title: 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.
abstract: 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.
authors.affiliation: 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).
authors.forename: Hong-Yun
authors.initials: HY
authors.lastname: Zhao
authors.forename: Gong-Yan
authors.initials: GY
authors.lastname: Chen
authors.forename: Yan
authors.initials: Y
authors.lastname: Huang
authors.forename: Xiao-Li
authors.initials: XL
authors.lastname: Li
authors.forename: Ji-Feng
authors.initials: JF
authors.lastname: Feng
authors.forename: Mei-Qi
authors.initials: MQ
authors.lastname: Shi
authors.forename: Ying
authors.initials: Y
authors.lastname: Cheng
authors.forename: Li-Xia
authors.initials: LX
authors.lastname: Ma
authors.forename: Yi-Ping
authors.initials: YP
authors.lastname: Zhang
authors.forename: Cui-Ping
authors.initials: CP
authors.lastname: Gu
authors.forename: Xiang-Qun
authors.initials: XQ
authors.lastname: Song
authors.forename: Da
authors.initials: D
authors.lastname: Zhou
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects; D015415:Biomarkers; D000069287:Capecitabine; D002681:China; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D018572:Disease-Free Survival; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D000069347:Erlotinib Hydrochloride; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D018773:Genes, erbB-1 / Q000235:genetics*; D011905:Genes, ras / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008297:Male; D009154:Mutation; D009367:Neoplasm Staging; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects; D013939:Thymidine Phosphorylase / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; D011799:Quinazolines; D003841:Deoxycytidine; D000069287:Capecitabine; D000069347:Erlotinib Hydrochloride; D013939:Thymidine Phosphorylase; D005472:Fluorouracil