2007年9月
Epidermal growth factor receptor mutation status and adjuvant chemotherapy with uracil-tegafur for adenocarcinoma of the lung
JOURNAL OF CLINICAL ONCOLOGY
- 巻
- 25
- 号
- 25
- 開始ページ
- 3952
- 終了ページ
- 3957
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1200/JCO.2007.11.8646
- 出版者・発行元
- AMER SOC CLINICAL ONCOLOGY
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% ( IC(50)s).
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 IC(50)s 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.
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% ( IC(50)s).
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 IC(50)s 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.
- リンク情報
-
- DOI
- https://doi.org/10.1200/JCO.2007.11.8646
- PubMed
- https://www.ncbi.nlm.nih.gov/pubmed/17761979
- Web of Science
- https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000249416000026&DestApp=WOS_CPL
- URL
- http://www.scopus.com/inward/record.url?eid=2-s2.0-34548530411&partnerID=MN8TOARS
- URL
- http://orcid.org/0000-0003-1761-6314
- ID情報
-
- DOI : 10.1200/JCO.2007.11.8646
- ISSN : 0732-183X
- ORCIDのPut Code : 23342068
- PubMed ID : 17761979
- SCOPUS ID : 34548530411
- Web of Science ID : WOS:000249416000026