OBJECTIVE: There are many predictive factors for gefitinib sensitivity, including epidermal growth factor receptor (EGFR) gene mutation, EGFR copy number, and k-ras mutation. To investigate all of them is too expensive. We evaluated the chemosensitivity for gefitinib in non-small-cell lung cancer (NSCLC) using a histoculture drug response assay (HDRA). METHODS: Surgically resected fresh tumor specimens from 22 patients with NSCLC were used. There were 13 male and 9 female patients, ranging in age from 49 to 84 (average 70) years old. Sixteen patients (73%) were smokers. Sixteen adenocarcinomas, four squamous cell carcinomas, and two other histological types were included. Small pieces of viable cancer tissue were placed on the collagen gel and then cultured for 7 days in the presence of gefitinib. RESULTS: The HDRA was successful in all specimens. A dose-response relation was observed between inhibition rates and gefitinib concentration (p = 0.016). The inhibition rate at 20 microg/ml (IR(20)) in adenocarcinoma without smoking (39.2% +/- 35.1%, n = 6) was higher than that with smoking (2.2% +/- 5.0%, n = 10, P = 0.001) and that of nonadenocarcinoma (16.9% +/- 23.6%, n = 6, P = 0.09). Gene mutation analysis was performed in two of three adenocarcinomas without smoking, which showed especially high IR(20) values, and sensitizing mutations were observed in these specimens. A cutoff inhibition rate of approximately 40%-50% appeared to be suitable for a concentration of 20 microg/ml. CONCLUSION: HDRA appears to be applicable for evaluating sensitivity to gefitinib in NSCLC. It provides a convenient method for predicting the response to gefitinib in patients with NSCLC whose fresh tumor specimens are available.
OBJECTIVE: There are many predictive factors for gefitinib sensitivity, including epidermal growth factor receptor (EGFR) gene mutation, EGFR copy number, and k-ras mutation. To investigate all of them is too expensive. We evaluated the chemosensitivity for gefitinib in non-small-cell lung cancer (NSCLC) using a histoculture drug response assay (HDRA). METHODS: Surgically resected fresh tumor specimens from 22 patients with NSCLC were used. There were 13 male and 9 female patients, ranging in age from 49 to 84 (average 70) years old. Sixteen patients (73%) were smokers. Sixteen adenocarcinomas, four squamous cell carcinomas, and two other histological types were included. Small pieces of viable cancer tissue were placed on the collagen gel and then cultured for 7 days in the presence of gefitinib. RESULTS: The HDRA was successful in all specimens. A dose-response relation was observed between inhibition rates and gefitinib concentration (p = 0.016). The inhibition rate at 20 microg/ml (IR(20)) in adenocarcinoma without smoking (39.2% +/- 35.1%, n = 6) was higher than that with smoking (2.2% +/- 5.0%, n = 10, P = 0.001) and that of nonadenocarcinoma (16.9% +/- 23.6%, n = 6, P = 0.09). Gene mutation analysis was performed in two of three adenocarcinomas without smoking, which showed especially high IR(20) values, and sensitizing mutations were observed in these specimens. A cutoff inhibition rate of approximately 40%-50% appeared to be suitable for a concentration of 20 microg/ml. CONCLUSION: HDRA appears to be applicable for evaluating sensitivity to gefitinib in NSCLC. It provides a convenient method for predicting the response to gefitinib in patients with NSCLC whose fresh tumor specimens are available.
Authors: Federico Cappuzzo; Marileila Varella-Garcia; Hisayuki Shigematsu; Irene Domenichini; Stefania Bartolini; Giovanni L Ceresoli; Elisa Rossi; Vienna Ludovini; Vanesa Gregorc; Luca Toschi; Wilbur A Franklin; Lucio Crino; Adi F Gazdar; Paul A Bunn; Fred R Hirsch Journal: J Clin Oncol Date: 2005-08-01 Impact factor: 44.544
Authors: T Kubota; N Sasano; O Abe; I Nakao; E Kawamura; T Saito; M Endo; K Kimura; H Demura; H Sasano Journal: Clin Cancer Res Date: 1995-12 Impact factor: 12.531
Authors: K Nakatani; M Takao; J Nishioka; K Yasuda; K Noma; A Hayashi; H Wada; T Nobori Journal: Eur J Cancer Care (Engl) Date: 2007-05 Impact factor: 2.520
Authors: Louise A Knight; Federica Di Nicolantonio; Pauline Whitehouse; Stuart Mercer; Sanjay Sharma; Sharon Glaysher; Penny Johnson; Ian A Cree Journal: BMC Cancer Date: 2004-11-23 Impact factor: 4.430
Authors: Eunsung Jun; Yejong Park; Woohyung Lee; Jaewoo Kwon; Song Lee; Moon Bo Kim; Ji Sun Lee; Ki Byung Song; Dae Wook Hwang; Jae Hoon Lee; Robert M Hoffman; Song Cheol Kim Journal: Sci Rep Date: 2020-07-20 Impact factor: 4.379
Authors: Ian R Powley; Meeta Patel; Gareth Miles; Howard Pringle; Lynne Howells; Anne Thomas; Catherine Kettleborough; Justin Bryans; Tim Hammonds; Marion MacFarlane; Catrin Pritchard Journal: Br J Cancer Date: 2020-01-02 Impact factor: 7.640