reduction confirmed 4 weeks later). Three patients (14{\%}, 95{\%} CI 0-28{\%}) had confirmed reductions in the PSA ranging from 10{\%} to 47{\%}. Statistically significant increases in the PSA doubling time (PSADT) were seen in three additional patients and no patient had a shorter PSADT after starting treatment. For the entire study population, the median PSADT increased from 7.8 months to 10.3 months (P = 0.03 by Wilcoxon signed rank test). CONCLUSIONS. Weekly high-dose calcitriol was found to be safe. The primary efficacy endpoint of 50{\%} reduction in the serum PSA was not achieved with this therapy. Randomized studies are needed to further examine the impact of this therapy on prostate carcinoma progression.",
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    T1 - High-dose weekly oral calcitriol in patients with a rising PSA after prostatectomy or radiation for prostate carcinoma

    AU - Beer, Tomasz (Tom)

    AU - Lemmon, Dianne

    AU - Lowe, Bruce A.

    AU - Henner, W. David

    PY - 2003/3/1

    Y1 - 2003/3/1

    N2 - BACKGROUND. In preclinical systems, calcitriol, the natural vitamin D receptor (VDR) ligand, has been found to demonstrate antiproliferative effects, although concentrations > 1 nM are required. Unlike daily dosing, weekly administration of oral calcitriol can safely achieve such blood calcitriol concentrations. This study sought to define the long-term toxicity of this regimen and measure its effect on serum prostate specific antigen (PSA) levels in patients with hormone-naïve prostate carcinoma. METHODS. Patients with a rising serum PSA after prostatectomy and/or radiation and no prior systemic therapy for prostate carcinoma recurrence maintained a reduced calcium diet and received calcitriol 0.5 μg/kg orally once each week until a maximum of a four-fold increase in the PSA. RESULTS. Twenty-two patients received treatment for a median of 10 months (range, 2-25+ months). Treatment was well tolerated with no Grade ≥ 3 toxicity and no hypercalcemia or renal calculi. No patient had a PSA response (50% reduction confirmed 4 weeks later). Three patients (14%, 95% CI 0-28%) had confirmed reductions in the PSA ranging from 10% to 47%. Statistically significant increases in the PSA doubling time (PSADT) were seen in three additional patients and no patient had a shorter PSADT after starting treatment. For the entire study population, the median PSADT increased from 7.8 months to 10.3 months (P = 0.03 by Wilcoxon signed rank test). CONCLUSIONS. Weekly high-dose calcitriol was found to be safe. The primary efficacy endpoint of 50% reduction in the serum PSA was not achieved with this therapy. Randomized studies are needed to further examine the impact of this therapy on prostate carcinoma progression.

    AB - BACKGROUND. In preclinical systems, calcitriol, the natural vitamin D receptor (VDR) ligand, has been found to demonstrate antiproliferative effects, although concentrations > 1 nM are required. Unlike daily dosing, weekly administration of oral calcitriol can safely achieve such blood calcitriol concentrations. This study sought to define the long-term toxicity of this regimen and measure its effect on serum prostate specific antigen (PSA) levels in patients with hormone-naïve prostate carcinoma. METHODS. Patients with a rising serum PSA after prostatectomy and/or radiation and no prior systemic therapy for prostate carcinoma recurrence maintained a reduced calcium diet and received calcitriol 0.5 μg/kg orally once each week until a maximum of a four-fold increase in the PSA. RESULTS. Twenty-two patients received treatment for a median of 10 months (range, 2-25+ months). Treatment was well tolerated with no Grade ≥ 3 toxicity and no hypercalcemia or renal calculi. No patient had a PSA response (50% reduction confirmed 4 weeks later). Three patients (14%, 95% CI 0-28%) had confirmed reductions in the PSA ranging from 10% to 47%. Statistically significant increases in the PSA doubling time (PSADT) were seen in three additional patients and no patient had a shorter PSADT after starting treatment. For the entire study population, the median PSADT increased from 7.8 months to 10.3 months (P = 0.03 by Wilcoxon signed rank test). CONCLUSIONS. Weekly high-dose calcitriol was found to be safe. The primary efficacy endpoint of 50% reduction in the serum PSA was not achieved with this therapy. Randomized studies are needed to further examine the impact of this therapy on prostate carcinoma progression.

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    KW - Calcitriol

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    KW - Phase II

    KW - Prostate carcinoma

    KW - Prostate specific antigen (PSA)

    KW - Vitamin D

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