Phase Ib study of chemoprevention with green tea polyphenon e and erlotinib in patients with advanced premalignant lesions (apl) of the head and neck
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American Association for Cancer Research Inc.
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. © 2020 American Association for Cancer Research.
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Adult, Aged, Antineoplastic combined chemotherapy protocols, Catechin, Erlotinib hydrochloride, Female, Head and neck neoplasms, Humans, Kaplan-meier estimate, Male, Maximum tolerated dose, Middle aged, Precancerous conditions, Progression-free survival, Protein kinase inhibitors, Tea, Alanine aminotransferase, Aspartate aminotransferase, Erlotinib, Mitogen activated protein kinase, Polyphenon e, Antineoplastic agent, Protein kinase inhibitor, Anemia, Anxiety, Article, Cancer free survival, Carcinoma in situ, Chemoprophylaxis, Clinical article, Diarrhea, Disease marker, Disease severity, Dose response, Drug dose escalation, Drug eruption, Drug safety, Dry skin, Dysplasia, Enzyme phosphorylation, Epistaxis, Fatigue, Hair disease, Head and neck disease, Histopathology, Human, Human tissue, Hyperglycemia, Hypertension, Hypokalemia, Indigestion, Laryngeal biopsy, Larynx disorder, Leukoplakia, Mouth carcinoma, Mouth disease, Nausea, Oral biopsy, Overall survival, Pain, Phase 1 clinical trial, Phase 2 clinical trial (topic), Precancer, Pruritus, Recommended drug dose, Side effect, Sleep disorder, Survival rate, Survival time, Thrombocytopenia, Tongue disease, Treatment duration, Treatment response, Chemistry, Clinical trial, Genetics, Head and neck tumor, Kaplan meier method, Pathology