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

Carter Van Waes, Clint T. Allen, Deborah Citrin, David Gius, A. Dimetrios Colevas, Nancy A. Harold, Susan Rudy, Liesl Nottingham, Christine Muir, Zhong Chen, Anurag K. Singh, Janet Dancey, John C. Morris

Research output: Contribution to journalArticlepeer-review

28 Scopus citations


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/m2 intravenously weekly × 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.

Original languageEnglish (US)
Pages (from-to)447-454
Number of pages8
JournalInternational Journal of Radiation Oncology Biology Physics
Issue number2
StatePublished - Jun 1 2010
Externally publishedYes


  • Epidermal growth factor receptor
  • Gefitinib
  • Head and neck cancer
  • Paclitaxel
  • Radiation

ASJC Scopus subject areas

  • Radiation
  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research


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