Epidermal Growth Factor Receptor Inhibitor Gefitinib Added to Chemoradiotherapy in Locally Advanced Head and Neck Cancer
Epidermal Growth Factor Receptor Inhibitor Gefitinib Added to Chemoradiotherapy in Locally Advanced Head and Neck Cancer
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DOI：
10.1200/jco.2009.27.0397
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发表时间：
2010-07-10
影响因子：
45.3
通讯作者：
Vokes, Everett E.
中科院分区：
文献类型：
--
作者：
Cohen, Ezra E. W.;Haraf, Daniel J.;Vokes, Everett E.
目的评价表皮生长因子受体（EGFR）抑制剂吉非替尼加用及维持治疗后的疗效和毒性，患者和方法III期至IV期LA-HNC患者接受两个周期的卡铂/紫杉醇诱导化疗（IC），随后进行分裂-化疗（IC-DC）。疗程CCRT：氟尿嘧啶、羟基脲、每日两次放疗（FHX）和吉非替尼（每日250 mg），随后继续吉非替尼治疗，共2年。主要终点为CCRT后的完全缓解（CR）率。EGFR基因拷贝数进行了评估，通过荧光原位hybridization.Results 69例（66与IV期疾病，37口咽原发性肿瘤，和67与性能状态0至1）入组，中位年龄为55岁。IC和CCRT期间主要的3级或4级毒性分别为中性粒细胞减少症（n = 20）和现场粘膜炎（n = 59）和皮炎（n = 23）。CCRT后CR率为90%。中位随访3.5年后，4年总体、无进展和疾病特异性生存率分别为74%、72%和89%。迄今为止，一名患者在呼吸消化道发生了第二个原发性肿瘤。在31例有可用组织的患者中，EGFR基因拷贝数高与总生存率差相关（P = 0.02）。结论吉非替尼可与FHX联合使用，并作为至少2年的维持治疗，显示CR率和生存率与既往经验相比是有利的。高EGFR基因拷贝数可能与接受该方案治疗的LA-HNC患者的不良结局相关。
Purpose Assess efficacy and toxicity of gefitinib, an epidermal growth factor receptor (EGFR) inhibitor, added to, and in maintenance after, concurrent chemoradiotherapy (CCRT) in locally advanced head and neck cancer (LA-HNC) and correlate outcomes with EGFR gene copy number alterations.Patients and Methods Patients with stage III to IV LA-HNC received two cycles of carboplatin/paclitaxel induction chemotherapy (IC) followed by split-course CCRT with fluorouracil, hydroxyurea, twice daily radiotherapy (FHX), and gefitinib (250 mg daily) followed by continued gefitinib for 2 years total. The primary end point was complete response (CR) rate after CCRT. EGFR gene copy number was assessed by fluorescent in situ hybridization.Results Sixty-nine patients (66 with stage IV disease, 37 with oropharynx primary tumors, and 67 with performance status 0 to 1) were enrolled with a median age of 55 years. Predominant grade 3 or 4 toxicities during IC and CCRT were neutropenia (n = 20) and in-field mucositis (n = 59) and dermatitis (n = 23), respectively. CR rate after CCRT was 90%. After median follow-up of 3.5 years, 4-year overall, progression-free, and disease-specific survival rates were 74%, 72%, and 89%, respectively. To date, one patient has developed a second primary tumor in the aerodigestive tract. In 31 patients with available tissue, high EGFR gene copy number was associated with worse overall survival (P = .02).Conclusion Gefitinib can be administered with FHX and as maintenance therapy for at least 2 years, demonstrating CR and survival rates that compare favorably with prior experience. High EGFR gene copy number may be associated with poor outcome in patients with LA-HNC treated with this regimen.