Epidermal growth factor receptor mutation detection using high-resolution melting analysis predicts outcomes in patients with advanced non small cell lung cancer treated with gefitinib.

Epidermal growth factor receptor mutation detection using high-resolution melting analysis predicts outcomes in patients with advanced non small cell lung cancer treated with gefitinib. Research Abstract Details 

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Epidermal growth factor receptor mutation detection using high-resolution melting analysis predicts outcomes in patients with advanced non small cell lung cancer treated with gefitinib. Abstract Text:

Toshimi Takano,Yuichiro Ohe,Koji Tsuta,Tomoya Fukui,Hiromi Sakamoto,Teruhiko Yoshida,Ukihide Tateishi,Hiroshi Nokihara,Noboru Yamamoto,Ikuo Sekine,Hideo Kunitoh,Yoshihiro Matsuno,Koh Furuta,Tomohide Tamura,Toshimi Takano,Yuichiro Ohe,Koji Tsuta,Tomoya Fukui,Hiromi Sakamoto,Teruhiko Yoshida,Ukihide Tateishi,Hiroshi Nokihara,Noboru Yamamoto,Ikuo Sekine,Hideo Kunitoh,Yoshihiro Matsuno,Koh Furuta,Tomohide Tamura,

PURPOSE: Epidermal growth factor receptor (EGFR) mutations, especially deletional mutations in exon 19 (DEL) and L858R, predict gefitinib sensitivity in patients with non-small cell lung cancer (NSCLC). In this study, we validated EGFR mutation detection using high-resolution melting analysis (HRMA) and evaluated the associations between EGFR mutations and clinical outcomes in advanced NSCLC patients treated with gefitinib on a larger scale. EXPERIMENTAL DESIGN: The presence of DEL or L858R was evaluated using HRMA and paraffin-embedded tissues and/or cytologic slides from 212 patients. In 66 patients, the results were compared with direct sequencing data. RESULTS: HRMA using formalin-fixed tissues had a 92% sensitivity and a 100% specificity. The analysis was successfully completed in 207 patients, and DEL or L858R mutations were detected in 85 (41%) patients. The response rate (78% versus 8%), time-to-progression (median, 9.2 versus 1.6 months), and overall survival (median, 21.7 versus 8.7 months) were significantly better in patients with EGFR mutations (P < 0.001). Even among the 34 patients with stable diseases, the time-to-progression was significantly longer in patients with EGFR mutations. Patients with DEL (n = 49) tended to have better outcomes than those with L858R (n = 36); the response rates were 86% and 67%, respectively (P = 0.037), and the median time-to-progression was 10.5 and 7.4 months, respectively (P = 0.11). CONCLUSIONS: HRMA is a precise method for detecting DEL and L858R mutations and is useful for predicting clinical outcomes in patients with advanced NSCLC treated with gefitinib.

Epidermal growth factor receptor mutation detection using high-resolution melting analysis predicts outcomes in patients with advanced non small cell lung cancer treated with gefitinib. Publishing Authors By Initials

T Takano,Y Ohe,K Tsuta,T Fukui,H Sakamoto,T Yoshida,U Tateishi,H Nokihara,N Yamamoto,I Sekine,H Kunitoh,Y Matsuno,K Furuta,T Tamura,T Takano,Y Ohe,K Tsuta,T Fukui,H Sakamoto,T Yoshida,U Tateishi,H Nokihara,N Yamamoto,I Sekine,H Kunitoh,Y Matsuno,K Furuta,T Tamura,

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Epidermal growth factor receptor mutation detection using high-resolution melting analysis predicts outcomes in patients with advanced non small cell lung cancer treated with gefitinib. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Clinical cancer research : an official journal of

VOLUME: 13

Page Numbers: 5385-90

Journal Abbreviation: Clin. Cancer Res.

ISSN: 1078-0432

DAY: 15

MONTH: Sep

YEAR: 2007

Epidermal growth factor receptor mutation detection using high-resolution melting analysis predicts outcomes in patients with advanced non small cell lung cancer treated with gefitinib. Information

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LANGUAGE: eng

NlmUniqueID: 9502500

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AFFILIATION: Division of Internal Medicine, National Cancer Center Hospital, Chuo-ku, Tokyo, Japan.

Country: United States

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MEDLINETA: Clin Cancer Res

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