Molecular and Clinical Responses in a Pilot Study of Gefitinib With Paclitaxel and Radiation in Locally Advanced Head-and-Neck Cancer

Journal Article · Tue Jun 01 00:00:00 EDT 2010 · International Journal of Radiation Oncology, Biology and Physics

DOI:https://doi.org/10.1016/j.ijrobp.2009.05.037· OSTI ID:21372292

Van Waes, Carter ^[1]; Allen, Clint T ^[1]; Citrin, Deborah; Gius, David ^[2]; Colevas, A Dimetrios ^[3]; Harold, Nancy A ^[4]; Rudy, Susan; Nottingham, Liesl ^[1]; Muir, Christine ^[4]; Chen, Zhong ^[1]; Singh, Anurag K ^[2]; Dancey, Janet ^[3]

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1. Head and Neck Surgery Branch, National Institute of Deafness and Communication Disorders, National Institutes of Health, Bethesda, MD (United States)
2. Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD (United States)
3. Investigational Drug Branch, Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, MD (United States)
4. Metabolism Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD (United States)

Purpose: Epidermal growth factor receptor (EGFR) overexpression in head-and-neck squamous cell carcinoma (HNSCC) stimulates tumor cell proliferation, inhibits apoptosis, and increases chemotherapy and radiation resistance. We examined the toxicity, safety and the effects on EGFR signaling in tumor biopsy samples from patients with locally advanced HNSCC treated with the EGFR signaling inhibitor gefitinib (GEF) combined with weekly intravenous paclitaxel (PAC) and radiation therapy (RT). Methods and Materials: This was a pilot Phase I dose-escalation study. Eligibility included Stage III to IVB HNSCC, age >=18 years, no prior RT or chemotherapy, adequate organ function, and informed consent. Endpoints included determination of maximum tolerated dose (MTD) and analysis of treatment effect on EGFR signaling, tumor cell proliferation, and apoptosis in biopsy samples. Results: Ten patients were treated. The MTD of this combination was GEF 250 mg/d with PAC 36 mg/m{sup 2} intravenously weekly x 6 with concurrent RT. Grade 3/4 toxicities included prolonged (>8 weeks) stomatitis (7 patients), infection (2 patients), and interstitial pneumonitis (1 patient). There were five complete responses (CR) and two partial responses (PR). Of 7 patients undergoing serial biopsies, only 1 patient demonstrated a reduction in phosphorylated EGFR, decreased downstream signaling, and reduced cellular proliferation after initiating GEF. Conclusions: Inhibition of EGFR by GEF was observed in only one of seven tumors studied. The addition of GEF to PAC and RT did not appear to improve the response of locally advanced HNSCC compared with our prior experience with PAC and RT alone. This treatment appeared to delay recovery from stomatitis.

• OSTI ID: 21372292
• Journal Information: International Journal of Radiation Oncology, Biology and Physics, Vol. 77, Issue 2; Other Information: DOI: 10.1016/j.ijrobp.2009.05.037; PII: S0360-3016(09)00819-0; Copyright (c) 2010 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; ISSN 0360-3016
• Country of Publication: United States
• Language: English

Related Subjects

62 RADIOLOGY AND NUCLEAR MEDICINE
APOPTOSIS
CARCINOMAS
CELL PROLIFERATION
CHEMOTHERAPY
EPIDERMIS
GROWTH FACTORS
HEAD
NECK
RADIOTHERAPY
RECEPTORS
TOXICITY
TUMOR CELLS
ANIMAL CELLS
ANIMAL TISSUES
BODY
DISEASES
EPITHELIUM
MEDICINE
MEMBRANE PROTEINS
MITOGENS
NEOPLASMS
NUCLEAR MEDICINE
ORGANIC COMPOUNDS
ORGANS
PROTEINS
RADIOLOGY
SKIN
THERAPY