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Updated: Aug 22, 2026
A Mouse Model of Incompletely Resected Soft Tissue Sarcoma for Testing (Neo)adjuvant Therapies
Published on: July 28, 2020
Phase II study of the antiangiogenic agent SU5416 in patients with advanced soft tissue sarcomas
John V Heymach1, Jayesh Desai, Judith Manola
1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Purpose:
SU5416 (semaxanib) is a small molecule inhibitor of the vascular endothelial growth factor (VEGF) receptor-2 and KIT receptor tyrosine kinases. This Phase II study was conducted to investigate the safety and efficacy of SU5416 for patients with soft tissue sarcomas.
Experimental Design:
Thirteen patients with locally advanced or metastatic soft tissue sarcomas were treated with SU5416 via intravenous infusion at a dose of 145 mg/m(2) twice weekly. In selected cases tumor biopsies were taken before and after 2 months of treatment.
Results:
The median progression-free survival was 1.8 months. Median overall survival was 22.8 months. No objective tumor responses were observed. There was evidence of shorter survival among patients with high baseline urine VEGF levels (P = 0.04). No grade 4 toxicities were observed. The most common grade 3 toxicities were headache and thrombosis. Other less serious toxicities included fatigue, nausea, and abdominal pain. The median systolic blood pressure increased from 118 mmHg at baseline to 133 after 1 month of treatment (P = 0.01). Post-treatment tumor biopsies showed no significant decreases in VEGF receptor phosphorylation compared with baseline in 3 evaluable patients. One patient with gastrointestinal stromal tumor who had rapid progression during SU5416 treatment was subsequently treated with another KIT inhibitor, imatinib mesylate, and had a partial response lasting >36 months.
Conclusions:
SU5416 was relatively well tolerated but did not demonstrate significant antitumor activity against advanced soft tissue sarcoma. Correlative studies suggest that VEGF receptor or KIT inhibition was incomplete in at least some cases, providing a possible explanation for the observed lack of activity.
Insights
SU5416 (semaxanib) showed limited efficacy in treating advanced soft tissue sarcomas, with no objective tumor responses observed. While generally well-tolerated, further research is needed to understand its therapeutic potential in sarcoma treatment.
Area of Science:
- Oncology
- Pharmacology
Background:
- Soft tissue sarcomas are a group of rare cancers.
- Vascular Endothelial Growth Factor (VEGF) receptor-2 and KIT receptor tyrosine kinases are implicated in sarcoma development.
Purpose of the Study:
- To evaluate the safety and efficacy of SU5416 (semaxanib) in patients with advanced soft tissue sarcomas.
- To investigate SU5416 as a targeted therapy for soft tissue sarcomas.
Main Methods:
- A Phase II study involving thirteen patients with locally advanced or metastatic soft tissue sarcomas.
- Treatment with SU5416 at 145 mg/m(2) intravenously twice weekly.
- Tumor biopsies were collected pre- and post-treatment for correlative analysis.
Main Results:
- Median progression-free survival was 1.8 months; median overall survival was 22.8 months.
- No objective tumor responses were observed; grade 3 toxicities included headache and thrombosis.
- VEGF receptor phosphorylation showed no significant decrease post-treatment in evaluable patients.
Conclusions:
- SU5416 was not significantly effective against advanced soft tissue sarcoma.
- Incomplete VEGF receptor or KIT inhibition may explain the lack of antitumor activity.
- SU5416 was relatively well-tolerated in this patient population.
