A Phase II study of SU5416 in patients with advanced or recurrent head and neck cancers.

Abstract

BACKGROUND:

SU5416 (semaxanib) is a synthetic small molecule inhibitor of the tyrosine kinase domain of vascular endothelial growth factor receptor 2 (VEGFR2). This Phase II study was conducted to determine the safety and efficacy of SU5416 in patients with recurrent or metastatic head and neck cancers.

PATIENTS AND METHODS:

This was an open label, single arm, Phase 2 study for patients who had received no more than 2 cytotoxic regimens. Thirty-five patients received intravenous SU5416 (145 mg/m(2)) twice per week by intravenous catheter. Radiologic imaging for response assessment was planned at the conclusion of each 8 week cycle. Serum VEGF levels and power Doppler ultrasound tumor imaging were explored as potential surrogate markers for SU5416 activity.

RESULTS:

Thirty-two patients had received prior radiotherapy, including 18 patients who received prior concurrent chemoradiotherapy. Twelve patients had received prior chemotherapy in the recurrent disease setting. Thirty-one patients were evaluable for response. There was one partial response and one minor response. The median number of 8-week cycles received was 1 (range 1-4). Median overall survival was 6.25 months. The most common > or = grade 3 toxicity was headache (31%). There was one fatal carotid artery hemorrhage. Fatigue, nausea, and vomiting were common grade 1-2 adverse events. Power Doppler ultrasound demonstrated decreased tumor vascularity in 5 of 7 patients.

CONCLUSIONS:

Treatment with SU5416 in patients with head and neck cancers is feasible, but objective responses are rare. Studies evaluating more potent anti-angiogenic agents in this disease are of interest.

• Authors: Matthew G Fury, Andrew Zahalsky, Richard Wong, Ennapadam Venkatraman, Eric Lis, Lucy Hann, Timothy Aliff, William Gerald, Martin Fleisher, David G Pfister
• Journal: Investigational new drugs (Invest New Drugs) Vol. 25 Issue 2 Pg. 165-72 (Apr 2007) ISSN: 0167-6997 [Print] United States
• PMID: 16983506 (Publication Type: Clinical Trial, Phase II, Journal Article)

Chemical References

• Angiogenesis Inhibitors
• Indoles
• Pyrroles
• Vascular Endothelial Growth Factor A
• Semaxinib

Topics

• Adult
• Aged
• Aged, 80 and over
• Angiogenesis Inhibitors (adverse effects, therapeutic use)
• Blood Pressure (drug effects)
• Female
• Head and Neck Neoplasms (blood supply, diagnostic imaging, drug therapy)
• Heart Rate (drug effects)
• Humans
• Indoles (adverse effects, therapeutic use)
• Male
• Middle Aged
• Neoplasm Recurrence, Local
• Neoplasms, Squamous Cell (blood supply, diagnostic imaging, drug therapy)
• Pyrroles (adverse effects, therapeutic use)
• Regional Blood Flow (drug effects)
• Ultrasonography
• Vascular Endothelial Growth Factor A (blood)