A randomized phase II trial of the antiangiogenic agent SU5416 in hormone-refractory prostate cancer

Walter M. Stadler, Dingcai Cao, Nicholas J. Vogelzang, Christopher Ryan, Kristin Hoving, Russell Wright, Theodore Karrison, Everett E. Vokes

Research output: Contribution to journalArticle

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Abstract

Purpose: To assess the activity of the antiangiogenic agent and VEGFR2 inhibitor SU5416 in hormone-refractory prostate cancer. Patients and Methods: Thirty-six chemotherapy naïve patients were randomized to treatment with SU5416 (145 mg/m2) and dexamethasone premedication or dexamethasone alone. Patients in the control arm could cross over to experimental therapy after progression. Prostate-specific antigen (PSA) was measured every 2 weeks, and radiological evaluation was performed every 8 weeks. In vitro assessment of SU5416 on PSA secretion was assessed in the LNCaP cell line. Baseline serum basic fibroblast growth factor and plasma vascular endothelial growth factor (VEGF) were explored as prognostic factors. Results: VEGF receptor-2 expression is detectable in prostate cancer cell lines, and SU5416 inhibited in vitro PSA secretion. No effect of SU5416 on PSA secretion or time to progression is detectable in patients. VEGF and basic fibroblast growth factor were not prognostic. Headache and fatigue were the most common SU5416 toxicities, but hyperglycemia, hyponatremia, lymphopenia, infection, and adrenal suppression, all attributable to steroids and the required central line, were common. Conclusion: No disease modifying effects of SU5416 were detectable in this small study. Modest toxicity, an inconvenient administration schedule, and availability of other VEGFR-targeted agents support the decision to halt further evaluation of SU5416 in prostate cancer.

Original languageEnglish (US)
Pages (from-to)3365-3370
Number of pages6
JournalClinical Cancer Research
Volume10
Issue number10
DOIs
StatePublished - May 15 2004
Externally publishedYes

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Angiogenesis Inhibitors
Prostatic Neoplasms
Hormones
Prostate-Specific Antigen
Fibroblast Growth Factor 2
Dexamethasone
Vascular Endothelial Growth Factor A
Cell Line
Vascular Endothelial Growth Factor Receptor-2
Investigational Therapies
Lymphopenia
Premedication
Semaxinib
Hyponatremia
Hyperglycemia
Fatigue
Headache
Appointments and Schedules
Steroids
Drug Therapy

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

A randomized phase II trial of the antiangiogenic agent SU5416 in hormone-refractory prostate cancer. / Stadler, Walter M.; Cao, Dingcai; Vogelzang, Nicholas J.; Ryan, Christopher; Hoving, Kristin; Wright, Russell; Karrison, Theodore; Vokes, Everett E.

In: Clinical Cancer Research, Vol. 10, No. 10, 15.05.2004, p. 3365-3370.

Research output: Contribution to journalArticle

Stadler, WM, Cao, D, Vogelzang, NJ, Ryan, C, Hoving, K, Wright, R, Karrison, T & Vokes, EE 2004, 'A randomized phase II trial of the antiangiogenic agent SU5416 in hormone-refractory prostate cancer', Clinical Cancer Research, vol. 10, no. 10, pp. 3365-3370. https://doi.org/10.1158/1078-0432.CCR-03-0404
Stadler, Walter M. ; Cao, Dingcai ; Vogelzang, Nicholas J. ; Ryan, Christopher ; Hoving, Kristin ; Wright, Russell ; Karrison, Theodore ; Vokes, Everett E. / A randomized phase II trial of the antiangiogenic agent SU5416 in hormone-refractory prostate cancer. In: Clinical Cancer Research. 2004 ; Vol. 10, No. 10. pp. 3365-3370.
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