Vasiliki A Papadimitrakopoulou1, Steven J Frank2, Ezra W Cohen3, Fred R Hirsch4, Jeffrey N Myers5, John V Heymach1, Heather Lin6, Hai T Tran1, Changhu R Chen7, Antonio Jimeno8, Lucien Nedzi9, Joseph R Vasselli10, Elizabeth S Lowe10, David Raben11. 1. Department of Thoracic Head and Neck Medical Oncology, MD Anderson Cancer Center, Houston, Texas. 2. Department of Radiation Oncology, MD Anderson Cancer Center, Houston, Texas. 3. Department of Medicine, University of Chicago, Chicago, Illinois. 4. University of Colorado Cancer Center, Aurora, Colorado. 5. Department of Head and Neck Surgery, University of Texas, MD Anderson Cancer Center, Houston, Texas. 6. Department of Biostatistics, MD Anderson Cancer Center, Houston, Texas. 7. Department of Radiation Oncology, University of Toledo, Toledo, Ohio. 8. Division of Medical Oncology, Department of Medicine, University of Colorado, Aurora, Colorado. 9. Department of Radiation Oncology, Southwestern Medical Center, Dallas, Texas. 10. AstraZeneca Pharmaceuticals, Wilmington, Delaware. 11. Department of Oncology, University of Colorado, Aurora, Colorado.
Abstract
BACKGROUND: Vandetanib, added to cisplatin and radiation therapy (RT) overcomes chemoradiation therapy (CRT) and epidermal growth factor receptor (EGFR) inhibitor resistance in head and neck squamous cell carcinoma (HNSCC) lines and models. METHODS: Patients with previously untreated HNSCC received vandetanib daily for 14 days (starting dose 100 mg) and then vandetanib + RT (2.2 Gy/day, 5 days/week) for 6 weeks (regimen 1) or vandetanib + RT (2 Gy/day, 5 days/week) + cisplatin (30 mg/m(2) weekly) for 7 weeks (regimen 2). The primary objective was the maximum tolerated dose (MTD) of vandetanib with RT +/- cisplatin. RESULTS: Of 33 treated patients, 30 completed therapy (regimen 1, n = 12; regimen 2, n = 18). MTD in regimen 2 was 100 mg (3 dose limiting toxicities [DLTs] at 200 mg), whereas regimen 1 was stopped because of poor recruitment (1 DLT at 200 mg). Most common grade ≥3 adverse events (AEs) were dysphagia (30%), stomatitis (33%), and mucosal inflammation (27%). Five patients discontinued vandetanib because of AEs. CONCLUSION: Vandetanib with CRT was feasible.
BACKGROUND: Vandetanib, added to cisplatin and radiation therapy (RT) overcomes chemoradiation therapy (CRT) and epidermal growth factor receptor (EGFR) inhibitor resistance in head and neck squamous cell carcinoma (HNSCC) lines and models. METHODS: Patients with previously untreated HNSCC received vandetanib daily for 14 days (starting dose 100 mg) and then vandetanib + RT (2.2 Gy/day, 5 days/week) for 6 weeks (regimen 1) or vandetanib + RT (2 Gy/day, 5 days/week) + cisplatin (30 mg/m(2) weekly) for 7 weeks (regimen 2). The primary objective was the maximum tolerated dose (MTD) of vandetanib with RT +/- cisplatin. RESULTS: Of 33 treated patients, 30 completed therapy (regimen 1, n = 12; regimen 2, n = 18). MTD in regimen 2 was 100 mg (3 dose limiting toxicities [DLTs] at 200 mg), whereas regimen 1 was stopped because of poor recruitment (1 DLT at 200 mg). Most common grade ≥3 adverse events (AEs) were dysphagia (30%), stomatitis (33%), and mucosal inflammation (27%). Five patients discontinued vandetanib because of AEs. CONCLUSION: Vandetanib with CRT was feasible.
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