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

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.

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.