Phase II Study of SU5416, a Small Molecule Vascular Endothelial Growth Factor Tyrosine Kinase Receptor Inhibitor, in Patients with Refractory Multiple Myeloma

Maurizio Zangari, Elias Anaissie, Alison Stopeck, Alyssa Morimoto, Nguyen Tan, Jeffrey Lancet, Maureen Cooper, Alison Hannah, Guillermo Garcia-Manero, Stephan Faderl, Hagop Kantarjian, Julie Cherrington, Maher Albitar, Francis J. Giles

Research output: Contribution to journalArticle

110 Scopus citations

Abstract

Purpose: Increased bone marrow angiogenesis and vascular endothelial growth factor (VEGF) levels are of adverse prognostic significance in patients with multiple myeloma (MM). VEGF, a soluble circulating angiogenic molecule, acts via receptor tyrosine kinases, including VEGF receptor 2. SU5416 is a small molecule VEGF receptor 2 inhibitor. Experimental Design: Adult patients with advanced MM were entered on a multicenter phase II study. Results: Twenty-seven patients (median age 69, range 39-79), median 4 (0-10) lines of prior therapy, 14 with prior thalidomide therapy, received SU5416 at 145 mg/m2 twice weekly i.v. for a median of two 4-week cycles (range 0.2-9). Grade 3/4 toxicities were rarely observed; the most frequent was thrombocytopenia (12%). Mild-to-moderate toxicities included nausea (63%), headache (56%), diarrhea, vomiting (both 37%), and fatigue (33%). There were three thromboembolic episodes and five cases of new onset hypertension. Two (7%) patients did not complete the first 4-week cycle of therapy because of adverse events (pneumonia and headache). There were no objective responses. Four patients had disease stabilization for ≥4 months. A decrease in median VEGF plasma levels was observed in patients with stable disease (n = 7) compared with patients with progressive disease (n = 5). Overall median survival was 42 weeks (range 3-92+). Conclusions: Although SU5416 had minimal clinical activity, signs of biological activity (decrease in plasma VEGF levels) suggest that angiogenic modulation may be of value in patients with MM.

Original languageEnglish (US)
Pages (from-to)88-95
Number of pages8
JournalClinical Cancer Research
Volume10
Issue number1 I
DOIs
StatePublished - Jan 1 2004

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Zangari, M., Anaissie, E., Stopeck, A., Morimoto, A., Tan, N., Lancet, J., Cooper, M., Hannah, A., Garcia-Manero, G., Faderl, S., Kantarjian, H., Cherrington, J., Albitar, M., & Giles, F. J. (2004). Phase II Study of SU5416, a Small Molecule Vascular Endothelial Growth Factor Tyrosine Kinase Receptor Inhibitor, in Patients with Refractory Multiple Myeloma. Clinical Cancer Research, 10(1 I), 88-95. https://doi.org/10.1158/1078-0432.CCR-0221-3