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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

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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Journal Title:

CLINICAL CANCER RESEARCH

Volume:

Volume 26, Number 22

Publisher:

, Pages 5860-5868

Type of Work:

Article

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.
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