Southwest oncology group phase II study of ispinesib in androgen-independent prostate cancer previously treated with taxanes

Tomasz (Tom) Beer, Bryan Goldman, Timothy W. Synold, Christopher Ryan, Lakshmi S. Vasist, Peter J. Van Veldhuizen, Shaker R. Dakhil, Primo N. Lara, Anibal Drelichman, Maha H A Hussain, E. David Crawford

    Research output: Contribution to journalArticle

    32 Citations (Scopus)

    Abstract

    Purpose: The mitotic spindle has proven to be an effective therapeutic target in antineoplastic efforts. In this study, we sought to assess the efficacy of ispinesib, a mitotic kinesin spindle protein (KSP) inhibitor in androgen-independent prostate cancer progressing after docetaxel. Patients and Methods: Patients were treated with ispinesib 18 mg/m2 every 21 days and assessed for prostate-specific antigen (PSA) and measurable disease response at regular intervals. Kinesin spindle protein expression in archival tumors, population ispinesib pharmacokinetics, and pharmacodynamic assessments of circulating lymphocytes were included. Results: The study was terminated after first stage because no responses were seen in the first 21 patients. Median duration of PSA or clinical progression-free survival was 9 weeks. Plasma concentrations of ispinesib were comparable with those observed in previous phase I investigations. Immunohistochemical analysis of archival tumor specimens did not demonstrate significant KSP expression in most of the prostate cancer cases studied. Pharmacodynamic assessments of circulating lymphocytes from patients receiving ispinesib showed an absence of monopolar spindle formation, as would be expected if the drug were having its expected effects. Conclusion: Ispinesib was inactive in this study of patients with androgen-independent, and largely docetaxelresistant, prostate cancer. The lack of efficacy might be explained by the low expression of the drug target seen in prostate cancer, whereas not detecting monopolar spindles in circulating lymphocytes with drug treatment likely reflects the lack of dividing cells in peripheral blood.

    Original languageEnglish (US)
    Pages (from-to)103-109
    Number of pages7
    JournalClinical Genitourinary Cancer
    Volume6
    Issue number2
    DOIs
    StatePublished - 2008

    Fingerprint

    Taxoids
    Androgens
    Prostatic Neoplasms
    Kinesin
    Spindle Apparatus
    docetaxel
    Lymphocytes
    Prostate-Specific Antigen
    Pharmaceutical Preparations
    Proteins
    Antineoplastic Agents
    Disease-Free Survival
    ispinesib
    Neoplasms
    Pharmacokinetics
    Therapeutics
    Population

    Keywords

    • Hela cells
    • Kinesin spindle protein
    • Mitosis
    • Peripheral blood
    • Prostate-specific antigen

    ASJC Scopus subject areas

    • Oncology
    • Urology

    Cite this

    Southwest oncology group phase II study of ispinesib in androgen-independent prostate cancer previously treated with taxanes. / Beer, Tomasz (Tom); Goldman, Bryan; Synold, Timothy W.; Ryan, Christopher; Vasist, Lakshmi S.; Van Veldhuizen, Peter J.; Dakhil, Shaker R.; Lara, Primo N.; Drelichman, Anibal; Hussain, Maha H A; Crawford, E. David.

    In: Clinical Genitourinary Cancer, Vol. 6, No. 2, 2008, p. 103-109.

    Research output: Contribution to journalArticle

    Beer, TT, Goldman, B, Synold, TW, Ryan, C, Vasist, LS, Van Veldhuizen, PJ, Dakhil, SR, Lara, PN, Drelichman, A, Hussain, MHA & Crawford, ED 2008, 'Southwest oncology group phase II study of ispinesib in androgen-independent prostate cancer previously treated with taxanes', Clinical Genitourinary Cancer, vol. 6, no. 2, pp. 103-109. https://doi.org/10.3816/CGC.2008.n.016
    Beer, Tomasz (Tom) ; Goldman, Bryan ; Synold, Timothy W. ; Ryan, Christopher ; Vasist, Lakshmi S. ; Van Veldhuizen, Peter J. ; Dakhil, Shaker R. ; Lara, Primo N. ; Drelichman, Anibal ; Hussain, Maha H A ; Crawford, E. David. / Southwest oncology group phase II study of ispinesib in androgen-independent prostate cancer previously treated with taxanes. In: Clinical Genitourinary Cancer. 2008 ; Vol. 6, No. 2. pp. 103-109.
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    AU - Beer, Tomasz (Tom)

    AU - Goldman, Bryan

    AU - Synold, Timothy W.

    AU - Ryan, Christopher

    AU - Vasist, Lakshmi S.

    AU - Van Veldhuizen, Peter J.

    AU - Dakhil, Shaker R.

    AU - Lara, Primo N.

    AU - Drelichman, Anibal

    AU - Hussain, Maha H A

    AU - Crawford, E. David

    PY - 2008

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