A Phase I Dose Escalation and Pharmacodynamic Study of SU5416 (Semaxanib) Combined with Weekly Cisplatin and Irinotecan in Patients with Advanced Solid Tumors

作者：Martin Ludmila K; Bekaii Saab Tanios^*; Serna Derek; Monk Paul; Clinton Steven K; Greyer Michael R; Kraut Eric H

来源：Onkologie, 2013, 36(11): 657-660.

DOI：10.1159/000355665

• SU5416
• Angiogenesis
• VEGF
• FDG-PET
• Solid tumors

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/m(2) and irinotecan 50 mg/m(2) weekly from week 1 to week 4, with SU5416 at either 65 mg/m(2) (dose level (DL)1) or 85 mg/m(2) (DL2) twice weekly for 6 weeks (1 cycle). Serial (18)fluorodeoxy-glucose-positron emission tomography ((18)FDG-PET) and O-15-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. (18)FDG-PET responses were documented but did not predict response according to the Response Evaluation Criteria in Solid Tumors (RECIST). Conclusions: SU5416 at 65 mg/m(2) twice weekly combined with cisplatin and irinotecan weekly for 4 of 6 weeks is well tolerated but without evidence of clinical activity. (18)FDG-PET may be a useful pharmacodynamic marker of SU5416 bioactivity but requires additional development.

• 出版日期2013-11