MOLECULAR AND CLINICAL RESPONSES IN A PILOT STUDY OF GEFITINIB WITH PACLITAXEL AND RADIATION IN LOCALLY ADVANCED HEAD-AND-NECK CANCER

被引：29

作者：

Van Waes, Carter ^{[1
,2
]}

Allen, Clint T. ^{[1
]}

Citrin, Deborah ^{[2
]}

Gius, David ^{[2
]}

Colevas, A. Dimetrios ^{[3
]}

Harold, Nancy A. ^{[4
]}

Rudy, Susan ^{[1
]}

Nottingham, Liesl ^{[1
]}

Muir, Christine ^{[4
]}

Chen, Zhong ^{[1
]}

Singh, Anurag K. ^{[2
]}

Dancey, Janet ^{[3
]}

Morris, John C. ^{[4
]}

机构：

[1] NIDCD, Head & Neck Surg Branch, NIH, Bethesda, MD USA

[2] NCI, Radiat Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA

[3] NCI, Invest Drug Branch, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA

[4] NCI, Metab Branch, Ctr Canc Res, Bethesda, MD 20892 USA

来源：

INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS | 2010年 / 77卷 / 02期

关键词：

Epidermal growth factor receptor; Head and neck cancer; Gefitinib; Paclitaxel; Radiation; GROWTH-FACTOR-RECEPTOR; SQUAMOUS-CELL CARCINOMA; NF-KAPPA-B; ZD1839; IRESSA; CYTOTOXIC AGENTS; TYROSINE KINASE; SIGNAL PATHWAYS; LUNG-CANCER; IN-VIVO; EXPRESSION;

D O I：

10.1016/j.ijrobp.2009.05.037

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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 EGER 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 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 ECM, decreased downstream signaling, and reduced cellular proliferation after initiating GEE. Conclusions: Inhibition of EGFR by GEE was observed in only one of seven tumors studied. The addition of GEE 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. (C) 2010 Elsevier Inc.

引用

页码：447 / 454

页数：8