BACKGROUND: Gefitinib has activity in patients with advanced squamous cell carcinoma of the head and neck (SCCHN) and skin toxicity has been postulated to be a predictor of response and improved outcome. METHODS: This open-label, multi-institution, phase II study evaluated the activity of gefitinib at individually escalated doses up to 750 mg to achieve the skin toxicity grade ≥2. RESULTS: Forty four patients were enrolled. Only twenty-three (52%) experienced skin rash grade ≥2. Of 44 patients, partial responses were noted in 3 (7%), stable disease in 8 (18%) and progressive disease in 33 patients. Median progression-free survival was 1.9 months (95% CI 1.6-2.2) and median overall survival was 5.1 months (95% CI 2.4-7.8). Grade of skin rash was not associated with response rate (p=0.169) nor tumor control rate (p=0.284); however, higher gefitinib trough levels were associated with disease control. Of the 11 tissue samples analyzed for EGFR gene copy by FISH, 7 were EGFR FISH positive, but this was not associated with improved tumor control or survival. CONCLUSIONS: Gefitinib has clinical activity as monotherapy in SCCHN. Dose escalation of gefitinib is feasible and may increase skin toxicity, but our data do not support increased activity.
BACKGROUND:Gefitinib has activity in patients with advanced squamous cell carcinoma of the head and neck (SCCHN) and skin toxicity has been postulated to be a predictor of response and improved outcome. METHODS: This open-label, multi-institution, phase II study evaluated the activity of gefitinib at individually escalated doses up to 750 mg to achieve the skin toxicity grade ≥2. RESULTS: Forty four patients were enrolled. Only twenty-three (52%) experienced skin rash grade ≥2. Of 44 patients, partial responses were noted in 3 (7%), stable disease in 8 (18%) and progressive disease in 33 patients. Median progression-free survival was 1.9 months (95% CI 1.6-2.2) and median overall survival was 5.1 months (95% CI 2.4-7.8). Grade of skin rash was not associated with response rate (p=0.169) nor tumor control rate (p=0.284); however, higher gefitinib trough levels were associated with disease control. Of the 11 tissue samples analyzed for EGFR gene copy by FISH, 7 were EGFR FISH positive, but this was not associated with improved tumor control or survival. CONCLUSIONS:Gefitinib has clinical activity as monotherapy in SCCHN. Dose escalation of gefitinib is feasible and may increase skin toxicity, but our data do not support increased activity.
Authors: Stefanie L Groenland; Ron H J Mathijssen; Jos H Beijnen; Alwin D R Huitema; Neeltje Steeghs Journal: Eur J Clin Pharmacol Date: 2019-06-07 Impact factor: 2.953
Authors: Huixin Yu; Neeltje Steeghs; Cynthia M Nijenhuis; Jan H M Schellens; Jos H Beijnen; Alwin D R Huitema Journal: Clin Pharmacokinet Date: 2014-04 Impact factor: 6.447
Authors: Julie E Bauman; Umamaheswar Duvvuri; William E Gooding; Tanya J Rath; Neil D Gross; John Song; Antonio Jimeno; Wendell G Yarbrough; Faye M Johnson; Lin Wang; Simion Chiosea; Malabika Sen; Jason Kass; Jonas T Johnson; Robert L Ferris; Seungwon Kim; Fred R Hirsch; Kimberly Ellison; John T Flaherty; Gordon B Mills; Jennifer R Grandis Journal: JCI Insight Date: 2017-03-23
Authors: Neil D Gross; Julie E Bauman; William E Gooding; William Denq; Sufi M Thomas; Lin Wang; Simion Chiosea; Brian L Hood; Melanie S Flint; Mai Sun; Thomas P Conrads; Robert L Ferris; Jonas T Johnson; Seungwon Kim; Athanassios Argiris; Lori Wirth; Marina N Nikiforova; Jill M Siegfried; Jennifer R Grandis Journal: Clin Cancer Res Date: 2014-04-11 Impact factor: 12.531