一线化疗后吉非替尼维持治疗晚期非小细胞肺癌的临床观察

Clinical observation of maintenance therapy with gefitinib after the first-line chemotherapy for patients with advanced non-small-cell lung cancer

目的评价晚期非小细胞肺癌（NSCLC）一线化疗获得部分缓解（PR）或稳定（sD）后予以吉非替尼单药维持治疗的临床疗效。方法应用前瞻性随机对照临床研究方法，将71例经标准的两药含铂方案一线化疗获得PR或sD的患者按随机数字表法分为两组，治疗组患者（36例）服用吉非替尼250mg，1次／d；对照组（35例）服用安慰剂，1次／d。两组患者均服用至疾病进展。结果治疗组总有效率（RR）为36．1％（13／36），其中1例（2．8％）完全缓解（CR），对照组RR为14．3％（5／35），两组差异有统计学意义（x^2=4．633，P=0．036）。治疗组疾病控制率（CR＋PR＋SD，DCR）为83．3％（30／36），对照组为42．9％（15／35），两组差异有统计学意义（X^2=14．782，P〈0．001）。治疗组无进展生存期（PFS）较安慰剂组显著延长（分别为13周和11周）（X^2=10．401，P=0．001）。治疗组中位生存期（0s）为13．2个月，对照组为10．4个月，两组差异有统计学意义（X^2=7．696，P=0．006）。治疗组女性患者中位Os（18．5个月）显著长于男性（11．2个月）（x^2=22．864，P=0．011）；不吸烟者中位OS（15-3个月）亦长于吸烟者（10．3个月）（x^2=0．389，P=0．007）；腺癌及肺泡细胞癌患者中位0S（16．0个月）亦显著长于鳞状细胞癌患者（10．2个月）（X^2=4．638，P=0．001）。治疗组不良反应以皮疹、腹泻、皮肤干燥瘙痒及乏力为主，多为I、Ⅱ度。结论晚期NSCLC一线化疗后吉非替尼维持治疗可以提高疗效、延长患者生存期，不良反应轻，可以耐受。

Objective To evaluate RR, DCR, PFS, OS and toxicities in a population affected by NSCLC using gefitinib as maintenance therapy after the first line chemotherapy. Methods From January, 2006 to January, 2008, seventy-one patients were enrolled with stable disease or partial response after first- line chemotherapy. They were divided into the observing group and the control group. Gefitinib was administered at the dose of 250 mg in observing group; placebo was also administered everyday in control group. Results Of 71 assessable patients ,overall response rate was 36.1% （13/36） in observing group and 14.3 % （5/35） in control group respectively （X ^2 = 4.633, P = 0.036）, and one patient （2.8 %） was observed complete response （CR） in observing group. The disease control rate was 83.3 % （30/36） in observing group and 42.9 % （15/35） in control group, respectively, （X^2 = 14.782, P 〈 0.OO1）. The median PFS （progression free survival time） was 13 weeks in observing group and 11 weeks in control group respectively （X 2 =10.401, P =0.001）. The median overall survival time （OS） was 13.2 months in observing group and 10.4 months in control group respectively （X^2 = 7.696, P = 0.006）. The median OS was 18.5 months in women and 11,2 months in men（x^2 =22.864, P =0.011） . The median OS was 15.3 months in non-smokers and 10.3 months in smokers （X^2 =10.389, P =0.007）. The median OS was 16.0 months in adenoearcinoma and alveolar cell carcinoma patients and 10.2 months in squamous cell carcinoma patients （X ^2 = 4.638, P = 0.001）. The most common toxicity was rash ,diarrhea,fatigue and dry skin itching, and most of them were I or 2 grade. Conclusion Maintenance therapy with gefitinib after first-line chemotherapy may improve overall survival time and progression free survival time in patients with NSCLC, and it is effective and safe.