Phase 1B Study of Chemoprevention with Green Tea Polyphenon E and Erlotinib in Patients with Advanced Premalignant Lesions (APL) of the Head and Neck
Mené sur 21 patients présentant des lésions précancéreuses de stade avancé de la cavité buccale ou du larynx, cet essai de phase 1b évalue la toxicité d'un traitement chimiopréventif combinant un extrait de thé vert (polyphénon E) et l'erlotinib pendant 6 mois
Purpose: Based on synergistic effects between green tea polyphenon E (PPE) and epidermal growth factor receptor-tyrosine kinase inhibitor in preclinical studies, we conducted a phase 1b study of the PPE and erlotinib combination in patients with advanced premalignant lesions (APL) of the oral cavity and larynx. Patients and Methods: Patients were treated with a fixed dose of PPE (200mg 3x day) and dose escalation of erlotinib (50, 75, 100 mg daily) for 6-months (6-M) with tissue biopsy at baseline and 6-M. Primary endpoints were safety and toxicity, secondary endpoints were evaluation of pathologic response, cancer free survival (CFS), overall survival (OS) and biomarker modulation. Results: Among 21 enrolled patients, 19 began treatment and 17 completed 6 months of treatment with PPE and erlotinib. Main characteristics of treated patients: 15 severe dysplasia or carcinoma in situ; 17 oral cavity. Only skin rash was associated with DLT and MTD. Recommended doses for phase 2 studies are PPE 600mg daily plus erlotinib 100mg daily for 6-M. Pathologic responses in 17 evaluable patients: pCR (47%) and pPR (18%). The 5-year CFS and OS were 66.3% and 93%, respectively. Among tested biomarkers, only pERK was correlated with response to treatment. Conclusion: Treatment with PPE and erlotinib combination was well tolerated in patients with APLs of the head and neck, and showed a high rate of pathologic response with excellent CFS. This combination deserves further investigation for the chemoprevention and/or prevention of second primary tumors in early stage head and neck cancer.