Double-blinded randomized study of high-dose calcitriol plus docetaxel compared with placebo plus docetaxel in androgen-independent prostate cancer

A report from the ASCENT investigators

Tomasz (Tom) Beer, Christopher Ryan, Peter M. Venner, Daniel P. Petrylak, Gurkamal S. Chatta, J. Dean Ruether, Charles H. Redfern, Louis Fehrenbacher, Mansoor N. Saleh, David M. Waterhouse, Michael A. Carducci, Daniel Vicario, Robert Dreicer, Celestia S. Higano, Frederick R. Ahmann, Kim N. Chi, W. David Henner, Alan Arroyo, Fong W. Clow

    Research output: Contribution to journalArticle

    246 Citations (Scopus)

    Abstract

    Purpose: To compare the safety and activity of DN-101, a new high-dose oral formulation of calcitriol designed for cancer therapy, and docetaxel with placebo and docetaxel. Patients and Methods: Patients with progressive metastatic androgen-independent prostate cancer and adequate organ function received weekly docetaxel 36 mg/m2 intravenously for 3 weeks of a 4-week cycle combined with either 45 μg DN-101 or placebo taken orally 1 day before docetaxel. The primary end point was prostate-specific antigen (PSA) response within 6 months of enrollment, defined as a 50% reduction confirmed at least 4 weeks later. Results: Two hundred fifty patients were randomly assigned. Baseline characteristics were similar in both arms. Within 6 months, PSA responses were seen in 58% in DN-101 patients and 49% in placebo patients (P = .16). Overall, PSA response rates were 63% (DN-101) and 52% (placebo), P = .07. Patients in the DN-101 group had a hazard ratio for death of 0.67 (P = .04) in a multivariate analysis that included baseline hemoglobin and performance status. Median survival has not been reached for the DN-101 arm and is estimated to be 24.5 months using the hazard ratio, compared with 16.4 months for placebo. Grade 3/4 adverse events occurred in 58% of DN-101 patients and in 70% of placebo-treated patients (P = .07). Most common grade 3/4 toxicities for DN-101 versus placebo were neutropenia (10% v 8%), fatigue (8% v 16%), infection (8% v 13%), and hyperglycemia (6% v 12%). Conclusion: This study suggests that DN-101 treatment was associated with improved survival, but this will require confirmation because survival was not a primary end point. The addition of weekly DN-101 did not increase the toxicity of weekly docetaxel.

    Original languageEnglish (US)
    Pages (from-to)669-674
    Number of pages6
    JournalJournal of Clinical Oncology
    Volume25
    Issue number6
    DOIs
    StatePublished - Feb 20 2007

    Fingerprint

    docetaxel
    Calcitriol
    Androgens
    Prostatic Neoplasms
    Placebos
    Research Personnel
    Prostate-Specific Antigen
    Survival
    Neutropenia
    Hyperglycemia
    Fatigue

    ASJC Scopus subject areas

    • Cancer Research
    • Oncology
    • Medicine(all)

    Cite this

    Double-blinded randomized study of high-dose calcitriol plus docetaxel compared with placebo plus docetaxel in androgen-independent prostate cancer : A report from the ASCENT investigators. / Beer, Tomasz (Tom); Ryan, Christopher; Venner, Peter M.; Petrylak, Daniel P.; Chatta, Gurkamal S.; Ruether, J. Dean; Redfern, Charles H.; Fehrenbacher, Louis; Saleh, Mansoor N.; Waterhouse, David M.; Carducci, Michael A.; Vicario, Daniel; Dreicer, Robert; Higano, Celestia S.; Ahmann, Frederick R.; Chi, Kim N.; Henner, W. David; Arroyo, Alan; Clow, Fong W.

    In: Journal of Clinical Oncology, Vol. 25, No. 6, 20.02.2007, p. 669-674.

    Research output: Contribution to journalArticle

    Beer, TT, Ryan, C, Venner, PM, Petrylak, DP, Chatta, GS, Ruether, JD, Redfern, CH, Fehrenbacher, L, Saleh, MN, Waterhouse, DM, Carducci, MA, Vicario, D, Dreicer, R, Higano, CS, Ahmann, FR, Chi, KN, Henner, WD, Arroyo, A & Clow, FW 2007, 'Double-blinded randomized study of high-dose calcitriol plus docetaxel compared with placebo plus docetaxel in androgen-independent prostate cancer: A report from the ASCENT investigators', Journal of Clinical Oncology, vol. 25, no. 6, pp. 669-674. https://doi.org/10.1200/JCO.2006.06.8197
    Beer, Tomasz (Tom) ; Ryan, Christopher ; Venner, Peter M. ; Petrylak, Daniel P. ; Chatta, Gurkamal S. ; Ruether, J. Dean ; Redfern, Charles H. ; Fehrenbacher, Louis ; Saleh, Mansoor N. ; Waterhouse, David M. ; Carducci, Michael A. ; Vicario, Daniel ; Dreicer, Robert ; Higano, Celestia S. ; Ahmann, Frederick R. ; Chi, Kim N. ; Henner, W. David ; Arroyo, Alan ; Clow, Fong W. / Double-blinded randomized study of high-dose calcitriol plus docetaxel compared with placebo plus docetaxel in androgen-independent prostate cancer : A report from the ASCENT investigators. In: Journal of Clinical Oncology. 2007 ; Vol. 25, No. 6. pp. 669-674.
    @article{05a08657bb8b4b33b72abd0f15710c7c,
    title = "Double-blinded randomized study of high-dose calcitriol plus docetaxel compared with placebo plus docetaxel in androgen-independent prostate cancer: A report from the ASCENT investigators",
    abstract = "Purpose: To compare the safety and activity of DN-101, a new high-dose oral formulation of calcitriol designed for cancer therapy, and docetaxel with placebo and docetaxel. Patients and Methods: Patients with progressive metastatic androgen-independent prostate cancer and adequate organ function received weekly docetaxel 36 mg/m2 intravenously for 3 weeks of a 4-week cycle combined with either 45 μg DN-101 or placebo taken orally 1 day before docetaxel. The primary end point was prostate-specific antigen (PSA) response within 6 months of enrollment, defined as a 50{\%} reduction confirmed at least 4 weeks later. Results: Two hundred fifty patients were randomly assigned. Baseline characteristics were similar in both arms. Within 6 months, PSA responses were seen in 58{\%} in DN-101 patients and 49{\%} in placebo patients (P = .16). Overall, PSA response rates were 63{\%} (DN-101) and 52{\%} (placebo), P = .07. Patients in the DN-101 group had a hazard ratio for death of 0.67 (P = .04) in a multivariate analysis that included baseline hemoglobin and performance status. Median survival has not been reached for the DN-101 arm and is estimated to be 24.5 months using the hazard ratio, compared with 16.4 months for placebo. Grade 3/4 adverse events occurred in 58{\%} of DN-101 patients and in 70{\%} of placebo-treated patients (P = .07). Most common grade 3/4 toxicities for DN-101 versus placebo were neutropenia (10{\%} v 8{\%}), fatigue (8{\%} v 16{\%}), infection (8{\%} v 13{\%}), and hyperglycemia (6{\%} v 12{\%}). Conclusion: This study suggests that DN-101 treatment was associated with improved survival, but this will require confirmation because survival was not a primary end point. The addition of weekly DN-101 did not increase the toxicity of weekly docetaxel.",
    author = "Beer, {Tomasz (Tom)} and Christopher Ryan and Venner, {Peter M.} and Petrylak, {Daniel P.} and Chatta, {Gurkamal S.} and Ruether, {J. Dean} and Redfern, {Charles H.} and Louis Fehrenbacher and Saleh, {Mansoor N.} and Waterhouse, {David M.} and Carducci, {Michael A.} and Daniel Vicario and Robert Dreicer and Higano, {Celestia S.} and Ahmann, {Frederick R.} and Chi, {Kim N.} and Henner, {W. David} and Alan Arroyo and Clow, {Fong W.}",
    year = "2007",
    month = "2",
    day = "20",
    doi = "10.1200/JCO.2006.06.8197",
    language = "English (US)",
    volume = "25",
    pages = "669--674",
    journal = "Journal of Clinical Oncology",
    issn = "0732-183X",
    publisher = "American Society of Clinical Oncology",
    number = "6",

    }

    TY - JOUR

    T1 - Double-blinded randomized study of high-dose calcitriol plus docetaxel compared with placebo plus docetaxel in androgen-independent prostate cancer

    T2 - A report from the ASCENT investigators

    AU - Beer, Tomasz (Tom)

    AU - Ryan, Christopher

    AU - Venner, Peter M.

    AU - Petrylak, Daniel P.

    AU - Chatta, Gurkamal S.

    AU - Ruether, J. Dean

    AU - Redfern, Charles H.

    AU - Fehrenbacher, Louis

    AU - Saleh, Mansoor N.

    AU - Waterhouse, David M.

    AU - Carducci, Michael A.

    AU - Vicario, Daniel

    AU - Dreicer, Robert

    AU - Higano, Celestia S.

    AU - Ahmann, Frederick R.

    AU - Chi, Kim N.

    AU - Henner, W. David

    AU - Arroyo, Alan

    AU - Clow, Fong W.

    PY - 2007/2/20

    Y1 - 2007/2/20

    N2 - Purpose: To compare the safety and activity of DN-101, a new high-dose oral formulation of calcitriol designed for cancer therapy, and docetaxel with placebo and docetaxel. Patients and Methods: Patients with progressive metastatic androgen-independent prostate cancer and adequate organ function received weekly docetaxel 36 mg/m2 intravenously for 3 weeks of a 4-week cycle combined with either 45 μg DN-101 or placebo taken orally 1 day before docetaxel. The primary end point was prostate-specific antigen (PSA) response within 6 months of enrollment, defined as a 50% reduction confirmed at least 4 weeks later. Results: Two hundred fifty patients were randomly assigned. Baseline characteristics were similar in both arms. Within 6 months, PSA responses were seen in 58% in DN-101 patients and 49% in placebo patients (P = .16). Overall, PSA response rates were 63% (DN-101) and 52% (placebo), P = .07. Patients in the DN-101 group had a hazard ratio for death of 0.67 (P = .04) in a multivariate analysis that included baseline hemoglobin and performance status. Median survival has not been reached for the DN-101 arm and is estimated to be 24.5 months using the hazard ratio, compared with 16.4 months for placebo. Grade 3/4 adverse events occurred in 58% of DN-101 patients and in 70% of placebo-treated patients (P = .07). Most common grade 3/4 toxicities for DN-101 versus placebo were neutropenia (10% v 8%), fatigue (8% v 16%), infection (8% v 13%), and hyperglycemia (6% v 12%). Conclusion: This study suggests that DN-101 treatment was associated with improved survival, but this will require confirmation because survival was not a primary end point. The addition of weekly DN-101 did not increase the toxicity of weekly docetaxel.

    AB - Purpose: To compare the safety and activity of DN-101, a new high-dose oral formulation of calcitriol designed for cancer therapy, and docetaxel with placebo and docetaxel. Patients and Methods: Patients with progressive metastatic androgen-independent prostate cancer and adequate organ function received weekly docetaxel 36 mg/m2 intravenously for 3 weeks of a 4-week cycle combined with either 45 μg DN-101 or placebo taken orally 1 day before docetaxel. The primary end point was prostate-specific antigen (PSA) response within 6 months of enrollment, defined as a 50% reduction confirmed at least 4 weeks later. Results: Two hundred fifty patients were randomly assigned. Baseline characteristics were similar in both arms. Within 6 months, PSA responses were seen in 58% in DN-101 patients and 49% in placebo patients (P = .16). Overall, PSA response rates were 63% (DN-101) and 52% (placebo), P = .07. Patients in the DN-101 group had a hazard ratio for death of 0.67 (P = .04) in a multivariate analysis that included baseline hemoglobin and performance status. Median survival has not been reached for the DN-101 arm and is estimated to be 24.5 months using the hazard ratio, compared with 16.4 months for placebo. Grade 3/4 adverse events occurred in 58% of DN-101 patients and in 70% of placebo-treated patients (P = .07). Most common grade 3/4 toxicities for DN-101 versus placebo were neutropenia (10% v 8%), fatigue (8% v 16%), infection (8% v 13%), and hyperglycemia (6% v 12%). Conclusion: This study suggests that DN-101 treatment was associated with improved survival, but this will require confirmation because survival was not a primary end point. The addition of weekly DN-101 did not increase the toxicity of weekly docetaxel.

    UR - http://www.scopus.com/inward/record.url?scp=33947610197&partnerID=8YFLogxK

    UR - http://www.scopus.com/inward/citedby.url?scp=33947610197&partnerID=8YFLogxK

    U2 - 10.1200/JCO.2006.06.8197

    DO - 10.1200/JCO.2006.06.8197

    M3 - Article

    VL - 25

    SP - 669

    EP - 674

    JO - Journal of Clinical Oncology

    JF - Journal of Clinical Oncology

    SN - 0732-183X

    IS - 6

    ER -