A Phase II study of SU5416 in patients with advanced or recurrent head and neck cancers Journal Article
| Authors: | Fury, M. G.; Zahalsky, A.; Wong, R.; Venkatraman, E.; Lis, E.; Hann, L.; Aliff, T.; Gerald, W.; Fleisher, M.; Pfister, D. G. |
| Article Title: | 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/m2) 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 ≥ 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. © 2006 Springer Science+Business Media, LLC. |
| Keywords: | vasculotropin; adult; cancer survival; clinical article; controlled study; aged; aged, 80 and over; middle aged; vascular endothelial growth factor a; clinical trial; fatigue; advanced cancer; diarrhea; drug dose reduction; drug efficacy; drug safety; hypertension; side effect; cancer radiotherapy; recurrent cancer; protein blood level; controlled clinical trial; infection; multiple cycle treatment; pain; phase 2 clinical trial; neoplasm recurrence, local; bleeding; nausea; dehydration; myalgia; dexamethasone; cancer pain; deep vein thrombosis; alanine aminotransferase blood level; dyspnea; hyperglycemia; pneumonia; chemotherapy induced emesis; drug induced headache; hyperkalemia; hyponatremia; prothrombin time; head and neck cancer; head and neck neoplasms; thrombosis; semaxanib; warfarin; diastolic blood pressure; systolic blood pressure; blood pressure; indoles; pyrroles; nasopharynx tumor; angiogenesis inhibitors; phase ii; small cell carcinoma; diphenhydramine; regional blood flow; paranasal sinus tumor; neoplasms, squamous cell; heart rate; larynx tumor; hypopharynx tumor; oropharynx tumor; mouth tumor; doppler flowmetry; famotidine; head and neck squamous cell cancer; su5416; vegfr2; pulse pressure |
| Journal Title: | Investigational New Drugs |
| Volume: | 25 |
| Issue: | 2 |
| ISSN: | 0167-6997 |
| Publisher: | Springer |
| Date Published: | 2007-04-01 |
| Start Page: | 165 |
| End Page: | 172 |
| Language: | English |
| DOI: | 10.1007/s10637-006-9011-x |
| PUBMED: | 16983506 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 35" - "Export Date: 17 November 2011" - "CODEN: INNDD" - "Source: Scopus" |
