Phase i study of vandetanib with radiation therapy with or without cisplatin in locally advanced head and neck squamous cell carcinoma

Vasiliki A. Papadimitrakopoulou, Steven J. Frank, Ezra W. Cohen, Fred R. Hirsch, Jeffrey N. Myers, John V. Heymach, Heather Lin, Hai T. Tran, Changhu R. Chen, Antonio Jimeno, Lucien Nedzi, Joseph R. Vasselli, Elizabeth S. Lowe, David Raben

Research output: Contribution to journalArticle

8 Citations (Scopus)

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/m2 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.

Original languageEnglish (US)
Pages (from-to)439-447
Number of pages9
JournalHead and Neck
Volume38
Issue number3
DOIs
StatePublished - Mar 1 2016

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Cisplatin
Radiotherapy
Maximum Tolerated Dose
Stomatitis
Deglutition Disorders
N-(4-bromo-2-fluorophenyl)-6-methoxy-7-((1-methylpiperidin-4-yl)methoxy)quinazolin-4-amine
Carcinoma, squamous cell of head and neck
Epidermal Growth Factor Receptor
Therapeutics
Inflammation
Cell Line

Keywords

  • cisplatin
  • head and neck squamous cell cancer
  • radiation therapy
  • vandetanib

ASJC Scopus subject areas

  • Otorhinolaryngology

Cite this

Papadimitrakopoulou, V. A., Frank, S. J., Cohen, E. W., Hirsch, F. R., Myers, J. N., Heymach, J. V., ... Raben, D. (2016). Phase i study of vandetanib with radiation therapy with or without cisplatin in locally advanced head and neck squamous cell carcinoma. Head and Neck, 38(3), 439-447. https://doi.org/10.1002/hed.23922

Phase i study of vandetanib with radiation therapy with or without cisplatin in locally advanced head and neck squamous cell carcinoma. / Papadimitrakopoulou, Vasiliki A.; Frank, Steven J.; Cohen, Ezra W.; Hirsch, Fred R.; Myers, Jeffrey N.; Heymach, John V.; Lin, Heather; Tran, Hai T.; Chen, Changhu R.; Jimeno, Antonio; Nedzi, Lucien; Vasselli, Joseph R.; Lowe, Elizabeth S.; Raben, David.

In: Head and Neck, Vol. 38, No. 3, 01.03.2016, p. 439-447.

Research output: Contribution to journalArticle

Papadimitrakopoulou, VA, Frank, SJ, Cohen, EW, Hirsch, FR, Myers, JN, Heymach, JV, Lin, H, Tran, HT, Chen, CR, Jimeno, A, Nedzi, L, Vasselli, JR, Lowe, ES & Raben, D 2016, 'Phase i study of vandetanib with radiation therapy with or without cisplatin in locally advanced head and neck squamous cell carcinoma', Head and Neck, vol. 38, no. 3, pp. 439-447. https://doi.org/10.1002/hed.23922
Papadimitrakopoulou, Vasiliki A. ; Frank, Steven J. ; Cohen, Ezra W. ; Hirsch, Fred R. ; Myers, Jeffrey N. ; Heymach, John V. ; Lin, Heather ; Tran, Hai T. ; Chen, Changhu R. ; Jimeno, Antonio ; Nedzi, Lucien ; Vasselli, Joseph R. ; Lowe, Elizabeth S. ; Raben, David. / Phase i study of vandetanib with radiation therapy with or without cisplatin in locally advanced head and neck squamous cell carcinoma. In: Head and Neck. 2016 ; Vol. 38, No. 3. pp. 439-447.
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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/m2 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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AU - Cohen, Ezra W.

AU - Hirsch, Fred R.

AU - Myers, Jeffrey N.

AU - Heymach, John V.

AU - Lin, Heather

AU - Tran, Hai T.

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AU - Jimeno, Antonio

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AU - Lowe, Elizabeth S.

AU - Raben, David

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N2 - 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/m2 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.

AB - 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/m2 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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