Epidermal growth factor receptor mutations are associated with docetaxel sensitivity in lung cancer

J Thorac Oncol. 2011 Oct;6(10):1658-62. doi: 10.1097/JTO.0b013e318221f71a.

Abstract

Introduction: 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.

Conclusion: The histoculture drug response assay indicated that lung cancers with EGFR mutations were less sensitive to DOC than EGFR wild-type tumors.

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / genetics
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / pharmacology*
  • Carcinoma, Squamous Cell / drug therapy
  • Carcinoma, Squamous Cell / genetics
  • Cisplatin / pharmacology
  • DNA Mutational Analysis
  • DNA, Neoplasm / genetics
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / pharmacology
  • Docetaxel
  • Drug Resistance, Neoplasm / genetics*
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / genetics*
  • Female
  • Follow-Up Studies
  • Gemcitabine
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics*
  • Male
  • Middle Aged
  • Mutation / genetics*
  • Neoplasm Staging
  • Polymerase Chain Reaction
  • Sensitivity and Specificity
  • Survival Rate
  • Taxoids / pharmacology*
  • Treatment Outcome
  • Tumor Cells, Cultured
  • Vinblastine / analogs & derivatives
  • Vinblastine / pharmacology
  • Vinorelbine

Substances

  • Antineoplastic Agents
  • DNA, Neoplasm
  • Taxoids
  • Deoxycytidine
  • Docetaxel
  • Vinblastine
  • EGFR protein, human
  • ErbB Receptors
  • Cisplatin
  • Vinorelbine
  • Gemcitabine