High dose pulse calcitriol, docetaxel and estramustine for androgen independent prostate cancer: A phase I/II study

Natasha M. Tiffany, Christopher W. Ryan, Mark Garzotto, Emily M. Wersinger, Tomasz M. Beer

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    Abstract

    Purpose: We determined the safety and preliminary efficacy of the combination of high dose pulse calcitriol (1,25-dihydroxycholecalciferol) with a standard regimen of docetaxel plus estramustine in patients with metastatic androgen independent prostate cancer. Materials and Methods: Patients were treated with 60 μg calcitriol orally on day 1, 280 mg estramustine orally 3 times daily on days 1 to 5 and 60 mg/m2 docetaxel on day 2 (70 mg/m2 after cycle 1) every 21 days for up to 12 cycles. Patients also received 325 mg aspirin and 1 or 2 mg warfarin orally daily. Regimen safety was assessed in the first 6 patients and a dose de-escalation scheme for calcitriol was planned if dose limiting toxicities were noted during treatment cycle 1 in greater than a third of patients. Results: A total of 24 patients, including 11 who were chemotherapy naïve and 13 who had previously been treated with docetaxel, were evaluable for toxicity and 22 for prostate specific antigen decrease data. The regimen was generally well tolerated. Treatment related grades 3 or greater toxicity seen in more than 1 patient included hypophosphatemia in 16.7% and neutropenia in 12.5%. Four patients had thromboembolic complications. Asymptomatic hypercalcemia was seen in 4 patients, including grades 2 and 1 in 1 and 3, respectively. Six of 11 evaluable, chemotherapy naïve patients (55%) met prostate specific antigen response criteria. One of 11 patients (9%) treated with prior docetaxel met these criteria. Conclusions: High dose calcitriol may be safely added to docetaxel and estramustine administered on a 21-day schedule.

    Original languageEnglish (US)
    Pages (from-to)888-892
    Number of pages5
    JournalJournal of Urology
    Volume174
    Issue number3
    DOIs
    StatePublished - Sep 2005

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    docetaxel
    Estramustine
    Calcitriol
    Androgens
    Prostatic Neoplasms
    Prostate-Specific Antigen
    Hypophosphatemia
    Safety
    Drug Therapy

    Keywords

    • Calcitriol
    • Docetaxel
    • Prostate
    • Prostatic neoplasms
    • Stramustine

    ASJC Scopus subject areas

    • Urology

    Cite this

    High dose pulse calcitriol, docetaxel and estramustine for androgen independent prostate cancer : A phase I/II study. / Tiffany, Natasha M.; Ryan, Christopher W.; Garzotto, Mark; Wersinger, Emily M.; Beer, Tomasz M.

    In: Journal of Urology, Vol. 174, No. 3, 09.2005, p. 888-892.

    Research output: Contribution to journalArticle

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    abstract = "Purpose: We determined the safety and preliminary efficacy of the combination of high dose pulse calcitriol (1,25-dihydroxycholecalciferol) with a standard regimen of docetaxel plus estramustine in patients with metastatic androgen independent prostate cancer. Materials and Methods: Patients were treated with 60 μg calcitriol orally on day 1, 280 mg estramustine orally 3 times daily on days 1 to 5 and 60 mg/m2 docetaxel on day 2 (70 mg/m2 after cycle 1) every 21 days for up to 12 cycles. Patients also received 325 mg aspirin and 1 or 2 mg warfarin orally daily. Regimen safety was assessed in the first 6 patients and a dose de-escalation scheme for calcitriol was planned if dose limiting toxicities were noted during treatment cycle 1 in greater than a third of patients. Results: A total of 24 patients, including 11 who were chemotherapy na{\"i}ve and 13 who had previously been treated with docetaxel, were evaluable for toxicity and 22 for prostate specific antigen decrease data. The regimen was generally well tolerated. Treatment related grades 3 or greater toxicity seen in more than 1 patient included hypophosphatemia in 16.7{\%} and neutropenia in 12.5{\%}. Four patients had thromboembolic complications. Asymptomatic hypercalcemia was seen in 4 patients, including grades 2 and 1 in 1 and 3, respectively. Six of 11 evaluable, chemotherapy na{\"i}ve patients (55{\%}) met prostate specific antigen response criteria. One of 11 patients (9{\%}) treated with prior docetaxel met these criteria. Conclusions: High dose calcitriol may be safely added to docetaxel and estramustine administered on a 21-day schedule.",
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    AU - Ryan, Christopher W.

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    N2 - Purpose: We determined the safety and preliminary efficacy of the combination of high dose pulse calcitriol (1,25-dihydroxycholecalciferol) with a standard regimen of docetaxel plus estramustine in patients with metastatic androgen independent prostate cancer. Materials and Methods: Patients were treated with 60 μg calcitriol orally on day 1, 280 mg estramustine orally 3 times daily on days 1 to 5 and 60 mg/m2 docetaxel on day 2 (70 mg/m2 after cycle 1) every 21 days for up to 12 cycles. Patients also received 325 mg aspirin and 1 or 2 mg warfarin orally daily. Regimen safety was assessed in the first 6 patients and a dose de-escalation scheme for calcitriol was planned if dose limiting toxicities were noted during treatment cycle 1 in greater than a third of patients. Results: A total of 24 patients, including 11 who were chemotherapy naïve and 13 who had previously been treated with docetaxel, were evaluable for toxicity and 22 for prostate specific antigen decrease data. The regimen was generally well tolerated. Treatment related grades 3 or greater toxicity seen in more than 1 patient included hypophosphatemia in 16.7% and neutropenia in 12.5%. Four patients had thromboembolic complications. Asymptomatic hypercalcemia was seen in 4 patients, including grades 2 and 1 in 1 and 3, respectively. Six of 11 evaluable, chemotherapy naïve patients (55%) met prostate specific antigen response criteria. One of 11 patients (9%) treated with prior docetaxel met these criteria. Conclusions: High dose calcitriol may be safely added to docetaxel and estramustine administered on a 21-day schedule.

    AB - Purpose: We determined the safety and preliminary efficacy of the combination of high dose pulse calcitriol (1,25-dihydroxycholecalciferol) with a standard regimen of docetaxel plus estramustine in patients with metastatic androgen independent prostate cancer. Materials and Methods: Patients were treated with 60 μg calcitriol orally on day 1, 280 mg estramustine orally 3 times daily on days 1 to 5 and 60 mg/m2 docetaxel on day 2 (70 mg/m2 after cycle 1) every 21 days for up to 12 cycles. Patients also received 325 mg aspirin and 1 or 2 mg warfarin orally daily. Regimen safety was assessed in the first 6 patients and a dose de-escalation scheme for calcitriol was planned if dose limiting toxicities were noted during treatment cycle 1 in greater than a third of patients. Results: A total of 24 patients, including 11 who were chemotherapy naïve and 13 who had previously been treated with docetaxel, were evaluable for toxicity and 22 for prostate specific antigen decrease data. The regimen was generally well tolerated. Treatment related grades 3 or greater toxicity seen in more than 1 patient included hypophosphatemia in 16.7% and neutropenia in 12.5%. Four patients had thromboembolic complications. Asymptomatic hypercalcemia was seen in 4 patients, including grades 2 and 1 in 1 and 3, respectively. Six of 11 evaluable, chemotherapy naïve patients (55%) met prostate specific antigen response criteria. One of 11 patients (9%) treated with prior docetaxel met these criteria. Conclusions: High dose calcitriol may be safely added to docetaxel and estramustine administered on a 21-day schedule.

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    KW - Docetaxel

    KW - Prostate

    KW - Prostatic neoplasms

    KW - Stramustine

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