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

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

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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

Beer, T. M., Goldman, B., Synold, T. W., Ryan, C. W., Vasist, L. S., Van Veldhuizen, P. J., ... Crawford, E. D. (2008). Southwest oncology group phase II study of ispinesib in androgen-independent prostate cancer previously treated with taxanes. Clinical Genitourinary Cancer, 6(2), 103-109. https://doi.org/10.3816/CGC.2008.n.016

Southwest oncology group phase II study of ispinesib in androgen-independent prostate cancer previously treated with taxanes. / Beer, Tomasz M.; Goldman, Bryan; Synold, Timothy W.; Ryan, Christopher W.; 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, TM, Goldman, B, Synold, TW, Ryan, CW, 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 M. ; Goldman, Bryan ; Synold, Timothy W. ; Ryan, Christopher W. ; 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 - Vasist, Lakshmi S.

AU - Van Veldhuizen, Peter J.

AU - Dakhil, Shaker R.

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