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

Autor: Carter Van Waes, Liesl Nottingham, Anurag K. Singh, David Gius, A. Dimetrios Colevas, Janet Dancey, John C. Morris, Deborah Citrin, Christine Muir, Zhong Chen, Nancy Harold, Clint T. Allen, Susan F. Rudy
Rok vydání: 2010
Předmět:
Male
Oncology
Cancer Research
Pathology
medicine.medical_treatment
Apoptosis
Pilot Projects
chemistry.chemical_compound
Antineoplastic Combined Chemotherapy Protocols
Medicine
Epidermal growth factor receptor
Aged
80 and over
Radiation
medicine.diagnostic_test
biology
Remission Induction
Gefitinib
Radiotherapy Dosage
Middle Aged
Combined Modality Therapy
Neoplasm Proteins
ErbB Receptors
Paclitaxel
Head and Neck Neoplasms
Carcinoma
Squamous Cell
Female
medicine.drug
Adult
medicine.medical_specialty
Maximum Tolerated Dose
Infections
Drug Administration Schedule
Article
Internal medicine
Biopsy
Carcinoma
Humans
Radiology
Nuclear Medicine and imaging
Aged
Cell Proliferation
Stomatitis
Chemotherapy
business.industry
Head and neck cancer
medicine.disease
Radiation therapy
chemistry
Drug Resistance
Neoplasm
Quinazolines
biology.protein
Lung Diseases
Interstitial
business
Zdroj: International Journal of Radiation Oncology*Biology*Physics. 77:447-454
ISSN: 0360-3016
DOI: 10.1016/j.ijrobp.2009.05.037
Popis: 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 2 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.
Databáze: OpenAIRE
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