Erlotinib plus capecitabine as first-line treatment for older Chinese patients with advanced adenocarcinoma of the lung (C-TONG0807): an open-label, single arm, multicenter phase II study.
Erlotinib plus capecitabine as first-line treatment for older Chinese patients with advanced adenocarcinoma of the lung (C-TONG0807): an open-label, single arm, multicenter phase II study.
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厄洛替尼联合卡培他滨作为中国老年晚期肺腺癌患者的一线治疗（C-TONG0807）：一项开放标签、单组、多中心 II 期研究。
DOI：
10.1097/md.0000000000000249
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发表时间：
2015-01
期刊：
影响因子：
1.6
通讯作者：
Zhang L
中科院分区：
文献类型：
--
作者：
Zhao HY;Chen GY;Huang Y;Li XL;Feng JF;Shi MQ;Cheng Y;Ma LX;Zhang YP;Gu CP;Song XQ;Zhou D;Zhang L
临床前研究表明，表皮生长因子受体（EGFR）酪氨酸激酶抑制剂和抗叶酸剂在实体瘤中具有协同作用。本研究旨在研究厄洛替尼联合卡培他滨一线治疗中国老年肺腺癌患者（≥ 65岁）的疗效和耐受性。 这是一项开放标签、单组、多中心II期临床试验。62例既往未经治疗的IIIB/IV期腺癌患者（年龄≥ 65岁）在中国的4家三级教学医院和2家省级医院入组; 58例患者符合研究要求。厄洛替尼（150 mg/天）和卡培他滨（1000 mg/m2，每日两次，第1-14天）在每21天周期内给药。 主要终点是12周时的非进展率。EGFR和K-ras基因突变率采用PCR法测定。使用免疫组织化学评估不同生物标志物的肿瘤表达。在58例患者的队列中，34例患者在治疗后12周没有疾病进展。客观有效率为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一年后的总生存期显著长于胸苷磷酸化酶阳性肿瘤患者。44例患者至少发生1起主要不良事件（AE），包括皮疹（n = 30）、3级AE（n = 17）和4级AE（n = 7）。 这是第一个II期临床试验，以评估厄洛替尼加卡培他滨联合治疗作为一线治疗老年肺腺癌患者。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显著更好。氟尿嘧啶衍生物用于肺腺癌的治疗值得进一步研究。
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.