A phase i dose escalation and pharmacodynamic study of SU5416 (Semaxanib) combined with weekly cisplatin and irinotecan in patients with advanced solid tumors

Ludmila K. Martin, Tanios Bekaii-Saab, Derek Serna, Paul Monk, Steven K. Clinton, Michael R. Grever, Eric H. Kraut

3 Scopus citations


Background: This phase I study evaluated the safety of SU5416, a potent and selective inhibitor of the vascular endothelial growth factor (VEGF) receptor tyrosine kinase Flk-1, in combination with weekly cisplatin and irinotecan in patients with advanced solid tumors. Methods: The patients received cisplatin 30 mg/m2 and irinotecan 50 mg/m2 weekly from week 1 to week 4, with SU5416 at either 65 mg/m2 (dose level (DL)1) or 85 mg/m 2 (DL2) twice weekly for 6 weeks (1 cycle). Serial 18fluorodeoxyglucose-positron emission tomography ( 18FDG-PET) and 15O-H2O-PET scans were obtained. Results: 13 patients were treated (7 on DL1, 6 on DL2); 7 patients completed at least 1 cycle of treatment. 3 patients experienced dose-limiting toxicity (DLT) at DL2 (grade 3 neutropenia and grade 3 thrombocytopenia causing treatment delay, grade 3 nausea/vomiting). No objective responses were observed at DL1, which was determined to be the maximum tolerated dose (MTD). 1 partial response (PR) was observed at DL2. 18FDG-PET responses were documented but did not predict response according to the Response Evaluation Criteria in Solid Tumors (RECIST). Conclusions: SU5416 at 65 mg/m2 twice weekly combined with cisplatin and irinotecan weekly for 4 of 6 weeks is well tolerated but without evidence of clinical activity. 18FDG-PET may be a useful pharmacodynamic marker of SU5416 bioactivity but requires additional development.

Original languageEnglish (US)
Pages (from-to)657-660
Number of pages4
JournalOnkologie(Czech Republic)
Issue number11
StatePublished - Nov 1 2013
Externally publishedYes



  • Angiogenesis
  • Solid tumors
  • SU5416
  • VEGF

ASJC Scopus subject areas

  • Oncology
  • Cancer Research
  • Hematology

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