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 M. Beer, Christopher W. 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

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    251 Scopus citations

    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

    ASJC Scopus subject areas

    • Oncology
    • Cancer Research

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    Beer, T. M., Ryan, C. W., Venner, P. M., Petrylak, D. P., Chatta, G. S., Ruether, J. D., Redfern, C. H., Fehrenbacher, L., Saleh, M. N., Waterhouse, D. M., Carducci, M. A., Vicario, D., Dreicer, R., Higano, C. S., Ahmann, F. R., Chi, K. N., Henner, W. D., Arroyo, A., & Clow, F. W. (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, 25(6), 669-674. https://doi.org/10.1200/JCO.2006.06.8197