This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Suehisa, H. Articles by Date, H. Search for Related Content PubMed PubMed Citation Articles by Suehisa, H. Articles by Date, H. Social Bookmarking                            What's this?

Epidermal Growth Factor Receptor Mutation Status and Adjuvant Chemotherapy With Uracil-Tegafur for Adenocarcinoma of the Lung

Hiroshi Suehisa, Shinichi Toyooka, Katsuyuki Hotta, Akiko Uchida, Junichi Soh, Yoshiro Fujiwara, Keitaro Matsuo, Mamoru Ouchida, Minoru Takata, Katsuyuki Kiura, Hiroshi Date

From the Departments of Cancer and Thoracic Surgery; Hematology, Oncology, and Respiratory Medicine; and Molecular Genetics, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama; Department of Human Genetics, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima; and the Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan

Address reprint requests to Shinichi Toyooka, MD, Department of Cancer and Thoracic Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1 Shikata-cho, Okayama 700-8558, Japan; e-mail: toyooka{at}md.okayama-u.ac.jp

Purpose Adjuvant chemotherapy with uracil-tegafur has been demonstrated to prolong survival among patients with resected lung adenocarcinomas. Epidermal growth factor receptor (EGFR) mutations have been reported to be present in lung adenocarcinomas. The present study evaluated whether the EGFR status could be used as a biologic predictor of the outcome of adjuvant chemotherapy with uracil-tegafur.

Patients and Methods The EGFR mutational status of 187 patients with resected lung adenocarcinomas was determined using a polymerase chain reaction–based assay for EGFR exons 19 and 21; the results were then correlated with the effect of adjuvant uracil-tegafur chemotherapy on survival. The antiproliferative effect of fluorouracil (FU) on adenocarcinoma cell lines with EGFR wild-type or mutant type status was examined by measuring the inhibitory concentrations at 50% (IC₅₀s).

Results Among the 187 patients, 68 received uracil-tegafur as adjuvant chemotherapy, and 119 were not treated with any chemotherapeutic agents. EGFR mutations were present in 79 patients (43%). Overall, the adjuvant chemotherapy with uracil-tegafur significantly prolonged survival compared with the control group (hazard ratio = 0.38; P = .005). The survival benefit of adjuvant chemotherapy with uracil-tegafur was also examined after stratifying the patients according to EGFR mutation status. Adjuvant chemotherapy significantly prolonged survival among patients with EGFR wild-type tumors (hazard ratio = 0.34; P = .013) but not among patients with EGFR mutant tumors. In an in vitro experiment, the IC₅₀s of EGFR mutant cells to FU were higher than those of wild-type cells, indicating that EGFR wild-type cells are more sensitive to FU than mutant cells.

Conclusion EGFR status influenced the effect of adjuvant chemotherapy with uracil-tegafur. Adjuvant chemotherapy could be customized based on EGFR status.

Supported by Grant-in-Aid No. 18790993 for scientific research from the Ministry of Education, Science, Sports, Culture and Technology of Japan.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				M.-C. Etienne-Grimaldi, J.-L. Formento, M. Francoual, E. Francois, P. Formento, N. Renee, P. Laurent-Puig, M. Chazal, D. Benchimol, J.-R. Delpero, et al. K-Ras Mutations and Treatment Outcome in Colorectal Cancer Patients Receiving Exclusive Fluoropyrimidine Therapy Clin. Cancer Res., August 1, 2008; 14(15): 4830 - 4835. [Abstract] [Full Text] [PDF]