title: Epidermal growth factor receptor mutations are associated with docetaxel sensitivity in lung cancer.
abstract: BACKGROUND
  A recent large randomized controlled trial revealed that patients with lung cancer with epidermal growth factor receptor (EGFR) mutations had better prognoses when treated with the EGFR-tyrosine kinase inhibitor, gefitinib, than with cytotoxic chemotherapeutic agents. Lung cancer with EGFR mutations is highly sensitive to EGFR-tyrosine kinase inhibitors. The previous trial implied that EGFR mutations might be predictive of the response to cytotoxic chemotherapy.
  
  
  METHODS
  Forty-six tumor tissue specimens (32 adenocarcinomas and 14 nonadenocarcinomas) were obtained from patients with lung cancer who underwent surgical resection. EGFR mutations were detected using polymerase chain reaction-invader assay. A histoculture drug response assay was used as an in vitro drug sensitivity test. The inhibition rates of cisplatin, docetaxel (DOC), vinorelbine, and gemcitabine were measured.
  
  
  RESULTS
  Sensitizing EGFR mutations were detected in samples from 14 patients, all with adenocarcinomas. The inhibition rate of cisplatin in tumors with EGFR mutations (group M) was 34.8 ± 15.5%, which was significantly lower (p = 0.0153) than in wild-type tumors (group W; 46.6 ± 14.0%). The inhibition rate of DOC in group M (18.8 ± 13.4%) was also significantly lower (p = 0.0051) than in group W (35.4 ± 19.1%). There were no significant differences in inhibition rates of gemcitabine and vinorelbine between groups M and W. Inhibition rates of DOC were significantly lower in group M (p = 0.0256) than in group W (32.6 ± 18.4) in samples from patients with adenocarcinoma.
  
  
  CONCLUSIONS
  The histoculture drug response assay indicated that lung cancers with EGFR mutations were less sensitive to DOC than EGFR wild-type tumors.
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, Wakayama Medical University, Wakayama, Japan. yositatu@wakayama-med.ac.jp
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Yoshimasu
authors.forename: Shoji
authors.initials: S
authors.lastname: Oura
authors.forename: Fuminori
authors.initials: F
authors.lastname: Ohta
authors.forename: Yoshimitsu
authors.initials: Y
authors.lastname: Hirai
authors.forename: Koma
authors.initials: K
authors.lastname: Naito
authors.forename: Rie
authors.initials: R
authors.lastname: Nakamura
authors.forename: Haruka
authors.initials: H
authors.lastname: Nishiguchi
authors.forename: Sayoko
authors.initials: S
authors.lastname: Hashimoto
authors.forename: Mitsumasa
authors.initials: M
authors.lastname: Kawago
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Okamura
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics; D002945:Cisplatin / Q000494:pharmacology; D004252:DNA Mutational Analysis; D004273:DNA, Neoplasm / Q000235:genetics; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000494:pharmacology; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D015996:Survival Rate; D043823:Taxoids / Q000494:pharmacology*; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured; D014747:Vinblastine / Q000031:analogs & derivatives / Q000494:pharmacology; D000077235:Vinorelbine; D000093542:Gemcitabine
chemical_list: D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D043823:Taxoids; D003841:Deoxycytidine; D000077143:Docetaxel; D014747:Vinblastine; C512478:EGFR protein, human; D066246:ErbB Receptors; D002945:Cisplatin; D000077235:Vinorelbine; D000093542:Gemcitabine