Lakshmi S Vasist

Publications (2)5.96 Total impact

• Article: 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
  [show abstract] [hide abstract]
  ABSTRACT: 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 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. 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. 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.
  Clinical Genitourinary Cancer 10/2008; 6(2):103-9. · 2.61 Impact Factor
• Article: Phase II study of ispinesib in recurrent or metastatic squamous cell carcinoma of the head and neck.

  Patricia A Tang, Lillian L Siu, Eric X Chen, Sebastien J Hotte, Stephen Chia, James K Schwarz, Gregory R Pond, Caitlin Johnson, A Dimitrios Colevas, Timothy W Synold, Lakshmi S Vasist, Eric Winquist
  [show abstract] [hide abstract]
  ABSTRACT: Ispinesib (SB-715992) inhibits the mitotic kinesin spindle protein (KSP), a novel target for anticancer therapy. A phase II study was conducted to examine the efficacy of ispinesib in recurrent or metastatic head and neck squamous cell carcinoma (RMHNSC). Patients with up to one prior line of chemotherapy for RMHNSC were treated with ispinesib 18 mg/m2 IV over 1 hour every 21 days. Twenty-one patients were enrolled onto this study with a target stage I sample size of 19. Of 20 evaluable patients, no objective responses were seen and stable disease > 2 cycles was observed in five patients (25%). The median time to progression was 1.4 (95% CI 1.3-2.3) months, median survival was 3.5 (95% CI 2.8-7.8) months, and 1 year overall survival was 20% (95% CI 8.3-48.1%). The most frequent attributable grades III-V adverse events were neutropenia (60% of patients) and leukopenia (55%). The pharmacokinetic profile was consistent with results from phase I studies. Archival tissues (n = 14) demonstrated low to moderate KSP expression by immunohistochemistry. In addition, no pharmacodynamic changes were observed in peripheral blood mononuclear cells. We detected no antitumor activity of ispinesib in RMHNSC on this dosing schedule.
  Investigational New Drugs 06/2008; 26(3):257-64. · 3.36 Impact Factor