A Phase I Trial of Erlotinib and Concurrent Chemoradiotherapy (CCR) for Stage III and IV (M0) Squamous Cell Carcinoma of the Head and Neck
Mené sur 18 patients âgés de 42 à 66 ans et atteints d'un carcinome épidermoïde de la tête et du cou de stade III ou IV sans métastase, cet essai de phase I évalue la toxicité et la tolérabilité de l'erlotinib en combinaison avec une chimioradiothérapie concomittante
Background: Erlotinib, an orally active EGFR tyrosine kinase inhibitor, exhibits anti-tumor activity in head and neck cancer (HNSCC). This Phase I dose-escalation study evaluated the safety, tolerability, pharmacokinetics and pharmacodynamics of erlotinib in combination with chemoradiotherapy in locally advanced HNSCC. Methods:The principal objective was Maximally Tolerated Dose of the combination of erlotinib, low dose daily cisplatin and standard fractionation radiation therapy. Erlotinib was given daily as a 14 day run in and continued until RT was completed. 18F-FDG PET was performed at baseline and at day 14. Standard fractionation radiotherapy started on day 15 and was given concurrently with low dose daily cisplatin at 6 mg/m2 and erlotinib. Results:The MTD of erlotinib in combination with chemoradiotherapy was defined as 150 mg/day. Grade 3 or 4 toxicities attributed to erlotinib included lymphopenia, diarrhea, rash and pneumonitis. 18F-FDG PET demonstrated significant decrease in avidity on day 14 of the run-in for several patients. Conclusions: Erlotinib plus low dose daily cisplatin and radiotherapy is well tolerated. Evidence of biological effect was noted within 14 days of erlotinib alone.