Phase Ib Study of Chemoprevention with Green Tea Polyphenon E and Erlotinib in Patients with Advanced Premalignant Lesions (APL) of the Head and Neck

• Authors: Zhengjia Chen, Emory University; Steven Roser, Emory University; Dong Shin, Emory University; Yuan Liu, Emory University; Fadlo Khuri, Emory University; Mihir Patel, Emory University; Mark El-Deiry, Emory University; Jonathan Beitler, Emory University; Conor Steuer, Emory University; Adam Klein, Emory University; Taofeek Owonikoko, Emory University; Suresh Ramalingam, Emory University; Nabil Saba, Emory University; Qiuying Shi, Emory University; S Nannapaneni, Emory University
• Journal Title: CLINICAL CANCER RESEARCH
• Volume: Volume 26, Number 22
• Publisher: AMER ASSOC CANCER RESEARCH | 2020-11-15, Pages 5860-5868
• Type of Work: Article
• Publisher DOI: http://doi.org/10.1158/1078-0432.CCR-20-2276
• Keywords: Science & Technology; Life Sciences & Biomedicine; Oncology; SQUAMOUS-CELL CARCINOMA; GROWTH-FACTOR RECEPTOR; 2ND PRIMARY TUMORS; EGCG INHIBITS ACTIVATION; LOW-DOSE ISOTRETINOIN; TYROSINE KINASE; BREAST-CANCER; SIGNALING PATHWAYS; 13-CIS-RETINOIC ACID; PROSTATE-CANCER

Abstract

Purpose: On the basis of synergistic effects between green tea polyphenon E (PPE) and EGFR-tyrosine kinase inhibitor in preclinical studies, we conducted a phase Ib 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 (200 mg three times a day) and dose escalation of erlotinib (50, 75, 100 mg daily) for 6 months with tissue biopsy at baseline and 6 months. 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 and 17 oral cavity. Only skin rash was associated with dose-limiting toxicity and MTD. Recommended doses for phase II studies are PPE 600 mg daily plus erlotinib 100 mg daily for 6 months. Pathologic responses in 17 evaluable patients: pathologic complete response (47%) and pathologic partial response (18%). The 5-year CFS and OS were 66.3% and 93%, respectively. Among tested biomarkers, only phosphorylated ERK was correlated with response to treatment. Conclusions: 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.