Zhao Hong-Yun, Chen Gong-Yan, Huang Yan, Li Xiao-Li, Feng Ji-Feng, Shi Mei-Qi, Cheng Ying, Ma Li-Xia, Zhang Yi-Ping, Gu Cui-Ping, Song Xiang-Qun, Zhou Da, Zhang Li
From the Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, China (H-YZ, YH, LZ); Department of Internal Medicine, Cancer Hospital of Ha'erbin Medical University, Haerbin, Heilongjiang, China (G-YC, X-LL); Department of Oncology, Jiangsu Cancer Hospital, Nanjing, Jiangsu, China (J-FF, M-QS); Department of Oncology, Jilin Cancer Hospital, Changchun, Jilin, China (YC, L-XM); Chemotherapy Center, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, China (Y-PZ, C-PG); and Department Chemotherapy, Cancer Hospital of Guangxi Medical University, Nanning, Guangxi, China (X-QS, DZ).
Medicine (Baltimore). 2015 Jan;94(2):e249. doi: 10.1097/MD.0000000000000249.
Preclinical studies have shown synergism between epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors and antifolates in solid tumors. This study is to investigate the efficacy and tolerability of erlotinib plus capecitabine as first-line treatment in older Chinese patients (≥ 65 years) with lung adenocarcinoma. This is an open-label, single arm, multicenter phase II clinical trial. Sixty- two patients with previously untreated stage IIIB/IV adenocarcinoma and age 65 years or above were enrolled at four tertiary teaching hospitals and 2 provincial hospitals in China; 58 patients fulfilled the study requirements. Erlotinib (150 mg/day) and capecitabine (1000 mg/m2 twice daily on days 1-14) were administered during every 21-day cycle. The primary endpoint was the non-progression rate at 12 weeks. EGFR and K-ras mutation rates were determined using PCR. Tumor expression of different biomarkers was assessed using immunohistochemistry. In a cohort of 58 patients, 34 patients had no disease progression at 12 weeks following treatment. The objective response rate was 29.3%, and the disease control rate was 75.9%. The objective response rate was significantly higher in patients with EGFR mutations than in those with wild-type EGFR. Patients with thymidine phosphorylase-negative tumors had significantly longer overall survival after one year than patients with thymidine phosphorylase-positive tumors. Forty-four patients had at least one primary adverse events (AEs), including skin rash (n = 30), grade 3 AEs (n = 17), and grade 4 AEs (n = 7). This is the first phase II clinical trial to assess erlotinib plus capecitabine combination therapy as first-line treatment in older patients with lung adenocarcinoma. Erlotinib/capecitabine chemotherapy was significantly better in patients with EGFR mutations and in those with thymidine phosphorylase-negative tumors. The use of fluorouracil derivatives for the treatment of lung adenocarcinoma warrants further study.
临床前研究表明，表皮生长因子受体（EGFR）酪氨酸激酶抑制剂与抗叶酸药物在实体瘤治疗中具有协同作用。本研究旨在探讨厄洛替尼联合卡培他滨作为老年中国肺腺癌患者（≥65岁）一线治疗的疗效和耐受性。这是一项开放标签、单臂、多中心II期临床试验。在中国的4家三级教学医院和2家省级医院招募了62例年龄65岁及以上、既往未接受治疗的IIIB/IV期腺癌患者；58例患者符合研究要求。在每21天的周期中给予厄洛替尼（150mg/天）和卡培他滨（1000mg/m²，第1 - 14天每日两次）。主要终点是12周时的无进展率。使用聚合酶链反应（PCR）测定EGFR和K-ras突变率。使用免疫组织化学评估不同生物标志物的肿瘤表达。在58例患者队列中，34例患者在治疗后12周无疾病进展。客观缓解率为29.3%，疾病控制率为75.9%。EGFR突变患者的客观缓解率显著高于野生型EGFR患者。胸苷磷酸化酶阴性肿瘤患者的一年总生存期明显长于胸苷磷酸化酶阳性肿瘤患者。44例患者至少发生1次主要不良事件（AE），包括皮疹（n = 30）、3级AE（n = 17）和4级AE（n = 7）。这是第一项评估厄洛替尼联合卡培他滨联合疗法作为老年肺腺癌患者一线治疗的II期临床试验。厄洛替尼/卡培他滨化疗在EGFR突变患者和胸苷磷酸化酶阴性肿瘤患者中效果显著更好。使用氟尿嘧啶衍生物治疗肺腺癌值得进一步研究。
